Mediterranean dietary adherence can reduce mortality risk in women

In a recent study published in JAMA Network Open, researchers from Harvard Medical School investigated the association between Mediterranean diet adherence and any-cause mortality risk. They also examined the relative contributions of cardiometabolic variables to risk reduction.

Study: Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women. Image Credit: Marian Weyo/Shutterstock.comStudy: Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women. Image Credit: Marian Weyo/


Nutrition and preventive recommendations prioritize dietary patterns above individual items concerning health consequences. The Mediterranean diet is frequently considered the healthiest recommended diet by the United States (US) Dietary Guidelines.

Guidelines by the American Heart Association, European Society of Cardiology, and Australian National Heart Foundation state that the Mediterranean diet can improve cardiometabolic health and cardiovascular disease (CVD) outcomes, 

Many large-scale observational epidemiological studies with lengthy follow-ups and meta-analyses show a link between increased Mediterranean diet adherence and a lower any-cause death risk.

However, evidence on underlying biological pathways with long follow-ups is limited, and long-term all-cause death statistics for asymptomatic women are sparse.

About the study

The present study investigated whether Mediterranean dietary adherence could lower mortality risk among female United States (US) residents. They also explored the biological mechanisms underlying the association.

The study included Women Health Study (WHS) participants aged ≥45 years who provided dietary data, blood samples, and biomarker measurements. Baseline information included self-documented demographics, anthropometric measures, lifestyle habits, social and medical history, medications, and food-frequency questionnaires.

Researchers collected data between April 1993 and January 1996 with data analysis performed between June 2018 and November 2023.

The study exposures were the Mediterranean diet scores (ranging between 0 and 9) derived from nine dietary parameters.

Using enzymatic assays, the researchers evaluated 33 serum biomarkers, including hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hs-CRP), lipoprotein (a), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apolipoproteins (apo) AI, B100 w, fibrinogen, soluble intracellular adhesion molecule 1 (sICAM-1), creatinine, and homocysteine.

Nuclear magnetic resonance (NMR) spectroscopy measured lipoprotein subfraction particles of HDL, LDL, very low-density lipoprotein cholesterol, triglyceride-rich lipoproteins (TRL), glycoprotein acetylation, cardiometabolic small molecules including alanine, citrate, brained-chain amino acids (BCAAs), and the insulin resistance index.

The team ascertained mortality and death causes from health and mortality records. They used Cox proportional hazard regressions to calculate the hazard ratios (HR) for Mediterranean dietary adherence and death risk.

Study covariates included smoking status, alcohol intake, physical activity, and menopause-related factors. The researchers performed mediation analyses to estimate the mediation effects of different biological markers.

They also conducted sensitivity analyses, comparing the mediation results for single biomarkers using the counterfactual framework and the standard mediation approach.


The study included 25,315 females, among whom the mean age at baseline was 55 years; 329 (1.30%) were Asian, 406 (1.60%) were black, 240 (0.90%) were Hispanic, 24,036 (95%) were white, and 95 belonged to other races and ethnicities.

The median score for Mediterranean dietary adherence was 4.0. Over 25 years, 3,879 deaths occurred, of which 935 resulted from cardiovascular disease and 1,531 from cancer.

Individuals with higher adherence to the Mediterranean diet had healthier lifestyles, lower body mass index values, higher consumption of nuts, fruits, fish, legumes, and whole grains, and lower processed and red meat intake.

Compared to the low Mediterranean dietary adherence (scores ranging from 0.0 to 3.0) group, the researchers observed reduced mortality risk among those in the middle (scores ranging from 4.0 to 5.0) and high (scores ranging from 6.0 to 9.0) adherence groups, with HR values of 0.840 and 0.770, respectively.

Lifestyle habit adjustments attenuated the mortality risk reductions, which remained significant (HR values of 0.92 and 0.89 for middle and high dietary adherence, respectively).

Among the biological markers, small-molecule metabolite substances (particularly alanine and homocysteine) and inflammatory biological markers had the most profound influences in lowering the death risk (explaining 15% and 13% of the relationship, respectively), followed by BMI (10%), TRLs (10%), and reduced insulin sensitivity (7.40%).

Other variables, including LDL, HDL, BCAAs, hypertension, and glycemic measures, had minor contributions of less than 3.0%. Sensitivity analyses yielded similar findings.


The study findings showed that adhering to Mediterranean dietary patterns could lower any-cause mortality risk by 23%.

Biological markers of small molecular metabolic substances, TRLs, inflammation, BMI, and insulin resistance had the most pronounced effects on lowering the mortality risk, with minimal contributions by glycemic and standard cholesterol measures.

Further research should involve individuals of all ages and backgrounds to improve the generalizability of the study findings and explore other pathways that might explain the decreased mortality linked to Mediterranean diets and cause-specific mortality.

Journal reference:
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.


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