Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women

Abstract

Importance: Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited. Objectives: To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction. Design, Setting, and Participants: This cohort study included initially healthy women from the Women's Health Study, who had provided blood samples, biomarker measurements, and dietary information. Baseline data included self-reported demographics and a validated food-frequency questionnaire. The data collection period was from April 1993 to January 1996, and data analysis took place from June 2018 to November 2023. Exposures: Mediterranean diet score (range, 0-9) was computed based on 9 dietary components. Main Outcome and Measures: Thirty-three blood biomarkers, including traditional and novel lipid, lipoprotein, apolipoprotein, inflammation, insulin resistance, and metabolism measurements, were evaluated at baseline using standard assays and nuclear magnetic resonance spectroscopy. Mortality and cause of death were determined from medical and death records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for Mediterranean diet adherence and mortality risk, and mediation analyses were used to calculate the mediated effect of different biomarkers in understanding this association. Results: Among 25315 participants, the mean (SD) baseline age was 54.6 (7.1) years, with 329 (1.3%) Asian women, 406 (1.6%) Black women, 240 (0.9%) Hispanic women, 24036 (94.9%) White women, and 95 (0.4%) women with other race and ethnicity; the median (IQR) Mediterranean diet adherence score was 4.0 (3.0-5.0). Over a mean (SD) of 24.7 (4.8) years of follow-up, 3879 deaths occurred. Compared with low Mediterranean diet adherence (score 0-3), adjusted risk reductions were observed for middle (score 4-5) and upper (score 6-9) groups, with HRs of 0.84 (95% CI, 0.78-0.90) and 0.77 (95% CI, 0.70-0.84), respectively (P for trend <3%). Conclusions and Relevance: In this cohort study, higher adherence to the Mediterranean diet was associated with 23% lower risk of all-cause mortality. This inverse association was partially explained by multiple cardiometabolic factors..