Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

Randomized, double-blind, placebo-controlled trial in 100 obese women aged 33–51 years with BMI ≥28 kg/m2 diagnosed with metabolic syndrome.

Histidine 4 g/day (two 1 g tablets after breakfast and two after dinner) for 12 weeks.

Histidine supplementation (4 g/day for 12 weeks) improved insulin resistance and metabolic risk factors in obese women with metabolic syndrome. Compared with placebo, HOMA-IR decreased by 1.09 units; BMI decreased by 0.86 kg/m2; waist circumference decreased by 2.86 cm; fat mass decreased by 2.71 kg; NEFA decreased by 173.26 μmol/L. Inflammatory markers TNF-α and IL-6 decreased by 3.96 pg/mL and 2.15 pg/mL, respectively; antioxidant enzymes SOD increased by 17.84 U/mL and GSH-Px increased by 13.71 nmol/mL; serum histidine increased by 18.23 μmol/L and adiponectin increased by 2.02 ng/mL. Changes in histidine correlated with changes in HOMA-IR and its risk factors. No adverse effects observed; liver and kidney function unaffected. In vitro, histidine reversed PA-induced insulin-signaling impairment (pAkt/Akt) and reduced IL6/TNF mRNA and NF-κB protein expression in adipocytes in a dose-dependent manner, with effects diminished by NF-κB inhibitor, suggesting a mechanism via NF-κB signaling. Conclusion: Histidine could improve insulin resistance and reduce inflammation and oxidative stress in obese women with metabolic syndrome, potentially via the NF-κB pathway.

Female-only sample; 12-week duration; 92 completers; limited generalizability to men or other populations; no long-term safety data.