Adherence to a Mediterranean diet was associated with lower risk for total stroke as well as ischemic and hemorrhagic stroke among women.

In a prospective cohort study of more than 105,000 women, investigators found that those with higher adherence to a Mediterranean diet had a 18% lower overall stroke risk than those with the lowest adherence, over a median follow-up of 21 years.

Moreover, women with the highest diet adherence had a 25% lower risk for hemorrhagic stroke, a relationship that prior research had not clearly established.

“Our study is among the largest prospective studies conducted to evaluate hemorrhagic stroke specifically among women,” lead investigator Ayesha Z. Sherzai, MD, clinical associate professor at Charles R. Drew University of Medicine and Science, Los Angeles, and colleagues wrote.

“Our study findings are thus notable in that we observed a statistically significant trend effect between MeDi [Mediterranean diet] and hemorrhagic stroke, where an increased MeDi score was associated with a lower risk of hemorrhagic stroke.”

The study was published online on February 4 in Neurology Open Access.

Weighing Diet and All-type Stroke Risk

Stroke is a leading cause of death and disability, and diet is a key modifiable risk factor. Yet fewer than 1% of US adults follow a healthy dietary pattern. While the Mediterranean diet has been linked to lower overall stroke risk, its effects on stroke subtypes are unclear. 

To address this knowledge gap, the investigators analyzed data from 105,614 women (mean age, 52.5 years; White, 87.3%) in the larger California Teachers Study, a prospective cohort of public school teachers and administrators enrolled between 1995 and 1996.

Dietary intake was assessed at baseline using a validated 100-item block food frequency questionnaire capturing consumption over the previous year. Investigators calculated adherence using a 9-point Mediterranean diet score, with higher scores indicating greater adherence. The score incorporated nine dietary components, including higher consumption of vegetables, fruits, legumes, cereals, fish, and olive oil; moderate alcohol intake; and reduced intake of meat and dairy. 

Stroke outcomes were identified through linkage with California hospitalization databases and national death records through 2020, with diagnoses classified using International Classification of Diseases, ninth revision (ICD-9), and ICD-10 codes into ischemic and hemorrhagic subtypes.

Investigators used multivariable Cox models to examine associations between Mediterranean diet adherence and stroke risk, adjusting for demographics, lifestyle factors, and vascular risks such as hypertension, diabetes, and atrial fibrillation. Models also accounted for smoking status, BMI, physical activity, menopausal status, and use of hormone therapy to reduce potential confounding.

At baseline, approximately 40% of participants were premenopausal, and many had BMI values within the normal range, the investigators noted. Participants were followed-up for an average of 20.5 years, totaling over 2.1 million person-years of observation.

Greater Adherence, Lower Risk

During follow-up, investigators identified 4083 incident stroke events, including 3358 ischemic strokes and 725 hemorrhagic strokes.

Women with the highest Mediterranean diet adherence scores (6-9) experienced a significantly lower stroke risk than those with the lowest scores (0-2).

In fully adjusted models, high adherence was associated with an 18% reduction in total stroke risk (hazard ratio [HR], 0.82; 95% CI, 0.74-0.92). The association demonstrated a significant dose-response trend (P-trend = .0014).

Higher adherence was also associated with reduced ischemic stroke risk. Participants with Mediterranean diet scores of 6-9 had a 16% lower risk for ischemic stroke than those with scores of 0-2 (HR, 0.84; 95% CI, 0.75-0.95; P-trend = .0331). Every 1-point increase in the Mediterranean diet score was associated with a 3% reduction in ischemic stroke risk (HR, 0.97; 95% CI, 0.95-0.99).

Notably, investigators observed a statistically significant association between Mediterranean diet adherence and hemorrhagic stroke. Women with the highest adherence scores had a 25% lower risk for hemorrhagic stroke than those with the lowest adherence (HR, 0.75; 95% CI, 0.58-0.97).

“The magnitude of the inverse association is somewhat more pronounced for hemorrhagic stroke than for ischemic stroke in the higher MeDi adherence categories when compared with the lower MeDi adherence,” the investigators noted. 

The associations remained consistent across analyses stratified by menopausal status and hormone replacement therapy use, supporting robustness of the findings.

The investigators acknowledged several limitations, including self-reported diet data, potential residual confounding, limited racial/ethnic diversity, and reliance on a single baseline dietary assessment.

Notable Reduction in Hemorrhagic Stroke

These findings, the investigators noted, add to growing evidence that supports diet as an important factor in stroke prevention. A Mediterranean-style diet may offer protective benefits for women. Following a healthier diet could be a practical strategy to lower stroke risk alongside other lifestyle interventions.

Co-study author Sophia S. Wang, PhD, professor in the Division of Health Analytics at City of Hope Comprehensive Cancer Center in Duarte, California, noted in a news release that the association with hemorrhagic stroke was particularly noteworthy.

“We were especially interested to see that this finding applies to hemorrhagic stroke, as few large studies have examined dietary influences on this stroke subtype,” Wang said.

However, she added, that “further studies are needed to confirm these findings and to help us understand the mechanisms behind them, so we could identify new ways to prevent stroke.”

This study and the California Teachers Study were supported by the National Cancer Institute (NCI) of the NIH and the National Institute of Environmental Health Sciences, as well as by the California Department of Public Health, the CDC’s National Program of Cancer Registries, and the NCI’s SEER Program.