Investigating the effect of Zinc supplementation on the metabolic profile and expression of Nrf2, PPARγ and IL-10 genes in patients undergoing Methadone Maintenance Treatment: A Randomized, Double-Blind, Placebo- Controlled Trial

Background: Methadone maintenance treatment (MMT) is associated with immunity dysfunction, increased inflammation, oxidative stress, and DNA damage. Zinc has various effects, including antioxidant and anti-inflammatory effects. In addition, zinc-finger proteins act as transcription factors regulating the expression of genes. In this study, we investigated the effect of Zinc supplement on the metabolic, and oxidative stress profiles, and expression of IL-10, NRF2, and PPARγ genes in heroin patients under MMT. Methods: : Randomized double-blind placebo-controlled clinical trial was carried out on 60 patients under MMT to receive 30 mg/day Zinc supplement (n=30) or placebo (n=30). Fasting blood samples were collected at the baseline and 12 weeks after intervention to quantify related markers, including metabolic, oxidative stress, and gene expression. Results: : At the end of the intervention, Zinc levels was significantly elevated in the intervention group in comparison with the placebo group (p=0.03). In addition, consuming Zink significantly changed the levels of HDL (p=0.04), insulin (p=0.01) and HOMA-IR (p=0.01). As well as the concentration of NO (p=0.02), GSH (p=0.01), TAC (p=0.04) were statistically significant between two groups. Taking Zink upregulated NRF2 gene expression (p< 0.05) in peripheral blood mononuclear cells of patients under MMT. Conclusion: Results of this study indicated that, Zinc supplement can be recommended as an adjunct to MMT which may have beneficial effects on metabolic profile, oxidative stress, and gene expression and decrease methadone side effects.