https://orcid.org/0000-0002-7823-1402
Urinary tartaric acid, a specific biomarker of wine consumption, provides objective quantification of intake, minimizing misclassification. The study demonstrates that moderate wine consumption, as assessed by urinary tartaric acid levels, is associated with reduced cardiovascular risk in a Mediterranean population at high CVD risk.
This editorial refers to ‘Urinary tartaric acid as a biomarker of wine consumption and cardiovascular risk: the PREDIMED trial’, by I. Domínguez-López et al., https://doi.org/10.1093/eurheartj/ehae804.
The relationship between alcohol consumption, particularly wine, and cardiovascular disease (CVD) risk remains a topic of ongoing debate despite decades of related research. Numerous studies have suggested that moderate wine consumption, often defined as one glass per day, preferably during meals, is associated with a reduced risk of total mortality and CVD.1 However, this apparent protective effect is clouded by persistent uncertainties. The paper by Inés Domínguez-López et al.,2 published in this issue of the European Heart Journal, sheds new light on this complex relationship by introducing an objective biomarker—urinary tartaric acid—as a measure of wine consumption and provides compelling evidence for its association with lower CVD risk.
The still unresolved debate on alcohol and cardiovascular health
Despite the wealth of epidemiological evidence supporting the cardiovascular benefits of moderate wine consumption, the question of whether wine truly protects against CVD still remains a matter of debate. This uncertainty is primarily due to the observational nature of the evidence, which is inherently limited by potential biases and confounders.3 Randomized controlled trials are the gold standard for establishing causal relationships, but ethical and practical challenges have precluded their use in studying alcohol consumption. Therefore, we must rely on observational studies, which, while informative, are prone to several potential types of bias. In more recent studies, however, the most important biases, such as exclusion of former drinkers from the reference group, participant selection, and lifestyle-related confounding factors, have been accounted for in order to achieve more accurate and reliable results.
One of the most important sources of bias in observational studies on alcohol and CVD is the assessment of alcohol consumption itself. Typically, studies rely on self-reported data, often collected through food frequency questionnaires. However, self-reports are subject to inaccuracies, including recall bias and social desirability bias. The latter, in particular, leads to under-reporting, where individuals may downplay their alcohol intake. This under-reporting can skew results, making it difficult to draw accurate conclusions about the relationship between alcohol consumption and CVD risk.4 Specifically, this under-reporting can distort the perceived minimum threshold of alcohol consumption required to observe cardiovascular benefits, when, in reality, the actual threshold may be higher than it appears if under-reporting occurs.
The need for objective measures
Given these challenges, there is a pressing need for objective, direct measures of alcohol consumption to strengthen the evidence base.3,4 The accuracy of methods used to evaluate alcohol consumption in the diet is a topic of ongoing debate, with the assumption that a significant portion of individuals provide inaccurate information, particularly those who claim to be abstinent or light drinkers. Humans, for various reasons, are often not truthful and tend to either deny or under-report their alcohol intake. Biomarkers, however, help detect the most notable discrepancies, which are typically cases of underestimation.5 Biomarkers, which can provide an unbiased reflection of exposure, offer a promising solution. In the context of wine consumption, urinary tartaric acid—a metabolite uniquely derived from wine—emerges as a particularly valuable biomarker.6 Unlike self-reported data, urinary tartaric acid levels can objectively quantify wine intake, thereby reducing the potential for misclassification and bias in studies of alcohol and health outcomes.
The study by Domínguez-López et al.2 represents a significant advancement in this field by using urinary tartaric acid as an objective biomarker for wine consumption within the PREDIMED trial, a large-scale study on cardiovascular health in a Mediterranean population.7 The authors show a strong correlation between urinary tartaric acid levels and self-reported wine consumption, supporting both the reliability of this biomarker as an indicator of wine intake and the validity of traditional self-reported wine consumption assessments.
