Hamadan University of Medical Sciences Avicenna Journal of Medical Biochemistry 2345-4113 13 1 2025 10 31 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 1 9 10.34172/ajmb.2589 EN Azam Ghaseminejad https://orcid.org/0000-0002-5070-2612 Amir Ghaderi https://orcid.org/0000-0001-9193-6039 Somayyeh Ghotloo https://orcid.org/0000-0002-4772-6365 Hadis Aboutalebian https://orcid.org/0009-0006-1420-1649 Hossein Akbari https://orcid.org/0000-0001-7486-8580 Esmat Aghadavood https://orcid.org/0000-0001-9456-9238 Hamid Reza Banafshe https://orcid.org/0000-0003-4450-8861 Nejat Kheiripour https://orcid.org/0000-0003-0684-7125 Journal Article 10.34172/ajmb.2589 2025 01 19 2025 04 22 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