Assessment of Zinc Administration on Metabolic Profile, Oxidative Stress, and Gene Expression in Patients Undergoing Methadone Maintenance Treatment: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Methadone maintenance treatment (MMT) causes important clinical problems, such as oxidative stress (OS) and inflammation. Zinc (Zn) has antioxidant and anti-inflammatory effects and regulates gene expression. Objectives: This study investigated the effects of Zn administration on the metabolic, OS, and expression of nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), and interleukin 10 genes in heroin patients undergoing MMT. Methods: This clinical trial was conducted on 45 patients under MMT who received 30 mg/d of Zn (n=23) or placebo (n=22). Fasting blood samples were collected at baseline and 12 weeks after the intervention to quantify metabolic parameters, OS, and gene expression. Results: Zn levels were significantly elevated in the intervention group compared to the placebo group. Further, consuming Zn could significantly improve high-density lipoprotein levels, insulin, homeostasis model assessment-estimated insulin resistance, and OS. Anxiety significantly decreased after 12 weeks of intervention. Finally, Zn up-regulated Nrf2 gene expression in patients under MMT. Conclusion: The results indicated that Zn administration could improve metabolic factors and gene expression in patients undergoing MMT