Changes in plasma metabolites and glucose homeostasis during omega-3 polyunsaturated fatty acid supplementation in women with polycystic ovary syndrome

Abstract

Background: Both fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA.

Methods and findings: In this six-week, randomized, 3-parallel arm, double-blinded study, 54 women received 3.5 g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end. As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, l-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and l-cysteine degradation.

Conclusion: Effects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary.

Keywords: Branched chain amino acids; Insulin resistance; PCOS; Plasma metabolites; n-3 Polyunsaturated fatty acids.

Graphical abstract

Fig. 1

Consort diagram.

Fig. 2

Effects of fish oil (FO), flaxseed oil (FLX) and soy bean oil (SBO) on early response (AIRg) measured by frequently sampled intravenous glucose tolerance test and on the cumulative insulin response measured by oral glucose tolerance test (AUC_Glucose: pmolU/ml·2 h), shown as changes as compared to the pretreatment values (means ± SD; n = 17 in each treatment arm, b: p < 0.05 as compared to soybean oil). Paired t-test was performed to determine the significance of within-group change. Inter-group comparisons were performed by analysis of covariance (ANCOVA), adjusted for the baseline values. When the overall difference among the groups was significant in ANCOVA, post-hoc pair wise group comparisons were performed using the Bonferroni multiple comparisons procedure to determine the significant differences.

Fig. 3

Effects of fish oil (FO), flaxseed oil (FLX) and soy bean oil (SBO) on fasting plasma amino acids, shown as changes as compared to the pretreatment values (mean ± SD; n = 17 in each treatment arm; *: p < 0.05 for the change from the baseline; a: p < 0.05 as compared to flaxseed oil). Paired t-test was performed to determine the significance of within-group change. Inter-group comparisons were performed by analysis of covariance (ANCOVA), adjusted for the baseline values. When the overall difference among the groups was significant in ANCOVA, post-hoc pair wise group comparisons were performed using the Bonferroni multiple comparisons procedure to determine the significant differences.