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Background: [alpha]-Linolenic acid (ALA) is associated with a low risk of cardiovascular disease; however, the underlying mechanism is not completely known. Objective: The objective was to examine whether habitual dietary ALA intake is associated with plasma concentrations of inflammatory biomarkers after control for shared genetic and common environmental factors. Design: We cross-sectionally studied 353 middle-aged male twins. Habitual diet was assessed with the Willett food-frequency questionnaire. Fasting plasma concentrations of interleukin-6 (IL-6) and its soluble receptor (sIL-6R), high-sensitivity C-reactive protein (hsCRP), and tumor necrosis factor-[alpha] (TNF-[alpha]) were measured. Linear mixed-effect regression analysis was used to partition the overall association into within- and between-pair associations. Results: A 1-g increment in habitual dietary ALA intake was associated with 11.0% lower concentrations of sIL-6R (P = 0.004) but not of IL-6 (P = 0.31), TNF-[alpha] (P = 0.16), or hsCRP (P = 0.36) after adjustment for energy intake, nutritional factors, known cardiovascular disease risk factors, and medications. After further control for shared genetic and common environmental factors by comparison of brothers within a twin pair, a twin with a 1-g higher ALA intake was likely to have 10.9% (95% CI: 3.7%, 17.6%; P = 0.004) lower sIL-6R concentrations than his co-twin with a low intake, whereas ALA intake was not significantly associated with plasma concentrations of IL-6, TNF-[alpha], or hsCRP. These results were validated by using 1000 bootstrap samples. Conclusions: Habitual dietary ALA intake is inversely associated with plasma sIL-6R concentrations independent of shared genetic and common environmental influences. Lowering sIL-6R may be a mechanism underlying the cardioprotective properties of habitual dietary ALA. This study was registered at clinicaltrials.gov as NCT00017836. Am J Clin Nutr 2010;92:177-85. doi: 10.3945/ajcn.2010.29305.

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.