Alcohol clinical trials

Is drinking wine good or bad for you?

If you love to drink wine you are probably concerned when you read the endless negative headlines in the newspapers about alcohol and its effect on your health. Most governments, public health organisations and even charities advise not drinking or very limited drinking of alcohol. This review aims to discuss the balance of evidence to help you decide whether alcohol and wine is good or bad for you.

Background to the debate on alcohol, wine and health

The dangers of excessive drinking and the benefits of moderate amounts of alcohol have been part of a continued debate within the health community for decades. For example, a World Health Organisation (WHO) study published in October 2015 ranked ethanol in alcoholic beverages as definitely carcinogenic in common with processed meats like salami and bacon. In January 2016, the U.K.'s Chief Medical officer (CMO), Dame Sally Davies reduced "safe" drinking guidelines to 14 units a week for both men and women. See CMO Alcohol report.

In March 2016 Stockwell et al published a new study in the Journal of Studies on Alcohol and Drugs, "Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality."

The new study was a systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. A total of 87 studies were examined and the paper concluded that when his team corrected for abstainer "biases" and certain other study-design issues, moderate drinkers no longer showed a longevity advantage stating that "Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking."

However other academics dispute Stockwell's analysis contesting strongly his assertion that abstainers were biased because many abstainer groups include people in poor health whod cut out alcohol and that his approach to dismiss many studies because of his group's reservations about design was over zealous.

Yet, whilst drinking too much wine is certainly not good for you and even with the debate about abstainer biases and "flawed design" raised by Stockwell and other academics, some major clinical studies with many hundreds of thousands of participants give strong evidence that moderate consumption (2-3 glasses of alcohol per day) has a beneficial impact on your overall health, reduce your risk of premature death and lower your chances of having a life threatening event like a heart attack. These studies were pioneered by scientists like Sir Richard Doll, noted for being one of the first to conclusively link smoking tobacco and lung cancer.

Clinical evidence in these large scale human studies is clear that total abstainers from alcohol are likely to die younger than those drinking a glass or two a day on average of alcohol. Conversely "binge drinking" or heavy daily consumption of any alcohol is not healthy, predominantly because of negative effects on the liver and increasing the risk of cancer. A moderate approach to wine consumption is therefore to be recommended for a happier, healthier and longer life!

In addition, certain types of wine may have a more beneficial effect on health than others. Laboratory studies confirm that red wines made from grapes with thick skins (e.g. Tannat & Malbec) have higher levels of a molecule called resveratrol which appears to have positive effects on the body. However some studies show an equal positive impact for both red and white wines leading some academics to suggest that it is alcohol itself which benefits health rather than any specific compound in wine or other drinks. 

Unpicking facts from fiction is a large task given the controversy and this review attempts to link the substantial human data relating to alcohol use and give a conclusion to the regular alcohol or wine drinker as to whether wine is good or bad for your health. 

Gene Ford in his 2003 book "The Science of Healthy Drinking" points out that antipathy to drinking became the norm in medicine when the American Medical Association passed a resolution in June 1917 which stated "alcohol as a beverage is detrimental to the human economy...or as a stimulant or as a food has no scientific basis...the use of alcohol as a therapeutic agent should be discouraged." This was followed by Prohibition in the United States between 1920 and 1933, a nationwide constitutional ban on the sale, production, importation, and transportation of alcoholic beverages.

Prohibition may have gone but temperance is a societal normal in many countries with a pattern of government sponsored bodies omitting drink positive research in disease articles and with a tendency to overstate the risks of abuse and addiction. Many highly regarded but conservative doctors still believe in a prohibitionary agenda despite the evidence that moderate consumption has a positive impact on health outcomes. Yet most doctors themselves are not abstainers!

Many drinkers worry about addiction but the evidence is substantial in the medical literature that only a very small percentage of alcohol drinkers will become addicted. Alcohol abusers tend to have underlying psychological or social problems which is linked to the addiction and certain genetic factors are key.

Positive studies associated with alcohol are explained away by some physicians by so called "confounding factors". They will argue that those who apparently had a lower risk of heart attacks or other negative health events may have been drinking more alcohol than abstainers but focus on the potential of better lifestyle in the alcohol drinking group. Others quote the 'sick quitter' hypothesis, an argument that the risks of not drinking were magnified as some people stop consuming alcohol because of problems with their health and therefore only lifelong abstainers should be studied.

Authors like Tony Edwards in "The Good news about Booze" summarise the picture that moderate drinking - or by today's puritanical standards, even relatively heavy drinking - reduces not only heart disease risk but overall mortality risk and the relationship is causal.

Dr Kari Poikolainen, a doctor of medical science and adjunct professor in public health (since 1983) at the University of Helsinki in Finland and Research Director at the Finnish Foundation for Alcohol Studies before he retired. In 2014 he published a very good book for those interested in alcohol and health called "Perfect Drinking and its enemies".

Dr Kari Poikolainen

Dr Kari Poikolainen

Poikolainen says "To sum up, the most likely estimate for increased health risk (from alcohol), compared with that of abstaining, is somewhat between 90 and 150g/day. Respectively, the optimal level might be 14-22g/day" (120 ml of wine, half a large glass = 12g of 100% alcohol). Furthermore he states that "Careful participant observations have found that many alcoholics consume much more, typically between 350 to 470g/day".

Those with a negative view of the alcohol benefit talk about "Even if moderate drinking does confer health benefits, which it probably does, they are rather modest - certainly not stronger than the effect of small daily doses of aspirin on heart health...the effect may be more in line with the apparent cardio-protective benefits of eating a modest portion of nuts each day" (Time magazine 2003). Yet clinical evidence from major studies indicates that drinking moderate amounts of alcohol has a more than "modest" benefit on risk of cardiovascular disease and overall mortality and in populations who are abstainers and are already eating healthily and perhaps using measures such as Aspirin the comparative benefit of drinking 2-3 glasses of alcoholic drinks are incrementally beneficial.

In 2006 Di Castelnuovo et al used a meta analysis technique where the results of 34 studies were collated and reviewed and published in the Archives of Internal Medicine. The study looked at the link between the amount of alcohol drunk and death rates in men & women in clinical trials conducted before the end of 2005 with over 1 million subjects. Yes over 1 million people!

A J-shaped relationship between alcohol and total mortality was confirmed in both men and women. Consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was inversely associated with total mortality or the chance of dying, maximum protection being 18% in women and 17% in men. Higher consumption of alcohol was detrimental. The results were consistent with studies by other research including Sir Richard Doll's 1994 study "Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors". 

Abigail Zuger wrote in the NYT in 2002 in the article "The case for drinking (All Together Now in Moderation), "Thirty years of research has convinced many experts of the health benefits of moderate drinking for some people. A drink or two of wine, beer or liquor is, experts say, often the single best non-prescription way to prevent heart attacks, better than a low fat diet or weight loss, better even than vigorous exercise. Moderate drinking can help prevent stokes, amputated limbs and dementia."

Zuger's view may be over eager but examples like the French Paradox (where despite a high fat diet and heavy smoking the people of several regions of France live a long life) show that moderate alcohol together with regular exercise, a good diet with olive oil/fish/nuts (in a regular, relaxed setting ideally non rushed eating) and not smoking is a key to long and healthy life. 

Do we need to drink wine - no! But life without wine would be a lot duller and wine is certainly an "antidote to civilisation". What do I mean by this? Well after a stressful or boring day at work, a rough day with the children, bad or good news, human beings sometimes need a reward. In earlier generations they may have smoked a few cigarettes to wind down and now in the modern world we need something else since we now know that the TAR in cigarettes isn't exactly positive (the risks certainly outweigh the benefits). The alclohol prohibitionists may say you don't need anything, "a glass of water will do", but we know that this suggestion isn't the same and the clinical evidence is there for all to see that less than half a bottle of wine a night is a lot better for you than smoking tobacco or cannabis or eating too much as comfort food - the benefits of moderate wine drinking certainly outweigh the risks. If you can do it with exercise and healthy eating even better! 

The evidence for Aspirin and Statins in reducing mortality plus risk of heart attack & stroke are substantial but given side effect concerns (e.g. gastrointestinal bleeds with Aspirin) the case for consuming 2-3 glasses of wine a day look equally compelling.

In the end it is all down to relative risk. Certain behaviours and environmental factors increase your risk of an event like cancer or heart attack. Although certain cancers such as Breast may rise in alcohol drinkers, the increase in risk is tiny compared with the absolute risk of dying in a car accident. Given the risk of dying prematurely in moderate drinkers seems convincingly lower, I for one am continuing my love of the fermented grape.

The debate and the controversy amongst academics will continue!

Negative effects of alcoholic drinks

  • Alcohol: high alcohol consumption (half a bottle of wine a day and over) results in a higher blood pressure and may cause hypertension at very high levels of drinking. It has a positive correlation with mouth, throat and gullet (oesophageal) cancer and under certain circumstances with liver cancer and liver cirrhosis. Some studies suggest a positive relationship between alcohol and breast & gastric cancer, though there is evidence that it may reduce the risk of kidney cancer. The relative risk of lung cancer for men who smoke is 2,300 percent higher than it is for men who don't smoke, whereas some studies show that alcohol may have a relative risk of around 100%, i.e. doubles your chance of getting cancer, which in many cases have a small absolute lifetime risk e.g. oesophageal (1 in 112) or liver (1 in 193). The most prevalent cancers are lung (most caused by smoking), prostate and breast.
  • Tannin: these compounds are plant polyphenols and may cause headaches. Tannins tend to bind starches while being digested. 
  • Sulfites / Sulphites: The term ‘sulfites’ is an inclusive term for sulphur dioxide (SO2). SO2 is a preservative and widely used in wine making because of its antioxidant and antibacterial properties. SO2 plays a very important role in preventing oxidisation and maintaining a wine’s freshness but some people seem to be sensitive to it and many higher quality wine makers are now trying to limit the addition of sulphite or eliminate it entirely.

