Critiques of Recent Publications

NOTE:  FOR AN ARCHIVE OF CRITIQUES, BY TOPIC, PUBLISHED BETWEEN APRIL, 2010 AND APRIL 2011, CLICK HERE.

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Critique 081:  Alcohol intake in the elderly affects risk of cognitive decline and dementia  –  22 May 2012

A well-done review paper on the association between alcohol consumption and cognition in the elderly provides an excellent summary of potential mechanisms by which alcohol may affect cognitive function and the risk of dementia, both adversely and favorably.  Current scientific data indicate that heavy drinking is associated with an increased risk of neurological disease and dysfunction, while regular light-to-moderate alcohol intake seems to be associated with a reduced risk of such dysfunction, including a lower risk of developing Alzheimer’s disease.

At present, the mechanisms by which the moderate intake of wine and other alcoholic beverages reduces the risk of cardiovascular diseases are much better defined than they are for cognition.  Forum members agree with the authors that further research is needed to evaluate a potential role that wine and other alcoholic beverages may play in reducing the risk of dementia.  Forum members also agree that, at present, the specific mechanisms of such putative protection are not well defined, and it would be premature to recommend light-to-moderate drinking for reducing the risk of dementia.  On the other hand, current epidemiologic and biomedical data suggest that most elderly subjects who are responsible and moderate drinkers would not benefit from being advised to stop their alcohol consumption.

Reference:  Kim JW, Lee DY, Lee BC, Jung MH, Kim H, Choi YS, Choi I-G.  Alcohol and Cognition in the Elderly: A Review.  Psychiatry Investig 2012;9:8-16;  On-line: http://dx.doi.org/10.4306/pi.2012.9.1.8

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here. 

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Critique 080:  Modest alcohol intake is associated with less inflammation among patients with the most common type of liver disease, non-alcoholic fatty liver disease (NAFLD)   —   15 May 2012

NAFLD (non-alcoholic fatty liver disease) is the most common type of liver disease in the developed world, affecting up to one-third of the US population.  NAFLD is often associated with obesity and other parameters of the so-called “metabolic syndrome,” which is a major risk factor for the development of cardiovascular disease.  In a well-done study among subjects with NAFLD, the investigators have demonstrated that modest alcohol consumption (an average of up to 20 grams of alcohol per day and no binge drinking) is associated with less evidence of inflammation of the liver (steatohepatitis), a condition known to markedly increase the risk of progression of liver disease to cirrhosis. 

Given that NAFLD and other conditions associated with the metabolic syndrome are so common, and are major risk factors for developing cardiovascular disease, the results of the present study are important.  They show that modest drinking is associated with decreased, not increased, inflammation of the liver.  Further, even among subjects with NAFLD, cardiovascular disease is a much more common cause of death than liver disease.  The authors suggest that intervention studies should be done to support their findings; if confirmed, subjects with NAFLD should not be advised to avoid all alcohol, which is the current advice usually given to such patients.

Reference:  Dunn W, Sanyal AJ, Brunt EM, Unalp-Arida A, Donohue M, McCullough AJ, Schwimmer JB.  Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD).  Journal of Hepatology 2012 (pre-publication release)

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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A Tribute to Federico Leighton Puga, MD    —   8 May 2012

Frederico Leighton Puga, MD, Professor and Director of the Center for Molecular Nutrition and Chronic Diseases of the Catholic University of Chile in Santiago, died on 27 April 2012 at the age of 74 years.  Dr. Leighton was a valued member of the International Scientific Forum on Alcohol Research, and was noted for his seminal work in nutrition, antioxidants, the health aspects of moderate wine consumption, and public health approaches for the prevention of chronic diseases.

Many Forum members knew and had worked with Dr. Leighton through many decades.  All feel a deep loss, of a great scientist, a loyal and good friend, and someone very concerned with the health of people everywhere.  As stated by one Forum member, “Federico was a great scientist motivated by curiosity and the desire to be useful for his country.  His culture and education and intellectual rigor were well integrated into his humanity and the sweetness of his character.”  Said another: “Federico had in abundance that indefinable quality known as ‘class.’”  The world has lost an honest and honorable scientist.   

For the full tribute to Dr. Leighton by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 079:  Moderate alcohol consumption both prior to, and following, a myocardial infarction is associated with lower risk of mortality  –  17 April 2012

In a very well-done analysis based on the follow up of more than 50,000 subjects from The Health Professionals Follow-up Study (HPFS), 1,818 men were confirmed with incident non-fatal myocardial infarction (MI).  Among MI survivors, 468 deaths were documented during up to 20 years of follow up.  Repeated reports were obtained on alcohol consumption  throughout follow up.  Average alcohol consumption was calculated prior to and then following the MI.

The overall results show that, in comparison with no alcohol consumption, the pre-MI and the post-MI intakes of light (0.1-9.9 g/day) and moderate (10.0-29.9 g/d) amounts of alcohol were both associated with lower risk of all-cause mortality and cardiovascular morality among these men.  The significant reductions in all-cause mortality risk (22% lower for 0.1-9.9 g/day and 34% lower for 10.0 – 29.9 g/day, in comparison with non-drinkers) were no longer present for consumers of ≥ 30 g/day; for this highest consumer group, the adjusted hazard ratio was 0.87 with 95% CI of 0.61-1.25.

There are a number of other informative and interesting results described from this study.   First, there was little change in reported alcohol prior to and following the MI: drinkers tended to remain drinkers of similar amounts.  Few non-drinkers began to drink after their MI; among heavier drinkers, there was a tendency to decrease the amount somewhat (but very few stopped drinking completely).  Further there were no significant differences in outcome according to type of beverage consumed although, interestingly, lower hazard ratios were seen for consumers of beer and liquor than of wine.  While the authors state that the effects of alcohol were stronger for the association with non-anterior MIs, the HRs for all-cause mortality were little different: among the moderately drinking men the HRs were 0.58 for anterior MI and 0.51 for other types of MI.

Even though exposures (such as alcohol) for cardiovascular events (such as MI and  cardiovascular mortality) may be different after a person has an event than it was before the event, in this study the reductions in risk were almost the same.  For example, both for alcohol intake reported prior to a MI, and that after a non-fatal MI, the risk of mortality was about 30% lower for moderate drinkers than it was for abstainers.  This suggests that, in terms of reducing cardiovascular disease, alcohol may have relatively short-term effects.  Frequent consumption (of moderate amounts) may result in the best health outcomes.

Reference:  Pai JK, Mukamal KJ, Rimm EB.  Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study.  European Heart Journal 2012;doi:10.1093/eurheartj/ehs047

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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 Critique 078:  An update on the association of alcohol consumption with risk of breast cancer  — 10 April 2012

An excellent review paper on the relation of alcohol consumption to the risk of breast cancer concludes that, overall, there is a positive dose-response relation between alcohol drinking and the risk of breast cancer.  The analysis shows that an increase in risk is seen even among women reporting an average of only about one drink/day.  Given the high prevalence of such light drinking in most female populations, the authors estimate that up to 1 to 2% of breast cancers in Europe and North America may be attributable to light drinking alone.  Thus, while alcohol appears to be a risk factor for breast cancer, it does not explain a very high percentage of cases.

Forum members considered this to be a well-done analysis, with a good review not only of epidemiologic studies but of potential mechanisms of effect of alcohol on breast cancer risk.  An increase in estrogen levels from alcohol seems to be the physiologic mechanism most commonly suggested for the increase in risk.

The meta-analysis is noteworthy in presenting risks specifically for women who consume up to one drink/day, which is the common pattern for a high proportion of women in western cultures.  On the other hand, the authors herefailed to discuss the potential modification of alcohol effects on cancer risk from folate in the diet; in many studies, high folate levels tend to diminish or eliminate an increase in risk from alcohol.  Further, the paper does not provide a discussion of the net effects of moderate drinking on mortality.  In older women, the decrease in the risk of cardiovascular disease (a much more common cause of death than breast cancer), greatly exceeds the potential increase in risk of death from breast cancer.

Reference:  Seitz HK, Pelucchi C, Bagnardi V, La Vecchia C.  Epidemiology and Pathophysiology of Alcohol and Breast Cancer: Update 2012.  Alcohol and Alcoholism 2012; doi: 10.1093/alcalc/ags011

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

 

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Critique 077:  Swedish study supports a “U-shaped” association of alcohol consumption with risk of pre-diabetes and diabetes mellitus  –  29 March 2012

Subjects in a cohort in Sweden, some of whom had been exposed to a community intervention program to prevent diabetes, were evaluated 8-10 years after baseline for the presence of diabetes mellitus or impaired glucose metabolism (“pre-diabetes”) in relation to a baseline report of alcohol consumption.  Approximately 2,000 men and 3,000 women had a normal glucose tolerance test at baseline; of these 105 men and 57 women developed type II diabetes.  Of subjects with pre-diabetes at baseline, 175 men and 98 women progressed to diabetes.  The authors report that total alcohol consumption and binge drinking increased the risk of pre-diabetes and diabetes in men, while low consumption decreased diabetes risk in women.  However, the authors did not discuss the fact that in essentially all comparisons, the highest risk of diabetes or pre-diabetes was among abstainers.

Forum reviewers had some concerns about the study.  For example, the study included some subjects who had been exposed to an intervention trial to prevent diabetes, yet no information is given on potential effects of the intervention.  It was not a population-based group.  Also, the sample was “enriched” with subjects who had a positive family history of diabetes, which may make it more difficult to judge the effects of environmental factors.  Ex-drinkers and never drinkers were included in the abstainer group.

It appears that the authors focused only on the “statistically significant” results rather than commenting on the overall pattern of association (lower risk of developing diabetes for moderate drinkers than for abstainers and heavier drinkers).  Further, the number of subjects in many of the sub-groups was very small, making it difficult to define specific cut-points for effects of alcohol on risk.

Nevertheless, reviewers considered that, overall, these analyses support the usual findings from previous research of a “U-shaped curve” for alcohol and diabetes for both men and women.  There appears to be a reduction in risk with moderate alcohol intake and possibly an increased risk for heavier drinking.

Reference:  Cullmann M, Hilding A, Östenson CG.  Alcohol consumption and risk of pre-diabetes and type 2 diabetes development in a Swedish population.  Diabet Med 2012;29:441–452.  DOI: 10.1111/j.1464-5491.2011.03450.x

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 076:  Evaluating the association of alcohol intake with cognitive functioning using a Mendelian randomization study design  — 22 March 2012

Many observational cohort studies have shown that moderate alcohol use is associated with better cognitive function.  However, since such studies are vulnerable to residual confounding by other lifestyle and physiologic factors, the authors conducted a Mendelian randomization study, using aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis.  Cognitive function was assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284) among men from the Guangzhou Biobank Cohort Study (2003–2008).  The authors had previously reported an association between reported alcohol intake and cognitive function  from a larger group of subjects from the same study finding that women reporting occasional alcohol intake and men reporting occasional or moderate intake had better scores related to cognitive function than did abstainers.¹

In the present Mendelian study, the authors found no significant association between groups defined by the ALDH2 genotype (as an “unbiased” estimate of alcohol consumption) and the two measures of cognitive functioning.  A problem with the present analysis is that ALDH2 genotypes explained only 3% of the variance in reported alcohol intake, which weakens the conclusions of the authors.  Further, differences in the predominant type of beverage consumed (rice wine), and probably marked differences in drinking patterns between these subjects and Europeans and Americans, make it difficult to know what the implications of this study are for western industrialized societies.

We agree with the authors that “Causality should be thoroughly verified in a variety of settings using different kinds of evidence, including experimental or genetic studies, rather than relying on simple observations in a particular setting.”  We strongly support future attempts at using Mendelian  randomization studies, hopefully using better instruments for estimating alcohol intake.  On the other hand, as stated by recent evaluations of various study designs for determining causality,³ we appreciate that Mendelian randomization sounds good, but it is not the “Holy Grail.”

Reference:  Au Yeung SL, Jiang CQ, Cheng KK, Liu B, Zhang WS, Lam TH, Leung GM, Schooling CM.  Evaluation of moderate alcohol use and cognitive function among men using a Mendelian randomization design in the Guangzhou Biobank Cohort Study.  Am J Epidemiol 2012; pre-publication release. DOI: 10.1093/aje/kwr462

Please click here for the full critique of this paper by members of the International Scientific Forum on Alcohol Research.

 

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Critique 075:  Moderate drinking associated with lower risk of stroke in women  –  15 March 2012

A well-done analysis from the Nurses’ Health Study shows that the risk of total stroke is slightly lower among light-to-moderate consumers of alcohol than among subjects reporting no alcohol intake.  In comparison with non-drinkers, the estimated risk is 17-21% lower for women averaging up to 15 grams of alcohol per day (a little over one drink/day by US definitions of approximately 12 grams of alcohol for a typical “drink.”).  For consumers of larger amounts of alcohol, the risk of stroke has a tendency to be slightly increased, but not statistically significantly so.

Data on the pattern of drinking (regularly, binge, etc.) were not reported.  Among these predominantly light drinkers, there were no differences between effects on the risk of the most common type of stroke, ischemic stroke (due to atherosclerotic obstruction of a artery or an embolic clot) or the less-common hemorrhagic stroke (bleeding into the brain).

The results, with full adjustment for other factors that may affect risk, suggest a “J-shaped” curve for total stroke, with reductions in risk for light-to-moderate drinking and possibly an increase with greater amounts.  In this study, the point at which the risk of drinkers exceeds that of non-drinkers was about 38 grams of alcohol per day (the equivalent of about 3 typical “drinks”), with a 95% confidence interval of 28 to 57 grams/day.

The study supports many previous reports from observational epidemiologic studies that have shown a slight reduction in risk of the ischemic type of stroke from moderate alcohol intake.  Some, but not all previous studies, show an increase in hemorrhagic stroke for any amounts of alcohol, but that was not seen in this study, possibly because there were few heavy drinkers in this group of nurses.

Reference:  Jimenez M, Chiuve SE, Glynn RJ, Stampfer MJ, Camargo Jr CA, Willett WC, Manson JE, Rexrode KM.  Alcohol Consumption and Risk of Stroke in Women.  Stroke 2012, pre-publication.  http://stroke.ahajournals.org.  DOI: 10.1161/STROKEAHA.111.639435

Please click here for the full critique of this paper by members of the International Scientific Forum on Alcohol Research.

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Critique 074:  Does moderate wine consumption improve lung function?  — 8 March 2012

An analysis based on a prospective study in the Netherlands assessed the impact of wine and resveratrol intake on lung function.  It also studied genetic factors (affecting sirtuin) that have been found to be mechanisms by which resveratrol relates to metabolism and longevity of life.  The authors report that resveratrol intake was associated with higher lung volumes and that white wine intake (but not red wine intake) was associated with lower risk of airway obstruction.  They report that the genetic factors studied did not relate to the associations found.

While several previous studies (as does this one) have reported that wine intake improves lung function, Forum reviewers were concerned about several aspects of the paper, and especially with the conclusions of the authors that resveratrol was the key factor in improved lung function.  A reviewer stated: “Resveratrol may well be just the bystander of something else present in wine.”  The beneficial effects on lung function are probably related to many compounds present in wine, and not just resveratrol.

Based on a number of scientific studies, moderate wine intake appears to have a favorable effect on lung function.  The doses of resveratrol seen in these epidemiologic studies are in the physiological range that could be expected from moderate wine consumption, unlike the huge doses of resveratrol being evaluated as a potential life-extending drug in pharmaceutical studies.

Reference:  Siedlinski M, Boer JMA, Smit HA, Postma DS, Boezen HM.  Dietary factors and lung function in the general population: wine and resveratrol intake.  Eur Respir J 2012; 39: 385–391;  DOI: 10.1183/09031936.00184110

Please click here for the full critique by members of the International Scientific Forum on Alcohol Research.

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Critique 073: The association of alcohol consumption with osteoporosis  — 5 March 2012

Osteoporosis is a key underlying factor in fractures among the elderly, which are increasingly a major health problem.  A review paper from France on the association between alcohol consumption and bone metabolism states that heavy alcohol intake may adversely affect bone mineral density and increase the risk of osteoporosis.  It states that lighter drinking may actually improve bone density, but presents very limited data to support this statement.  Forum members were disappointed that the paper did not carry out a meta-analysis or other synthesis of the data; further, data from a number of key epidemiologic studies on the subject were not discussed in the paper.

