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  • Published: 08 June 2023

Alcohol consumption and risks of more than 200 diseases in Chinese men

  • Pek Kei Im   ORCID: orcid.org/0000-0002-2624-9766 1 ,
  • Neil Wright   ORCID: orcid.org/0000-0002-3946-1870 1 ,
  • Ling Yang   ORCID: orcid.org/0000-0001-5750-6588 1 , 2 ,
  • Ka Hung Chan   ORCID: orcid.org/0000-0002-3700-502X 1 , 3 ,
  • Yiping Chen   ORCID: orcid.org/0000-0002-4973-0296 1 , 2 ,
  • Huaidong Du   ORCID: orcid.org/0000-0002-9814-0049 1 , 2 ,
  • Xiaoming Yang 1 ,
  • Daniel Avery   ORCID: orcid.org/0000-0002-9823-9575 1 ,
  • Shaojie Wang 5 ,
  • Canqing Yu   ORCID: orcid.org/0000-0002-0019-0014 6 , 7 ,
  • Jun Lv 6 , 7 ,
  • Robert Clarke   ORCID: orcid.org/0000-0002-9802-8241 1 ,
  • Junshi Chen 8 ,
  • Rory Collins 1 ,
  • Robin G. Walters   ORCID: orcid.org/0000-0002-9179-0321 1 , 2 ,
  • Richard Peto 1 ,
  • Liming Li   ORCID: orcid.org/0000-0001-5873-7089 6 , 7   na1 ,
  • Zhengming Chen   ORCID: orcid.org/0000-0001-6423-105X 1 , 2   na1 ,
  • Iona Y. Millwood   ORCID: orcid.org/0000-0002-0807-0682 1 , 2   na1 &

China Kadoorie Biobank Collaborative Group

Nature Medicine volume  29 ,  pages 1476–1486 ( 2023 ) Cite this article

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  • Epidemiology
  • Genetics research
  • Risk factors

Alcohol consumption accounts for ~3 million annual deaths worldwide, but uncertainty persists about its relationships with many diseases. We investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of >512,000 adults (41% men), including 168,050 genotyped for ALDH2 - rs671 and ADH1B - rs1229984 , with >1.1 million ICD-10 coded hospitalized events. At baseline, 33% of men drank alcohol regularly. Among men, alcohol intake was positively associated with 61 diseases, including 33 not defined by the World Health Organization as alcohol-related, such as cataract ( n  = 2,028; hazard ratio 1.21; 95% confidence interval 1.09–1.33, per 280 g per week) and gout ( n  = 402; 1.57, 1.33–1.86). Genotype-predicted mean alcohol intake was positively associated with established ( n  = 28,564; 1.14, 1.09–1.20) and new alcohol-associated ( n  = 16,138; 1.06, 1.01–1.12) diseases, and with specific diseases such as liver cirrhosis ( n  = 499; 2.30, 1.58–3.35), stroke ( n  = 12,176; 1.38, 1.27–1.49) and gout ( n  = 338; 2.33, 1.49–3.62), but not ischemic heart disease ( n  = 8,408; 1.04, 0.94–1.14). Among women, 2% drank alcohol resulting in low power to assess associations of self-reported alcohol intake with disease risks, but genetic findings in women suggested the excess male risks were not due to pleiotropic genotypic effects. Among Chinese men, alcohol consumption increased multiple disease risks, highlighting the need to strengthen preventive measures to reduce alcohol intake.

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Genomic prediction of alcohol-related morbidity and mortality

Alcohol consumption is a major risk factor for poor physical and mental health, accounting for about 3 million deaths and over 130 million disability-adjusted life years worldwide in 2016 (ref. 1 ). Since the 1990s, alcohol consumption has increased in many low- and middle-income countries, including China, where it almost exclusively involves men 2 , 3 . Among Chinese men, those who reported alcohol consumption in the past 12 months increased from 59% to 85% and yearly per-capita alcohol consumption increased from 7.1 to 11.2 l between 1990 and 2017 and these have been predicted to increase in future years 2 .

Previous epidemiological studies conducted in mainly western populations have provided consistent evidence about the hazards of alcohol drinking for several major diseases, including several types of cancers and cardiovascular diseases (CVDs), liver cirrhosis, infectious diseases (for example tuberculosis and pneumonia) and injuries 4 , 5 , 6 , 7 , 8 , 9 . Large western cohort studies with linkage to hospital records have also investigated the associations of alcohol with risks of several less-common or non-fatal disease outcomes (for example certain site-specific cancers 10 , 11 , 12 , dementia 13 , falls 14 and cataract surgery 15 ). For some (for example stomach cancer), there was suggestive evidence of weak positive associations with heavy drinking 10 , 11 , whereas for others (for example cataract) the limited available evidence has been contradictory 10 , 12 , 13 , 15 ; however, the evidence from western populations, even for diseases known to be associated with alcohol, may not be generalizable to Chinese populations, where the prevalence and types of alcohol drinking (mainly spirits), patterns of diseases (for example high stroke rates) and differences in the ability to metabolize alcohol 8 , 9 , 16 differ markedly from those in western populations 4 , 17 .

For many diseases, including those considered by the World Health Organization (WHO) 4 to be alcohol-related (for example ischemic heart disease (IHD) and diabetes), uncertainty remains about the causal relevance of these associations, which can be assessed in genetic studies using a Mendelian randomization (MR) approach 18 . In such studies, genetic variants can be used as instruments for alcohol consumption to investigate the potential causal relevance of alcohol drinking for diseases, which can limit the biases of confounding and reverse causality common in conventional observational studies 18 . Such studies are particularly informative in East Asian populations where two common genetic variants ( ALDH2 - rs671 and ADH1B - rs1229984 ), which are both rare in western populations, greatly alter alcohol metabolism and strongly affect alcohol intake 19 . Several studies have explored the causal relevance of alcohol consumption with CVD risk factors and morbidity 19 , 20 , 21 , 22 and cancer 16 using these genetic variants, yet findings remain inconclusive for certain diseases (for example IHD) and evidence for other diseases is sparse.

To address these questions, we conducted analyses using observational and genetic approaches to evaluate the associations between alcohol consumption and the risks of a wide range of disease outcomes in the prospective China Kadoorie Biobank (CKB).

Among the 512,724 participants (Supplementary Fig. 1 ), the mean age at baseline was 52 (s.d. 10.7) years, 41% were men and 56% lived in rural areas. Among men, 33% reported drinking alcohol regularly (at least once a week) at baseline (current drinkers), consuming on average 286 g of alcohol per week, mainly from spirits (Supplementary Tables 1 and 2 ). Non-drinkers and ex-drinkers were older and more likely to report poor self-rated health or previous chronic diseases, compared to occasional or current drinkers (Table 1 ). Compared to moderate drinkers (<140 g per week), heavier drinkers were more likely to be rural residents, had received lower education and had more unhealthy lifestyle factors (for example smoking and infrequent fresh fruit intake), higher mean blood pressure and longer duration of drinking (Supplementary Table 3 ). Among male current drinkers, 62% reported drinking daily and 37% engaging in heavy episodic drinking (Supplementary Table 2 ). Among women, only 2% drank alcohol at least weekly (mean intake 116 g per week), but there were similar associations with other baseline characteristics (Table 1 and Supplementary Tables 3 and 4 ) compared to those in men.

During a median of 12.1 (interquartile range 11.1–13.1) years of follow-up, 134,641 men (44,027 drinkers) and 198,430 women (4,420 drinkers) experienced at least one reported hospitalization event or death at age-at-risk 35–84 years, involving a total of 1,111,495 hospitalization episodes. Among men, there were 333,541 (107,857 in current drinkers) recorded events from 207 diseases across 17 International Classification of Diseases Tenth Revision (ICD-10) chapters studied that had at least 80 cases each among current drinkers (Table 2 ), while among women there were 476,986 (11,773) events from 48 diseases across 18 ICD-10 chapters (Supplementary Table 5 ).

Observational associations of alcohol with disease risks

Among men, alcohol drinking was significantly associated with higher risks of 61 disease outcomes from 15 ICD-10 chapters based on two separate analyses, (1) comparing ever-regular versus occasional drinkers and (2) dose–response among current drinkers (Table 2 and Extended Data Fig. 1 ). In each of the analyses in men, there were significant associations of alcohol consumption with 42 diseases (or outcomes), of which 23 were significant in both analyses and the remainder were directionally consistent with one exception (transient cerebral ischemic attacks, ICD-10 code G45) (Fig. 1 ). In further analyses covering all alcohol consumption categories, there were typical U-shaped or J-shaped associations, with excess risks in male ex-drinkers and non-drinkers compared to occasional or moderate drinkers for most of these diseases (Supplementary Table 6 ). Among male ex-drinkers, the overall excess morbidity risks were more considerable for alcohol-associated diseases than for other diseases, but these excess risks were lower with increasing duration after stopping drinking (Extended Data Fig. 2 ).

figure 1

Cox models ( a ) comparing ever-regular drinkers with occasional drinkers or ( b ) assessing the dose–response per 280 g per week higher usual alcohol intake within current drinkers, were stratified by age at risk and study area and were adjusted for education and smoking. Each solid square represents HR with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. Diseases considered to be alcohol-related by the WHO are indicated with ‘W’ under the ‘WHO’ column. The individual diseases listed included all that showed FDR-adjusted significant associations with alcohol (FDR-adjusted P  < 0.05, indicated with ‘Y’ under the ‘FDR sig.’ column) and WHO alcohol-related diseases that showed nominally significant associations with alcohol ( P  < 0.05). All P values are two-sided. † Included less-common ICD-10 codes within the corresponding ICD-10 chapter that were not individually investigated in the present study. ‘Less-common psychiatric and behavioral conditions’ consisted of ICD-10 codes F00–F99, excluding F32, F33 and F99. ‘Less-common circulatory diseases’ consisted of ICD-10 codes I00–I99, excluding I10, I11, I20, I21, I24, I25, I27, I42, I46, I48–I51, I60–I67, I69, I70, I80 and I83. ‘Less-common injury, poisoning and other external causes’ consisted of ICD-10 codes S00–T98, excluding S06, S09, S22, S32, S42, S52, S62, S72, S82, S92 and T14.

Of the 61 diseases positively associated with alcohol intake in male participants, 28 were considered by the WHO to be alcohol-related diseases, including tuberculosis (A15–A19 and B90), six site-specific cancers including cancers in the larynx (C32), esophagus (C15), liver (C22), colon (C18), rectum (C19 and C20) and lips, oral cavity and pharynx (C00–C14), diabetes (E10–E14), epilepsy (G40 and G41), several hypertensive diseases (I10 and I11) and cerebrovascular diseases (I61, I63, I65, I66, I67, I69 and G45), chronic IHD (I25), cardiomyopathy (I42), pneumonia (J12–J18), alcoholic liver disease (K70) and liver cirrhosis (K74), pancreatitis (K85 and K86) and external causes including self-harm (X60–X84), falls (W00–W19), transport accidents (V01–V99) and other external causes (rest of V–Y) (Fig. 1 and Extended Data Fig. 3 ). Of these 28 diseases, 22 showed significant dose–response associations with alcohol intake. The hazard ratios (HRs) per 280 g per week higher intake for the aggregated WHO alcohol-related diseases were 1.22 (95% confidence interval (CI) 1.19–1.25) (Supplementary Table 7 for detailed outcome classification), ranging from 1.12 (1.05–1.20) for pneumonia to 1.97 (1.80–2.15) for esophageal cancer.

The 33 other diseases showing false discovery rate (FDR)-adjusted significant positive associations with alcohol drinking in men included lung (C34) and stomach (C16) cancers, cataract (H25 and H26), six digestive diseases such as gastroesophageal reflux disease (K21) and gastric ulcer (K25), three musculoskeletal conditions, including gout (M10), three fracture types (S22, S42 and S72), and the aggregates of less-common psychiatric and behavioral conditions and circulatory diseases (Fig. 1 and Extended Data Fig. 4 ). Of these 33 diseases, 22 showed significant dose–response associations, with HRs per 280 g per week higher intake ranging from 1.16 (95% CI 1.04–1.30) for lung cancer to 1.94 (1.43–2.63) for purpura and other hemorrhagic conditions (D69) and 1.20 (1.16–1.24) for the aggregated CKB new alcohol-associated diseases. In contrast, three diseases showed FDR-adjusted significant inverse associations with alcohol drinking (other nontoxic goiter (E04), hyperplasia of prostate (N40) and inguinal hernia (K40)). Overall, for all-cause morbidity, the HR per 280 g per week higher intake was 1.12 (1.10–1.14) in male current drinkers.

Supplementary Figs. 2 – 4 show the dose–response associations for all disease outcomes investigated in male current drinkers. For alcohol-associated diseases and for total morbidity, the dose–response associations were unaltered after additional covariate adjustments or excluding participants with poor baseline health conditions (Supplementary Fig. 5 and Supplementary Table 8 ). Moreover, the associations were similar across various male population subgroups, but seemed to be stronger in younger men, urban residents and higher socioeconomic groups for new alcohol-associated diseases (Supplementary Fig. 6 ).

Among male current drinkers, drinking daily, heavy episodic drinking and drinking spirits were each associated with higher risks for alcohol-related diseases, but most of these associations were attenuated to the null after adjusting for total alcohol intake (Extended Data Fig. 5 ); however, for a given total alcohol intake among male current drinkers, drinking daily was associated with 30–40% higher risks of alcohol-related cancers (1.30, 1.17–1.45) and liver cirrhosis (1.39, 1.13–1.72), compared to non-daily drinking. Similarly, heavy episodic drinking was associated with higher risks of diabetes (1.23, 1.12–1.34) and IHD (1.11, 1.03–1.19), whereas drinking outside of meals was associated with 49% (1.49, 1.19–1.86) higher risk of liver cirrhosis than drinking with meals. The risks of all major alcohol-associated diseases were higher with longer duration of alcohol consumption in men (Extended Data Fig. 6 ).

Among women, due to few reported current drinkers there was a lack of statistical power to detect any associations of self-reported alcohol intake with disease risks (Supplementary Table 5 , Extended Data Fig. 7 and Supplementary Fig. 7 ).

Genetic associations of alcohol with disease risks

A genetic instrument for alcohol intake was derived using ALDH2 - rs671 (G > A) and ADH1B - rs1229984 (G > A) genotypes. The overall A-allele frequency was 0.21 for ALDH2 - rs671 and 0.69 for ADH1B - rs1229984 , with both A-alleles being more common in southern than northern study areas (Supplementary Table 9 ). Both ALDH2 - rs671 and, to a lesser extent, ADH1B - rs1229984 were strongly associated with alcohol drinking in men, but much less so in women (Supplementary Table 10 ). In men, the derived genetic instrument predicted a >60-fold difference (range 4–255 g per week, C1 to C6) in mean alcohol intake, whereas in women mean alcohol intake remained low (<10 g per week) across genetic categories (Supplementary Table 11 ). Both variants and the derived instrument were not associated with smoking or other major self-reported baseline characteristics, except for a small difference in fresh fruit intake by ALDH2 - rs671 genotype in men.

Among men, genotype-predicted mean alcohol intake was positively associated with higher risks of CKB WHO alcohol-related (HR per 280 g per week higher genotype-predicted mean male alcohol intake: 1.14, 95% CI 1.09–1.20) and CKB new alcohol-associated (1.06, 1.01–1.12) diseases (Fig. 2 ), both of which were slightly weaker than the conventional associations. For certain diseases, however, the genetic associations were stronger, with HRs of 1.38 (1.27–1.49) for stroke, 2.30 (1.58–3.35) for liver cirrhosis and 2.33 (1.49–3.62) for gout, in men (Fig. 3 and Extended Data Fig. 8 ). For individual genetic variants, the associations were directionally consistent (Extended Data Figs. 9 and 10 ). Conversely, there were no significant dose–response genotypic associations with IHD, inguinal hernia or hyperplasia of prostate in men. For other alcohol-associated diseases, higher genotype-predicted mean male alcohol intake was significantly associated with higher risks of esophageal cancer, cataract, occlusion and stenosis of cerebral arteries, sequelae of cerebrovascular disease, essential primary hypertension and fractures of ribs, sternum or thoracic spine. There were also suggestive positive genotypic associations with several digestive tract cancer types (liver, colon and stomach) and circulatory and digestive diseases, and significant inverse associations with lung cancer and other chronic obstructive pulmonary disease (J44) in men (Extended Data Figs. 8 – 10 ). Sensitivity analyses using different analytical methods to adjust for confounding by study area, or a two-stage least-squares MR approach, did not alter the main genetic findings in men (Supplementary Table 12 ). In contrast, genotypes that increased alcohol intake in men were not adversely associated with most alcohol-related disease risks among women (for example HR 1.00 (0.97–1.04) for all morbidity among female non-drinkers; Supplementary Fig. 7 and Extended Data Figs. 8 – 10 ).

figure 2

Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard within subplot. The vertical lines indicate group-specific 95% CIs. Conventional epidemiological analyses relate self-reported drinking patterns to risks of diseases (reference group is occasional drinkers), using Cox models stratified by age at risk and study area and adjusted for education and smoking. Within current drinkers, HRs were plotted against usual alcohol intake and were calculated per 280 g per week higher usual alcohol intake. Genetic epidemiological analyses relate genetic categories to risks of diseases (reference group is the genotype group with lowest genotype-predicted mean male alcohol intake), using Cox models stratified by age at risk and study area and adjusted for genomic principal components. The HR per 280 g per week higher genotype-predicted mean male alcohol intake was calculated from the inverse-variance-weighted mean of the slopes of the fitted lines in each study area. The corresponding slopes in women were summarized in text and the slopes of the fitted line by sex were compared and assessed for heterogeneity using chi-squared tests (indicated by P for heterogeneity by sex). All P values are two-sided. Analyses of these aggregated outcomes were based on first recorded event of the aggregate during follow-up and participants may have had multiple events of different types of diseases. ‘All alcohol-related diseases’ includes the first recorded event from ‘CKB WHO alcohol-related diseases’ or ‘CKB new alcohol-associated diseases’ during follow-up.

figure 3

Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard within subplot. The vertical lines indicate group-specific 95% CIs. Conventional epidemiological analyses relate self-reported drinking patterns to risks of diseases (reference group is occasional drinkers), using Cox models stratified by age at risk and study area and adjusted for education and smoking. Within current drinkers, HRs were plotted against usual alcohol intake and were calculated per 280 g per week higher usual alcohol intake. Genetic epidemiological analyses relate genetic categories to risks of diseases (reference group is the genotype group with lowest genotype-predicted mean male alcohol intake), using Cox models stratified by age at risk and study area and adjusted for genomic principal components. The HR per 280 g per week higher genotype-predicted mean male alcohol intake was calculated from the inverse-variance-weighted mean of the slopes of the fitted lines in each study area. The corresponding slopes in women were summarized in text and the slopes of the fitted line by sex were compared and assessed for heterogeneity using chi-squared tests (indicated by P for heterogeneity by sex). All P values are two-sided. Corresponding ICD-10 codes, IHD (I20–I25); stroke (I60, I61, I63 and I64); liver cirrhosis (K70 and K74); gout (M10); inguinal hernia (K40); hyperplasia of prostate (N40).

Hospitalizations associated with alcohol drinking

Among men, ever-regular drinkers had higher numbers of hospitalizations for any causes than occasional drinkers, particularly for cancer hospitalizations, and these differences increased with increasing age at risk, except for CVD hospitalizations (Supplementary Fig. 8 ).

This prospective study provides a comprehensive assessment of the impact of alcohol consumption on a very wide range of disease outcomes in Chinese adults. Among men, alcohol consumption was associated with significantly higher risks of 61 diseases, including 33 not previously reported as alcohol-related diseases by the WHO, and higher risks of hospitalizations for any causes. For a given total amount, drinking daily, heavy episodic drinking and drinking outside of meals exacerbated the risks of four major diseases in Chinese men. Moreover, most of these associations in Chinese men were confirmed in genetic analyses, at least when assessed collectively, and are likely to reflect the effects alcohol consumption itself rather than any pleiotropic effects of the genetic instruments.

Based primarily on observational findings in western populations, alcohol consumption has been considered by the WHO 4 and the Global Burden of Disease (GBD) study 23 to be related to about 20 distinct disease categories, involving chronic diseases and cancers largely in the gastrointestinal system, several CVD types, infectious diseases and injuries. The observational analyses largely confirmed these known associations (Supplementary Table 13 ), but also provided insights into additional hazards of certain drinking patterns suggested by previous studies 8 , 9 , 24 , 25 . Moreover, this study discovered 33 additional alcohol-associated diseases across various body systems in Chinese men that had not been previously reported by the WHO. For these 33 disease outcomes, their associations with alcohol intake were confirmed in genetic analyses, at least collectively as well as for certain specific diseases (for example gout), as was the case for a similar number of WHO alcohol-related diseases. The somewhat smaller relative (but not absolute) risks of alcohol drinking with major diseases at older than younger age in men from observational analyses were consistent with previous studies of other risk factors (for example blood pressure 26 and smoking 27 ), which could be driven by a number of factors such as selection bias 27 and comorbidities.

For certain major WHO alcohol-related diseases, particularly IHD and ischemic stroke, observational studies, including this study, have consistently reported J-shaped associations, with those who drank moderately (for example 1–2 units a day) having the lowest risks 6 , 28 ; however, these apparent protective effects of moderate drinking probably largely reflect residual confounding (for example non-drinkers having worse health and socioeconomic profiles than occasional drinkers) and uncontrolled reverse causation (for example sick-quitter effect where pre-existing poor health or changes in health conditions lead to alcohol cessation), including the difficulty in defining abstainers (for example ex-drinkers may be reported as non-drinkers) as the reference group in many previous studies 3 , 29 . In this study, we used occasional drinkers rather than non-drinkers as the reference group, which, together with separate dose–response analyses among current drinkers, helped to reduce but not eliminate any such biases, which could largely be mitigated in genetic analyses using an MR approach.

To date the existing MR studies for alcohol have focused mainly on CVD types 30 , 31 , 32 and cancers 33 , 34 , 35 , with limited data for other diseases. Moreover, previous studies mainly involved European-ancestry populations and hence were constrained by availability of relatively weak genetic instruments. Using genetic instruments specific to East Asian populations that predicted >60-fold difference in alcohol consumption, we previously reported evidence for the causal relevance and apparent dose–response effects of alcohol consumption on upper-aerodigestive tract cancers 16 and stroke 19 . These findings were further corroborated by subsequent European ancestry-based MR studies 30 , 32 , 36 and the analyses presented in this study with additional follow-up data. In contrast to stroke, we found no reliable genetic evidence for a cardioprotective, nor harmful, effect of moderate drinking on risk of IHD in men, consistent with findings in other MR studies 30 , 32 . The present study also demonstrated a log-linear genetic association of alcohol with liver cirrhosis and suggestive positive associations for several WHO alcohol-related digestive tract cancers in men. Moreover, separate genetic analyses among women suggests that the excess risks observed among men were due chiefly to alcohol per se rather than to potential pleiotropic effects of the alcohol-related genotypes. Further larger genetic studies are required to confirm and elucidate the potential causal relevance for each of the other WHO alcohol-related diseases individually.

For the new alcohol-associated diseases identified in this study, the available prospective epidemiological evidence has been sparse and mostly confined to western populations. For gout, previous western prospective studies have reported positive associations 37 , 38 and an MR study of 8,000 Korean men has also reported positive associations of alcohol consumption with hyperuricemia, a risk factor for gout 39 . The present study provides genetic evidence that alcohol drinking increases the risk of gout. Consistent with the present study, previous European-ancestry-based observational studies 40 , 41 and one MR study 42 also reported positive associations of alcohol intake with risks of several fracture types. The available prospective evidence on associations between alcohol drinking and risk of cataract has been conflicting 15 , 43 and one European-ancestry-based MR study reported no genetic associations 44 . We found a significant dose–response association between alcohol and risk of cataract among Chinese men in observational analyses, which was supported by the present genetic analyses.

For several other diseases (for example gastroesophageal reflux disease and gastric ulcer), the observational findings provide additional evidence to the existing literature 5 , 45 , 46 , 47 , but the supporting genetic evidence is still constrained by limited statistical power. Similarly, our observational findings for lung and stomach cancers were generally consistent with evidence provided by previous prospective studies 7 , 11 , 48 , 49 ; however, the causal relevance of these associations remains to be elucidated in future larger MR studies with appropriate consideration of the potential gene–environment interactions between ALDH2 - rs671 and alcohol intake (the effect of alcohol intake on cancer risks being modified by ALDH2 - rs671 genotype due to excessive acetaldehyde) 16 and other aldehyde exposures 50 in cancer risks, which might similarly affect the genetic associations for respiratory diseases and other potential acetaldehyde-related diseases. In observational analyses, we found significant inverse associations for inguinal hernia, prostate hyperplasia and other nontoxic goiter, but not for several other diseases previously inversely associated with alcohol drinking, including non-Hodgkin lymphoma 48 , kidney cancer 48 , thyroid cancer 48 and gallstones 51 . The genetic analyses, albeit with limited power, did not provide reliable evidence supporting the inverse associations with these outcomes. Future well-powered genetic investigations are warranted for less-common diseases in different populations.

The strengths of this study include the prospective design, large sample size, detailed information on alcohol consumption and drinking patterns, completeness of follow-up and a wide range of morbidity outcomes analyzed. We were also able to assess the potential causal relevance of the associations using two powerful East Asian genetic variants. Moreover, the extremely low drinking prevalence in women (regardless of their genotypes) enabled assessment for potential pleiotropy, further supporting the genetic findings among men.

Nevertheless, the study also has limitations. First, it is still possible that heavy drinking was under-reported, which could have underestimated the hazards of heavy episodic drinking. Second, as in many population-based cohort studies, extreme problematic drinkers and certain alcohol-related disease events may be under-represented, but this should not affect the assessment of the associations of alcohol with most disease outcomes. Third, while the repeated measures of alcohol consumption available in the re-survey subsets allowed us to estimate long-term usual mean alcohol intake at the group level to account for regression dilution bias, we were unable to study the effects of longitudinal alcohol drinking trajectories on health. Fourth, we were unable or underpowered to study diseases that do not normally require hospitalization (for example dementia and depression), nor alcohol-related diseases only affecting women, given the low proportion of female drinkers (for example <70 cases of breast cancer in female drinkers). While the low female drinking prevalence in CKB was consistent with findings in a nationwide survey 52 , it is possible that women may be more likely to under-report drinking than men for cultural and social reasons. Hence our null findings in women should be interpreted with caution and not be taken as a lack of alcohol-related harms in women in general, especially in the context of rising alcohol consumption among Asian women 2 . Fifth, as spirits were the main beverage type and our genetic instrument did not distinguish between beverage types, we were unable to assess beverage-specific effects on disease risks, including wine consumption, which is uncommon in China 17 and has been proposed as potentially cardioprotective due to other non-alcoholic components in red wine 53 . Sixth, although our genetic analyses allowed comparison of the overall genetic effects of negligible, moderate and high mean alcohol intake levels for major and overall morbidities, we had limited power to confidently clarify any small threshold effects in the low consumption end, especially for individual diseases. Finally, the genetic analyses lacked statistical power to assess the associations with several individual alcohol-associated diseases so these findings should still be viewed as hypothesis-generating.

In recent decades, several studies have estimated the alcohol-attributable disease burden, involving predominantly WHO alcohol-related diseases. These estimates were based mainly on observational evidence and included the potentially biased U- or J-shaped associations with IHD and ischemic stroke 1 , 23 , 54 . We have demonstrated in both conventional and genetic analyses that alcohol drinking is associated with hazards in a dose–response manner with a much wider range of disease outcomes than previously considered by the WHO 4 and the GBD study 23 and do not find any evidence for protective effects for IHD or stroke, suggesting that the actual alcohol-attributable disease burden is likely to be much greater than widely believed.

Overall, the present study demonstrated substantial hazards of alcohol consumption with a wide range of disease outcomes among Chinese men. The findings reinforce the need to lower population mean levels of alcohol consumption as a public health priority in China. Future estimation of the alcohol-attributable disease burden worldwide and in specific regions should incorporate new genetic evidence from the present and any future studies about the likely causal relevance of alcohol consumption for a broad range of disease outcomes.

Study population

Details of the CKB study design and methods have been previously reported 55 . Briefly, 512,724 adults aged 30–79 years were recruited from ten geographically diverse (five rural and five urban) areas across China during 2004–2008. At local study assessment clinics, trained health workers administered a laptop-based questionnaire recording sociodemographic factors, lifestyle (for example alcohol drinking, smoking, diet and physical activity) and medical history; undertook physical measurements (for example blood pressure and anthropometry); and collected a blood sample for long-term storage. Two resurveys of ~5% randomly selected surviving participants were subsequently conducted in 2008 and 2013–2014 using similar procedures.

Ethics approval

Ethical approval was obtained from the Ethical Review Committee of the Chinese Centre for Disease Control and Prevention (Beijing, China, 005/2004) and the Oxford Tropical Research Ethics Committee, University of Oxford (UK, 025-04). All participants provided written informed consent.

Assessment of alcohol consumption

Detailed questionnaire assessment of alcohol consumption has been described previously 3 , 17 , 56 . In the baseline questionnaire, participants were asked how often they had drunk alcohol during the past 12 months (never or almost never, occasionally, only at certain seasons, every month but less than weekly or usually at least once a week). Those who had not drunk alcohol at least weekly in the past 12 months were asked whether there was a period of at least a year before that when they had drunk some alcohol at least once a week. Based on their past and current drinking history, participants were classified into: non-drinkers (had never drunk alcohol in the past year and had not drunk in most weeks in the past); ex-drinkers (had not drunk alcohol in most weeks in the past year but had done so in the past); occasional drinkers (had drunk alcohol but less than weekly in the past year and had not drunk alcohol in most weeks in the past); and current drinkers (had drunk alcohol on a weekly basis (regularly) in the past year).

Current drinkers were asked further questions about their drinking patterns, including frequency, beverage type (beer, grape wine, rice wine, weak spirits with <40% alcohol content and strong spirits with ≥40% alcohol content) and amount consumed on a typical drinking day, mealtime drinking habits, age started drinking in most week and their experience of flushing or dizziness after drinking.

Alcohol intake level was estimated based on the reported frequency (taken as the median of the reported frequency intervals; 1.5 for 1–2 d per week, 4 for 3–5 d per week, 6.5 for 6–7 d per week), beverage type and amount consumed, assuming the following alcohol content by volume (v/v) typically seen in China: beer 4%, grape wine 12%, rice wine 15%, weak spirits 38% and strong spirits 53% 57 . Among current drinkers, men were grouped into four consumption categories (<140, 140–279, 280–419 and 420+ g per week) and women into three categories (<70, 70–139 and 140+ g per week), broadly based on the recommended cutoffs for alcohol categories by the WHO 58 and national drinking guidelines. Heavy episodic drinking was defined as consuming >60 g of alcohol on a typical drinking occasion for men and >40 g per occasion for women 58 . Drinking outside of meals was defined as usually drinking between or after meals or having no regular patterns (versus usually drinking with meals). Duration of drinking was derived by the difference in years between age at baseline and age started drinking.

Ex-drinkers were asked how long (in years) ago they had stopped drinking in most weeks. Ex-drinkers were grouped with current drinkers as ‘ever-regular drinkers’.

Follow-up for mortality and morbidity

The vital status of participants was obtained periodically from local death registries, supplemented by annual active confirmation through local residential, health insurance and administrative records. Additional information on morbidity was collected through linkage with disease registries (for cancer, stroke, IHD and diabetes) and the national health insurance system, which record any episodes of hospitalization and almost has universal coverage. All events were coded with ICD-10 codes, blinded to the baseline information. By 1 January 2019, 56,550 (11%) participants had died, 311,338 (61%) were ever hospitalized, but only 4,028 (<1%) were lost to follow-up.

Outcome measures

To enable a ‘phenome-wide’ investigation, all recorded diseases and injuries (referred to as ‘diseases’ for simplicity) coded by three-character ICD-10 codes were reviewed. ICD-10 codes were combined (where appropriate) based on disease characteristics and their potential relationships with alcohol consumption 4 , 8 , 10 , 59 . Disease end points were curated based on diseases considered to be causally impacted by alcohol by the WHO 4 , 59 and major diseases previously shown to be related to alcohol in CKB and other large prospective cohort studies 8 , 10 , while retaining maximal granularity. Diseases with at least 80 cases recorded during follow-up among current drinkers, separately by sex, were analyzed individually to capture a wide range of specific conditions while ensuring reasonable statistical power (around 60–80% power to detect a HR of 2.00 per 280 g per week higher usual alcohol intake at P  < 0.01 and P  < 0.05, respectively). Within each ICD-10 chapter, diseases with <80 events were grouped into a ‘less-common’ category. Several ICD-10 chapters considered not directly relevant in this population (for example perinatal-origin diseases (chapter XVI) and congenital conditions (XVII); pregnancy-related diseases (XV) in men) were excluded.

Major diseases defined by the WHO as likely to be causally related with alcohol consumption 4 , including several cancers (mouth and throat, esophagus, colon-rectum, liver and female breast), diabetes mellitus, IHD, stroke, liver cirrhosis and external causes, were also selected a priori for detailed analyses of associations with drinking patterns (daily drinking, heavy episodic drinking, mealtime habit, spirit drinking and drinking duration). Similarly, diseases that were significantly and adversely associated with alcohol in the ‘phenome-wide’ investigations (either with ever-regular versus occasional drinking or in dose–response associations with amounts consumed) were further categorized as ‘CKB WHO alcohol-related diseases’ and ‘CKB new alcohol-associated diseases’ respectively for genetic investigation of causality. Detailed outcome classifications are reported in Supplementary Table 7 .

Genotyping and alcohol genetic instruments

The two East Asian genetic variants ( ALDH2 - rs671 and ADH1B - rs1229984 ) were genotyped in 168,050 participants (151,347 randomly selected, 16,703 selected as part of nested case–control studies of CVD and chronic obstructive pulmonary disease, which were only included in analyses of relevant outcomes; Supplementary Fig. 1 ) using Affymetrix Axiom ( n  = 100,396) or custom Illumina GoldenGate ( n  = 93,125) arrays at BGI (Shenzhen, China), with some overlap between them. Among 25,471 participants genotyped with both arrays, the concordance was >99.9% for both variants. Where discordant, genotypes obtained from the Affymetrix Axiom array were used.

The genetic instrument for alcohol was derived from ALDH2 - rs671 and ADH1B - rs1229984 and ten study areas from the random genotyped subset of male participants to avoid potential selection bias, using a previously developed method in CKB 19 . Briefly, nine genotype combinations were defined based on the genotypes for each of the two variants (each AA, AG or GG). As alcohol use varies greatly by study area, among men, mean alcohol intake was calculated for each of these nine genotype across ten study areas (that is a total of 90 genotype-area combinations) to reflect a wide range of alcohol consumption, assigning an intake of 5 g per week to occasional drinkers and excluding ex-drinkers from the calculation. Ex-drinkers were excluded from the calculation of mean alcohol intake as their baseline intake did not reflect their long-term intake; nevertheless, they were included in subsequent genetic analyses once they had been assigned a genetic group. These 90 combinations were then grouped into six categories (C1–C6) according to their corresponding mean intake values, at cutoff points of 10, 25, 50, 100 and 150 g per week, selected to facilitate investigation of the causal effects of alcohol across a wide range of mean alcohol intakes while allowing adequate sample size in each category for reliable comparisons. In this way participants (including ex-drinkers) were classified only based on their genotypes and study area, but not on individual self-reported drinking patterns. Comparisons of these six genetic categories can, where analyses are stratified by area, be used to estimate the genotypic effects on disease risks.

