Adipokines, Inflammation, and Metabolic Diseases · Journal article
BMC Sports Science Medicine and Rehabilitation · August 12, 2026
Encouraging direction, but not yet definitive.
This small double-blind RCT demonstrates that 12 weeks of combined functional and aerobic training plus 500 μg daily folic acid supplementation produced greater reductions in body weight, body fat, fasting glucose, insulin, and HOMA-IR, and greater increases in serum Isthmin-1, compared to training alone or supplementation alone in young obese men. The finding is supported by consistent reductions in inflammatory cytokines across all active intervention groups and an inverse correlation between Isthmin-1 and insulin resistance, but the very small sample size and use of surrogate endpoints limit confidence and generalizability.
Double-blind randomized controlled trial, four parallel groups. Young men with obesity, age 23–32 years, BMI ≥ 30 kg/m², enrolled in Iran (prospectively registered at Iranian Registry of Clinical Trials).. Intervention: Combined Training + Supplementation: 12 weeks of progressive functional exercises (stability, strength, interval training) combined with treadmill-based aerobic exercise, plus 500 μg folic acid daily. Compared with: Control (no intervention); Folic Acid Supplementation alone (500 μg daily); Combined Training alone (no supplementation). n = 44. Iran.
Body weight and BMI decreased significantly only in the CTS group (P = 0.001) Body fat percentage and fat mass reductions were significantly greater in the CTS group versus CT group (P = 0.001) Fasting glucose, insulin, and HOMA-IR decreased significantly in S, CT, and CTS groups, with most pronounced improvements in CTS (P < 0.05)
All endpoints are surrogate biomarkers; no hard clinical outcomes (cardiovascular events, mortality, type 2 diabetes incidence) reported. No reporting of dropout rates, adherence, or potential harms; allocation concealment method not described.
If confirmed in larger trials with longer follow-up, these findings suggest that combining structured aerobic and functional training with folic acid supplementation may offer superior metabolic benefits to either intervention alone in obese men. Clinicians should recognize this as preliminary evidence supporting a multimodal intervention strategy, but should not adopt this as standard practice based on this small trial alone.
A small double-blind RCT with clear surrogate endpoints (inflammatory markers, insulin resistance, body composition) showing favourable effects of combined training plus folic acid, but limited by small sample size (n=44, 11 per group) and surrogate rather than hard clinical outcomes.
As stated by the source record.
Quoted from the source exactly as published.
If confirmed in larger trials with longer follow-up, these findings suggest that combining structured aerobic and functional training with folic acid supplementation may offer superior metabolic benefits to either intervention alone in obese men. Clinicians should recognize this as preliminary evidence supporting a multimodal intervention strategy, but should not adopt this as standard practice based on this small trial alone.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Obesity is a complex systemic metabolic disorder characterized by chronic low-grade inflammation and insulin resistance. This study aimed to investigate the effects of a 12-week intervention combining functional and aerobic training with folic acid supplementation on serum levels of Isthmin-1 (ISM1), key inflammatory markers (MCP-1, TNF-α, IL-6), and insulin resistance in young men with obesity. In this double-blind randomized experimental trial, 44 men with obesity (age: 23–32 years, BMI ≥ 30 kg/m²) were randomly allocated into four equal groups ( n = 11 per group): Control (CG), Folic Acid Supplementation (S), Combined Training (CT), and Combined Training + Supplementation (CTS). The training protocol consisted of 12 weeks of progressive functional exercises (focusing on stability, strength, and interval training) combined with treadmill-based aerobic exercise. The supplemented groups consumed 500 μg of folic acid daily. Blood samples were collected 48 h before the initiation and 48 h after the completion of the 12-week intervention to assess biochemical, inflammatory, and glycemic indices. Data were analyzed using a 2×4 mixed-design repeated measures ANOVA, followed by Bonferroni post-hoc pairwise comparisons, with the significance level set at P < 0.05. Body weight and BMI decreased significantly only in the CTS group ( P = 0.001). While both the CT and CTS groups exhibited significant reductions in body fat percentage and fat mass, the magnitude of these reductions was significantly greater in the CTS group ( P = 0.001). Regarding glycemic control, all three active intervention groups (S, CT, and CTS) demonstrated significant reductions in fasting glucose, insulin, and HOMA-IR, with the most pronounced improvements observed in the CTS group ( P < 0.05). Serum ISM1 levels increased significantly in both the CT and CTS groups (P < 0.05), whereas serum levels of MCP-1, TNF-α, and IL-6 decreased significantly in all three intervention groups ( P = 0.001). Furthermore, serum ISM1 levels exhibited a significant inverse correlation with both inflammatory markers and insulin resistance indices. The findings suggest that 12 weeks of combined functional and aerobic training with folic acid supplementation may offer potential benefits for improving metabolic status and insulin sensitivity in obese men; however, these preliminary outcomes should be interpreted with caution due to the limited sample size. https://www.ncbi.nlm.nih.gov/mesh/68009765. https://www.ncbi.nlm.nih.gov/mesh/68015444. https://www.ncbi.nlm.nih.gov/mesh/68005492. https://www.ncbi.nlm.nih.gov/mesh/68007249. https://www.ncbi.nlm.nih.gov/mesh/68007333. https://www.ncbi.nlm.nih.gov/mesh/2007061. The trial was prospectively registered at the Iranian Registry of Clinical Trials ( https://fa.irct.ir/trial/87438 (accessed on 26 November 2025) under registration number (IRCT20120129008863N15).
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.