Positive effects of alcoholic drinks

Risk of premature death

  • Risk of dying early up to 40% lower in drinkers than abstainers, with lower benefit for women and Asians
  • Moderate drinking increases longevity for all causes by about 3%

Reducing coronary heart disease

Epidemiological studies confirm that wine changes body fat levels with total cholesterol lower, bad LDL cholesterol and higher good high density lipoprotein (HDL) levels in drinkers than abstainers.

  • Alcohol significantly reduces incidence of cardiovascular disease, total mortality with lower incidence of angina pain and heart attacks
  • Daily alcohol intake reduces atherosclerotic plaque build up (arteriosclerosis), key in reducing the risk of strokes and heart attacks
  • Nearly a 50% reduction in heart attack risk amongst moderate daily alcohol drinkers has been reported with superior benefits to using daily Aspirin

High blood pressure

  • Light drinkers show favourable blood pressure profiles and less blood pressure induced strokes

Strokes 

  • Light alcohol consumption reduces risk of stroke, whilst lifelong abstention increases risk

Cancer

  • Two to three alcoholic drinks per day reduce some cancer rates e.g. prostate and kidney

Alzheimer's disease and dementia

  • The Polyphenols in wine have an antioxidant and free radical scavenging action which may explain their positive benefit in reducing the risks of dementia. High doses of resveratrol which is found in wine has been shown to reduce the level of amyloid beta protein in blood (where it probably accumulates in the brain causing the classic symptoms of dementia). 

Diabetes

  • Detrimental metabolic factors are reduced in diabetics who consumer moderate amount of alcohol e.g. LDL cholesterol

Colds and Flu

  • Moderate daily drinking has been shown to reduce the risk of catching the common cold

Why is wine probably healthier than other alcoholic drinks?

In Arranz S 2011 "Wine, Beer, Alcohol and Polyphenols on Cardiovascular Disease and Cancer" they said that "The mechanisms responsible for the healthy effects of wine are extremely complex due to the many different pathways involved. Both alcohol and polyphenolic compounds have been extensively studied, despite the continued controversy as to which component is the most active. The underlying mechanisms to explain these protective effects against CHD include an increase in high-density lipoprotein (HDL) cholesterol, a decrease in platelet aggregation, a reduction in the levels of fibrinogen and an increase in insulin sensitivity, which have been attributed to the ethanol content in wine. Other studies have provided evidence that wine exhibits beneficial properties which are independent of the presence of alcohol, and should be attributed to their polyphenolic content.".

They conclude that "Wine consumption should not replace a healthy lifestyle. However, light-to-moderate wine drinkers, without medical complications, may be assured that their wine consumption is a healthy habit."

Cordova AC 2009 in "Polyphenols are medicine: Is it time to prescribe red wine for our patients?" states that "The habit of having one or two drinks of red wine every day with meals may translate to a longer, healthier and better quality of life."

Are certain wines better for you than others?

Red wine polyphenols are a complex mixture of flavonoids (such as anthocyanins and flavan-3-ols) and nonflavonoids (such as resveratrol, cinnamates and gallic acid). Flavan-3-ols are the most abundant, with polymeric procyanidins (condensed tannins) composing up to 50% of the total phenolic constituents. These compounds act as potent antioxidants as they reduce low-density lipoprotein (LDL) cholesterol oxidation, modulate cell signaling pathways, and reduce platelet aggregation. Red wine contains more polyphenols than white wine (around 10-fold) because during the wine making process, red wine, unlike white wine, is macerated for weeks with the skin which is one of the parts of the grape with the highest concentrations of phenolic compounds. The concentrations in red wine range from around 1.2 to 3.0 g/L.

Certain wines seem to be more healthy than others and one theory is those with the healthiest credentials have the highest amount of procyanidins (proanthocyanidins) - proC, which is a polyphenol.  

The effects of proC include anti oxidant and free radical neutralisation, reducing blood fat, and inhibiting destruction of collagen, the most abundant protein in the body. They may also prevent cardiovascular disease by reducing the negative effects of high cholesterol on the blood vessels. These effects explain their apparent benefits in reducing the incidence of cardiovascular disorders. 

The amount of polyphenols varies from wine to wine, country to country and grape to grape.  The method of production can also significantly impact the amount of procyanidins.

In N Gall 2001 "Is wine good for your heart? A critical review" he says " Is there evidence to enable us to advise what to drink? Although the epidemiological evidence suggests not, there are at least theoretical reasons why red wines rich in flavonoids and resveratrol may hold extra benefit. Flavonoids, being found particularly in grape skins, occur in the highest concentrations in grape varieties with thick skins grown in hot climates.Cabernet sauvignon based wines from Australia, South America, and the southern Mediterranean are particularly rich sources. Syrah (shiraz) and merlot are good too. Fungal vine infection is more common in cooler, damper regions and occurs in significant quantities in pinot noir. Wines from this grape form Burgundy, Sancerre, New Zealand, and the north west United States are particularly rich in resveratrol. Merlot, gammay, syrah, zinfandel, and pinotage wines may also be too. May I advise: Nuits-St-Georges Premier Cru, Clos des Porrets, 1997, one nocte. As the French say, Salut."

What is Resveratrol and why is it important?

 

Other evidence points to the importance of the concentration of a stilbenoid, a type of natural phenol, called resveratrol in wine and some producers have sought to exploit higher concentrations of this chemical in their wines. 

Resveratrol is found in the skin of red grapes. For example, the Malbec grape, used extensively in Argentina and the Tannat grape found in Uruguay, have thick skins and contains high levels of resveratrol. Vine grapes grown in cooler climates have higher resveratrol levels than those from warmer climates such as Australia.

However, the science behind healthy wine is controversial with some scientists arguing that polyphenols are unimportant, and that factors such as the pips used or manufacturing process are more significant.For example,  see http://www.bbc.co.uk/news/health-23985540, "Red wine - what's behind its healthy reputation?"

tannat.jpeg

Tannat - seemingly the grape with the highest health benefits

It is said that the tannat grape is the grape with the greatest health benefits. Tannat is used extensively in Madiran wine from SW France (not to be confused with Madeira Wine, a fortified Portuguese wine made in the Madeira Islands) and in Uruguay.

tannat grape vines

More recently wine makers in the Central Coast Region of California are beginning to grow the grape in larger quantities.

The other main factor in the health benefits of a Red Wine may be the method of duration of fermentation and maceration (which is the process of soaking crushed grapes, seeds, and stems in a wine must to extract coluor and aroma compounds as well as tannins). The long fermentation and maceration times that go into the production of Madiran Red Wine may be important factors in its apparent healthiness. The more mass produced Red Wines wines generally don’t conform to these criteria and usually have very low levels of procyanidins.

Procyanidin levels around the world (reds):

Dr. Roger Corder is an author of many scientific papers detailing his research into the flavonoids of foods, but wine in particular. He summarised his findings in "The Red Wine Diet, 2007". 

roger.jpeg

Among the important observations Corder makes is that regions of the world with the greatest longevity also correspond to regions with the highest procyanidin flavonoids in their wines. 

"Although differences in the amount of procyanidins in red wine clearly occur because of the grape variety and the vineyard environment, the winemaker holds the key to what ends up in the bottle. The most important aspect of the winemaking process for ensuring high procyanidins in red wines is the contact time between the liquid and the grape seeds during fermentation when the alcohol concentration reaches about 6 percent. Depending on the fermentation temperature, it may be two to three days or more before this extraction process starts. Grape skins float and seeds sink, so the number of times they are pushed down and stirred into the fermenting wine also increases extraction of procyanidins. Even so, extraction is a slow process and, after fermentation is complete, many red wines are left to macerate with their seeds and skins for days or even weeks in order to extract all the color, flavor, and tannins. Wines that have a contact time of less than seven days will have a relatively low level of procyanidins. Wines with a contact time of 10 to 14 days have decent levels, and those with contact times of three weeks or more have the highest."

He points out that deeply-coloured reds are more likely to be richer in procyanidins. Wines rich in procyanidins provide several-fold more, such that a single glass can provide the same purported health benefit as several glasses of a procyanidin-poor wine.

  • Australian: on average, low levels, except Cabernet Sauvignon which is moderate.
  • Argentine: Argentinian Malbec have some of the highest levels of procyanidins 
  • Californian: Those with the Tannat grape variety have the highest levels, but Cabernet Sauvignon has also a high content.
  • Chile: Cabernet Sauvignon stands out, then only moderate in content.
  • French: Bordeaux is moderate for procyanidins, Burgundy wines are low to moderate; Languedoc-Roussillon red wines moderate to high levels; Côtes du Rhône red Wines moderate to high. South-West France is a region with superior longevity of its residents. Wine of the Cahors appellation is mainly made from the Malbec grape. The wine with the highest procyanidin content is a wine grown in the Gers region of southwest France. The wines here are made with the tannat grape within the Madiran appellation; wines labeled "Madiran" must contain 40% or more tannat to be so labeled.
madiran.jpeg
  • Italian:The southern Italian wines from Sicily, Sardinia, and the mainland have high levels of procyanidins while most northern varieties are moderate.
  • Spanish: Moderate levels 
  • United States: Cabernet Sauvignon is the standout for procyanidin content, with the Napa Valley a major production area.