To facilitate the comparison of genotypic effects between sexes (pleiotropic effects), women were classified into the same six categories as men based on their genotypes and study area, regardless of female alcohol intake. This allowed comparison of genotypic effects between men (where genotype were strongly associated with alcohol intake) and women (where alcohol intake was low in all genotypic categories) (Supplementary Tables 10 and 11 ).

Statistical analysis

Given the extremely low alcohol use among women 3 , 17 , the analyses were conducted separately by sex but focused chiefly on men. All CKB participants and the genotyped subset with genomic principal components (PCs; derived from genome-wide genotyping array data and were informative for CKB population structure) 60 were included in conventional and genetic analyses, respectively (Supplementary Fig. 1 ). Means and percentages of baseline characteristics were calculated by self-reported alcohol consumption patterns and by genotype categories, adjusted for age (in 10-year intervals), ten study areas and (for genetic analysis) genomic PCs 60 to control for differences in genetic distribution due to population stratification, as appropriate.

For conventional observational analyses, Cox proportional hazard models were used to estimate HRs for individual diseases associated with different alcohol consumption categories (in three broad categories: occasional drinkers, ever-regular drinkers, non-drinkers; and in 6–7 detailed categories: occasional drinkers, ex-drinkers, non-drinkers, 3–4 further current drinker groups defined by alcohol intake level) and among current drinkers with continuous levels of alcohol intake (per 280 g per week in men, per 100 g per week in women) or with categories of alcohol intake (<140, 140–279, 280–419 and 420+ g per week in men; <70, 70–139 and 140+ g per week in women). The Cox models were stratified by age at risk (5-year groups between 35–84 years) and ten areas and adjusted for education (four groups: no formal school, primary school, middle or high school and technical school/college or above) and smoking status (six groups in men: never, occasional, ex-regular, current <15, current 15–24, current ≥25 cigarettes equivalent per day; four groups in women: never, occasional, ex-regular and current). Smoking data have been previously validated against exhaled carbon monoxide 61 . Competing risks from all-cause mortality for disease events were handled by censoring participants at death from any cause to estimate cause-specific HRs comparing event rates in participants who were alive and free of the disease of interest 62 . To reduce biases from residual confounding and uncontrolled reverse causation related to the choice of using non-drinkers (for example sick-quitter effect, pre-existing poor health or social disadvantages leading to alcohol cessation or abstinence) as the reference group 3 , 29 , we used occasional drinkers as the reference group, together with separate dose–response analyses among current drinkers. To account for within-person variation of alcohol intake over the follow-up period, repeat alcohol measures for participants who attended the two resurveys were used to estimate usual alcohol intake (Supplementary Table 1 ) and correct for regression dilution bias 9 , 63 . The shapes of dose–response associations between alcohol and disease risks were assessed among current drinkers by plotting the HRs of predefined baseline consumption categories against the corresponding mean usual alcohol intake. Log HR estimates and the corresponding standard errors for baseline alcohol intake, modeled as a continuous variable, were divided by the regression dilution ratio (0.53 for both men and women; calculated using the McMahon–Peto method 64 ) to obtain estimated HRs per 280 g per week higher usual alcohol intake among male current drinkers and HRs per 100 g per week among female current drinkers. For analyses involving drinking patterns, additional adjustments were conducted for total alcohol intake (continuous) and baseline age (continuous; for drinking duration analysis) where appropriate.

Sensitivity analyses were performed by (1) additional adjustments for further covariates (household income (<10,000, 10,000–19,999, 20,000–34,999 and ≥35,000 yuan per year), fresh fruit intake (4–7 d per week and ≤3 d per week), physical activity (continuous, in metabolic equivalent of task per hour per day), body mass index (<22, 22–24.9, 25–26.9 and ≥27 kg m 2 ); and (2) excluding individuals with poor self-reported health or previous major chronic diseases (including self-reported coronary heart diseases, stroke, transient ischemic attack, tuberculosis, emphysema or bronchitis, liver cirrhosis or chronic hepatitis, peptic ulcer, gallstone or gallbladder disease, kidney disease, rheumatoid arthritis, cancer and diabetes) at baseline. For all aggregated end points (for example CKB WHO alcohol-related, CKB new alcohol-associated and all morbidity), subgroup analyses were conducted by baseline age (<55, 55–64 and ≥65 years), area (urban and rural), education (primary school or below, middle school, high school or above), household income (<10,000, 10,000–19,999 and 20,000+ yuan per year) and smoking status (ever-regular and never-regular), with heterogeneity or trend assessed by chi-squared tests 65 . HRs for diseases associated with years of stopping among ex-drinkers compared to occasional drinkers were also estimated.

In genetic analyses, Cox regression, stratified by age at risk and study area and adjusted for 11 genomic PCs 60 , were used to estimate HRs for major alcohol-related diseases associated with the six genetic categories (C1–C6). Log HRs were plotted against the genotype-predicted mean male alcohol intake in the six categories. To control for potential confounding by population structure, similar analyses were repeated within each study area using age-at-risk-stratified and genomic PC-adjusted Cox models. A line of best fit was fitted through the log HRs against genotype-predicted mean male alcohol intake in the genetic categories present in the corresponding study area, using meta-regression. These within-area slopes (each reflecting purely genotypic effects) were combined by inverse-variance-weighted meta-analysis to yield the overall area-stratified genotypic associations, which controlled for any potential bias resulted from variations due to population structure, summarized as HR per 280 g per week higher genotype-predicted mean male alcohol intake. For total morbidity and aggregated alcohol-associated outcomes, sensitivity analyses were performed by (1) using age-at-risk- and area-stratified and genomic PC-adjusted Cox models to estimate HR per 280 g per week (area-adjusted genotypic associations); and (2) using a two-stage least-squares approach 66 .

Genotypic analyses in women were conducted not to assess the health effects of alcohol in women, but to investigate the extent to which the genotypes studied in men had pleiotropic effects (genotypic effects not mediated by drinking patterns). As few women consumed alcohol, any genotypic effects of the six genetic categories that are mediated by drinking alcohol should be much smaller in women than in men, but any other pleiotropic genotypic effects should be similar in both sexes. Hence, among women, we used the same genetic categories as in men and related the genotypic effects in women to the mean male alcohol intake in these six categories, which allows comparisons of genetic findings by sex and assessment of potential pleiotropy. To further remove the small genotypic effects on alcohol use in women (Supplementary Tables 10 and 11 ), we restricted the genetic analyses to female non-drinkers in sensitivity analyses.

The genotypic associations of individual genetic variants ( rs671 , rs1229984 ; GG versus AG genotype) with alcohol-related disease risks were also assessed using a similar area-stratified approach.

The proportional hazards assumption was tested using scaled Schoenfeld residuals for the pre-specified major diseases (no clear evidence of violation was found). For analyses involving more than two exposure categories, the floating absolute risks were used to estimate group-specific 95% CIs for all categories including the reference group 9 , 19 , 67 . All P values were two-sided. Statistical significance (at the 5% level) was evaluated using both FDR-adjusted P values applied within ICD-10 chapters to correct for multiple testing in the ‘phenome-wide’ investigation 68 , 69 , 70 and conventional P values for hypothesis testing for observational analyses of WHO alcohol-related diseases, analyses of drinking patterns and genetic analyses.

To assess the cumulative burden of alcohol consumption, the total number of hospitalizations were estimated for ever-regular versus occasional drinkers using the mean cumulative count, which does not assume independence between hospitalizations and all-cause mortality 71 , 72 , 73 . All analyses used R software (v.4.0.5).

Ethics and inclusion statement

In accordance with the Nature Portfolio journals’ editorial policies, the research has included local researchers from China throughout the research process, including study design, study implementation, data ownership and authorship. The roles and responsibilities were agreed among collaborators ahead of the research and capacity-building plans, including data collection and study implementation skills for local researchers, were discussed and delivered. This research is locally relevant to the studied country and included local collaborative partners in all aspects of the study, thus, will provide local and regional organizations with epidemiological evidence on the health impacts of alcohol consumption to inform public health policies.

This research was not restricted nor prohibited in the setting of the researchers. The study was approved by local ethics review committee. The research raised no risks related to stigmatization, incrimination, discrimination, animal welfare, the environment, health, safety, security or other personal or biorisks. No biological materials, cultural artifacts or associated traditional knowledge has been transferred out of the country. In preparing the manuscript, the authors have reviewed and cited local and regional relevant studies.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

Data availability

The CKB is a global resource for the investigation of lifestyle, environmental, blood biochemical and genetic factors as determinants of common diseases. The CKB study group is committed to making the cohort data available to the scientific community in China, the United Kingdom and worldwide to advance knowledge about the causes, prevention and treatment of disease. For detailed information on what data are currently available to open access users, how to apply for them and the timeline for data access (12–16 weeks), please visit the CKB website: https://www.ckbiobank.org/data-access . Researchers who are interested in obtaining the raw data from the CKB study that underlines this paper should contact [email protected]. A research proposal will be requested to ensure that any analysis is performed by bona fide researchers and, where data are not currently available to open access researchers, is restricted to the topic covered in this paper. Further information is available from the corresponding authors upon request.

Code availability

The codes used for the data analyses in this study can be made available by contacting the corresponding authors. Access to codes will be granted for requests for academic use within 4 weeks of application.

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Acknowledgements

The chief acknowledgment is to the participants, the project staff and the China National Centre for Disease Control and Prevention (CDC) and its regional offices for assisting with the fieldwork. We thank J. Mackay in Hong Kong; Y. Wang, G. Yang, Z. Qiang, L. Feng, M. Zhou, W. Zhao. and Y. Zhang in China CDC; L. Kong, X. Yu and K. Li in the Chinese Ministry of Health; and S. Clark, M. Radley and M. Hill in the CTSU, Oxford, for assisting with the design, planning, organization and conduct of the study. A complete list of members of the China Kadoorie Collaborative Group is provided in the Supplementary Information. The CKB baseline survey and the first re-survey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up of the CKB study has been supported by Wellcome grants to Z.C. at Oxford University (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z) and grants to L.L. from the National Natural Science Foundation of China (82192901, 82192904 and 82192900) and from the National Key Research and Development Program of China (2016YFC0900500). DNA extraction and genotyping was supported by grants to Z.C. from GlaxoSmithKline and the UK Medical Research Council (MC-PC-13049, MC-PC-14135). The UK Medical Research Council (MC_UU_00017/1, MC_UU_12026/2, MC_U137686851), Cancer Research UK (C16077/A29186; C500/A16896) and the British Heart Foundation (CH/1996001/9454) provide core funding to the CTSU and Epidemiological Studies Unit at Oxford University for the project. P.K.I. is supported by an Early Career Research Fellowship from the Nuffield Department of Population Health, University of Oxford. K.H.C. acknowledges support from the British Heart Foundation Centre of Research Excellence, University of Oxford (RE/18/3/34214). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. For the purpose of Open Access, the author has applied a CC-BY public copyright license to any author accepted manuscript version arising from this submission.

Author information

These authors jointly supervised this work: Liming Li, Zhengming Chen, Iona Y. Millwood.

Authors and Affiliations

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK

Pek Kei Im, Neil Wright, Ling Yang, Ka Hung Chan, Yiping Chen, Huaidong Du, Xiaoming Yang, Daniel Avery, Robert Clarke, Rory Collins, Robin G. Walters, Richard Peto, Zhengming Chen, Iona Y. Millwood, Maxim Barnard, Derrick Bennett, Ruth Boxall, Johnathan Clarke, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Dan Schmidt, Becky Stevens, Iain Turnbull, Baihan Wang, Lin Wang & Pang Yao

Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK

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  • , Zhengming Chen
  • , Robert Clarke
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  • , Maria Kakkoura
  • , Christiana Kartsonaki
  • , Hubert Lam
  • , Kuang Lin
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  • , Saredo Said
  • , Dan Schmidt
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Contributions

P.K.I., I.Y.M., L.Y. and Z.C. contributed to the conception of this paper. P.K.I., N.W., K.H.C., I.Y.M. and Z.C. planned the statistical analysis. P.K.I. analyzed the data and drafted the manuscript. P.K.I., I.Y.M. and Z.C. contributed to the interpretation of the results and the revision of manuscript. R. Collins, R.P., J.C., L.L. and Z.C. designed the study. L.L., Z.C., I.Y.M., L.Y., Y.C., Y.G., H.D., S.W., C.Y., J.L., J.C., R. Collins, R. Clarke and R.G.W. contributed to data acquisition and general study management. X.Y. and D.A. provided administrative and technical support. All authors critically reviewed the manuscript and approved the final submission.

Corresponding authors

Correspondence to Zhengming Chen or Iona Y. Millwood .

Ethics declarations

Competing interests.

The authors declare no competing interests.

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Nature Medicine thanks Shiu Lun Au Yeung, Yan-Bo Zhang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Ming Yang, in collaboration with the Nature Medicine team.

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Extended data

Extended data fig. 1 adjusted hrs for icd−10 chapter−specific morbidities associated with ever-regular drinking and with usual alcohol intake, in men..

Cox models comparing ever-regular drinkers with occasional drinkers, or assessing the dose–response per 280 g/week higher usual alcohol intake within current drinkers, were stratified by age-at-risk and study area and adjusted for education and smoking. Each solid square or diamond represents HR with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. CI, confidence interval; HR hazard ratio; ICD-10, International Classification of Diseases, 10th Revision.

Extended Data Fig. 2 Adjusted HRs for different aggregated and all-cause morbidities associated with years after stopping drinking, in men.

Cox models comparing ex-drinker groups with occasional drinkers were stratified by age-at-risk and study area and were adjusted for education and smoking. Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard within subplot. The vertical lines indicate group-specific 95% CIs for various ex-drinker groups. The shaded strip indicate the group-specific 95% CIs for occasional drinkers. The numbers above the error bars are point estimates for HRs. CI, confidence interval; HR hazard ratio; CKB, China Kadoorie Biobank; WHO, World Health Organization.

Extended Data Fig. 3 Associations of alcohol consumption with risks of 28 diseases previously defined as alcohol-related by the WHO, in male current drinkers.

Cox models were stratified by age-at-risk and study area and were adjusted for education and smoking. HRs were plotted against usual alcohol intake and were calculated per 280 g/week higher usual alcohol intake. All specific diseases displayed were significantly associated with alcohol intake (ever-regular drinking or per 280 g/week higher usual alcohol intake) after multiple testing correction (FDR-adjusted p<0.05), except transient cerebral ischemic attacks and related syndromes (ICD-10 code: G45), occlusion and stenosis of precerebral arteries (I65) and pancreatitis (K85-K86) which showed statistical significance at nominal level (p<0.05). Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard within subplot. The vertical lines indicate group-specific 95% CIs. The numbers above the error bars are point estimates for HRs and the numbers below are number of events. All P values are two-sided. CI, confidence interval; HR hazard ratio; CKB, China Kadoorie Biobank; FDR, false discovery rate; ICD-10, International Classification of Diseases, 10th Revision; WHO, World Health Organization.

Extended Data Fig. 4 Associations of alcohol consumption with risks of 36 diseases not previously defined as alcohol-related, in male current drinkers.

Cox models were stratified by age-at-risk and study area and were adjusted for education and smoking. HRs were plotted against usual alcohol intake and were calculated per 280 g/week higher usual alcohol intake. All specific diseases displayed were significantly associated with alcohol intake (ever-regular drinking or per 280 g/week higher usual alcohol intake) after multiple testing correction (FDR-adjusted p<0.05). Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard within subplot. The vertical lines indicate group-specific 95% CIs. The numbers above the error bars are point estimates for HRs and the numbers below are number of events. All P values are two-sided. CI, confidence interval; HR hazard ratio; CKB, China Kadoorie Biobank; FDR, false discovery rate.

Extended Data Fig. 5 Adjusted HRs for major diseases associated with drinking patterns, in male current drinkers.

Cox models were stratified by age-at-risk and study area and were adjusted for education and smoking and for total alcohol intake where indicated. Each solid square or diamond represents HR with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. CI, confidence interval; HR hazard ratio; HED, heavy episodic drinking; CKB, China Kadoorie Biobank; WHO, World Health Organization.

Extended Data Fig. 6 Adjusted HRs for major diseases associated with duration of drinking, in male current drinkers.

Cox models were stratified by age-at-risk and study area and were adjusted for education, smoking, total alcohol intake and baseline age in (A). (B) had the same model specifications as (A) plus further adjustments for income, physical activity, fruit intake and body mass index. (C) had the same model specifications as (A) and excluded participants with poor self-reported health or prior chronic disease at baseline. Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard. The horizontal lines indicate group-specific 95% CIs. All P values are two-sided. CI, confidence interval; HR hazard ratio; CKB, China Kadoorie Biobank; WHO, World Health Organization.

Extended Data Fig. 7 Adjusted HRs for ICD−10 chapter−specific morbidities associated with ever-regular drinking and with usual alcohol intake, in women.

Cox models comparing ever-regular drinkers with occasional drinkers, or assessing the dose–response per 100 g/week higher usual alcohol intake within current drinkers, were stratified by age-at-risk and study area and adjusted for education and smoking. Each solid square or diamond represents HR with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. CI, confidence interval; HR hazard ratio; ICD-10, International Classification of Diseases, 10th Revision.

Extended Data Fig. 8 Adjusted HRs per 280 g/week higher genotype-predicted mean male alcohol intake for specific alcohol-associated diseases by ICD-10 chapters, in men and women.

Cox modes, stratified by age-at-risk and adjusted for genomic principal components, were used to relate genetic categories to risks of diseases within each study area. The HR per 280 g/week higher genotype-predicted mean male alcohol intake was calculated from the inverse-variance-weighted mean of the slopes of the fitted lines in each study area. Each solid square or diamond represents HR per 280 g/week higher genetically-predicted mean male alcohol intake, with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. Diseases considered to be alcohol-related by the WHO are indicated with ‘Y’ under the ‘WHO’ column. The ‘RC’ column indicates the number of study areas that contributed to the overall area-stratified genotypic associations, as for certain less common diseases some study areas may not have enough number of cases to contribute to the inverse-variance-weighted meta-analysis. The ‘P het’ column indicates the p-value from a \(\chi\) 2 test for heterogeneity between sexes. All P values are two-sided. † Included less common ICD-10 codes within the corresponding ICD-10 chapter which were not individually investigated in the present study. CI, confidence interval; HR hazard ratio; ICD-10, International Classification of Diseases, 10th Revision; WHO, World Health Organization.

Extended Data Fig. 9 Adjusted HRs associated with GG versus AG genotype of ALDH2 - rs671 for specific alcohol-associated diseases by ICD-10 chapters, in men and women.

Area-specific genotypic effects (GG vs. AG genotype) were estimated within each study area (thus each reflecting the purely genotypic effects) using age-at-risk-stratified and genomic principal components-adjusted Cox models and were combined by inverse-variance-weighted meta-analysis to yield the overall area-stratified genotypic associations. Each solid square represents HR for GG vs. AG genotype, with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. Diseases considered to be alcohol-related by the WHO are indicated with ‘Y’ under the ‘WHO’ column. The ‘RC’ column indicates the number of study areas that contributed to the overall area-stratified genotypic associations, as for certain less common diseases some study areas may not have enough number of cases to contribute to the inverse-variance-weighted meta-analysis. The ‘P het’ column indicates the P value from a \(\chi\) 2 test for heterogeneity between sexes. All P values are two-sided. † Included less common ICD-10 codes within the corresponding ICD-10 chapter which were not individually investigated in the present study. CI, confidence interval; HR hazard ratio; ICD-10, International Classification of Diseases, 10th Revision; WHO, World Health Organization.

Extended Data Fig. 10 Adjusted HRs associated with GG versus AG genotype of ADH1B - rs1229984 for specific alcohol-associated diseases by ICD-10 chapters, in men and women.

Supplementary information, supplementary information.

Supplementary Figs. 1–8 and Supplementary Tables 1–13.

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Im, P.K., Wright, N., Yang, L. et al. Alcohol consumption and risks of more than 200 diseases in Chinese men. Nat Med 29 , 1476–1486 (2023). https://doi.org/10.1038/s41591-023-02383-8

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BMI indicates body mass index; SES, socioeconomic status.

a Variables smoking status, SES, drinking pattern, former drinker bias only, occasional drinker bias, median age, and gender were removed.

b Variables race, diet, exercise, BMI, country, follow-up year, publication year, and unhealthy people exclusion were removed.

eAppendix. Methodology of Meta-analysis on All-Cause Mortality and Alcohol Consumption

eReferences

eFigure 1. Flowchart of Systematic Search Process for Studies of Alcohol Consumption and Risk of All-Cause Mortality

eTable 1. Newly Included 20 Studies (194 Risk Estimates) of All-Cause Mortality and Consumption in 2015 to 2022

eFigure 2. Funnel Plot of Log-Relative Risk (In(RR)) of All-Cause Mortality Due to Alcohol Consumption Against Inverse of Standard Error of In(RR)

eFigure 3. Relative Risk (95% CI) of All-Cause Mortality Due to Any Alcohol Consumption Without Any Adjustment for Characteristics of New Studies Published between 2015 and 2022

eFigure 4. Unadjusted, Partially Adjusted, and Fully Adjusted Relative Risk (RR) of All-Cause Mortality for Drinkers (vs Nondrinkers), 1980 to 2022

eTable 2. Statistical Analysis of Unadjusted Mean Relative Risk (RR) of All-Cause Mortality for Different Categories of Drinkers for Testing Publication Bias and Heterogeneity of RR Estimates From Included Studies

eTable 3. Mean Relative Risk (RR) Estimates of All-Cause Mortality Due to Alcohol Consumption up to 2022 for Subgroups (Cohorts Recruited 50 Years of Age or Younger and Followed up to 60 Years of Age)

Data Sharing Statement

  • Errors in Figure and Supplement JAMA Network Open Correction May 9, 2023

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Zhao J , Stockwell T , Naimi T , Churchill S , Clay J , Sherk A. Association Between Daily Alcohol Intake and Risk of All-Cause Mortality : A Systematic Review and Meta-analyses . JAMA Netw Open. 2023;6(3):e236185. doi:10.1001/jamanetworkopen.2023.6185

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Association Between Daily Alcohol Intake and Risk of All-Cause Mortality : A Systematic Review and Meta-analyses

  • 1 Canadian Institute for Substance Use Research, University of Victoria, Victoria, British Columbia, Canada
  • 2 Department of Psychology, University of Portsmouth, Portsmouth, Hampshire, United Kingdom
  • Correction Errors in Figure and Supplement JAMA Network Open

Question   What is the association between mean daily alcohol intake and all-cause mortality?

Findings   This systematic review and meta-analysis of 107 cohort studies involving more than 4.8 million participants found no significant reductions in risk of all-cause mortality for drinkers who drank less than 25 g of ethanol per day (about 2 Canadian standard drinks compared with lifetime nondrinkers) after adjustment for key study characteristics such as median age and sex of study cohorts. There was a significantly increased risk of all-cause mortality among female drinkers who drank 25 or more grams per day and among male drinkers who drank 45 or more grams per day.

Meaning   Low-volume alcohol drinking was not associated with protection against death from all causes.

Importance   A previous meta-analysis of the association between alcohol use and all-cause mortality found no statistically significant reductions in mortality risk at low levels of consumption compared with lifetime nondrinkers. However, the risk estimates may have been affected by the number and quality of studies then available, especially those for women and younger cohorts.

Objective   To investigate the association between alcohol use and all-cause mortality, and how sources of bias may change results.

Data Sources   A systematic search of PubMed and Web of Science was performed to identify studies published between January 1980 and July 2021.

Study Selection   Cohort studies were identified by systematic review to facilitate comparisons of studies with and without some degree of controls for biases affecting distinctions between abstainers and drinkers. The review identified 107 studies of alcohol use and all-cause mortality published from 1980 to July 2021.

Data Extraction and Synthesis   Mixed linear regression models were used to model relative risks, first pooled for all studies and then stratified by cohort median age (<56 vs ≥56 years) and sex (male vs female). Data were analyzed from September 2021 to August 2022.

Main Outcomes and Measures   Relative risk estimates for the association between mean daily alcohol intake and all-cause mortality.

Results   There were 724 risk estimates of all-cause mortality due to alcohol intake from the 107 cohort studies (4 838 825 participants and 425 564 deaths available) for the analysis. In models adjusting for potential confounding effects of sampling variation, former drinker bias, and other prespecified study-level quality criteria, the meta-analysis of all 107 included studies found no significantly reduced risk of all-cause mortality among occasional (>0 to <1.3 g of ethanol per day; relative risk [RR], 0.96; 95% CI, 0.86-1.06; P  = .41) or low-volume drinkers (1.3-24.0 g per day; RR, 0.93; P  = .07) compared with lifetime nondrinkers. In the fully adjusted model, there was a nonsignificantly increased risk of all-cause mortality among drinkers who drank 25 to 44 g per day (RR, 1.05; P  = .28) and significantly increased risk for drinkers who drank 45 to 64 and 65 or more grams per day (RR, 1.19 and 1.35; P  < .001). There were significantly larger risks of mortality among female drinkers compared with female lifetime nondrinkers (RR, 1.22; P  = .03).

Conclusions and Relevance   In this updated systematic review and meta-analysis, daily low or moderate alcohol intake was not significantly associated with all-cause mortality risk, while increased risk was evident at higher consumption levels, starting at lower levels for women than men.

The proposition that low-dose alcohol use protects against all-cause mortality in general populations continues to be controversial. 1 Observational studies tend to show that people classified as “moderate drinkers” have longer life expectancy and are less likely to die from heart disease than those classified as abstainers. 2 Systematic reviews and meta-analyses of this literature 3 confirm J-shaped risk curves (protective associations at low doses with increasing risk at higher doses). However, mounting evidence suggests these associations might be due to systematic biases that affect many studies. For example, light and moderate drinkers are systematically healthier than current abstainers on a range of health indicators unlikely to be associated with alcohol use eg, dental hygiene, exercise routines, diet, weight, income 4 ; lifetime abstainers may be systematically biased toward poorer health 5 ; studies fail to control for biases in the abstainer reference group, in particular failing to remove “sick quitters” or former drinkers, many of whom cut down or stop for health reasons 2 ; and most studies have nonrepresentative samples leading to an overrepresentation of older White men. Adjustment of cohort samples to make them more representative has been shown to eliminate apparent protective associations. 6 Mendelian randomization studies that control for the confounding effects of sociodemographic and environmental factors find no evidence of cardioprotection. 7

We published 2 previous systematic reviews and meta-analyses that investigated these hypotheses. The first of these focused on all-cause mortality, 8 finding negligible reductions in mortality risk with low-volume alcohol use when study-level controls were introduced for potential bias and confounding, such as the widespread practice of misclassifying former drinkers and/or current occasional drinkers as abstainers (ie, not restricting reference groups to lifetime abstainers). 8 Our alcohol and coronary heart disease (CHD) mortality meta-analysis of 45 cohort studies 9 found that CHD mortality risk differed widely by age ranges and sex of study populations. In particular, young cohorts followed up to old age did not show significant cardio-protection for low-volume use. Cardio-protection was only apparent among older cohorts that are more exposed to lifetime selection biases (ie, increasing numbers of “sick-quitters” in the abstainer reference groups and the disproportionate elimination of drinkers from the study sample who had died or were unwell).

The present study updates our earlier systematic review and meta-analysis for all-cause mortality and alcohol use, 8 including studies published up to July 2021 (ie, 6.5 years of additional publications). The study also investigated the risk of all-cause mortality for alcohol consumption according to (1) median ages of the study populations (younger than 56 years or 56 years and older), replicating the methods of Zhao et al 9 ; (2) the sex distribution of the study populations, and (3) studies of cohorts recruited before a median age of 51 years of age and followed up in health records until a median age of at least 60 years (ie, with stricter rules to further minimize lifetime selection biases). Because younger cohorts followed up to an age at which they may experience heart disease are less likely to be affected by lifetime selection biases, 9 we hypothesized that such studies would be less likely to show reduced mortality risks for low-volume drinkers. Finally, we reran the analyses using occasional drinkers (<1 drink per week) as the reference, for whom physiological health benefits are unlikely. Occasional drinkers are a more appropriate reference group, given evidence demonstrating that lifetime abstainers may be biased toward ill health. 10

The present study updates the systematic reviews and meta-analyses described above 8 by including studies published up to July 2021 to investigate whether the risk differed for subgroups. The study protocol was preregistered on the Open Science Framework. 11 Inclusion criteria, search strategy, study selection, data extraction, and statistical analytical methods of the study are summarized in later sections (see eAppendix in Supplement 1 for more details).

The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guideline. 12 The review sought cohort studies of all-cause mortality and alcohol consumption. We identified all potentially relevant articles published up to July 31, 2021, regardless of language, by searching PubMed and Web of Science, through reference list cross-checking of previous meta-analyses (eFigure 1 in Supplement 1 ). There were 87 studies identified by Stockwell et al. 8 After inclusion of 20 new studies meeting inclusion criteria, there were a total of 107 cohort studies (eTable 1 in Supplement 1 ). 13 - 32

Three coders (J. Z., F. A., and J. C.) reviewed all eligible studies to extract and code data independently from all studies fulfilling the inclusion criteria. Data extracted included (1) outcome, all-cause mortality; (2) measures of alcohol consumption; (3) study characteristics, including cohort ages at recruitment and follow-up; (4) types of misclassification error of alcohol consumers and abstainers; (5) controlled variables in individual studies. Alcoholic drinks were converted into grams per day according to country-specific definitions if not otherwise defined. 33 , 34

We also assessed publication bias, heterogeneity, and confounding of covariates that might potentially affect the association of interest using several statistical approaches. 35 - 41 Relative risk (RR), including hazard ratios or rate ratios, were converted to natural log-transformed formats to deal with skewness. Publication bias was assessed through visual inspection of the funnel plot of log-RR of all-cause mortality due to alcohol consumption against the inverse standard error of log-RR 42 and Egger’s linear regression method. 36 We also plotted forest graphs of log-RR of all-cause mortality for any level of drinking to assess heterogeneity among studies. 42 The between-study heterogeneity of RRs were assessed using Cochran Q 37 and the I 2 statistic. 38 If heterogeneity was detected, mixed-effects models were used to obtain the summarized RR estimates. Mixed-effects regression analyses were performed in which drinking groups and control variables were treated as fixed-effects with a random study effect because of significant heterogeneity. 43

All analyses were weighted by the inverse of the estimated variance of the natural log relative risk. Variance was estimated from reported standard errors, confidence intervals, or number of deaths. The weights for each individual study were created using the inverse variance weight scheme and used in mixed regression analysis to get maximum precision for the main results of the meta-analysis. 42 In comparison with lifetime abstainers, the study estimated the mean RR of all-cause mortality for former drinkers (ie, now completely abstaining), current occasional (<9.1 g per week), low-volume (1.3-24.0 g per day), medium-volume (25.0-44.0 g per day), high-volume (45.0-64.0 g) and highest-volume drinkers (≥65.0 grams per day). The analyses adjusted for the potential confounding effects of study characteristics including the median age and sex distribution of study samples, drinker biases, country where a study was conducted, follow-up years and presence or absence of confounders. Analyses were also repeated using occasional drinkers as the reference group. We used t tests to calculate P values, and significance was set at .05. All statistical analyses were performed using SAS version 9.4 (SAS Institute) and the SAS MIXED procedure was used to model the log-transformed RR. 44 Data were analyzed from September 2021 to August 2022.

There were 724 estimates of the risk relationship between level of alcohol consumption and all-cause mortality from 107 unique studies 13 - 32 , 45 - 131 , including 4 838 825 participants and 425 564 deaths available for the analysis. Table 1 describes the sample characteristics of the metadata. Of 39 studies 13 , 15 , 18 , 21 , 23 - 26 , 29 , 31 , 45 - 47 , 49 , 50 , 52 - 54 , 57 - 59 , 62 , 64 , 70 , 80 , 81 , 85 , 87 , 91 , 94 , 96 , 100 , 104 , 107 , 118 , 124 , 125 , 127 , 130 reporting RR estimates for men and women separately, 33 14 , 17 , 48 , 51 , 61 , 63 , 66 , 68 , 69 , 72 , 76 , 79 , 83 , 84 , 86 , 88 , 90 , 92 , 93 , 97 , 98 , 101 , 103 , 105 , 109 - 111 , 113 - 115 , 119 , 120 , 128 were for males only, 8 16 , 65 , 73 , 99 , 102 , 108 , 112 , 123 for females only, and 30 13 , 19 - 22 , 26 - 30 , 32 , 55 , 56 , 67 , 71 , 74 , 75 , 77 , 78 , 82 , 84 , 89 , 95 , 106 , 116 , 117 , 121 , 122 , 126 , 129 for both sexes. Twenty-one studies 13 , 17 , 19 , 21 , 22 , 26 , 27 , 45 - 58 (220 risk estimates) were free from abstainer bias (ie, had a reference group of strictly defined lifetime abstainers). There were 50 studies 14 - 16 , 18 , 20 , 23 - 25 , 29 , 59 - 99 (265 risk estimates) with both former and occasional drinker bias; 28 studies 28 , 30 - 32 , 100 - 122 , 130 (177 risk estimates) with only former drinker bias; and 8 studies 123 - 129 , 131 (62 risk estimates) with only occasional drinker bias.

Unadjusted mean RR estimates for most study subgroups categorized by methods/sample characteristics showed markedly or significantly higher RRs for alcohol consumers as a group vs abstainers. Exceptions were for studies with less than 10 years of follow-up and those with some form of abstainer bias ( Table 1 ). Bivariable analyses showed that mortality risks for alcohol consumers varied considerably according to other study characteristics, such as quality of the alcohol consumption measure, whether unhealthy individuals were excluded at baseline, and whether socioeconomic status was controlled for ( Table 1 ).

No evidence of publication bias was detected either by inspection of symmetry in the funnel plot of log-RR estimates and their inverse standard errors (eFigure 2 in Supplement 1 ) or by Egger linear regression analysis (eTable 2 in Supplement 1 , all P > .05 for each study group). Significant heterogeneity was observed across studies for all drinking categories confirmed by both the Q statistic ( Q 723  = 5314.80; P  < .001) and I 2 estimates (all >85.87%). (See eFigure 3 in Supplement 1 for forest plot of unadjusted risk estimates of mortality risks for the 20 newly identified studies).

Pooled unadjusted estimates (724 observations) showed significantly higher risk for former drinkers (RR, 1.22; 95% CI, 1.11-1.33; P  = .001) and significantly lower risk for low-volume drinkers (RR, 0.85; 95% CI, 0.81-0.88; P  = .001) compared with abstainers as defined in the included studies ( Table 2 ; eFigure 4 in Supplement 1 ). In the fully adjusted model, mortality RR estimates increased for all drinking categories, becoming nonsignificant for low-volume drinkers (RR, 0.93; 95% CI, 0.85-1.01; P  = .07), occasional drinkers (>0 to <1.3 g of ethanol per day; RR, 0.96; 95% CI, 0.86-1.06; P  = .41), and drinkers who drank 25 to 44 g per day (RR, 1.05; 95% CI, 0.96-1.14; P  = .28). There was a significantly increased risk among drinkers who drank 45 to 64 g per day (RR, 1.19; 95% CI, 1.07-1.32; P  < .001) and 65 or more grams (RR, 1.35; 95% CI, 1.23-1.47; P  < .001). The Figure shows the changes in RR estimates for low-volume drinkers when removing each covariate from the fully adjusted model. In most cases, removing study-level covariates tended to yield lower risk estimates from alcohol use.

