Critique #292 – Long-term alcohol consumption and incident health risk conditions related to cardiometabolic risk markers: A 20-year prospective cohort study – 30 June 2025

Authors

Choi S., Park T., Je Y.

Citation

Addiction. 2025; May 21; https://doi: 10.1111/add.70092. Online ahead of print.

Author’s Abstract

Background Amid questions about a perceived association between low-to-moderate alcohol consumption and reduced cardiovascular risk from recent studies, research examining the impact of alcohol consumption on cardiometabolic risk markers has reported inconsistent results. We measured the association between long-term alcohol consumption and incident health risk conditions related to cardiometabolic risk markers.

Methods A prospective cohort analysis was conducted using data from a population-based cohort (2001–2020) of 4708 Koreans aged 40–69 years who were free of chronic diseases, including metabolic syndrome, at baseline. Alcohol consumption and incident cases related to cardiometabolic risk markers were assessed biennially using interviewer-administered questionnaires or health examinations. The average alcohol intake was calculated to reflect long-term consumption. Alcohol consumption was categorized as none or rarely (0–2 g/day), light (2 <−16 g/day, within guideline limits), medium (16 < −32 g/day) and heavy (>32 g/day).

Results After full adjustment for covariates, light, medium or heavy alcohol consumption was positively associated with metabolic syndrome [hazard ratio (HR) = 1.55, 95% confidence interval (CI) = 1.32–1.83], abdominal obesity (HR = 1.41, 95% CI = 1.17–1.70), hyperglycemia (HR = 1.91, 95% CI = 1.62–2.26), high blood pressure (HR = 2.04, 95% CI = 1.72–2.41) and hypertriglyceridemia (HR = 1.59, 95% CI = 1.30–1.93), with the results presented for heavy alcohol consumption only (p-values for trend <0.001 for all cases). By sex, positive associations between light alcohol intake and hyperglycemia and high blood pressure were observed only in women (p-values for interaction and p-values for trend <0.05 for all cases).

Conclusion Long-term light (within guideline limits), medium or heavy alcohol consumption appears to be positively and linearly associated with incident health risk conditions related to cardiometabolic risk markers. The threshold dose of alcohol for developing hyperglycemia and high blood pressure appears to be lower in women.

Forum Summary

Choi et al. (2025) investigate whether consuming alcohol may worsen existing health risk conditions, such as metabolic syndrome, hypertriglyceridemia, low HDL cholesterol, hyperglycaemia, and high blood pressure.

This is an interesting area that is not frequently investigated. It is relevant, however, because dietary guidelines on alcohol consumption, which are meant for apparently healthy individuals, usually advise drinking no more than 1 or 2 US glasses of an alcoholic beverage daily. An underlying disease can place a strain on the body’s physiology and, as a result, worsen the condition.

It appears that the moderate drinking group (up to 32 g alcohol per day) has increased relative risks for five out of eight health risk conditions, which means that this group, which already had an increased risk of abdominal obesity, also faced a higher risk of metabolic syndrome and other factors. The question is whether drinking up to 32 g of alcohol daily directly causes these risk increases, or if other health risks are partly responsible.

Risks for light drinkers compared to non-drinkers were approximately 1.00 or 1.01 for three outcomes and below 1.00 for five outcomes, including a value of 0.86 for metabolic syndrome. Applying a linear model to interpret these associations would be inappropriate, as linearity only applied to two of the eight health risks examined. These limitations weaken the overall assertion that any alcohol consumption increases risks in this group of unhealthy individuals. 

Forum Comments

Background

Long-term alcohol consumption and health is a longstanding topic in scientific literature. Initially, the association between alcohol consumption and total mortality was studied. These first studies showed a reduced risk of mortality in both men (Blackwelder et al., 1980; Boffetta & Garfinkel, 1990) and women (Fuchs et al., 1995) for moderate drinkers. These findings have been confirmed over the years up to recently (Di Castelnuovo et al., 2022; Muraki et al., 2023; Neumann et al., 2022).

As a follow-up, researchers were interested in identifying the diseases that were negatively associated with moderate drinking and contributed to the reduced mortality risk. Further research showed that moderate alcohol consumption was associated with a reduced risk for cardiovascular diseases, mainly with a reduced risk of myocardial infarction (Hennekens et al., 1978; Klatsky et al., 1974). These findings are also confirmed by recent epidemiological research (Muraki et al., 2023; Tian et al., 2023).

Cardiometabolic risk markers are indicators or factors that increase the likelihood of developing cardiovascular diseases and type 2 diabetes. They include traditional risk factors like high blood pressure, high cholesterol, insulin resistance and obesity, and biomarkers like the inflammation marker hsCRP and hypertriglyceridemia (Kempel et al., 2021, Tahir and Gerszten, 2023).

Nutrition interventions indicated that the mechanisms underlying a protective cardiovascular effect may include increased HDL cholesterol levels, improved haemostasis, and improved glucose homeostasis (Brien et al., 2011, Mukamal et al., 2006, Hendriks, 2020).

Some scientists and public health practitioners criticize these epidemiological findings (Zhao et al., 2017). They believe that methodological issues may have confounded these findings. Alternatively, moderate drinking may contribute to unknown risks related to cardiovascular or other diseases. The prospective cohort study by Choi et al. (2025) contributes to the discussion by researching the impact of alcohol consumption on cardiometabolic risk markers. The authors conclude that inconsistent results have been reported and that the association between long-term alcohol consumption and incident health risk conditions related to cardiometabolic risk markers needs further study. They also conclude that long-term light, medium, and heavy alcohol consumption appears to be positively and linearly associated with incident health risk conditions related to cardiometabolic risk markers.

Critique

This paper by Choi et al. (2025) investigates whether consuming alcohol may worsen existing health risk conditions. This is an interesting area that is not frequently investigated. In general, dietary guidelines on alcohol consumption advise drinking no more than 1 or 2 US glasses of an alcoholic beverage daily (National Academies of Sciences, Engineering, 2025). They are intended for apparently healthy persons. Underlying disease may place a burden on the physiology of the diseased body and, as such, worsen a condition.

This population was an unhealthy population. Usually, healthy populations are studied to ensure that the relative risks attributable to alcohol consumption are rather than the additional risks attributable to underlying diseases or general poor health. The condition of this group is not only reflected in their poor health, but also evident from their poor lifestyle, most have a low-quality diet (in approximately 50% of this population) and low physical activity (on average less than 150 MET/week).

This paper is, however, written as if alcohol consumption will be detrimental for all who consume alcohol. Unfortunately, the authors did not clearly state that this study did not include healthy persons who would respond quite differently to light and moderate alcohol consumption (Blackwelder et al., 1980; Fuchs et al., 1995; Neumann et al., 2022; Tian et al., 2023). The authors present and discuss their findings as contradictory to those studies concerning healthy individuals.

This longitudinal study reports on a relatively small group of people (4,708 persons in total) consisting of 2,352 men and 2,356 women, all having metabolic syndrome defined as having at least three of the following four conditions: metabolic syndrome, hypertriglyceridemia, low HDL cholesterol, hyperglycaemia, and high blood pressure. This small group was further split into even smaller groups having abdominal obesity, hyperglycaemia, high blood pressure, hypertriglyceridemia, low HDL-cholesterol or high hsCRP. This allowed the researchers to analyse the association with alcohol consumption in these smaller groups, sometimes consisting of several tens of persons. Groups of this size may be close to or even under the minimum needed for reliable epidemiological analysis. In Table 3, men and women are separated, leading to group sizes of four or 10 with no women in the heavy drinking group. This may seriously hamper the authors’ overall conclusions and specifically those on heavy alcohol consumption.

Furthermore, it is unclear whether those in the hypertensive group, for instance, had one or more other health risk conditions. Therefore, the groups generated for analysis may be very heterogeneous, which makes it hard to draw accurate conclusions.

The results show that light drinking (up to 16 g alcohol per day for both men and women) does not change much in these persons with health risks. Of the eight investigated health risk conditions, only two have an increased relative risk in light drinkers, namely persons with hyperglycaemia and persons with hypertension. These observations are also surprising. A previous larger study in hypertensives showed that those drinking in moderation may or may not have increased their hypertension but had a decreased risk for myocardial infarction (Beulens et al., 2007). Also, increases in alcohol consumption over time were associated with a lower risk of type 2 diabetes among initially light drinkers (Joosten et al., 2011). This type of study is, unfortunately, not discussed.

The medium drinking group (up to 32 g alcohol per day) has increased relative risks for five out of eight health risk conditions with relative risks of about 25-20%, which means that this group which had an increased risk of abdominal obesity also had an increased risk of metabolic syndrome, hyperglycaemia, hypertriglyceridemia and high blood pressure, which makes it hard to distinguish cause and effect in these groups. Is drinking up to 32 g of alcohol per day leading to these risk increases or are other health risks (partly) responsible?

Their conclusion that long-term light, medium, or heavy alcohol consumption appears to be positively and linearly associated with incident health risk conditions is based on trend analysis. Whereas the authors could calculate a significant trend for six out of eight health risks, linearity only existed for two out of eight health risks evaluated. Therefore, this conclusion overstates the findings and may be perceived as tendentious.