The paper provides important information on the mechanisms by which alcohol may affect bone metabolism.  The authors describe effects of alcoholic beverages on bone density, bone microarchitecture, bone remodeling, and other mechanisms, which help explain how alcohol and polyphenols and other constituents of beer and wine may relate to the risk of fractures in the elderly.

Unfortunately, despite what the authors’ conclude, the paper does not provide a summation of the scientific data upon which public health policy can be based.  Overall, current scientific data suggest that bone mineral density and the risk of fractures are favorably affected by light-to-moderate drinking, but adversely affected by heavy drinking and alcoholism.

Reference:  Maurel DB, Boisseau N, Benhamou CL, Jaffre C.  Alcohol and bone: review of dose effects and mechanisms.  Osteoporos Int (2012) 23:1–16; DOI 10.1007/s00198-011-1787-7.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 072:  Obesity may modify the association between alcohol consumption and the risk of colorectal cancer. 23 February 2012

A case-control study from Newfound/Labrador has reported that greater alcohol intake may increase the risk of colorectal cancer among obese subjects, but not among non-obese subjects.  This is not a particularly large study, and only 45-60% of subjects who were recruited by telephone ended up providing data.  Further, it is a case-control comparison, rather than a cohort analysis, making bias in the results more likely.

In this study, there was no relation of alcohol with the risk of CRC when considering the entire population.  However, when subjects were stratified by BMI (<30 versus ≥ 30), the data indicate an increase in CRC risk for obese subjects who were “drinkers” (OR=2.2, 95% CI 1.2-4.0), especially among subjects reporting 5 or more drinks/daily (OR=3.7, CI 1.5-9.0).  On the other hand, even among obese subjects there was not a clear dose-response effect noted, i.e., there was not a step-wise increase in CRC risk with greater number of drinks/day  For example, the odds ratio (OR) was 2.3 times that of non-drinkers for obese subjects reporting 1-2 drinks/daily and 1.3 for those reporting 3-4 drinks/daily.

It will be interesting to determine if other studies show that there is modification of the association between alcohol intake and colorectal cancer by obesity.  If such is the case, it could help understand some of the mechanisms for the development of cancer and provide better guidelines for screening for CRC.

Reference:  Zhao J, Zhu Y, Wang PP, et al.  Interaction between alcohol drinking and obesity in relation to colorectal cancer risk: a case-control study in Newfoundland and Labrador, Canada.  BMC Public Health 2012, 12:94 doi:10.1186/1471-2458-12-94

Please click here for the full critique of this paper by members of the International Scientific Forum on Alcohol Research.

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Critique 071:  Forum Comments on proposed new dietary guidelines for Australia  –  16 February 2012

Members of the International Scientific Forum on Alcohol Research have provided comments on the chapter related to alcohol intake that has been included in “A review of the evidence to address targeted questions to inform the revision of the Australian Dietary Guidelines,” by the Australian Government Department of Health and Ageing and National Health and Medical Research Council (NHMRC), November 2011, ISBN Online 1864965304.

Forum members considered that the authors of the report should be commended on their work.  Criticisms are primarily about the restriction in the time frame of the review, and minimal consideration of key nuances, such as quantity of alcohol consumed and its relation to risk or benefit, patterns of drinking, the balance between risks and benefits, and making statements at all when the evidence is too weak.  More details (e.g. considering cardiovascular mechanisms to widen the search) would have added weight to the conclusions.

For the full comments of the International Scientific Forum on Alcohol Research, please click here.

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Critique 070:  Potentially important new mechanisms found for the anti-aging effects of resveratrol, a phenolic compound found in red wine  — 9 February 2012

A well-conducted experimental study in mice has provided potentially important new insights into the association of the intake of resveratrol and like compounds with health benefits.  Resveratrol is a constituent of red wine and other vegetable products, and is being evaluated in high-doses as a pharmaceutical.  The biologic mechanisms demonstrated in this study could provide key new approaches for the prevention or treatment of a number of chronic diseases in humans, especially those related to vascular and metabolic diseases and to the risk of mortality.

More than two decades ago, particularly through publicity related to the so-called “French Paradox,” the public became aware of the potential reduction in the risk of coronary heart disease from the moderate consumption of red wine, and the media focused on a single constituent in red wine, resveratrol, as being the “key” factor.  We now know that resveratrol is only one of hundreds of phenolic compounds in wine, many of which have been shown to have beneficial effects on vascular function, and that alcohol itself (present in wine, beer or spirits) also provides considerable protection against heart disease.  Still, there has remained considerable attention paid to resveratrol, and extensive scientific research on resveratrol and related  substances have shown that, in high doses, they may increase longevity of life and reduce metabolic diseases of aging.

In general, Forum reviewers thought that this was a very well-done study.  Their concerns related to the dose used in these experiments; while the levels of resveratrol and like compounds might be accessible with pharmaceutical doses, the suggestion that similar levels could be connected with wine consumption is misleading.  Further, in humans, resveratrol in the diet will interact with many other chemicals to achieve an effect, as whole plant extracts consist of many active and inactive micronutrients that may play a role in health and disease.  To ascribe a specific effect on health from one chemical found in wine or other plant products could be misleading.”

Still, the reviewers believed that this paper was an important contribution to our knowledge about the mechanisms by which resveratrol and other chemicals may play a role in cardiovascular and other diseases.  Such knowledge could help develop approaches for the prevention and treatment of human disease and for increasing the longevity of a healthy life.

Reference:  Park S-J, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH.  Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.  Cell 2012;148:421-433.  DOI 10.1016/j.cell.2012.01.017.

Click here for the full critique of this paper by the International Scientific Forum on Alcohol Research.

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Critique 069:  Little effect of binge drinking on heart disease or mortality among moderate drinkers in Denmark — 2 February 2012

In a well-done, population-based analysis from Denmark, it was found that subjects who were overall “light-to-moderate” drinkers but reported an episode of “binge drinking” (consumption >5 drinks on an occasion) did not show differences in risk of ischemic heart disease (coronary disease) or total mortality than did other moderate drinkers who did not report such an episode.  These results are somewhat different from results of many other epidemiologic studies that have shown increased risk of health problems (even higher risk of coronary disease) to be associated with what was referred to as “binge drinking.”

Why there were no adverse effects of such drinking in the present study has provoked considerable discussion among members of the Forum.  The general consensus of opinion has to do with inconsistencies in the definition of “binge drinking.”  The rapid consumption of more than 5 drinks on an empty stomach surely has different effects than the consumption of alcohol over several hours with food, such as during a prolonged dinner.  The rate of consumption strongly affects the consequences of alcohol; in fact, some have suggested that the consumption of more than 2 or 3 drinks in less than two hours may constitute a better definition of binge that the total number of drinks.

The Forum continues to suggest that “binge drinking,” however defined, is not a healthy pattern of alcohol consumption.  But the circumstances of consumption (rate of consumption, with or without food, etc.) may also be important in its definition and in judging its effects on health.

Reference:  Skov-Ettrup LS, Eliasen M, Ekholm O, Grønbaek M, Tolstrup JS.  Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study.  Scandinavian Journal of Public Health 2011;39:880–887.

Click here for the full critique of this study by the International Scientific Forum on Alcohol Research.

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Critique 068.  Heavier alcohol consumption may increase risk of colon cancer in people with a family history of such cancer  — 30 January 2012

An analysis based on a large number of subjects being followed in the Nurses’ Health Study and the Health Professionals Follow-up Study, relates alcohol consumption to the risk of colon cancer according to whether or not the subjects had a positive family history of colon cancer.  Their results indicate that subjects with a family history whose average alcohol intake was 30 or more grams per day (about 2 ½ typical drinks by US standards) have an increase in their risk of colon cancer; there was not a significant association between alcohol and colon cancer among subjects without a positive family history.

Forum reviewers were somewhat concerned that the pattern of drinking (regularly or binge drinking) was not assessed, and that there was not a clear dose-response curve between the level of alcohol consumption and the risk of cancer (i.e., there was not a consistent increase in risk of cancer with greater alcohol intake).  Further, folate intake was found to modify the association, with the highest risk for subjects with a positive family history of colon cancer, low levels of folate, and in the highest category of alcohol consumption.

The present study provides some support for an association between higher levels of alcohol intake and the risk of colon cancer among subjects with a positive family history of such cancer.  However, there have been changes in the guidelines for screening for cancer (by endoscopy, with removal of pre-malignant tumors) and other preventive measures for people with a positive family history of colon cancer.  Such measures could modify the effects of all risk factors for colon cancer in future analyses.

Reference:  Cho E, Lee JE, Rimm EB, Fuchs CS, Giovannucci EL.  Alcohol consumption and the risk of colon cancer by family history of colorectal cancer.  Am J Clin Nutr 2012;95:413–419.

Click here for the full critique of this paper by the International Scientific Forum on Alcohol Research.

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Critique 067:  Comparison of effects of red wine versus white wine on hormones related to breast cancer risk 19 January 2012

Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogens, and could play a role in the development of breast cancer.  This study of 36 pre-menopausal women consisted of a cross-over intervention trial to determine if there were differences between red wine and white wine in their effects on AIs.  Subjects sequentially consumed eight ounces of red wine, followed by white wine (or vice versa), each beverage for a one-month period.  The investigators concluded that red wine, but not white wine, was associated with significant effects on some indices of estrogen metabolism; free testosterone and luteinizing hormone were increased, but no significant differences were noted in estrogen levels.

Forum reviewers considered the results interesting and that they contribute to our understanding of the relation of wine to hormonal levels.  On the other hand, they were concerned about methodological problems, including a lack of baseline data and variations in the timing during the menstrual period of blood sampling (which could affect estrogen levels).  Also, no significant effect of the interventions was seen on blood levels of estradiol.

Further, the Forum thought that it should be pointed out that data are inconsistent on the relation of red wine consumption to the risk of breast cancer; many studies do not show beverage-specific effects on risk.  More research will be needed to determine if the polyphenols in red wine can play a role in lowering the risk of breast cancer.

Reference:  Shufelt C, Bairey Merz CN, Yang YC, Kirschner J, Polk D, Stanczyk F, Paul-Labrador M, Braunstein GD.  Red versus white wine as a nutritional aromatase inhibitor in premenopausal women.  J Women’s Health, 2011;DOI: 10.1089/jwh.2011.3001

Click here for the full critique of this paper by members of the International Scientific Forum on Alcohol Research.

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Critique 066: Is it the alcohol or the polyphenols in red wine (or both) that decrease cardiovascular disease in wine drinkers?                                                                                                                                                16 January 2012

Human randomized intervention trials of wine and alcohol are not common.  This randomized, cross-over study was based on 67 male volunteers in Spain who were considered to be at “high-risk” of cardiovascular disease.  The subjects agreed to not consume any alcohol for a baseline period, then for three one-month periods consumed 30 g/day of alcohol as red wine or as gin, or an equivalent amount of phenolics from dealcoholized red wine.  The effects of each intervention on a large number of adhesion molecules and chemokines that affect inflammation and relate to the development of vascular disease were evaluated.

The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease.  Specifically, the authors conclude that “the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease.”  Thus, this study provides important new mechanistic evidence that the reduced risk of cardiovascular disease among red wine drinkers observed in most epidemiologic studies may result from a combination of both the alcohol and the polyphenols in the wine.

Reference:  Chiva-Blanch G, Urpi-Sarda M, Llorach R, Rotches-Ribalta M, Guillèn M, Casas R, Arranz S, Valderas-Martinez P, Portoles O, Corella D, Tinahones F, Lamuela-Raventos RM, Andres-Lacueva C, Estruch R.  Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial.  Am J Clin Nutr 2012. doi: 10.3945/ajcn.111.022889.

Click here for the full critique of this paper by members of the International Scientific Forum on Alcohol Research.

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Critique 065: Are there differences in mortality between people consuming wine and those consuming other types of alcoholic beverages?                                                                                                                                    20 December 2011

Wine consumers, especially in comparison with spirits drinkers, have been shown to have higher levels of education and income, to consume a healthier diet, be more physically active, and have other characteristics that are associated with better health outcomes.  However, epidemiologic studies have been inconsistent in showing that, after adjustment for all associated lifestyle factors, consumers of wine have lower risk of cardiovascular disease and mortality than do consumers of other beverages.

A study based on the long-term follow up of a group of older Americans concluded that the associated lifestyle habits and environmental factors of wine consumers largely explained their better health outcomes.  Forum reviewers were concerned about some of the methodological approaches used, and believed that the data presented in the paper were inadequate to support such a conclusion.  This was a small study, had only a single estimate of alcohol intake (at baseline but not throughout 20 years of follow up), and the authors may have over-adjusted for large differences in lifestyle factors between what they termed as “low-wine” and “high-wine” consumers.  The study did confirm a lower mortality risk for alcohol consumers than for non-drinkers.

Experimental studies have clearly indicated that the polyphenols and other constituents that are present in wine and some beers have independent protective effects against most cardiovascular risk factors.  Whether or not such advantages are seen among moderate drinkers of wine (or beer) in epidemiologic studies is difficult to determine, as comparisons are not being made between wine, beer, and spirits but between humans who consume one or other such beverage.  In almost all populations, drinkers of a specific beverage differ in many ways other than just the type of beverage they consume.

Reference:  Holahan CJ, Schutte KK, Brennan PL, North RJ, Holahah CK, Moos BS, Moos RH.  Wine consumption and 20-year mortality among late-life moderate drinkers.  J Stud Alcohol Drug 2012; 73: 80–88.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 064:  Association of lifestyle and environmental factors with the risk of cancer  — 13 December 2111

It has been well established that certain lifestyle habits relate to the risk of certain cancers (e.g., smoking and lung cancer).  In a well-done analysis, the authors estimate the proportion of cancer in the population associated with a variety of lifestyle and environmental factors.  They find that smoking has, by far, the largest effect on the risk of cancer, with 19.4% of cancer cases in the UK attributable to tobacco use.  A poor diet (less intake of fruits and vegetables and fiber and greater intake of meat and salt), obesity, and alcohol are the next most important factors that relate to cancer, with alcohol being calculated to relate to 4.0% of cancer cases in the UK.

Forum reviewers considered this to be a well-done paper that used epidemiologic methods that are preferable to those used in some previous such analyses.  Generally, they disagreed with the authors that no alcohol consumption was the theoretical “optimum exposure level,” as the risk of certain cancers seems to increase primarily from heavy drinking.  Further, they found reason to believe that the purported effects related to diet may have been over-estimated.

Nevertheless, this paper provides considerable new information on lifestyle and environmental factors that may relate to the risk of cancer.  It puts into perspective the importance of targeting certain behaviors for the potential reduction in the risk of cancer.

Reference:  Parkin DM, Boyd L, Walker LC.  The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Summary and conclusions.  British Journal of Cancer 2011;105:S77 – S81.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 063: Genes modify the risk of liver disease among alcoholics  — 5 December 2011

It has been widely observed that only a small percentage of alcoholics develop cirrhosis of the liver, the most advanced form of alcoholic liver disease (ALD); the reason why all alcoholics do not develop such disease is not known.  The present study from Spain, that includes original work and a meta-analysis, evaluates whether genetic polymorphisms that determine levels of glutathione-S-transferases (GST) relate to the risk of developing ALD among alcoholics.  Alcoholics with certain genetic GST polymorphisms were found to be at significant excess risk for such liver disease in comparison with alcoholics without these polymorphisms.

As stated by the authors, the theory that these enzymes may affect risk is based on the ability of certain GST alleles to detoxify harmful ethanol metabolites in the liver by conjugating acetaldehyde and ROS to reduced glutathione.  The specific polymorphisms that they found to be associated with increased liver disease are among those that would be expected to lower the activity of the corresponding GST enzymes; this would permit higher levels of toxic metabolites of alcohol and oxidative stress to be present for longer periods of time after excessive alcohol consumption.

Some Forum reviewers thought that while the study was well done, the authors were unclear as to how these data could directly lead to “potential therapeutic targets” for liver disease in alcoholics.  Nevertheless, the original study and meta-analysis provide important data on how specific genetic factors relate to the development of liver disease among alcoholics and could theoretically lead to better strategies for the prevention and treatment of alcoholic liver disease. 