Table 2 presents the RR estimates when occasional drinkers were the reference group. In fully adjusted models, higher though nonsignificant mortality risks were observed for both abstainers and medium-volume drinkers (RR, 1.04; 95% CI, 0.94-1.16; P  = .44 and RR, 1.09; 95% CI, 0.96-1.25; P  = .19, respectively). There were significantly elevated risks for both high and higher volume drinkers (RR, 1.24; 95% CI, 1.07-1.44; P  = .004 and RR, 1.41; 95% CI, 1.23-1.61; . P  = 001, respectively).

As hypothesized, there was a significant interaction between cohort age and mortality risk ( P  = .02; F 601  = 2.93) and so RR estimates for drinkers were estimated in analyses stratified by median age of the study populations at enrollment ( Table 3 ). In unadjusted and partially adjusted analyses, older cohorts displayed larger reductions in mortality risk associated with low-volume consumption than younger cohorts. However, in fully adjusted analyses with multiple covariates included for study characteristics, these differences disappeared. Younger cohorts also displayed greater mortality risks than older cohorts at higher consumption levels. Among studies in which participants were recruited at age 50 years or younger and followed up to age 60 years (ie, there was likely reduced risk of lifetime selection bias) higher RR estimates were observed for all drinking groups vs lifetime abstainers. These differences were significant in all drinking groups except low-volume drinkers (eTable 3 in Supplement 1 ).

Across all levels of alcohol consumption, female drinkers had a higher RR of all-cause mortality than males ( P for interaction  = .001). As can be seen in Table 4 , all female drinkers had a significantly increased mortality risk compared with female lifetime nondrinkers (RR, 1.22; 95% CI, 1.02-1.46; P  = .03). Compared with lifetime abstainers, there was significantly increased risk of all-cause mortality among male drinkers who drank 45 to 64 g per day (RR, 1.15; 95% CI, 1.03-1.28; P  = .01) and drank 65 or more (RR, 1.34; 95% CI, 1.23-1.47; P  < .001), and among female drinkers who drank 25 to 44 g per day (RR, 1.21; 95% CI, 1.08-1.36; P  < .01), 45 to 64 g (RR, 1.34; 95% CI, 1.11-1.63; P  < .01) and 65 or more grams (RR, 1.61; 95% CI, 1.44-1.80; P  = .001).

In fully adjusted, prespecified models that accounted for effects of sampling, between-study variation, and potential confounding from former drinker bias and other study-level covariates, our meta-analysis of 107 studies found (1) no significant protective associations of occasional or low-volume drinking (moderate drinking) with all-cause mortality; and (2) an increased risk of all-cause mortality for drinkers who drank 25 g or more and a significantly increased risk when drinking 45 g or more per day.

Several meta-analytic strategies were used to explore the role of abstainer reference group biases caused by drinker misclassification errors and also the potential confounding effects of other study-level quality covariates in studies. 2 Drinker misclassification errors were common. Of 107 studies identified, 86 included former drinkers and/or occasional drinkers in the abstainer reference group, and only 21 were free of both these abstainer biases. The importance of controlling for former drinker bias/misclassification is highlighted once more in our results which are consistent with prior studies showing that former drinkers have significantly elevated mortality risks compared with lifetime abstainers.

In addition to presenting our fully adjusted models, a strength of the study was the examination of the differences in relative risks according to unadjusted and partially adjusted models, including the effect of removing individual covariates from the fully adjusted model. We found evidence that abstainer biases and other study characteristics changed the shape of the risk relationship between mortality and rising alcohol consumption, and that most study-level controls increased the observed risks from alcohol, or attenuated protective associations at low levels of consumption such that they were no longer significant. The reduced RR estimates for occasional or moderate drinkers observed without adjustment may be due to the misclassification of former and occasional drinkers into the reference group, a possibility which is more likely to have occurred in studies of older cohorts which use current abstainers as the reference group. This study also demonstrates the degree to which observed associations between consumption and mortality are highly dependent on the modeling strategy used and the degree to which efforts are made to minimize confounding and other threats to validity.

It also examined risk estimates when using occasional drinkers rather than lifetime abstainers as the reference group. The occasional drinker reference group avoids the issue of former drinker misclassification that can affect the abstainer reference group, and may reduce confounding to the extent that occasional drinkers are more like low-volume drinkers than are lifetime abstainers. 2 , 8 , 132 In the unadjusted and partially adjusted analyses, using occasional drinkers as the reference group resulted in nonsignificant protective associations and lower point estimates for low-volume drinkers compared with significant protective associations and higher point estimates when using lifetime nondrinkers as the reference group. In the fully adjusted models, there were nonsignificant protective associations for low-volume drinkers whether using lifetime abstainers or occasional drinkers as the reference group, though this was only a RR of 0.97 for the latter.

Across all studies, there were few differences in risk for studies when stratified by median age of enrollment above or below age 56 years in the fully adjusted analyses. However, in the subset of studies who enrolled participants aged 50 years or younger who were followed for at least 10 years, occasional drinkers and medium-volume drinkers had significantly increased risk of mortality and substantially higher risk estimates for high- and higher-volume consumption compared with results from all studies. This is consistent with our previous meta-analysis for CHD, 9 in which younger cohorts followed up to older age did not show a significantly beneficial association of low-volume consumption, while older cohorts, with more opportunity for lifetime selection bias, showed marked, significant protective associations.

Our study also found sex differences in the risk of all-cause mortality. A larger risk of all-cause mortality for women than men was observed when drinking 25 or more grams per day, including a significant increase in risk for medium-level consumption for women that was not observed for men. However, mortality risk for mean consumption up to 25 g per day were very similar for both sexes.

A number of limitations need to be acknowledged. A major limitation involves imperfect measurement of alcohol consumption in most included studies, and the fact that consumption in many studies was assessed at only 1 point in time. Self-reported alcohol consumption is underreported in most epidemiological studies 133 , 134 and even the classification of drinkers as lifetime abstainers can be unreliable, with several studies in developed countries finding that the majority of self-reported lifetime abstainers are in fact former drinkers. 135 , 136 If this is the case, the risks of various levels of alcohol consumption relative to presumed lifetime abstainers are underestimates. Merely removing former drinkers from analyses may bias studies in favor of drinkers, since former drinkers may be unhealthy, and should rightly be reallocated to drinking groups according to their history. However, this has only been explored in very few studies. Our study found that mortality risk differed significantly by cohort age and sex. It might be that the risk is also higher for other subgroups, such as people living with HIV, 137 a possibility future research should investigate.

The number of available studies in some stratified analyses was small, so there may be limited power to control for potential study level confounders. However, the required number of estimates per variable for linear regression can be much smaller than in logistic regression, and a minimum of at least 2 estimates per variable is recommended for linear regression analysis, 138 suggesting the sample sizes were adequate in all models presented. It has been demonstrated that a pattern of binge (ie, heavy episodic) drinking removes the appearance of reduced health risks even when mean daily volume is low. 139 Too few studies adequately controlled for this variable to investigate its association with different outcomes across studies. Additionally, our findings only apply to the net effect of alcohol at different doses on all-cause mortality, and different risk associations likely apply for specific disease categories. The biases identified here likely apply to estimates of risk for alcohol and all diseases. It is likely that correcting for these biases will raise risk estimates for many types of outcome compared with most existing estimates.

This updated meta-analysis did not find significantly reduced risk of all-cause mortality associated with low-volume alcohol consumption after adjusting for potential confounding effects of influential study characteristics. Future longitudinal studies in this field should attempt to minimize lifetime selection biases by not including former and occasional drinkers in the reference group, and by using younger cohorts (ie, age distributions that are more representative of drinkers in the general population) at baseline.

Accepted for Publication: February 17, 2023.

Published: March 31, 2023. doi:10.1001/jamanetworkopen.2023.6185

Correction: This article was corrected on May 9, 2023, to fix errors in the Figure and Supplement.

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Zhao J et al. JAMA Network Open .

Corresponding Author: Jinhui Zhao, PhD, Canadian Institute for Substance Use Research, University of Victoria, PO Box 1700 STN CSC, Victoria, BC V8Y 2E4, Canada ( [email protected] ).

Author Contributions: Drs Zhao and Stockwell had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Zhao, Stockwell, Naimi, Churchill, Sherk.

Acquisition, analysis, or interpretation of data: Zhao, Stockwell, Naimi, Clay.

Drafting of the manuscript: Zhao, Stockwell, Clay.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Zhao, Churchill.

Obtained funding: Zhao, Stockwell, Sherk.

Administrative, technical, or material support: Zhao, Stockwell, Naimi.

Supervision: Zhao, Stockwell, Naimi.

Conflict of Interest Disclosures: Dr Stockwell reported receiving personal fees from Ontario Public Servants Employees Union for expert witness testimony and personal fees from Alko outside the submitted work. Dr Sherk reported receiving grants from Canadian Centre on Substance Use and Addiction (CCSA) during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was partly funded by the CCSA as a subcontract for a Health Canada grant to develop guidance for Canadians on alcohol and health.

Role of the Funder/Sponsor: Health Canada had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. CCSA staff conducted a preliminary search to identify potentially relevant articles but did not participate in decisions about inclusion/exclusion of studies, coding, analysis, interpretation of results or approving the final manuscript.

Data Sharing Statement: See Supplement 2 .

Additional Contributions: We gratefully acknowledge contributions by Christine Levesque, PhD (CCSA), and Nitika Sanger, PhD (CCSA), who conducted a preliminary literature search for potentially relevant articles. We also acknowledge the leadership of Drs Catherine Paradis, PhD (CCSA), and Peter Butt, MD (University of Saskatchewan), who cochaired the process of developing Canada’s new guidance on alcohol and health, a larger project which contributed some funds for the work undertaken for this study. We are grateful to Fariha Alam, MPH (Canadian Institute for Substance Use and Research), for her help coding the studies used in this study. None of them received any compensation beyond their normal salaries for this work.

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The Effects of Alcohol Consumption on Recovery Following Resistance Exercise: A Systematic Review

Affiliation.

  • 1 Sport and Exercise Research Unit, Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, 90144 Palermo, Italy.
  • PMID: 33467356
  • PMCID: PMC7739274
  • DOI: 10.3390/jfmk4030041

Background: The aim of this manuscript was to describe the effects of alcohol ingestion on recovery following resistance exercise.

Methods: A literature search was performed using the following database: Web of Science, NLM Pubmed, and Scopus. Studies regarding alcohol consumption after resistance exercise evaluating recovery were considered for investigation. The main outcomes took into account biological, physical and cognitive measures. Multiple trained researchers independently screened eligible studies according to the eligibility criteria, extracted data and assessed risk of bias.

Results: A total of 12 studies were considered eligible and included in the quantitative synthesis: 10 included at least one measure of biological function, 10 included at least one measure of physical function and one included measures of cognitive function.

Conclusions: Alcohol consumption following resistance exercise doesn't seem to be a modulating factor for creatine kinase, heart rate, lactate, blood glucose, estradiol, sexual hormone binding globulin, leukocytes and cytokines, C-reactive protein and calcium. Force, power, muscular endurance, soreness and rate of perceived exertion are also unmodified following alcohol consumption during recovery. Cortisol levels seemed to be increased while testosterone, plasma amino acids, and rates of muscle protein synthesis decreased.

Keywords: muscle function; muscle mass; performance; strength; training.

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The author declares no conflict of interest.

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The Effect of Alcohol Consumption on the Academic Performance of Undergraduate Students

Idoko Joseph Onyebuchukwu

Counselling Centre, Covenant University, Ota, Ogun State, Nigeria

Muyiwa Adeniyi Sholarin

Department of Psychology, School of Human Resource Development, College of Leadership & Development Studies, Covenant University, Ota, Ogun State, Nigeria

Agoha Benedict Chico Emerenwa

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alcohol consumption researchgate

Most people know that academic performance generally refers to how well a student is accomplishing his or her tasks and studies, but there are numbers of factors that determine the level and quality of students’ academic performance. This study investigated the effect of alcohol consumption on the academic performance of undergraduate students. A survey research design was used. A pilot study was carried out with 30 students to validate and determine the psychometric properties of the questionnaires used in this study. Total of 200 respondents, 114 male and 86 females with ages ranging between 13 and 25 years participated in this study. Three hypotheses were tested using Pearson r, T-test, Anova, and simple regression analysis. The result revealed that there is a significant relationship between alcohol consumption and academic performance (R2=0.74,P<.O5), there is a significant difference in academic performance of students that drink alcohol and those that do not (R2=12.22,P<.05), there is a significant effect of alcohol consumption on academic performance(R2=4.474,P<.05). The study has recommendations.

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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License ( ), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

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Copyright © The Author(s), 2015. Published by Science Publishing Group

Alcohol, Consumption, Academics, Performance, Undergraduates

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[10] A. O. Ademuya, B. A. Ola, O. O. Aloba, B. M. Mapayi, O. I. Ibigbami, T. A. Adewumi (2007). Nigeria Journal of Psychiatry. Vol.5 (1) pp.5-9.
[11] Odejide, A. O.& Ohaeri, J. U. (1994).Awareness and drug abuse among patients attending primary facilities in a rural community. Nigerian Medical Journal.26;18-22.
[12] Oshodi,C.O.(1972).Drug dependence and addiction, my studies in Kaduna; Nigerian Journal of Psychiatry. 1 (3) 194-203.
[13] Ebitin,N. William & Adamson A.Taiwo (2005). Neuropsychiatric Hospital Aro, Abeokuta.
[14] Adelaka, M. L., Abiodun, O. A., Imoukhome, Obayan A. O., Oni G. A. & Ogunremi O.O.(1993). Psychological correlates of Alcohol, Tobacco and Cannabis use. Finding from Nigerian University. Drug and Alcohol Dependence,33,234-256.
[15] Olley. B. O. (2008). Advanced psychopathology note book. University of Ibadan, Ibadan.
[16] Nwobu, I. W.(2011). Nigeria. Same old tale about National I.ID. card. Available at http:// Leadership. ng.nga articles/8652/201. Accessed, 3 July 2012.
[17] Kegite club, University of Ibadan, Ibadan.
[18] Anumonye N., Omoniwa N., & Adaranijo H.(1977). Excessive Alcohol use and related Problems in Nigeria. Drug and Alcohol Dependence, vol.2,23-30.
[19] Aworemi J. R., Adegoke A. I., Olabode S.O.(2010). Analytical study of the causal factors of road Traffic crashes in south western Nigeria. Educational Research, vol.1 (4) 118-124.
[20] National institute on Alcohol abuse and Alcoholism, (2005) Historical Document.
[21] David Ducthman & Philip Murphy (2008) Alcohol effect on student performance, Edge hill University.

Idoko Joseph Onyebuchukwu, Muyiwa Adeniyi Sholarin, Agoha Benedict Chico Emerenwa. (2015). The Effect of Alcohol Consumption on the Academic Performance of Undergraduate Students. Psychology and Behavioral Sciences , 4 (4), 147-153. https://doi.org/10.11648/j.pbs.20150404.12

alcohol consumption researchgate

Idoko Joseph Onyebuchukwu; Muyiwa Adeniyi Sholarin; Agoha Benedict Chico Emerenwa. The Effect of Alcohol Consumption on the Academic Performance of Undergraduate Students. Psychol. Behav. Sci. 2015 , 4 (4), 147-153. doi: 10.11648/j.pbs.20150404.12

Idoko Joseph Onyebuchukwu, Muyiwa Adeniyi Sholarin, Agoha Benedict Chico Emerenwa. The Effect of Alcohol Consumption on the Academic Performance of Undergraduate Students. Psychol Behav Sci . 2015;4(4):147-153. doi: 10.11648/j.pbs.20150404.12

Department of Psychology, School of Human Resource Development, College of Leadership & Development Studies, Covenant University, Ota, Ogun State, Nigeria

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alcohol consumption researchgate

My Longevity Experiment

alcohol consumption researchgate

4 Major Health Benefits to Drinking Beer

13-year study shows the protective effect of beer on longevity.

alcohol consumption researchgate

Introduction

When it comes to enjoying a cold beer, many might question its health benefits. However, recent studies suggest that moderate beer consumption can offer several health advantages. It’s important to emphasize that these benefits are linked to moderate drinking and not heavy or frequent consumption. This article reviews a meta-analysis published in the international, peer-reviewed journal 'Nutrients,' conducted by a team of nutrition and food science researchers from Spain. They examined studies from 2007 to 2020, exploring the effects of mostly alcoholic beverages on people’s health. Interestingly, some studies suggested that the naturally occurring nutrients in beer, not just the alcohol, contribute to these health benefits.

1. Cardiovascular Health

One of the significant findings from the researchers is the positive impact of moderate beer consumption on cardiovascular health. Five out of six studies reviewed indicated "a protective effect of moderate alcohol drinking on cardiovascular disease." This benefit was observed in individuals who consumed up to 13.5 ounces of beer per week compared to abstainers and occasional drinkers. Additionally, men who abstained from drinking had a significantly higher risk of developing abnormal glucose regulation than those who drank beer occasionally, suggesting that occasional beer consumption might offer some protection against diabetes in men.

My Longevity Experiment is a reader-supported publication. To receive new posts and support my work, please consider becoming a free or paid subscriber.

2. Bone Health

Beer consumption also appears to have benefits for bone health. The researchers found that "very low levels of consumption were associated with a decreased fracture risk" among older individuals. They noted that the non-alcoholic components of beer, such as phytoestrogens, might work synergistically with silicon to stimulate osteoblast cells, which improve bone structure and aid in natural bone and tooth repair. This finding is crucial considering that sarcopenia, a condition associated with bone and muscle loss, results in 27,000 deaths annually in the USA. Improving bone health can significantly impact longevity and reduce the risk of conditions like osteoporosis.

3. Cholesterol Management

Moderate beer consumption may also promote better cholesterol levels. The researchers highlighted studies suggesting that beer helps increase 'good cholesterol' (HDL) and regulates the body's processing of 'bad cholesterol' (LDL). This effect is largely attributed to the antioxidants found in well-brewed beer. Although this benefit was noted with very small amounts of beer (between half an ounce and an ounce per day), it’s reassuring to know that even minimal consumption can contribute positively.

4. Diabetes Protection

The meta-analysis revealed that men who abstained from alcohol had a higher risk of developing abnormal glucose regulation compared to occasional beer drinkers. This suggests that moderate beer consumption could have a protective effect against diabetes, specifically in men. It's another reason why beer, in moderation, can be part of a healthy lifestyle.

While the findings from this meta-analysis are promising, it’s essential to remember that moderation is key. The researchers recommend that women should limit themselves to one drink per day and men to two drinks per day to maximize health benefits and minimize risks. Moreover, the benefits discussed are not just due to the alcohol content but also the naturally occurring nutrients in beer. This is good news for those who prefer non-alcoholic beer options.

Enjoying beer responsibly can offer several health benefits, from improving cardiovascular health and bone density to promoting good cholesterol levels and protecting against diabetes. As always, it’s best to consult with a healthcare professional about your drinking habits and health goals.

Lipid Caveat

The terms "good cholesterol" (HDL) and "bad cholesterol" (LDL) are now generally considered outdated and possibly misleading. This is because both types of cholesterol play complex roles in the body that cannot be simply categorized as "good" or "bad." HDL, while generally protective, can sometimes become dysfunctional and contribute to inflammation. Conversely, LDL is essential for transporting cholesterol to cells but can be harmful when oxidized. Moreover, the focus on LDL and HDL levels alone doesn't capture the full picture of cardiovascular risk, which involves various factors like particle size and number, and the presence of other lipoproteins​.

Link to YouTube Video:

https://shorturl.re/7eted

Links to Studies:

https://pubmed.ncbi.nlm.nih.gov/27118108/

https://www.nmcd-journal.com/article/S0939-4753(16)30004-7/fulltext

https://www.sciencedirect.com/science/article/pii/S0939475316300047

https://cpncampus.com/biblioteca/files/original/72b564de4ac956a4ec130eea579283de.pdf

https://europepmc.org/article/MED/27118108

https://www.researchgate.net/publication/299576450_Effects_of_moderate_beer_consumption_on_health_and_disease_A_consensus_document

https://beerandhealth.eu/wp-content/uploads/2017/04/S3P2-De-Gaetano.pdf

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IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Alcohol Consumption and Ethyl Carbamate. Lyon (FR): International Agency for Research on Cancer; 2010. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 96.)

Cover of Alcohol Consumption and Ethyl Carbamate

Alcohol Consumption and Ethyl Carbamate.

1 exposure data, 1.1. types and ethanol contents of alcoholic beverages, 1.1.1. types of alcoholic beverage.

Most cultures throughout the world have traditionally consumed some form of alcoholic beverages for thousands of years, and local specialty alcoholic beverages still account for the majority of all those that exist. Only a small number have evolved into commodities that are produced commercially on a large scale. In world trade, beer from barley, wine from grapes and certain distilled beverages are sold as commodities. Other alcoholic beverages are not sold on the international market. In many developing countries, however, various types of home-made or locally produced alcoholic beverages such as sorghum beer, palm wine or sugarcane spirits continue to be the main available beverage types ( WHO, 2004 ).

It is difficult to measure the global production or consumption of locally available beverages, and few data exist on their specific chemical composition (see Section 1.6 ). A discussion of unrecorded alcohol production, which includes these traditional or home-made beverages, is given in Section 1.3 . Although these types of alcoholic beverage can be important in several countries at the national level, their impact is fairly small on a global scale.

This monograph focuses on the main beverage categories of beer, wine and spirits unless there is a specific reason to examine some subcategory, e.g. alcopops or flavoured alcoholic beverages. These categories are, however, not as clear-cut as they may seem. There are several beverages that are a combination of two types (e.g. fortified wines, in which spirits are added to wine). The categorization above is based on production methods and raw materials, and not on the ethanol content of the beverages (see Section 1.2 ).

Another classification of beverages is the Standard International Trade Classification (SITC) that has four categories: wine from fresh grapes, cider and other fermented beverages, beer and distilled alcoholic beverages (for further details, see SITC Rev 3 at United Nations Statistics Division (2007 ; http://unstats.un.org/unsd/cr )).

1.1.2. Alcohol content of different beverages

In this monograph, percentage by volume (% vol) is used to indicate the ethanol content of beverages; this is also called the French or Gay-Lussac system. The American proof system is double the percentage by volume; a vodka which is 40% by volume is thus 80 proof in the USA ( IARC, 1988 ).

The standard approach to measuring the amount of ethanol contained in a specific drink is as follows. The amount of alcoholic beverage typically consumed for each type of beverage (e.g. a 330-mL bottle of beer or a 200-mL glass of wine) is multiplied by the ethanol conversion factor, i.e. the proportion of the total volume of the beverage that is alcohol. Ethanol conversion factors differ by country, but are generally about 4–5% vol for beer, about 12% vol for wine and about 40% vol for distilled spirits. Thus, the ethanol content of a bottle of beer is calculated as (330 mL) × (0.04) = 13.2 mL ethanol. In many countries, ethanol conversion factors are used to convert the volume of beverage directly into grams of ethanol. In other countries, volumes of alcohol may be recorded in ‘ounces’. Relevant alcohol conversion factors for these different measures are ( WHO, 2000 ): 1 mL ethanol = 0.79 g; 1 United Kingdom fluid oz = 2.84 cL = 28.4 mL = 22.3 g; 1 US fluid oz = 2.96 cL = 29.6 mL = 23.2 g.

The ethanol content in beer usually varies from 2.3% to over 10% vol, and is mostly 5–5.5% vol. In some countries, low-alcohol beer, i.e. below 2.3% vol, has obtained a considerable share of the market. In general, beer refers to barley beer, although sorghum beer is consumed in large quantities in Africa.

The ethanol content of wine usually varies from 8 to 15% vol, but light wines and even non-alcoholic wines also exist.

The ethanol content of spirits is approximately 40% vol, but may be considerably higher in some national specialty spirits. Also within the spirits category are aperitifs, which contain around 20% vol of alcohol. Alcopops, flavoured alcoholic beverages or ready-to-drink beverages usually contain 4–7% vol of alcohol, and are often pre-mixed beverages that contain vodka or rum.

1.2. Production and trade of alcoholic beverages

1.2.1. production, (a) production methods.

Most yeasts cannot grow when the concentration of alcohol is higher than 18%. This is therefore the practical limit for the strength of fermented beverages, such as wine, beer and sake (rice wine). In distillation, neutral alcohol can be produced at strengths in excess of 96% vol of alcohol.

(i) Beer production

The process of producing beer has remained unchanged for hundreds of years. The basic ingredients for most beers are malted barley, water, hops and yeast. Barley starch supplies most of the sugars from which the alcohol is derived in the majority of beers throughout the world. Other grains used are wheat and sorghum. The starch in barley is enclosed in a cell wall, and these wrappings are stripped away in the first step of the brewing process, which is called malting. Removal of the wall softens the grain and makes it more readily milled. The malted grain is milled to produce relatively fine particles and these are then mixed with hot water in a process that is called mashing. The water must process the right mix of salts. Typically, mashes contain approximately three parts of water to one part of malt and are maintained at a temperature of ∼65 °C. Some brewers add starch from other sources such as maize (corn) or rice to supplement the malt. After ∼1 h of mashing, the liquid portion is recovered by either straining or filtering. The liquid (the wort) is then boiled for ∼1 h. Boiling serves various functions, including sterilization and the removal of unpleasant grainy contents that cause cloudiness. Many brewers add sugar or at least hops at this stage. The hopped wort is then cooled and pitched with yeast. There are many strains of brewing yeast and brewers tend their strains carefully because of their importance to the identity of the brand. Fundamentally, yeasts can be divided into lager and ale strains. Both types need a little oxygen to trigger off their metabolism. Ale fermentations are usually complete within a few days at temperatures as high as 20 °C, whereas lager fermentations, at temperatures which are as low as 6 °C, can take several weeks. Fermentation is complete when the desired alcohol content has been reached and when an unpleasant butterscotch flavour, which develops during all fermentation, has been removed by the yeast. The yeast is then harvested for use in the next fermentation. Nowadays, the majority of beers receive a relatively short conditioning period after fermentation and before filtration. This is performed at −1 °C or lower (but not so low as to freeze the beer) for a minimum of 3 days. This eliminates more proteins and ensures that the beer is less likely to cloud in the packaging or glass. The filtered beer is adjusted to the required degree of carbonation before being packed into cans, kegs, or glass or plastic bottles ( Bamforth, 2004 ).

(ii) Wine production

A great majority of wine is produced from grapes, but it can also be produced from other fruits and berries. The main steps in the process of wine making are picking the grapes, crushing them and possibly adding sulfur dioxide to produce a wine must. After addition of Saccharomyces , a primary/secondary fermentation then takes place. This newly fermented wine is then stabilized and left to mature, after which the stabilized wine is bottled (and possibly left to mature further in the bottle).

Red grapes are fermented with the skin, and yield ∼20% more alcohol than white grapes. Ripe fruit should be picked immediately before it is to be crushed. Harvesting is becoming increasingly mechanical although it causes more physical damage to the grapes, and sulfur dioxide may be added during the mechanical harvesting. The grapes are then stemmed and crushed. The stems are not usually left in contact with crushed grapes to avoid off-flavours. An initial crushing separates grapes from stems with the aim of achieving an even breakage of grapes. It is not necessary to separate the juice from the skins immediately for red wine, but it is for white, rosé or blushwines. The juice is settled at a low temperature (< 12 °C), after which it is drained and pressed. To accelerate juice settling and obtain a clearer product, pectic enzyme is frequently added at the crushing stage. Once the juice is separated from the skins, it is held overnight in a closed container. Thereafter, it is centrifuged before the addition of yeast. In locations where the grapes do not ripen well because of a short growing season, it may be necessary to add sugar (sucrose). Dried yeast is usually used in wine making (contrary to beer brewing). Oxygen is introduced to satisfy the demand of the yeast. White wines are fermented at 10–15 °C, whereas red wines are fermented at 20–30 °C. Fermentation is complete within 20–30 days. Wine is usually racked off the yeast when the fermentation is complete, although some winemakers leave the yeast for several months to improve the flavour. After fermentation, the wine is clarified with different compounds depending on the type of wine (bentonite, gelatine, silica gels). Maintaining them in an anaerobic state then stabilizes the wines and prevents spoilage by most bacteria and yeast. Wines tend to benefit from ageing, which is performed in either a tank, barrel or bottle. The extent of ageing is usually less for white than for red wines. During ageing, the colour, aroma, taste and level of sulfur dioxide are monitored. If wine is aged in oak barrels, some characteristics are derived from the barrel.

Residual oxygen is removed during packaging and some winemakers add sorbic acid as a preservative to sweet table wines. To avoid the use of additives, attention must be paid to cold filling and sterility, and to avoid taints, corks should be kept at a very low moisture content. The shelf life of wine is enhanced by low-temperature storage ( Bamforth, 2005 ).

(iii) Production of spirits

The neutral alcohol base used for several different spirits is frequently produced from cereals (e.g. corn, wheat), beet or molasses, grapes or other fruit, cane sugar or potatoes. These basic substances are first fermented and then purified and distilled. Distillation entails heating the base liquid so that all volatile substances evaporate, collecting these vapours and cooling them. This liquid may be distilled several times to increase purity. The process leads to a colourless, neutral spirit, which may then be flavoured in a multitude of ways. For some spirits, such as cognac and whisky, the original flavouring of the base liquid is retained throughout the distilling process, to give the distinct flavour. After distillation, water is added to give the desired strength of the beverage.

Vodka is a pure unaged spirit distilled from agricultural products and is usually filtered through charcoal. Neutral alcohol is the base for vodka, although many flavourings can be found in modern vodkas, such as fruit and spices. Other beverages based on neutral distilled alcohol are gin, genever, aquavit, anis and ouzo. For example, the distinct flavour of gin comes from distillation in the presence of plants such as juniper, coriander and angelica, and the peel of oranges and lemons.

Rum is produced from molasses or cane sugar; whisky is produced from a mash of cereals and is matured for a minimum of 3 years. Brandy comes from distilled wine and needs to mature in oak. Fruit spirits may be produced by fermentation and distillation of a large number of fruit and berries, such as cherries, plums, peaches, apples, pears, apricots, figs, citrus fruit, grapes, raspberries or blackberries ( Bamforth, 2005 ).

(b) Production and trade volumes

According to the SITC (SITC Rev. 3.1, code 155; United Nations Statistic Division 2007 ), the activity of manufacture of alcoholic beverages is divided into three categories:

1551 - Distilling, rectifying and blending of spirits; ethyl alcohol production from fermented materials . This class includes: the manufacture of distilled, potable, alcoholic beverages: whisky, brandy, gin, liqueurs and ‘mixed drinks’; the blending of distilled spirits; the production of ethyl alcohol from fermented materials; and the production of neutral spirits.

1552 – Manufacture of wine . This class includes: the manufacture of wine from grapes not grown by the same unit; the manufacture of sparkling wine; the manufacture of wine from concentrated grape must; the manufacture of fermented but not distilled alcoholic beverages: sake, cider, perry, mead, other fruit wines and mixed beverages containing alcohol; the manufacture of vermouth and similar fortified wines; the blending of wine; and the manufacture of low-alcohol or non-alcoholic wine.

1553 – Manufacture of malt liquors and malt . This class includes: the manufacture of malt liquors, such as beer, ale, porter and stout; the manufacture of malt; and the manufacture of low-alcohol or non-alcoholic beer.

According to the alcoholic beverage industry, the global market for alcoholic drinks reached a volume of 160.2 billion litres of alcohol in 2006. The market is forecasted to grow further in the coming years. The compound annual average growth rate in volume has been around 2% per year from 2000 to 2006. A similar growth rate is expected in the coming 5 years. The value of the global drinks market in 2006 was 812.4 billion US $ (Market is valued according to retail selling price including any applicable taxes). Both volume and value grow at a steady rate of around 1–2% per year.

The sales of beer, cider and flavoured alcoholic beverages dominate the market with a 48.7% share of the global value. Wine is the second highest in value at 28.3% and is followed by spirits at 22.9%.

Europe continues to be the largest alcoholic drinks market and accounts for 59% of the global market value. Europe is followed by the USA (23.7%) and the Asia-Pacific region (17.2%).

On-trade (on-premises) sales distribute alcoholic products worth 38.7% of the total market revenue, followed by supermarkets/hypermarkets (20.8%) and specialist retailers (12.1%) ( Datamonitor, 2006 , Datamonitor does not cover all countries as it is more focused on developed countries; for e.g. Africa, the data are almost non-existent).

The market for alcoholic beverages shows considerable variation in growth. In most developed economies, the market is mature, i.e. stable but not growing. In these countries, most people have reached an economic status where they can buy alcoholic beverages if they wish to do so. However, Brazil, the Russian Federation, China, India and some transitional economies in Europe have a market that is greatly increasing in value. In general, low- and middle-income countries tend to move from locally produced alcoholic beverages to commercial brands as their economic status improves. Simultaneously, they also show a shift from other beverages to beer. In developed markets, sales volumes for beer are static or declining, with intensified competition from wine and spirits ( ICAP, 2006 ). Regarding beverage-specific production, Table 1.1 presents the 10 largest beer-producing countries in 2002. Of these, Germany, Mexico and the Netherlands are especially prominent exporters of beer (see Section 1.2.2 ). In Brazil, China, Japan and the Russian Federation, most of the beer produced is consumed in the domestic market.

Table 1.1. Top 10 beer producers.

Top 10 beer producers.

The largest wine producers ( Table 1.2 ) are the traditional European wine-producing countries such as France, Spain and Italy, but also include those from the New World such as South Africa. It is clear that the major wine-producing countries are also the greatest wine-exporting countries.

Table 1.2. Top 10 wine (including all fermented) producers.

Top 10 wine (including all fermented) producers.

With regard to the production of spirits, China and India are the largest producers ( Table 1.3 ). All of the developing countries listed (plus Japan and the Russian Federation) are large producers of spirits but are not prominent exporters of their products; they are all predominantly spirit-drinking countries.

Table 1.3. Top 10 spirits producers.

Top 10 spirits producers.

An overall observation is that developing countries, such as Brazil, China and India are prominent among the largest producers of beer and/or spirits.

1.2.2. Trade in alcoholic beverages

(a) trends in trade.

Overall, trade in alcoholic beverages has increased almost 10-fold over the past 30 years. The increase is, however, proportional to the overall increase in world trade of all goods. Alcoholic beverages hold a stable 0.5% of the total value of global trade. This would mean that for every 200 US $ in global trade, 1 US $ involves alcoholic beverages. The trends in trade do not correlate to trends in consumption.

(b) Countries with highest imports or exports

Over the past 30 years, France, Italy, the United Kingdom and the USA have been the largest importers of beer. The major change is that the USA have increased their share of the world trade from 29% in 1992 to 42% in 2005. For beer exports, Mexico features prominently, and has had an increase in trade share from 5.8% in 1992 to 18.8% in 2005 (see Table 1.4 ).

Table 1.4. Principal importers and exporters of beer in 2005.

Principal importers and exporters of beer in 2005.

Regarding wine imports, two new countries have emerged as principal traders—Japan and the Russian Federation. Global export is still dominated by the traditional large wine-producing countries, such as France, although the share of French wines has decreased from nearly 50% in 1992 to 33% in 2005. Two more recent wine-producing countries—South Africa and New Zealand—have entered the list of large wine traders (see Table 1.5 ).

Table 1.5. Principal importers and exporters of wine in 2005.

Principal importers and exporters of wine in 2005.

The Russian Federation is now a major importer of spirits. For the principal exporting countries, there has been more fluctuation over the past 30 years than for other beverages. For example, Mexico and Spain have been on and off the list of major exporters, and Germany and Sweden became major exporters in 2005 (see Table 1.6 ).

Table 1.6. Principal importers and exporters of distilled alcoholic beverages in 2005.

Principal importers and exporters of distilled alcoholic beverages in 2005.

