Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?

Aim: To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, beta-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid.Methods and results: One hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3 months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6 g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (K-G-value) were evaluated by the intravenous glucose tolerance test (IVGTT).Fish oil did not have any effect on SI, FPIR, K-G-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Delta SI 0.42 +/- 0.34 on fish oil vs 0.14 +/- 0.23 on placebo for those with n-6/n-3 <4.85; -1.03 +/- 0.47 on fish oil vs -0.27 +/- 0.32 on placebo for those with n-6/n-3 >4.85) (M +/- SE), FPIR (Delta FPIR 135.9 +/- 78.9 vs 157.2 +/- 157.5 pmol/L; 38.8 +/- 181.7 vs 357.1 +/- 181.7 pmol/L), K-G-value (Delta K-G 0.14 +/- 0.15 vs 0.12 +/- 0.11; -0.32 +/- 0.16 vs 0.15 +/- 0.15) or disposition index (Delta disposition index 1465.4 +/- 830.4 vs 953.8 +/- 690.0; -1641.6 +/- 1034.3 vs 446.6 +/- 905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of KG-value (p = 0.02).Conclusions: in healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, beta-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.