Reference:  Marcos M, Pastor I, Chamorro A-J, Ciria-Abad S, González-Sarmiento R, Laso F-J.  Meta-analysis: glutathione-S-transferase allelic variants are associated with alcoholic liver disease.  Aliment Pharmacol Ther 2011;34:1159–1172.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 062:  Similar effects of beer and wine on the risk of cardiovascular disease and of total mortality  — 22 November 2011

The authors carried out an updated meta-analysis on the relationship between wine, beer or spirit consumption and cardiovascular outcomes, using state-of-the-art statistical techniques.  Their meta-analysis provides evidence of J-shaped relationships between both wine and beer intake and vascular risk, with maximal protection of about 33% at a level of 25 g/day of alcohol (approximately 2 drinks/day by US standards).  A statistically significant association between spirits intake and vascular disease was not found.

The key result of this meta-analysis is the finding of a very similar inverse association between the consumption of beer and the consumption of wine in relation to cardiovascular outcomes.  While a similar associationwas not seen for spirits consumption, the data presented do not permit the conclusion that the key effects on cardiovascular disease are primarily due to the polyphenols in beer and wine.  Similarly, the results do not permit the conclusion that the effect on cardiovascular disease is due primarily to the alcohol in these beverages.  The lack of a similar J-shaped association for spirits may have been due to different drinking patterns (e.g., more binge drinking among consumers of spirits), as the pattern of drinking was not included as a confounder in the analyses.

Reference: Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G.  Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis.  Eur J Epidemiol 2011;DOI 10.1007/s10654-011-9631-0

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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A response from the Alcohol Policy Coalition of Australia to the Forum Critique #058: “A misguided statement on alcohol and health from a coalition in Australia,” which was published on the Forum web-site on 28 September 2011.

The Alcohol Policy Coalition of Australia has provided a response to Forum critique #058, “A misguided statement on alcohol and health from a coalition in Australia,” that was published on the Forum web-site on 28 September 2011.

The original Forum critique is available under Recent Reviews, #058 (click Critique o58).  A description of the Forum, its members, the goals of the Forum, a disclosure statement, etc., are available from the home page of the web-site.

The response from the Alcohol Policy Coalition is now published in full on our web-site, dated 18 November 2011. To read the response to our critique # 058 provided by the Alcohol Policy Coalition, please click here.

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Critique 061: The reduction in risk of coronary heart disease from alcohol consumption may involve mechanisms other than an increase in HDL-cholesterol. 10 November 2011

In a prospective, observational study of approximately 150,000 Norwegians, the investigators found that alcohol consumption was associated with a large decrease in the risk of death from coronary artery disease.  For men, the fully adjusted hazard ratio for cardiac death was 0.52 (95% CI 0.39 – 0.69) when comparing subjects reporting more than one drink/week in comparison with those reporting never or rarely drinking; for women, it was 0.62 (0.32–1.23).  There was little change in the hazard ratio when HDL-cholesterol (HDL) was added to the model, suggesting that very little of the lower risk of heart disease was due to an increase in HDL from alcohol consumption.

Forum members considered this a well-done analysis.  They were surprised at the very low amounts of alcohol intake reported by the subjects, with only 16% of males and about 8% of females reporting more than one drink/week.  It is possible that the low levels of drinking, or perhaps over-adjustment in the multivariable analysis, led to the lack of effect of HDL.  Most other studies have shown a much larger proportion of the effect of alcohol on heart disease risk to be associated with an increase in HDL.

Reference:  Magnus P,  Bakke E,  Hoff DA,  Høiseth G,  Graff-Iversen S,  Knudsen GP,  Myhre R,  Normann PT,  Næss Ø,  Tambs K,  Thelle DS, Mørland J.  Controlling for High-Density Lipoprotein Cholesterol Does Not Affect the Magnitude of the Relationship Between Alcohol and Coronary Heart Disease.  Circulation 2011;124: DOI: 10.1161/CIRCULATIONAHA.111.036491

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 060:   A new analysis from the Nurses’ Health Study on the association of alcohol with risk of breast cancer 3 November 2011

In a well-done analysis using prospectively collected data from the Nurses’ Health Study, the risk of breast cancer was found to be modestly increased among consumers of alcohol, even those whose total alcohol consumption was reported to be in the range of 3 to 6 drinks/week.  Similar small increases in the risk of breast cancer have been found from alcohol consumption in the majority of previous studies observational studies.  A strength of this study was the very large number of subjects, permitting the investigators to attempt to determine if both the amount of alcohol and the frequency of consumption were important in this association; strong effects were not found for either.  A weakness is the failure to report the effects of folate intake on the association between alcohol and cancer; the same investigators have previously shown that folate is a potential moderator of the effects of alcohol on breast cancer risk.

The authors describe well the dilemma that women face regarding alcohol intake, which may increase slightly the risk of breast cancer but markedly decrease the risk of other more common diseases, especially cardiovascular conditions.   For example, the authors state that regarding breast cancer, “We did find an increased risk at low levels of use, but the risk was quite small.”  Forum members agree with the statement of the authors that “An individual will need to weigh the modest risks of light to moderate alcohol use on breast cancer development against the beneficial effects on cardiovascular disease to make the best personal choice regarding alcohol consumption.”

Reference:  Chen WY, Rosner B, Hankinson SE, Colditz GA, Willett WC.  Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk.  JAMA 2011;306:1884-1890.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 059:   Association of quantity of alcohol and frequency of consumption with cancer mortality

20 October 2011

A paper from the National Institutes of Health in the United States attempts to evaluate the separate and combined effects of the frequency of alcohol consumption and the average quantity of alcohol per occasion as they relate to the risk of mortality from all cancers, as well as cancer-specific mortality.  It is based on repeated administrations of the National Health Interview Survey in the United States, with a total of more than 300,000 subjects and over 8,000 deaths from cancer, and reports on total cancer deaths and deaths from lung, colorectal, prostate, and breast cancers.

For total alcohol consumption (frequency x quantity), the data indicate a significant reduction in the risk of all-site cancers (RR=0.87, CI 0.80-0.94) which, interestingly, is not emphasized by the authors and is not included in their abstract.  Moderate drinking consistently shows no effect, and only heavier drinking is associated with an increase in all-site cancer risk.  For site-specific cancers, an increase in risk of lung cancer was seen only for heavier drinkers, with a tendency for less cancer among light drinkers.  There was no evidence of an effect of total alcohol consumption on colorectal, prostate, or breast cancer.

The authors excluded non-drinkers in a second analysis in which they used categories of usual daily quantity and of frequency of consumption in an attempt to investigate their separate effects.  For all-site cancer and for lung cancer, these results again show an increase in risk only for drinkers reporting greater amounts of alcohol.  The data also show an increase in cancer risk from more frequent drinking among women but not among men.  For colorectal, prostate, and breast cancer, there is no clear pattern of an increase in risk from quantity of alcohol consumed.  For frequency of drinking, again there is a suggestion of an increase in risk with more frequent drinking, although the trends are not statistically significant.

The overall message of this analysis is that light to moderate alcohol intake does not appear to increase the risk of all-site cancer (and light drinking was shown in this study to be associated with a significant decrease in risk).  Similarly, light to moderate consumption was not associated with site-specific cancers of the lung, colorectum, breast, or prostate.  Heavier drinking is known to be associated with a large number of adverse health effects, including certain cancers, as was shown in this study.

When considering cancer, alcohol consumption should not be considered in isolation, but in conjunction with, other lifestyle behaviors (especially smoking).  We agree with the authors that both quantity and frequency of consumption need to be considered when evaluating the relation of alcohol to cancer; further, beverage-specific effects need to be further evaluated.

Reference:  Rosalind A. Breslow RA, Chen CM, Graubard BI, Mukamal KJ.   Prospective study of alcohol consumption quantity and frequency and cancer-specific mortality in the US population.  Am J Epidemiol 2011; DOI: 10.1093/aje/kwr210.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 058:   A misguided statement on alcohol and health from a coalition in Australia. 28 September 2011

A group known as the Alcohol Policy Coalition in Australia has released a document entitled Cancer, Cardiovascular Disease and Alcohol Consumption.  Forum members agree that excessive alcohol use has many adverse effects on the individual and on society, and efforts to reduce such use are important.  On the other hand, they were disturbed that the coalition statement was limited almost exclusively to the effects of abusive drinking, was based primarily on extremely limited sources of information (mainly position statements by other organizations, and not publications based on sound research), and indicated a strong bias against alcohol.

Forum members contend that the Australian report misrepresents the extensive scientific data available on alcohol and health.  The report specifically ignores scientific data indicating that in all developed countries, moderate consumers of alcohol are at much lower risk of essentially all of the diseases of ageing: coronary heart disease, ischemic stroke, diabetes, and dementia.  And conspicuously absent from the Australian report is a description of the lower total mortality among middle-aged and elderly people associated with moderate alcohol consumption, a finding that has been found consistently throughout the world.  Further, there is no mention in the report of the key relevance of the pattern of drinking, although regular moderate drinking (versus binge drinking only on week-ends, even when the total volume of alcohol is the same) has been shown to be a strong determinant of beneficial effects of alcohol consumption.

Scientific data over many decades have shown that while excessive or irresponsible alcohol use has severe adverse health and societal effects, regular moderate drinking is associated with beneficial effects on health.  And a very large number of experimental studies, including results from human trials, have described biological mechanisms for the protective effects of both alcohol and the polyphenolic components of wine.

There have been a number of comprehensive meta-analyses published that Forum members believe can provide much more accurate, up to date, and scientifically balanced views of the current status of the health effects of alcohol consumption.  Such documents are better sources of data upon which policy decisions should be based.

Reference:  Alcohol Policy Coalition Position Statement.  “Cancer, Cardiovascular Disease and Alcohol Consumption.”  Released in Australia, September 2011.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click  here.

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Critique 057:      Differences in effects on atherosclerosis of regular moderate drinking and binge drinking.   An experimental study in mice.                                                                                                              20 September 2011

An excellent study among experimental animals has reported very dramatic differences between the effects of alcohol administered in moderation on a daily basis and the same total weekly amount of alcohol administered on only two days of the week: binge drinking.  The mice used in the study that were given regular moderate amounts of alcohol showed no weight gain, improved lipid values, and much less development of atherosclerosis than did control animals.  However, those given alcohol in a binge-drinking pattern showed worse outcomes than control animals, and much worse outcomes than those given regular moderate alcohol.

This experimental study provides strong support for the frequent finding among humans in epidemiologic studies: benefits from regular moderate drinking, adverse effects from binge drinking.  It is especially important since, being an experimental study, the potential confounding effects of other lifestyle habits are not an issue, as is always the case for observational studies among humans.

Reference:  Liu W, Redmond EM, Morrow D, Cullen JP.  Differential effects of daily-moderate versus weekend-binge alcohol consumption on atherosclerotic plaque development in mice.  Atherosclerosis 2010, doi:10.1016/j.atherosclerosis.2011.08.034

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 056:  Relation of alcohol consumption to colorectal cancer 13 September 2011

A meta-analysis of case-control and cohort studies on the association of alcohol consumption with colorectal cancer was carried out, based on 22 studies from Asia, 2 from Australia, 13 from Western Europe, and 24 from North America.  The paper provides evidence that alcohol, at least at higher levels of consumption, is associated with an increase in the risk of colorectal cancer.  Overall, there was no increase in the risk for consumers reporting an average intake of up to 1 drink per day, but a modest increase (of 21%) for what the authors defined as “moderate drinking” (averaging up to 49.9 g of alcohol, or about 4 typical drinks, per day).  The increase in risk was greater (52%) for consumers of 50 or more grams of alcohol per day.

Forum reviewers thought that this was, in general, a very well-done study that used appropriate statistical techniques for meta-analysis.  There were some key concerns, however, including the following: (1) the authors’ definition of “moderate drinking” extended well above the usual recommended limits for sensible drinking; effects of consumption in categories of 1 to 2 drinks/day, 2 to 3 drinks/day, etc., were not given; (2) no results were provided according to type of beverage even though many previous studies have shown differences between health effects for consumers of wine, or wine/beer, and other beverages; and (3) no data were available on the pattern of drinking.  Many studies have shown that regular, moderate drinking on most days of the week has very different health outcomes than drinking only on week-ends or binge drinking.

Despite these concerns, Forum members agreed that current data indicate that alcohol intake, especially heavier drinking, is associated with an increase in the risk of colorectal cancers.  Future studies are needed to help determine if there is a threshold level of alcohol that increases the risk, if there are differences by type of beverage, and if the pattern of drinking (regular versus binge drinking) affects the risk.

Reference:  FedirkoV, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, et al.  Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies.  Annals of Oncology 22: 1958–1972, 2011, doi:10.1093/annonc/mdq653

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 055. Alcohol intake and “successful ageing” 8 September 2111

Among 13,894 women in the Nurses’ Health Study, investigators prospectively examined alcohol use assessed at midlife in relation to “successful ageing,” which was defined as survival to age 70 years, not having a major chronic disease (such as coronary disease, cancer, stroke, diabetes), and having no major cognitive impairment, physical impairment, or mental health problems.  Only 11% of the women met these criteria.

The results indicate that moderate drinkers, especially those consuming wine and drinking regularly, were more likely to exhibit successful ageing.  For average amount consumed, the largest benefit (an increase of 28%) was among women who reported 15.1 – 30 g of alcohol per day (an average of just over 1 to 2 ½ drinks per day), when compared with non-drinkers.  The frequency of drinking was especially important: in comparison with nondrinkers, women who drank only on 1 to 2 days per week had little increase in their risk of successful ageing, but those drinking on at least 5 days per week had almost a 50% greater chance of successful ageing.

Forum reviewers had some questions about the definition of “successful ageing” used in this study.  It is believed that a much greater percentage of people who may not meet these criteria make huge contributions to society and should be considered “successful.”

In summary, these results support the findings of earlier studies showing that many aspects of successful ageing, in addition to just survival, are favorably affected by regular, moderate consumption of alcohol.

Reference:  Sun Q, Townsend MK, Okereke OI, Rimm EB, Hu FB, Stampfer MJ, Grodstein F.  Alcohol consumption at midlife and successful ageing in women: A prospective cohort analysis in the Nurses’ Health Study.  PLoS Med 8(9): e1001090. doi:10.1371/journal.pmed.1001090

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 054.  Role of alcohol intake and smoking on upper aerodigestive cancers       -         6 September 2011

This paper provies an extensive analysis of the proportion of the risk of upper aero-digestive tract (UADT) cancers in the population (the population attributable risk) may be due to alcohol consumption and/or smoking.  The analyses provide strong evidence that smoking is the most important factor in the risk of these cancers, and the risk is enhanced among those who also consume 2 or more drinks per day.  Alcohol alone (i.e., among non-smokers) has little effect on the risk.

The authors state that their observations “are consistent with the hypothesis that alcohol acts as a carcinogen primarily because of its promoting effect on tobacco smoke.”  In terms of the population-attributable risk, the authors conclude that “Our findings confirm that tobacco and alcohol together explain 73% of total UADT cancer burden in Europe.”  Overall, tobacco use alone explained 28.7%, the combination of smoking and drinking 43.9%, and alcohol use alone only 0.4% of the population attributable risk.  Among women, the risk of these cancers was higher among smokers than among those who both smoked and consumed alcohol; this perhaps suggests that the moderate intake of wine, the most common beverage among European women, may play a role in reducing the risk associated with smoking.

Forum reviewers thought that this was a very good paper, but hoped that in the future we would have more studies that evaluated the effects on risk of varying levels of alcohol consumption, differential effects of various beverages, and even differential effects according to subjects’ genetically determined differences in alcohol metabolizing enzymes.

Reference:  Anantharaman D, Marron M, Lagiou P, Samoli E, Ahrens W, Pohlabeln H, et al. Population attributable risk of tobacco and alcohol for upper aerodigestive tract cancer.  Oral Oncology 2011;47:725–731.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 053:  An extensive review of the effects of alcohol consumption on the risk of cognitive impairment and dementia                                                                                                                                               25 August 2011

The authors of this paper have carried out an excellent review of the relation of alcohol consumption to the risk of cognitive impairment and dementia.  They reviewed a total of 143 previous publications on the topic. There were 74 studies, based on a total of more than 250,000 subjects, that provided risk estimates for varying levels of alcohol consumption which allowed the investigators to include them in a comprehensive meta-analysis.  These papers were published mainly after 1998, were predominantly among older subjects (92% were ≥ 55 years of age and 70% ≥ 65 years of age), and almost all employed mental status examinations to define cognitive impairment/dementia.