Overall, the ranking of countries for both imports and exports of all beverages has been fairly stable over the years. Almost no low-income countries are among the top 10. Only a small minority of countries worldwide are involved in any significant trade at the global level and mostly the same countries are implicated for all beverages.

1.3. Trends in consumption

1.3.1. indicators of alcoholic beverage consumption.

Three methods exist to measure consumption of alcoholic beverages in a population: surveys of a representative sample of a country or a large region of a country; determination of consumption from available statistics, such as production and sales/taxation records; and determination of consumption based on indirect indicators such as availability of raw materials to produce alcohol (e.g. sugar, fruit).

Overall, surveys have been shown in general to underestimate consumption compared with estimates from production and sales records ( Gmel & Rehm, 2004 ), at least in developed countries. One reason for this underestimation is that surveys do not usually include people who live outside a household and who drink heavily, such as institutionalized people or the homeless. The degree of underestimation varies, and can range from 70% in some cases up to almost full coverage in others. For this reason, international comparisons of total consumption between developed countries mostly use production and sales-based statistics ( Rehm et al. , 2003 ). Whenever possible, recorded consumption should be supplemented by estimates of unrecorded consumption. This is especially important in developing countries, where unrecorded consumption is on average more common and, in some regions of the world, constitutes more than 50% of the overall consumption.

1.3.2. Assessment of total consumption per head (per-capita consumption)

(a) measurement of adult per-capita consumption of recorded alcoholic beverages.

Data on per-capita alcoholic beverage consumption provide the consumption in litres of pure alcohol per inhabitant in a given year. They are available for the majority of countries, often given over time, and avoid the underestimation of total volume of consumption that is commonly inherent in survey data (e.g. Midanik, 1982 ; Rehm, 1998 ; Gmel & Rehm, 2004 ). Adult per-capita consumption, i.e. consumption by all persons aged 15 years and above, is preferable to per-capita consumption per se since alcoholic beverages are largely consumed in adulthood. The age pyramid varies in different countries; therefore, per-capita consumption figures based on the total population tend to underestimate consumption in countries where a large proportion of the population is under the age of 15 years, as is the case in many developing countries. For more information and guidance on estimating per-capita consumption, see WHO (2000) .

Three principal sources for per-capita estimates are national government data, information from the Food and Agriculture Organization of the United Nations (FAO) and data from the alcoholic beverage industry ( Rehm et al. , 2003 ). Where available, the best and most reliable information stems from national governments, usually based on sales figures, tax revenue and/or production data. Generally, sales figures are considered to be the most accurate, provided that sales of alcoholic beverages are separated from those of any other possible items sold at a given location, and that they are beverage-specific. One of the drawbacks of production figures is that they are always dependent on accurate export and import data; if these are not available, the production figures will yield an under- or an overestimation.

The most complete and comprehensive international data set on per-capita consumption was published by FAO (until 2003). FAOSTAT, the database of the FAO, publishes production and trade information for different types of alcoholic beverage for almost 200 countries. The estimates are based on official reports of production by national governments, mainly by the Ministries of Agriculture in response to an annual FAO questionnaire. The statistics on imports and exports derive mainly from Customs Departments. If these sources are not available, other government data such as statistical yearbooks are consulted. The accuracy of the FAO data relies on reporting by member nations. The information from member nations probably underestimates informal, home and illegal production, but these sources are still covered more accurately by the FAO than by estimates based solely on production or sales figures.

The third main source of information is the alcoholic beverage industry. In this category the most widely used is World Drinks Trends (WDT), published by the Commission for Distilled Spirits ( World Advertising Research Centre Ltd, 2005 ). The WDT estimates are based on total sales in litres divided by the total mid-year population and use conversion rates that are not published. WDT also tries to calculate the consumption of both incoming and outgoing tourists. Currently, at least partial data are available for 58 countries. Other sources from the alcoholic beverage industry, as well as market research companies, are less systematic, entail fewer countries and are more limited in providing information over time.

The WHO Global Alcohol Database (undated) systematically collects and compares per-capita data from different sources on a regular basis (for procedures and further information, see Rehm et al. , 2003 ; WHO, 2004 ) using data from the United Nations for population estimates. The information in this section derives from this database, which has explicit rules for selecting and processing data to ensure their comparability.

The main limitations of adult per-capita estimates are twofold: they do not incorporate most unrecorded consumption (see below); and they are only aggregate statistics that cannot easily be disaggregated into sex and age groups. Thus, surveys have to play a crucial role in any analysis of the effect of consumption of alcoholic beverages on the burden of disease (see below).

(b) Assessment of adult per-capita consumption of unrecorded alcoholic beverages

Most countries have at least a low level of so-called unrecorded alcoholic beverage consumption. Unrecorded alcoholic beverages simply means that the alcoholic beverages produced and/or consumed are not recorded in official statistics of sales, production or trade. In some countries, unrecorded alcoholic beverages are the major source of such commodities (see Table 1.7 ). Unrecorded consumption stems from a variety of sources ( Giesbrecht et al. , 2000 ): home production, illegal production and sales, illegal (smuggling) and legal imports (cross-border shopping) and other production and use of alcoholic beverages that are not taxed and/or are not included in official production and sales statistics.

Table 1.7. Characteristics of alcoholic beverage consumption by country 2002 (average of available data 2001–03).

Characteristics of alcoholic beverage consumption by country 2002 (average of available data 2001–03).

A portion of the unrecorded alcoholic beverages derives from different local or traditional beverages that are produced and consumed in villages or homes. The production may be legal or illegal, depending on the strength of the beverage. Worldwide, information on these alcoholic beverages and their production or consumption volumes is scarce. Local production consists mostly of the fermentation of seeds, grains, fruit, vegetables or parts of palm trees, and is a fairly simple process. The alcohol content is quite low and the shelf life is usually short—1 or 2 days before the beverage is spoilt. In terms of pricing, locally produced traditional alcoholic beverages tend to be considerably cheaper than their western-style, commercially produced counterparts.

In many regions of the world, illegal alcoholic beverages are approximately 2–6 times cheaper ( McKee et al. , 2005 ; Lang et al. , 2006 ) than commercial alcoholic beverages and are thus most likely to be consumed by those who are on the margins of society, are very heavy drinkers or are dependent on alcohol, all of whom are commonly underrepresented in surveys. In spite of the higher price, industrially produced alcoholic beverages are gaining popularity in many of these countries.

1.3.3. Global consumption in 2002

Although the global average consumption is 6.2 L of pure alcohol per capita per year, there is wide variation around the world ( Table 1.8 ). The countries with the highest overall consumption are those in eastern Europe that surround the Russian Federation; however, other areas of Europe also have high overall consumption. The Americas have the next highest overall consumption. Except for some individual countries, alcoholic beverage consumption is lower in other parts of the world. Globally, 55.2% of adult men and 34.4% of adult women consume alcoholic beverages; in 2002, this constituted more than 1.9 billion adults. The fraction of unrecorded consumption is higher in less developed parts of the world, and is thus highest in the poorest regions of Africa, Asia and South America. In addition, unrecorded consumption is estimated to be proportionally high in the Eastern Mediterranean Region where many of the countries are Islamic, although the level of consumption is very low. Table 1.8 gives further details on consumption.

Table 1.8. Characteristics of alcoholic beverage consumption throughout the world in 2002.

Characteristics of alcoholic beverage consumption throughout the world in 2002.

Table 1.9 shows the rates of drinking more than 40 g pure alcohol per day in different parts of the world. As expected from the per-capita figures, there is huge variation between sexes and by region, with highest prevalence in eastern Europe (Russian Federation and surrounding countries) and lowest prevalence in the WHO Eastern Mediterranean Region where countries are mostly Islamic.

Table 1.9. Consumption of more than 40 g pure alcohol per day by sex and WHO region, 2002.

Consumption of more than 40 g pure alcohol per day by sex and WHO region, 2002.

1.3.4. Trends in recorded per-capita consumption

Figs. 1.1 – 1.4 give an overview of trends in alcoholic beverage consumption over the past 40 years. Trends of unrecorded consumption are not available because of the lack of data. However, in regions that have relatively high recorded consumption, these figures also reflect the trend of overall consumption.

Recorded overall adult per-capita consumption of alcoholic beverages in six WHO Regions: Africa, Americas, Eastern Mediterranean, Europe, South-East Asia and Western Pacific, 1961–2003 a

Adult per-capita consumption of spirits in six WHO Regions: Africa, Americas, Eastern Mediterranean, Europe, South-East Asia and Western Pacific, 1961–2003 a

Changes in the trend of overall alcoholic beverage consumption have varied between different countries and regions. In Europe, consumption declined in the 1980s and has been stable since 1990. The European trend obscures various developments in different countries, such as an increase in countries with formerly lower consumption such as the Nordic countries, and a decline in consumption in traditional wine-producing countries such as France, Italy, Portugal and Spain. Other regions have remained relatively stable, but consumption in the Western Pacific Region, mostly influenced by China because of the large population there, has almost steadily increased.

Recorded adult per-capita beer consumption in six WHO Regions: Africa, Americas, Eastern Mediterranean, Europe, South-East Asia and Western Pacific, 1961–2003 a

Recorded adult per-capita wine consumption in six WHO Regions: Africa, Americas, Eastern Mediterranean, Europe, South-East Asia and Western Pacific, 1961–2003 a

The trends in beer consumption follow the same pattern. In addition, beer consumption has been increasing in the Americas; this region now has the biggest beer consumption per capita in the world.

Europe and, to a much lesser degree, America are the only regions with notable consumption of wine. The seemingly high consumption in Africa is due to the fact that FAO has been recording fermented beverages under this category since the mid 1990s.

Finally, spirits are the most commonly consumed beverage type around the world. They have also contributed to the large increase in consumption in the Western Pacific Region. In a global perspective, the Western Pacific Region, and especially China, is now the region with the highest consumption of spirits in the world. It should also be noted that the consumption of spirits has decreased in the Americas, where this type of beverage has been replaced by beer.

1.4. Sociodemographic determinants of alcoholic beverage consumption

1.4.1. introduction.

As noted in Section 1.3 , per-capita consumption figures offer overall a comparable picture of alcoholic beverage consumption across countries and avoid the problems of underestimation as well as other sources of bias present in survey methods (e.g. recall bias). However, per-capita consumption does not provide any information on patterns of consumption within a country; that is, the frequency and quantity of consumption as well as occasions on which a large amount of alcoholic beverages may be consumed at one time. Also, with per-capita consumption, it is not known which subgroups engage in particular patterns of drinking. Survey data, although imperfect in certain respects, still provide the only method to obtain knowledge on the patterns of consumption within a population.

Key measures of patterns of consumption include the assessment, within a given period, of the proportion of the population that drinks at all and, conversely, the proportion that abstains from drinking. Among those who drink, central measures include the frequency of drinking over a pre-defined period and the total amount or volume of ethanol consumed over that period. It is also informative to gather this information for the three major classes of beverage: beer, wine and spirits. In addition, it is helpful to calculate the average amount of alcoholic beverages consumed per day as well as the number of drinking days. The former measure is often used to communicate safe drinking limits to the public (e.g. British Medical Association, 1995 ). A final important indicator of patterns of consumption is a measure of so-called ‘heavy episodic drinking’. This is defined as an intake of ethanol sufficient to lead to intoxication in a single session of drinking, and is usually 60 g ethanol or more ( WHO, 2000 ).

Knowledge of the patterns and habits of alcoholic beverage consumption in various countries and among cultures has increased markedly over the past decade. This has been due to efforts of various cross-cultural social-epidemiological studies as well as initiatives of various regional and global institutions such as the European Commission and the WHO to conduct general population surveys. Despite these advances, gaps in knowledge still exist; however, it is now possible to obtain a general picture of drinking habits in various regions of the world, which was not the case previously. Such information can help to indicate which geographic and demographic groups may be at greater risk from certain exposures to alcoholic beverage consumption than others.

1.4.2. Gender

It has been often observed that men are more frequently drinkers of alcoholic beverages, drink larger amounts and drink more often than women ( Wilsnack et al. , 2000 , 2005 ). This appears to be a universal gender difference in human social behaviour. However, the magnitude of these gender differences varies by age group, socioeconomic group and by region and/or culture.

With respect to the European Region, gender differences in the rates of current drinkers are small, with gender ratios (i.e. the value of a variable for men divided by that for women) that range between 1.0 and 1.2 (calculated from Mäkelä et al. , 2006 ). In the adult drinking population (20–64 years), gender ratios for overall drinking frequency are between 1.8 and 2.5. Larger variation exists for beverage-specific drinking frequency: men and women are most similar in their wine-drinking habits and the least similar in their beer-drinking habits. This basic pattern holds true for beverage-specific volume. Although in some countries women may drink wine more frequently than men, men almost always consume more of each beverage than women. Gender ratios for mean quantities of specific beverages consumed per drinking day have a narrow range for wine (1.0–1.8) and a wider range for spirits (1.1–2.0) and beer (1.3–2.2). For total mean volume and frequency of heavy episodic drinking, gender ratios are larger than those for drinking status or drinking frequency and most range between 1.8 and 5.8 across the European Region. Gender differences are smaller in the northern European countries for current drinking, frequency of drinking and frequency of heavy episodic drinking, but gender ratios for mean consumption reveal no clear regional pattern ( Mäkelä et al. , 2006 ).

In the 14 WHO regions, more women than men are abstainers, yet the rates of current drinking for both men and women are similar across the regions, showing that, where the level of current drinking for men is high, that for women is also high. The gender ratios are extremely variable: western Europe and the Western Pacific (e.g. Australia and Japan) have low ratios of 1.1 while the Eastern Mediterranean (e.g. Afghanistan and Pakistan) has a ratio of 17 and South-East Asia (e.g. Bangladesh and India) has a ratio of 6.5 ( Wilsnack et al. , 2005 ). Furthermore, the percentage of alcoholic beverages consumed by women also varies greatly across regions. In Europe, the share of alcoholic beverages consumed by women generally varies between 20% and 30% ( Mäkelä et al. , 2006 ). In developing countries, the percentage share can be much lower: based on recently conducted surveys, it is, for example, 8% in China, 10% in India and 15% in Ecuador ( WHO, 2004 ).

Data – as yet unpublished – obtained from a recent general population survey in many countries (Argentina, Australia, Austria, Brazil, Costa Rica, Czech Republic, Denmark, Finland, France, Germany, Hungary, Iceland, India, Israel, Italy, Japan, Mexico, the Netherlands, Nigeria, Norway, Spain, Sri Lanka, Sweden, Uganda, United Kingdom, USA, Uruguay) in various regions of the world through the GENACIS project ( Rahav et al. , 2006 ) confirm the previously mentioned variations in drinking by gender: men are more likely to be drinkers than women, women are more likely to be lifetime abstainers, men are more likely to drink heavily and more frequently and women drinkers are more likely to be light drinkers. These gender differences are more marked for countries outside North America and northern Europe.

The relationship of age to drinking habits is very much affected by gender and culture. In general terms, however, among adult populations in the developed world, abstention rates increase with older age and, among those who drink, frequency of drinking increases. Heavy episodic drinking is most frequent among the younger age groups; however, in some countries (e.g. central Europe), such rates do not always decline.

As stated, these general tendencies are very much affected by both age and region. For example, in Europe, a decrease in current drinking rates with age (age categories of 20–34, 35–49, 50–64 years) has been seen for some (e.g. northern and eastern Europe) but not all European countries ( Mäkelä et al. , 2006 ). Men and women tend to have similar current drinking rates at a given age. In many European countries, drinking frequency increases with increasing age, which can be attributed mostly to an increase in the frequency of drinking wine. This holds for both sexes. Typical amounts of alcoholic beverage consumed also generally decrease with age across many European countries and across the genders, although a slight increase in wine consumption with increasing age can be observed in France ( Mäkelä et al. , 2006 ). In most northern European countries, heavy episodic drinking clearly declines with increasing age, but such reductions are not as observed in more central European countries.

Age also interacts variously with gender across the GENACIS study countries. For example, drinking status and frequency of drinking do not decline with age everywhere. For most European countries, the gender ratio for current drinking status remains rather stable across age groups and, in low- and middle-income countries, there is no clear pattern of the gender gap being larger at younger or older ages. The proportion of heavy drinkers (e.g. 23.2 g ethanol per day or more) tends to decline with increasing age (age categories of 18–34, 35–49, 50–65 years) among the North American and European countries (central and southern European countries tend to be exceptions). The non-European, non-North American countries have varying patterns: in several low- and middle-income countries (e.g. Brazil, India, Nigeria) as well as Japan, heavy drinking is positively correlated with increasing age, especially among men. Heavy episodic drinking has much clearer patterns. In almost all of the GENACIS study countries, the prevalence of heavy episodic drinking decreases with increasing age. However, this reduction is not always proportional across the sexes, leading to higher gender ratios in the older age categories ( Rahav et al. , 2006 ).

1.4.4. Socioeconomic status

In developed economies, people with higher socioeconomic status are more likely to be current drinkers than those with lower socioeconomic status. Among those who drink, drinking frequency is higher among those with higher status. Heavy drinking and heavy episodic drinking are, in general, found to be more common among women of higher socioeconomic status; for men, the trend for both indicators is converse (e.g. Bloomfield et al. , 2006 ). Further, in the USA, it is known that household income, education and employment status are positively associated with current drinking status and more frequent drinking, but are negatively correlated with measures of heavier drinking such as weekly heavy drinking ( Midanik & Clark, 1994 ; Greenfield et al. , 2000 ).

In the Netherlands, van Oers et al. (1999) found that lower educational status was positively related to abstinence from alcohol for both men and women; however, among men, very excessive drinking was more prevalent in the lowest educational group. Among women, higher educational level was associated with fewer reports of psychological dependence and symptomatic drinking, while among men higher educational level was associated with fewer reports of social problems.

Bloomfield et al. (2000) investigated socioeconomic status and drinking behaviour in a sample of the German general population and found, in comparison with men of high socioeconomic status, that men of middle status had increased odds for heavy episodic drinking, while men of lower status had higher odds for symptoms of alcohol dependence. Women of middle socioeconomic status had significantly lower odds for reporting alcohol-related problems and symptoms of alcohol abuse in comparison with women of higher status.

Marmot (1997) examined data from the Whitehall II Study in the United Kingdom and found variations in prevalence of alcoholic beverage consumption by grade of employment. Higher rates of abstention were evident for both sexes among those in the lower employment grades. More moderate drinking was found among men in the higher employment grades, but the proportion of heavier drinkers was rather constant from the highest to lowest grades. However, among women, there was not only a higher proportion of women in the higher grades who drank moderately, but also a much higher rate of heavier drinking.

In a comparative study of socioeconomic position and health, Kunst et al. (1996) found differing associations between heavy drinking and level of education among men and women in eight European countries. Excessive (four glasses or more per day) alcoholic beverage consumption was more common among men with a lower level of education. Among women, no substantial differences were found.

A less consistent pattern has emerged in some low- and middle-income countries such as Brazil, where the higher classes tend to have higher rates of heavier drinking among both genders ( Almeida-Filho et al. , 2005 ; Bloomfield et al. , 2006 ). Similarly, among Argentinean men, more of those with a low level of education (less than 8 years of schooling) are abstainers, while more of those who drink weekly or engage in heavy episodic drinking are more highly educated; for Argentinean women, however, more of those who usually drink three or more drinks or engage in heavy episodic drinking are less educated ( Munné, 2005 ). In a regional sample of China, Wei et al. (2001) reported that men and women with a lower level of education (0–6 years of schooling) were more frequently abstainers, but also more men with a lower level of education drank daily or more frequently than those with a higher level.

1.4.5. Socioeconomic status and beverage preferences

Those who prefer wine compared with beer, spirits or a more mixed consumption come from higher sociodemographic backgrounds (higher socioeconomic status, higher education) and are more frequently light or moderate drinkers. Men and younger individuals more frequently tend to be beer drinkers and women and older people are more frequently wine drinkers (see e.g. the literature reviews in Wannamethee & Shaper, 1999 ; Graves & Kaskutas, 2002 ; Klatsky et al. , 2003 ; Nielsen et al. , 2004 ). With regard to age, Gmel et al. (1999) have shown, in a longitudinal study in Switzerland with clearly different drinking cultures between the German- and Latin-speaking regions, that young people across all regions more often preferred beer, but were more likely when growing older to change to the typical regional pattern. The preference for beer at younger ages was probably related to the fact that beer is the cheapest alcoholic beverage.

Most of the studies on background characteristics of individuals who have different beverage preferences were conducted in only very few countries such as the North American countries, the United Kingdom or Denmark, which are commonly ‘beer countries’, and thus wine consumption might be more closely associated with the habits of the more prosperous sectors of the population. Some similarities have also been found for southern European ‘wine’ countries, such as a higher proportion of heavy drinkers among those who do not drink exclusively wine in Greece ( San José et al. , 2001 ) , consumption of more beer and spirits compared with wine among younger individuals in Spain ( Del Rio et al. , 1995 ) and the proportion of beer in total alcoholic beverage consumption increasing with total ethanol intake in France ( Ruidavets et al. , 2002 ). There is nevertheless sufficient evidence that harm from chronic heavy drinking of wine is found in southern European countries where wine is the culturally preferred and therefore often also the cheapest alcoholic beverage.

The price of alcoholic beverages seems to be a main determinant of which type of beverage is usually preferred, and thus wine as the ‘drink of moderation’ in many established market economies may reflect the better economical status of wine drinkers, which in turn is related to better education and other healthier lifestyles. Decades ago, excessive drinkers or even alcoholics in the USA were called ‘winos’ because they drank the cheapest wines from which they could obtain the most alcohol for their money ( Klatsky, 2002 ). It has been argued that there has been a worldwide shift away from cheap wines to quality wines marketed to middle-class consumers, which may have helped to make table wine the more frequent choice of alcoholic beverage among the better-educated segments of society in Denmark, the USA and some other countries.

Outside the established market economies, the gender and sociocultural backgrounds of beverage preferences are much less consistent. It appears that beverage preference is mostly determined by economic conditions, and the poorest people drink the cheapest and most readily available beverages, which can be wine, beer or locally produced beverages. In contrast, people who have a higher standard of living drink the more expensive beverages, which can be industrial, lager type beers or foreign spirits such as whiskies ( WHO, 2005 ).

According to Benegal (2005) , 95% of the total alcoholic beverages consumed in India by both male and female drinkers is in the form of licit and illicitly distilled spirits; the remainder is mainly beer. The market for wine is small and wine is mainly drunk by people in high socioeconomic classes and predominantly by women. In contrast, consumption of illicit ‘moonshine’ by women was more frequently found among rural and working classes. Men who drink beer consume less alcohol than those who drink spirits in India. On the basis of equal quantities of alcohol, beer is more expensive than spirits, and thus beer is drunk by the middle and upper socioeconomic classes ( Saxena, 1999 ). Beer is also more expensive in Brazil than locally produced spirits such as cachaça and thus the latter is more often consumed by heavy drinkers and is preferred by the poorest and least educated ( Carlini-Cotrim, 1999 ). In Mexico ( Romero-Mendoza et al. , 2005 ), most women drink beer and spirits, but not table wine. Table wine is consumed by the highest socioeconomic classes, whereas the poorest people drink pulque and aquardiente which are often produced illicitly ( Medina-Mora, 1999 ). Among men, more than half of the pulque drinkers were heavy drinkers. In Nigeria ( Ibanga et al. , 2005 ), although wine is the only alcoholic beverage consumed by more women than men, a higher percentage of women (but fewer men) drink beer and local beverages such as burukutu, palmwine and ogogoro (distilled from palmwine) compared with wine. Among men, lower socioeconomic classes prefer traditional African beers and other local beverages whereas commercial western-style beers are preferred by higher socioeconomic classes ( Gureje, 1999 ). In Zimbabwe, the traditional opaque beer is most frequently consumed. Among people with higher incomes, this is replaced by clear (lager-style) beer, fortified wines and imported spirits that are more expensive than the cheapest opaque beer ( Jernigan, 1999 ). Beer and cheap local brews are also more popular than wine among women who drink in Sri Lanka ( Hettige & Paranagama, 2005 ) where women in higher socioeconomic classes also drink wine and whisky, and those in the lower classes also drink hard liquor such as arrak and illicit liquor. In Papua New Guinea ( Marshall, 1999 ), beer is again by far the most popular beverage, followed by rum and Scotch whiskies. White wines are consumed regularly by only a small number of modern, well educated urban women.

The poorest populations and those on the fringe of society, very heavy drinkers and those who are dependent on alcohol are also the people who show the highest prevalence of consumption of surrogate and illegally produced alcoholic beverages (see Sections 1.3 and 1.5 ). The reasons for using illicit and surrogate alcoholic beverages are mainly twofold. Illegal alcoholic beverages are much cheaper, e.g. around 2–6 times less expensive in Estonia and the Russian Federation ( McKee et al. , 2005 ; Lang et al. , 2006 ) than commercial alcoholic beverages. Another reason can be the restricted availability of alcoholic beverages during particular periods (e.g. war or economic crises), or in particular regions such as the native American reservations in the USA (see Section 1.4 ). Particularly in developing countries, illegally produced alcoholic beverages are often the main source of alcohol intake in the lower socioeconomic groups ( Marshall, 1999 ; WHO, 2001 ).

Few representative population surveys on the use of illicit and surrogate alcoholic beverages have been carried out to date. Nevertheless, there is evidence from small-scale studies that their use can be substantial. Lang et al. (2006) reported that 8% of alcoholic beverage consumers in Estonia drink illegal and surrogate alcohols. McKee et al. (2005) estimated that among 25–54-year-olds in Izhevsk, the Russian Federation, 7.3% have drunk surrogate alcoholic beverages in the past year and 4.7% drink them weekly. Consumption of illegally produced alcoholic beverages is very high and can represent up to more than 50% of total alcoholic beverage consumption (see Section 1.5 ) in developing countries ( WHO, 2001 ).

1.5. Non-beverage alcohol consumption

Particularly in central and eastern Europe, but also in developing countries, large discrepancies between recorded alcoholic beverage consumption and potentially alcohol-related mortality can be found. One example is Hungary where mortality from liver disease is approximately fourfold higher than that in countries with similar percapita consumption of alcohol (e.g. Szücs et al. , 2005 ; Rehm et al. , 2007 ). One reason might be the particularly high unrecorded consumption in parts of eastern and central Europe (see Section 1.4 ), which may account for even more alcoholic beverage consumption from unrecorded sources in some countries than from recorded sources ( Szücs et al. , 2005 ). In addition to smuggled commercial and illegally produced, homemade alcoholic beverages, the latter of which are commonly called ‘samogon’ in the Russian Federation or ‘moonshine’ in the USA, a proportion of unrecorded consumption is so-called ‘surrogate alcohol’.

Surrogate alcohol is not defined consistently in the literature. Some authors also include under ‘surrogate alcohol’ illegally produced alcoholic beverages that are intended for consumption as well as alcohols that are not initially intended for consumption ( McKee et al. , 2005 ). Others define surrogate alcohol more strictly as substances that contain ethanol but are ‘not intended’ for consumption such as medicinal alcohol, aftershaves, technical spirits or fire-lighting liquids. Even more strictly, Nordlund and Osterberg (2000) divided the ‘not intended for consumption alcohols’ into alcohol produced for industrial, technical and medical purposes and what they call ‘surrogate alcohol’, namely denatured spirits, medicines and car chemicals that contain alcohol, but which are meant, for example, for car washing. In this section, only surrogate alcohol that is apparently not intended for consumption is discussed. In fact, as argued by McKee et al. (2005) , in some countries, mainly in eastern Europe, it is questionable that part of the production of surrogate alcohols is truly not intended for consumption, e.g. medicinal alcohols sold in bottles with colourful labels that are much larger than those in western Europe or aftershaves that have no discernible warning labels such as ‘for external use only’.

A few studies have used gas chromatography/mass spectrometry to analyse the compounds in such products, mainly in eastern Europe. In these, surrogate alcohol commonly consisted of relatively pure ethanol but at a very high concentration: medicinal spirits contained 60–70% vol ethanol, aftershaves slightly less and other nonmedicinal (fire-lighting liquids) contained very high concentrations of > 90% ( McKee et al. , 2005 ; Lang et al. , 2006 ). Methanol was undetected in theses studies. This, however, might be related to the kind of surrogate alcohol that was analysed, namely medicines, aftershaves and fire-lighting liquids and not industrial alcohol, and to the way in which the alcohol was denatured (e.g. by bitter constituents or methanol) to make it undrinkable. [The Working Group noted that the usual denaturing agents were not analysed in these studies, but the undetected methanol points to the fact that only bitterants were used.] Alcohol is denatured for the purposes of exemption from excise duty. Different substances may be used, e.g. 5 L methylene per 100 L ethanol. Methylene is raw methanol and is produced from the dry distillation of wood that contains at least 10% by weight acetone or a mixture of methylene and methanol. Other denaturing substances include methylethylketone (approx. 1 L per 100 L alcohol) or bitterants such as denatonium benzoate ( Lachenmeier et al. , 2007 ).

Industrial alcohol is often denatured by addition of up to 5% methanol (methylated). So-called ‘meths’ drinking is known all over the world and often has fatal consequences. One of the problems is unintentional ‘meths’ drinking. Alcohol that is offered for consumption on the illegal market is often adulterated by non-drinkable alcohol (e.g. sold as aquardiente in Mexico) ( Medina-Mora, 1999 ), and thus consumers are not aware of the potential risks. However, there is also evidence that some heavy drinkers, commonly the most economically disadvantaged, mix beverage alcohol with industrial methylated alcohol. Although there is no comprehensive review of ‘meths’ drinking worldwide, it probably occurs in numerous countries. Examples are mainly found in developing countries such as Papua New Guinea ( Marshall, 1999 ), Mexico ( Medina-Mora, 1999 ) and India ( Saxena, 1999 ). However, ‘meths’ drinking was also reported not to be uncommon in New Zealand ( Meyer et al. , 2000 ), and the use of denatured alcohol, particularly in form of hairspray and spray disinfectants (‘Montana Gin’), was reported to be widespread among native Americans, at least in the 1980s ( Burd et al. , 1987 ). Ingestion of hairspray still seems to exist in the USA ( Carnahan et al. , 2005 ). The use of industrial alcohol denatured by bitterants (bitrex) was also reported in the late 1980s in Sweden among heavily intoxicated drivers. According to Nordlund and Osterberg (2000) , the phenomenon of drinking surrogate alcohol (mainly medicinal alcohol) still exists in Nordic countries but only on a very small scale.

1.6. Chemical composition of alcoholic beverages, additives and contaminants

1.6.1. general aspects.

Ethanol and water are the main components of most alcoholic beverages, although, in some very sweet liqueurs, the sugar content can be higher than that of ethanol. Ethanol for human consumption is exclusively obtained by the alcoholic fermentation of agricultural products. The use of synthetic ethanol manufactured from the hydration of ethylene for food purposes is not permitted in most parts of the world. However, surrogate alcohol, denatured alcohol or illegally produced alcohol may be used for consumption in certain parts of the world because they may be less expensive than food-grade alcohol.

  • Chem. Abstr. Services Reg. No.: 64–17.5
  • Formula: C 2 H 5 OH
  • Relative molecular mass : 46.07
  • Synonyms: Absolute alcohol, anhydrous alcohol, dehydrated alcohol, ethanol, ethyl alcohol, ethyl hydrate, ethyl hydroxide
  • Description: Clear, colourless, very mobile, flammable liquid; pleasant odour; burning taste
  • Melting-point: −114.1 °C
  • Boiling-point. 78.5 °C
  • Density: d 4 20 0.789
  • Refractive index: n D 20 1.361

Ethanol is widely used in laboratories and in industry as a solvent for resins, fats and oils. It is also used in the manufacture of denatured alcohol, in pharmaceuticals and cosmetics (lotions, perfumes), as a chemical intermediate and as a fuel, either alone or in mixtures with gasoline.

In addition to ethanol and water, wine, beer and spirits may contain volatile and non-volatile compounds. Although the term ‘volatile compound’ is rather diffuse, most of the compounds that occur in alcoholic beverages can be grouped according to whether they are distilled with alcohol and steam or not. Volatile compounds include aliphatic carbonyl compounds, alcohols, monocarboxylic acids and their esters, nitrogen- and sulfur-containing compounds, hydrocarbons, terpenic compounds, and heterocyclic and aromatic compounds. Non-volatile extracts of alcoholic beverages comprise unfermented sugars, di- and tribasic carboxylic acids, colouring substances, tannic and polyphenolic substances and inorganic salts. The flavour composition of alcoholic beverages has been described in detail in several reviews ( Rapp, 1988 , 1992 ; Jackson, 2000 ; Ribéreau-Gayon et al. , 2000 ; Briggs et al. , 2004 ). During maturation, unpleasant flavours disappear. Extensive investigations on the maturation of wine and distillates in oak casks have shown that many compounds are liberated by alcohol from the walls of the casks ( Mosedale & Puech, 1998 ).

The distillation procedure influences the occurrence and concentration of volatile flavour compounds in the distillate. Particularly in the manufacture of strong spirits, it is customary to improve the flavour of the distillate by the removal of low-boiling and high-boiling compounds to a greater or lesser degree.

Extensive literature is available on aroma components that are usually present at low levels. A list of more than 1100 aroma compounds in wine has been provided ( Rapp, 1988 ). Approximately 1300 substances were listed in Appendix 1 of the previous IARC monograph on alcohol drinking ( IARC, 1988 ). Due to advances in analytical chemistry with improved detection limits down to the picograms per litre range, the compilation of such a list would now go beyond the scope of this monograph.

The following text gives only a summarized overview of the main components of individual alcoholic beverages. For further information, the publications of Jackson (2000) and Ribéreau-Gayon et al. (2000) on wine, those of Briggs et al. (2004) and Bamforth (2004) on beer and those of Kolb (2002) and Bryce and Stewart (2004) on spirits are recommended.

The main focus of this section is on additives and contaminants of alcoholic beverages and especially potentially carcinogenic substances.

1.6.2. Compounds in grape wine

Other than alcohol, wines generally contain about 0.8–1.2 g/L aromatic compounds, which constitute about 1% of their ethanol content. The most common aromatic compounds are fusel alcohols, volatile acids and fatty acid esters. Of these, fusel alcohols often constitute 50% of all volatile substances in wine. Although present in much smaller concentrations, carbonyls, phenols, lactones, terpenes, acetals, hydrocarbons and sulfur and nitrogen compounds are more important to the varietal and unique sensory features of wine fragrance ( Jackson, 2000 ).

The taste and oral/lingual sensations of a wine are primarily due to the few compounds that occur individually at concentrations above 0.1 g/L. These include water, alcohol (ethanol), fixed acids (primarily tartaric and malic or lactic acids), sugars (glucose and fructose) and glycerol. Tannins are important sapid substances in red wines, but they rarely occur in significant amounts in white wines without maturation in oak casks ( Jackson, 2000 ).

(a) Alcohols

Ethanol is indisputably the most important alcohol in wine. Under standard conditions of fermentation, ethanol can reach up to about 14–15% vol. The prime factors that control ethanol production are sugar content, temperature and strain of yeast ( Jackson, 2000 ). The alcoholic strength of wine is generally about 100 g/L (12.6% vol) ( Ribéreau-Gayon et al. , 2000 ).

Methanol is not a major constituent in wines, nor is it considered important in the development of flavour. Within the usual range (0.1–0.2 g/L), methanol has no direct sensory effect. The limited amount of methanol that is found in wine is primarily generated from the enzymatic breakdown of pectins. After degradation, methyl groups associated with pectin are released as methanol. Thus, the methanol content of fermented beverages is primarily a function of the pectin content of the fermentable substrate. Unlike most fruit, grapes have a low pectin content. As a result, wine generally has the lowest methanol content of any fermented beverage ( Jackson, 2000 ). Red wines have a higher methanol concentration than rosé wines, while white wines contain even less ( Ribéreau-Gayon et al. , 2000 ).

