So Where Are We up to with Alcohol and Health?

First, let me come clean – I am a moderate drinker. No doubt about it. Five nights a week on a mean of two glasses, and two nights on a mean of three glasses. These are average sized glasses, so let’s say 24 units (1.5 x 16) per week. I love wine and seek good news…

The story so far:

  1. There is a ‘J-shaped’ curve of the association between alcohol and many diseases.[1]
    093 - Alcohol j curve
    * Cancer does not follow this pattern. Cancers of mouth, throat and gullet are almost certainly increased, and probably breast too.[2]
  2. But Mendelian randomisation (inheriting genes predisposing to alcohol consumption) does not show a J-shaped curve – risk rises incrementally.[3]
  3. Longitudinal studies show that, on one dimension of cognition, decline is faster in linear relationship to alcohol dose, and this finding ‘triangulates’ with a drop in right-sided hippocampal volume (detected by MRI) in relation to alcohol intake.[4]

Conclusion: the J-shaped curve is an artefact of selection bias.

So what’s new? First, a meta-analysis of longitudinal studies [5] shows a substantial protective effect against dementia for low to moderate alcohol intake (RR 0.63, 0.53-0.75) and also in Alzheimer’s disease (RR 0.57, 0.44-0.74). Second, there some evidence from these studies that chronic drinking is protective of cognitive decline, while episodic drinking is harmful at the same total intake. Third, a new longitudinal study suggests that chronic (i.e. non-binge) drinking is indeed protective against cognitive impairment in older people.[6]

This new study (the Rancho Bernardo study) is based on a cohort of 6,339 middle-class residents of a suburb in San Diego. Of the surviving residents, 2,479 attended a research clinic in 1985 where detailed alcohol histories were elicited. The participants were followed up every four years with cognitive tests. Co-variates were collected and added sequentially to a logistic regression model, starting with those (e.g. sex and age) least likely to be on the causal pathway linking alcohol to outcome. The APOE genotype was examined as an interaction term. Potential confounding effects of diet were also examined. Various sensitivity analyses were conducted. Drinking up to 3 units per day after age 65, and 4 units per day at a younger age significantly increased the chance of healthy survival, with an odds ratio exceeding 2. The J curve is there in the data, with the probability of healthy longevity increasing through no, low, moderate and even heavy drinking, only to decline again when drinking was ‘excessive’ (meaning over 4 drinks per day aged under 65 and over 3 per day for men over 65, and 3 or 2 drinks per day in younger or older women. And, yes, more frequent drinking is better than episodic drinking at a given intake – ORs of Cognitively Health Longevity increased three-fold with daily drinking vs. not drinking at all, but only two-fold if drinking was ‘infrequent’. Conclusions were robust to various sensitivity analyses.

What is the truth? No person knoweth it! But the idea that regular, moderate drinking offers some protective effects to trade-off against cancer risk has empirical support. I wonder if there are different genes predisposing to binge vs. steady drinking? I hypothesise that the genes are associated with poor impulse control leading to binge drinking. I hope that this hypothesis will now be put to an empirical test. Another question, of course, concerns the type of drink. The middle-class people in the Rancho Bernardo study may have favoured wine over other drinks – I hope so!

— Richard Lilford, CLAHRC WM Director

References:

  1. Di Castelnuovo A, Costanzo  S, Bagnardi  V, Donati  MB, Iacoviello  L, de Gaetano    Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies.  Arch Intern Med. 2006; 166(22): 2437-45.
  2. Lilford RJ. Oh Dear – Evidence Against Alcohol Accumulates. NIHR CLAHRC West Midlands News Blog. 7 December, 2017.
  3. Holmes MV, Dale CE, Zuccolo L, et al. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014; 349: g4164.
  4. Lilford RJ. Alcohol and its Effects. NIHR CLAHRC West Midlands News Blog. 18 August, 2017.
  5. Peters R, Peters J, Warner J, Beckett N, Bulpitt C. Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 2008; 37(5): 505-12.
  6. Richard EL, Kritz-Silverstein D, Laughlin GA, Fung TT, Barrett-Connor E, McEvoy LK. Alcohol Intake and Cognitively Healthy Longevity in Community-Dwelling Adults: The Rancho Bernardo Study. J Alzheimer’s Dis. 2017; 59: 803-14.
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