Resveratrol concentrations in wine

Media coverage of wine health controversy

Prescription wine? - Horizon - Do I drink too much?

In this BBC documentary Dr William McCrea prescribes red wine to his patients in the Cardiac Ward of Scotland's Great Western Hospital.

William McCrea is now consultant cardiologist at the Great Western Hospital in Swindon, 58. He says

"There's a great deal of evidence that in moderation, alcohol is not harmful. And in people who've always had it in moderation, it's actually healthy. Two small glasses of red wine a day are good for you in terms of preventing heart disease. I personally have this every night at home, unless I'm on call or driving somewhere. 

And I prescribe red wine to mycardiac patients, apart from those with obvious contra-indications, such as liver or stomach disease or a history of addiction. 

Look at the French paradox: there is a far lower death rate from cardiovascular disease in France compared with the U.S. - that's not because of the cheese or the Gauloises cigarettes, is it? 

I occasionally have a cider, too - scrumpy has good antioxidants, which stop your blood clotting and keeps the inside of your blood vessels smooth. 

Antioxidants are good in general, but moderation is key: while two units a day gives you the optimal benefits, if you go up to four, it's bad news. 

The French Wine Paradox - CBS 60 Minutes

The ground breaking CBS feature on wine which changed the mindset of many an American when it comes to alcohol consumption and the impact on their health.

Eat well, Drink Wisely, Live Longer - Wine Spectator

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The French Paradox

The term "French paradox" was coined by Serge Renaud, a scientist from Bordeaux University in France, and has been in use since the early 1990s. His paper was published in 1992 "Wine, alcohol, platelets, and the French paradox for coronary heart disease".

Renaud et al based on the MONItoring system for CArdiovascular disease (MONICA) project which included seven million men and women between 35 and 64 years of age from 37 European, American and Asian populations, including the US, Canada, United Kingdom, France and China, among others. The World Health Organisation followed the subjects over a period of 10 years, from the mid-1980s to the mid-1990s. France presented a markedly lower annual mortality from CAD (coronary artery disease) compared with other industrialised nations, despite the fact that cardiovascular risk factors such as cigarette smoking, blood pressure, body mass index and serum cholesterol concentration were similar among these countries; furthermore, it had a three-fold higher intake of saturated fats than that of the US and the United Kingdom, which are not well known for their healthy eating .

Renaud's observations regarding the apparent disconnect between French patterns of high saturated fat consumption and their low rates of cardiovascular disease can be quantified using data from the Food and Agriculture Organisation of the United Nations. In 2002, the average French person consumed 108 grams per day of fat from animal sources, while the average American consumed only 72 grams. The French eat four times as much butter, 60 percent more cheese and nearly three times as much pork. Although the French consume only slightly more total fat (171 g/d vs 157 g/d), they consume much more saturated fat because Americans consume a much larger proportion of fat in the form of vegetable oil, with most of that being soybean oil. However, according to data from the British Heart Foundation, in 1999, rates of death from coronary heart disease among males aged 35–74 years were 115 per 100,000 people in the U.S. but only 83 per 100,000 in France.

Possible explanations for the French Paradox:

  • High per capita consumption and appreciation of wine in France, particularly red table wine - Resveratrol, Procyanidins and polyphenols
  • Aspects of the French diet - The French diet is rich in vitamin K2, it is rich in short-chain saturated fatty acids and low in trans fats despite dishes like Fois Gras, Confit de Canard etc.  
  • Whole diet - Higher fruit and vegetable intake, more fish, Early life nutrition
  • Generally don't tend to over eat and don't eat quickly - quality over quantity, portion control and lack of over consumption
  • Limited processed and packaged ready meal type foods (many of which are high in sugar and salt)
  • Less snacking and more moderate exercise
CardiovascularDeathsAHA.jpg

American Heart Association - This shows rates of death from cardiovascular diseases (heart attack and strokes combined) for men in several countries, ranked from worst to best.

France stands out as a country with a high wine consumption but with a correspondingly low level of death caused by heart attacks and strokes.

Detailed clinical evidence - the health effects of alcohol consumption

For more detailed information on the health effects of alcohol and wine consumption on health outcomes such as heart disease and death with key clinical studies please see the link below:

A summary of the effect of alcohol and wine on diabetes

There is good clinical data to suggest that moderate consumption of wine can reduce the risk of diabetes. Animal studies are suggestive that the polyphenol in wine, resveratrol, may be helpful in preventing and treating some metabolic diseases, including diabetes.

Salas-Salvadó J review  in 2011 "The role of diet in the prevention of type 2 diabetes" stated that "The conclusion is that there is no universal dietary strategy to prevent diabetes or delay its onset. Together with the maintenance of ideal body weight, the promotion of the so-called prudent diet (characterized by a higher intake of food groups that are generally recommended for health promotion, particularly plant-based foods, and a lower intake of red meat, meat products, sweets, high-fat dairy and refined grains) or a Mediterranean dietary pattern rich in olive oil, fruits and vegetables, including whole grains, pulses and nuts, low-fat dairy, and moderate alcohol consumption (mainly red wine) appears as the best strategy to decrease diabetes risk, especially if dietary recommendations take into account individual preferences, thus enabling long-time adherence."

In the 2011 review by Tomasz Szkudelski and Katarzyna Szkudelska "Anti-diabetic effects of resveratrol" (*Note that resveratrol is present in wine) they stated that "In the last few years, rodent studies and experiments in vitro provided evidence that resveratrol (3,5,4′-trihydroxystilbene)—a naturally occurring phytoalexin present in numerous plant species—exerts beneficial effects in the organism and may be helpful in preventing and treating some metabolic diseases, including diabetes. In general, the management of diabetes involves three main aspects: reduction of blood glucose, preservation of β cells, and, in the case of type 2 diabetes, improvement in insulin action. Data from the literature indicate that the beneficial effects of resveratrol in relation to diabetes comprise all these aspects". 

In a 2014 review by Khemayanto H "Role of Mediterranean diet in prevention and management of type 2 diabetes" where the authors identified 451 articles with the key words: “Mediterranean diet” and “diabetes” up to 14 April 2014 the authors summarised:

"Daily moderate intake of alcohol (usually after a meal) in the form of red wine is one of the characteristic of Mediterranean diet. Moderate alcohol drinking is associated with 30% reduction of the risk of type 2 diabetes in both genders. The strongest inverse association was observed at 22–25 g/day. However, heavy consumption in both men and women (above 50 g/day for women and 60 g/day for men) were no longer provided protective effect but actually increased the risk for diabetes. Moderate alcohol consumption (40 g/day) for 17 days enhanced insulin sensitivity and plasma adiponectin levels, without any changes in the plasma tumor necrosis factor α (TNFα). Adiponectin stimulated glucose utilization and fatty acid oxidation. Adherence to the Mediterranean diet was associated with higher levels of adiponectin because of moderate consumption of red wine, which is inversely related to diabetes."

"Numerous studies on diabetic rats revealed the anti-hyperglycemic action of resveratrol. Among different beneficial effects of resveratrol found in diabetes, the ability of this compound to reduce hyperglycemia seems to be the best documented. The anti-hyperglycemic action of resveratrol was demonstrated in obese rodents and in two animal models of diabetes: in rats with streptozotocin- induced diabetes or with streptozotocin- nicotinamide-induced diabetes. Some studies also revealed that administration of resveratrol to diabetic rats resulted in diminished levels of glycosylated hemoglobin (HbA1C), which reflects the prolonged reduction of glycemia."

"The anti-hyperglycemic effect of resveratrol observed in diabetic animals is thought to result from its stimulatory action on intracellular glucose transport. Increased glucose uptake by different cells isolated from diabetic rats was found in the presence of resveratrol. Interestingly, in experiments on isolated cells, resveratrol was able to stimulate glucose uptake in the absence of insulin. The stimulation of glucose uptake induced by resveratrol seems to be due to increased action of glucose transporter in the plasma membrane. Studies on rats with experimentally induced diabetes demonstrated increased expression of the insulin-dependent glucose transporter, GLUT4, as a result of resveratrol ingestion, compared with diabetic animals not given resveratrol. It should be mentioned, however, that in some experiments on rats with streptozotocin-induced diabetes, resveratrol appeared to be ineffective and failed to decrease blood glucose."

Alcohol, heart health and risk of dying (mortality) - A summary of clinical evidence

dead body.

The debate about alcohol and health benefits, the J-Shaped Curve and "Sick Quitter" Hypothesis

There has been consistent evidence in large scale clinical trials that moderate consumption of alcoholic drinks reduces the risk of dying prematurely versus being an abstainer - the so called J-shaped curve.

However, some have argued that the benefits are only applicable to a minority e.g. Knot et al 2015, BMJ "Compared with never drinkers, age stratified analyses suggest that beneficial dose-response relations between alcohol consumption and all cause mortality may be largely specific to women drinkers aged 65 years or more, with little to no protection present in other age-sex groups.". 

