Background: Evidence suggests that omega-3 polyunsaturated fatty acids (n-3PUFAs) restore obesity-induced insulin resistance (IR), however results from human intervention trials have been equivocal. Recent findings report that n-3PUFA status is inversely associated with type 2 diabetes in females but not males, suggesting a sex-dependent effect.
Objective: The aim is to determine whether n-3PUFA interventions affect IR in a sexually dimorphic manner.
Design: Five databases were searched (Medline, EMBASE, CINHAL, Scopus and Pre-Medline) for randomized controlled trials. Search terms included: omega-3 OR n3PUFA OR fish oil OR EPA OR DHA OR alpha linolenic acid and insulin resistance OR insulin sensitivity OR HOMA-IR OR QUICKI OR Matsuda OR euglycaemic clamp OR type 2 diabetes. Searches were limited to English language, and adults aged >18 years. Studies were excluded if they were conducted in cancer, HIV, surgical patients, or enteral/parenteral nutrition. Where possible, studies were pooled for meta-analysis. The principle summary measure was the standardized mean difference between groups (SMD). Protocol was registered with PROSPERO (CRD42015017940).
Results: Thirty-two eligible trials were identified with a total of 1895 participants (males: 46.4%; weighted mean ± SD age: 52.3 ± 8.1 years; weighted mean ± SD BMI: 29.4 ± 3.0kg/m2). Seven studies were in females; five in males; the remainder males and females together. Twenty-seven trials were pooled for meta-analysis (males: n=3; females: n=6). With all (n=27) studies pooled there was no effect of n-3PUFA on IR at the group level (SMD (95%CI): 0.098 (-0.088, 0.283), p=0.303). In trials > 6 weeks duration a significant improvement in IR is seen in females (SMD (95%CI): -0.266 (-0.524, -0.007), p=0.045) but not males (SMD (95%CI): 0.420 (-0.072, 0.912), p=0.094).
Conclusion: This analysis provides evidence of a sex-dependent response of IR to n-3PUFA intervention. Additional studies >8 weeks duration should be conducted to clarify sex-dependent associations and elucidate potential mechanisms involved.