Specific Comments from Forum Members

Forum Member Harding considers that, as already pointed out, “this was an unhealthy cohort, so the main finding that long-term alcohol intake within guideline limits may still increase the risk of developing chronic disease, including CVD for the general population cannot be reasonably drawn.

I was pleased to see that possible mechanisms were proposed to explain the observed associations in the Discussion, but some of those proposed do not apply to moderate drinkers.  For example, Reference #25 concluded that those consuming seven or more drinks per week (an average of one drink per day) had a higher risk of developing metabolic syndrome. The mechanisms proposed to explain this (Reference #48, #49 and #50), however, only apply to very heavy drinkers, that is, alcohol-related liver disease, alcohol-induced hypertension, and alcohol-induced liver damage in rats, respectively, and, therefore, are not relevant to moderate consumers.

Forum Member Ellison noted that“many of the subjects in the cohort used for these analyses already had cardiovascular risk factors or disease at baseline.  The investigators excluded more than 3,500 such subjects from their analyses. The remaining subjects may not, however, have represented the general population, making the applicability of their findings to other groups uncertain. 

The investigators were able in their multivariable analyses to adjust for age, BMI, education, income, smoking status, and other relevant factors, but alcohol exposure was estimated mainly based on the reported number of drinks.  A crucial aspect for assessing alcohol’s effects is drinking patterns, including whether alcohol was consumed with or without food, drinking frequency, and beverage type, with wine consumption with food showing the most consistent health benefits.  In some secondary analyses, the investigators separated subjects mainly consuming spirits from a category labelled ‘non-liquor’. The effects for wine drinkers, however, were combined with those of beer, rice wine, and some Korean beverages. 

More importantly, it seems that the investigators only conducted linear analyses of alcohol and outcomes, while evidence suggests that alcohol’s relationship with disease is nonlinear; often, a J-shaped curve is observed. Focusing on data for men only (since the number of women was too small for reliable results), it is evident that for the eight outcomes studied (metabolic syndrome, obesity, lipid abnormalities, inflammation markers, etc.), the so- called’ light drinkers’- those within recommended limits- did not exhibit the same effects as heavier drinkers. For the main outcomes in men (from Table 3), the hazard ratios for light drinkers versus non-drinkers were roughly 1.00 or 1.01. 01 for three outcomes and below 1.00 for five outcomes, including a value of 0.86 for metabolic syndrome. Using a linear model to interpret these associations would be inappropriate.  These limitations weaken the overall claim that any alcohol consumption increases risk. 

Finally, although the outcomes were clearly defined, it would have been helpful for the investigators to include data on major health events related to these risk factors, such as myocardial infarction, other types of coronary heart disease, ischaemic stroke, and mortality. These outcomes are essential for prevention efforts. Given the cohort size, there may have been sufficient occurrences of such serious outcomes to report on them as well.

Forum member McIntosh states that “this is a curious piece. Given the literature to which the authors refer, one might have expected a retrospective study on the topics that these traditionally examine, like CHD, cancer, stroke, and possibly diabetes. None of these are considered here; instead, the authors analyse metabolic syndrome, abdominal obesity and hyperglycaemia etc. The main focus of the paper is to analyse the durations of the onset of these maladies. Their main result is that respondents who drink more will suffer these maladies significantly earlier than those in the lowest drinking category.

The data used is about half the data available since respondents with disease histories are eliminated from consideration. The average age of the sample is around 50 years. It is unclear what the consequences of this selection are on the results, since many in the population suffer from these maladies at ages younger than 50 years. To what extent does eliminating respondents with CHD or other diseases remove respondents who suffer from metabolic syndrome (MS)?  I would like to have seen the model run on the entire sample using diseases like CHD, cancer, for example, as regressors.

In Table 2, the numbers of MS are given for each alcohol consumption category. Means for the four alcohol categories calculated from this data are 0.446, 0.398, 0.498, and 0.527. First, one would like to know whether there are significant differences in these means. This can’t be done since the authors provide no information on the standard deviations of these four outcomes. Second, it would also be of interest to see whether the events themselves are explained by alcohol consumption. These outcomes are binary, and a simple logistic model could be used to get this result.

References

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The following ISFAR members provided comments on and endorsed this critique:

Henk Hendriks, PhD, Netherlands

Creina Stockley, PhD, MBA, Independent consultant and Adjunct Senior Lecturer in the School of Agriculture, Food and Wine at the University of Adelaide, Australia

Richard Harding, PhD, Formerly Head of Consumer Choice, Food Standards and Special Projects Division, Food Standards Agency, UK

R. Curtis Ellison, MD, Section of Preventive Medicine/Epidemiology, Boston University School of Medicine, Boston, MA, USA

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway

James McIntosh, PhD, Retired Professor of Economics, Concordia University, Montreal, Canada

Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

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