Alcohols that have more than two carbon atoms are commonly called higher or fusel alcohols. Most of the higher alcohols that are found in wine occur as by-products of yeast fermentation. They commonly account for about 50% of the aromatic constituents of wine, excluding ethanol. Quantitatively, the most important higher alcohols are the straight-chain alcohols, 1-propanol, 2-methyl-1-propanol (isobutyl alcohol), 2-methyl-1-butanol and 3-methyl-1-butanol (isoamyl alcohol). 2-Phenylethanol is the most important phenol-derived higher alcohol ( Jackson, 2000 ).

Unfermented sugars are collectively termed residual sugars. In dry wines, the residual sugar content consists primarily of pentose sugars, such as arabinose, rhamnose and xylose, and small amounts of unfermented glucose and fructose (approximately 1–2 g/L). These levels may increase slightly during maturation in oak casks through the breakdown of glycosides in the wood. The residual sugar content in dry wine is generally less than 1.5 g/L ( Jackson, 2000 ).

(c) Polyols and sugar alcohols

The diol 2,3-butanediol can be found in wine. By far the most prominent polyol in wine is glycerol. In dry wine, it is commonly the most abundant compound, after water and ethanol. Glycerol has a slightly sweet taste but this is probably not noticeable in a sweet wine. It may be slightly noticeable in dry wines, in which the concentration of glycerol often surpasses the sensory threshold for sweetness (> 5 g/L).

Sugar alcohols, such as alditol, arabitol, erythritol, mannitol, myo-inositol and sorbitol, are commonly found in small amounts in wine ( Jackson, 2000 ).

For the majority of table wines, a range of 5.5–8.5 g/L total acidity is desired. It is typically preferred that white wines be at the higher end of the scale and that red wines be at the lower end. Thus, a pH range of 3.1–3.4 is the goal for white wines and that of 3.3–3.6 for most red wines.

Acidity in wine is customarily divided into two categories—volatile and fixed. Volatile acidity refers to acids that can readily be removed by steam distillation, whereas fixed acidity describes those acids that are only slightly volatile. Total acidity is the combination of both categories. As a group, acids are almost as important to wines as alcohols. They not only produce a refreshing taste (or sourness, if in excess), but they also modify the perception of other tastes and oral/lingual sensations.

Acetic acid is the main volatile acid but other carboxylic acids, such as formic, butyric and propionic acids, may also be involved. Small amounts of acetic acid are produced by yeasts during fermentation. At normal levels in wine (< 300 mg/L), acetic acid is a desirable flavourant and adds to the complexity of taste and odour. It is equally important for the production of several acetate esters that give wine a fruity character.

Fixed acidity is dominated by tartaric and malic acid. However, lactic acid may also occur if so-called malolactic fermentation by lactic acid bacteria is encouraged. The major benefit of malolactic fermentation is conversion of the harsher-tasting malic acid to the smoother-tasting lactic acid ( Jackson, 2000 ).

(e) Aldehydes and ketones

Acetaldehyde (ethanal) is the major aldehyde found in wine, and often constitutes more than 90% of the aldehyde content. It is one of the early metabolic by-products of fermentation. As fermentation approaches completion, acetaldehyde is transported back into yeast cells and is reduced to ethanol. Thus, the acetaldehyde content usually falls to a low level by the end of fermentation. [The Working Group noted that it is therefore not possible to specify an average acetaldehyde content in wine.] For information on acetaldehyde as a direct metabolite of ethanol in the human body, see Section 4 of this monograph. Other aldehydes that occur in wine are hexanal, hexenal, furfural and 5-(hydroxymethyl)-2-furaldehyde. Phenolic aldehydes such as cinnamaldehyde and vanillin may accumulate in wines that have matured in oak casks.

Only few ketones are found in grapes, but those that are present usually survive fermentation. Examples are the norisoprenoid ketones, β-damascenone, α-ionone and β-ionone. Diacetyl (2,3-butanedione) and 2,3-pentanedione may be produced during fermentation ( Jackson, 2000 ).

Of all the functional groups in wine, esters are the most frequently encountered. Over 160 specific esters have been identified ( Jackson, 2000 ).

The most prevalent ester in wine is ethyl acetate. A small quantity is formed by yeast during fermentation, but larger amounts result from the activity of aerobic bacteria, especially during maturation in oak barrels. Ethyl acetates of fatty acids, mainly ethyl caproate and ethyl caprylate, are also produced by yeast during fermentation. Ethyl acetates of fatty acids have very pleasant odours of wax and honey, which contribute to the aromatic finesse of white wines. They are present at total concentrations of a few milligrams per litre. The formation of esters continues throughout the ageing process due to the presence of many different acids and large quantities of ethanol. In vintage wines, approximately 10% of the acids are esterified ( Ribéreau-Gayon et al. , 2000 ).

(g) Lactones

Volatile lactones are produced during fermentation and probably contribute to the aroma of wine. The best known is γ-butyrolactone, which is present in wine at milligram-per-litre concentrations. Lactones may also derive from the grapes, as is the case in Riesling wines in which they contribute to the varietal aroma. Lactones are released into wine during ageing in oak barrels. The cis and trans isomers of 3-methyly-octalactone are known as ‘oak lactones’ or ‘whisky lactones’. Concentrations in wine are of the order of a few tens of milligrams per litre ( Ribéreau-Gayon et al. , 2000 ).

(h) Terpenes

Approximately 40 terpene compounds have been identified in grapes. Some of the monoterpene alcohols are among the most odiferous, especially linalool, a-terpineol, nerol, geraniol, citronellol and ho-trienol. Furthermore, the olfactory impact of terpene compounds is synergistic. They play a major role in the aromas of grapes and wines from the Muscat family ( Ribéreau-Gayon et al. , 2000 ). The monoterpenes found in wine have been reviewed ( Mateo & Jiménez, 2000 ).

(i) Nitrogen-containing compounds

Many nitrogen-containing compounds are found in wine. These include inorganic forms, such as ammonia and nitrates, and diverse organic forms, including amines, amides, amino acids, pyrazines, nitrogen bases, pyrimidines, proteins and nucleic acids ( Jackson, 2000 ). Red wines have average nitrogen concentrations that are almost twice those of white wines. The total nitrogen concentration in red wines varies from 143 to 666 mg/L, while values in white wines range from 77 to 377 mg/L ( Ribéreau-Gayon et al. , 2000 ).

Several simple volatile amines have been found in wine, including ethylamine, phenethylamine, methylamine and isopentylamine. Wine also contains small amounts of non-volatile amines, the most well studied of which is histamine. Other physiologically active amines include tyramine and phenethylamine. Polyamines such as putrescine and cadaverine may be present as a result of bacterial contamination ( Jackson, 2000 ).

Urea is found at concentrations of less than 1 mg/L in wine, and is significant in winemaking as it may be a precursor of ethyl carbamate ( Ribéreau-Gayon et al. , 2000 ). For a detailed discussion of the occurrence of ethyl carbamate in wine, see Section 1 in the monograph on ethyl carbamate in this Volume.

(j) Sulfur-containing compounds

Hydrogen sulfide and sulfur-containing organic compounds generally occur in trace amounts in finished wines, except for non-volatile proteins and sulfur-containing amino acids ( Jackson, 2000 ). Sulfur-containing compounds in wine have been studied extensively because of their effect on wine aroma. The significance of organic sulfur compounds in wine aroma has been reviewed ( Mestres et al. , 2000 ).

(k) Phenols and phenyl derivatives

Phenols are a large and complex group of compounds that are of particular importance to the characteristics and quality of red wine. They are also significant in white wines, but occur at much lower concentrations ( Jackson, 2000 ).

Phenolic compounds are partly responsible for the colour, astringency and bitterness of wine. The term ‘phenolic’ or ‘polyphenolic’ describes the compounds that possess a benzenic ring substituted by one or several hydroxyl groups (-OH). Their reactivity is due to the acidic character of the phenolic function and to the nucleophilic character of the benzene ring. Based on their carbon skeleton, polyphenols are classified in non-flavonoid and flavonoid compounds. Grapes contain non-flavonoid compounds mainly in the pulp, while flavonoid compounds are located in the skin, seeds and stems. The phenolic composition of wines is conditioned by the variety of grape and other factors that affect the development of the berry, such as soil, geographical location and weather conditions. In contrast, winemaking techniques play an important role in the extraction of polyphenols from the grape and in their further stability in wine; the duration of maceration and fermentation in contact with grape skins and seeds, pressing, maturation, fining and bottle ageing are all factors that affect the phenolic composition of wines ( Monagas et al. , 2005 ).

In recent years, much effort has been devoted to the study of grape and wine polyphenols, an area that is essential to evaluate the potential of different varieties of grape, to optimize enological processes, to obtain products with peculiar and improved characteristics and to achieve a better understanding of the polyphenolic properties of wine. The main types of phenolic compound found in wine include hydroxybenzoic and hydroxycinnamic acids, stilbenes, flavones, flavonols, flavanonols, flavanols and anthocyanins ( Monagas et al. , 2005 ).

Phenolic compounds in wine have been reviewed ( Ribéreau-Gayon et al. , 2000 ; Monagas et al. , 2005 ; Makris et al. , 2006 ).

(l) Inorganic anions and cations

The chloride concentration in most wines is below 50 mg/L, but may exceed 1 g/L in wine made from grapes that are grown near the sea. Natural wine contains only low concentrations of sulfates (between 100 and 400 mg/L), but these may gradually increase during ageing due to repeated sulfuring and oxidation to sulfur dioxide. In heavily sulfured sweet wines, sulfate concentrations may exceed 2 g/L after a few years of barrel ageing. White wine contains 70–500 mg/L phosphate, whereas concentrations in red wines range from 150 mg/L to 1 g/L. These wide variations are related to the addition of diammonium phosphate to must to facilitate alcoholic fermentation.

Potassium is the dominant cation in wine, and concentrations range between 0.5 and 2 g/L, with an average of 1 g/L. Sodium concentrations range from 10 to 40 mg/L, and calcium concentrations range between 80 and 140 mg/L in white wines, but are slightly lower in red wines. Wine contains more magnesium (60–150 mg/L) than calcium and concentrations do not decrease during fermentation or ageing ( Ribéreau-Gayon et al. , 2000 ).

Further inorganic constituents and contaminants are discussed in detail in Section 1.6.7 of this monograph.

1.6.3. Compounds in beer

Beer is currently a highly consistent commodity. Despite its reliance on agricultural products, the control and predictability of the processes by which beer is made provide that seasonal and regional variations can be overcome such that the taste, appearance and composition of a beer are generally consistent from batch to batch. Vintage in brewing does not exist ( Bamforth, 2004 ).

Most beers comprise at least 90% water, with ethanol and carbon dioxide being quantitatively the next major individual components. Beer also contains a wide range of chemical species in relatively small quantities that determine its properties in respect to appearance and flavour ( Bamforth, 2004 ). More than 450 constituents of beer have been characterized; in addition, it contains macromolecules such as proteins, nucleic acids, polysaccharides and lipids ( Briggs et al. , 2004 ).

Beers vary substantially in their alcoholic strength from brand to brand; however, most are in the range of 3–6% vol. In the United Kingdom, the mean alcohol content of all beers is 4.1% vol whereas, in the USA, the average alcoholic strength is 4.6% vol ( Bamforth, 2004 ). Other authors reported a mean alcoholic strength of 5.5% vol for ales and 5.3% vol for lagers on the US market ( Logan et al. , 1999 ; Case et al. , 2000 ). In the United Kingdom, the average alcoholic strength of the top five best-selling brands was 3.7% vol for ales and 4.5% vol for lagers ( Thomas, 2006 ).

(b) Carbon dioxide

Carbon dioxide is produced together with ethanol during fermentation, and plays a substantial role in establishing the quality of beer. Apart from its influence in oral/lingual sensation, carbon dioxide determines the extent of foam formation and naturally influences the delivery of volatiles into the headspace of beers. Most cans or bottles of beer contain between 2.2 and 2.8 volumes of carbon dioxide (that is, between 2.2 and 2.8 cm 3 carbon dioxide is dissolved in every cubic centimetre of beer) ( Bamforth, 2004 ).

(c) Non-volatile constituents

While most of the sugar found in wort is fermented to ethanol by yeast, some carbohydrates remain in the beer. The carbohydrates that survive in beer from the wort are non-fermentable dextrins and some polysaccharide material ( Bamforth, 2004 ).

Quantitatively, glycerol is an important constituent of beers, in which a range of 436–3971 mg/L has been found. Significant amounts of higher polyols have not been found, but beer contains butane-2,3-diol (up to 280 mg/L) and smaller amounts of pentane-2,3-diol together with 3-hydroxybutan-2-one (acetoin; 3–26 mg/L) and 3-hydroxypentan-2-one. These are reduction products of volatile vicinal diketones. Cyclic acetals (1,3-dioxolanes) may be formed between butan-2,3-diol and acetaldehyde, isobutanal or isopentanal. Another non-volatile alcohol found in beer is tyrosol ( Briggs et al. , 2004 ).

A range of non-volatile acids (C 4 –C 18 ) was found in beer. The highest levels of lactic acid were found in Belgian ‘acid’ beers ( Briggs et al. , 2004 ). The normal levels of lactic acid in uninfected bottom-fermented beers are up to 200–300 mg/L, whereas top-fermented beer may contain up to 400–500 mg/L ( Uhlig & Gerstenberg, 1993 ). The native content of citric acid in beer is in the range of 140–232 mg/L (average, 187 mg/L). Lower contents may be found due to decomposition of citrate by lactic acid bacteria or by the use of adjuncts (e.g. rice, maize or sugars) ( Gerstenberg, 2000 ).

Autoxidation of linoleic acid gives rise to isomers of dihydroxy- and trihydroxyoctadecenoic acids. These hydroxyl acids are potential precursors of 2- trans -nonenal, which contributes a cardboard flavour to stale beer ( Briggs et al. , 2004 ). The formation of 2- trans -nonenal and other stale flavours has been reviewed ( Vanderhaegen et al. , 2006 ). During storage, the chemical composition may change, which alters the sensory properties. In contrast to some wines, the ageing of beer is usually considered to be negative for flavour quality.

(d) Volatile constituents

One hundred and eighty-two volatile compounds were recently detected in beer samples ( Pinho et al. , 2006 ). The majority of the volatile constituents of beer are fermentation products. As in wine, the largest group of volatile constituents in beer are higher alcohols, principally 3-methylbutanol (isoamyl alcohol), 2-methylbutanol, isobutyl alcohol, propanol and phenylethanol. Other volatile constituents are 4-vinylphenol and 4-vinylguaiacol, which are regarded as off-flavours in most beers. However, 4-vinylguaiacol, which has a clove-like flavour, provides part of the essential character of wheat beer ( Briggs et al. , 2004 ).

Only low levels of aldehydes are found in beer, the principal of which is acetaldehyde. During the storage of bottled beer, higher alcohols are oxidized to aldehydes by melanoidins. During fermentation, acetaldehyde is normally reduced to ethanol but it can be oxidized to acetic acid, which is the major volatile acid in beer ( Briggs et al. , 2004 ). Minor aldehydes identified in beer include the so-called Strecker aldehydes—2-methylpropanal, 2-methylbutanal, 3-methylbutanal, methional and phenylacetaldehyde. The increase in these aldehydes may play a central role in flavour changes during the ageing of beer. Aldehydes related to the autoxidation of linoleic acid are pentanal and hexanal ( Vesely et al. , 2003 ).

Flavour-active esters have been reviewed ( Verstrepen et al. , 2003 ). Ethyl acetate is the major ester found in beer (8–32 mg/L); further aroma-active esters in lager beer include isoamyl acetate (0.3–3.8 mg/L), ethyl caproate (0.05–0.3 mg/L), ethyl caprylate (0.04–0.53 mg/L) and phenyl ethyl acetate (0.10–0.73 mg/L).

Odour-active compounds derived from hops include linalool, geraniol, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate and ethyl 2-methylpropanoate ( Kishimoto et al. , 2006 ); 40 odour-active constituents were identified in Pilsner beer, among which ethanol, β-damascenone, linalool, acetaldehyde and ethyl butanoate had the highest values for odour activity, followed by ethyl 2-methylpropanoate and ethyl 4-methylpentanoate ( Fritsch & Schieberle, 2005 ). The concentration of linalool was found to be correlated with the intensity of the aroma of hops ( Steinhaus et al. , 2003 ).

(e) Nitrogen-containing compounds

Most beers contain 300–1000 mg/L total nitrogen ( Briggs et al. , 2004 ). The breakdown of a wide range of amino acids was determined during the ageing in beer. The content of phenylalanine, histidine and tyrosine decreased most rapidly followed by that of isoleucine, leucine and lysine. The decrease in amino acids was greater in beers that had a higher content of dissolved oxygen ( Basarová et al. , 1999 ).

The presence of biogenic amines in beer is important toxicologically. During brewing, the types of amine are dependent on the raw materials used in the beverage as well as the method of brewing and any microbiological contamination that may have occurred during the brewing process or during storage. The amines in beer can be divided into two groups. One includes putrescine, spermidine, spermine and agmatine and can be considered as natural beer constituents that primarily originate from the malt, while the other, which includes mainly histamine, tyramine and cadaverine, usually indicates the activity of contaminating lactic acid bacteria during brewing ( Kalac & Kriżek, 2003 ). The level of biogenic amines in beer was found to reflect the microbiological quality of the fermentation process ( Loret et al. , 2005 ).

(f) Sulfur-containing compounds

Beer contains 100–400 mg/L sulfate. The major non-volatile organic sulfur compounds in beer are the amino acids, cysteine and methionine, and the peptides and proteins that contain them. Dimethyl sulfide is an important flavour component of lager beers. It is mainly formed by the breakdown of S -methylmethionine which is present in malt ( Briggs et al. , 2004 ). Sulfur compounds, including thioesters, thiophenes, polysulfides, terpens and thiols, may also derive from hops ( Lermusieau & Collin, 2003 ). Polyfunctional thiols were recently detected in lager beers ( Vermeulen et al. , 2006 ).

(g) Flavours and constituents from hops

Of all the herbs that have been used to flavour and preserve beer over the ages, only the hop (Humulus lupulus L.) is now regarded as a raw material that is essential to brewing throughout the world ( Moir, 2000 ).

α-Acids can account for between 2% and 15% of dry weight of hops, depending on the variety and the environment. When wort is boiled, α-acids are isomerized to form iso -α-acids, which are much more soluble and stable than α-acids. In addition to imparting bitterness to beer, iso -α-acids also promote foaming by cross-linking the hydrophobic residues on polypeptides with their own hydrophobic side-chains. Furthermore, they have strong antimicrobial properties ( Bamforth, 2004 ). Bitter acids in beer have been reviewed ( de Keukeleire et al. , 1992 ; Schönberger, 2006 ). The amount of iso -α-acids varies significantly between different types of beer; Pilsner-type beers usually contain the largest amount of bitter hop substances ( Lachenmeier et al. , 2006a ).

Hop is the raw material in beer that serves as an important source of phenolic compounds (see below). A recent review summarized 78 known phenolic constituents of beer ( Gerhäuser, 2005 ). Xanthohumol and related prenylflavonoids have also been reviewed ( Stevens & Page, 2004 ).

(h) Phenolic compounds and antioxidants

Phenolic constituents of beer are derived from malt (70–80%) and hops (20–30%). Structural classes include simple phenols, benzoic and cinnamic acid derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins, (prenylated) chalcones and flavonoids as well as the previously mentioned α- and iso -α-acids derived from hops ( Gerhäuser, 2005 ).

According to some studies, levels of antioxidants in beer are of the same order of magnitude as those found in fruit juices, teas and wines ( Vinson et al. , 1999 ; Gorinstein et al. , 2000 ). Beer may provide more antioxidants per day than wine in the US diet ( Vinson et al. , 2003 ). More than 80% of the antioxidant activity of beer in vitro derives from non-tannin non-flavonoid compounds (mainly phenolic acids). However, there is some concern about the activity of different classes of phenols in vivo due to low bioavailability and breakdown into inactive fragmentation products ( Fantozzi et al. , 1998 ).

(i) Vitamins

Beer contains many water-soluble vitamins, notably folate, riboflavin, pantothenic acid, pyridoxine and niacin. As much as 10% of the daily intake of folate may derive from beer in some countries. Fat-soluble vitamins do not survive in beer and are lost with insoluble components during processing. Some beers contain vitamin C, because this material may be added to protect the beer from oxidation ( Bamforth, 2004 ). Half a litre of beer could cover 20–25% of the daily requirements of riboflavin, niacin and pyridoxine ( Billaud & Delestre, 2000 ).

(j) Minerals

Beer is rich in magnesium and potassium but relatively deficient in iron, zinc and calcium. The presence of iron in beer is avoided deliberately by brewers because it acts as a pro-oxidant ( Bamforth, 2004 ). Beer may also be a main nutritional source of selenium ( Darret et al. , 1986 ). The inorganic composition of beer has been reviewed ( Briggs et al. , 2004 ). Further inorganic constituents and contaminants in beer are discussed in detail in Section 1.6.7 of this monograph.

1.6.4. Compounds in spirits

A large range of very diverse products constitute the category ‘spirits’. The alcoholic strength of spirits is usually higher than 15% vol and may be up to 80% vol in some kinds of absinthe. The typical alcoholic strength of the most common spirits (e.g. brandy, whisky and tequila) is ∼40% vol.

A classification of spirits can be made according to their sugar content. Several spirits contains no sugar, or sugar is used only to soften the final taste of the product (up to 10 g/L of sugar). Spirits with high sugar contents (> 100 g/L) are commonly designated as ‘liqueurs’.

Another differentiation can be made between spirits produced exclusively by alcoholic fermentation and distillation of natural products (e.g. sugar cane, fruit and cereals) and products that are made from highly rectified ethanol of agricultural origin (so-called neutral alcohol; e.g. gin, aniseed-flavoured spirit drinks and most liqueurs).

The volatile compounds in alcoholic beverages are usually expressed in units of ‘g/hL pure alcohol’ or ‘g/hL of 100% vol alcohol’ (i.e. the concentrations are standardized with regard to alcoholic strength). This enables high-proof distillates and distillates diluted to drinking strength to be compared directly.

Because the chemical compositions of the various types of spirits differ significantly (e.g. the methanol content may vary from not detectable concentrations in vodka up to about 1000 g/hL pure alcohol in certain fruit spirits), some types of spirits are discussed separately in the following sections. The groups of spirits were selected on the basis of knowledge of their production methods and constituents and not necessarily because of their prevalence in the world market. [The Working Group noted that the major focus of research in the past has been on European-style spirits, and found a lack of information on Asian-type products.]

(a) Sugar-cane spirits (rum, cachaça)

The two most important types of sugar-cane spirits are rum (usually produced in the Carribean) and cachaça from Brazil.

The production of rum has been reviewed ( Delavante, 2004 ). The sugar in cane molasses is used as the fermentation substrate in the production of rum. The chemical constituents of rum were found to be so heterogeneous that it was not possible to determine an average composition. The contents of 1-propanol, isobutanol and amyl alcohols were < 10–400, 70 and 100 g/hL pure alcohol, respectively. Some samples also showed high levels of acetaldehyde and 1,1-diethoxyethan, whereas these constituents were not detected in other samples. The number of detectable esters in rum was smaller than that in brandies, whiskies or fruit spirits ( Postel & Adam, 1982a ). The concentrations of volatile fatty acids, acetic acid and formic acid varied greatly between different samples of rum. The maxima were 12 mg/L propionic acid, 5.1 mg/L butyric acid and 24 mg/L decanoic acid ( Sponholz et al. , 1990 ). Low concentrations of ethyl hexanoate, ethyl octanoate, ethyl decanoate and ethyl dodecanoate were found in white rums ( Pino et al. , 2002 ). The average level of ketones in rum was 2.15 mg/L acetone, 0.35 mg/L cyclopentanone and 1.75 mg/L 2,3-butanedione ( Cardoso et al. , 2003 ).

The production of cachaça has been reviewed ( Faria et al. , 2004 ). The Brazilian spirits, cachaça, caninha and aguardente de cana, are made from fermented sugar-cane juice. The term caipirinha refers to the lemon drink made from cachaça. The major volatile compounds in cachaça are the higher alcohols, isoamyl alcohol, isobutyl alcohol and propanol; however, significant variations were detected depending on the strain of yeast used for fermentation ( Souza Oliveira et al. , 2005 ). During ageing in wood casks, the levels of higher alcohols decrease, whereas the concentrations of aldehydes, ethyl acetate and acetic acid increase ( Bolini et al. , 2006 ). The most abundant acid in cachaça is acetic acid, which represents up to 90–95% of the total content of acids found. The concentration of acids (C 2 –C 18 ) in cachaça is in the same order of magnitude as that in whiskies, rums and cognacs ( Ferreira Do Nascimento et al. , 2000 ). The major aldehyde in cachaça is acetaldehyde (average, 11 g/hL pure alcohol). Minor aldehydes include formaldehyde, 5-hydroxymethylfurfural, acrolein, furfural, propionaldehyde, butyraldehyde, benzaldehyde, isovaleraldehyde and n -valeraldehyde (all below 5 g/hL pure alcohol) ( Nascimento et al. , 1997 ). The levels of 5-hydroxymethylfurfural can be attributed to the use of very old barrels or barrels that undergo no treatment before re-utilization. Other markers of ageing detected in cachaça include gallic acid, vanillic acid, syringic acid, vanillin, syringaldehyde, coniferaldehyde, sinapaldehyde and coumarin ( de Aquino et al. , 2006 ). Quantification of ketones in cachaças yielded the following average levels: 3.31 mg/L acetone, 1.24 mg/L acetophenone, 1.15 mg/L cyclopentanone and 4.34 mg/L 2,3-butanedione. Except for acetophenone, cachaça and rum exhibited the same qualitative profile of ketones ( Cardoso et al. , 2003 ). Large variations in the phenol content of cachaça were noted. Concentrations of total phenols were between 1.5 and 70 mg/L, and those of flavonoids were from below detection to 3.5 mg/L ( Bettin et al. , 2002 ).

Differences in the composition of cachaça and rum were found using multivariate data analysis. Protocatechuic acid, propanol, isobutanol, isopentanol, copper, manganese and magnesium were selected as chemical discriminators from a range of volatile components, acids, polyphenols and metals ( Cardoso et al. , 2004 ). Flavour differences between cachaça and rum were easily recognizable; the flavour compounds P-damascenone, ethyl butyrate, isobutyrate and 2-methylbutyrate were found at the same levels in both cachaça and rum, whereas levels of spicy-smelling eugenol, 4-ethylguaiacol and 2,4-nonadienal were much higher in cachaça ( de Souza et al. , 2006 ).

(b) Whisky or whiskey

Scotch whisky has been reviewed ( Halliday, 2004 ). Further important international types of whisky include American whiskey (e.g. bourbon) and Canadian whiskey, and the production of whiskey has also been reviewed ( Ströhmer, 2002 ).

Scotch whisky and Irish whiskey are produced exclusively from the distillation of a mash made from malted cereals that has been saccharified, fermented by the action of yeast and distilled by one or more distillations at less than 94.8% vol, so that the distillate has an aroma and taste derived from the raw materials. The final distillate must mature for at least 3 years in wooden casks that do not exceed 700 L in capacity. The minimum alcoholic strength of such beverages is 40% vol ( European Council, 1989 ).

The composition of the different whiskies was compared and significant differences in their volatile composition were detected ( Postel & Adam, 1977 , 1978 , 1979 ). The American bourbons contained the largest amount of volatile compounds (> 500 g/hL pure alcohol), followed by Scotch (∼250 g/hL pure alcohol) and Canadian blends (∼100 g/hL pure alcohol) ( Postel & Adam, 1982b ). In a more recent study, 40 blended Scotch whiskies were characterized, and four categories could be distinguished. Deluxe blends contained higher concentrations of ethyl (C 6 –C 10 ) esters, isoamyl hexanoate and alcohol. Standard blends were differentiated by their contents of acetate esters (dodecyl, phenyl ethyl and 3-methylbutyl acetates). In contrast, retailer blends were dominated by high contents of longer (> C 10 ) aliphatic esters, alcohols and unsaturated fatty acid ethyl esters. Furfural, ethyl benzoate, isobutyl octanoate and medium-chain esters, notably ethyl nonanoate, were characteristic of West Highland blends ( Lee et al. , 2001 ). Seventy volatile compounds were identified in Scotch whisky—mainly fatty acid ethyl esters, higher alcohols, fatty acids, carbonyl compounds, monoterpenols, C 13 norisoprenoids and some volatile phenols. The ethyl esters form an essential group of aromatic compounds in whisky, to which they confer a pleasant aroma with fruity odours. Qualitatively, isoamyl acetate, which has a ‘banana’ aroma, was the most interesting. Quantitatively, significant components were ethyl esters of caprilic, capric and lauric acids. The highest concentrations of fatty acids were observed for caprilic and capric acids. Of the higher alcohols, fusel oils (3-methylbutan-1-ol and 2-phenylethanol) were the most abundant ( Câmara et al. , 2007 ). The nature and origin of flavours in whiskies have been reviewed ( Lee et al. , 2001 ). Furfural and 5-hydroxymethyl-2-furaldehyde were proposed as a standard to identify authentic straight American whiskeys as opposed to those blended with neutral spirit ( Jaganathan & Dugar, 1999 ).

The production of brandy has been reviewed ( Ströhmer, 2002 ). Brandies are typically derived from distilled wine. Traditional products include the French ‘cognac’ and ‘armagnac’, the Spanish ‘brandy de Jerez’ and the German ‘Weinbrand’. European legislation prescribes that brandy must be produced from wine spirit (the term ‘brandy’ may not be used for other products such as fruit spirits). Brandies must be matured for at least 1 year in oak receptacles or for at least 6 months in oak casks with a capacity of less than 1000 L. They must contain a quantity of volatile substances (other than ethanol and methanol) that is equal to or exceeds 125 g/hL pure alcohol and derived exclusively from the distillation or redistillation of the raw materials used. The maximum methanol content is 200 g/hL pure alcohol. The minimum alcoholic strength of brandy is 36% vol ( European Council, 1989 ).

The volatile composition of brandy differs according to the region of origin. In all brandies, acetaldehyde, 1,1-diethoxyethan and furfural are the main carbonyl compounds, amyl alcohols, isobutanol, propanol-1 and methanol are the major alcohols and ethyl acetate and ethyl lactate are the major esters. German brandies showed a larger variation in their volatile composition than cognac and armagnac. Brandies usually contain a larger amount of volatile substances than that legally required of about 500 g/hL pure alcohol ( Postel & Adam, 1982c ). The amounts of ethyl ester vary widely, depending on the different raw materials used and the technology applied. Methyl esters are present in very small amounts only, generally less than 0.05 g/hL pure alcohol. Ethyl heptoate and ethyl nonanoate contents are generally less than 0.1 g/hL pure alcohol ( Postel & Adam, 1984 ). In comparison with German and French brandies, Spanish brandies contain on average larger amounts of methanol, acetaldehyde and 1,1-diethoxyethane and smaller amounts of higher alcohols and higher esters ( Postel & Adam, 1986a , b ). Later investigations showed that the average composition of German or French brandy had not changed considerably; however, considerable differences exist between the various brands ( Postel & Adam, 1987 , 1990a , b , c ). In German brandy, the methanol content was in the range of 46–110 g/hL pure alcohol, the content of higher alcohols varied between 235 and 382 g/hL pure alcohol ( Postel & Adam, 1987 ), acetaldehyde content was in the range of 18–45 g/hL pure alcohol, the sum of carbonyls and acetals was in the range of 30–77 g/hL pure alcohol, the concentrations of terpenes were in the range of 0.06–0.38 g/hL pure alcohol ( Postel & Adam, 1988a ) and the amount of esters was between 27 and 101 g/hL pure alcohol ( Postel & Adam, 1988b ). Trace volatile compounds in cognac were studied by Ledauphin et al. (2004 , 2006a ). Compounds specific to cognac include numerous hexenyl esters and norisoprenoidic derivatives.

Esterification and formation of methyl ketone may be two of the most important processes in the ageing of cognac over a long time period. Using multivariate regression of 17 volatile compounds (13 ethyl esters and four methyl ketones), it was possible to predict the age of a cognac with a high degree of accuracy ( Watts et al. , 2003 ). In brandy de Jerez, an increase in sugar concentration during ageing was detected, and arabinose was especially strongly correlated with ageing ( Martínez Montero et al. , 2005 ). Caramel, which is used as a colouring agent, may be detected by the ratio between furfural and 5-hydroxymethylfurfural which is greater than 1 in brandies that do not contain caramel and lower than 1 in those that do contain caramel ( Quesada Granados et al. , 1996 ). Genuine ageing in oak is also indicated by a total syringyl compound content that is higher than the total vanillyl compound content. An increase in vanillin concentration indicates added substances, possibly almond shells ( Delgado et al. , 1990 ). The quality control of cognacs and cognac spirits was recently reviewed and methods to detect adulterated samples were given ( Savchuk & Kolesov, 2005 ).

(d) Grape marc spirit

Grappa is the most prominent example of grape marc spirit, and may be produced solely in Italy ( European Council, 1989 ). Marc spirit contains a significantly higher content of volatile compounds than brandy (about 2000 g/hL pure alcohol) ( Postel & Adam, 1982c ). The maximum methanol content is 1000 g/hL pure alcohol and the minimum alcoholic strength of marc is 37.5% vol.

Fusel alcohols were quantitatively the largest group of flavour compounds in Portuguese marcs of the Alvarinho and Loureiro varieties, and their concentrations ranged from 395 to 2029 mg/L. Ethyl acetate and ethyl lactate were the most abundant esters, with concentrations ranging from 176 to 9614 and from 0 to 310 mg/L, respectively. The duration of fermentation most strongly affected the composition of marcs in terms of higher alcohols, while the addition of pectinases and the material of the containers most strongly affected composition in terms of methanol (concentration range, 2694–6960 mg/L) and 2-butanol (concentration range, 0–279 mg/L). The addition of pectinase had the most statistically significant effect on methanol content, whereas duration of fermentation time had the most significant effect on the 2-butanol content ( Luz Silva & Xavier Malcata, 1998 ).

(e) Fruit spirits

Fruit spirits (formerly sometimes called ‘fruit brandies’) are relatively inhomogeneous chemically, because their composition varies greatly between the different types of fruit. In Europe, fruit spirits must be produced exclusively by the alcoholic fermentation and distillation of fleshy fruit or must of such fruit, with or without stones. In general, the quantity of volatile substances (other than ethanol and methanol) should exceed 200 g/hL pure alcohol and the maximum methanol content is 1000 g/hL pure alcohol ( European Council, 1989 ).

Methanol is quantitatively the main component of stone and pome fruit spirits in addition to water and ethanol. Plum, mirabelle and Williams distillates generally contain more than 1000 g/hL pure alcohol (an exception to the maximum methanol content was made for these fruits), whereas cherry distillates contain less. Since a certain minimum amount of methanol is formed by enzymatic cleavage of pectin during fermentation of the fruit mash, the methanol content of fruit spirits may be used to evaluate their authenticity and possible adulteration such as by the addition of neutral alcohol ( Postel & Adam, 1989 ). These high methanol concentrations in fruit spirits are nevertheless below the concentration of 2% vol that was proposed as a tolerable concentration in alcoholic beverages ( Paine & Davan, 2001 ). However, with regard to the toxicological effects of methanol, a reduction is desirable to ensure a greater margin of safety. Several ways to decrease the methanol content have been discussed, such as heat treatment of the mash to inactivate proteolytic enzymes ( Postel & Adam, 1989 ). Other authors demonstrated that acid treatment of the mash might delay methanol deesterification and reduce methanol content by up to 50% ( Glatthar et al. , 2001 ). A significant linear decrease in methanol in cherry spirits was noted between 1980 and 2003 ( Lachenmeier & Musshoff, 2004 ).