As stated by the authors, “These studies overwhelmingly found that moderate drinking either reduced or had no effect on the risk of dementia or cognitive impairment.”  Overall, in the new meta-analysis based on these studies, the average ratio of risk for cognitive risk associated with moderate drinking of alcohol was 0.77, with nondrinkers as the reference group.  This estimate is close to the estimates of reduction in the risk of cognitive dysfunction (RR of 0.73 and 0.74) seen in other recent selective meta-analyses.  The present study found that both light and moderate drinking provided a similar benefit, but heavy drinking was associated with non-significantly higher cognitive risk for dementia and cognitive impairment.

Forum reviewers of this paper were particularly pleased that the authors attempted to answer a number of specific questions on this topic that have been raised from previous research.  Their results included finding no appreciable differences whether or not “sick quitters” were included in the reference group, little effect from adjustments for other lifestyle factors, and no significant differences between alcohol’s effects on dementia, Alzheimer’s dementia, or vascular dementia (but, based on a small number of studies, no significant reduction in risk of cognitive decline over time).  The investigators concluded that there were no differences between results in men and women.  Their analyses also led to the conclusion that wine is associated with more beneficial effects on cognition than beer or spirits, but the authors caution that these results are based on a limited number of reports, and that many studies show no significant differences according to type of beverage.

Forum reviewers agreed with the conclusions of the authors that “Overall, light to moderate drinking does not appear to impair cognition in younger subjects and actually seems to reduce the risk of dementia and cognitive decline in older subjects.”

Reference:  Neafsey EJ, Collins MA.  Moderate alcohol consumption and cognitive risk.  Neuropsychiatric Disease and Treatment 2011:7:465–484.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 052:  Does moderate alcohol consumption increase body weight? 16 August 2011

A paper from Spain provides an extensive review of the association between alcohol consumption and body weight.  It includes descriptions of cross-sectional and prospective studies (and a few small intervention studies) among subjects who varied in age (adolescence to old age), culture (from Americans and Europeans to Asians), and principal type of beverage consumed and pattern of drinking.  The authors state that many of the studies they reviewed appear to be contradictory in their results.  However, based on their review, they conclude that “as positive associations between alcohol and weight gain were mainly found in studies with data on higher levels of drinking, it is possible that an effect on weight gain or abdominal adiposity may only be experienced by heavy drinkers.”  A second conclusion of the authors is that “the type of alcoholic beverage might play an important role in modifying the effect of alcohol consumption on weight gain,” with more favorable effects generally seen among consumers of wine.  A formal meta-analysis is not provided.  Forum members were uncertain whether the higher risk seen for spirits drinkers in this study was due to the beverage they chose or to their consumption of larger amounts of alcohol.

The overall conclusions of the authors is that it is currently unclear whether alcohol consumption a risk factor for weight gain, but if so it appears to occur mainly among heavier drinkers.  They also state that “light-to-moderate alcohol intake, especially of wine, may be more likely to protect against, rather than promote, weight gain.”

Forum reviewers agreed with most of the conclusions of the authors, especially that current data do not clearly indicate if moderate drinking increases weight; further, the biologic mechanisms relating alcohol to changes in body weight are not well understood.  The Forum review comments on the strong protective effects of moderate drinking on the risk of metabolic syndrome and diabetes, both of which relate to increasing obesity.  And some studies suggest that even very obese people may be at lower risk of diabetes if they are moderate drinkers.  Forum members also reviewed some of the distinctive mechanisms by which alcohol is metabolized in the body (it provides calories that are rapidly absorbed and are not stored in fat) that could explain differences in the effects of calories from alcohol and from other foods.

Forum members agree with the authors of this paper that future research efforts should be directed towards assessing the specific roles of different types of alcoholic beverages, taking into account drinking patterns, and perhaps including in the analysis the propensity of individual subjects to gain weight in the past.  For now, there is little evidence that someone consuming small to moderate amounts of alcohol on a regular basis is increasing his or her risk of becoming obese.

Reference:  Sayon-Orea C, Martinez-Gonzalez MA, Bes-Rastrollo M.  Alcohol consumption and body weight: a systematic review.  Nutrition Reviews 2011;69:419-431.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 051:  Types of alcohol in relation to acute pancreatitis                                                11 August 2011

A very well-done analysis from scientists in Sweden has related the type of alcoholic beverage, and the amount consumed per occasion, to the risk of acute pancreatitis.  The study suggests that a greater number of drinks per occasion (“binge drinking”) of spirits increases the risk of acute pancreatitis, but no such relation was seen for the consumption of beer or wine.  Forum reviewers suggested that a faster rate of drinking, with a greater rise in BAC, for spirits drinkers may be an important factor in the observed higher risk of pancreatitis; the increased risk may not necessarily be due to lower levels of antioxidants or to the presence of other toxic substances in spirits.

In any case, the average total alcohol consumption did not affect the risk of pancreatitis; instead, it was the number of drinks consumed per occasion (of spirits, in this study) that was associated with an increase in risk.  Residual confounding by the pattern of drinking, diet, or by other lifestyle factors could still be operating, and it will require replication of these results in other studies to support the conclusions of the authors.

Reference:  Azodi OS, Orsini N, Andrén-Sandberg Å, Wolk A.  Effect of type of alcoholic beverage in causing acute pancreatitis.  Brit J Surgery 2011;DOI: 10.1002/bjs.7632.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 050:  Multiple maternal risk factors for fetal alcohol disorders                                                 7 August 2011

An extremely well researched and written review on the relation of maternal drinking during pregnancy to adverse fetal outcomes has been published by scientists from the University of New Mexico Center on Alcoholism, Substance Abuse, and Addictions.  It covers many factors (host, agent exposure, and environment) that have been found to relate to the occurrence of fetal alcohol spectrum disorders (FASD).  Such factors modify the risk associated with alcohol consumption during pregnancy, although the risk of abnormalities is clearly increased with frequent consumption of large amounts of alcohol, and is greater among women who are alcoholics.  While current data do not show that light or occasional alcohol consumption during pregnancy increases the risk of FASD, Forum members do not believe that pregnant women should be encouraged to drink.

Forum members agree with the authors that “More research is needed to more clearly define what type of individual behavioral, physical, and genetic factors are most likely to lead to having children with FASD.”  Evaluating these multidimensional factors should help identify women at particular risk for having a child with FASD and lead to interventions to prevent such fetal abnormalities.

Reference:  May PA, Gossage JP.  Maternal risk factors for fetal alcohol spectrum disorders.  Not as simple as it might seem.  Alcohol Research & Health 2011;34:15-26.

For the full critique of this article by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 049:  Effects of smoking and alcohol use on risk of upper aero-digestive cancers 1 August 2011

A case-control analysis from subjects living in areas of South America with high rates of upper aero-digestive tract cancers showed that both alcohol consumption and smoking tended to increase the risk of such cancers.  However, the predominant cause of these cancers was the combination of smoking and alcohol consumption, with much higher risk than either exposure alone.  The effects on risk were greater for smoking than for alcohol: for non-smokers, there was little effect of alcohol on risk.  For non-drinkers, the risk of cancer associated with smoking was still increased, but was lower than it was for current drinkers.

An especially important finding in this study was that, among ex-drinkers and former smokers, the increased risks associated with alcohol and tobacco use decreased steadily as the time since quitting increased.  As stated by the authors, most of these cancers “could be prevented by quitting the use of either of these two agents.”

Reference:  Szymańska K, Hung RJ, Wűnsch-Filho V, Eluf-Neto J, Curado MP, Koifman S, Matos E, Menezes A, Fernandez L, Daudt AW, Boffetta P, Brennan P.   Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case–control study.  Cancer Causes Control (2011) 22:1037–1046.  DOI 10.1007/s10552-011-9779-7

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For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 048:  A new report on drinking guidelines and the association of alcohol with risk of cancer. 18 July 2011

The Canadian Medical Association Journal has published a commentary by some French scientists relating drinking guidelines to the association between alcohol and cancer.  They conclude that the current guidelines for sensible drinking for the general population are not adequate for the prevention of cancer, and revisions and eventual exclusion of such guidelines are needed.

Forum reviewers agree that alcohol consumption, especially heavy intake, increases the risk of certain types of cancer.  However, they consider that the opinions of the authors in the paper (labeled as an “Analysis” rather than an editorial or comments) do not reflect current sound scientific data, that the report is highly selective in citing a small number of papers that support their opinions, and that the authors have ignored a huge amount of recent data from more scientifically sound research that have largely discredited such studies.  Further, the report provides no mention of the consistent finding from studies around the world that moderate drinkers tend to have lower all-cause mortality risk than do abstainers.

Scientific data over many decades have shown that excessive or irresponsible alcohol use has severe adverse health effects, including an increase in the risk of certain cancers.  On the other hand, moderate drinking is associated with lower risk of cardiovascular disease and many other diseases of ageing and with all-cause mortality.  A very large number of experimental studies, including results from human trials, have described biological mechanisms for the protective effects of alcoholic beverages against such diseases.  A number of comprehensive meta-analyses provide much more accurate, up to date, and scientifically balanced views than does the current paper; such documents may be better sources of data upon which guidelines to the public regarding alcohol consumption should be based.

Reference: Latino-Martel P, Arwidson P, Ancellin R, Druesne-Pecollo N, Hercberg S, Le Quellec-Nathan M, Le-Luong T, Maraninchi D. Alcohol consumption and cancer risk: revisiting guidelines for sensible drinking.  CMAJ 2011. DOI:10.1503. /cmaj.110363

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 047:  Overall health effects of alcohol consumption.  Comments on a WHO report                10 July 2011

The World Health Organization (WHO) has released its global status report on alcohol and health for 2011.  Forum members largely agreed with the discussion in the report of the serious health and societal problems associated with the misuse of alcohol, which contributes to accidents, many diseases, and premature deaths.  On the other hand, Forum members were disturbed that the report was limited almost exclusively to abusive drinking, was based primarily on out-dated information, and minimized the beneficial health effects associated with moderate drinking.  The report ignored a massive amount of scientific data indicating that in all developed countries, moderate consumers of alcohol are at much lower risk of essentially all of the diseases of ageing: coronary heart disease, ischemic stroke, diabetes, dementia, and osteoporosis.  And conspicuously absent from the WHO report is a description of the decrease in total mortality among middle-aged and elderly people associated with moderate alcohol consumption, a finding that has been found consistently throughout the world.

Epidemiologic studies over many decades have shown that while excessive or irresponsible alcohol use has severe adverse health and societal effects, moderate drinking is associated with lower risk of cardiovascular disease and other diseases of ageing.  And a very large number of experimental studies, including results from human trials, have described biological mechanisms for the protective effects of both alcohol and the polyphenolic components of wine.  A number of comprehensive meta-analyses are cited by Forum reviewers which they consider to provide much more accurate, up to date, and scientifically balanced views of the current “status” of the health effects of alcohol consumption.  Such documents are better sources of data upon which policy decisions should be based.

Reference:  Global status report on alcohol and health.  World Health Organization 2011.  ISBN 978 92 4 156415 1 (NLM classification: WM 274)

For the full critique of this publication by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 046: All-cause mortality rates are lower among moderate drinkers than among abstainers.  4 July 2011

The author of this paper set out to determine the extent to which potential “errors” in many early epidemiologic studies led to erroneous conclusions about an inverse association between moderate drinking and coronary heart disease (CHD).  His analysis is based on prospective data for more than 124,000 persons interviewed in the U.S. National Health Interview Surveys of 1997 through 2000 and avoids the pitfalls of some earlier studies.  He concludes that the so-called “errors” have not led to erroneous results, and that there is a strong protective effect of moderate drinking on CHD and all-cause mortality.

The results of this analysis support the vast majority of recent well-done prospective studies.  In the present paper, non-drinkers had much higher risk of death than did almost all categories of subjects consuming alcohol.  The author contends that these results lend credence to the argument that the relationship between alcohol and mortality is causal.

While some Forum reviewers felt that this analysis only replicates what has been shown in many other papers, it appears that erroneous information continues to be used by some policy groups.  Thus, most reviewers believe that this new analysis provides important information on potential health effects of moderate drinking.

Reference:  Fuller TD.  Moderate alcohol consumption and the risk of mortality.  Demography 2011.  DOI 10.1007/s13524-011-0035-2

For the full review of this publication by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 045:  Alcohol drinking in the elderly: Risks and benefits.  26 June 2011

The Royal College of Psychiatrists of London has published a report related primarily to problems of unrecognized alcohol misuse among the elderly.  The report provides guidelines for psychiatrists and family physicians on how to find and how to treat elderly people with misuse of alcohol and drugs.  The report also mentions lower “sensible limits” for older people in comparison with younger people.  The Forum reviewers point out, however, inherent difficulties in providing guidelines for a very non-homogenous group of individuals whose only criterion for inclusion is being above the age of 65 years.  Such a group includes individuals varying from marathon runners to very sick, frail people.  Forum reviewers thought that advice to lower limits of drinking for everyone in this age group is not based on reliable research, and would certainly not apply to all in this age group.

The Forum reviewers were also struck by the absence in the Royal College report of any discussion of the strong positive effects of moderate drinking on most of the diseases of ageing, especially cardiovascular diseases, diabetes, and dementia, which are leading causes of morbidity and mortality in this age group.  For healthy moderate and responsible drinkers, advice to reduce or stop all alcoholic beverage intake would not be in the best health interests of such individuals.

Reference:  Royal College of Psychiatrists, London.  Our invisible addicts.  First Report of the Older Persons’ Substance Misuse Working Group of the Royal College of Psychiatrists, College Report CR165.  June 2011

For the full review of this publication by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 044:  The association of alcohol drinking with migraine headache 12 June 2011

An excellent paper from a headache center in Italy summarizes the scientific data relating alcohol ingestion to migraine headaches.  The factors that trigger an attack of migraine, or of other headaches as well, are poorly understood.  While retrospective studies tend to include alcohol as a trigger for an attack, the authors describe that in a recent prospective study (in which information on the factors that could potentially trigger an attack were collected prior to the migraine attack), menstruation, stress, and fatigue were found most commonly to relate to a subsequent attack, but not alcohol consumption (in fact, beer consumption on the previous day reduced the risk of a migraine attack).  In the present paper, the authors reviewed the role and mechanism of action of alcohol or other components of alcoholic drinks in relation to alcohol-induced headache.  They conclude from their review that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine.

Forum members thought that this was a very balanced review of the subject, and that it provided straightforward and sensible advice.  Although some individuals surely have the onset of a migraine or other type of headache after the consumption of wine or alcohol, the findings are not consistent.  Forum members suggest that given that subjects reporting migraine headaches have been found to be at increased risk of cardiovascular disease, it would not be appropriate to advise all such sufferers to avoid alcohol.  As suggested by the authors of this paper, it may be reasonable for those subjects who had a desire to consume alcohol to drink small amounts of specific beverages to see if each beverage was tolerated or not.  After seeing the effects, and factoring in symptoms versus potential benefits from moderate drinking, a reasonable discussion can be carried out with respect to continued alcohol use by subjects with migraine.

Reference:  Panconesi A, Bartolozzi ML, Guidi L.  Alcohol and migraine: What should we tell patients?  Curr Pain Headache Rep 2011;15:177–184.  DOI 10.1007/s11916-011-0184-4.

For the full critique of this paper by members of  the International Scientific Forum on Alcohol Research, please click here.

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Critique 043:  Frequent moderate drinking of alcohol is associated with a lower risk of fatty liver disease.                                                                                                                                                                                23 May 2011

In a large study of men in Japan, the presence of fatty liver disease by ultrasonography showed an inverse association with the frequency of alcohol consumption; there was some suggestion of an increase in fatty liver disease with higher volume of alcohol consumed per day.  Moderate drinkers had lower levels of obesity than did non-drinkers, and both obesity and metabolic abnormalities were positively associated with fatty liver disease.

These findings support the results of a number of other recent studies showing that moderate drinking does not increase the risk of this common type of liver disease; instead, it is associated with a lower risk of its occurrence.  We agree with the implications of these studies as stated by the authors: “These results suggest that lifestyle modifications aimed at fighting central obesity and metabolic abnormalities should be the most important recommendations for the management of fatty liver.  In addition, it seems unlikely that the risk of fatty liver can be reduced by the discontinuation and/or reduction of alcohol consumption alone.”

