The highest probability of reaching 90 years was found for those drinking 5– < 15 g alcohol/day; although not significant, the risk estimates also indicate to avoid binge drinking

Alcohol consumption in later life and reaching longevity: the Netherlands Cohort Study. Piet A van den Brandt, Lloyd Brandts. Age and Ageing, afaa003, February 9 2020. https://academic.oup.com/ageing/advance-article/doi/10.1093/ageing/afaa003/5730334

Abstract
Background: whether light-to-moderate alcohol intake is related to reduced mortality remains a subject of intense research and controversy. There are very few studies available on alcohol and reaching longevity.

Methods: we investigated the relationship of alcohol drinking characteristics with the probability to reach 90 years of age. Analyses were conducted using data from the Netherlands Cohort Study. Participants born in 1916–1917 (n = 7,807) completed a questionnaire in 1986 (age 68–70 years) and were followed up for vital status until the age of 90 years (2006–07). Multivariable Cox regression analyses with fixed follow-up time were based on 5,479 participants with complete data to calculate risk ratios (RRs) of reaching longevity (age 90 years).

Results: we found statistically significant positive associations between baseline alcohol intake and the probability of reaching 90 years in both men and women. Overall, the highest probability of reaching 90 was found in those consuming 5– < 15 g/d alcohol, with RR = 1.36 (95% CI, 1.20–1.55) when compared with abstainers. The exposure-response relationship was significantly non-linear in women, but not in men. Wine intake was positively associated with longevity (notably in women), whereas liquor was positively associated with longevity in men and inversely in women. Binge drinking pointed towards an inverse relationship with longevity. Alcohol intake was associated with longevity in those without and with a history of selected diseases.

Conclusions: the highest probability of reaching 90 years was found for those drinking 5– < 15 g alcohol/day. Although not significant, the risk estimates also indicate to avoid binge drinking.

Keywords: alcohol, longevity, aging, dose–response relationship, mortality, cohort studies, older people

Discussion

In this large prospective study, we found statistically significant positive associations between alcohol intake and the probability of reaching 90 years in both men and women. Overall, the highest probability was found in those consuming 5– < 15 g/d alcohol, which corresponds to 0.5–1.5 glass of alcoholic beverage per day. The exposure–response relationship was significantly non-linear in women, but not in men. Whereas the probability of longevity was decreasing in women with alcohol intakes above 15 g/d, it remained elevated at higher alcohol consumption levels in men. In beverage-specific analyses, wine intake was positively associated with longevity (notably in women), whereas liquor was positively associated with longevity in men and inversely in women. Binge drinking was not significantly associated with longevity, but the risk estimates indicate to avoid binge drinking. In subgroup analyses, alcohol intake was associated with longevity in those with or without a history of selected diseases.

Previous prospective studies on longevity from the US and France that reported on alcohol were rather limited (no alcohol focus) and found no significant associations using longevity cut-offs of 75 [12] and 90 years [13, 25]. However, higher alcohol intakes were seen in survivors compared to non-survivors [25], and in subsequent analyses (85+ years) of the Framingham Heart Study [26]. The Physicians Health Study amongst US male physicians (survival cut-off 90) reported small and non-significantly increased chances of longevity for various drinking categories compared to rarely/never alcohol drinkers, with no dose–response relationship [13]. The association between alcohol drinking and longevity was studied twice in the Honolulu Heart Program (HHP) amongst Japanese-American men using 85 years as longevity cut-off [10, 11]. Heavy alcohol intake, measured at baseline age 45–68 years, was significantly inversely related to longevity (OR = 0.63, for 3+ drinks/day versus drinking less) [10]. In the second analysis, moderate-heavy alcohol intake around 75 years was also significantly inversely related to longevity (OR = 0.66, for drinking >14.5 g/day versus less) [11]. The fact that the HHP study was conducted amongst men of Japanese ancestry may (partly) explain the more negative association of alcohol with longevity, and suggests a potential mechanism. It is known that East Asians are less efficient alcohol metabolizers due to a common loss-of-function variant of the ALDH2-gene, which decreases breakdown of acetaldehyde, the first, toxic alcohol metabolite [27]. It could be that those who nevertheless drink experience a higher mortality risk.

