Association between adherence to the Mediterranean diet and oxidative stress

Am J Clin Nutr. 2008 Nov;88(5):1364-70. doi: 10.3945/ajcn.2008.26528.


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

Objective: 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.

Design: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Twin Study

MeSH terms

  • Bias
  • Biomarkers / blood
  • Cardiovascular Diseases / prevention & control
  • Cluster Analysis
  • Diet Surveys
  • Diet, Mediterranean*
  • Glutathione / blood
  • Glutathione / metabolism*
  • Glutathione Disulfide / blood
  • Glutathione Disulfide / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Patient Compliance
  • Risk Factors
  • Surveys and Questionnaires
  • Twins, Dizygotic*
  • Twins, Monozygotic*


  • Biomarkers
  • Glutathione
  • Glutathione Disulfide