Large 10-year genetic study finds no protective benefits to light drinking

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AlcoholEven light-to-moderate drinking increases blood pressure and the chances of having a stroke, according to a large genetic study of half a million people for 10 years, countering previous studies that one or two drinks a day could be protective.

BBC News reports the UK and Chinese researchers followed 500,000 Chinese people for 10 years. They say the findings are relevant to all populations and the best evidence yet on the direct effects of alcohol.

It is already known that heavy drinking is harmful to health and increases stroke risk – but some studies have suggested drinking small amounts can be good for the health, while others indicate there is no safe level of alcohol consumption.

The researchers, from the University of Oxford, Peking University and the Chinese Academy of Medical Sciences, found that: one to two drinks a day increased stroke risk by 10-15%; and four drinks a day increased the risk of having a stroke by 35%

For the purposes of their study, one drink was defined as either: a small glass of wine; a bottle of beer; a single measure of spirits

According to Professor David Spiegelhalter, from the University of Cambridge, that’s an increase in total stroke risk of 38% for every half a bottle of wine drunk per day. He said: “It is very roughly the opposite effect of taking a statin”, which are drugs prescribed by doctors to help lower cholesterol levels in the blood and prevent heart attacks and strokes. The study also found no evidence of light or moderate drinking having a protective effect, in other words, reducing the risk of stroke.

When it came to the effect of alcohol on heart attack risk, the researchers said the effects were not clear cut and more data needed to be collected over the next few years. “Claims that wine and beer have magical protective effects is not borne out,” said study author Professor Richard Peto, from the University of Oxford.

Dr Iona Millwood, study author and senior epidemiologist at the University of Oxford, said: “Our genetic analyses have helped us understand the cause and effect relationships.”

The researchers say in the report that their key message is that there is now clear evidence of no protective effect of moderate drinking on stroke. That means drinking even small amounts of alcohol each day can increase the chances of having a stroke.
This is reflected in the current UK guidance – which advises a limit of 14 units of alcohol a week, with several alcohol-free days to keep health risks low.

Dr Stephen Burgess, from the University of Cambridge, said there were some limitations to the study – that it only looked at a Chinese population and focused mainly on the drinking of spirits and beer, not wine. But he said the research reflected the culmination of many years of research into the impact of alcohol consumption.

“It strongly suggests that there is no cardiovascular benefit of light drinking and that risk of stroke increases even with moderate light alcohol consumption,” he said. “Risk of stroke increases proportionally with the amount of alcohol consumed, so if people do choose to drink, then they should limit their alcohol consumption.”

Professor Kevin McConway, emeritus professor of applied statistics at the Open University, said the study didn’t answer every question. “It has certainly advanced what we know about the role of alcohol in some diseases but it can’t be the last word,” he said. “The new study doesn’t tie down exactly how alcohol works to increase stroke risk but doesn’t appear to increase heart attack risk.”

Spiegelhalter, Winton professor for the public understanding of risk, at the University of Cambridge, said the study was making him waver. “I have always been reasonably convinced that moderate alcohol consumption was protective for cardiovascular disease, but now I am having my doubts,” he said.

Abstract
Background: Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink).
Methods: The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology—ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake.
Findings: 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14 930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week—ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1·58, 95% CI 1·36–1·84, p<0·0001) than for ischaemic stroke (1·27, 1·13–1·43, p=0·0001). For myocardial infarction, however, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0·96, 95% CI 0·78–1·18, p=0·69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0·0001). Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or myocardial infarction.
Interpretation: Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction.

Authors
Iona Y Millwood, Robin G Walters, Xue W Mei, Yu Guo, Ling Yang, Zheng Bian, Derrick A Bennett, Yiping Chen, Caixia Dong, Ruying Hu, Gang Zhou, Bo Yu, Weifang Jia, Sarah Parish, Robert Clarke, George Davey Smith, Rory Collins, Michael V Holmes, Liming Li, Richard Peto, Zhengming Chen

BBC News report
The Lancet article summary


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