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Am J Clin Nutr. 2008 Nov;88(5):1364-70.

Association between adherence to the Mediterranean diet and oxidative stress.

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Department of Medicine, Division of Cardiology, Emory Program in Cardiovascular Outcomes Research and Epidemiology, Emory University School of Medicine, Atlanta, GA 30306, USA.



The cardioprotective property of the Mediterranean diet has been attributed to its antioxidant capacity, but direct investigation of this mechanism has been limited.


We examined the association between the Mediterranean diet and an established plasma marker of oxidative stress, the ratio of reduced to oxidized glutathione (GSH/GSSG), in a well-controlled study of twins.


We administered the Willett food-frequency questionnaire to 138 monozygotic and dizygotic twin pairs and to 21 unpaired twins and derived a score measuring adherence to the Mediterranean diet. Fasting plasma GSH and GSSG concentrations were measured to calculate the GSH/GSSG ratio. The higher the ratio, the lower the oxidative stress. Mixed-effect regression analysis was used to partition the association into between- and within-twin pair differences. When within-pair effects are examined, twins are matched for sociodemographic and familial factors.


A one-unit increment in the diet score was associated with a 7% higher GSH/GSSG ratio (P = 0.03) after adjustment for energy intake, other nutritional factors, cardiovascular disease risk factors, and medication use. The association persisted within twin pairs: a one-unit within-pair absolute difference in the diet score was associated with a 10% (95% CI: 2.7, 18.0) higher GSH/GSSG ratio in the twin with the higher score than in the co-twin with the lower score (P = 0.007). Results were similar in monozygotic and dizygotic twin pairs.


The association between the Mediterranean diet and plasma oxidative stress is robust and is not confounded by genetic or shared environmental factors. Decreased oxidative stress is a plausible mechanism linking the Mediterranean diet to reduced cardiovascular disease risk.

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