Effect of dietary fat and Omega-3 fatty Acids on Urinary Eicosanoids and Sex Hormone Concentrations in Postmenopausal Women: A Randomized Controlled Feeding Trial
Effect of dietary fat and Omega-3 fatty Acids on Urinary Eicosanoids and Sex Hormone Concentrations in Postmenopausal Women: A Randomized Controlled Feeding Trial
Year: 2011
Authors: Young, L.R. Kurzer, M.S. Thomas, W. Redmon, J.B. Raatz, S.K.
Publication Name: Nutrition and Cancer
Publication Details: Volume 63; Number 6; Pages 930-939.
Abstract:
Substantial evidence relates increased sex hormone concentrations with increased breast cancer risk. Varying omega-3 (n-3) fatty acid (FA) intake may lead to alterations in eicosanoid balance and changes in circulating sex hormones that reduce risk. To clarify effects of dietary fat and n-3 FA intake on breast cancer risk markers, circulating sex hormones and urinary eicosanoids were measured in response to controlled feeding of diets designed to increase plasma concentrations of n-3 FA. A controlled cross-over feeding trial in postmenopausal women was conducted using 3 diets: high fat (HF; 40% energy from fat), low fat (LF; 20% energy from fat), and low fat plus n-3 FA (LFn3; 20% of energy from fat plus 3% of energy from n-3 FA) in 8-wk feeding periods. Plasma phospholipid fatty acid n-3 increased with the LFn3 relative to HF and LF (P < 0.0001). Plasma estradiol increased by 51% with HF (P = 0.03). Urinary prostaglandin E metabolite increased with HF relative to LF (P = 0.02) and urinary 11-dehydro-thromboxane B2 increased with HF (P = 0.01). These results do not support a role of n-3 FA in the reduction of sex hormone levels. (Author's abstract)
Evidence appears to support a positive association of total fat and saturated, monounsaturated, and polyunsaturated fat intake and breast cancer incidence. Reduction of tumorigenesis may be mediated by the inhibitory effects of n-3 FA on the synthesis of inflammatory eicosanoids derived from arachidonic acid (AA), an omega-6 (n-6) FA, and subsequent alteration of sex hormone metabolism. The objective of this well-controlled feeding study was to determine the effects of fat content (high- vs. low-fat diet) and n-3 FA on urinary eicosanoids and plasma sex hormones in postmenopausal women. The consumption of a HF diet for 8 wk resulted in a significantly increased ratio of n-6 to n-3 plasma phospholipid fatty acids compared to two LF diets, one of which was enriched in n-3 FA. These differences in FA profiles were accompanied by increased PGE-M and TxB-M and differences in plasma sex hormone profiles with the HF resulting in higher levels of total E2 and a trend toward increased free E2. An unexpected result was that SHBG concentrations trended lower with the LF. A reduction in TxB-M or PGE-M with the LFn3. Other studies have observed significant changes in eicosanoid metabolism with feeding a fish-rich diet or n-3 FA supplements. In this study, subjects were fed a known amount of n-3 FA with the LFn3 diet and plasma PLFA levels of 18:3n-3 and 20:5n-3. 22:6n-3 and total n-3 increased significantly, whereas 18:2n-6, 20:4n-6, total n-6, and n-6:n-3 ratio decreased significantly. A weakness of the current study is that the randomization schemas were not balanced. Also, the sample size may be too small, the dose of n-3 FA may have been too low, or the length of intervention too limited to detect the differences in sex hormone concentrations. In addition, biochemical markers of compliance for the HF and LF diet interventions were not included. Compliance with the LFn3 diet was estimated by incorporation of n-3 FA into phospholipid fatty acids. In conclusion, breast cancer risk factors appear to be increased by the HF. Relative to the HF, the LF appears to confer decreased risk. At the dose of n3 provided and time duration of the investigation, the LFn3 did not result in significant changes in sex hormones at the levels of ALA, EPA, and DHA provided. (Editor's comments)