In comparison with other groups of spirits, fruit spirits contain large amounts of 1-propanol, 1-butanol, 2-butanol and 1-hexanol. Concentrations of isobutanol and amyl alcohols are approximately in the same range as those in other groups of spirits such as whiskies and brandies. Some terpene compounds, such as a-terpineol, geraniol, linalool, cis - and trans -linalooloxide, were found in fruit spirits (< 1 g/hL pure alcohol). Among the carbonyl compounds, acetaldehyde and 1,1-diethoxyethane dominate; the mean values of their concentrations range from 9 to 17 and 4.5 to 9.5 g/hL pure alcohol, respectively. Other carbonyl compounds present in fruit spirits are propionaldehyde, isobutyraldehyde, acrolein, benzaldehyde, furfural, acetone, methylethylketone, acetoin and 1,1,3-triethoxypropane and some others in minor amounts. There are marked differences between stone- and pome-fruit distillates. Stone-fruit distillates are characterized by relatively large amounts of benzyl alcohol and benzaldehyde and pome-fruit distillates by large amounts of 1-hexanol. In general, terpenes were found at higher concentrations in stone-fruit spirits than in pome-fruit spirits ( Postel & Adam, 1989 ).

The main ester component of fruit spirits is ethyl acetate followed by ethyl lactate; together, these two compounds amount to ∼80% or more of the total ester content. The number of other esters is large, but their concentrations are relatively small. Most of the esters are ethyl esters beginning with formate up to palmitate, phenylacetate, benzoate and cinnamate, including some hydroxyl esters. The number of isoamyl and methyl esters is smaller; in addition, propyl, butyl, hexyl, 2-phenethyl and benzyl esters (mainly acetates) are also present. Moreover, fruit spirits (as well as pomace distillates) are the only groups of spirits that have higher levels of methyl acetate, which occurs only in traces in grape wine brandies and whiskies ( Postel & Adam, 1989 ).

The ethyl carbamate content of stone-fruit spirits is reviewed in Section 1 of the monograph on ethyl carbamate in this Volume.

(f) Mexican spirits (mezcal, tequila)

The Agave genus comprises more than 200 species that are native to arid and tropical regions from southern USA to northern South America and throughout the Carribean. The most important economic use of Agave is the production of alcoholic beverages such as mezcal ( Agave angustifolia Haw., A. potatorum Zucc., A. salmiana Otto, and other species), sotol ( Dasylirion ssp. ,) and bacanora ( A. angustifolia Haw.). All of these spirits are obtained from the fermentation of agavins (fructooligosaccharides) from the different Agave species ( Lachenmeier et al. , 2006b ). However, the most popular contemporary alcoholic beverage made from Agave is tequila, which is recognized worldwide. The production of tequila is restricted to the blue Agave ( A. tequilana Weber var. azul , Agavaceae) and to defined geographical areas, primarily to the State of Jalisco in West Central Mexico ( Lachenmeier et al. , 2006b ). Two basic categories of tequila can be distinguished: ‘100% agave’ and ‘mixed’ tequila. For the high-quality category, ‘100% agave’, only pure agave juice is permitted to be fermented and distilled ( Cedeño, 1995 ).

Following the bestowal of the appellation of origin of tequila, other distilled Agave beverages from the States of Oaxaca, Guerrero, San Luis Potosi, Chiapas, Guajanuato and Zacatecas (mezcal), Chihuahua, Coahuila and Durango (sotol) and Sonora (bacanora) were granted equal recognition. All of these regional drinks are subject to official standards, and their production is supervised by the Mexican Government. Until now, only tequila, and more recently, mezcal have reached international recognition. Especially in the last decade, the consumption of tequila has increased tremendously worldwide. Tequila and mezcal are protected under the North American Free Trade Agreement and an agreement between the European Union and the United Mexican States on the mutual recognition and protection of designations for spirit drinks ( Lachenmeier et al. , 2006b ).

Due to their production from plant material that contains oxalate, all Agave spirits contain significant concentrations of this compound (0.1–9.7 mg/L). The composition of Mexican Agave spirits was found to vary over a relatively large range. The two tequila categories (‘100% agave’ and ‘mixed’) showed differences in concentrations of methanol, 2-/3-methyl-1-butanol and 2-phenylethanol, with lower concentrations in the ‘mixed’ category ( Lachenmeier et al. , 2006b ).

Quantitative differences in ethyl esters were found in tequila depending on the duration of ageing. Ethyl hexadecanoate and octadecanoate were the most abundant ethyl esters in all tequila types; Anejo (extra aged) tequila presented the highest concentration of ethyl esters ( Vallejo-Cordoba et al. , 2004 ). Isovaleraldehyde, isoamyl alcohol, β-damascenone, 2-phenylethanol and vanillin were the most powerful odourants of tequila from a range of 175 components identified ( Benn & Peppard, 1996 ). The most potent odourants were: phenylethanol and phenylethyl acetate in Blanco tequila; phenylethanol, phenylethyl acetate and vanillin in Reposado (aged) tequila; and phenylethanol, vanillin and an unknown substance in Anejo tequila ( López & Dufour, 2001 ).

Considerably higher concentrations of 2-furaldehyde and 5-methylfuraldehyde were found in tequilas than in brandies. Furthermore, 100% agave tequilas contained higher levels of these two compounds (mean values, 18.6 and 5.97 mg/L, respectively) than the mixed brands (mean values, 6.46 and 3.30 mg/L). The profile of furanic aldehydes depends on the type of fructans contained in the raw material and also on heat treatment before fermentation. In contrast to other polysaccharides, inulin hydrolyses at elevated temperature and the contribution of Maillard browning reactions increases the production of furanic compounds ( Munoz-Rodriguez et al. , 2005 ).

Saturated alcohols, ethyl acetate, ethyl 2-hydroxypropanoate and acetic acid are the major compounds in mezcal produced from A. salmiana. Minor compounds in mezcal include other alcohols, aldehydes, ketones, large-chain ethyl esters, organic acids, furans, terpenes, alkenes and alkynes. Most of the compounds found in mezcals are similar to those present in tequilas and other alcoholic beverages. However, mezcals contain unique compounds such as limonene and pentyl butanoate, which can be used as markers for the authenticity of mezcal produced from A. salmiana. Mezcals (but not tequilas) are sometimes conditioned with one to four larvae of Agave worms. Only mezcals with worms contained the compounds 6,9-pentadecadien-1-ol, 3-hexen-1-ol, 1,8-nonadiene and 1-dodecine. Thus, it may be possible that these unsaturated compounds come from the larvae ( De León-Rodríguez et al. , 2006 ).

(g) Wood maturation of distilled beverages

A wide range of distilled beverages, including whisky and cognac, are matured for many years in oak barrels. Other spirits, such as rum, cachaça, tequila and fruit spirits, are also often matured in oak. During maturation, a range of physical and chemical interactions take place between the barrel, the surrounding atmosphere and the maturing spirit which transform both the flavour and composition of the drink. The effects and time required for maturation are highly variable and are influenced by a wide range of factors, particularly the type of barrel used ( Mosedale & Puech, 1998 ). Wood ageing is the most probable source of phenols and furans in distilled spirits. Ellagic acid was the phenol present at the highest concentration in 12 categories of spirit. Moderate amounts of syringaldehyde, syringic acid and gallic acid, as well as lesser amounts of vanillin and vanillic acid, were measurable in most samples of whisky, brandy and rum. 5-Hydroxymethylfurfural was the predominant furan, notably in cognac, followed by 2-furaldehyde. Beverages that are subjected to wood ageing also contain significant antioxidant activity, the level of which is between the ranges observed in white and red wines. Highest total antioxidant values were exhibited in armagnac, cognac and bourbon whiskey, and no antioxidants were found in rum, vodka, gin and miscellaneous spirits, correlating with low or undetectable phenol concentrations in these spirits ( Goldberg et al. , 1999 ).

Vodka is a spirit beverage produced by rectifying ethanol of agricultural origin or filtering it through activated charcoal, possibly followed by straightforward distillation or an equivalent treatment. This selectively reduces the organoleptic characteristics of the raw materials. Flavouring may be added to give the product special organoleptic characteristics, such as a mellow taste ( European Council, 1989 ). The raw spirit put through rectification is usually produced from grain (rye and wheat) and potatoes. In the production of vodka, the quality of the water used is of the utmost importance. For premium vodka brands, demineralized water is filtered through activated carbon to absorb unwanted organic and inorganic materials.

The contents of anions in Russian vodkas usually lie in the ranges of 0.5–10 mg/L chloride, 0.5–3.5 mg/L nitrate, 3.5–30 mg/L sulfate and < 0.1 mg/L phosphate ( Obrezkov et al. , 1997 ). Vodkas bottled in Germany were found to contain significantly higher amounts of anions (up to 147.6 mg/L) ( Lachenmeier et al. , 2003 ).

Since vodkas are manufactured in such a way that they have no distinctive aroma or taste, residual congeners are present at levels much lower than those found in other spirits that have various flavour characteristics. The congeners present at microgram per litre levels were isolated using solid-phase microextraction. Ethyl esters of C 8 –C 18 fatty acids were detected and differentiation between Canadian and American vodkas was possible ( Ng et al. , 1996 ).

(i) Spirits produced from neutral alcohol

In contrast to spirits such as whisky or brandy, which are manufactured by fermentation and retain the organoleptic properties of the raw materials, a range of spirits is manufactured using highly rectified alcohol (so-called ‘neutral alcohol’ or ‘ethanol of agricultural origin’). The European requirements for neutral alcohol are shown in Table 1.10 . Neutral alcohol contains significantly lower concentrations of volatile constituents than the spirits discussed previously (e.g. whisky, rum, brandy). However, the composition of vodka is relatively similar to that of neutral alcohol. The typical components and flavour characteristics of spirits manufactured from neutral alcohol derive from other materials and not from the alcohol or fermentation products.

Table 1.10. Properties of neutral alcohol in Europe.

Properties of neutral alcohol in Europe.

A prominent type of a spirit manufactured from neutral alcohol is gin. The most popular is London Dry Gin. It belongs to the ‘distilled gin’ class in European legislation and is produced by redistillation of neutral alcohol in the presence of juniper berries (Juniperus communis) and other natural ingredients ( European Council, 1989 ). Gin was found to contain over 70 components (mainly mono- and sesquiterpenic compounds) ( Vichi et al. , 2005 ).

Most liqueurs are also produced by mixing neutral alcohol with sugars and a wide range of plant extracts or fruit juices. For example, Italian lemon liqueurs (Limoncello) are obtained by alcoholic extraction of essential oils from lemon peel and dilution with sugar syrup. The liqueur, therefore, shows a composition similar to lemon essential oil with a high content of β-pinene, myrcene, trans-α-bergamottene and β-bisabolene ( Versari et al., 2003 ). Another example is traditional walnut liqueur that contains phenolic compounds extracted from walnut husks ( Stampar et al. , 2006 ).

1.6.5. Compounds in other alcoholic beverages

(a) cider (apple wine).

Cider is an alcoholic beverage made from apples and has very different characteristics according to the origin of the fruit and methods of production. French cider (Breton and Norman) has a low alcohol content and contains significant residual unfermented sugar. German cider, mostly from the state of Hessen, is fully fermented and very dry. Spanish (mostly Asturian) cider is characterized by a high volatile acidity and by its foaming characteristics when served. Modern English ciders are for the most part characterized by light flavours, which arise from chaptalization with glucose syrup before fermentation to give high-alcohol apple wines, which are then diluted with water and sweetener before retailing ( Lea, 2004 ).

The differences between English, French and German ciders are compared in Table 1.11 .

Table 1.11. Differences in the composition of ciders from England, France and Germany.

Differences in the composition of ciders from England, France and Germany.

The standard German ‘apple wine’ should have an alcoholic strength of 7.0% vol, a total dry extract of 25 g/L, a sugar content of 2 g/L, a pH of 3.1, a volatile acidity of 0.5 g/L, a glycerine content of 4.7 g/L, a potassium content of 1100 mg/L, a magnesium content of 60 mg/L, a calcium content of 60 mg/L and a copper content of 0.3 mg/L ( Scholten, 1992 ).

French ciders can be classified according to their residual sugar content into ‘brut’ (< 28 g/L of residual sugar), ‘demi-sec’ (28–42 g/L of residual sugar) and ‘doux’ (< 3% vol alcohol and > 35 g/L of residual sugar) ( Anon., 1992 ).

During the fermentation of apple juice, organic acids undergo several changes. It was shown that concentrations of malic and citric acid decrease, while those of lactic and succinic acid increase ( Blanco Gomis et al. , 1988 ).

More than 200 volatile flavour components, 100 of which could be identified, were found in apple wines manufactured from Turkish apples ( Yavas & Rapp, 1992 ). The flavour composition of two Spanish ciders was studied by Mangas et al. (1996a) . The major aromatic components were amyl alcohols (134–171 mg/L) and 2-phenylethanol (57–185 mg/L); minor compounds were alcohols, esters and fatty acids.

Forty-three compounds identified in Chinese Fuji apple wine were mainly esters, alcohols and lower fatty acids, as well as lesser amounts of carbonyls, alkenes, terpenes and phenols. Total concentrations of esters, alcohols and lower fatty acids were 242 mg/L, 479 mg/L and 297 mg/L, respectively. The highest concentration of aromatic components in apple wine was for isoamyl alcohol (232 mg/L) which constituted 32% of the total esters and alcohols ( Wang et al. , 2004 ).

A total of 16 phenolic compounds (catechol, tyrosol, protocatechuic acid, hydrocaffeic acid, chlorogenic acid, hydrocoumaric acid, ferulic acid, (−)-epicatechin, (+)-catechin, procyanidins B2 and B5, phloretin-2'-xyloglucoside, phloridzin, hyperin, avicularin and quercitrin) were identified in natural ciders from the Asturian community (Spain). A fourth quercetin derivative, one dihydrochalcone-related compound, two unknown procyanidins, three hydroxycinnamic derivatives and two unknown compounds were also found. Among the low-molecular-mass polyphenols, hydrocaffeic acid was the most abundant compound, and represented more than 80% of total polyphenolic acids. Procyanidins were the most important family among the flavonoid compounds. Discriminant analysis allowed correct classification of more than 93% of the ciders according to the year of harvest; the most discriminant variables were an unknown procyanidin and quercitrin ( Rodríguez Madrera et al. , 2006 ).

The polyphenolic profile was used to identify ciders according to their geographical origin (Basque or French regions). Polyphenolic contents of Basque ciders are lower than those of French ciders, which indicates that Basque cider-making technology involves a higher loss of native apple polyphenols, probably due to oxidation processes and microflora metabolism ( Alonso-Salces et al. , 2004 ). The polyphenolic composition may also be used to distinguish ciders made with Basque apples from those made with apples imported from other parts of Europe to Spain ( Alonso-Salces et al. , 2006 ).

Free amino acids were studied in Spanish sparkling ciders. The amount of amino acids significantly decreased during second fermentation in the bottle, and their composition was dependent on the yeast strain and the duration of ageing ( Suárez Valles et al. , 2005 ). The average level of total biogenic amines in Spanish ciders was 5.9±8.4 mg/L. Putrescine, histamine and tyramine were the prevailing amines and were present in 50, 38 and 33% of the ciders studied, respectively; very small amounts of ethylamine and phenylethylamine were observed in only one sample. Ciders that had lower glycerol contents and larger amounts of 1,3-propanediol had much higher levels of histamine, tyramine and putrescine, which suggests a high activity of lactic acid bacteria during cider making and thus the need for their effective control ( Garai et al. , 2006 ).

Acrolein may be formed in apple-derived products through the degradation of glycerol. Due to its high volatility and high reactivity, acrolein disappears rapidly from ciders. The concentration of acrolein in two French ciders was 7 and 15 µg/L. Acrolein was also detected in freshly distilled calvados (a distillate of cider) at concentrations of between 0.7 and 5.2 mg/L; however, the concentrations decreased during ageing ( Ledauphin et al. , 2006b ). Ledauphin et al. (2004 , 2006a ) provided information on a range of volatile compounds in distilled calvados. The method of production of cider (by traditional methods or from concentrates) influences the composition of the resulting calvados. The spirits manufactured from traditional ciders had higher concentrations of decanoic and dodecanoic esters and long-chain fatty acids ( Mangas et al. , 1996b ).

(b) Other fruit wines

Berry fruit or stone fruit are predominantly used to manufacture wine. The manufacture of fruit wine has been reviewed ( Röhrig, 1993 ).

Fruit wines produced from different varieties of sour cherry contained 7.7–9.6% vol alcohol, 8.4–9.9 g/L total acid and 35–60 g/L residual sugar. The concentrations of colourless polyphenols varied considerably. Neochlorogenic acid (48–537 mg/L), chlorogenic acid (31–99 mg/L) and 3-cumaroylquinic acid (43–196 mg/L) were the predominant phenolcarbonic acids followed by the flavonoids, procyanidin B1 (6–32 mg/L), catechin (2–27 mg/L) and epicatechin (8–130 mg/L). Quercetin glycosides were present at concentrations of 12–46 mg/L. The four major anthocyanins were identified as cyanidin-3-(2 G -glucosylrutinoside), cyanidin-3-(2 G -xylosylrutinoside), cyanidin-3-rutinoside and peonidin-3-rutinoside and were present at concentrations of 147–204 mg/L and in a rather constant ratio of 72:3:22:3. Among aromatic substances, the secondary aroma arising during the fermentation process was dominant. The main components were ethyl esters of hexanoic acid, octanoic acid and decanoic acid, as well as the fruity esters, isoamyl acetate, butanoic acid ethyl ester, acetic acid butyl ester and acetic acid hexyl ester. The endogenous fruit aroma was mainly composed of acetic acid ethyl ester, phenylethyl alcohol, decanal, benzaldehyde, 1-hexanol, 1-octanol, nonanal, trans -nerolidol and linalool ( Will et al. , 2005 ).

The mineral composition of different fruit wines was generally comparable with that of red wine, and potassium was the most abundant mineral found in all wine categories. However, the level of calcium was significantly higher in cranberry wine than in other wines. The biogenic amine histamine was present only in small amounts in non-traditional fruit wines compared with red wines ( Rupasinghe & Clegg, 2007 ).

Mandarin wine obtained from clementines ( Citrus reticula Blanco) was studied by Selli et al. (2004) ; 19 volatile compounds were identified including esters, higher alcohols, monoterpenes and furfural compounds. The major compounds were ethyl octanoate, ethyl decanoate, isoamyl alcohol, ethyl hexanoate and isoamyl acetate.

The composition of wines made from blackcurrants and cherries was studied by Czyzowska and Pogorzelski (2002 , 2004 ). Blackcurrant musts contained 4800–6600 mg/L and cherry musts contained 3060–3920 mg/L total polyphenols. The fermentation process caused a decrease in polyphenol content of approximately 25%. During the production of fruit wines, the method of treatment of the pulp had a considerable effect on the total polyphenol content. The highest extraction of polyphenols was obtained after enzymatic pectinolysis. In musts and wines, the presence of the following derivatives of hydroxycinnamic acid was determined: neochlorogenic, chlorogenic, caffeic, para-coumaric and ferulic acids. The content of neochlorogenic acid was the highest and amounted to 24.7–35.3 mg/L for blackcurrants and 44.5–71.4 mg/L for cherries. Furthermore, the flavan-3-ols, catechin, epicatechin, dimer B 2 and trimer C 1 , were identified in cherry musts and wines. In the cherry wines studied, the variants subjected to pectinolysis and fermentation of the pulp contained smaller amounts of epicatechin than catechin whereas it was predominant in the wines subjected to thermal treatment. In the blackcurrant musts and wines, the flavanols, gallocatechin, catechin, epigallocatechin, dimer B 2 , epicatechin and trimer C 1 , were identified. In cherry musts and wines, the anthocyanin pigments, cyanidin 3-glucoside, cyanidin 3-rutinoside and cyanidin 3-glucosylrutinoside, have been identified, the last of which was the most abundant. Anthocyanins identified in blackcurrant musts and wines were delphinidine and cyanidine glycosides: delphinidin 3-glucoside, delphinidin 3-rutinoside, cyanidin 3-glucoside and cyanidin 3-rutinoside; their aglycones were also found.

The antioxidant effects of fruit wines were studied by Pinhero and Paliyath (2001) . On the basis of specific phenolic content, summer cherry, blackberry and blueberry wines were 30–40% more efficient at scavenging superoxide radicals than red grape wine. From among several different fruit wines, elderberry, blueberry and blackcurrant wines were identified by Rupasinghe and Clegg (2007) as having the highest concentrations of phenolic compounds compared with red wine.

In contrast, Lehtonen et al. (1999) found that the amounts of phenolic compounds in berry and fruit wines were much smaller than those in red grape wines, which indicates that these compounds are more effectively extracted from red grapes than from berries and fruits. The total amount of phenolic compounds ranged from 18 to 132 mg/L in berry and fruit wines and liqueurs derived from apples, blackcurrants, bilberries, cowberries, crowberries, cherries, strawberries and arctic brambles. Anthocyanins and flavan-3-ols were the most abundant. The main anthocyanins were cyanidin and delphinidin in wine made from blackcurrants and black crowberries. Wines made from crowberries and from blackcurrants and strawberries were richest in flavan-3-ols and contained 79 and 76 mg/L, respectively. In addition, ellagic acid was found in strawberry and blackcurrant wines (44 mg/L) and in cherry liqueur (117 mg/L).

Fruit wines may also be manufactured from guava ( Anderson & Badrie, 2005 ), peach ( Joshi et al. , 2005 ), banana ( Brathwaite & Badrie, 2001 ; Jackson & Badrie, 2002 ; Akubor et al. , 2003 ; Jackson & Badrie, 2003 ), mango ( Reddy & Reddy, 2005 ), cashew apples ( Garruti et al. , 2006 ) or Brazilian jabuticaba fruit ( Asquieri et al. , 2004 ) but their composition has not been studied in detail.

(c) Alcoholic beverages produced in Asia

In general, information on the composition of Asian alcoholic beverages is scarce but spirits produced in Japan and other East Asian countries have been reviewed ( Minabe, 2004 ).

Shochu is a traditional Japanese distilled spirit. The category consists of two types of product. It is produced either from barley, maize or sugar cane by continuous distillation using a column still (the product is very similar to vodka) or from barley, rice or sweet potato using a pot-still. Saccharification in the second type is accomplished using fungi cultures (so-called koji—a mould grown on rice). The role of koji is analogous to that of malt in beer and whisky production ( Iwami et al. , 2005 ). Barley shochu contains 20–30% vol alcohol. The flavour of shochu is closely associated with ethyl acetate, isoamyl acetate and ethyl caproate ( Iwami et al. , 2006 ).

Another well known Japanese alcoholic beverage is sake. Despite its relatively high average alcoholic strength of 15% vol, sake is not a distilled beverage. It is manufactured from rice, koji and yeast. The koji degrades the starch to form glucose, which is immediately converted by yeast to form alcohol. Over 300 components have been identified in sake ( Yoshizawa, 1999 ). Apart from ethanol, the main contributors to the flavour of sake are alcohols (1-propanol, isoamyl alcohol, 2-phenylethanol and isobutanol), esters (ethyl acetate, ethyl caproate and isoamyl acetate) and acids (succinic, malic, citric, acetic and lactic acids) ( Bamforth, 2005 ).

Korean traditional lotus spirit made from lotus blossom and leaves contained 14% ethanol, 0.95% organic acids, 1.4% carbohydrate and polyphenol compounds (1063 mg/L) ( Lee et al. , 2005 ).

An overview of alcoholic beverages from China was given by Chen and Ho (1989) and Chen et al. (1999) . Alcoholic drinks from Nepal were discussed by Dahal et al. (2005) .

In India, so-called ‘Indian-made foreign liquors’ are manufactured. They include the typical European spirit groups such as whisky, rum or brandy ( Baisya, 2003 ). Due to problems of availability of cereals, Indian-made foreign liquors are generally manufactured from molasses, contrary to the practices followed in other countries ( Sen & Bhattacharjya, 1991 ). In addition, ‘country liquor’ is manufactured in India, and is so named to indicate its local origin and to differentiate from the more expensive foreign liquor ( Narawane et al. , 1998 ). Country liquors are the most popular alcoholic beverage consumed among low socioeconomic groups in India. It is either brewed locally or made in distilleries by distilling molasses supplied by sugar factories. A popular country liquor that is consumed by the lower socioeconomic group in South India is toddy, which is a non-distilled alcoholic beverage. It is obtained by natural fermentation of coconut palm ( Cocos nucifera ) sap, which is collected by tapping the unopened inflorescence of the coconut palm ( Lal et al. , 2001 ). Several other types of country liquor are produced in India: for example, tharrah in Uttar Pradesh, chang in Punjab, arrack in Tamil Nadu, mahua in West Bengal, laopani in Assam and darru in Rajasthan. The Bureau of Indian Standards had difficulty in identifying every type of country liquor and devising individual standards. However, requirements have been set for the three major types of distilled country liquor. Plain country liquor is an alcoholic distillate of fermented mash of different agricultural products (e.g. cereals, potatoes, fruit, coconut). Blended country liquor is a pot-still distillate, rectified spirit and/or neutral alcohol. Spiced country liquor is plain or blended country liquor that is flavoured and/or coloured ( Sen & Bhattacharjya, 1991 ).

(d) Alcopops

Alcopops are also known as ‘ready-to-drink’ or ‘flavoured alcoholic beverages’; they tend to be sweet, to be served in small bottles (typically 200–275 mL) and to contain between 5 and 7% vol alcohol.

In a recent study, the alcoholic strength of alcopops was in the range of 2.4–8% vol with an average of 4.7% vol. A significant deviation was detected in the volatile composition of alcopops that contain beer, wine and spirits. Alcopops derived from wine alcohol showed concentrations of volatile compounds (especially methanol, 1-propanol and 2-/3-methylbutanol-1) that were 10–100 times higher than those in products derived from spirits. However, this study noted the variability in alcopop composition, and the possibility of changes in recipes has to be taken into consideration even if the brand name of a given product has not been changed ( Lachenmeier et al. , 2006c ).

The recent practice of combined consumption of alcohol and so-called energy drinks has rapidly become popular. The main components of the marketed energy drinks are caffeine, taurine, carbohydrates, gluconolactone, inositol, niacin, pantenol and B-complex vitamins ( Ferreira et al. , 2006 ). The levels of taurine in such alcoholic energy drinks were recently determined and large variations were detected. Ready-mixed energy drinks with spirits contained 223–4325 mg/L taurine (median, 314 mg/L), energy drinks with beer contained 112–151 mg/L taurine (median, 151 mg/L) and energy drinks with wine contained 132–4868 mg/L taurine (median, 305 mg/L) ( Triebel et al. , 2007 ). However, valid scientific information on interactions between the ingredients of energy drinks (for example, taurine and caffeine) and alcohol was not available.

Another category of alcoholic beverages that is relatively similar to alcopops in their presentation is hemp beverages. Typical products are so-called hemp beers, which are flavoured with dried hemp ( Cannabis ) inflorescences, and hemp liqueurs. Δ9-Tetrahydrocannabinol, the main psychoactive substance found in the Cannabis plant, was not detected in hemp beers ( Lachenmeier & Walch, 2005 ).

1.6.6. Additives and flavourings

(a) additives.

The Codex Standard for Food Additives includes several additives that are recognized as suitable for use in alcoholic beverages ( Codex alimentarius , 2006) ( Table 1.12 ). In addition, a list of 179 additives that are permitted for use in food in general is provided. These additives (including organic acids, alginates, salts, gases (e.g. carbon dioxide, nitrogen) and sugars) may be used in alcoholic beverages with the exception of grape wine that is excluded from the general conditions. The additives listed in this standard were determined to be safe by the Joint FAO/WHO Expert Committee on Food Additives.

Table 1.12. Additives suitable for alcoholic beverages and maximum levels (mg/kg).

Additives suitable for alcoholic beverages and maximum levels (mg/kg).

Many countries provide stricter regulations on food additives than the Codex alimentarius . For example, the German beer purity law of 1516, which is still in force today, states that only barley malt, hops, yeast and water are permitted in beer production ( Donhauser, 1988 ). According to European law, no additives are permitted in most traditional spirits, e.g. rum, whisky, brandy, fruit spirits and many other types ( European Council, 1989 ). In contrast, additives are regularly added to liqueurs (artificial colourings) or alcopops (artificial colourings, preservatives). Some national regulations also permit the use of additives other than those listed by the Codex alimentarius , e.g. a multitude of artificial colourings, sweeteners or further preservatives (e.g. sorbic acid). Caramel colouring is frequently used to ensure colour consistency of aged products ( Boscolo et al. , 2002 ).

The most frequent additives in alcoholic beverages are sulfur dioxide and sulfites. Sulfite additives have been associated with allergic-like asthmatic responses in certain individuals ( Vally & Thompson, 2003 ). For this reason, many countries require the labelling of sulfur dioxide and sulfites used as ingredients at concentrations of more than 10 mg/L (expressed as sulfur dioxide) ( Lachenmeier & Nerlich, 2006 ).

In conjunction with added sulfite, natural sulfite may evolve in alcoholic beverages during fermentation by the metabolism of yeasts ( Ilett, 1995 ).

Sulfite is a desirable component in beer because it has an antioxidative effect as a scavenger and binds to carbonyl compounds that cause a stale flavour. In contrast, during the early phases of fermentation, high concentrations of sulfite may cause an undesirable flavour ( Guido, 2005 ). The formation of sulfite is strongly influenced by predisposition of the yeast and parameters that affect yeast growth during fermentation, such as the physiological state of the yeast and the availability of nutrients and oxygen ( Wurzbacher et al. , 2005 ). The average residual quantities of sulfur dioxide were 7.5 mg/L in French beer and 25 mg/L in cider ( Mareschi et al. , 1992 ). In a recent study, the average concentrations expressed as sulfur dioxide were 4.2 mg/L for beer (195 samples) and 1.0 mg/L for spirits (101 samples). The concentrations of sulfite in spirits were found to be significantly lower than those in beer ( P < 0.0001) ( Lachenmeier & Nerlich, 2006 ).

Generally higher levels of sulfur dioxide were determined in wine than in spirits or beer. However, during the last decade, a decrease in the sulfite content of wine has been detected that is probably due to new technological processes that improve the stability of wine using a smaller quantity of sulfite ( Leclercq et al. , 2000 ). In a large survey of wines conducted in the 1980s, 3655 samples of Italian wine and 8061 samples of French wine that were analysed had mean sulfite contents of 135 mg/L and 136 mg/L, respectively ( Ough, 1986 ). In later studies, an average of 92 mg/L sulfite was determined in 85 samples of wine in Italy ( Leclercq et al. , 2000 ), whereas in France, the mean concentrations were 75 mg/L ( Mareschi et al. , 1992 ).

(b) Flavourings

The Codex alimentarius (1987) provides general requirements for natural flavourings. Some flavourings contain biologically active substances for which maximum levels are specified ( Table 1.13 ). It must be noted that the biologically active substances (with the exception of quinine and quassine) should not be added as such to food and beverages, and may only be incorporated through the use of natural flavourings, provided that the maximum levels in the final product ready for consumption are not exceeded.

Table 1.13. Maximum levels for biologically active substances contained in natural flavourings.

Maximum levels for biologically active substances contained in natural flavourings.

Of the biologically active substances listed, the largest body of information available is on thujone. This derives from the fact that the prohibition of absinthe was overruled after adoption of the Codex alimentarius recommendation into European law in 1988. The thujone-containing wormwood plant ( Artemisia absinthium L.) gave absinthe its name and is, together with alcohol, the main component of this spirit drink. Currently, more than 100 types of absinthe are legally available in Europe. Absinthe was recently reviewed by Lachenmeier et al. (2006d) and Padosch et al. (2006) . The majority of 147 absinthe samples examined (95%) did not exceed the Codex alimentarius maximum level for thujone of 35 mg/kg for bitters. In fact, more than half of the samples examined (55%) contained less than 2 mg/kg thujone. This emphasized that thujone values in absinthes produced according to historical recipes can be conform to the Codex alimentarius maximum levels. Several studies on the experimental production of absinthes and the analyses of vintage absinthes consistently showed that they contained only relatively low concentrations of thujone (< 10 mg/L) ( Lachenmeier et al. , 2006e ). The thujone content of absinthe is irrespective of the quality of the spirit as there are several different wormwood chemotypes that have a large variance in thujone content (0–70.6% in essential oil) ( Lachenmeier, 2007a ). The easiest way to avoid thujone totally is to use the thujone-free wormwood herb, which is available in certain cultivation areas and appears to be perfect for use in the spirits industry. Some authors concluded that thujone concentrations of both pre-prohibition and modern absinthes may not cause detrimental health effects other than those encountered in common alcoholism ( Strang et al. , 1999 ; Padosch et al. , 2006 ).

The Joint FAO/WHO Expert Committee on Food Additives has evaluated the safety of approximately 1150 individual flavouring agents ( Munro & Mattia, 2004 ). Similarly, the expert panel of the Flavor and Extract Manufacturers' Association of the USA has evaluated the safety of nearly 1900 substances ( Smith et al. , 2005 ). As a result of these evaluations, certain flavourings used in alcoholic beverages now have the status of ‘generally recognized as safe’ (GRAS).

In alcoholic beverages, the most prominent GRAS substance is ( E )-1-methoxy-4-(1-propenyl)benzene (anethole). Anethole is a volatile substance that occurs naturally in several herbs and spices. Macerates, distillates or extracts of the plants star-anise (Illicium verum H ook . F il .), aniseed ( Pimpinella anisum L.) or fennel ( Foeniculum vulgare M ill .), the essential oils of which contain approximately 80–90% anethole, are used to flavour spirits. After extensive toxicological evaluations, anethole was determined to be GRAS ( Newberne et al. , 1998 , 1999 ). Certain spirits that contain anise, such as pastis, sambuca or mistra, must contain minimum and maximum levels of anethole (usual range, 1–2 g/L) ( Lachenmeier et al. , 2005a ). Raki spirits from Turkey contained 1.5–1.8 g/L anethole ( Yavas & Rapp, 1991 ). In arak from the Lebanon, levels of anethole varied from 1.2 to 3.8 g/L in commercial and from 0.5 to 4.2 g/L in artisanal samples. The variations in levels of anethole were found to be in direct relation to the amounts of aniseed used in the anization step of arak manufacture ( Geahchan et al. , 1991 ). Twenty-one different brands of pacharan (a traditional Spanish beverage obtained by maceration of sloe berries ( Prunus spinosa L. )) contained between 0.015 and 0.069 g/L anethole ( Fernández-García et al. , 1998 ).

(c) Acetaldehyde

In addition to being an intermediate product of the metabolism of ethanol in humans and animals, acetaldehyde (ethanal) is a potent volatile flavouring compound found in many beverages and foods ( Liu & Pilone, 2000 ). No current systematic surveys of acetaldehyde in alcoholic beverages were available. In general, the concentration of acetaldehyde in alcoholic beverages is below 500 mg/L and the flavour threshold varies between 30 and 125 mg/L ( Liu & Pilone, 2000 ). During the production of spirits, acetaldehyde is enriched in the first fraction of the distillate, which is generally discarded due to its unpleasant flavour.

The levels of acetaldehyde in alcoholic beverages vary considerably. However, the acetaldehyde formed from the metabolism of alcohol in the oral cavity and the further digestive pathway is many times higher than the levels specified above.

