Effects of dietary fat and omega-3 fatty acids on eicosanoids, endogenous sex hormones and the insulin-like growth factor pathway

Abstract

This dissertation details a clinical trial that investigated the effects of three controlled, 8-week duration test diets: a high fat diet (HF; 40% of energy from fat), a low fat diet (LF; 20% of energy from fat), and a low fat diet high in omega-3 (n-3) fatty acids (LFn3; 23% energy from fat including 3% of energy from n-3 fatty acids) on breast cancer risk markers including plasma and urinary sex hormones, urinary eicosanoids, and insulin-like growth factor (IGF) pathway endpoints in postmenopausal women. Chapter 1 contains a review of the literature providing context for the clinical trial. Chapter 2 describes the effects of the three test diets on plasma phospholipid fatty acids (PLFA), urinary eicosanoids, and plasma sex hormones. The LFn3 diet significantly increased plasma n-3 PLFA and the HF diet significantly increased estradiol and urinary eicosanoids. These results indicate that high fat diet increases breast cancer risk markers, but are inconclusive with respect to n-3 fatty acids. Chapter 3 describes the effect of the three test diets on urinary sex hormones and metabolites. Urinary excretion of estrone was significantly greater after the LF and LFn3 compared to the HF; however in the context of all the urinary hormones and metabolites measured, this indicates that no clinically significant alterations were observed following the test diets. Chapter 4 details the effects of the test diets on IGF pathway endpoints. LFn3 increased IGF-I and IGF binding protein-3 (IGFBP-3) and the LF increased IGFBP-3. These results indicate that low fat diet may reduce free IGF-I while the addition of n-3 fatty acids to the low fat diet may increase free IGF-I concentrations. The impact on breast cancer risk mediated by the increase in IGF-I with the LFn3 is unknown, but an increase in circulating IGF-I may have an impact on reducing the effects of aging. In conclusion, the test diets had pronounced effects on PLFA but modest effects on plasma and urinary sex hormones. The LFn3 unexpectedly increased IGF-I concentrations, which may demonstrate a role of n-3 in preventing the effects of aging.