Reference:  Hiramine Y, Imamura Y, Uto H, Koriyama C, Horiuchi M, Oketani M, Hosoyamada K, Kusano K, Ido A, Tsubouchi H.  Alcohol drinking patterns and the risk of fatty liver in Japanese men.  J Gastroenterol 2011 46:519–528.  DOI 10.1007/s00535-010-0336-z.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 042:  An increase in risk of certain types of gastric cancer from heavy drinking, but no increase from moderate alcohol consumption 17 May 2011

A very well-done meta-analysis supports other data generated on the risk of alcohol consumption and gastric cancer – that is – that the risk may be real for heavy alcohol consumption but not for moderate intake.  The type of gastric cancer relating to heavier alcohol intake in this study tended to be tumors involving the noncardia, but differences between the association with tumors of the gastric cardia were not significant.

There was no increased risk of gastric cancer from alcohol among Asians; this may be due to lower alcohol intake; there is a greater prevalence among Asians of the inactive ALDH2 genotype that is associated with flushing and other adverse effects of alcohol, and such subjects tend to drink less alcohol.  However, a number of studies have shown higher risk for upper aero-digestive cancers for subjects with this ALDH2 genotype, so the overall reason for the lower risk among Asians in this study remains unclear.  The main outcome of the study is that there is no increase in the risk of gastric cancer associated with the moderate intake of alcohol.

Reference:  Tramacere I, Negri E, Pelucchi C, Bagnardi V, Rota M, Scotti L, Islami F, Corrao G, La Vecchia C, Boffetta P.  A meta-analysis on alcohol drinking and gastric cancer risk.  Ann Oncology 2011;doi:10.1093/annonc/mdr135

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 041:  Estimated health effects of changes in advice for alcohol consumption between the 2005 and 2010 Dietary Guidelines for Americans 6 May 2011

This paper from the National Institute on Alcohol Abuse and Alcoholism in the US suggests that the changes in wording of the alcohol recommendations in the Dietary Guidelines for Americans between 2005 and 2010 indicate that some at-risk drinkers could be classified as moderate drinkers.  The authors carried out an analysis using data from a large, nationally representative sample of U.S. adults to estimate differences between subjects following the 2005 recommendations and a “gray zone” of subjects who exceed the 2005 recommendations but fall within the moderate guidelines according to the 2010 recommendations.  The differences between these two groups were minimal; other than the gray zone subjects having an increased risk of alcohol dependence (which is unlikely to relate to their slight differences in consumption), the only other differences between the two groups related to alcohol-related interpersonal relations and job loss.  And, as the authors state, “There were no associations with medical conditions or mental disorders.”

More importantly, the authors state that “Moreover, of the gray area drinkers who experienced incident alcohol dependence and interpersonal problems, 89% of the former and 94% of the latter had moved out of the gray area and into the highest-risk consumption group over the course of the follow-up interval.”  Problems were thus very rare in those who remained in the gray zone of drinking during follow up.

Obviously, drinking 3 or 4 drinks/day (other than doing so only occasionally) should not be considered a healthy way to consume alcohol.  But if, as the authors state, almost all of the estimated effects on health are due to subjects who increase their drinking above this “gray zone,” there is little support for their argument that the changes in guidelines make a difference.

Reference:  Dawson DA, Grant BF.  The “Gray Area” of consumption between moderate and risk drinking.  J Stud Alcohol Drugs 2011;72:453–458.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 040:  Lower risk of coronary heart disease from alcohol, even with heavy drinking 27 April 2011

Using data from The 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions study (the NESARC study, n = 43,093), the authors of this paper conclude that alcohol may have cardioprotective effects not only in moderate drinkers, but also in individuals with patterns of use traditionally considered as “hazardous.”  While such a finding has been shown in some population studies, there were questions by Forum reviewers as to the adequacy of the method for diagnosing coronary artery disease: self-report, with most subjects listing angina pectoris, a “soft” criterion for coronary disease.

In addition, the categories of drinking used in this study were very broad: rare or only occasional drinkers were combined with regular drinkers up to 7 or 14 drinks per week in the “moderate” category; the “hazardous” category included a broad range of drinkers, from a minimal increase over the recommended limits to very heavy drinkers.  The pattern of drinking (especially the number of days per week that alcohol was consumed) was not reported, making it difficult to separate regular from heavy week-end drinkers.  The effects of heavier drinking on other conditions (such as alcohol-related liver disease, mortality, etc.) were not included in this analysis.

It is physiologically possible that even hazardous use of alcohol, like moderate use, may well lead to cleaner arteries and therefore lower rates of coronary artery disease.  If this is the case, an explanation for the increases in cardiovascular mortality reported for heavy drinkers in many studies may relate not directly to coronary artery disease, but to conditions such as cardiomyopathy or cardiac arrhythmias.  However, the rates of accidents, suicide and other morbidity associated with hazardous alcohol use may well overcome any protective effects on coronary disease.

Reference:  Le Strat Y, Gorwood P.  Hazardous drinking is associated with a lower risk of coronary heart disease: Results from a national representative sample.  Am J Addict 2011;20:257–263.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 039:  The role that alcohol drinking may play in the risk of cancer 17 April 2011

A large group of distinguished scientists have published a very detailed and rather complex paper describing the association between alcohol consumption and cancer.  It is based on data from the EPIC study in Europe, with a mean follow up of 8.8 years for more than 300,000 subjects.  The authors describe an increase in risk of many cancers from alcohol intake, but do not give data permitting the detection of a threshold of intake for an adverse effect on cancer risk.  The investigators conclude that “In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits.”

Members of the Forum were concerned that the authors did not separate moderate consumption from heavy consumption for their main analyses, ignored the demonstrated benefits of moderate drinking on total mortality, and did not point out other environmental influences (such as smoking, diet, obesity, etc.) that often have much larger effects on the risk of many cancers than does alcohol consumption.  The authors make statements such as alcohol has negative effects on total mortality that are not supported by the data presented in their paper, and are contradicted by most large-scale population-based studies.  Overall, while this paper supports the well-known association between heavy drinking and an increased risk of upper aero-digestive and certain other cancers, it adds little information useful for the prevention of most types of cancer.

Reference:  Schűtze M, Boeing H, Pischon T, et al, Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study.  BMJ 2011; 342:d1584 doi: 10.1136/bmj.d1584 (Published 7 April 2011)

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click  here.

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Critique 038:  Effects of a large reduction in alcohol prices on mortality in Finland 7 April 2011

Time series intervention analysis modeling was applied to the monthly aggregations of deaths in Finland for the period 1996–2006 to assess the impact of a reduction in alcohol prices in 2004.  The authors report that alcohol-related deaths increased in men aged 40–49 years, and in men and women aged 50–69 years: the mean rate of alcohol-related mortality increased by 17%, 14%, and 40%, respectively, which implies 2.5, 2.9 and 1.6 additional monthly deaths per 100,000 person-years following the price reduction.  In contrast to alcohol-related mortality, CVD and all-cause mortality decreased among men and women in the highest age category.  The changes were consistent with 19 and 25 fewer monthly deaths per 100,000 person-years for CVD and 42 and 69 fewer monthly deaths for all-cause mortality.

Forum members agreed that both potentially harmful and beneficial effects resulting from changes in alcohol intake should be considered when estimating population effects.  They were unsure whether all of the reported effects in the elderly should be attributed to changes in alcohol intake, as decreases in CVD and all-cause mortality rates were occurring prior to the change in alcohol intake.

Reference:  Herttua K, Mäkelä P, Martikainen P.  An evaluation of the impact of a large reduction in alcohol prices on alcohol-related and all-cause mortality: time series analysis of a population-based natural experiment.  Int J Epidemiol 2011;40:441-454; doi:10.1093/ije/dyp336.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 037:  Genes found to relate to level of alcohol consumption among Asians                    27 March 2011

In a study of 1,721 Korean male drinkers aged 40–69 y in an urban population–based cohort, and another sample of 1,113 male drinkers from an independent rural cohort, information on average daily alcohol consumption was collected and DNA samples were collected for genotyping.  In a genome-wide association (GWA) study, 12 single-nucleotide polymorphisms (SNPs) on chromosome 12q24 had genome-wide significant associations with alcohol consumption.  These polymorphisms were closely related to genes that determine levels of ALDH, low levels of which relate to flushing after even small amounts of alcohol.  Such enzymes are much more common among Asians than among westerners.  Further, associations were tested only with the weekly amount of alcohol consumed, not the pattern of drinking; hence, these findings are not direct measures of alcoholism.

The editorial by Freedman et al states “epidemiologic literature suggests that those who begin drinking at an early age may be at greater risk for a maladaptive and more genetically pronounced form of alcohol consumption, and other environmental milieus affect the risk of alcoholism.”   It will be important to investigate the interplay of genes and environmental factors when seeking the determinants of alcohol abuse.  Despite the findings of this study, our understanding of factors associated with alcoholism remains very limited.

Reference:  Baik I, Cho NH, Kim SH, Han B-G, Shin C.  Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men.  Am J Clin Nutr 2011;93:809–816.

Accompanying Editorial:  Agrawal A, Freedman ND, Bierut LJ.  Genome-wide association studies of alcohol intake—a promising cocktail?  Am J Clin Nutr 2011;93:681–683.

For the full critique of this article by the International Scientific Forum on Alcohol Research, please click here.

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Critique 036:  Alcohol consumption after age 75 associated with lower risk of developing dementia

7 March 2011

A population-based study of elderly Germans, aged 75 and older, evaluated the association between alcohol consumption and incident overall dementia and Alzheimer dementia over 3 years.  There was good ascertainment of the development of dementia, even among subjects who died during follow up.

Of 3,202 subjects free of dementia at baseline, 217 subjects met criteria of dementia during follow up.  Subjects consuming alcohol had approximately 30% less overall dementia and 40% less Alzheimer dementia than did non-drinking subjects.  Unlike many previous studies showing greater effects of wine on reducing risk of dementia, no significant differences were seen according to the type of alcoholic beverage consumed.  Overall, these results are similar to several previous studies in the very elderly and suggest that moderate drinking is associated with less dementia, even among individuals aged 75 years and older.

Reference:  Weyerer S, Schaufele M, Wiese B, Maier W, Tebarth F, van den Bussche H, Pentzek M, Bickel H, Luppa M, Riedel-Heller SG, for the German AgeCoDe Study Group (German Study on Ageing, Cognition and Dementia in Primary Care Patients).   Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older.  Age and Ageing 2011; 0: 1–7; doi: 10.1093/ageing/afr007.

For the full critique of this article by the International Scientific Forum on Alcohol Research, please click here.

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Critique 035:  A review of the association of alcohol consumption with cardiovascular disease outcomes 5 March 2011

In an excellent summary, the authors of this paper have synthesized results from longitudinal cohort studies comparing alcohol drinkers with non-drinkers for the outcomes of overall mortality and mortality from cardiovascular disease (CVD), incident coronary heart disease (CHD), mortality from CHD, incident stroke, and mortality from stroke.  They conclude that light to moderate alcohol consumption is associated with a reduced risk of multiple cardiovascular outcomes.  Further, they suggest that current scientific data satisfy Hill criteria indicating causality, that alcohol intake is the cause of the lower risk of cardiovascular disease among moderate drinkers.

Forum members thought that this was a very well-done, comprehensive summary of a large number of studies on alcohol and cardiovascular disease.  Some believed that two topics were not adequately discussed: (1) greater benefits from wine than from other beverages, a result seen in many studies, and (2) the importance of the pattern of drinking on the health effects of alcohol.  However, Forum members welcomed the discussion in the paper as to causality and regarding future directions in research, with more emphasis into how physicians and individual patients might respond to encouragement to consume alcohol for its potentially beneficial effects on cardiovascular disease.  Most believe that there is no substitute for balanced judgment by a knowledgeable, objective health professional when discussing alcohol intake, and this requires is a synthesis of common sense and the best available scientific facts as they apply to the individual.

Reference:  Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA.  Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis.  BMJ 2011;342:d671; doi:10.1136/bmj.d671

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 034:  A review of interventional studies in humans showing effects of alcohol on risk factors for cardiovascular disease 5 March 2011

A summary paper on the effects of alcohol consumption on biologic mechanisms associated with coronary heart disease provides an excellent review of a large number of intervention studies in humans.  Appropriate analyses were done and the results are presented in a very clear fashion, although there was little discussion of the separate, independent effects of alcohol and polyphenols on risk factors.

The trials the authors reviewed have demonstrated that the moderate intake of alcoholic beverages leads to increases in HDL-cholesterol, apolipoprotein A1, and adiponectin and decreases in fibrinogen, all factors associated with a lower risk of heart disease.  The findings described in this paper strengthen the case for a causal link between alcohol intake and a reduced risk of coronary heart disease, suggesting that the lower risk of heart disease observed among moderate drinkers is caused by the alcoholic beverage itself, and not by other associated lifestyle factors.

Reference:  Brien SE, Ronksley PE,Turner BJ, Mukamal KJ, Ghali WA.  Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies.  BMJ 2011;342:d636; doi:10.1136/bmj.d636.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 033:  Moderate-to-heavy alcohol intake may increase risk of atrial fibrillation                  12 February 2011

A number of well-done studies have shown an increase in the risk of atrial fibrillation to be associated with heavy alcohol intake or with alcoholism.  Most previous studies suggest little if any increase in risk from light-to-moderate drinking.  The present study was a meta-analysis based on 14 studies from Europe or North America.  It showed an increase in risk with alcohol, but there were limited dose-response data to determine if there was a threshold above which the risk was increased.

Overall, the scientific evidence from many studies suggests that at least heavy drinking may increase the risk of atrial fibrillation, although whether light-to-moderate intake increases the risk seems unlikely.  Previous basic scientific data of mechanisms of atrial fibrillation have suggested that alcohol has little effect on this arrhythmia.

Reference:  Kodama S, Saito K, Tanaka S, Horikawa C, Saito A, Heianza Y, Anasako Y, Nishigaki Y, Yachi Y, Iida KT, Ohashi Y, Yamada N, Sone H.  Alcohol consumption and risk of atrial fibrillation.  A meta-analysis.  J Am Coll Cardiol 2011;57:427–436.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, click here.

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Critique 032:  Comments on alcohol in newly released Dietary Guidelines for Americans, 2010        9 February 2011

The United States has released new Dietary Guidelines for Amercans, 2010.  While the Key Recommendations regarding alcohol remain similar to those of earlier guidelines, there were some changes in the text that reflect increasing scientific data indicating potential health benefits of moderate drinking.  The key recommendation is as follows:

“If alcohol is consumed, it should be consumed in moderation—up to one drink per day for women and two drinks per day for men—and only by adults of legal drinking age.”

Within the main body of the guidelines, comments on alcohol include the following:

“The consumption of alcohol can have beneficial or harmful effects, depending on the amount consumed, age, and other characteristics of the person consuming the alcohol. Alcohol consumption may have beneficial effects when consumed in moderation. Strong evidence from observational studies has shown that moderate alcohol consumption is associated with a lower risk of cardiovascular disease. Moderate alcohol consumption also is associated with reduced risk of all-cause mortality among middle-aged and older adults and may help to keep cognitive function intact with age. However, it is not recommended that anyone begin drinking or drink more frequently on the basis of potential health benefits because moderate alcohol intake also is associated with increased risk of breast cancer, violence, drowning, and injuries from falls and motor vehicle crashes.”

Reference: www.cnpp.usda.gov/Publications/DietaryGuidelines/2010/PolicyDoc/Chapter3.pdf

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To see a copy of the section on alcohol from the new Dietary Guidelines, click here.

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Critique 031:  Wine polyphenols have a variety of beneficial effects on health 30 January 2011

Much of the protection against cardiovascular disease attributed to wine intake may relate not only to the alcohol in wine, but to its polyphenolic constituents.  This review article summarizes research into the chemistry, bioavailability, metabolism and excretion of polyphenols as well as mechanisms of their action.  As stated by the authors, “These protective effects could be due to one or many components of the complex mixture of bioavailable and bioactive compounds present in red wine including ethanol, resveratrol, flavonols, flavan-3-ols, anthocyanins, phenolic acids as well as their metabolites formed either in the tissues or in the colon by the microflora.”  The authors describe their cardioprotective effects, effects on vascular function and atherosclerosis, anti-platelet effects, effects on myocardial ischemia, and anti cancer and anti-diabetic effects.