Acetaldehyde at low levels gives a pleasant fruity aroma, but at high concentrations it possesses a pungent irritating odour ( Miyake & Shibamoto, 1993 ). In alcoholic beverages, acetaldehyde may be formed by yeasts, acetic acid bacteria and coupled autooxidation of ethanol and phenolic compounds ( Liu & Pilone, 2000 ). In other foods, acetaldehyde may be added as a flavouring substance. The JECFA included acetaldehyde in the functional class ‘flavouring agent’ and commented that there is no safety concern at current levels of intake when it is used as a flavouring agent ( Joint FAO/WHO Expert Committee on Food Additives 1997 ). Acetaldehyde is formed in mild beer as a result of light oxidation. It is also a degradation product of poly(ethylene terephthalate), which is increasingly used as packaging choice for milk and beverages. The migration of acetaldehyde from the container into the product is an issue to be explored, particularly in the water industry, for which low acetaldehyde grades of poly(ethylene terephthalate) have been developed ( van Aardt et al. , 2001 ).

Acetaldehyde is extremely reactive and binds readily to proteins, the peptide glutathione (GSH) or individual amino acids to generate various flavour compounds ( Miyake & Shibamoto, 1993 ; Liu & Pilone, 2000 ).

(d) Illegal additives, adulteration and fraud

Occasionally, illegal additives, which may be very toxic and which are not permitted for use in commercial production in most countries, have been identified in alcoholic beverages. These include methanol, diethylene glycol (used as sweetener) and chloroacetic acid or its bromine analogue, sodium azide and salicylic acid, which are used as fungicides or bactericides ( Ough, 1987 ). The fungicide methyl isothiocyanate has been added illegally to wine to prevent secondary fermentation ( Rostron, 1992 ).

The authenticity of wine and detection of its adulteration have been reviewed ( Médina, 1996 ; Arvanitoyannis et al. , 1999 ; Guillou et al. , 2001 ; Ogrinc et al. , 2003 ). Beet sugar, cane sugar or concentrated rectified must are added to grape must or wine before or during fermentation to increase the natural content of ethanol and therefore the value of the wine. Another type of economic fraud is mixing high-quality wines with low-quality wines that often originate from other geographical regions or countries. Nuclear magnetic resonance spectroscopy in combination with chemometric methods is a suitable approach to study the adulteration of wine in terms of varieties, regions of origin and vintage and also to detect the addition of undesirable or toxic substances ( Ogrinc et al. , 2003 ). The 13 C/ 12 C isotope ratio of ethanol and the 18 O/ 16 O isotope ratio of water determined by isotopic ratio mass spectrometry can be used to detect adulteration of wine that involves the addition of cane sugar and watering ( Guillou et al. , 2001 ). Wine differentiation is also possible using multivariate analysis of different constituents such as minerals, phenolic compounds, volatile compounds or amino acids ( Médina, 1996 ; Arvanitoyannis et al. , 1999 ).

The detection of illicit spirits has been reviewed ( Savchuk et al. , 2001 ). The adulteration of spirits includes blending high-quality distillates with ethanol made from a cheaper raw material, adding synthetic volatile components to neutral alcohol or misleading labelling of the variety and origin of the raw material ( Bauer-Christoph et al. , 1997 ). The classic approach to the authentication of spirits is gas chromatographic analysis of volatile compounds (congeners of alcoholic fermentation). However, the wide range of components in each type of spirit and the considerable overlap between them renders the unambiguous identification of many spirit types difficult. In addition, if a high degree of rectification takes place during distillation, the content of volatile components will be reduced and the application of gas chromatography for the identification of the raw material becomes inappropriate. In these cases, the natural isotope ratios may be used as discriminant analytical parameters ( Bauer-Christoph et al. , 1997 ). For example, rums and corn alcohols from C 4 plants (cane and corn) can easily be distinguished from alcohols from C 3 plants such as grape, potato or beet or C 3 cereal alcohols (pure malt whisky). Isotopic criteria may also be used for short-term dating of brandies and spirits (i.e. the time of storage in casks) ( Martin et al. , 1998 ).

Recently, infrared spectroscopy with multivariate data analysis was successfully applied for the authentication of fruit spirits and other spirits, ( Lachenmeier, 2007b ; Lachenmeier et al. , 2005b ). Direct infusion electrospray ionization mass spectrometry was applied for chemical fingerprinting of whisky samples for type, origin and quality control ( Moller et al. , 2005 ).

Another problem of premium spirits is the economic incentive to mix or completely substitute one brand with another less expensive brand. In such cases, the brand fraud can often be easily determined by analysing the composition of inorganic anions ( Lachenmeier et al. , 2003 ). A mobile device that measures ultraviolet/visible absorption spectra was used for the authentication of Scotch whisky under field test conditions ( MacKenzie & Aylott, 2004 ).

The same approaches as those in wine and spirit analysis were used for the authentication of beer. More recently, high-resolution nuclear magnetic resonance spectroscopy in combination with multivariate analysis was found to be adequate to distinguish beers according to their composition (e.g. differentiation between beers made with pure barley or adjuncts) or according to brewing site and date of production ( Almeida et al. , 2006 ).

1.6.7. Contaminants, toxins and residues

For the purposes of this section of the monograph, the term ‘contaminant’ is used according to the definition given by the Codex alimentarius . A contaminant is any substance that is not intentionally added to food but which is present in such food as a result of the production, manufacture, processing, preparation, treatment, packing, packaging, transport or holding of such food, or as a result of environmental contamination. The Codex definition of a contaminant implicitly includes naturally occurring toxicants such as those produced as toxic metabolites of certain microfungi that are not intentionally added to food (mycotoxins) ( Codex alimentarius , 1997 ). Some of these contaminants have known toxic properties and, in some cases, carcinogenic effects (see Table 1.14 ).

Table 1.14. Summary of carcinogens that may be present in alcoholic beverages.

Summary of carcinogens that may be present in alcoholic beverages.

(a) Nitrosamines

The chemical class of nitrosamines includes the Group 2A carcinogen N-nitrosodimethylamine (NDMA) ( IARC 1978 ; IARC, 1987 ). The occurrence and formation of N-nitroso compounds in food and beverages have been reviewed ( Tricker & Kubacki, 1992 ; Lijinsky, 1999 ).

In alcoholic beverages, NDMA was first found in German beers in 1978 ( Spiegelhalder et al. , 1979 ), when concentrations of up to 68 µg/L caused worldwide concern. Subsequent research established that NDMA was a contaminant of malt that had been kilned by direct firing, which was the predominant production method at that time. Once the source of the contaminant and the mechanism of its formation had been elucidated, control was achieved by changing to indirect firing of the malt kiln. The possibilities for minimizing nitrosamine formation during malt kilning have been reviewed ( Flad, 1989 ; Smith, 1994 ). As a result of the improvements in the quality of malt, a technical threshold value of 0.5 µg/kg NDMA in beer was established as a recommendation to the brewing industry. In Germany, this value was exceeded by 70% of all samples in 1978. In the most recent reports (2001–05), the technical threshold value was exceeded by only one of 363 German beers (0.2%) ( Baden-Württemberg, 2006 ). Fig 1.5 demonstrates the decrease in levels of NDMA in German beers.

Development of maximum concentration of N-nitrosodimethylamine (µg/kg) in German beer (data from Table 1.15)

The concentrations of NDMA in beer that have been determined in different countries are summarized in Table 1.15 . The data reflect the successful efforts of the malting and brewing industries to reduce the formation of NDMA.

Table 1.15. N-nitrosodimethylamine in beer.

N -nitrosodimethylamine in beer.

Shin et al. (2005) analysed nitrosamines in a range of alcoholic beverages in the Republic of Korea in two surveys in 1995 and 2002, and included the first reports on the traditional Korean beverages chungju (fermented rice alcohol), takju (fermented cereal alcohol) and soju (distilled from fermented cereal alcohol). NDMA was detected in the 1995 survey in chungju (< 0.1 µg/kg) and soju (mean, 0.2 µg/kg) but in none of the samples in the 2002 survey. For domestic Korean beers, an average of 0.8 µg/kg and 0.3 µg/kg were reported in 1995 and 2002, respectively. Whisky and liqueurs contained an average of less than 0.1 µg/kg in both surveys.

Sen et al. (1996) noted that higher levels of NDMA might be present in beers in developing countries than in those in North America or Europe. The malt-drying techniques in various countries are unknown, and continuous monitoring and control of imported beers might therefore be necessary. As an example, high levels of nitrosamines were found in a survey of 120 Indian beers with an average of 3.2 µg/kg and a maximum of 24.7 µg/kg ( Prasad & Krishnaswamy, 1994 ). [The Working Group noted the lack of data on nitrosamine contents of beer in developing countries.]

In a single study, volatile N -nitrosamines in mixed beverages containing beer (e.g. beer-cola, shandy) were reported. The contents were below 0.3 µg/kg in all samples. The formation of nitrosamines that might arise due to the low pH value of these beverages was not detected ( Fritz et al. , 1998 ).

Tricker and Preussmann (1991) reviewed food surveys on NDMA. Dietary intake of NDMA was approximately 0.5 µg/day or less in most countries, which is about one-third of the intake in 1979–80. Previously, beer was the major source of NDMA in human nutrition (65% contribution). In 1990, beer was estimated to contribute to about 31% of total NDMA intake.

(b) Mycotoxins

Mycotoxins are fungal secondary metabolites produced by many important phytopathogenic and food-spoilage fungi including Aspergillus, PeniciUium, Fusarium and alternaria. Various control strategies to prevent the growth of mycotoxigenic fungi and inhibit mycotoxin biosynthesis have recently been reviewed ( Kabak et al. , 2006 ). Mycotoxins survive ethanol fermentation to different degrees but are not carried over to distilled ethanol ( Bennett & Richard, 1996 ). Therefore, alcoholic beverages manufactured without distillation (e.g. wine, cider, beer) are the main focus of research on mycotoxins.

(i) Mycotoxins in wine

Recent research on wine has been focused on ochratoxin A, which has been classified Group 2B—possibly carcinogenic to humans ( IARC, 1993a ). Human ochratoxicosis has been reviewed ( Creppy, 1999 ). Ochratoxin A survives the fermentation process ( Kabak et al. , 2006 ) and is stable in wine for at least 1 year ( Lopez de Cerain et al. , 2002 ). It was indicated that fungi that produce ochratoxin A are already present on grapes in the vineyard before the harvest. Location of the vineyard has more influence on the levels of ochratoxin A than the variety of grape. Weather patterns also seem to influence these levels ( Kozakiewicz et al. , 2004 ). A study of Spanish wines reflected very different levels of contamination by ochratoxin A between 2 years of harvest: 85% of 1997 wine samples versus 15% of 1998 wine samples ( Lopez de Cerain et al. , 2002 ). The 1997 harvest was judged to be worse than that of 1998 probably because of differences in the weather conditions during the summer that led to lower production and several problems of contamination with fungi. On the contrary, in 1998, no sanitary problems were encountered during cultivation of the grapevines. The storage conditions and subsequent processing of grapes were very similar in both cases. These results corroborate the notion that ochratoxin A is present in the grapes before the wine is produced and demonstrate the great importance of climate, which obviously depends on the latitude but also on the particular circumstances in any given year. The occurrence, legislation and toxicology of ochratoxin A have been reviewed ( Höhler, 1998 ). Systematic surveys of ochratoxin A in wine are summarized in Table 1.16 .

Table 1.16. Ochratoxin A in wine.

Ochratoxin A in wine.

Otteneder and Majerus (2000) reported the results of a meta-analysis that evaluated more than 850 wine samples tested for ochratoxin A. According to these data, ochratoxin A is detected much more commonly and its concentration is remarkably higher in red wines than in rosé and white wines: it was detected in 25% of white, 40% of rosé and 54% of red wine samples. The same result was found when wines from southern and northern regions of Europe were compared. Red wine samples from the northern area showed a contamination of 12% in contrast to those from the southern area, which showed a contamination of about 95%. The differences were explained by wine-making procedures that are totally different with respect to red and white wines. White grapes are pressed out directly, whereas red grapes are left mashed for a certain length of time, which obviously permits fungal growth and production of the toxin ( Höhler, 1998 ).

There is only limited information on the occurrence of other mycotoxins in wine. The occurrence of trichotecin from Trichotecium roseum in German wine was studied by Majerus and Zimmer (1995) . Results showed that most samples were free from trichotecin. Low concentrations (∼28 µg/L) were detected in a small proportion of samples from a vintage that was severely affected by fungal spoilage. Lau et al. (2003) reported the occurrence of alternariol from Alternaria alternata in a single wine sample (1.9 µg/L). In a limited survey of 66 wines on the Canadian market ( Scott et al. , 2006 ), alternariol was found in 13/17 Canadian red wines at levels of 0.03–5.02 µg/L and in all of seven imported red wines at 0.27–19.4 µg/L, usually accompanied by lower concentrations of alternariol monomethyl ether. White wines (23 samples) contained little or no alternariol.

(ii) Mycotoxins in apple cider

Patulin, a mycotoxin produced in apples by several Penicillium and Aspergillus species, may be found in apple cider. To date, inadequate data are available for the classification of patulin (Group 3) ( IARC, 1987 ). Although patulin is a fairly reactive compound in an aqueous environment, it is especially stable at low pH and survives the processes involved in the commercial production of apple juice. The complete destruction of patulin occurs during alcoholic fermentation of apple juice to cider ( Moss & Long 2002 ). However, Wilson and Nuovo (1973) detected patulin in five of 100 samples of apple cider at levels of up to 45 mg/L. These very high levels were only found in cider that was produced when decayed apples had not been discarded or when apples had been stored in bins for very long periods. When these practices were changed, patulin was no longer detected. Tsao and Zhou (2000) found that infected apples may contain extremely high concentrations of patulin (> 100 µg/L), and that one ‘bad’ apple could cause the maximal acceptable level of 50 µg/L in apple cider to be exceeded.

A recent study confirmed that patulin is a good indicator of the quality of apples used to manufacture cider. Patulin was not detected in cider pressed from culled treepicked apples stored for 4–6 weeks at 0–2 °C, but was found at levels of 0.97–64.0 µg/L in cider pressed from unculled fruit stored under the same conditions. Cider from apples that were culled before pressing and stored in controlled atmospheres contained 0–15.1 µg/L patulin, while cider made from unculled fruit contained 59.9–120.5 µg/L. The washing of ground-harvested apples before pressing reduced levels of patulin in cider by 10–100%, depending on the initial levels and the type of wash solution used. The avoidance of ground-harvested apples and the careful culling of apples before pressing are good methods for reducing the levels of patulin in cider ( Jackson et al. , 2003 ).

(iii) Mycotoxins in beer

Mycotoxins in beer have been reviewed ( Odhav, 2005 ). Mycotoxins may be transmitted to beers from contaminated grains during brewing. Various surveys have indicated that a variety of mycotoxins reach the final product, but generally in limited concentrations ( Odhav, 2005 ).

Advances in methodology have enabled detection and quantitation of much lower levels (< 1 µg/L) of important mycotoxins such as ochratoxin A and aflatoxins in beer. Consequently, in recent years, reported incidences of ochratoxin A have increased in European and North American beers ( Table 1.17 ). The highest levels of contamination with mycotoxin in beer from these parts of the world is caused by deoxynivalenol. Local beer brewed in Africa may have high incidences and concentrations of aflatoxins and zearalenone ( Scott, 1996 ).

Table 1.17. Ochratoxin A in beer.

Ochratoxin A in beer.

Mycotoxins—aflatoxins, ochratoxin A, patulin, Fusarium toxins (zearalenone, fumonisins, trichlothecenes, nivalenol, desoxynivalenol)—that originate from barley or grain adjuncts survive malting and brewing processes to different extents ( Scott, 1996 ; Dupire, 2003 ).

Deoxynivalenol, nivalenol and zearalenone are not classifiable as to their carcinogenicity to humans (Group 3) ( IARC, 1993a ). Surveys of the occurrence of deoxynivalenol and nivalenol in beer are summarized in Tables 1.18 and 1.19 , respectively. Papadopoulou-Bouraoui et al. (2004) observed that the level of alcohol as well as the type of fermentation had a significant effect on the amount of deoxynivalenol in beer. In general, beers that contained higher levels of alcohol contained significantly larger amounts of deoxynivalenol. Spontaneously fermenting beers contained significantly higher levels of deoxynivalenol than top- or bottom-fermenting beers, while top-fermenting beers contained significantly higher concentrations than bottom-fermenting beers. A positive correlation between original gravity and levels of deoxynivalenol was reported by Curtui et al. (2005) .

Table 1.18. Deoxynivalenol in beer.

Deoxynivalenol in beer.

Table 1.19. Nivalenol in beer.

Nivalenol in beer.

The most abundant naturally occurring fumonisin analogues produced by Fusarium species are fumonisins B 1 , B 2 and B 3 ( Rheeder et al. , 2002 ). Fumonisin B 1 was classified as a Group 2B carcinogen ( IARC, 2002 ). Concentrations of fumonisin B 1 in beer are shown in Table 1.20 . Shephard et al. (2005) showed that fumonisin B 1 was the major fumonisin analogue present in South African home-brewed maize beer and accounted for a mean of 76% in samples that contained all three analogues. The amounts of fumonisin in maize beer were up to two orders of magnitude larger than those observed in beers from other parts of the world in which maize or maize products are not usual ingredients or are used merely as adjuncts. There is little information available on mycotoxin contamination of beer in Africa.

Table 1.20. Fumonisin B1 in beer.

Fumonisin B 1 in beer.

Naturally occurring aflatoxins are carcinogenic to humans (Group 1) ( IARC, 2002 ). Studies on aflatoxins in beer are summarized in Table 1.21 . Nakajima et al. (1999) conducted a worldwide survey of aflatoxins in beer. Aflatoxins were detected in beer samples from countries where aflatoxin contamination might be expected to occur because of the warm climate. Except for one sample, beers contaminated with aflatoxins were also contaminated with ochratoxin A. Generally, with the exception of a negative survey on 75 bottled Kenyan lager beers ( Mbugua & Gathumbi, 2004 ), much higher concentrations of aflatoxins have been found in both commercial and home-brewed African beers ( Scott, 1996 ; Odhav & Naicker, 2002 ). Mably et al. (2005) confirmed in a large worldwide survey that beers from warmer countries such as Mexico have a higher median concentration of aflatoxin B 1 . The highest incidence and concentrations of aflatoxins B 1 and B 2 occurred in beer from India. Other countries where aflatoxin B 1 was detected in beer were Mexico, Spain and Portugal, but levels found in positive samples were much lower. Beers from Canada and the USA were negative for aflatoxins in a reasonably large sampling from these countries.

Table 1.21. Aflatoxins in beer.

Aflatoxins in beer.

(c) Ethyl carbamate (urethane)

Ethyl carbamate is evaluated in detail in a separate Monograph in this Volume.

(d) Inorganic contamination

The mineral content of wine depends on many factors, including the type of soil, variety of grape, climate conditions, viticultural practices and pollution ( Frías et al. , 2003 ). The mineral content of beer was found to be reduced during beer production by about 50–80% (lead, cadmium, copper and zinc). Primarily, the main fermentation and the absorption capacity of beer yeast are responsible for the reduction in the lead, cadmium and zinc contents. In contrast, the amount of copper is reduced during the filtration phase ( Mäder et al. , 1997 ).

Metallic lead is considered to be a possible carcinogen (Group 2B) ( IARC, 1987 ) whereas inorganic lead compounds are probably carcinogenic to humans (Group 2A) ( IARC, 2006 ). Lead in wine has been reviewed ( Eschnauer, 1992 ; Eschnauer & Scollary, 1996 ). The concentrations of lead in alcoholic beverages are given in Table 1.22 .

Table 1.22. Lead in alcoholic beverages.

Lead in alcoholic beverages.

Many authors ascribed the main sources of contamination by lead in wine to winery equipment ( Kaufmann, 1998 ; Rosman et al. , 1998 ), lead capsules ( Eschnauer, 1986 ; Pedersen et al. , 1994 ), lead crystal wine glasses ( Hight, 1996 ) and atmospheric pollution ( Lobiński et al. , 1994 ; Teissedre et al. , 1994 ; Médina et al. , 2000 ). The levels of lead were significantly raised by pesticide treatment with azoxystrobin and sulfur ( Salvo et al. , 2003 ). The Codex alimentarius recommends a maximum level of 0.20 mg/kg lead in wine ( Codex alimentarius , 2003 ).

In a recent study, the contents of lead in wine were found to be very low (< 87 µg/L) in all samples. The mean values of lead in red wines (30 µg/L) were higher than those in white wines (22 µg/L), but there was no significant difference in lead content between red and white wines ( Kim, 2004 ). Tahvonen (1998) reported means of 33 µg/L in white wines and of 34 µg/L in red wines. Previous studies have shown higher values of lead in wines ( Sherlock et al. , 1986 ) compared with more recent results; the mean concentrations of lead in red wines were 106 µg/L, while those in white wines were 74 µg/L. Significant differences between red (65.7 µg/L), rosé (49.5 µg/L) and white (38 µg/L) wines were also determined by Andrey et al. (1992) .

The lead content of wine has tended to decrease over the last few decades. Eschnauer and Ostapczuk (1992) detected a significant reduction in the content of lead in wines of various vintages between the eighteenth and twentieth centuries (see Fig. 1.6 ). A reduction was also detected in vintages of French wine between 1950 and 1991 ( Rosman et al. , 1998 ). Médina et al. (2000) showed a decrease from about 250 µg/L in the early 1950s to less than 100 µg/L. Kaufmann (1998) reported that the average wine in vintage 1990 contained 55 µg/L lead while the concentration in vintage 1980 was 109 µg/L. Statistical analysis revealed that the vintage and the colour but not the age of the wine were the most significant factors that correlated with the lead content.

Lead concentrations in wine since the eighteenth century (data from Eschnauer & Ostapczuk, 1992)

The code of practice for the prevention and reduction of lead contamination in foods recommends that lead foil capsules should not be used on wine bottles because this practice may leave residues of lead around the mouth of the bottle that can contaminate wine upon pouring ( Codex alimentarius , 2004 ). Currently, wine capsules are made from other materials.

Before leaded gasoline was banned in the 1990s, atmospheric deposition was a main source of lead in wines ( Teissedre et al. , 1994 ; Médina et al. , 2000 ). During this period, organolead species from automotive sources were recorded in a series of wine collected in southern France ( Lobiński et al. , 1994 ). At present, the contribution of road traffic to the levels of lead in the atmosphere is much smaller than in the past due to the reduction of natural lead content of the combustibles used in car engines ( Kim, 2004 ). Kaufmann (1998) reported that brass (a lead alloy that was widely used in traditional wine cellars) was also a main source of lead contamination of wines. The gradual replacement of brass by stainless steel has resulted in a steady decrease in levels of lead in wine. Nevertheless, the wines produced at present still contain significant amounts of lead, and it is important that all of the sources of this metal be known to enable their removal or minimization ( Kim, 2004 ). Almeida and Vasconcelos (2003) confirmed that marked reductions in the lead content of wines would occur if the sources of lead were removed from the tubes and containers used in the vinification system, particularly by using lead-free welding alloys and small fittings.

The lead contents of beers were negligible, and low values for beer were also reported in earlier studies ( Tahvonen, 1998 ). Donhauser et al. (1987) found a mean content of 1.6 µg/L in 100 beer samples. Only three-piece tinplate cans with a soldered body seam, which must have been damaged, contained beer with higher lead values of up to 15 µg/L. The tin-coating of welded cans may also contribute some of the lead. According to Jorhem and Slorach (1987) , foods packed in unlacquered welded cans contained substantially more lead than foods conserved in lacquered welded cans. Previously, old equipment was found to be a source of lead in draft-beer samples ( Smart et al. , 1990 ). After the elimination of sources of lead contamination such as bronze and brass fittings, successful reduction was observed between two surveys in the United Kingdom ( Sherlock et al. , 1986 ; Smart et al. , 1990 ).

(ii) Cadmium

Cadmium and cadmium compounds are carcinogenic to humans (Group 1) ( IARC, 1993b ). In a recent study, the mean contents of cadmium in red wines were higher than those in white wines but without statistically significant differences ( Kim, 2004 ). The data (average, 0.5 µg/L) were in accordance with those reported previously ( Table 1.23 ). There was no significant difference in lead and cadmium contents of wines with different countries of origin ( Kim, 2004 ). In contrast, Barbaste et al. (2003) reported significant differences in the mean cadmium content among the three types of wine: the lowest and the highest mean content were found for red and white wines, respectively. These differences may be related to variations in the wine-making process. The wide variability of these data may result from different factors, both natural and exogenous. Natural factors include soil composition and grape variety. Exogenous factors are the fermentation process, the wine-making system, processing aids (filter materials) or different types of contamination ( Kim, 2004 ). The high concentration of cadmium found in some wine samples could be due to the use of pesticides or fertilizers that contained salts of this metal ( Mena et al. , 1996 ).

Table 1.23. Cadmium in alcoholic beverages.

Cadmium in alcoholic beverages.

In the samples of beer analysed by Mena et al. (1996) , the mean concentration of cadmium was 0.21 µg/L. Canned beers contained the highest levels, probably due to the fact that low-quality cans had been used, with values that varied from 0.50 to 0.80 µg/L; lower concentrations were found in draft beers, with a mean value of 0.20 µg/L. In the other alcoholic beverages that were analysed, the highest concentrations were found in brandy (5.31 µg/L) and whisky (3.20 µg/L) samples; the lowest values were found in samples of liquor and anisette (0.13 and 0.04 µg/L, respectively) ( Mena et al. , 1996 ).

(iii) Arsenic

Arsenic is included in the Group 1 of carcinogens ( IARC, 1987 ).

The mean arsenic content of red wines was significantly lower than that of rosé and white wines ( Barbaste et al. , 2003 ). These differences were attributed by Aguilar et al. (1987) to the different methods of vinification used for rosé and red wines. Typical arsenic concentrations in alcoholic beverages are shown in Table 1.24 .

Table 1.24. Arsenic in alcoholic beverages.

Arsenic in alcoholic beverages.

(iv) Copper

The copper contents of alcoholic beverages are summarized in Table 1.25 .

Table 1.25. Copper in alcoholic beverages.

Copper in alcoholic beverages.

Copper may occur in wine because copper alone or formulated with other agrochemicals is an important substance for the prevention of the outbreak of fungal diseases. During fermentation, the concentration of copper in wine may decrease due to sedimentation as insoluble sulfides together with yeasts and lees ( García-Esparza et al. , 2006 ). The contents of metals were increased in samples treated with organic or inorganic pesticides. In particular, the use of quinoxyfen, dinocap-penconazole and dinocap considerably increased the copper(II) and zinc(II) contents of white and red wines ( Salvo et al. , 2003 ).

In whisky, copper can be traced to two major sources: the copper stills used for distillation and the barley from which the spirit is distilled. However, the use of copper stills mainly determines the amount of copper, and the influence of the raw material can virtually be ignored (3%) ( Adam et al. , 2002 ). In Brazilian sugar-cane spirits, the copper content was correlated with the acidity of the distillate and was higher in the tail fractions. Therefore, the copper content may be reduced if the distillation is stopped at a higher alcoholic grade ( Boza & Horii, 2000 ). Another possibility to reduce the copper levels in Brazilian sugar-cane spirits is storage in oak barrels. A significant reduction in copper levels of 74% was observed during 6 months of ageing ( Ferreira Lima Cavalheiro et al. , 2003 ).

(v) Chromium

The amounts of chromium in Spanish wines varied widely, and differences in the chromium contents of red (32.5 g/L) and white (19.5 µg/L) wines have been reported ( Lendinez et al. , 1998 ). Cabrera-Vique et al. (1997) found levels of chromium that ranged from 6.6 to 90.0 µg/L in French red wines (mean, 22.6 µg/L), from 6.6 to 43.9 µg/L in French white wines (mean, 21.3 µg/L) and from 10.5 to 36.0 µg/L in champagne (mean, 25.1 µg/L). On the basis of analyses of different vintage wines from the same vineyard and winery, it was suggested that concentrations of chromium significantly increase with the age of the wine. Italian wines contained 20–50 µg/L chromium ( Marengo & Aceto, 2003 ) and Greek wines contained 0.01–0.41 mg/L chromium ( Lazos & Alexakis, 1989 ).

Significant differences were also observed among beer samples; in which the chromium content ranged from 3.94 to 30.10 µg/L. Canned and draft beers had the highest values, and lower concentrations were found in bottled beers. Among other alcoholic beverages, mean concentrations of chromium ranged from 7.50 µg/L in rum to 24.45 µg/L in anisette. The highest values were obtained for beverages that contained sugar ( Lendinez et al. , 1998 ). The average chromium content of 100 German beers was given as 7.5 µg/L (range, 1–42 µg/L) ( Donhauser et al. , 1987 ). Danish beers had a mean chromium concentration of 9 µg/L (range, < 2–32 µg/L) ( Pedersen et al. , 1994 ). Fifty-two samples of Brazilian cachaça contained chromium at concentrations of 0.64–1.53 µg/L ( Canuto et al. , 2003 ). A large variation in chromium levels from undetectable to 520 µg/L was reported in an international selection of beverages ( Nascimento et al. , 1999 ).

(vi) Other metals

Selenium was determined in sweet and dry bottled wines from Spain; the concentration varied between 1.0 and 2.0 µg/L in sweet wines and between 0.6 and 1.6 µg/L in dry wines ( Frías et al. , 2003 ). Another survey of Spanish beverages showed 0.15–0.38 µg/L selenium in wine (mean, 0.26 µg/L) and 0.89–1.13 µg/L in beer (mean, 1.007 µg/L) ( Díaz et al. , 1997 ). The mean selenium concentration of 100 German beers was 1.2 µg/L (range, < 0.4–7.2 µg/L) ( Donhauser et al. , 1987 ).

Concentrations of mercury ranged from 2.6 to 4.9 µg/L in sweet Spanish wines and from 1.5 to 2.6 µg/L in dry Spanish wines ( Frías et al. , 2003 ). Mercury was detected in only two of 100 German beers at concentrations of 0.4 and 0.8 µg/L ( Donhauser et al. , 1987 ). In wine and beer on the Danish market, all samples analysed for mercury were below the detection limit of 6 µg/L ( Pedersen et al. , 1994 ).

Antimony levels in 52 samples of cachaça from Brazil varied from undetectable to 39 µg/L ( Canuto et al. , 2003 ). Italian wines contained antimony at concentrations in the range of 0.01–1.00 µg/L ( Marengo & Aceto, 2003 ).

Nickel concentrations in beverages on the Danish market have been reported. Average nickel contents were 49 µg/L in red wine, 42 µg/L in white wine, 93 µg/L in fortified wine and 23 µg/L in beer ( Pedersen et al. , 1994 ). Italian wines contained 15–210 µg/L nickel ( Marengo & Aceto, 2003 ) and Greek wines contained 0–0.13 mg/L ( Lazos & Alexakis, 1989 ). Whisky contained 0.002–0.6 mg/L nickel ( Adam et al. , 2002 ).

Iron concentrations in sugar-cane spirits from Brazil ranged between 0.01 and 0.78 mg/L with an average of 0.21 mg/L ( Bettin et al. , 2002 ). The iron concentration in whisky varied considerably between 0.02 and 28 mg/L ( Adam et al. , 2002 ). The large variance in iron levels in spirits was confirmed by Nascimento et al. (1999) (range, 0.009–2.24 mg/L) and Cameán et al. (2000) (range, not detected-2.03 mg/L). Wine contained concentrations of iron in a range of 1.35–27.8 mg/L ( Marengo & Aceto, 2003 ) or 0.70–7.30 mg/L ( Lazos & Alexakis, 1989 ).

Zinc was determined in 251 wine samples on the Swiss market, with a mean concentration of 614 µg/L ( Andrey et al. , 1992 ), in Italian wine which had a range of 0.135–4.80 mg/L ( Marengo & Aceto, 2003 ) and in Greek wines which had a range of 0.05–1.80 mg/L ( Lazos & Alexakis, 1989 ). The concentrations of zinc in whisky ranged between 0.02 and 20 mg/L ( Adam et al. , 2002 ). Various spirits contained concentrations of zinc between not detectable and 0.573 mg/L; manganese, cobalt and nickel were found in ranges of 0.002–0.657 mg/L, 0.003–0.063 mg/L and 0.001–0.684 mg/L, respectively ( Nascimento et al. , 1999 ). Sherry contained zinc (0–0.829 mg/L), manganese (0–0.157 mg/L) and aluminium (0.02–1.37 mg/L) ( Cameán et al. , 2000 ).

Thallium was regularly found in very low quantities in wine; red wines contained 0.2 µg/L, which was about half that in white wine ( Eschnauer et al. , 1984 ). With a detection limit of 10 µg/L, thallium could be detected in none of 700 wines of worldwide origin ( Kaufmann, 1993 ). More sensitive analyses showed a range of 10–95 ng/L thallium in Italian wine ( Marengo & Aceto, 2003 ).

Only limited data are available on alkali metals and alkaline earth metals in alcoholic beverages. Wine was found to contain lithium (0.008–0.045 mg/L), sodium (3.4–200 mg/L), potassium (750–1460 mg/L), calcium (30–90 mg/L) and magnesium (70–115 mg/L) ( Marengo & Aceto, 2003 ). Another study of wine reported the presence of lithium (0–0.09 mg/L), sodium (5.5–150 mg/L), potassium (955–2089 mg/L), calcium (14–47.5 mg/L) and magnesium (82.5–122.5 mg/L) ( Lazos & Alexakis, 1989 ). Sodium (2–24 mg/L), calcium (0.5–4 mg/L) and magnesium (0.02–4 mg/L) were determined in whisky by Adam et al. (2002) . In a survey of 100 spirits, lithium (0.004–1.26 mg/L), sodium (0.612–94.3 mg/L), potassium (0.34–31.3 mg/L), magnesium (0.40–80.7 mg/L) and calcium (1.36–44.6 mg/L) were detected ( Nascimento et al. , 1999 ). Sherry brandies contained sodium (17.8–635 mg/L), potassium (0.11–70.06 mg/L), calcium (0–14.8 mg/L) and magnesium (0.19–11.2 mg/L) ( Cameán et al. , 2000 ).

Further elements determined in Italian wines include aluminium, boron, iodine, phosphorus, rubidium, silicone, strontium and tin in the milligram per litre range, barium, beryllium, cerium, cesium, cobalt, gallium, germanium, lanthanum, neodymium, palladium, tellurium, tungsten, vanadium, yttrium and zirconium in the microgram per litre range and dyprosium, erbium, europium, gadolinium, hafnium, holmium, molybdenum, nobelium, praseodymium, rhodium, samarium, terbium, thorium, thulium, titanium, uranium and ytterbium in the nanogram per litre range ( Marengo & Aceto, 2003 ).

(vii) Inorganic anions

The fluoride content of alcoholic beverages was found to be very variable. The mean concentration ranged from 0.06 to 0.71 mg/L in beer available in the United Kingdom. Ciders contained a mean of 0.086 mg/L fluoride and wines a mean of 0.131 mg/L fluoride ( Warnakulasuriya et al. , 2002 ).

(viii) Organometals

Organolead compounds are not classifiable as to their carcinogenicity to humans (Group 3) ( IARC, 2006 ) .

