Prevention of Post-Prandial Hypoglycemia Using n-3/n-6 PUFA in PCOS

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DESCRIPTION (provided by applicant): This proposal is in response to the PAR-04-087 (The GCRC Complementary and Alternative Medicine Research Program) and utilizes the resources of the UC Davis GCRC. The aim is to determine whether the essential and/or the long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) can prevent postprandial hypoglycemia and its unfavorable endocrine consequences in polycystic ovary syndrome (PCOS). PCOS affects 1 in 16 women and manifests with insulin resistance, hyperinsulinemia, androgen excess, hirsutism, infertility, and commonly with obesity. Treatment of insulin resistance and obesity improves ovarian function and infertility. We demonstrated that PCOS patients frequently develop postprandial hypoglycemia, which in turn stimulates secretion of cortisol and adrenal androgens. Since these hormones promote central obesity, insulin resistance and possibly hirsutism, prevention of postprandial hypoglycemia can be very beneficial. Our previous research suggests that n-3 PUFA supplementation may be useful in preventing postprandial hypoglycemia in PCOS. The hypothesis is: In women with PCOS, both the essential and the long-chain n-3 PUFAs can prevent postprandial hypoglycemia, but possibly through different mechanisms: The long-chain n-3 PUFAs from fish oil decrease insulin secretion, whereas the essential n-3 PUFA from flax seed oil re-sets the pancreatic glucose sensor to a higher threshold. This hypothesis will be tested in 90 women with PCOS using a randomized, double- blinded, placebo-controlled, parallel-design intervention that has two phases: I. Lead-in (4 weeks) and II. Intervention (6 weeks). During the lead-in period all participants will receive a placebo. During the intervention, the participants will be randomized to 3 treatment arms: placebo, fish oil or flax seed oil. Changes in blood glucose, insulin sensitivity, insulin secretion, pancreatic reserve and hypoglycemic symptoms will be investigated. We anticipate that n-3 PUFAs will prevent hypoglycemia, and thus secretion of cortisol and adrenal androgens. This R21 proposal will determine the best n-3 PUFA supplement to be tested in future large clinical trials in order to decrease obesity, central obesity, insulin resistance, hirsutism, and the risks for diabetes and infertility in young women with PCOS --an understudied population. Polycystic ovary syndrome (PCOS) is a common disease that affects 1 out of 16 women. There are almost 7 million PCOS patients in the USA. This disease causes infertility, facial hair growth, and increases the risk for obesity, diabetes and heart disease. We discovered that PCOS patients experience low blood sugars (hypoglycemia) frequently. In turn, hypoglycemia causes sugar craving and overeating, and increases secretion of the hormones that lead to obesity and diabetes. Avoiding hypoglycemia may protect these patients from gaining additional weight and becoming diabetic. We think we can achieve this goal by using fish oil and/or flax seed oil supplements. We do not know yet however which one of these supplements would be the better choice. Our aim is to identify the best supplement that can prevent hypoglycemia and its unwanted consequences in these young women-an under-studied patient population.