The authors conclude that “Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of wine, fruits and vegetables.”  Their review provides an extensive scientific literature on polyphenols in wine; it suggests multiple mechanisms by which such substances may have beneficial effects on health.

Reference:  Rodrigo R, Miranda A, Vergara L.  Modulation of endogenous antioxidant system by wine polyphenols in human disease.  Clin Chim Acta 2011;412:410-424

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research please click here.

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Critique 030:  Young rats given red wine polyphenols show less deterioration in endothelial function with ageing.                                                                                                                                                                  30 January 2011

The gradual decrease in endothelial function over time is a key factor in the development of diseases associated with ageing, especially cardiovascular disease (CVD).  Many epidemiologic studies suggest greater protection against CVD from wine than from other beverages containing alcohol, with at least one factor being the polyphenols in red wine (RWPs).

The present study in rats found that the administration of red wine polyphenols protected against ageing-induced endothelial dysfunction.  As stated by the authors: “The present findings indicate that regular intake of RWPs in the drinking water starting at young age (16 week-old) prevented the aging-related endothelial dysfunction most likely by reducing the excessive oxidative stress in the arterial wall.”  They further suggest an important role of NADPH oxidase and possibly also the angiotensin system in the abnormal vascular response in aging.  Their study showed that, “RWPs intake had also a physiological beneficial effect since it improved the physical exercise capacity of old rats.”

Forum members thought that this was an excellent paper, as it begins to delve into mechanisms by which polyphenols improve health.  A mechanism is addressed and results are consistent with the working hypothesis of a specific interaction between polyphenols and peculiar enzymes. There is a satisfying agreement between basic mechanisms and pathophysiology.

Some scientists believe that interventions to improve endothelial function (such as the consumption of red wine or other sources of polyphenols) should begin earlier in life to slow down the endothelial dysfunction that occurs with ageing.  This study in rats tends to support such a belief.

Reference: Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB.  Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: Role of NADPH oxidase.  Biochem Biophys Res Commun 2011;404:743-749

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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Critique 029:  Differing opinions on the message to the public regarding alcohol consumption 16 January 2011

A Letter to the Editor entitled “What should we advise about alcohol consumption?” was recently published by Maurizio Ponz de Leon in Intern Emerg Med.¹ Dr. de Leon argues that the message of health benefits of moderate drinking “seems to me hazardous and extremely dangerous to diffuse in the general population.”  His reasons included (1) many people may be unable to distinguish between low–moderate and high consumption of wine, beer or spirits, and alcohol metabolism may differ remarkably from one subject to another; (2) alcohol remains a frequent cause of car crash, and governments (in almost all western countries) try to convince or force people to abstain from drinking before driving; and (3) to consider alcohol as a medication whose consumption may contribute to improved health is another source of concern.  Dr. de Leon asks: “Are we truly at the point of prescribing alcohol consumption in order to reduce the risk of stroke and coronary damage?”  He concluded that “more studies are needed before we can give sensible recommendations on alcohol consumption to the general population.”

The de Leon editorial has prompted considerable response from other scientists, including further Letters to the Editor of the journal by Di Castelnuovo, Costanzo, Donati, Iacoviello, and de Gaetano,² and by Estruch and Lamuela-Raventos.³ In addition, the original editorial has stimulated considerable debate among members of the International Scientific Forum on Alcohol Research.  Among key arguments presented by the Forum members, all experts in scientific research on alcohol, are that messages to the public should not be “paternalistic” (we will tell you what is best for you since you are not smart enough to understand the facts), and that guidelines must always be based on sound, balanced scientific data rather than on uninformed opinion.  Forum members emphasized that there are certain people who should not drink at all (including former abusers of drugs or alcohol, people with certain medical conditions, children and adolescents, and people with religious or moral proscriptions against alcohol), and there can never be a general recommendation for everybody to consume alcohol.  On the other hand, physicians should not withhold from their patients and the public scientifically sound and balanced data on alcohol and health.  And the data are extremely strong supporting a role for moderate alcohol intake, for appropriate adults, for the reduction in risk of coronary artery disease and other diseases of ageing.

Several Forum members pointed out that it was unfortunate that the journal had chosen to publish the original letter that castigates alcohol from an author with good scientific credentials, but little to no apparent research expertise in the subject of alcohol and health.  Many Forum members disagreed with the statement of de Leon that “Many people may be unable to distinguish between low–moderate and high consumption of wine, beer or spirits.”  A leading scientist dealing with this subject for decades, Dr. Arthur Klatsky, has written: “Most people know very well what the difference is between light to moderate drinking and binge or excessive drinking.  While some patients may rationalize their heavy drinking because of its purported health effects, I have yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking.”  Medical practitioners, in his view, “have a ‘solemn duty’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.”  While pointing out that certain individuals will not benefit from the consumption of alcohol, several Forum members believed that it would be unethical for physicians to withhold from middle-aged or elderly subjects at risk of cardiovascular disease information on the potential benefits of light-to-moderate drinking

References:

1.  Maurizio Ponz de Leon.  What should we advise about alcohol consumption?  Intern Emerg Med, DOI 10.1007/s11739-010-0487-1.

2.  Augusto Di Castelnuovo, Simona Costanzo, Maria Benedetta Donati, Licia Iacoviello, Giovanni de Gaetano. What should we advise about alcohol consumption?  Reply letter by A. Di Castelnuovo.  Intern Emerg Med, DOI 10.1007/s11739-010-0502-6.

3.  Ramon Estruch • Rosa Ma Lamuela-Raventos.  What should we advise about alcohol consumption: reply letter by R. Estruch.  Intern Emerg Med; DOI 10.1007/s11739-010-0503-5.

For the full critique of these publications by members of the International Scientific Forum on Alcohol Research, click here.

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Critique 028:  Changes over time in relation of social class to mortality from cirrhosis 9 January 2011

To explore the nature of the social class gradient of cirrhosis mortality in England and Wales across the 20^th century, data on male cirrhosis mortality by social class were obtained from the Registrar General’s Decennial Supplements for the years 1921–1991.  This paper describes a dramatic change during the 20th century in the association between social class and mortality from liver cirrhosis.  While deaths from cirrhosis were more common among higher social classes in the early part of the century, the pattern changed so that deaths from cirrhosis were much more common among the lower social classes by the end of the century.

Suggested reasons for the lower current rates among subjects at higher social class include different patterns of alcohol consumption, with regular moderate consumption (especially of wine with meals) becoming more common with higher social class subjects while binge drinking (especially of beer and spirits) remaining more common in lower social classes.  However, a number of other factors may relate to the class differences in rates of hepatic cirrhosis, including a less healthy diet and greater rates of obesity (associated with hepatic fatty liver and cirrhosis) among lower social class subjects and social class differences in hepatitis rates.  Further, certain medications, coffee consumption, and many other lifestyle factors are associated with hepatic cirrhosis.  The actual reasons for the changes over time reported in this paper remain unclear.

Reference:  Crombie IK, Precious E.  Changes in the social class gradient of cirrhosis mortality in England and Wales across the 20th century.  Alcohol and Alcoholism 2011;46:80–82.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, click here.

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Critique 027:  Effects of resveratrol and quercetin on inflammation and insulin resistance                  – 20 December 2010

A study was carried out to examine the extent to which quercetin and trans-resveratrol (RSV) prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-a (TNF-a)—an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals.  Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-a.  Subsequently, gene and protein markers of inflammation and insulin resistance were measured.  The authors report that quercetin, and to a lesser extent trans-RSV, attenuated the TNF-a–induced expression of inflammatory genes such as interleukin (IL)-6, IL-1b, IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1.

Forum members were concerned about certain aspects of the study, especially the extrapolation of in vitro results to in vivo situations.  The in vitro conditions the authors describe are minimally representative of an in vivo condition.  In vivo, after consumption of quercetin or resveratrol, these compounds undergo extensive metabolism, leading to glucuronidated, sulphated or methylated compounds.  In a previous study, quercetin 3-glucoside was transformed to 3,4-dihydroxyphenylacetic acid, acetate and butyrate in cells from human gut; only 3′-methylquercetin has been detected in human plasma, present at a concentration of 0.1 to 0.2 µM after 3 h.  The authors of the current paper are using concentrations up to 60 µM, concentrations which have not been found in vivo.

There were also concerns with the work on cell uptake of quercetin and resveratrol.  Primary adipocytes were incubated with the polyphenols, but it is not clear whether or not the concentrations used were subtoxic.  Our current knowledge is limited about local concentration of the molecules we are studying in subcellular compartments, their interaction with alternative targets, and eventually their transformation into products that could be more or less active on a given specific pathway.  The real difficult and important issue is the identification of a reasonable convergence — if not agreement — between data originating from extremely distant approaches.  In this case, the notion that metabolic diseases are related to a homeostatic imbalance in adipose tissue, linked to a different redox status, linked to activation of specific pathways, and that different redox sensitive polyphenols do have a protective effect, encompasses the evidence produced by extremely distant approaches.

From a clinical point of view, the role of phytochemicals acting as antioxidants and anti-inflammatory agents could be extremely important in inflammation-associated chronic conditions such as cardiovascular disease, diabetes, and cancer.  Quercetin and resveratrol may indeed play an important role in this regard, and need to be investigated further to establish the clinical importance of natural dietary compounds in the prevention of chronic degenerative conditions.

Reference:  Chuang C-C, Martinez K, Xie G, Kennedy A, Bumrungpert A, Overman A, Jia W, McIntosh MK.  Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-a–mediated inflammation and insulin resistance in primary human adipocytes.  Am J Clin Nutr 2010;92:1511–1521.

For the full critique of this paper by the International Scientific Forum on Alcohol Research please click here.

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Critique 026: Chinese study suggests that alcohol increases angiographically significant coronary artery disease 8 December 2010

Among a large number of Chinese men presenting with chest pain or EKG changes, sequential subjects undergoing cardiac angiography were evaluated for obstructive coronary artery disease (CAD) lesions according to their reported recent alcohol intake.  The study population consisted of 1,476 consecutive men 36 to 84 years of age; participants were categorized as nondrinkers, light drinkers, moderate drinkers, or heavy drinkers.

Adjusted odds ratios for angiographically proved CAD for light, moderate, and heavy drinking were 1.16 (95% confidence interval 0.68 to 1.94), 1.78 (1.35 to 2.27), and 2.18 (1.46 to 3.25).  Compared to non-drinking, adjusted odds ratios were 1.03 (0.54 to 1.87) for drinking 0 to 15 years, 1.61 (1.28 to 2.14) for 16 to 30 years, and 1.98 (1.23 to 3.05) for >30 years.  The authors concluded that moderate-to-heavy alcohol consumption increased the risk of CAD in Chinese men.  CAD risk tended to increase with an increase in frequency and duration of drinking.

This was a very select group of patients (those presenting with chest pain or EKG changes), and not typical of the Chinese population.  No information was available on drinking patterns or on previous alcohol intake.  Further, a recent large population-based study from mainland China showed that consumers of alcohol were less likely to develop coronary disease, results similar to those in most Western populations.  It is not possible from the present study to say that the association of alcohol intake with CAD is different between Chinese and Western populations, as the present study gives results only for a very select group of patients.

The most important outcome regarding CAD is the occurrence of clinical events (myocardial infarction, cardiac death, etc.).  The detection of such events requires long-term follow-up studies to be able to judge the overall effects of alcohol drinking on CAD.

Reference:  Zhou X, Li C, Xu W, Hong X, Chen J.  Relation of alcohol consumption to angiographically proved coronary artery disease in Chinese men.  Am J Cardiol 2010;106:1101–1103.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 025:  Pattern of drinking and type of beverage affect the relation of alcohol intake to coronary heart disease 1 December 2010

Using cohort data from Belfast and France, investigators related weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed to risk of coronary heart disease (CHD) events over a 10 year follow-up period.  Overall, 60.5% of subjects from N. Ireland and 90.6% of French reported drinking alcohol at least once a week.  Among drinkers, 12% of men in Belfast drank alcohol every day compared with 75% of men in France.  Mean alcohol consumption was 22.1 g/ day in Belfast and 32.8 g/day in France.  Binge drinkers comprised 9.4% and 0.5% of the Belfast and France samples, respectively.

Results showed that, after multivariate adjustment, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 – 3.22) for binge drinkers, 2.03 (95% CI 1.41 – 2.94) for never drinkers, and 1.57 (95% CI 1.11 – 2.21) for former drinkers.  The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking.  Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country.

The authors conclude that regular and moderate alcohol intake throughout the week, the typical pattern in middle-aged men in France, is associated with a low risk of ischemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.

While a strong inverse association between moderate alcohol consumption and cardiovascular disease has been demonstrated for decades, more recent research has emphasized the importance of the pattern of drinking (regular moderate versus episodic or binge drinking).  Further, there continues to be debate about the potential greater effect of wine versus other beverages containing alcohol.  This study shows that regular moderate drinking (especially of wine) is associated with lower risk of MI, but episodic or binge drinking (especially of beer or whiskey) increases the risk.  Lifetime abstinence has a similar adverse relation to CHD as does episodic or binge drinking.

Reference: Ruidavets J-B, Ducimetièere P, Evans A, Montaye M, Haas B, Bingham A, Yarnell J, Amouyel P, Arveiler D, Kee F, Bongard V, Ferrières J.  Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).  BMJ 2010;341:c6077 doi:10.1136/bmj.c6077.

For the detailed critique of this study by the International Scientific Forum on Alcohol Research, please click here.

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Critique 024:  Moderate alcohol consumption lowers risk of metabolic diseases in a population with high mean alcohol intake. 28 November 2010

A cross-sectional analysis of data from subjects in Switzerland related varying levels of alcohol intake to the presence of diabetes mellitus, the “metabolic syndrome,” and an index of insulin resistance (HOMA-IR).  The strengths of this paper include being population-based and having a large number of subjects who reported that they consumed 14 or more drinks/week.  Also, there was a good percentage (27%) of subjects reporting no alcohol intake during the one week of assessment used for classifying subjects.  Another strength is the careful confirmation of drinking status with state-of-the-art laboratory tests.  In multivariate analysis, the prevalence of the metabolic syndrome, diabetes and mean HOMA-IR decreased with low-risk drinking and increased with high-risk drinking.  No differences were noted according to the type of beverage consumed.

This is a cross-sectional analysis, so a causative relation between alcohol intake and the metabolic outcomes cannot be assessed.  Still, the data support much that has been shown in prospective studies.  Several Forum members commented on potential problems when considering a number of physiologic conditions as the “metabolic syndrome” and focusing therapy on the syndrome; they believed that each metabolic factor should be evaluated and treated singly.

Reference:  Clerc O, Nanchen D, Cornuz J, Marques-Vidal P, Gmel G, Daeppen J-B, Paccaud F, Mooser V, Waeber G, Vollenweider P, Rodondi N.  Alcohol drinking, the metabolic syndrome and diabetes in a population with high mean alcohol consumption.  Diabet Med 2010;27:1241–1249.

For the detailed critique of this study by the International Scientific Forum on Alcohol Research, please click here.

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Critique 023:  Evidence that PPAR-gamma is a mechanism for the effects of wine polyphenolics on cardiovascular risk.                                                                                                                                                                  27 November 2010

It is important that biological mechanisms are identified for the observed inverse relation between the moderate consumption of wine and cardiovascular disease shown in most epidemiologic studies.  A paper by Zoechling et al is an elegant example of the needed effort to provide a biochemical mechanism for the biological effects of wine.  Data on binding of different wine component were produced and this result is interpreted in light of epidemiological evidence.

It would have been appropriate to provide evidence also for the actual shift of gene expression primed by the same wine component in a cell or animal model.  In this respect, results must be rated appropriate but still as preliminary; a ligand could have different effects.  Further, biological evidence is not provided to support the contention that these polyphenols act through the PPAR-gamma receptor.  The sort of evidence that should have been provided is a comparison with rosiglitazone in a cell population known to respond to PPAR-gamma agonists (e.g. adipocytes).

Further, the analytical data does not describe the amounts of any of the “active” substances.  So while there is a lot of discussion of the active components, it is not possible to compare any wine’s “activity” with the amount of the key substances.  Lacking such a comparison, it is very hard to conclude that these substances are in fact the responsible factors in the observed activity.