The paper says "The J-shaped relation is contentious, however, with some arguing that protective effects may be confounded by the common classification of heterogeneous non-drinking groups into a single referent category. Specifically, former drinkers have been found to exhibit poorer self reported health,higher levels of depression,and increased risk of mortality than never drinkers. As such, protective associations identified among light drinkers may be less a consequence of a beneficial biological mechanism and more a statistical artefact resulting from the application of a pooled non-drinking category. Indeed, when former drinkers were excluded from meta-analysis,the protective effect between alcohol consumption and total mortality was attenuated (P<0.01). Such a finding suggests that protective effects may have been over-estimated by existing studies."

Critics of the 2015 study point out that because the authors gathered data which clearly showed health benefits from moderate drinking and then divided it into so many subgroups that it was almost impossible for them to produce statistically significant results. In the end the only people who appeared to benefit from drinking were post-menopausal women.

The proponents of the "sick quitter" hypothesis that state that endorse the idea that teetotallers are more than those who do drink because they are chronically ill or because they are ex-alcohol drinkers and have damaged their bodies with alcohol. They argue that alcohol doesn't protect health its just that teetotallers are unusually sickly.

Rimm EB et al 2007, "Alcohol and Coronary Heart Disease: Drinking Patterns and Mediators of Effect" took on the "sick quitter" hypothesis saying "A recent meta-analysis raised questions about systematic misclassification error in observational studies because of inclusion among “non drinkers” of ex-drinkers and/or occasional drinkers. However, misclassification among a small percentage of non drinkers cannot fully explain the inverse relation, and there is substantial evidence to refute the “sick quitter” hypothesis. Furthermore, it has been shown that moderate alcohol consumption reduces CHD and mortality in individuals with hypertension, diabetes, and existing CHD. To address the issue of residual confounding by healthy lifestyle in drinkers, in a large prospective study we restricted analysis to only “healthy” men (who did not smoke, exercised, ate a good diet, and were not obese). Within this group, men who drank moderately had a relative risk for CHD of 0.38 (95% CI, 0.16–0.89) compared with abstainers, providing further evidence to support the hypothesis that the inverse association of alcohol to CHD is causal, and not confounded by healthy lifestyle behaviors."

There was further controversy when Stockwell et al published a new study in the March 2016 issue of the Journal of Studies on Alcohol and Drugs, "Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality."

The new study was a systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. A total of 87 studies were examined.

Tim Stockwell, Ph.D., the lead researcher on the analysis and director of the University of Victoria's Centre for Addictions Research in British Columbia, Canada said that "Most often, studies have compared moderate drinkers (people who have up to two drinks per day) with "current" abstainers. The problem is that this abstainer group can include people in poor health who've cut out alcohol. A fundamental question is, who are these moderate drinkers being compared against?"

The paper concluded that when his team corrected for those abstainer "biases" and certain other study-design issues, moderate drinkers no longer showed a longevity advantage. Further, only 13 of the 87 studies avoided biasing the abstainer comparison group--and these showed no health benefits. It stated that "Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking. These findings have implications for public policy, the formulation of low-risk drinking guidelines, and future research on alcohol and health."

Further reading on the J-Curve debate
Eric Crampton "Moderate drinking and health"

Eric Crampton "he J-Curve: science vs politics"

Christopher Snowdon "Teetotallers die younger, don't let 'em fool you"

Key studies Alcohol,cardiovascular protection and mortality

Meta Analysis and summary studies

Rimm EB 1996, "Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits" reporting "Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found an association for beer, and four for spirits.

Rimm concluded "Results from observational studies, where alcohol consumption can be linked directly to an individual's risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink."

Rimm EB et al 1999 in "Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors" reported that "61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol. On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease." and they concluded that "Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors"

Iestra JA 2005 in "Effect size estimates of lifestyle and dietary changes on all-cause mortality in coronary artery disease patients: a systematic review" presented " A literature search was performed on the effect of lifestyle and dietary changes on mortality in CAD patients. Prospective cohort studies and randomized controlled trials of patients with established CAD were included if they reported all-causes mortality and had at least 6 months of follow-up. The effect estimates of smoking cessation (relative risk [RR], 0.64; 95% CI, 0.58 to 0.71), increased physical activity (RR, 0.76; 95% CI, 0.59 to 0.98), and moderate alcohol use (RR, 0.80; 95% CI, 0.78 to 0.83) were studied most extensively. For the 6 dietary goals, data were too limited to provide reliable effect size estimates. Combinations of dietary changes were associated with reduced mortality (RR, 0.56; 95% CI, 0.42 to 0.74)."

Di Castelnuovo et al 2006 "Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies" used a meta analysis technique where the results of 34 studies were collated and reviewed. The study looked at the link between alcohol dose and mortality in both sexes in clinical trials conducted before the end of 2005 with over 1 million subjects. The scale of the overall analysis is therefore impressive.

The study reported that "A J-shaped relationship between alcohol and total mortality was confirmed in both men and women. Consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was inversely associated with total mortality or the chance of dying, maximum protection being 18% in women and 17% in men Higher doses of alcohol were associated with increased chances of dying with women having a lower level than men before the chances of dying increased. ".

Concluding that "Low levels of alcohol intake (1-2 drinks per day for women and 2-4 drinks per day for men) are inversely associated with total mortality in both men and women. Our findings, while confirming the hazards of excess drinking, indicate potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival."

Patra J et al 2010 "Alcohol consumption and the risk of morbidity and mortality for different stroke types--a systematic review and meta-analysis" reported "The dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity." and concluded that "These results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed."

Ronksley PE  2011 "Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis" reported "The pooled adjusted relative risks for alcohol drinkers relative to non-drinkers in random effects models for the outcomes of interest were 0.75 (95% confidence interval 0.70 to 0.80) for cardiovascular disease mortality (21 studies), 0.71 (0.66 to 0.77) for incident coronary heart disease (29 studies), 0.75 (0.68 to 0.81) for coronary heart disease mortality (31 studies), 0.98 (0.91 to 1.06) for incident stroke (17 studies), and 1.06 (0.91 to 1.23) for stroke mortality (10 studies). Dose-response analysis revealed that the lowest risk of coronary heart disease mortality occurred with 1-2 drinks a day, but for stroke mortality it occurred with ≤1 drink per day. Secondary analysis of mortality from all causes showed lower risk for drinkers compared with non-drinkers (relative risk 0.87 (0.83 to 0.92))."

They concluded  "Light to moderate alcohol consumption is associated with a reduced risk of multiple cardiovascular outcomes."

Costanzo S 2011 "Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis" reported "previous studies evaluating whether different alcoholic beverages would protect against cardiovascular disease, a J-shaped relationship for increasing wine consumption and vascular risk was found; however a similar association for beer or spirits could not be established. An updated meta-analysis on the relationship between wine, beer or spirit consumption and vascular events was performed. Articles were retrieved through March2011 by PubMed and EMBASE search and a weighed least-squares regression analysis pooled data derived from studies that gave quantitative estimation of the vascular risk associated with the alcoholic beverages. From 16 studies, evidence confirms a J-shaped relationship between wineintake and vascular risk. A significant maximal protection-average 31% (95% confidence interval (CI): 19-42%) was observed at 21 g/day of alcohol. Similarly, from 13 studies a J-shaped relationship was apparent for beer (maximal protection: 42% (95% CI: 19-58%) at 43 g/day of alcohol). From 12 studies reporting separate data on wine or beer consumption, two closely overlapping dose-response curves were obtained (maximal protection of 33% at 25 g/day of alcohol). This meta-analysis confirms the J-shaped association between wine consumption and vascular risk and provides, for the first time, evidence for a similar relationship between beer and vascular risk. In the meta-analysis of 10 studies on spirit consumption and vascular risk, no J-shaped relationship could be found."

Krenz et al in the 2012 review, "Moderate ethanol ingestion and cardiovascular protection: From epidemiologic associations to cellular mechanisms" said the following:

"Abundant epidemiologic evidence and the results interventional mechanistic studies conducted in animal models and cell culture systems strongly support the notion that antecedent ethanol exposure at moderate levels confers protective cardiovascular effects."

"Given the well-established pathologic effects of heavy drinking, wine lovers world-wide no doubt rejoiced when large-scale epidemiological studies first emerged showing that regular consumption of light to moderate amounts of alcoholic beverages, in particular red wine, was associated with a cardio-protective effect. One of the first studies showing a significant negative association between alcohol consumption and the risk of a subsequent first myocardial infarction that was well-controlled for cigarette smoking and other risk factors was published in 1974 . Over the following 4 decades, numerous epidemiological studies including several meta-analyses have consistently reported that an average alcohol consumption in the range of 0.5 to 2 standard drinks per day reduces coronary heart disease-related risks and ischemic stroke compared to non-drinkers."

"Interestingly, initial work suggested that the protective effects associated with light to moderate intake of alcoholic beverages may be due to the polyphenols in grapes, wine, and dark beer. In particular, the stilbene resveratrol has been a major focus of research interest because this and other red wine constituent polyphenols exert powerful antioxidant actions, upregulate eNOS gene expression, enhance NO production and have been found to reduce morbidity and mortality due to cardiovascular disease. In the human diet, red wine is one of the richest sources of polyphenols and moderate red wine drinkers consume these compounds at levels well above the population average. Despite the demonstrated protective actions of resveratrol and flavonoids, discrimination between the effects of these red wine constituent polyphenols versus ethanol per se to induce protection associated with consumption of alcoholic beverages is controversial, in part owing to low levels of the former achieved in the blood following red wine ingestion. Indeed, flavonoids and other wine polyphenols are extensively metabolized during absorption, resulting in formation of glucuronidated, sulfated, and methylated derivatives of the parent polyphenol, which have not been extensively evaluated for their protective effects. As a consequence, the highest plasma concentrations achieved after ingestion of resveratrol-rich beverages by humans range between 1 and 10 μM. These concentrations are lower than those typically evaluated in cell culture models and in animal studies. To further complicate the distinction between ethanol- and resveratrol-specific effects, the downstream molecular mechanisms so far identified for the two compounds show substantial overlap."