The cardiovascular benefits of moderate wine consumption
Most notably, the study finds that moderate wine consumption, as measured by tartaric acid levels, is associated with a lower risk of CVD. Participants with tartaric acid concentrations of 3–12 and 12–35 μg/mL (equivalent to 3–12 and 12–35 glasses per month) exhibited hazard ratios (HRs) of 0.62 (95% confidence interval [CI] 0.38–1.00) and 0.50 (95% CI 0.27–0.95), respectively, compared with those with lower tartaric acid levels (corresponding to < 1 glass per month). This finding aligns with the broader literature suggesting that light-to-moderate wine consumption may confer cardiovascular benefits.8
Interestingly, the study also provides intriguing evidence that changes in urinary tartaric acid levels over time are relevant to cardiovascular risk. Participants with tartaric acid levels >3 µg/mL at baseline, who experienced an increase over 1 year, had a 59% lower risk of CVD compared with those whose levels decreased during the same period. This dynamic association suggests that not only the baseline level of wine consumption but also changes over time may influence CVD risk. It underscores the importance of considering both baseline exposure and longitudinal changes in future studies of alcohol/wine and health.
However, it is critical to note that the study’s findings reinforce the notion that these cardiovascular benefits are limited to moderate wine consumption. Higher levels of tartaric acid, corresponding to non-moderate wine consumption, were indeed not associated with a reduced risk of CVD. This observation is consistent with a large literature, which cautions against heavy alcohol consumption due to its well-documented adverse health effects.9 Thus, the results of Domínguez-López et al.2 reinforce the message that any potential benefits of wine are limited to moderate consumption and that exceeding these levels may negate its cardiovascular advantages.
Implications for future research
The implications of this study are far-reaching, particularly in the context of nutritional epidemiology and public health recommendations. The use of an objective biomarker such as urinary tartaric acid represents a significant methodological advancement in alcohol research. It offers a more accurate and reliable measure of wine consumption, which could help resolve some of the ongoing debates about the health effects of alcohol.
Moreover, the findings suggest that wine consumption in real-life conditions, unaffected by the often artificial influences of a clinical trial setting, might have a more beneficial impact on cardiovascular health than previously thought. This observation is supported by evidence from other studies,10 including the Health Professionals Follow-up Study11 and the Global Burden of Disease Study 2020.12
However, Domínguez-López et al.2 also highlight the complexity of studying the effects of alcohol on health. While biomarkers such as urinary tartaric acid provide a more objective measure of exposure to wine, they do not capture the broader context of alcohol consumption, such as drinking patterns, lifestyle factors, and possible interactions with other dietary components. This limitation underscores the need for more refined research that captures the complexity of dietary patterns and their impact on health.13,14
Conclusion
The study by Domínguez-López et al.2 represents an important step forward in our understanding of the complex relationship between wine consumption and cardiovascular health. By leveraging urinary tartaric acid as an objective biomarker, the authors provide robust evidence that moderate wine consumption is associated with lower CVD risk in a Mediterranean population at high cardiovascular risk. This work not only highlights the value of objective biomarkers in nutritional epidemiology but also supports the notion that light-to-moderate wine consumption may be part of a heart-healthy diet. However, the findings also remind us of the risks associated with higher levels of consumption, underscoring the importance of moderation.15 Future research should continue to explore the potential of biomarkers in unravelling the intricate links between dietary habits, lifestyle, and health outcomes.
Declarations
Disclosure of Interest
G.d.G. is a member of the International Scientific Forum on Alcohol Research (http://alcoholresearchforum.org), an independent organization of scientists that prepares critiques of emerging research reports on alcohol and health. The members of the Forum receive no financial support for their contributions to critiques. The Forum itself receives no support from any organization or company in the alcoholic beverage industry. However, whether the support for individual members is from governmental agencies, universities, private foundations, or other groups, none of these organizations has any input into the conclusions presented in the critiques published on the Forum website. A detailed disclosure statement signed by each member of the Forum is available at http://alcoholresearchforum.org/disclosure-statement. He is also a corresponding member of the non-profit Accademia Italiana della Vite e del Vino.
References
Author notes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
