How Mediterranean Diets Might Cut Mortality in Women: New Insights

Women who adhere to the Mediterranean diet benefit from a survival advantage over time, partially driven by improvements in multiple cardiometabolic factors, according to new data from the Women’s Health Study.

The findings add to prior evidence showing that the effects of a Mediterranean diet, which is heavy in unprocessed grains, fruits and vegetables, legumes, nuts, and olive oil and promotes seafood as the animal protein of choice, are just as strong in women as in men. But it also helps explain why.

“The current study is unique in being conducted prospectively over more than a quarter of a century and with very detailed evaluation of numerous risk factors and biomarker pathways,” lead author Shafqat Ahmad, PhD (Brigham and Women’s Hospital, Boston, MA), told TCTMD in an email. “Our study confirmed that the benefits on longevity extended long-term, and that modest changes in traditionally measured as well as novel risk factors accounted for part (but not most) of the benefit of the Mediterranean diet on all-cause risk and may have important downstream consequences for primary prevention.”

Commenting on the study for TCTMD, Dariush Mozaffarian, MD, DrPH (Food is Medicine Institute at Tufts University, Boston, MA), said it confirms the real-world benefits of the Mediterranean diet that have been observed now in several randomized controlled trials.

“Importantly, the magnitude of the benefits is very similar to what was observed in the RCTs,” he said in an email. “Also importantly, the findings for the mediating biomarkers are entirely consistent with known physiologic benefits of the Med diet, strongly supporting causality of the findings.”

Because of this, Mozaffarian said, “it’s time to consider a Med Diet ‘standard of care’ for reducing cardiovascular and metabolic risk and apply it widely in clinical practice.”

Sarah Zaman, MBBS, PhD (The University of Sydney, Australia), who also commented on the study for TCTMD, agreed. While it wasn’t unexpected that the Mediterranean diet improved multiple cardiovascular risk factors, she said in an email, “what was surprising is that this effect did not seem to be mediated through the traditional major CVD modifiable risk factors of cholesterol (eg, LDL-C) or blood pressure.”

What is most important, Zaman added, is that the findings uncover more about the mechanisms behind this mortality benefit, as seen through lowering of small-molecule metabolites, inflammation, triglycerides, body mass index (BMI), and insulin resistance. “These all likely contribute to the known effect of a Med diet on lowering risk of CVD, death, and cancer and explain the mechanism of this effect,” she said, noting that it was “interesting” that the Mediterranean diet was not associated with substantial effects on traditional biomarkers like cholesterol or lipoprotein(a).

Mortality Benefits

For the study, published online last week in JAMA Network Open, Ahmad and colleagues included data from 25,315 participants in the Women’s Health Study (mean baseline age 54.6 years; 94.9% white) who were enrolled between 1993 and 1996 then followed for a mean of 24.7 years. The median Mediterranean diet adherence score—which ranges from zero to nine based on nine dietary components—was 4.0.

Overall, 3,879 participants died (24.1% due to CVD and 39.5% due to cancer) with mortality risk inversely associated with adherence to a Mediterranean diet. Specifically, compared with those with low adherence (score 0-3), those with middle (score 4-5) and high adherence (score 6-9) had lower adjusted risks of all-cause mortality (HR 0.84; 95% CI 0.78-0.90 and HR 0.77; 95% CI 0.70-0.84, respectively; P for trend < 0.001).

Reductions in cancer mortality were tied more closely to Mediterranean diet adherence than were drops in CVD mortality, with the highest scores (≥ 6) associated with a 17% reduced risk of CVD mortality (HR 0.83; 95% CI 0.69-0.99; P for trend = 0.03) and a 20% reduced risk of cancer mortality (HR 0.80; 95% CI 0.69-0.92; P for trend = 0.002).

These risk reductions remained significant when the models were further adjusted for lifestyle factors like smoking, physical activity, alcohol intake, and menopause status for both the middle (HR 0.92; 95% CI 0.85-0.99) and upper adherence groups (HR 0.89; 95% CI; 0.82-0.98; P for trend = 0.001).

Of the 33 biomarkers the researchers examined, small molecule metabolites and inflammatory biomarkers contributed most to the lower mortality risk, explaining 14.8% and 13.0% of the total risk, respectively. Triglyceride-rich lipoproteins (10.2%), BMI (10.2%), and insulin resistance (7.4%) also contributed substantially. But biomarkers like branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension each contributed to less than 3% of the total risk.

“We were not expecting such a long-term consistent benefit that was over a quarter of a century based on what women reported eating so many years before,” Ahmad said. “It was interesting also that the biomarkers related to small metabolites, inflammatory markers, triglyceride-rich measures, insulin resistance, and adiposity were potentially explaining some of the benefit.”

But since the biomarkers they looked at could not explain the totality of the survival advantage associated with the Mediterranean diet, Ahmad said it’s likely that additional factors “are also involved in benefit, such as the gut microbiome, neurohormonal regulation, and/or other pathways.”

Other Mechanisms?

Zaman was pleased with the results but predicted they won’t change clinical practice, as the Mediterranean diet “is already the most recommended diet in guidelines and clinical cardiology.”

Still, this study “paves the way for future research into understanding the mechanisms for dietary intake on cardiovascular disease risk,” she said. “It also is exciting in that it suggests that diet could be individualized in the future. For example, a Mediterranean diet clearly has major effects on inflammation and, in individuals where this is the main driver for CVD, it could have huge benefits. However, in individuals where the main driver for CVD is elevated LDL cholesterol, then perhaps a different dietary pattern would have a larger impact.”

Future work into the additional unknown mechanisms at play are also warranted, according to Zaman. “As is evident from other work, residual CVD risk exists, and future work needs to identify new risk factors and biomarkers for CVD,” she said, adding that dietary studies in more diverse groups of participants are also needed.

Ahmad said he would specifically like to see more studies explore “vascular endothelium markers, arterial stiffness and vulnerability, gut microbiome, [and] neurohormonal regulation.” Also, he said, “it will be important to see how changes in the diet relate to benefit.”