Nevertheless, this paper provides important data on potential mechanisms by which the constituents of wine and certain other beverages may act to reduce the risk of cardiovascular disease.

Reference:  Zoechling A, Liebner F, Jungbauer A.  Red wine: A source of potent ligands for peroxisome proliferator-activated receptor γ.  Food & Function, Journal of the Royal Society of Chemistry, in press.  DOI: 10.1039/c0fo00086h.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, click here.

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Critique 022: Alcohol consumption decreases with the development of disease – 21 November 2010

In a cross-sectional study from the 2004 and 2007 Australian National Drug Strategy Household (NDSH) surveys, respondents were questioned about their current and past drinking, the presence of formal diagnosis for specific diseases (heart disease, type 2 diabetes, hypertension, cancer, anxiety, depression) and self-perceived general health status.  The sample sizes for the 2004 and 2007 NDSH surveys were 24,109 and 23,356, respectively.

The authors report that respondents with a diagnosis of diabetes, hypertension, or anxiety were more likely to have reduced or stopped alcohol consumption in the past 12 months.  The likelihood of having reduced or ceased alcohol consumption in the past 12 months increased as perceived general health status declined from excellent to poor (although the authors do not point out that lifetime abstainers were more likely than moderate drinkers to report less than excellent health status).

The authors conclude that the experience of ill health is associated with subsequent reduction or cessation of alcohol consumption (“sick quitters), which is consistent with most prospective epidemiologic studies.  The authors also conclude that this may at least partly underlie the observed ‘J-shaped’ function relating alcohol consumption to premature mortality.  On the other hand, most modern epidemiologic studies are careful not to include “sick quitters” within the non-drinking category, and relate health effects of drinkers with those of lifetime abstainers.  Further, prospective studies in which alcohol intake is assessed at different times (rather than having “changes” based only on recall at one point in time, as was done in this study) usually indicate that subjects who decrease their intake are more likely to subsequently develop adverse health outcomes, especially related to cardiovascular disease, than those who continue moderate drinking.

Reference:  Liang W, Chikritzhs T.  Reduction in alcohol consumption and health status.  Addiction 2010; in press (doi:10.1111/j.1360-0443.2010.03164.x).

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 021:   Alcohol consumption affects risk of cataracts 25 October 2010

A population-based prospective study from Australia utilized repeated lens photographs over a period of 5 to 10 years to diagnose cataracts among more than 2,500 subjects.  The investigators related the risk of their development, and the risk of cataract surgery, to the reported alcohol intake of subjects.  Previous research has provided some biological mechanisms that make an association between alcohol and cataracts plausible.

Overall, the present study showed few statistically significant relations between alcohol and cataracts, although adjusted results suggested a “U-shaped” association between total alcohol intake and development of cataracts (a lower risk for moderate drinkers, higher risk for both abstainers and heavier drinkers).  The U-shaped association with alcohol consumption was stronger for the risk of cataract surgery.  These results are consistent with previous cohort studies.  On inspection of the data presented, the potential reduction in risk of cataract was primarily for wine and beer.  While some types of cataract may be reduced by moderate drinking, larger intake of alcohol may be associated with increased risk.

Reference:  Kanthan GL, Mitchell P, Burlutsky G, Wang JJ.  Alcohol Consumption and the Long-Term Incidence of Cataract and Cataract Surgery: The Blue Mountains Study.  Am J Ophthalmol 2010;150:434–440.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, click here.

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Critique 20:  New data on effects of alcohol during pregnancy                                                                                                 12 October 2010

A very large population-based observational study from the UK found that at the age of 5 years, the children of women who reported light (no more than 1-2 units of alcohol per week or per occasion) drinking did not show any evidence of impairment on testing for behavioral and emotional problems or cognitive ability.  There was a tendency for the male children of women reporting “heavy/binge” drinking during pregnancy (7 or more units per week or 6 or more units per occasion) to have poorer behavioral scores, but the effects were less clear among female offspring.

Scientific data continue to indicate that higher intake of alcohol during pregnancy may adversely affect the fetus, and could lead to very severe developmental or other problems in the child.  However, most recent publications (as does this one) show little or no effects of occasional or light drinking by the mother during pregnancy.  They also demonstrate how socio-economic, education, and other lifestyle factors of the mother may have large effects on the health of the fetus and child; these must be considered when evaluating the potential effects of alcohol during pregnancy.

Overall, current scientific data indicate that while drinking during pregnancy should not be encouraged, there is little evidence to suggest that an occasional drink or light drinking by the mother is associated with harm.  Heavy drinking, however, may be associated with serious developmental defects in the fetus.

Reference: Kelly YJ, Sacker A, Gray R, Kelly J, Wolke D, Head J, Quigley MA.  Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age?  J Epidemiol Community Health 2010; doi:10.1136/jech.2009.103002

Addendum:  After the above critique was prepared, a new paper has been published on the topic by O’Leary et al (O’Leary CM, Nassar N, Kurinczuk JJ, de Klerk N, Geelhoed E, Elliott EJ, Bower C.  Prenatal Alcohol Exposure and Risk of Birth Defects  Pediatrics 2010;126;e843-e850; DOI: 10.1542/peds.2010-0256).  Overall, the results of that study are similar to those of the study by Kelly et al, with no increase in risk of birth defects in children born of women reporting low or moderate drinking during pregnancy but with an increased risk of defects among children of women reporting heavy drinking.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 019:  Both alcohol and caffeinated coffee intake are associated with lower risk of diabetes in African-American women.                                                                                                                  27 September 2010

In a very large cohort of African-American women in the US, the association between the consumption of alcohol, tea, and coffee was related to the development of type 2 diabetes mellitus over a follow-up period averaging 12 years.  Tea and decaffeinated coffee showed no relation with diabetes, but the intake of both caffeinated coffee and alcohol showed a significant inverse association.

This paper is particularly important because some previous studies have not shown a strong association between alcohol and the risk of cardiovascular disease among African-Americans.  African-Americans, especially women, tend to drink little alcohol, yet are at markedly increased risk of diabetes.  In the present study, the approximately 30% lower risk for moderate alcohol drinkers was about the same in these African-American women as has been found in many previous studies of whites.

Reference

Boggs DA, Rosenberg L, Ruiz-Narvaez EA, Palmer JR.  Coffee, tea, and alcohol intake in relation to risk of type 2 diabetes in African American women.  Am J Clin Nutr 2010;92:960–966.

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 018: Alcohol consumption following diagnosis of early-stage breast cancer may increase risk of recurrence of cancer but not total mortality risk 14 September 2010

In the Life After Cancer Epidemiology (LACE) study, 1,897 participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years post-breast cancer diagnosis were evaluated for the association between alcohol intake and breast cancer recurrence and death.  The women, who were generally light drinkers, were followed for an average of 7.4 years.  The study reported an increase in risk of breast cancer recurrence and breast cancer death, but no effect on total mortality, to be associated with consumption of 3 to 4 or more drinks per week when compared with women not drinking following their cancer diagnosis.

Previous research has been mixed on this topic.  Almost all large studies have shown no increase in all-cause mortality for women who drink moderately following a diagnosis of breast cancer (as does this study).  As for recurrence of breast cancer, most have shown no increase in risk, although one previous study of women with estrogen-receptor + tumors found an increased risk of a primary cancer developing in the contralateral breast to be associated with alcohol intake of more than 7 drinks per week.

Because of conflicting results among studies on this topic, further research will be needed to determine the extent to which alcohol following a diagnosis of breast cancer may relate to subsequent disease and death.

Reference:  Kwan ML, Kushi LH, Weltzien E, Tam EK, Castillo A, Sweeney C, Caan BJ.  Alcohol Consumption and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer:The Life After Cancer Epidemiology Study.  J Clin Oncol 2010;28 (published ahead of print, 10.1200/JCO.2010.29.2730)

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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Critique 017:  Moderate alcohol intake is associated with a lower risk of total mortality than are either abstinence or heavy drinking                                                                                                                            5 September 2010

In a study based on data from 1,824 predominantly Caucasian Americans from the Western part of the United States, alcohol consumption at baseline was related to mortality risk during a 20-year follow-up period.  Subjects were recruited into a longitudinal project that has examined late-life patterns of alcohol consumption and drinking problems.  Lifetime abstainers were not included in the study, which focused on stress and coping processes among problem drinkers and non-problem drinkers.  The sample at baseline included only subjects aged 55 to 65 years who had had outpatient contact with a health care facility in the previous 3 years.

The database at baseline included information on daily alcohol consumption, sociodemographic factors, former problem drinking status, health factors, and social-behavioral factors.  Subjects who were not lifetime abstainers but did not report drinking at the time of the baseline examination were classified as “abstainers.”  Data on potential changes in alcohol consumption during the course of the study were not collected.  Death during follow up was confirmed primarily by death certificate.

The key results of the paper are that even when adjusting for sociodemographic factors, former problem drinking status, health factors, and social-behavioral factors, moderate drinking was associated with considerably lower risk of all-cause mortality.  In comparison with “moderate drinkers” (subjects reporting up to 3 drinks/day), abstainers had 51 % higher mortality risk and heavy drinkers had 45% higher risk.  The study supports most previous scientific studies showing that moderate drinking, in comparison with both abstinence and heavy drinking, is associated with lower risk of total mortality.

Reference:  Holahan CJ, Schutte KK, Brennan PL, Holahan CK, Moos BS, Moos RH.  Late-Life Alcohol Consumption and 20-Year Mortality.  Alcoholism: Clinical and Experimental Research 2010;34:in press, November 2010

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, click here.

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Critique 016:  Association of alcohol with breast cancer risk varies according to subtype of tumor

29 August 2010

Most studies show a slight increase in the risk of breast cancer for women who consume alcohol.  The association is thought to relate to alcohol’s effects on hormones, and alcohol use tends to be more strongly associated with hormonally sensitive breast cancers than tumors not sensitive to hormones.  Few studies have evaluated how alcohol-related risk varies by breast cancer subtype.  In the present study, follow-up data from 87,724 women in the Women’s Health Initiative Observational Study prospective cohort were evaluated for the relation of baseline alcohol consumption with subsequent breast cancer.

A total of 2,944 invasive breast cancer patients were diagnosed during follow up.  In multivariable-adjusted analyses alcohol consumption was associated with an increase in the risk of lobular carcinoma (which makes up approximately 15-20% of breast cancers), but there was not a statistically significant association with the more-common ductal type of carcinoma.  Hormone + cancers showed an association with alcohol intake, but not hormone – cancers.  The findings support the importance of hormonal mechanisms in mediating the relation between alcohol use and breast cancer risk.

Reference Li CI, Chlebowski RT, Freiberg M, Johnson KC, Kuller L, Lane D, Lessin L, O’Sullivan MJ, Wactawski-Wende J, Yasmeen S, Prentice R.  Alcohol consumption and risk of postmenopausal breast cancer by subtype: the Women’s Health Initiative Observational Study.  J Natl Cancer Inst 2010 Aug 23. [Epub ahead of print]

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, click here : Critique 016.

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Critique 015: Moderate drinking does not appear to increase risk of breast cancer among women with a BRCA gene mutation                                                                                                                 22 August 2010

A large study was carried out to assess the effects of alcohol consumption on breast cancer risk among women with a BRCA1 or a BRCA2 gene mutation, both of which markedly increase the risk of breast cancer.  Comparisons were made between women with a gene mutation who had developed invasive breast cancer matched with women with the same gene mutation who had not developed breast cancer.  After a number of appropriate exclusions, there were 1,480 matched pairs with BRCA1 mutations and 445 pairs with BRCA2 mutations.

Data from the study support an earlier report suggesting no increase in breast cancer risk from alcohol intake for women with either gene mutation.  In the previous study on this topic, a slight lowering of breast cancer risk was noted with light drinking among women with the BRCA2 mutation but not among those with the BRCA1 mutation.  In the present study, a possible reduction in risk of breast cancer was seen for moderately drinking women with the BRCA1 mutation, but not the BRCA2 mutation.  Further, in the present study, the reduction is risk of breast cancer was seen only for wine consumers.  While one should not over-interpret epidemiologic data in the absence of identified biologic mechanisms, there have been a very large number of experimental studies showing that certain polyphenols present in wine actively impede the initiation and growth of cancer cells.

Overall, current scientific data suggest that alcohol in moderation does not increase the risk of breast cancer among women with a BRCA mutation, and wine may be somewhat protective.  If this is indeed the case and given the high risk associated with these genetic mutations, it would be important to inform women with such a mutation that moderate alcohol does not appear to increase their risk of breast cancer.

Reference:  Dennis J, Ghadirian P, Little J, et al:  The Hereditary Breast Cancer Clinical Study Group.  Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers.  The Breast 2010; e-pub.

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, click here.

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Critique 014: Moderate drinking, especially of wine, is associated with better cognitive function   13 August 2010

A large prospective study of men and women in northern Norway reported that moderate wine consumption was independently associated with better performance on cognitive tests after 7 years of follow up.  There was no consistent association between consumption of beer or spirits and cognitive test results.  The authors also reported that abstinence was associated with significantly lower cognitive performance in women.  As noted by the authors, in any observational study there is the possibility of residual confounding by other lifestyle habits affecting cognitive function, and the present study was not able to adjust for certain ones (e.g., diet, income, or profession) but did adjust for age, education, body mass index, depression, and cardiovascular disease and its major risk factors.

The results of this study support findings from a number of observational, prospective studies that have shown that the moderate consumption of alcohol, especially of wine, may have favorable effects on cognitive function.  Such effects could relate to the presence in wine of a number of polyphenols and other substances that reduce the risk of cognitive decline with ageing.  Mechanisms that have been suggested for such protection against cognitive dysfunction include effects on atherosclerosis, coagulation, inflammation, as well as direct neuroprotective effects.

Reference:  Arntzen KA, Schirmer H, Wilsgaard T,  Mathiesen EB.  Moderate wine consumption is associated with better cognitive test results: a 7 year follow up of 5033 subjects in the Tromsø Study.  Acta Neurol Scandd 2010; Suppl 190:23-29.

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, click here.

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Critique 013:   Greater than moderate alcohol intake increases the risk of liver cirrhosis 27 July 2010

A new meta-analysis shows that alcohol consumption is a strong factor in the development of cirrhosis of the liver.  The study also supports the theory that there is a threshold of drinking above which the risk is increased, as some of their analyses suggest that the risk increases only with intake of more than 24 grams/day of alcohol for women (about 2 typical drinks by US standards) and 36 grams/day of alcohol for men (about 3 typical US drinks).

Despite some concerns about the approach used, our Forum agrees that the present meta-analysis supports previous studies indicating a strong role of heavy alcohol drinking in the development of cirrhosis.  The differences found by the investigators between the effects of moderate alcohol intake on cirrhosis morbidity and on cirrhosis mortality are difficult to explain, but may relate to misclassification of alcohol intake (heavy drinkers reporting less alcohol), always a problem in observational studies of the effects of alcohol.

The results related to morbidity suggest that small amounts of alcohol are not associated with an increased risk of cirrhosis, and may be associated with lower risk of disease.  Thus, the data provide evidence for a “threshold effect” of alcohol intake for the development of cirrhosis.  Limited previous data are available suggesting that wine consumption may be associated with lower risk of cirrhosis than the intake of other beverages, but essentially all studies show heavy drinking of any type of beverage increases the risk.

Reference:  Rehm J, Taylor B, Patra SM, Irving H, Baliunas D, Patra J, Roerecke M.  Alcohol as a risk factor for liver cirrhosis: A systematic review and meta-analysis.  Drug and Alcohol Review 2010,29,437–445.  DOI: 10.1111/j.1465-3362.2009.00153.x

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, click here.

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Critique 012: Moderate drinking in the elderly is associated with lower total mortality 23 July 2010

The effects of alcohol consumption in the elderly may be modified by a decreased ability to metabolize alcohol, an altered volume of distribution due to reduced lean body mass and total body water, and an increased prevalence of co-morbid conditions.  These factors make this study of the net effects of drinking among a large number of community-dwelling elderly men and women especially important.

In large prospective studies from Australia of men aged 60-79 and women aged 70-75 years of age, men consuming up to 4 drinks/day and women up to 2 drinks/day had considerably lower risk of dying (total mortality) than did non-drinkers.  For subjects reporting 1-2 drinks/day, their total mortality risk was about 20-30% lower than that of abstainers.

