Omega-3 Supplementation Reduces Inflammation, Improves Glucose

Systemic inflammation and its chronic release of cytokines and other inflammatory markers is a major health concern, especially for individuals struggling with obesity. In a sense, having extra adipose (fat) tissue, acts as a generator of inflammation, and aside from physical mobility and comfort, it can affect a person’s immune response and blood sugar.

This clinical study found that supplementation with a high-dose omega-3 supplement for three months reduced inflammatory markers and improved glucose metabolism by 25 percent in individuals with high blood sugar numbers.

The researchers found that omega-3 supplementation increased the activity of the apolipoprotein E (APOE), which produces the APOE protein that helps transport lipids like cholesterol through the bloodstream. It also has anti-inflammatory properties, and that may account for additional improvements in health as well.

While omega-3 supplements are popular, it pays to be selective when adding any to a regimen. Rather than choosing fish oils, where the omega-3 fatty acids are bound to triglycerides, consider phospholipid-bound forms of omega-3 supplements made from a single source, like salmon. The beneficial fatty acids on those forms are closer to a natural state, more stable, and include phospholipids and peptides, which provide benefits for the heart, brain, and eyes.


Hernandez JD, Li T, Rau CM, LeSuer WE, Wang P, Coletta DK, Madura JA 2nd, Jacobsen EA, De Filippis E. ω-3PUFA supplementation ameliorates adipose tissue inflammation and insulin-stimulated glucose disposal in subjects with obesity: a potential role for apolipoprotein E. Int J Obes (Lond). 2021 Jun;45(6):1331-1341. doi: 10.1038/s41366-021-00801-w. Epub 2021 Mar 22. PMID: 33753887; PMCID: PMC8159741.

Background: Long chain omega-3 polyunsaturated fatty acids (ω-3PUFA) supplementation in animal models of diet-induced obesity has consistently shown to improve insulin sensitivity. The same is not always reported in human studies with insulin resistant (IR) subjects with obesity.

Objective: We studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation in IR subjects with obesity.

Methods: Thirteen subjects (BMI = 39.3 ± 1.6 kg/m2) underwent 80 mU/m2·min euglycemic-hyperinsulinemic clamp with subcutaneous (Sc) AT biopsy before and after 3 months of ω-3PUFA (DHA and EPA, 4 g/daily) supplementation. Cytoadipokine plasma profiles were assessed before and after ω-3PUFA. AT-specific inflammatory gene expression was evaluated on Sc fat biopsies. Microarray analysis was performed on the fat biopsies collected during the program.

Results: Palmitic and stearic acid plasma levels were significantly reduced (P < 0.05) after ω-3PUFA. Gene expression of pro-inflammatory markers and adipokines were improved after ω-3PUFA (P < 0.05). Systemic inflammation was decreased after ω-3PUFA, as shown by cytokine assessment (P < 0.05). These changes were associated with a 25% increase in insulin-stimulated glucose disposal (4.7 ± 0.6 mg/kg ffm•min vs. 5.9 ± 0.9 mg/kg ffm•min) despite no change in body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with Apolipoprotein E (APOE) being one of the most upregulated genes.

Conclusion: High dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT, and systemic inflammation. These findings are associated with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as among the most differentially regulated gene after ω-3PUFA supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.

Here is the link to the full text study: ω-3PUFA supplementation ameliorates adipose tissue inflammation and insulin-stimulated glucose disposal in subjects with obesity: a potential role for apolipoprotein E