Omega-3 Fatty Acids and Insulin Sensitivity

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents,
but data in humans is ambiguous. No existing studies have systematically evaluated the
influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant,
non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of
purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin
sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals.
Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase
the content and function of mitochondria in skeletal muscle, measured using a combination of
in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA
supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant
humans, and this improvement will be associated with mitochondrial biogenesis and attenuated
lipid accumulation in skeletal muscle and liver.

Inclusion criteria:

1. Age 18-65 years

2. Insulin resistant (HOMA IR ≥2.6)

Exclusion criteria:

1. Current use of omega-3 nutritional supplements

2. Fasting plasma glucose ≥126 mg/dL

3. Active coronary artery disease

4. Participation in structured exercise (>2 times per week for 30 minutes or longer)

5. Smoking

6. Medications known to affect muscle metabolism (e.g., beta blockers, corticosteroids,
tricyclic-antidepressants, benzodiazepines, opiates, barbiturates, anticoagulants)

7. Renal failure (serum creatinine > 1.5mg/dl)

8. Chronic active liver disease (AST>144IU/L and ALT>165IU/L)

9. Anti-coagulant therapy (warfarin/heparin)

10. INR >3

11. Use of systemic glucocorticoids

12. Chronic use of NSAIDS or aspirin

13. Pregnancy or breastfeeding

14. Alcohol consumption greater than 2 glasses/day

15. Hypothyroidism

16. Fish or shellfish allergy