As mentioned previously, organolead contamination in wine from automotive sources has rapidly decreased due to the use of unleaded fuel since the 1980s ( Lobiński et al. , 1994 ; Teissedre et al. , 1994 ); only limited information is available on the presence of organometals in other alcoholic beverages. Organotin residues in wine and beer could result from the use of organotin pesticides, contaminated irrigation water or the use of non-food-grade polyvinyl chloride products in storage or production facilities ( Forsyth et al. , 1992a , b ). A preliminary survey of wines and beers on the Canadian market indicated that butyltins are the principal organotin contaminants present in these products. Very low levels of phenyl- and cyclohexyltin compounds were detected in both wine and beer ( Forsyth et al. , 1992a ). In a larger survey, 29 of 90 wines (32%) came out positive for organotin compounds. Dibutyltin (23%) and monobutyltin (16%) were the predominant species. Tributyltin, monooctyltin and dioctyltin were found in single instances ( Forsyth et al. , 1994 ). In 44 samples of Chinese and international alcoholic beverages, the amounts of monobutyltin and dibutyltin ranged from < 0.016 to 5.687 and from < 0.0022 to 33.257 µg/L, respectively. Tributyltin concentrations were much lower, with a highest level of 0.269 µg/L ( Liu & Jiang, 2002 ).

Organic arsenic species were studied in beer and wine ( Herce-Pagliai et al. , 1999 , 2002 ). In table wines and sherry, the percentages of total inorganic arsenic were 18.6 and 15.6% lower than those of the organic species; dimethylarsinic acid and monomethylarsonic acid were the predominant compounds, respectively. In most wine samples, dimethylarsinic acid was the most abundant species, but the total fraction of inorganic arsenic was considerable, and represented 25.4% of the total concentration of the element. In beer, a predominant occurrence of organic arsenic species was determined; the contribution of monomethyl arsonic acid was more significant in alcoholic beers than in alcohol-free beers.

(e) Pesticides

Pesticide residues in grapes, wine and their processing products have recently been reviewed ( Cabras & Angioni, 2000 ). The principal parasites of vines in Mediterranean countries are the grape moth ( Lobesia botrana ), downy mildew ( Plasmopora viticola ), powdery mildew ( Uncinula necator ) and grey mould ( Botrytis cinerea ). To control these parasites, insecticides and fungicides were used and, at harvest time, pesticide residues were found on grapes and could pass into the processed products, depending on the technological processing and the concentration factor of the fruit. The application rates of fungicide were only a few tens of grams per hectare and, consequently, fungicide residues on grapes (cyproconazole, hexaconazole, kresoximmethyl, myclobutanil, penconazole, tetraconazole and triadimenol) were very low after treatment and were not detectable at harvest. Pyrimethanil residues were constant up to harvest, whereas fluazinam, cyprodinil, mepanipyrim, azoxystrobin and fludioxonil showed different disappearance rates (half-lives of 4.3, 12, 12.8, 15.2 and 24 days, respectively). The decay rate of organophosphorus insecticides was very fast with a half-life ranging between 0.97 and 3.84 days. The residue levels of benalaxyl, phosalone, metalaxyl and procymidone on sun-dried grapes equalled those on fresh grapes, whereas residue levels were higher for iprodione (1.6 times) and lower for vinclozolin and dimethoate (one-third and one-fifth, respectively). In the oven-drying process, benalaxyl, metalaxyl and vinclozolin showed the same residue value in fresh and dried fruit, whereas iprodione and procymidone residues were lower in raisins than in fresh fruit.

The wine-making process begins with the pressing of grapes where pesticides on the grape surface come into contact with the must. After fermentation, pesticide residues in wine were always smaller than those on the grapes and in the must, except for those pesticides that did not show a preferential partition between the liquid and solid phase (azoxystrobin, dimethoate and pyrimethanil) and were present in wine at the same concentration as that on the grapes. In some cases (mepanipyrim, fluazinam and chlorpyrifos), no detectable residues were found in the wines at the end of fermentation. Comparison of residues in wine obtained by vinification with and without skins showed that their values generally did not differ. Among the clarifying substances commonly used in wine, charcoal completely eliminated most pesticides, especially at low levels, whereas the other clarifying substances were ineffective. The use of pesticides according to good agricultural practice guaranteed no residues, or levels lower than maximum residue limits at harvest.

Wine and its by-products (cake and lees) are used to produce alcohol and alcoholic beverages by distillation. Fenthion, quinalphos and vinclozolin passed into the distillate from the lees only if present at very high concentrations, but with a very low transfer percentage (2, 1 and 0.1%, respectively). No residue passed from the cake into the distillate, whereas fenthion and vinclozolin passed from the wine, but only at low transfer percentages (13 and 5%, respectively) ( Cabras & Angioni, 2000 ).

The status of pesticide residues in grapes and wine in Italy has been reviewed ( Cabras & Conte, 2001 ). The Italian Ministry of Health reported that, of 1532 grape samples analysed from 1996 to 1999, 1.0, 0.9, 1.8 and 1.9% in each year, respectively, were contaminated. The Italian National Residue Monitoring Programme found that, of 481, 1195 and 1949 grape samples analysed in 1996, 1998 and 1999, 7.9, 6.5 and 2.5%, respectively, were contaminated, while no residues were detected in 259 wine samples. Of the 846 grapes samples and 190 wine samples collected by the National Observatory on Pesticide Residues in 1998 and 1999, a total of 6.1 and 2.1%, respectively, of grapes and 0% of all wine samples were found to contain residues. The low incidence of pesticides in wine was explained by the combined effect of technological processes that lead to a decrease in residues and the fact that large wineries collect grapes from farmers who use different pesticides. Mixing these different grape batches causes a decrease in residues by dilution.

A total of 92 commercial Greek and Yugoslavian wine samples were screened for residues of 84 pesticides. No residues were detected in any of the wine samples from either country ( Avramides et al. , 2003 ).

A total of 51 samples of wines imported in Germany (from Spain, Chile and South Africa) were analysed for residues of 27 pesticides. Gverall, vinclozolin was detected in 80%, methidathion, captan, quintozene, iprodione and dichlofluanid were detected in 33–61% and tetradifon was found in 6% of the samples. Other pesticides were not detected in any sample. The wine samples from Spain contained no iprodione, but often contained quintozene and methidathion. South African wines contained no methidathion. All Spanish and South African wines, but only 68% of Chilean wines, contained vinclozolin. Most pesticides occurred more commonly in red than in white wines ( Pietschman et al. , 2000 ).

A recent survey of pesticide residues in wines on the Swiss market was reported by Edder and Ortelli (2005) ; 176 wines from conventional cultures were analysed and residues were found in 95% of the samples, which indicated that pesticide treatments were frequently used. Approximately 25 active substances used as fungicides or insecticides were detected. For example, the fungicide fenhexamid was present in 61% of the samples at a maximum concentration of 0.59 mg/L and a Swiss maximum residue level of 1.5 mg/L. The following pesticides were found in less than 5% of the samples: spiroxamine, procymidone, diethofencarb, benodanil, chlorothalonil, cyproconazole, tebufenozide, metalaxyl, spinosad, dimethoate, fuberidazole, oxadixyl, pyrifenox and thiabendazol. The total pesticide residues measured ranged between 1 and 700 µg/L. All samples complied with the legal requirements and none exceeded the maximum residue level. It was observed that Swiss wines are generally more heavily contaminated than imported wines. This was explained by the fact that the climate in Switzerland is more favourable to fungal diseases than that in southern countries. The high level of pesticide residue in Swiss wines was mainly caused by one fungicide, fenhexamide, which is currently one of the fungicides most frequently used in vineyard protection.

Edder and Ortelli (2005) also reported results from 70 organic wines sold on the Geneva area market. Unlike conventional culture, the use of synthetic pesticides is totally forbidden in organic wine growing. Most of the samples were Swiss wines (52), particularly from Geneva producers, and the rest were mostly from France and Italy. Approximately half of the organic wines (33 samples) contained no detectable traces of pesticide residues and 29 samples contained only very low levels (below 10 µg/L). Traces were found, in eight samples, in concentrations ranging between 10 and 34 µg/L. The levels of pesticide residues found in organic wines were much lower than those in conventional wines. Traces below 10 µg/L in organic wines were probably due to environmental contamination.

In beer, pesticide residues may be present in the hops, barley or other cereals that are used as raw materials, and may remain in beer produced from contaminated ingredients. During the first steps (malting, mashing and boiling), pesticides on the barley can pass into the wort in various proportions, depending on the process used, although the removal of material in the form of trub and spent grain tends to reduce the level of contaminants, especially pesticides, that are often relatively insoluble in water. Recent research showed that dinitroaniline herbicide residues (pendimethalin and trifluralin) practically disappeared (< 0.3%) after boiling the wort, whereas the percentages of the remaining insecticides (fenitrothion and malathion) ranged from 3.5 to 4.3%, respectively. No residues of dinitroaniline compounds were detected in young beer, whereas there was a significant reduction in fenitrothion (58%) and malathion (71%) residues during fermentation. Lagering and filtering processes also reduced the content of organophosphorus insecticides (33–37%). After the storage period (3 months), the content of fenitrothion was reduced by 75%, and malathion residues were below the limit of detection ( Navarro et al. , 2006 ).

Miyake et al. (1999) showed that none of the agrochemicals spiked into hop pellets were detected in beer because of their loss during boiling and fermentation; however, the levels of these agrochemicals were sufficiently high to be detected in beer when they were not lost through these processes. The same was shown for commercially treated hops. Pesticide residues were not found to carry over into the beer at an appreciable level, except for dimethomorph. Nevertheless, the level of residue was still very low relative to the high levels found on the raw commodity. The potential risk of exposure to pesticide from the consumption of beer produced from hops treated with the agrochemicals studied is low ( Hengel & Shibamoto, 2002 ).

(f) Thermal processing contaminants

In recent years, several heat-generated contaminants have been detected in food, including the chloropropanols, acrylamide and furan. The most probable alcoholic beverage to contain these substances is beer because malt, the main ingredient of beer, is manufactured through heating processes (e.g. kilning or roasting). All three groups of contaminants readily dissolve in aqueous foodstuffs such as beer ( Baxter et al. , 2005a ).

The most abundant chloropropanol found in foodstuff is 3-monochloropropane-1,2-diol (3-MCPD) and, to a lesser degree, 1,3-dichloropropan-2-ol; they have been the centre of scientific, regulatory and media attention as they are considered to be carcinogens ( Tritscher, 2004 ). [3-MCPD is genotoxic in vitro , but there is no evidence of its genotoxicity in vivo (reviewed by Lynch et al. (1998) .] The Scientific Committee on Food of the European Commission considered a level of 2 µg/kg bw as an allowable daily intake for 3-MCPD ( Scientific Committee on Food, 2001 ).

3 -MCPD is not present in lager or ale malts, but is formed when raw or malted cereals are exposed to temperatures above about 120 °C. 3-MCPD is soluble in water, is readily extracted during mashing and can persist into the beer. However, because of the relatively small proportions of specialty products used in the grist, most beers do not contain detectable levels of 3-MCPD. The precursors for 3-MCPD are lipid and chloride, which occur naturally in raw barley in sufficient quantities to allow the formation of 3-MCPD when the grain is heated; no other inputs are involved ( Dupire, 2003 ).

3-MCPD was found in nine of 24 malt products analysed from food suppliers in the United Kingdom at concentrations above 0.01 mg/kg. Significantly, 3-MCPD was only found in coloured malts, and the highest levels were found in the most intensely coloured samples. Additional heat treatments, which include heavy kilning or roasting, were assumed to be a significant factor in the formation of 3-MCPD in malt ( Hamlet et al. , 2002 ). Breitling-Utzmann et al. (2003) analysed a series of German pale and dark brewing malts and malt flours. In the malt flours and the pale brewing malts, only trace amounts of 3-MCPD could be detected, whereas dark brewing malt contained 247 µg/kg 3-MCPD. However, 3-MCPD was not found at levels above 10 µg/kg in lightly or darkly coloured types of beer. The fact that 3-MCPD can react with other food ingredients such as alcohol, aldehydes or acids was given as the reason for the low concentrations in beer. Recent tests by Baxter et al. (2005a) found no 3-MCPD in 55 beers in the United Kingdom, with a quantification limit of 10 µg/L.

3-MCPD can occur in foods and food ingredients either as a free compound or esterified with higher fatty acids. Svejkovská et al. (2004) reported concentrations of free and bound 3-MCPD in Czech malts. A light malt sample (Pilsner type) contained a free 3-MCPD level of about 0.01 mg/kg and a bound 3-MCPD level of less than 0.05 mg/kg. A sample of dark malt had a free 3-MCPD level of about 0.03 mg/kg, while the bound 3-MCPD level reached 0.58 mg/kg.

Similar to 3-MCPD, highest levels of acrylamide were found in specialty malts. Acrylamide is formed in association with Maillard reactions that occur at two main stages in the malting and brewing process: during wort boiling and in the manufacture of specialty malts, which are made by the caramelization of green malts ( Baxter et al. , 2005a ).

Acrylamide is probably carcinogenic to humans (Group 2A) ( IARC, 1994 ). Precursors of acrylamide formation (free sugars and amino acids) are generated during the ‘stewing’ phase of crystal malt manufacture, and acrylamide has been detected in these types of specialty malt ( Baxter et al. , 2005a ). Studies using a pilot scale roaster have identified heating conditions that produce crystal malts with significantly lower concentrations of acrylamide without increasing levels of 3-MCPD ( Baxter et al. , 2005b ).

There are only few reports on acrylamide contents in beer. Spiking experiments revealed that acrylamide remained stable in beer ( Hoenicke & Gatermann, 2005 ). Tareke et al. (2002) analysed three beer samples from the Swedish market. All samples had acrylamide concentrations below the detection limit of 5 µg/kg. Gutsche et al. (2002) analysed 11 German beers and found that only one wheat beer had a detectable acrylamide concentration of 72 µg/kg. Dupire (2003) reported that acrylamide is found in many beers although at much lower concentrations than in other foods. There was a pronounced association with beer colour; little or no acrylamide was detected in either the very palest or the darkest beers, but higher levels were found in beers of intermediate colour. No beers tested contained more than 10 µg/kg. No acrylamide could be detected in ale or lager malt, or in very dark roasted barleys or malts. However, specialty products such as amber and crystal malts did contain significantly higher levels. It appeared that acrylamide is degraded or lost at higher roasting temperatures.

Furan, a very volatile and colourless liquid, has been classified by the IARC as a possible human carcinogen (Group 2B) ( IARC, 1995 ).

EFSA (2004) reported furan concentrations between 5 and 13 µg/kg in six beer samples. Baxter et al. (2005a) found equally low levels in a range of beers; the maximum concentration detected was below 20 µg/L. The low levels of furan in beer, together with a lack of correlation with beer colour, suggest that much of the furan present in the raw materials is lost during brewing due to its high volatility.

Despite the relatively low concentrations of all three classes of thermal processing contaminants in beer, Baxter et al. (2005a) observed that beer could still make a significant contribution to dietary exposure because of the high volume of its consumption.

(g) Benzene

Benzene is carcinogenic to humans (Group 1) ( IARC, 1987 ). Benzene has been reported in carbonated drinks due to contaminated industrial carbon dioxide. Because relatively low levels of carbonation are used in beer and since there is an indigenous source of carbon dioxide from the fermentation process, the average level of benzene found in products due to the use of contaminated gas was below 10 µg/L and did not exceed 20 µg/L ( Long, 1999 ). In the presence of ascorbic acid and the preservative sodium benzoate, benzene might be formed under certain conditions ( Gardner & Lawrence, 1993 ). Contamination of soft drinks with benzene was recently reported ( Hileman, 2006 ). In mixtures of alcoholic beverages and soft drinks (e.g. alcopops, shandy), contamination with benzene may occur; however, the Working Group noted an absence of studies on this topic.

(h) Miscellaneous contaminants

Several contaminants have been found in single cases in alcoholic beverages. Due to a lack of systematic surveys, the relevance of these contaminants cannot be evaluated.

Monostyrene that may derive from polyester tanks was determined in 168 wines originating from 12 countries. The maximum level found was 7.8 µg/L. In 29% of all products, no monostyrene could be detected ( Hupf & Jahr, 1990 ).

Contamination with polydimethylsiloxanes (0.15–0.35 mg/kg) was detected in four brands of Italian wine ( Mojsiewicz-Pieńkowska et al. , 2003 ).

Traces of halogenated acetic acids in beers and wines may arise if the equipment is not cleaned diligently after use of such disinfectants ( Gilsbach, 1986 ; Fürst et al. , 1987 ).

Analysis of nine beer and two wine samples showed the presence of the polycyclic aromatic hydrocarbons (PAH) benzo[ b ]fluoranthene, benzo[ k ]fluoranthene, benzo[ a ]pyrene, benz[ ghi ]perylene and indeno[1,2,3- cd ]pyrene and, in some cases, traces of fluoranthene, benz[ a ]anthracene and dibenz[ a,h ]anthracene. Total contents of PAHs ranged from trace amounts to 0.72 µg/kg ( Moret et al. , 1995 ). PAHs were also present in 18 brands of whisky. Concentrations of the indicator carcinogen benzo[ a ]pyrene were 0.3–2.9 ng/L ( Kleinjans et al. , 1996 ). The sum of the analysed PAH concentrations in 26 aged alcoholic beverages ranged from zero for a white wine to 172 ng/L for a ‘brandy de Jerez solera’. Benzo[ a ]pyrene was found at concentrations below 10 ng/L ( García-Falcón & Simal-Gandara, 2005 ).

1.7. Biomarkers, biomonitoring and aspects of survey measurement

In the following, two aspects of the measurement of alcohol are highlighted that are particularly relevant to epidemiological assessment of alcoholic beverage consumption: the use of biomarkers and the assessment of lifetime exposure. For a recent overview of other aspects of measurement, see Gmel and Rehm (2004) .

1.7.1. Biomarkers and biomonitoring

(a) blood alcohol concentration.

No laboratory test is sufficiently reliable alone to support a diagnosis of alcoholism. Sensitivities and specificities vary considerably and depend on the population concerned. The merits and limitations of traditional and newer biomarkers for alcohol abuse (and abstinence) have been examined critically and reviewed ( Sharpe, 2001 ; Musshoff, 2002 ).

Some conventional biomarkers are described briefly below ( Sharpe, 2001 ).

(b) Ethanol in body fluids

Measurement of alcohol concentrations in blood, urine and breath has a limited, but important role. The results provide no information regarding the severity of alcohol drinking but, when positive, do give objective evidence of recent drinking and can identify increased tolerance.

(c) Serum γ-glutamyl transferase

Serum γ-glutamyl transferase (γGT) activity is increased in the serum of patients with hepatobiliary disorders and in individuals with fairly heavy consumption of alcohol. Serum levels of γGT have been found to be elevated in about 75% of individuals who are alcohol-dependent, with a range in sensitivity of 60–90%. In the general population, progressively higher serum γGT activities are associated with levels of alcohol consumption. Elevated serum γGT is found in 20% of men and 15% of women who consume ∼40 g alcohol per day and in 40–50% of men and 30% of women who drink more than 60 g/day. γGT is primarily an indicator of chronic consumption of large amounts of alcohol and is not increased by binge drinking in non-alcohol abusers, unless there is concomitant liver disease. The half-life of γGT is between 14 and 26 days and its level usually returns to normal in 4–5 weeks after drinking ceases. As well as low sensitivity in some clinical situations, one of the major drawbacks to γGT as a marker of excessive alcohol consumption is its lack of specificity, which can vary from 55 to 100%. Numerous other disorders and drugs can elevate γGT and produce false-positive results, including biliary tract disease, non-alcoholic liver disease, obesity, smoking, diabetes mellitus , inflammation and antidepressants. Although γGT is not an ideal screening marker, it is useful in the confirmation of a clinical suspicion of alcoholism.

(d) Serum transaminases

Aspartate aminotransferase (AST) and alanine aminotranferase (ALT) concentrations in serum are often higher in patients who are alcoholics, although generally not more than 2–4 times the upper normal limits; sensitivities are 25–60% for AST and 15–40% for ALT. Serum levels depend markedly on the degree of liver damage and how recently alcohol has been consumed. Acute alcohol intakes of 3–4 g/kg body weight (bw) can lead to a moderate transient increase in AST in healthy subjects within 24–48h. The AST:ATL ratio improves the test: a ratio > 1.5 strongly suggests, and a ratio > 2.0 is almost indicative of, alcohol-induced damage of the liver. One study has shown that the AST:ALT ratio is the best of several markers to distinguish between alcohol-induced and non-alcoholic liver diseases.

(e) Mean corpuscular volume

An increased mean corpuscular volume (MCV) follows chronic heavy alcohol drinking and correlates with both the amount and frequency of alcohol ingestion, but it may take at least 1 month of drinking more than 60 g alcohol daily to raise the MCV above the reference range. It then takes several months of abstinence for MCV to return to normal. The main weakness of MCV is its low sensitivity (40–50%), but its specificity is high (80–90%) and very few abstainers and social drinkers have elevated MCV values.

Although increased high-density lipoprotein cholesterol or triglycerides can raise suspicion of excessive alcoholic beverage consumption, neither has sufficient sensitivity or specificity to be of use in diagnosis and monitoring.

The conventional marker γGT continues to be the test that combines greatest convenience and sensitivity. Its diagnostic accuracy can be enhanced by combination with other traditional markers such as AST, ALT and MCV ( Sharpe, 2001 ).

The development in chromatographic techniques has enhanced the possibilities for the determination of new and innovative biomarkers of alcohol abuse. New tests have been shown to be useful not only to indicate previous ethanol ingestion, but also to approximate intake and the time when ethanol ingestion has occurred. For such purposes, the determination of ethyl glucuronide in serum or urine samples, the analysis of 5-hydroxytryptophol in urine or the analysis of fatty acid ethyl esters appear to be useful ( Musshoff, 2002 ). These new markers could also be detected in hair ( Fig. 1.7 ).

Possible markers of chronically elevated alcohol consumption in hair

A well known advantage of hair analysis is that compounds with a relative short lifetime in blood can be entrapped and are detectable for a long time and at a relatively high concentration in this sample material; hair analysis could provide a good test for the measurement of alcohol consumption ( Pragst et al. , 2000 )

1.8. Regulations on alcohol

1.8.1. regulations on the composition of alcoholic beverages.

The Codex alimentarius was created in 1963 by FAO and WHO to develop international food standards and guidelines. For alcoholic beverages, the Codex Standards for food additives ( Codex alimentarius , 2006 ), for natural flavourings ( Codex alimentarius , 1987 ) and contaminants ( Codex alimentarius , 1997 ) are of special interest. These standards are discussed in detail in Sections 1.6.6 and 1.6.7 . In general, the standards provide some information about suitable additives for alcoholic beverages with maximum levels for certain substances. Maximum levels are also given for certain biologically active substances in natural flavourings. Due to advances in food production and surveillance, the concentrations of some contaminants (e.g. nitrosamines in beer, lead in wine) have been significantly reduced over the past years (see Section 1.6.7 for details). The standards have been incorporated into the national legislation of the majority of countries. However, some countries may impose more specific or more stringent regulations. For example, the European Union has published detailed regulations for food additives and even defines certain categories of spirits such as whisky, rum and vodka ( European Council, 1989 ).

1.8.2. Regulations on alcoholic beverage consumption

The available data on regulations for alcoholic beverages for the majority of the WHO Member States have been reviewed by the Global Status Report: Alcohol Policy ( WHO, 2004 ), and the following brief discussion relies mainly on that report.

Regulations for alcoholic beverages are often referred to as alcohol policy or alcohol control policy. Alcohol policy can be defined as measures put in place to control the supply and/or affect the demand for alcoholic beverages, minimize alcohol-related harm and promote public health in a population. This includes education and treatment programmes, alcohol control and harm-reduction strategies. To alleviate or mitigate the burden of alcoholic beverages on societies, most countries have employed some strategies across time to limit or regulate alcoholic beverage consumption and the distribution of alcoholic beverages. Some of these measures have been due to public health concerns, and others have been based on religious considerations or quality control of products, or have been introduced to eliminate private-profit interest or increase government revenue. The different measures can be broadly divided into three main groups: population-based policies, problem-directed policies and direct interventions. The first group are policies that are aimed at altering levels of alcoholic beverage consumption among the population as a whole. They include taxation, advertising, availability controls (from prohibition to state monopolies, regulations on density of outlets, hours and days of sale), drinking locations, minimum drinking age limits, health-promotion campaigns and school-based education. The second group of policies are aimed at specific alcohol-related problems such as drinking and driving (e.g. promoting random breath testing) or alcohol-related offences. The third group are interventions that are aimed at individual drinkers and include brief interventions, treatment and rehabilitation programmes.

Countries emphasize various policies differently, since each country is unique in its needs and requirements, but there is mounting evidence that strategies are available which clearly impact levels and patterns of alcoholic beverage drinking in a population when implemented with sufficient popular support and continuously enforced. Over the past 20 years, considerable progress has been made in the scientific understanding of the relationship between alcohol policies, levels of alcoholic beverage consumption and alcohol-related harm. The existing evidence ideally should be the basis for formulating polices that protect health, prevent disability and address the social problems associated with alcoholic beverage consumption.

A study of the alcohol policies of 117 WHO Member States looked at the following areas of alcohol policy: restrictions on availability, drink–driving, price and taxation, advertising and sponsorships, and alcohol-free environments. The following gives some examples of the measures implemented, but it should be noted that the study does not cover all countries ( WHO, 2004 ).

About 15% of countries have retail state monopolies, while 74% have alcoholic beverage licensing requirements to sell or serve alcohol. For off-premises sales, many countries also have restrictions on places of sale (59%) and hours of sale (46%) and, to a lesser degree, on days of sale (27%) and density of the outlets (19%).

Only 18% of countries do not have any age requirements for the purchase and consumption of alcoholic beverages. In the majority of countries, the age limit is set at 18 years (61%).

Seven per cent of countries do not have a legal drink-driving limit in place, while most countries (39%) fall in the middle category of having a blood alcohol concentration level of 0.04–0.06 g/100 mL. Of the countries that have existing drink-driving legislation, 46% have no testing or only test rarely for the sobriety of drivers through random breath testing.

With regard to the pricing of alcoholic beverages, the 118 countries showed great differences; however, with regard to median values of relative prices across the countries, a bottle of wine would cost the same as two bottles of beer and a bottle of spirits the same as two bottles of wine. In general, relative price seems closely related to economic development—the more developed a country is, the lower are the prices relative to the average income. In addition, countries that have large domestic production of a beverage tend to have lower prices for this product.

Countries have banned or restricted the advertisement of alcoholic beverages in different media to a varying degree. Television and radio are more controlled than print media and billboards, and advertising of spirits is more strictly controlled than that of beer and wine. About 24% of countries restrict sponsorship of youth or sports events by the alcohol industry. In countries where advertising of alcohol is allowed, 33% require a health warning of some sort on the advertisement.

Many countries ban drinking in different public domains such as in educational buildings (58%), health care facilities (55%), government offices (48%), workplaces (47%) and public transport (45%). Less controlled are sporting events (26%), parks/streets (24%) and leisure events such as concerts (16%).

Regulations on alcohol are occasionally beverage-specific. Some countries regulate and tax beer according to its strength—the stronger the beer, the higher the tax and the more strict are regulations, for example, on advertising. In a mainly European context, so called alcopops have received special attention. Media, politicians and public health advocates have called for legal restrictions specifically on alcopops, which have been introduced through increased prices, e.g. in France, Germany and Switzerland. The beverage industry avoids the legal restriction on alcopops by creating new designer drinks such as beerpops that do not fall under the special tax ( Wicki et al. , 2006 ). In Germany, solid alcopops in powder form were developed to evade the alcopop tax. The alcohol is bound to a sugar matrix and, after dissolution in water, the product contains about 4.8% vol alcohol ( Bauer-Christoph & Lachenmeier, 2005 ).

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Alcohol Consumption

  • January 2013
  • In book: Encyclopedia of Behavioral Medicine (pp.61-65)
  • Chapter: Alcohol consumption

Susan E Collins at Washington State University

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  • Cosme Alvarado-Esquivel
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COMMENTS

  1. (PDF) Alcohol consumption trends and patterns of drinking

    estimate of 32.8 g of alcohol per day and per drinker corresponds appr oximately to. the following average co nsumption per week: almost 6 litres of beer (5% alcohol by. volume), or three bottles ...

  2. (PDF) Alcohol consumption among older adults in the ...

    Context Alcohol consumption is responsible for numerous life-threatening diseases, including liver cirrhosis, heart disease, and various cancers. ... ResearchGate has not been able to resolve any ...

  3. The Effects of Alcohol Consumption on Academic ...

    ResearchGate has not been able to resolve any citations for this publication. ... Alcohol consumption among secondary school students is a major public health issue worldwide; however, the extent ...

  4. The risks associated with alcohol use and alcoholism

    Alcohol consumption, particularly heavier drinking, is an important risk factor for many health problems and, thus, is a major contributor to the global burden of disease. In fact, alcohol is a necessary underlying cause for more than 30 conditions and a contributing factor to many more. The most common disease categories that are entirely or ...

  5. Strategies to cut down drinking, alcohol consumption, and usual

    Methods: We use a continuous repeat cross-sectional survey and one-week drinking diary collected by the market research company Kantar; these provide detailed information on alcohol consumption during a diary week and on how individuals try to moderate alcohol use for 49,204 British adults trying to reduce their drinking from 2013 to 2019. We ...

  6. Alcohol consumption in relation to cardiovascular diseases and

    For alcohol consumption as exposure, non-drinkers would make an obvious control group. Likewise, in some cultures women tend to abstain from alcohol and therefore could be valid negative controls as well. Sometimes, the validity of the third assumption can be assumed when the biological function of the genetic instrument is known. For both the ...

  7. Influence of eating habits and alcohol consumption on the academic

    Furthermore, a significant relation was observed between alcohol consumption and academic performance (Figure 2). These findings are in line with the results of previous studies associating alcohol consumption with academic difficulties and less hours of study (Mekonen et al., 2017b)(El Ansari et al., 2013). This may be related to various ...

  8. The Risks Associated With Alcohol Use and Alcoholism

    Alcohol consumption has been identified as an important risk factor for illness, disability, and mortality (Rehm et al. 2009b).In fact, in the last comparative risk assessment conducted by the World Health Organization (WHO), the detrimental impact of alcohol consumption on the global burden of disease and injury was surpassed only by unsafe sex and childhood underweight status but exceeded ...

  9. Alcohol consumption and risks of more than 200 diseases in ...

    We investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of >512,000 adults (41% men), including 168,050 genotyped for ALDH2- rs671 and ADH1B ...

  10. (PDF) The Impact of Alcohol Consumption on Food Choice ...

    2014). In 2008, 69% of college students re-. ported drinking alcohol in the past month. (Ilgen et al., 2011). Drinking alcohol can. reduce students' inhibitions and lead them to. engage in ...

  11. Alcohol outlets and alcohol consumption in changing ...

    Alcohol consumption was assessed as days per week (pw), drinks pw, high consumption (≥8 drinks pw), and binge drinking. Availability of off-premise alcohol outlets was assessed using 1-mile density and distance. Regression models adjusted for age, gender, race/ethnicity, income, education, health status, state and population density. ...

  12. Daily Alcohol Intake and Risk of All-Cause Mortality

    The study also investigated the risk of all-cause mortality for alcohol consumption according to (1) median ages of the study populations (younger than 56 years or 56 years and older), replicating the methods of Zhao et al 9; (2) the sex distribution of the study populations, and (3) studies of cohorts recruited before a median age of 51 years ...

  13. Effects of Alcohol Consumption on Driving: A Systematic Review

    Starkey N. J., Charlton S. G. (2014). The effects of moderate alcohol concentrations on driving and cognitive performance during ascending and descending blood alcohol concentrations. Human Psychopharmacology: Clinical and Experimental, 29(4), 370-383.

  14. Health Risks and Benefits of Alcohol Consumption

    The effects of alcohol on the liver include inflammation (alcoholic hepatitis) and cirrhosis (progressive liver scarring). The risk for liver disease is related to how much a person drinks: the risk is low at low levels of alcohol consumption but increases steeply with higher levels of consumption ( Edwards et al. 1994 ).

  15. Current alcohol consumption and associated factors among school

    Alcohol consumption is a strong contributing factor to the mental and behavioral disorders of school adolescents and youths. ... (after requesting full texts from the corresponding authors via email and/or ResearchGate) and articles with missing or insufficient outcomes were excluded. Also, studies conducted in nonhuman subjects, reviews ...

  16. The Effect of Alcohol Consumption on the Academic ...

    The result revealed that there is a significant relationship between alcohol consumption and academic performance (R 2 =0.74,P<.O5), there is a significant difference in academic performance of ...

  17. PDF The Effects of Alcohol Consumption on Academic Performance: A

    alcohol consumption and their academic performance, with higher levels of alcohol use being associated with lower levels of academic achievement. [6]. A study in the United States investigated the impact of alcohol binge drinking and students' self-reported GPA. By performing separate regression analysis using OLS with marijuana and alcohol use as

  18. Poor progress on reducing alcohol consumption in Europe

    On July 29, 2024, the WHO Regional Office for Europe (WHO/Europe) issued a statement warning that the region was making very little progress in cutting consumption of alcohol. Two-thirds of adults in the WHO European region drink alcohol and an estimated 11% have an alcohol use disorder. Average consumption works out at 9·2 L of pure alcohol per year for every adult in the region.

  19. The Effects of Alcohol Consumption on Recovery Following ...

    Force, power, muscular endurance, soreness and rate of perceived exertion are also unmodified following alcohol consumption during recovery. Cortisol levels seemed to be increased while testosterone, plasma amino acids, and rates of muscle protein synthesis decreased. Keywords: muscle function; muscle mass; performance; strength; training.

  20. Chronic Alcohol Consumption and its Impact on Bone and Metabolic Health

    In India, according to the Sample Registration Survey conducted in 2014, the prevalence of alcohol consumption among adult males was found to be 10%.[] In a similar study done in southern part of India, it was found that 67% of alcohol consumers had a problematic drinking pattern with 52.5% having a hazardous/harmful drinking pattern and 14.7% being dependent alcoholics.[]

  21. (PDF) Effects of Alcohol Consumption on Various Systems ...

    Blood pressure (BP) is increased by regular alcohol consumption in a dose‐dependent manner, with a relative risk for hypertension (systolic BP > 140 mm Hg or diastolic > 90 mm Hg) of 1.7 for 50 ...

  22. The Effect of Alcohol Consumption on the Academic Performance of

    The result revealed that there is a significant relationship between alcohol consumption and academic performance (R2=0.74,P.O5), there is a significant difference in academic performance of students that drink alcohol and those that do not (R2=12.22,P.05), there is a significant effect of alcohol consumption on academic performance(R2=4.474,P ...

  23. (PDF) Alcohol Consumption in China Before and During ...

    For alcohol consumption (a key driver of obesity, metabolic disorders, cardiovascular disease, and related complications), men were found to engage in more risky drinking behavior (43.2% vs. 9.3% ...

  24. 4 Major Health Benefits to Drinking Beer

    Interestingly, some studies suggested that the naturally occurring nutrients in beer, not just the alcohol, contribute to these health benefits. 1. Cardiovascular Health. One of the significant findings from the researchers is the positive impact of moderate beer consumption on cardiovascular health.

  25. Exposure Data

    The ethanol content in beer usually varies from 2.3% to over 10% vol, and is mostly 5-5.5% vol. In some countries, low-alcohol beer, i.e. below 2.3% vol, has obtained a considerable share of the market. In general, beer refers to barley beer, although sorghum beer is consumed in large quantities in Africa.

  26. Alcohol Consumption

    January 2013. DOI: 10.1007/978-1-4419-1005-9_626. In book: Encyclopedia of Behavioral Medicine (pp.61-65) Chapter: Alcohol consumption. Authors: Susan E Collins. Washington State University. Megan ...