While the authors concluded that not consuming alcohol on 1 or 2 days per week was associated with better outcomes, this conclusion is not in accordance with their own data.  The benefit of one or two “alcohol-free” days per week has never been substantiated with solid evidence from any large epidemiological study.

Our Forum review concludes that in terms of total mortality risk, recommendations for very low levels of drinking among the elderly may be overly restrictive, as this study showed lower total mortality for up to 4 drinks/day for elderly men and 2 drinks/day for elderly women.  Further, this study does not provide support for the conclusion that mortality is lower for people who have 1 or 2 “alcohol-free” days per week.

Reference:  McCaul KA, Almeida OP, Hankey GJ, Jamrozik K, Byles JE, Flicker L. Alcohol use and mortality in older men and women.  Addiction 2010.  On-line prior to publication:  doi:10.1111/j.1360-0443.2010.02972.x

For the full critique of this paper by the International Scientific Forum on Alcohol Research, click here

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Critique 011:  A Review of the Proposed New US Dietary Guidelines                                                       14 July 2010

Members of our International Scientific Forum on Alcohol Research have submitted a detailed review of the draft recently circulated by the United States Department of Agriculture for proposed new US Dietary Guidelines for 2010.  In general, Forum members were very pleased with the alcohol recommendations in the proposal, finding them interesting, balanced, and accurate.  Many commented that, rather than just focusing on warnings against heavy drinking, the new Guidelines appear to take into account the large amount of recent epidemiologic and experimental data that support many potential beneficial health effects of moderate drinking.

Among specific recommendations from the Forum were the following:

■          A stronger statement is needed of the effects of light-to-moderate drinking on total mortality, in that recent prospective studies show a considerably lower of risk of death for moderate drinkers.

■          Additional emphasis is needed on the reduced risk of developing diabetes for moderate drinkers, and the much lower risk of cardiovascular disease among diabetics who consume some alcohol.

■          Further information should be presented on the consistent scientific data showing that women who drink moderately are at reduced, not increased, risk of weight gain in adult life.

There were a number of topics not discussed in the draft Guidelines that members of the Forum thought deserved consideration for inclusion.

■          Recent reports have consistently shown that among people who have already had a myocardial infarction or other cardiovascular event, moderate drinking is associated with a reduced risk of further cardiovascular events and death.

■          More emphasis in the Guidelines should be put on the pattern of drinking (regular moderate rather than occasional binge drinking) and also on the much lower blood alcohol levels after drinking when the beverage is consumed with food, rather than on an empty stomach.

■          It was also suggested to the Guidelines Committee that the beneficial effects on cardiovascular risk of polyphenols and other substances in wine and certain beers, in addition to alcohol, be discussed more adequately.

There were also some suggestions from ISFAR regarding future research needs in the field.

■          The Forum strongly supports the need for further research on the risks and benefits of light-to-moderate alcohol consumption, rather than focusing research only on alcohol abuse.

■          The Forum proposed emphasis on future research dealing with targeting recommendations for groups of people according to age, gender, other behaviors, etc., although there was some disagreement among Forum members as to whether or not moderate drinking has strong health effects in the young and not just in middle-aged and older adults.

■          ISFAR considers moderate drinking, unless contraindicated by certain conditions (e.g, former abuse, some types of severe liver disease), to be an important aspect of a healthy lifestyle.  It should be a complement, not an alternative, to other lifestyle factors such as not smoking, getting exercise, eating a healthy diet, and avoiding obesity.

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The draft of the proposed new Dietary Guidelines is available at http://www.cnpp.usda.gov/DGAs2010-DGACReport.htm.

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For the full ISFAR critique of the proposed new Guidelines, click here

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Summary Critique 010                                                                                            30 June 2010

Should moderate alcohol consumption be advised following a heart attack?

There has been considerable recent interest in the effects of alcohol consumption following an acute myocardial infarction (AMI).  In an observational study among 325 subjects who were moderate drinkers prior to an AMI, 84% continued to drink and 16% quit.  While most of the outcome measures showed no statistically significant effects between the two groups of patients, all outcomes showed a tendency towards better physical and mental health outcomes for persistent drinkers in comparison with those who quit drinking.

A key problem with this analysis, and with all observational epidemiologic studies on this topic, is that the reason that some subjects stopped drinking after having an AMI, while others continued to drink, is not known.  Even though adjustments were made for many known related factors, there is always the possibility that subjects who stopped drinking were “sicker” in many ways than those who persisted in their alcohol consumption.

It may well require a randomized trial, in which some subjects having an AMI are randomly advised to continue to drink and others advised to stop drinking, to be able to determine reliably the effects on the clinical course of the persistence of alcohol intake following an AMI.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here:  Critique 010

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Summary:  Critique 009                                                                                   25 June 2010

Should moderate alcohol consumption be advised for its health effects?

A report from a conference that took place at the Medicine Grand Rounds at Beth Israel Deaconess Medical Center, Boston, Massachusetts, on January 15, 2009 has recently been published in the Journal of the American Medical Association, JAMA.  It provides a discussion by an epidemiologist with a broad knowledge in the field in response to a theoretical question, as from a middle-aged patient, as to the advisability of consuming some alcohol “for his health.”

The paper provides an excellent discussion of a theoretical question about drinking and health.  It focuses on the potential risks and benefits associated with moderate drinking for a middle-aged male patient.  Most members of the International Scientific Forum on Alcohol Research (ISFAR) were pleased with the discussion of the topic.  It was noted how uncommon it is that such knowledgeable, detailed, and mostly objective data appear in the mainstream medical literature.  It was thought to be “readable, informative and thoughtful.”

The ISFAR critique points out a number of topics that were covered incompletely in the paper, including inadequate information on the importance of the pattern of drinking: moderate regular consumption versus binge drinking.  Further, there was a notable lack of information on the beneficial effects on many pathophysiologic processes of polyphenols and other non-alcohol substances present in wine and certain other foods and beverages.

Overall, it was believed that the paper provided important information for physicians who may be discussing alcohol consumption with their patients.

Reference

Clinical Crossroads: Conferences with patients and doctors.  A 42-year-old man considering whether to drink alcohol for his health.  Kenneth J. Mukamal, MD, MPH, Discussant.  JAMA 2010;303:2065-2073. (doi:10.1001/jama.2010.550)

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here:  Critique 009.

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Summary: Critique 008: 13 June 2010

Further evidence that moderate alcohol consumption may play a role in the prevention of Alzheimer’s Disease

In a case-control study from Spain on the effects of smoking and alcohol use on the risk of Alzheimer’s Disease (AD), the authors found that the risk of AD was unaffected by any measure of tobacco consumption.  On the other hand, alcohol consumers showed a 47% lower risk of developing AD than did never consumers, with effects mainly among women and among never smokers.  No differences were noted by type of alcoholic beverage consumed.  The authors conclude that mean daily total consumption of alcohol showed increasingly protective dose-response relationships in women.

The numbers in this analysis were rather small, and there is always the possibility of confounding by other lifestyle factors.  Still, the study supports a number of previous epidemiologic studies showing a lower risk of developing AD for moderate consumers of alcohol.

Reference

García AM, Ramón-Bou N, Porta M.   Isolated and joint effects of tobacco and alcohol consumption on risk of Alzheimer’s Disease.   Journal of Alzheimer’s Disease 2010;20:577–586. (DOI 10.3233/JAD-2010-1399).

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: Critique 08.

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Summary:  Critique 007                                                                  9 June 2010

People may change to a “healthier” pattern of drinking as they age

In a prospective longitudinal study of a cohort of Americans in the “Baby Boomer” generation, subjects’ drinking habits were assessed at two points, when they were approximately 53 years of age and again when they were approximately 64 years of age.  As the subjects got older, they began to consume fewer drinks per occasion but to consume alcohol more frequently; the net effect was little change in total alcohol intake for women but a slight increase for men.

In most epidemiologic studies, regular moderate drinking is the pattern associated with lower risk of many chronic diseases; hence, the described change in drinking pattern in this study (smaller amounts on more frequent occasions) can be considered a “healthy” change.  Most long-term observational studies show a decrease in total alcohol intake with ageing, although reasons for such are poorly understood.

This paper emphasizes the importance of knowing the pattern of drinking, and not just the total number of drinks consumed over a week, when evaluating the impact of alcohol consumption on health and disease.

Reference

Molander RC, Yonker JA, Krahn DD.  Age-related changes in drinking patterns from mid- to older age: results from the Wisconsin Longitudinal Study.  Alcoholism: Clinical and Experimental Research 2010;34 (Published early online 7 May 2010).

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: Critique 07.

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Summary:  Critique 006 2 June 2010

For patients who already have cardiovascular disease, continued moderate alcohol consumption may reduce their risk of death

This review paper in Circuation summarizes data from 8 epidemiologic studies of subjects with cardiovascular disease (CVD) as to their subsequent mortality (both CV and total-mortality) according to their alcohol consumption.  Most studies showed significantly lower risk of both CV and total mortality for patients with CVD who were consumers of alcohol.

Despite these clear-cut findings, the authors were very cautious in their conclusions, focusing on the dangers of excessive drinking and not encouraging cardiovascular patients who do not drink to start regular drinking.   They state that moderate consumers of alcohol who have CV disease should not be advised to stop drinking, but should be advised to not consume alcohol more heavily.

It is interesting that these authors published the meta-analysis upon which this review is largely based in the Journal of the American College of Cardiology earlier in 2010.  In that paper, their conclusions were less restrained: “Cardiologists should be aware that regular, moderate alcohol consumption, in the context of a healthy lifestyle (increased physical activity, no smoking), dietary habits (decreased dietary fat intake, high consumption of fruit and vegetables), and adequate drug therapy, would put their patients at a level of cardiovascular or mortality risk substantially lower than either abstainers or heavy or binge drinkers.”

Reference

Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G.  Contemporary Reviews in Cardiovascular Medicine.   Cardiovascular and overall mortality risk in relation to alcohol consumption in patients with cardiovascular disease.  Circulation 2010;121;1951-1959.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: CRITIQUE 006.

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Summary: Critique 005                                                                   27 May 2010

Alcohol in young women may increase their risk of benign breast disease

Among more than 6,000 young women being followed in a longitudinal study, 67 confirmed cases of benign breast disease (BBD) were diagnosed.  Alcohol consumption was reported on 57 women who developed BBD when they were 16 – 23 years of age, with all but 8 subjects being 18 or older when they reported alcohol intake, and no data were presented on potential exposures earlier following menarche.  A significant increase in the risk of BBD was associated with alcohol intake, although many key factors that have been shown to relate to BBD were not reported in the paper.  Hence, while the number of cases is small, and a number of potential risk factors are not included, this study suggests that BBD may be increased by alcohol consumption in young women.

Reference

Berkey CS; Willett WC; Lindsay Frazier A; Rosner B; Colditz GA; Rockett RH; Helaine RM.  Prospective study of adolescent alcohol consumption and risk of benign breast disease in young women.  Pediatrics 2010;125:e1081-e1087.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: CRITIQUE 005.

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Summary: Critique 004                                                                 24 May 2010

Moderate alcohol consumption is associated with other healthy lifestyle factors

An analysis based on a very large number of subjects in France demonstrates, as have most other studies, that moderate consumers of alcohol have many associated healthy lifestyle habits: lower levels of body mass index, blood glucose, heart rate, stress and depression scores; higher subjective health status, HDL-cholesterol values, levels of physical activity and social status.   The authors suggest that alcohol is not related causally to any of these factors, and that the other lifestyle factors, not alcohol consumption, are the reason that moderate drinkers have less cardiovascular disease.  They chose a very narrow group of citations from the literature to support this contention.

The authors ignore a large number of well-conducted prospective epidemiologic studies showing that moderate drinkers are at lower risk over time of developing certain risk factors.  Further, the authors of this paper ignore an immense basic science literature that suggests that alcohol is an important factor in the development of biological risk factors, atherosclerosis, and cardiovascular disease.  Further, they do not describe a number of studies that have shown specifically that moderate drinking is associated with less cardiovascular disease and diabetes among subjects who are otherwise very healthy (non-smokers, not obese, physically active, and on a healthy diet).

There is no doubt that confounding by associated lifestyle factors can play a role in the lower risk of chronic diseases among moderate drinkers, who tend to also have other healthy behaviors.  However, there is now a large body of scientific evidence that indicates that alcohol is an important factor in the lower rates of such diseases; current scientific data do not support the conclusions of the authors of this paper.

Reference

Hansel B, Thomas F, Pannier B, Bean K, Kontush A, Chapman MJ, Guize L, Bruckert E.  Relationship between alcohol intake, health and social status and cardiovascular risk factors in the urban Paris-Ile-De-France Cohort: is the cardioprotective action of alcohol a myth?  European J Clin Nutrition, advance online publication, doi:10:1038/ejcn.2010.61.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: CRITIQUE 004.

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Summary: Critique 003                                                                17 May 2010

Moderate alcohol consumption markedly reduces the risk of diabetes mellitus, even among subjects with otherwise very healthy lifestyles

In a very well-done analysis from a large Dutch population, it was shown that moderate drinking considerably lowers the risk of developing type 2 diabetes even among subjects who are otherwise following a healthy lifestyle (not obese, non-smokers, physically active, eating a healthy diet).  Thus, it indicates that the effect of moderate drinking on lowering the risk of diabetes cannot be explained by other healthy lifestyle habits of such drinkers.  Moderate drinking should be considered as a complement, and not as an alternative, to other healthy lifestyle habits that lower the risk of chronic diseases such as diabetes and coronary heart disease.

Reference

Joosten MM, Grobbee DE, van der A DL, Verschuren WWM, Hendriks HFJ, Beulens JWJ.  Combined effect of alcohol consumption and lifestyle behaviors on risk of type 2 diabetes.  Am J Clin Nutr 2010;91: 1777-1783.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: CRITIQUE 003.

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Summary: Critique 002                                                                 26 April 2010

Red wine, but not other types of alcohol, improve endothelial function in a randomized trial

The healthy state of cells that form the lining of arteries, assessed by indices of endothelial function, is a key factor associated with preventing the development and progression of atherosclerosis and coronary heart disease.  In a randomized trial among healthy young adults, the daily consumption of about 3 ounces of red wine for three weeks led to significant improvement in endothelial function.  Such improvements were not seen with the consumption of water, or of beer or vodka containing similar amounts of alcohol.

Further, in a series of in-vitro studies, the authors showed very similar effects from red wine and from a high concentration of resveratrol (but not from beer or ethanol) on factors associated with improved endothelial function.  The study supports many epidemiologic and animal experiments suggesting that certain non-alcoholic constituents of red wine have additional beneficial effects on cardiovascular risk over those of just the alcohol itself.

Reference

Huang PH, Chen YH, Tsai HY, Chen JS, Wu TC, Lin FY, Sata M, Chen JW, Lin SJ.  Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability.  Arteriosclerosis Thrombosis and Vascular Biology 2010;30:869-877.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: CRITIQUE 002.

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Summar: Critique 001                                                                         24 April 2010

Genetic effects on alcohol metabolism modify the relation of alcohol to breast cancer

A study from Germany compared the association between alcohol and breast cancer risk according to genetic variations affecting levels of alcohol dehydrogenase, an enzyme that clears alcohol from the blood stream.  The authors conclude that genetic factors associated with the slow clearance of alcohol are associated with increased risk of breast cancer for drinkers; an increase in cancer risk was not seen for drinkers with genetic factors leading to fast clearance of alcohol.  Such a finding would suggest that alcohol itself is the cause of an increase in breast cancer risk among drinkers.

Unfortunately, some previous studies have shown the opposite, that an increase in breast cancer risk occurs only among women who have genes associated with fast, rather than slow, alcohol metabolism.  Overall, current scientific data indicate that breast cancer’s relation to drinking is not resolved, remaining murky and conflicted, and perhaps overemphasized. This facet of that murkiness is itself also conflicted.  As of now, it is unclear the degree to which genes affecting alcohol dehydrogenase modify the association between alcohol and the risk of breast cancer and other diseases.

Reference

Larsen SB, Vogel U, Christensen J, Hansen RD, Wallin H, Overvad K,     Tjønneland A, Tolstrup I.    Interaction between ADH1C Arg²⁷²Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer.  Cancer Letters, 2010, in press.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here: CRITIQUE 001.

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