"Some epidemiological studies have shown that consumption of red wine is more protective than other types of alcohol, whereas other studies failed to identify an additional advantage associated with red wine."

"The health effects of ethanol are dependent on the amount of alcohol consumed and the pattern of intake. Nearly all epidemiologic studies report a J-shaped curve, whereby light to moderate ethanol consumption (1-2 standard drinks per day) exhibit less risk for adverse cardiovascular events and overall mortality than abstainers, while heavy drinkers (3-4 or more drinks per day) demonstrate increased risk. As with liver injury induced by ethanol, this varies by sex, with women benefiting from 1 standard drink per day, whereas daily consumption of 1-2 drinks by males was associated with reduced total mortality. On the other hand, increased mortality occurs in females with daily intake of 2 or more alcohol beverages and in men consuming more than 3 drinks per day."

"The effects of light to moderate ethanol consumption appear to be most clearly related to cardiovascular benefits, with most studies reductions in risk for heart disease by 30-35% Regular alcohol consumption at low to moderate levels is associated with significant reductions in the incidence of myocardial infarction in both males and females, regardless of age in adults. Importantly, this effect was noted in higher risk populations, including individuals with diabetes, hypertension, hypercholesterolemia, known heart disease, or who are overweight, as well as in cigarette smokers."

"Cardiovascular disease risk is also lowered by moderate ethanol consumption in individuals adhering to healthy lifestyle behaviors. Indeed, it has been reported that men who exercised regularly for at least 30 min/day, abstained from smoking, adhered to a healthy diet, and maintained their body mass index at less than 25 kg/m2 derived a health benefit from regular alcohol intake at moderate levels, demonstrating a 40-50% reduction in risk for myocardial infarction. Moderate wine drinking also appears to strengthen the cardioprotective effects of fish consumption, an observation that links two important components of the Mediterranean diet, namely omega-3 fatty acids and wine."

In addition to reducing the incidence and severity of myocardial infarction, low to moderate alcohol consumption is also associated with lower risk for ischemic stroke, dementia, congestive heart failure, peripheral artery disease, intestinal and hepatic I/R injury, and frequency of Raynaud’s phenomenon."

"Although the concept that moderate intake of ethanol exerts protective effects in the cardiovascular system is now well accepted, important issues have been raised which challenge this premise. For example, it has been argued that uncontrolled confounding influences by lifestyle factors may play a role in the association between moderate alcohol intake and cardiovascular risk. Some work has led to the suggestion that individuals who regularly consume alcohol beverages exhibit healthier habits with regard to diet and/or exercise and enjoy superior sociodemographic factors, which could explain the reduced risk for ischemic myocardial disease . However, systematic review and meta-analysis of interventional studies directed at the association between alcohol consumption and disease markers associated with risk for cardiovascular disease in adults without known cardiovascular disease argues against this supposition, as do the results of studies designed to better control for confounding sociodemographic factors and differences in dietary patterns and exercise adherence.

"While the association between alcohol consumption and decreased cardiovascular risk is clear, it remains uncertain as to whether these correlative findings imply causation. However, a number of points regarding the aforementioned epidemiologic findings suggest that the association may indeed represent a cause-and-effect relationship. First, there is a temporal relation between alcohol use and prevention of cardiovascular disease. Second, greater protection is observed with increasing ethanol dose over the protective range of alcohol intake. Third, the protective association between ethanol consumption and adverse cardiovascular events has been consistently observed in diverse patient populations and in both men and women. Fourth, the reduction in risk remains significant even after the influences of potential confounders such as cigarette smoking, diet, and exercise are factored into the analysis. Fifth, the association is specific for lowering rates of cardiovascular disease but does correlate with protection in other conditions such as cancer. Finally, the coupling of the aforementioned epidemiologic associations with the interventional mechanistic studies discussed below, provides compelling support for the notion that ethanol intake may indeed confer protection against the deleterious effects of I/R."

Chiva-Blanch G 2013 "Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: evidences from human studies" stated "Heavy or binge alcohol consumption unquestionably leads to increased morbidity and mortality. Nevertheless, moderate alcohol consumption, especially alcoholic beverages rich in polyphenols, such as wine and beer, seems to confer cardiovascular protective effects in patients with documented CVD and even in healthy subjects." and " In conclusion, wine and beer (but especially red wine) seem to confer greater cardiovascular protection than spirits because of their polyphenolic content. However, caution should be taken when making recommendations related to alcohol consumption."

Knot et al 2015, "All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts" reported that "In unadjusted models, protective effects were identified across a broad range of alcohol usage in all age-sex groups. These effects were attenuated across most use categories on adjustment for a range of personal, socioeconomic, and lifestyle factors. After the exclusion of former drinkers, these effects were further attenuated. Compared with self reported never drinkers, significant protective associations were limited to younger men (50-64 years) and older women (≥65 years). Among younger men, the range of protective effects was minimal, with a significant reduction in hazards present only among those who reported consuming 15.1-20.0 units/average week (hazard ratio 0.49, 95% confidence interval 0.26 to 0.91) or 0.1-1.5 units on the heaviest day (0.43, 0.21 to 0.87). The range of protective effects was broader but lower among older women, with significant reductions in hazards present ≤10.0 units/average week and across all levels of heaviest day use. Supplementary analyses found that most protective effects disappeared where calculated in comparison with various definitions of occasional drinkers."

The authors concluded that "Beneficial associations between low intensity alcohol consumption and all cause mortality may in part be attributable to inappropriate selection of a referent group and weak adjustment for confounders. Compared with never drinkers, age stratified analyses suggest that beneficial dose-response relations between alcohol consumption and all cause mortality may be largely specific to women drinkers aged 65 years or more, with little to no protection present in other age-sex groups. These protective associations may, however, be explained by the effect of selection biases across age-sex strata."

 Stockwell et al published a new study in the March 2016 issue of the Journal of Studies on Alcohol and Drugs, "Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality."

The new study was a systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. A total of 87 studies were examined.

They reported that  "Without adjustment, meta-analysis of all 87 included studies replicated the classic J-shaped curve, with low-volume drinkers (1.3-24.9 gethanol per day) having reduced mortality risk (RR = 0.86, 95% CI [0.83, 0.90]). Occasional drinkers (<1.3 g per day) had similar mortality risk (RR = 0.84, 95% CI [0.79, 0.89]), and former drinkers had elevated risk (RR = 1.22, 95% CI [1.14, 1.31]). After adjustment for abstainer biases and quality-related study characteristics, no significant reduction in mortality risk was observed for low-volume drinkers (RR = 0.97, 95% CI [0.88, 1.07]). Analyses of higher-quality bias-free studies also failed to find reduced mortality risk for low-volume alcohol drinkers. Risk estimates for occasional drinkers were similar to those for low- and medium-volume drinkers."

Stockwell concluded that "Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking. These findings have implications for public policy, the formulation of low-risk drinking guidelines, and future research on alcohol and health."

Individual studies

Klatsky AL in 1992 "Alcohol and mortality" reported that "Heavier drinkers were at greater risk for death from noncardiovascular causes (relative risk at ≥ 6 drinks per day compared with no alcohol = 1.6, 95% Cl, 1.3 to 2.0) especially cirrhosis, unnatural death, and tobacco-related cancers. This alcohol-associated risk was higher in women (relative risk for death from all causes at ≥ 6 drinks per day = 2.2; Cl, 1.4 to 3.8) and younger persons (for persons < 50 years of age, relative risk for death from all causes at ≥ 6 drinks per day = 1.9; Cl, 1.3 to 2.9). Lighter drinkers were at lower risk for death from cardiovascular disease, especially coronary heart disease (relative risk at 1 to 2 drinks per day = 0.7; Cl, 0.6 to 0.9), independent of baseline risk, with the greatest reduction of risk in older persons. Lighter drinkers over 60 years of age also had a slightly lower risk for noncardiovascular death, but this finding was not independent of baseline coronary heart disease risk.

He concluded that  "Women and younger persons appear more susceptible to the increased mortality risk of heavy drinking. The reduced cardiovascular risk of lighter drinkers is more pronounced in older persons. Lower coronary disease prevalence may reduce the noncardiovascular mortality risk of lighter drinkers."

