PREDIMED Analysis May Rekindle Hope for Wine’s Heart Benefits

After several years of studies suggesting no amount of alcohol is healthy, a new analysis based on direct measurements of wine intake—rather than self-reported consumption—may pump fresh hope into the hypothesis that daily, moderate wine consumption is good for the heart.

In an observational analysis drawing on the landmark PREDIMED study, participants who drank one to two glasses of wine per day, confirmed through levels of urinary tartaric acid, had lower cardiovascular event rates over follow-up.

A J-shaped relationship between wine consumption and cardiovascular health was observed, however, with moderate intake associated with lower CV risk—individuals drinking more than 35 glasses of wine per month did not show a reduction in CV events.

“Our results support this dose-response pattern, as we observed that high levels of urinary tartaric acid were not associated with lower CVD risk,” Inés Domínguez-López, PhD (University of Barcelona, Spain), and colleagues write in the European Heart Journal. “However, moderate consumption has been defined as one to two drinks/day, which aligns with the higher doses we identified as associated with a reduced risk of CVD.”

Senior investigator Ramon Estruch, MD, PhD (University of Barcelona/Hospital Clinic Barcelona), noted that moderate wine consumption is one component of the Mediterranean diet that participants adhered to in PREDIMED, but stressed this is distinctly different from binge drinking—something increasingly linked to harm, not health.

“Consuming one glass of wine with meals each day over a week is not the same as having seven glasses of wine in a single day outside of meals,” he told TCTMD via email. “The effects on health may be diametrically opposite. Another important issue is what accompanies your glass of wine. It is not the same to have a Mediterranean meal as it is to have a burger from a fast-food shop.”

For teetotalers, it’s best to keep it that way. “For participants who do not drink, we do not advise consuming any alcohol,” Estruch added. 

Jamal Rana, MD, PhD (The Permanente Medical Group, Oakland, CA), who has investigated the relationship between alcohol intake and coronary heart disease, said the study needs to be interpreted conservatively given the limitations.

“I would strongly caution that by no means is this study a license for everybody to start drinking wine saying, ‘Oh, it's good for our heart,’” said Rana. “Context is very, very important.”

Prior epidemiological research has suggested there may be cardiovascular benefits of light-to-moderate wine consumption, but the field is rife with debate. The American Heart Association advises that women have no more than a single drink per day while men can have up to two drinks, but they stress that people should not start or continue drinking to improve their cardiovascular health. The European Society of Cardiology suggests alcohol should be limited to a maximum of 100 g per week (alcoholic beverages range from 8 to 14 g of alcohol per drink).

In 2022, the World Heart Federation broke new ground when they stated that no amount of alcohol is considered good for the heart.  

No Benefit to Heavier Drinking

The uncertainty around alcohol’s potential benefits, particularly wine, stems from the lack of randomized, controlled studies. Observational research has traditionally relied on self-reported data, which can be inaccurate. With that in mind, the researchers measured tartaric acid, which is primarily produced by grapes, as an objective marker to evaluate wine consumption in PREDIMED.

The trial, which was first published in 2013, included nearly 7,500 participants at high cardiovascular risk (presence of type 2 diabetes or at least three major risk factors) and showed that a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the risk of major cardiovascular events. For this nested case-cohort study, investigators included all individuals with incident CVD and available urine samples (n = 685) and 625 random participants.

Participants with urinary tartaric acid concentrations of 3-12 and 12-35 µg—corresponding to three-12 and 12-35 glasses per month—had a significant 38% and 50% lower risk of major cardiovascular events (CV death, MI, stroke, or heart failure) when compared with those who had less than one glass of wine per month. There was no benefit to drinking one to three glasses or more than 35 glasses of wine per month.

Stratified by sex, the inverse association between light and moderate alcohol consumption and major cardiovascular disease was significant in men only, which may be explained by the lower number of CVD events in women. Estruch noted that men in PREDIMED drank “somewhat more” than women, but said they didn’t explore the reason for the differing results further.

To TCTMD, Rana pointed out the study is small and includes older Spanish patients who are consuming a healthy Mediterranean diet, which makes the generalizability, particularly to a US population, difficult. He also noted the potential for “healthy patient bias” whereby sick quitters, or those who had problems with alcohol, were not included in the analysis. Additionally, there is genetic epidemiology research from the UK Biobank study showing that any amount of alcohol consumption was associated with increased CVD risk, said Rana.

“I would not recommend to my 70-year-old patient to start drinking wine based on these findings,” he said. If they currently drink alcohol, he’d suggest limiting it to one or two drinks per week. “We have to remember that alcohol is a group 1 carcinogen,” said Rana. “We can’t discount the other side effects of alcohol over time.”

In an editorial, Giovanni de Gaetano, MD, PhD (IRCCS Neuromed Hospital, Pozzilli, Italy), and colleagues say the measurement of tartaric acid provides a compelling new twist to understanding the relationship between wine consumption and CVD risk. However, the study still doesn’t completely end the debate.

“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,” they write.

Additionally, the editorialists stress the importance of never exceeding more-than-moderate drinking. “Higher levels of tartaric acid, corresponding to nonmoderate wine consumption, were indeed not associated with a reduced risk of CVD,” add de Gaetano et al. “This observation is consistent with a large literature, which cautions against heavy alcohol consumption due to its well-documented adverse health effects.”