Do ω-3 PUFAs affect insulin resistance in a sex-specific manner? A systematic review and meta-analysis of randomized controlled trials 1 , 2

Kylie A Abbott, Tracy L Burrows, Rohith N Thota, Shamasunder Acharya, Manohar L Garg

Evidence has suggested that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve obesity-induced insulin resistance (IR); however, results from human intervention trials have been equivocal. Recently it has been reported that n-3 PUFA status is inversely associated with type 2 diabetes in women but not in men, suggesting a sex-dependent effect. We aimed to determine whether n-3 PUFA interventions affect IR in a sex-dependent manner. Five databases were searched (Medline, EMBASE, CINAHL, Scopus, and Pre-Medline) for randomized controlled trials. Searches were limited to the English language and to studies with adults aged >18 y. When possible, studies were pooled for a meta-analysis. The principle summary measure was the standardized mean difference (SMD) between groups. Thirty-one eligible trials were identified with a total of 1848 participants [men: 45.1%; weighted mean ± SD age: 52.5 ± 8.2 y; weighted body mass index (in kg/m(2)): 28.8 ± 3.0]. Seven studies were conducted in women, 4 studies were conducted in men, and the remaining studies pooled men and women together. Twenty-six trials were pooled for the meta-analysis (men: n = 2; women: n = 6). With all studies (n = 26) pooled, there was no effect of n-3 PUFA on IR at the group level (SMD: 0.089; 95% CI: -0.105, 0.283; P = 0.367). In trials of ≥6 wk, a significant improvement in IR was seen in women (SMD: -0.266; 95% CI: -0.524, -0.007; P = 0.045) but not in men (SMD: 0.619; 95% CI: -0.583, 1.820; P = 0.313). With this analysis, we provide preliminary evidence of a sex-dependent response of IR to an n-3 PUFA intervention. Additional studies are needed to confirm sex-dependent associations and to elucidate the potential mechanisms that are involved. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015017940.