LAUSR

Objectives Carotenoids including β-carotene, α-carotene, lutein + zeaxanthin, lycopene, and β-cryptoxanthin may be protective against cancer and cardiometabolic disease through inhibition of oxidative stress and inflammation pathways. Little is known about which pathway would be more important for the beneficial effects of carotenoids. Methods From 2003-2009 the Sister Study enrolled 50,884 US women aged 35-74 who had a sister with breast cancer but had never had breast cancer themselves. From this cohort, 524 post-menopausal women were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Plasma carotenoids were quantified by HPLC and adjusted for batch and season. Urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured by GC/MS and adjusted for creatinine. The biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation. To separate the 8-iso-PGF2α biomarker into a more specific oxidative stress component versus inflammation, a novel 8-iso-PGF2α/PGF2αmodeled ratio approach was used, exploiting the fact that the required biomarker, prostaglandin F2α (PGF2α) was also quantitated by our GC/MS assay. Multivariable linear regression models were used to assess the associations of dietary and plasma carotenoids with the measured and calculated biomarker levels. Results Total plasma carotenoids were inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M levels (P trend across quartiles = 0.02 and 0.004). This inverse association was also apparent for the 8-iso-PGF2α/PGF2α ratio (P trend across quartile = 0.01), suggesting a greater suppressive effect on oxidative stress. β-carotene and α-carotene were also associated with significant decreases in the fraction of 8-iso-PGF2α from oxidative stress. Interestingly, lutein + zeaxanthin was associated with decreases in both oxidative stress and inflammation, suggesting strong biological effects. Dietary carotenoids were not associated with these oxidative stress markers. Conclusions Plasma carotenoids were associated with decreased levels of both 8-iso-PGF2α and its metabolite. Health effects of plasma carotenoids may be primarily due to their antioxidant effects. Specific carotenoids might have additional anti-inflammatory effects. Funding Sources NIH Office of Dietary Supplements and National Institute of Environmental Health Sciences.