Doll R et al 1994, "Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors" reported that "Men were divided on the basis of their response to the 1978 questionnaire into two groups according to whether or not they had ever had any type of vascular disease, diabetes, or "life threatening disease" and into seven groups according to the amount of alcohol they drank. By 1991 almost a third had died. All statistical analyses of mortality were standardised for age, calendar year, and smoking habit. There was a U shaped relation between all cause mortality and the average amount of alcohol reportedly drunk; those who reported drinking 8-14 units of alcohol a week (corresponding to an average of one to two units a day) had the lowest risks. The causes of death were grouped into three main categories: "alcohol augmented" causes (6% of all deaths: cirrhosis, liver cancer, upper aerodigestive (mouth, oesophagus, larynx, and pharynx) cancer, alcoholism, poisoning, or injury), ischaemic heart disease (33% of all deaths), and other causes. The few deaths from alcohol augmented causes showed, at least among regular drinkers, a progressive trend, with the risk increasing with dose. In contrast, the many deaths from ischaemic heart disease showed no significant trend among regular drinkers, but there were significantly lower rates in regular drinkers than in non-drinkers. The aggregate of all other causes showed a U shaped dose-response relation similar to that for all cause mortality. Similar differences persisted irrespective of a history of previous disease, age (under 75 or 75 and older), and period of follow up (first five and last eight years). Some, but apparently not much, of the excess mortality in non-drinkers could be attributed to the inclusion among them of a small proportion of former drinkers.

Doll concluded that "The consumption of alcohol appeared to reduce the risk of ischaemic heart disease, largely irrespective of amount. Among regular drinkers mortality from all causes combined increased progressively with amount drunk above 21 units a week. Among British men in middle or older age the consumption of an average of one or two units of alcohol a day is associated with significantly lower all cause mortality than is the consumption of no alcohol, or the consumption of substantial amounts. Above about three units (two American units) of alcohol a day, progressively greater levels of consumption are associated with progressively higher all cause mortality."

Grønbaek M et al 2005, "Mortality associated with moderate intakes of wine, beer, or spirits." reported that "The risk of dying steadily decreased with an increasing intake of wine--from a relative risk of 1.00 for the subjects who never drank wine to 0.51 (95% confidence interval 0.32 to 0.81) for those who drank three to five glasses a day. Intake of neither beer nor spirits, however, was associated with reduced risk. For spirits intake the relative risk of dying increased from 1.00 for those who never drank to 1.34 (1.05 to 1.71) for those with an intake of three to five drinks a day. The effects of the three types of alcoholic drinks seemed to be independent of each other, and no significant interactions existed with sex, age, education, income, smoking, or body mass index. Wine drinking showed the same relation to risk of death from cardiovascular and cerebrovascular disease as to risk of death from all causes. "

They concluded that "Low to moderate intake of wine is associated with lower mortality from cardiovascular and cerebrovascular disease and other causes. Similar intake of spirits implied an increased risk, while beer drinking did not affect mortality."

Thun et al 1997 "Alcohol consumption and mortality among middle-aged and elderly U.S. adults" reported "Causes of death associated with drinking were cirrhosis and alcoholism; cancers of the mouth, esophagus, pharynx, larynx, and liver combined; breast cancer in women; and injuries and other external causes in men. The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6). The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers, with little relation to the level of consumption. The overall death rates were lowest among men and women reporting about one drink daily. Mortality from all causes increased with heavier drinking, particularly among adults under age 60 with lower risk of cardiovascular disease. Alcohol consumption was associated with a small reduction in the overall risk of death in middle age (ages 35 to 69), whereas smoking approximately doubled this risk."

Thun concluded "In this middle-aged and elderly population, moderate alcohol consumption slightly reduced overall mortality. The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco."

Leong et al in 2014 "Patterns of Alcohol Consumption and Myocardial Infarction Risk: Observations from 52 Countries in the INTERHEART Case-Control Study" reported " We included 12,195 cases of first MI and 15,583 age- and sex-matched controls from 52 countries. Current alcohol use was associated with a reduced risk of MI (compared to non-users, adjusted odds ratio 0.87; 95% CI 0.80-0.94, p=0.001), however the strength of this assocation was not uniform across different regions (region-alcohol interaction p<0.001). Heavy episodic drinking (≥6 drinks) within the preceding 24 hours was associated with an increased risk of MI (odds ratio 1.4; 95% CI 1.1-1.9, p=0.01). This risk was particularly elevated in older individuals (for age >65 years, odds ratio 5.3; 95% CI 1.6-18, p=0.008).".

They concluded that "In most participants, low levels of alcohol use are associated with a moderate reduction in the risk of MI, however the strength of this association may not be uniform across different countries. An episode of heavy drinking is associated with an increased risk of acute MI in the subsequent 24 hours, particularly in older individuals."

Gaziano JM et al 2000 "Light-to-moderate alcohol consumption and mortality in the physicians’ health study enrollment cohort" reported that "There were 3,216 deaths over 5.5 years of follow-up. We observed a U-shaped relationship between alcohol consumption and total mortality. Compared with rarely/never drinkers, consumers of 1, 2 to 4 and 5 to 6 drinks per week and 1 drink per day had significant reductions in risk of death (multivariate relative risks [RRs] of 0.74, 0.77, 0.78 and 0.82, respectively) with no overall benefit or harm detected at the ≥2 drinks per day level (RR = 0.95; 95% confidence interval (CI), 0.79 to 1.14). The relationship with CVD mortality was inverse or L-shaped with apparent risk reductions even in the highest category of ≥2 drinks per day (RR = 0.76; 95% CI, 0.57 to 1.01). We found no clear harm or benefit for total or common site-specific cancers. For remaining other cancers, there was a non-significant 28% increased risk for those consuming ≥2 drinks per day."

The study concluded "These data support a U-shaped relation between alcohol and total mortality among light-to-moderate drinking men. The U-shaped curve may reflect an inverse association for CVD mortality, no association for common site-specific cancers and a possible positive association for less common cancers."

Grønbaek M 2000 "Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer" stated that "During 257 859 person-years of follow-up, 4833 participants died. J-shaped relations were found between total alcohol intake and mortality at various levels of wine intake. Compared with nondrinkers, light drinkers who avoided wine had a relative risk for death from all causes of 0.90 (95% CI, 0.82 to 0.99) and those who drank wine had a relative risk of 0.66 (CI, 0. 55 to 0.77). Heavy drinkers who avoided wine were at higher risk for death from all causes than were heavy drinkers who included wine in their alcohol intake. Wine drinkers had significantly lower mortality from both coronary heart disease and cancer than did non-wine drinkers (P = 0.007 and P = 0.004, respectively)."

The authors concluded "Wine intake may have a beneficial effect on all-cause mortality that is additive to that of alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer."

In 2004, Britton, "Different measures of alcohol consumption and risk of coronary heart disease and all-cause mortality: 11-year follow-up of the Whitehall II Cohort Study" reported "A U-shaped relationship was found between volume of alcohol consumed per week and outcome. Compared to those who drank moderately (10-80 g alcohol per week), non-drinkers and those drinking more than 248 g per week had approximately a twofold increased risk of mortality. The optimal frequency of drinking was between once or twice a week and daily, after adjustment for average volume consumed per week. Those drinking twice a day or more had an increased risk of mortality (male hazard ratio 2.44 95% CI 1.31-4.52) compared to those drinking once or twice a week. Drinking only once a month or only on special occasions had a 50% increased risk of mortality. The usual amount consumed per drinking session was not indicative of increased health risk in this cohort."

They concluded that "Epidemiological studies should collect information on frequency of drinking in addition to average volume consumed in order to inform sensible drinking advice."

Buelens JW 2007 "Alcohol consumption and risk for coronary heart disease among men with hypertension" reported that "During follow-up, 653 patients with MI were documented. Compared with patients abstaining from alcohol, the haz-
ard ratio for participants with MI consuming 0.1 to 4.9 grams of alcohol per day was 1.09 (95% CI, 0.86 to 1.37); consuming 5 to 9.9 grams of alcohol per day was 0.81 (CI, 0.60 to 1.08 g/d); consuming 10 to 14.9 grams of alcohol per day was 0.68 (CI, 0.51 to 0.91 g/d); consuming 15 to 29.9 grams of alcohol per day was 0.72 (CI, 0.54 to 0.97 g/d); consuming 30 to 49.9 grams of alcohol per day was 0.67 (CI, 0.48 to 0.94 g/d); and consuming 50 ormore grams of alcohol per day was 0.41 (CI, 0.22 to 0.77 g/d) (P0.001 for trend). Associations were similar for fatal and non-fatal MI. Alcohol consumption was not associated with total death or death due to CVD. Risks for total and ischemic stroke for patients consuming 10 to 29.9 g of alcohol per day were 1.40 (CI,0.93 to 2.12) and 1.55 (CI, 0.90 to 2.68) compared with that of
abstainers. When corrected for measurement error in alcohol consumption, dietary variables, and body mass index, the hazard ratio for participants with MI per 12.5 grams per day increment of alcohol intake was 0.68 (CI, 0.46 to 1.00).

They concluded that "In this population of men with hypertension, moderate alcohol consumption was associated with a decreased risk for MI but not with risks for total death or death due to CVD. As in the general population, men with hypertension who drink moderately and safely may not need to change their drinking habits."

Holahan CJ et al 2012, "Wine Consumption and 20-Year Mortality Among Late-Life Moderate Drinkers" reported "After adjusting for all covariates, both high-wine-consumption and low-wine-consumption moderate drinkers showed reduced mortality risks compared with abstainers. Further, compared with moderate drinkers for whom a high proportion of ethanol came from wine, those for whom a low proportion of ethanol came from wine were older, were more likely to be male, reported more health problems, were more likely to be tobacco smokers, scored lower on socioeconomic status, and (statistical trend) reported engaging in less physical activity. Controlling only for overall ethanol consumption, compared with moderate drinkers for whom a high proportion of ethanol came from wine, those for whom a low proportion of ethanol came from wine showed a substantially increased 20-year mortality risk of 85%. However, after controlling for all covariates, the initial mortality difference associated with wine consumption was no longer significant."

