Marine ω-3 PUFA Supplementation Enhances FFAR4 Activation and Reduces Inflammatory Markers in PBMC of Subjects with Obesity: A Randomized Controlled Trial (EPICO).

EPA and DHA supplementation enhanced FFAR4 activation in peripheral blood mononuclear cells at the end of the 8-week intervention.

• Participants received 1080 mg EPA and 720 mg DHA daily for 8 weeks
• FFAR4 activation was measured in peripheral blood mononuclear cells (PBMC)
• The active placebo group received 1.6 g/day of alpha-linolenic acid (ALA) for comparison
• Both groups followed a calorie-restricted dietary regimen alongside supplementation

Marine ω-3 PUFA supplementation reduced expression of JNK and IKKβ genes in PBMC.

• JNK and IKKβ are pro-inflammatory signaling genes measured in PBMC
• Reductions in gene expression were observed in the marine ω-3 group (EPA+DHA) following the intervention
• These genes are associated with inflammatory pathways that can impair insulin sensitivity

Serum levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-18 were reduced following the intervention in the marine ω-3 PUFA group.

• TNF-α, IL-6, and IL-18 were measured in serum samples before and after the 8-week intervention
• Reductions were observed in the group supplemented with 1080 mg EPA and 720 mg DHA per day
• These cytokines are markers of the low-grade chronic inflammation associated with obesity

IL-10 levels increased significantly both within and between groups following the dietary and supplementation intervention.

• IL-10 is an anti-inflammatory cytokine
• Significant increases were observed both within each group over time and between the two groups
• This suggests that the calorie-restricted dietary regimen may have contributed to IL-10 increases independent of the specific supplement type

Both the marine ω-3 PUFA group and the active placebo group showed significant improvements in body composition and biochemical parameters following the intervention.

• The study was conducted over 8 weeks with 55 obese individuals aged 25–59 years
• Both groups followed progressive calorie restriction: −200 kcal/day during weeks 0–4 and −400 kcal/day during weeks 4–8
• Improvements in body composition and biochemical parameters were observed in both groups, suggesting a contribution from the dietary regimen
• The trial was double-blind and randomized (NCT05068557)

The study was a double-blind, randomized controlled trial involving 55 obese individuals conducted over two months.

• Trial registration: NCT05068557
• Participants were aged 25–59 years and classified as obese
• Random assignment to either active placebo (1.6 g/day ALA) or marine ω-3 group (1080 mg EPA + 720 mg DHA/day)
• Duration was 8 weeks with both supplementation and progressive calorie restriction applied to all participants

EPA and DHA have been identified as agonists of the free fatty acid receptor 4 (FFAR4), which regulates anti-inflammatory pathways associated with enhanced insulin sensitivity.

• FFAR4 expression and activation in PBMC was described as poorly investigated in humans prior to this study
• FFAR4 activation is associated with anti-inflammatory pathways
• The receptor is also linked to enhanced insulin sensitivity