Does omega-3 fatty acids supplementation affect circulating leptin levels? A systematic review and meta-analysis on randomized controlled clinical trials

Clin Endocrinol (Oxf). 2015 Feb;82(2):221-8. doi: 10.1111/cen.12508. Epub 2014 Jul 7.


Background: Omega-3 fatty acids have attracted researchers for their effect on circulatory hormone-like peptides affecting weight control.

Objective: Our objective was to conduct a systematic review and meta-analysis on randomized controlled trials (RCTs) assessed the effects of omega-3 supplementation on serum leptin concentration and to find the possible sources of heterogeneity in their results.

Methods: We searched PubMed/Medline, Google Scholar, Ovid, SCOPUS and ISI web of science up to April 2014. RCTs conducted among human adults, examined the effect of omega-3 fatty acid supplements on serum leptin concentrations as an outcome variable were included. The mean difference and standard deviation (SD) of changes in serum leptin levels were used as effect size for the meta-analysis. Summary mean estimates with their corresponding SDs were derived using random effects model.

Results: Totally 14 RCTs were eligible to be included in the systematic review, and the meta-analysis was performed on 13 articles. Our analysis showed that omega-3 supplementation significantly reduces leptin levels (mean difference (MD) = -1·71 ng/ml 95% confidence interval (CI): -3·17 to -0·24, P = 0·022). Subgroup analysis based on BMI status showed that the omega-3 supplementation reduces leptin when used for nonobese subjects (MD = -3·60 ng/ml; 95% CI -6·23 to -0·90; P = 0·011); however, this was not true for obese participants (MD = -0·86 ng/ml; 95% CI: -2·63 to -0·90; P = 0·296). Subgroup analysis based on omega-3 source also showed that omega-3 from marine sources may significantly reduce leptin levels (MD = -1·73 ng/ml; 95% CI -3·25 to -0·2; P = 0·026), but plant sources do not significantly affect serum leptin levels (MD = -1·48 ng/ml; 95% CI -6·78 to 3·23; P = 0·585). Our results were highly sensitive to one study.

Conclusions: Omega-3 supplementation might moderately decrease circulatory leptin levels only among nonobese adults. RCTs with longer follow-up period, using higher doses for obese adults and exploring the effect in different genders, are needed to replicate our results.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Body Weight / physiology
  • Dietary Supplements*
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Humans
  • Leptin / blood*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic / statistics & numerical data*


  • Fatty Acids, Omega-3
  • Leptin