Holahan concluded "Among older adults who are moderate drinkers, the apparent unique effects of wine on longevity may be explained by confounding factors correlated with wine consumption."





Alcohol and Cancer - A summary of the clinical evidence

healthy living

Risk explained

Relative risk

Relative risk is the number that tells you how much changing something can change your risk compared to your risk of not doing anything at all. It is expressed as a percentage decrease or increase. If something you do or take doesn't change your risk, then the relative risk reduction is 0% (no difference). If something you do or take lowers your risk by 50% compared to someone who doesn't do the same, then that action reduces your relative risk by 50%. If something you do doubles your risk, then your relative risk increases 200%.

Absolute risk 

Absolute risk is the size of your own risk. Absolute risk reduction is the number of percentage points your own risk goes down if you do something protective, such as losing weight. The size of your absolute risk reduction depends on what your risk is to begin with.

Hazard Ratios

A hazard ratio considers your absolute risk to be 1. If something you do or take doesn't change your risk, then the hazard ratio is 1. If something you do or take lowers your risk by 25% compared to someone who doesn’t take the same step, then that action makes your hazard ratio 0.75, which means that the risk is 75% of what it was without taking the step (so your risk is 25% lower). If something you do doubles your risk, then your hazard ratio is 2.0.

Intrinsic and Extrinsic risk of developing cancer

A study published in Nature January 2016, "Substantial contribution of extrinsic risk factors to cancer development" by Song Wu et al appeared to confirmed that many cancers are caused by so called extrinsic or environmental factors. 

External factors like smoking, diet, sun, HPV (Human Papilloma Virus) and exposure to toxic chemicals cause more cancer than intrinsic factors like random cell mutations. Intrinsic factors accounted for just 10% to 30% of people’s lifetime risk of getting cancer, whilst extrinsic risks accounted for 70% to 90% for most common cancer types. 

The results are at odds with the results of a study in January 2015 published in Science which found that cell division and random mutations in DNA play the major role in the development of cancer.  "Variation in cancer risk among tissues can be explained by the number of stem cell divisions", Cristian Tomasetti. They concluded that "Why do some tissues give rise to cancer in humans a million times more frequently than others? Tomasetti and Vogelstein conclude that these differences can be explained by the number of stem cell divisions. By plotting the lifetime incidence of various cancers against the estimated number of normal stem cell divisions in the corresponding tissues over a lifetime, they found a strong correlation extending over five orders of magnitude. This suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development. Remarkably, this “bad luck” component explains a far greater number of cancers than do hereditary and environmental factors."

So in summary, the situation is very confused!

Summary of evidence reviewing Cancer and Alcoholic drinks

Food, nutrition, physical activity and the prevention of cancer WCRF/AICR

In 2007 the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published the results of an analysis of the effects of food, nutrition and physical activity based on a pooling of many hundreds of clinical trials.  The study was called "Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. This has been described as the most comprehensive report ever produced on the links between lifestyle and cancer risk and is the most notable source of information on the link between alcohol and cancer. The WCRF/AICR analysis is ongoing and the next report is due 2017.

In 2015 Klatsky AL et al published "Alcohol Intake, Beverage Choice, and Cancer: A Cohort Study in a Large Kaiser Permanente Population" and reported that "With lifelong abstainers as referent, heavy drinking (≥ 3 drinks per day) was associated with increased risk of 5 cancer types: upper airway/digestive tract, lung, female breast, colorectal, and melanoma, with light-to-moderate drinking related to all but lung cancer. No significantly increased risk was seen for 12 other cancer sites: stomach, pancreas, liver, brain, thyroid, kidney, bladder, prostate, ovary, uterine body, cervix, and hematologic system. For all cancers combined there was a progressive relationship with all levels of alcohol drinking. These associations were largely independent of smoking, but among light-to-moderate drinkers there was evidence of confounding by inferred underreporting. Beverage choice played no major independent role."

Klatsky concluded "Heavy alcohol drinking is related to increased risk of some cancer types but not others. Because of probable confounding, the role of light-to-moderate drinking remains unclear."

Bowel cancer - increased risk at greater than 30g of alcohol per day but a mixed picture

The WCRF report states that "The evidence that consumption of alcohol of more than 30g/day of ethanol from alcoholic drinks is a cause of colorectal cancer in men is convincing, and probably also in women."

Cho et al in 2004 in their paper "Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies" saw that "In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. "

In 2007, Ferrari et al reported on the link between rectal and colon cancers in Europe concluding that "In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day."

The 2009 Park JY et al with participants from Norfolk concluded that "Total alcohol consumption was not associated with CRC risk before or after adjustment for age, sex, weight, height, and smoking status . No significant associations were observed between consumption of specific alcoholic beverages (beer, sherry, or spirits) and CRC risk when compared with non-drinkers after adjustment for lifestyle and dietary factors. Daily consumption of > or =1 unit of wine appeared inversely related to CRC risk (HR: 0.61, 95% CI: 0.40-0.94). No evidence was found for sex-specific relationships, and further exclusion of cases incident within 3 years of baseline did not change the associations observed. In this population-based UK cohort, we did not find any significant adverse effect of alcohol over the moderate range of intake on colorectal cancer risk.". So a 40% lower risk with daily consumption of wine!

In the 2010 UK study by Park et al, which looked at alcohol intake and risk of colorectal cancer (CRC) concluded that "No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. " (up to 30g/day).

Hjartaker et al in 2013 looked at "subsite specific dietary risk factors for Colorectal cancer: A review of cohort studies" . The paper stated that "Ten articles were included in the review. Three analyses for both sexes combined consistently showed a higher risk of rectal cancer with increasing alcohol consumption and no significant associations for any of the colon subsites . In the EPIC studyan increased risk was reported both for rectal and distal colon cancer, whereas in the UK dietary cohort consortium (part of which is included in the EPIC study) a significantly increased risk was found for distal colon cancer only."

Breast cancer - contradictory in part but appears to be evidence that alcohol increases relative risk at levels over 30g of alcohol per day

The WCRF report confirms high heterogenicity (inconsistent findings) between studies, "Twelve cohort studies investigated ethanol intake and all-age breast cancer.Eight cohort studies showed increased risk for the highest intake group when compared to the lowest which was statistically significant in six.Four studies showed decreased risk which was statistically significant in one. Meta-analysis was possible on nine cohort studies, giving a summary effect estimate of 1.10 (95% CI 1.06–1.14) per 10 g/day, with high heterogeneity. Heterogeneity could be partly explained by differential adjustment for age and reproductive history."

Kuper et al in 2000 "Alcohol and breast cancer risk: the alcoholism paradox" reported that "A population-based cohort study of 36 856 women diagnosed with alcoholism in Sweden between 1965 and 1995 found that alcoholic women had only a small 15% increase in breast-cancer incidence compared to the general female population. It is therefore apparent, contrary to expectation, that alcoholism does not increase breast-cancer risk in proportion to presumed ethanol intake."

In 2006 Terry et al reported on lifetime alcohol intake and breast cancer risk, stating "Consumption of 15-30 grams/day (approximately one to two drinks) throughout life was associated with a modest 33% increase in risk (odds ratio [OR] = 1.33, 95% confidence interval (CI) = 1.01-1.74), but heavier consumption (> or = 30 grams per day) was not. Risk did not vary with alcohol type (beer, wine, or hard liquor) or by patterns of use, such as recent use, intake prior to age 20 years, or whether use began at an early age. The association with lifetime intake was limited to women with a BMI < 25 (OR = 2.13, 95% CI = 1.29-3.54).".

Mørch et al 2007 published "Alcoholic drinking, consumption patterns and breast cancer amongst Danish nurses:a cohort study" stated that "The relative risk of breast cancer was 2.30 [Confidence interval (CI): 1.56–3.39] for alcohol intake of 22–27 drinks per week, compared to 1–3 drinks per week. Among alcohol consumers, weekly alcohol intake increased the risk of breast cancer with 2% for each additional drink consumed. Weekend consumption increased the risk with 4% for each additional drink consumed friday through sunday. Binge drinking of 4–5 drinks the latest weekday increased risk with 55%, compared with consumption of one drink. A possible threshold in risk estimates was found for consumption above 27 drinks per week. Conclusions: For alcohol consumption above the intake most frequently reported, the risk of breast cancer is increased. The risk is minor for moderate levels but increases for each additional drink consumed during the week. Weekend consumption and binge drinking imply an additional increase in breast cancer risk." 

*However, nurses who drank small amounts of alcohol reduced breast cancer risk compared with abstainers, an effect which persisted to 24g per day. Between 24 and 36g per day, risk doubled and then fell back to +25% over 36g. 

In 2008 Barnett et al in the paper, "Risk factors for the incidence of breast cancer: do they affect survival from the disease?" said that "Improved prognosis was seen with increasing current alcohol consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit of alcohol consumed per week."

Bessaoud et al in 2008 published "Patterns of alcohol (especially wine) consumption and breast cancer risk: a case-control study among a population in Southern France" and reported that "Women who had an average consumption of less than 1.5 drinks per day had a lower risk (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.34-0.97) when compared with nondrinkers. This protective effect was due substantially to wine consumption since the proportion of regular wine drinkers is predominant in our study population. Furthermore, women who consumed between 10 and 12 g/d of wine had a lower risk (OR = 0.51; 95% CI = 0.30-0.91) when compared with non-wine drinkers. Above 12 g per day of wine consumption, the risk of breast cancer increased, but the association was non-significant.

no association between the pattern of total alcohol consumption and breast cancer was found, the type of alcoholic beverage seemed to play an important role in this association. Our results support the hypothesis that there is a threshold effect that risk decreased or was not modified for consumption under a certain threshold. Above that threshold, risk increased, however. The drinking pattern of each type of specific beverage, especially wine, seems important in terms of alcohol-breast cancer association. Low and regular wine consumption does not increase breast cancer risk."

