Tier 2 — strong

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

Alipour M, Saeidi A, Hejazi K, Laher I, Zouhal H
Journal of the International Society of Sports Nutrition 2026 23(1):2679718

Bibliography

PubMed
PMID 42218768
PubMed Central
PMC13224698
DOI
10.1080/15502783.2026.2679718
Funding
There is no funding or specific grant (per the published Funding statement).
Competing interests
No potential conflict of interest was reported by the author(s) (per Disclosure statement).

Study snapshot

Design12-week, 4-arm, parallel-group randomised controlled trial.
ModelObese adult men (BMI over 30 kg/m2).
Sample107 assessed for eligibility, 60 randomised (15 per arm: control-placebo, fisetin-only, training-placebo, training+fisetin), 44 completed and were analysed per-protocol (11 per arm) after 16 withdrawals (6 scheduling conflicts, 5 minor non-training illnesses, 5 lack of readiness to maintain exercise frequency; no adverse events or exercise-induced injuries).
InterventionFisetin 200 mg/day, daily continuous dosing, alone or combined with interval resistance-aerobic training (8 resistance exercises at 60% 1RM with active rest, followed by progressive aerobic bouts at 50-70% max heart rate), for 12 weeks.
Duration12 weeks
EndpointsPlasma Maresin-1; IL-6; TNF-alpha; Fasting blood glucose; Insulin; HOMA-IR

What the study showed, in plain terms

This is a genuine completed human RCT testing daily fisetin (200 mg/day, not the pulsed senolytic dose) in obese men, alone and combined with structured exercise, on inflammation and metabolic markers over 12 weeks — a different population and a different question from the frailty/senescence trials, but real human dosing data with a positive result.

The training-plus-fisetin group showed the largest improvements: increased Maresin-1 (a specialised pro-resolving inflammatory mediator), decreased IL-6 and TNF-alpha, and improved fasting glucose, insulin, and HOMA-IR (a marker of insulin resistance). Fisetin alone (without training) also improved IL-6 and TNF-alpha, though less than the combined arm.

This adds real, if population-specific, human evidence for fisetin's anti-inflammatory and metabolic effects at a continuous daily dose closer to what commercial capsules actually deliver — complementary to, but distinct from, the pulsed high-dose senolytic protocol used in the frailty trials.

Key findings

  • Significant group x time interactions were observed for Maresin-1 (p=0.034), IL-6 (p=0.001), TNF-alpha (p=0.001), fasting blood glucose (p=0.001), insulin (p=0.001), and HOMA-IR (p=0.001).
  • Maresin-1 increased significantly in the training-placebo and training-fisetin groups (both p=0.001).
  • IL-6 decreased in the training-only, training-fisetin, and fisetin-only groups.
  • TNF-alpha decreased significantly in all three active intervention groups (fisetin, training-placebo, training-fisetin) (p=0.002).
  • Fasting glucose, insulin, and HOMA-IR decreased significantly in all active arms, with the greatest reductions in the training-plus-fisetin group.

What this study can and cannot tell us

  • Moderate sample size (44 analysed across four arms, 11 per arm) -- modest statistical power for detecting smaller effects.
  • Single population studied (sedentary obese adult men, single geographic region -- Kurdistan, Iran) -- findings may not generalise to women, non-obese adults, or older frailty-focused populations.
  • Daily continuous 200 mg dosing, not the pulsed 20 mg/kg protocol used in the frailty and osteoarthritis trials -- results speak to a different dosing paradigm and should not be conflated with senolytic-dose evidence.
  • Confirmed via full-text cross-reference: this trial and the companion Nutrients paper on asprosin and adipokines (Alipour et al., same registration IRCT20120129008863N14, same Hakim Sabzevari University ethics approval IR.HSU.REC.1404.044, identical 107-to-60 recruitment funnel and exclusion breakdown) report the SAME underlying randomised trial and the same 60 participants, split into two outcome-focused publications -- this one covering Maresin-1/inflammatory/insulin-resistance markers, the companion paper covering asprosin/adipokines/lipid profile. Treat as two facets of one trial, not independent replication. Note the two papers also used different primary analysis populations for reporting (this paper: per-protocol, n=44; companion paper: intention-to-treat with group-mean imputation, N=60), which readers should not mistake for a discrepancy in underlying data.

Related papers in the corpus

Tier 2
The Effects of Interval Resistance-Aerobic Training and Fisetin Supplementation on Asprosin and Selected Adipokines in Obese Men: A Double-Blind Randomized Control Trial
Alipour M et al. · Nutrients · 2026

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability