12‑weeks fisetin supplementation and interval resistance with aerobic training: changes in Maresin‑1 and inflammatory markers in men with obesity: a randomized controlled trial.

2026-05-31
Journal of the International Society of Sports Nutrition 23(1)
- Mehran Alipour
- Ayoub Saeidi
- Keyvan Hejazi
- Ismail Laher
- Hassane Zouhal

PubMed: 42218768
DOI: 10.1080/15502783.2026.2679718

Study Design

Type: Randomized Controlled Trial (RCT)
Population: 44 obese adult males (BMI > 30 kg/m²)
Methods: 12-week parallel-group randomized controlled trial; four interventions: control-placebo, fisetin (200 mg/day), training-placebo, or training-fisetin; training comprised eight resistance exercises at 60% 1RM with active rest followed by progressive aerobic bouts (50%-70% HRmax)
Duration: 12 weeks

Background

Obesity is characterized by low‑grade chronic inflammation and impaired insulin sensitivity. Maresin‑1 (MaR1), a specialized pro‑resolving mediator, plays a critical role in terminating inflammation and supporting metabolic homeostasis; however, interventional data in humans remain scarce. This study examined whether fisetin supplementation augments the effects of concurrent interval resistance-aerobic training on Maresin‑1, pro‑inflammatory markers, and insulin resistance in obese men.

Methods

In a 12‑week parallel‑group randomized controlled trial, 44 obese adult males (BMI > 30 kg/m²) completed one of four interventions: control-placebo (CP), fisetin (F) (200 mg/day), training-placebo (TP), or training-fisetin (TF). Training comprised eight resistance exercises at 60% 1RM with active rest followed by progressive aerobic bouts (50%-70% HRmax). Anthropometric and biochemical parameters, including plasma Maresin‑1, interleukin-6 (IL‑6), tumor necrosis factor-alpha (TNF‑α), fasting blood glucose (FBS), insulin, and HOMA‑IR, were assessed pre‑ and post‑intervention.

Results

Significant group × time interactions were observed for Maresin‑1 (p = 0.034), IL‑6 (p = 0.001), TNF‑α (p = 0.001), FBS (p = 0.001), insulin (p = 0.001), and HOMA‑IR (p = 0.001). Maresin‑1 increased in the TP (p = 0.001) and TF (p = 0.001) groups. IL‑6 decreased in T (p = 0.006), TF (p = 0.001), and F (p = 0.013) groups. TNF‑α decreased in all intervention groups (F, TP, and TF) (p = 0.002). FBS, insulin, and HOMA‑IR decreased significantly in all active arms (p = 0.003), with the greatest reductions in the TF group.

Conclusion

Twelve weeks of concurrent interval resistance-aerobic training, especially when combined with fisetin, improved inflammatory resolution (↑Maresin‑1, ↓IL‑6, and ↓TNF‑α) and metabolic control (↓FBS, ↓insulin, and ↓HOMA‑IR) in obese men. The synergy between exercise‑induced adaptations and fisetin's anti‑inflammatory properties offers a promising non‑pharmacological strategy for mitigating obesity‑related metabolic risk.

Research Insights

Fisetin→Increased Maresin-1 Level
Maresin‑1 increased in the TP (p = 0.001) and TF (p = 0.001) groups
Effect
Neutral
Effect size
Small
Dose
200 mg/day
Fisetin→Reduced Fasting Blood Glucose Levels
FBS, insulin, and HOMA‑IR decreased significantly in all active arms (p = 0.003), with the greatest reductions in the TF group
Effect
Beneficial
Effect size
Small
Dose
200 mg/day
Fisetin→Reduced HOMA-IR
FBS, insulin, and HOMA‑IR decreased significantly in all active arms (p = 0.003), with the greatest reductions in the TF group
Effect
Beneficial
Effect size
Small
Dose
200 mg/day
Fisetin→Reduced Insulin Levels
FBS, insulin, and HOMA‑IR decreased significantly in all active arms (p = 0.003), with the greatest reductions in the TF group
Effect
Beneficial
Effect size
Small
Dose
200 mg/day
Fisetin→Reduced Interleukin-6 Levels
IL‑6 decreased in T (p = 0.006), TF (p = 0.001), and F (p = 0.013) groups
Effect
Beneficial
Effect size
Small
Dose
200 mg/day
Fisetin→Reduced Tumor Necrosis Factor Alpha
TNF‑α decreased in all intervention groups (F, TP, and TF) (p = 0.002)
Effect
Beneficial
Effect size
Small
Dose
200 mg/day