Chen et al in 2011 looked at moderate alcohol consumption and breast cancer risk reporting that " Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk."

Chen also published in 2011, "Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk." and reported "During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk." and "Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk."

Schutze et al 2011 "Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study" reported that " If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women."

*Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Participants 109 118 men and 254 870 women, mainly aged 37-70.

In 2013 McDonald et al published "Alcohol Intake and Breast Cancer Risk: Weighing the Overall Evidence" and concluded that "Moderate alcohol consumption has been linked to an approximate 30-50% increased risk in breast cancer. Case-control and cohort studies have consistently observed this modest increase. We highlight recent evidence from molecular epidemiologic studies and studies of intermediate markers like mammographic density that provide additional evidence that this association is real and not solely explained by factors/correlates of the exposure and outcome present in non-randomized studies. "

Liver Cancer - unclear as to the risks due to variable data but wine would appear to have little or no effect

The WCRF report states that there is "high heterogenicity" with a "dose response relationship apparent in case control but not cohort data".

"Data are available from 15 cohort studies. Eleven cohort studies showed increased risk for the highest intake group when compared to the lowest,which was statistically significant in two.Two studies showed non-significant decreased risk. Two studies stated that there was no significant difference but did not provide further data.. Heterogeneity is partially explained by differences in whether and how studies have adjusted for hepatitis virus status. Data are available from 33 case-control studies. Twenty-eight case-control studies showed increased risk for the highest intake group when compared to the lowest,which was statistically significant in 12 (one of these studies reported a non-significant decreased risk in women, but a statistically significant increased risk in men).Two studies showed non-significant decreased risk. Three studies stated that there was no significant effect on risk. Metaanalysis was possible on five studies, giving a summary effect estimate of 1.18 (95% CI 1.11–1.26) per drink/week, with high heterogeneity. A dose-response relationship is apparent from case-control but not cohort data."

"Three cohort studies and one case-control study reported separately on wine drinking. One cohort study showed non-significant increased risk with increased intake. Two studies stated that there was no significant effect on risk.The single case-control study showed non-significant increased risk."

Kidney (Renal) Cancer - evidence that alcohol reduces risk

The WCRF state state that "It is unlikely that alcohol increases the risk of kidney cancer, though a protective effect cannot be excluded".

Lee et al in 2007 reported on "Alcohol intake and renal cancer in a pooled analysis of 12 prospective studies" that in "A total of 1430 (711 women and 719 men) cases of incident renal cell cancer were identified. The study-standardized incidence rates of renal cell cancer were 23 per 100,000 person-years among nondrinkers and 15 per 100,000 person-years among those who drank 15 g/day or more of alcohol. Compared with nondrinking, alcohol consumption (> or = 15 g/day, equivalent to slightly more than one alcoholic drink per day) was associated with a decreased risk of renal cell cancer (pooled multivariable RR = 0.72, 95% confidence interval = 0.60 to 0.86; P(trend)<.001); statistically significant inverse trends with increasing intake were seen in both women and men. No difference by sex was observed (P(heterogeneity) = .89). Associations between alcohol intake and renal cell cancer were not statistically different across alcoholic beverage type (beer versus wine versus liquor) (P = .40)." and concluding  that "Moderate alcohol consumption was associated with a lower risk of renal cell cancer among both women and men in this pooled analysis."

Pelucchi C et al in 2008 in "Alcohol consumption and renal cell cancer risk in two Italian case control studies" reported "Compared with non-drinkers, the multivariate odds ratios (ORs) of RCC were 0.87 [95% confidence interval (CI) 0.73–1.04] for ≤4 drinks per day, 0.76 (95% CI 0.59–0.99) for >4 to ≤8 drinks per day and 0.70 (95% CI 0.50–0.97) for >8 drinks per day of alcoholic beverages, with a significant inverse trend in risk (P value = 0.01). The ORs were 0.85 (95% CI 0.71–1.02) for wine, 0.84 (95% CI 0.68–1.03) for beer and 0.86 (95% CI 0.70–1.05) for spirits consumption, as compared with abstainers. No trend in risk of RCC emerged with duration (P value = 0.94) and age at starting alcohol consumption (P value = 0.81). Results were consistent in men and women, as well as in strata of age, smoking and body mass index.". Pelucchi concluded that "This pooled analysis found an inverse association between alcohol drinking and RCC. Risks continued to decrease even above eight drinks per day (i.e. >100 g/day) of alcohol intake, with no apparent levelling in risk."

Stomach (Gastric) Cancer - evidence that moderate alcohol drinkers have lower incidence and particularly wine drinkers

Barstad B et al 2005 in "Intake of wine, beer and spirits and risk of gastric cancer" reported "The objective was to study prospectively the relation between quantity and type of alcohol and risk of gastric cancer. In a pooled database from three population studies conducted in 1964-1992, a total of 15,236 men and 13,227 women were followed for a total of 389,051 person-years. During follow-up 122 incident cases of gastric cancer were identified. Total alcohol intake itself was not associated with gastric cancer, but type of alcohol seemed to influence risk. Compared with non-wine drinkers, participants who drank 1-6 glasses of wine had a relative risk ratio of 0.76 (95% confidence interval (CI) 0.50-1.16), whereas those who drank >13 glasses of wine per week had a relative risk ratio of 0.16 (95% CI 0.02-1.18). Linear trend test showed a significant association with a relative risk ratio of 0.60 (95% CI 0.39-0.93) per glass of wine drunk per day. These relations persisted after adjustment for age, gender, educational level, body mass index, smoking habits, inhalation and physical activity. There was no association between beer or spirits drinking and gastric cancer." and  "In conclusion, the present study suggests that a daily intake of wine may prevent development of gastric cancer. "

Duell EJ et al 2011 "Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort" reported that "Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed.", and concluded that "Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort."

Tramacere I et al published in 2012 "A meta analysis on alcohol drinking and gastric cancer risk" reported "Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01-1.13] for alcohol drinkers and 1.20 (95% CI 1.01-1.44) for heavy alcohol drinkers (≥4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers=1.17, 95% CI 0.78-1.75) than for gastric cardia (RR=0.99, 95% CI 0.67-1.47) adenocarcinoma. The dose-risk model estimated a RR of 0.95 (95% CI 0.91-0.99) for 10 g/day and 1.14 (95% CI 1.08-1.21) for 50 g/day." and concluded that "This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking."

Gullet, throat, mouth (oesophageal, mouth, larynx, pharynx) Cancer - link with alcohol but small compared with smoking and evidence that wine has no effect

The WCRF state "There is ample and consistent evidence, both from case-control and cohort studies, with a dose-response relationship. There is robust evidence for mechanisms operating in humans. The evidence that alcoholic drinks are a cause of mouth, pharynx, and larynx cancers is convincing. Alcohol and tobacco together increase the risk of these cancers more than either acting independently. No threshold was identified."

On  mouth, pharynx, and larynx cancers "Twenty-six case-control studies and four ecological studies reported separately on wine drinking. Most of the case-control studies showed increased risk with increased intake which was statistically significant in less than half. Five studies showed decreased risk,which was statistically significant in one. Meta-analysis was possible on 11 case-control studies, giving a summary effect estimate of 1.02 (95% CI 1.01–1.03), with high heterogeneity.All studies adjusted for smoking. All four ecological studies showed statistically significant increased risk."

On Oesophagus and wine "Ten case-control studies,one crosssectional study and five ecological studies reported separately on wine drinking. All but one of the case-control studies showed increased risk with increased intake,which was statistically significant in seven.About half of the studies adjusted for smoking. The single cross-sectional study showed non-significant increased risk. Most ecological."

Prostate Cancer - evidence of reduced risk with wine

Schoonen WM 2005, "Alcohol consumption and risk of prostate cancer in middle-aged men." reported that "No clear association with prostate cancer risk was seen for overall alcohol consumption. Each additional glass of red wine consumed per week showed a statistically significant 6% decrease in relative risk (OR = 0.94; 95% CI = 0.90-0.98), and there was evidence for a decline in risk estimates across increasing categories of red wine intake (trend p = 0.02). No clear associations were seen for consumption of beer or liquor. Our present study suggests that consumption of beer or liquor is not associated with prostate cancer. There may be, however, a reduced relative risk associated with increasing level of red wine consumption. Further research is needed to evaluate the potential negative association between red wine intake and prostate cancer risk."

Key clinical evidence for alcohol (wine) and health

The following is a list of key clinical studies which have examined the impact of alcohol and wine consumption on health and risk of dying prematurely. The list of studies is by no means exhaustive but includes many of the pivotal ones which have been highly influential over the last few decades.

Studies relating to alcohol addiction have not been included as the literature evidence linking abuse with alcohol is well documented and generally associated with other psychological or social problems except in special groups such as teenagers or the mentally ill.

Alcohol and cancer

For a full review of the evidence for the association between alcohol and wine and different cancers see below.

Heart disease, Mortality and Alcohol

For a full review of the clinical data click on the link below.