Effects of Omega-3 and Omega-9 Fatty Acid Supplementation on HOMA-IR and Inflammatory Markers in Children with Obesity and Insulin Resistance: A Triple-Blind RCT with Post-Intervention Follow-Up.

Active supplementation with combined omega-3 and omega-9 significantly reduced fasting insulin and HOMA-IR during the 3-month treatment period.

• The Combined group showed significant reductions in fasting insulin and HOMA-IR (p < 0.001).
• The Omega-9 group also showed significant reductions in fasting insulin (p = 0.010) and HOMA-IR (p = 0.006).
• The study included 97 children aged 8-17 years with overweight/obesity and baseline insulin resistance (HOMA-IR > 3.0).
• Participants received 1.8 g/day of omega-3 (n = 32), omega-9 (n = 34), or combined supplementation (n = 31) for 3 months.

Only the Combined supplementation group maintained significant reductions in fasting insulin and HOMA-IR at the 2-month post-intervention follow-up.

• At month 5 (2 months after treatment discontinuation), only the Combined group maintained significant reductions in both fasting insulin and HOMA-IR.
• The Omega-3 and Omega-9 groups did not maintain significant reductions in these metabolic markers at follow-up.
• Assessments were conducted at baseline (T1), end of treatment (T2), and follow-up (T3).

No significant between-group differences in HOMA-IR or fasting insulin were observed at any timepoint.

• Despite within-group reductions, between-group differences were not statistically significant at baseline, end of treatment, or follow-up.
• The absence of significant between-group differences was consistent across all three timepoints.
• This finding was described as 'consistent with response magnitude reflecting baseline status and adiposity reduction rather than treatment group per se.'

IL-6 and leptin decreased across all three supplementation groups during the intervention and remained reduced at the 2-month follow-up.

• Reductions in IL-6 and leptin were observed in the omega-3, omega-9, and combined groups during active treatment.
• These inflammatory and adipokine reductions persisted at the post-intervention follow-up (T3) across all groups.
• This suggests a sustained anti-inflammatory effect independent of which specific fatty acid supplementation was used.

Multivariable regression analysis identified baseline metabolic status and concurrent BMI reduction as the strongest predictors of metabolic response, not intervention group.

• The multivariable regression analysis included 96 participants.
• Intervention group was not an independent predictor of metabolic response in the regression model.
• Intervention group was also not a consistent independent predictor of inflammatory outcomes.
• One exception was a smaller IL-4 increase associated with omega-9 supplementation (p = 0.043), which was not confirmed in GEE analysis.

The study was a prespecified secondary analysis of a multicenter, randomized, triple-blind, three-arm parallel trial.

• The trial is registered as NCT05488223.
• The study used a triple-blind design with three parallel arms.
• The primary outcome was the change in HOMA-IR from baseline (T1) to end of treatment (T2).
• Insulin resistance was defined as HOMA-IR > 3.0 at baseline.
• Metabolic and inflammatory markers were measured at three timepoints: baseline, end of 3-month treatment, and 2-month post-intervention follow-up.

The authors characterize combined omega-3 and omega-9 supplementation as a potential metabolic adjuvant rather than a standalone therapy for HOMA-IR-defined insulin resistance in pediatric obesity.

• This conclusion was based on the lack of significant between-group differences despite within-group reductions.
• The authors note that metabolic outcomes were assessed via anthropometric and biochemical rather than imaging-based measures.
• The authors describe the supplementation as 'a potential metabolic adjuvant—not a standalone therapy—for HOMA-IR-defined insulin resistance in pediatric obesity.'