Overall, the results of previous longevity studies seem quite limited. Our detailed analyses show significantly positive associations between alcohol and longevity in both men and women, which is in agreement with the PHS [13]. Overall in men and women combined in the NLCS, the highest probability of reaching 90 was found in those consuming 5– < 15 g/d alcohol, with a HR of 1.36 compared to abstainers. Women experience higher blood alcohol concentrations than men of similar weight due to lower total body water [15]. Thus, adverse effects of higher alcohol intakes may appear earlier in women. This might explain the non-linear exposure–response relationship in women and not in men. We also found that wine intake was positively associated with longevity, whereas liquor was positively associated with longevity in men, and inversely in women. Before speculating on reasons for these beverage differences, future longevity studies are needed to replicate these sex-specific findings, with those on pattern and binge drinking. In mortality studies, there was no clear indication for sex differences [2, 5], and although beneficial associations with wine have been described for mortality, e.g. [2], this topic remains controversial.

As in observational studies on alcohol and mortality [1, 2, 8], studies on alcohol and longevity may be hampered by possible biases (selection and residual confounding biases). Here, selection bias can refer to abstainer bias (when the reference category of non-drinkers also includes sick quitters), the healthy drinker/survivor bias (when cohorts of older participants may be overrepresented by healthier drinkers who may have survived adverse effects of alcohol). Reverse causation may occur because health status may influence alcohol drinking [8], which could be addressed by restricting analyses to healthy people at baseline. Incomplete adjustment for confounding factors may lead to residual confounding. In our longevity analysis, we tried to address these possible biases by: (i) excluding ex-drinkers from the reference category; (ii) limiting analyses to stable drinkers and abstainers by taking alcohol consumption 5 years before baseline into account; (iii) restricting analyses to participants without prevalent diseases and (iv) adjusting for a large range of possible confounders with detailed information. These analysis strategies do not necessarily provide a full remedy against all possible biases [8], but these were the possibilities with the available data from our cohort. For example, we had no information on lifetime alcohol consumption or consumption on various ages during lifetime, so our analysis of past consumption was limited. After excluding ex-drinkers from the reference category, the analyses in the stable subgroup were essentially similar to what was seen overall. We also found that alcohol intake was associated with longevity in the subgroup without a history of selected diseases. Still, other diseases might have affected alcohol use or longevity. Residual confounding by socioeconomic status is also possible, because we only controlled for educational level.

It should be noted that the percentages of never drinkers were relatively high in the NLCS: 15% in men and 35% in women, making this common behaviour a logical reference category. These percentages were substantially higher than in other cohorts, e.g. 8% in male and 16% in female PLCO-participants [2], and 6% in male and 16% in female EPIC-participants [28]. Strengths of the NLCS are the prospective design and high completeness of follow-up, making information bias and selection bias due to differential follow-up unlikely. The validation study of the food frequency questionnaire has shown that it performs relatively well with respect to alcohol [19], but measurement error may still have attenuated associations. The lack of possibilities to update alcohol intake or other lifestyle data during follow-up may have resulted in some attenuated associations too. Our study was aimed at measuring alcohol intake at 68–70 years. Therefore, our study results are limited to alcohol drinking in later life; future longevity studies preferably include lifetime consumption. The alcohol measures in our study were not aimed to get an all-encompassing indication of risky drinking, like in the Alcohol Use Disorders Identification Test/AUDIT [29]. Our cut-off for binge drinking (>6 drinks per occasion) as used in the 1980s/1990s [29, 30] is somewhat higher than current cut-offs [29]. Because we were interested in the association of late life drinking with longevity, our study likely examined a resilient population that survived already until 68 years despite possible earlier risky drinking.

While older people perceive themselves as controlled responsible drinkers, according to a recent thematic synthesis of qualitative studies, they consider alcohol use often as important part of social occasions, and report that alcohol helps creating feelings of relaxation [31]. A possible beneficial effect of light-moderate alcohol intake on longevity (with inverted J-shaped dose-response on longevity) may also be related to hormesis [32, 33]. With higher consumption in older people, medication may be negatively affected by alcohol, and there is decreased physiological tolerance [34].

In conclusion, in this prospective study of men and women aged 68–70 years at baseline, we found the highest probability of reaching 90 years of age for those drinking 5– < 15 g alcohol/day. This does not necessarily mean that light-to-moderate drinking improves health. The estimated RR of 1.36 implies a modest absolute increase in this probability and should not be used as motivation to start drinking if one does not drink alcoholic beverages. Although no significant association was found, the risk estimates also indicate to avoid binge drinking.