The Effects of Magnesium and Zinc Co-Supplementation on Biomarkers of Inflammation and Oxidative Stress, and Gene Expression Related to Inflammation in Polycystic Ovary Syndrome: a Randomized Controlled Clinical Trial (Publication with Expression of Concern)

Magnesium and zinc are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. To our knowledge, data on the effects of magnesium and zinc co-supplementation on biomarkers of inflammation and oxidative stress and gene expression related to inflammation in subjects of polycystic ovary syndrome (PCOS) are scarce. This study was conducted to evaluate the effects of magnesium and zinc co-supplementation on biomarkers of inflammation and oxidative stress and gene expression related to inflammation in subjects with PCOS. This randomized double-blind, placebo-controlled trial was conducted among 60 subjects with PCOS diagnosed according to the Rotterdam criteria, aged 18-40 years old. Participants were randomly assigned into two groups to take either 250 mg of magnesium oxide plus 220 mg of zinc sulfate (containing 50 mg zinc) supplements (n = 30) or placebo (n = 30) twice a day for 12 weeks. Biomarkers of inflammation and oxidative stress were assessed at baseline and at end of treatment. Gene expression related to inflammatory cytokines was assessed in peripheral blood mononuclear cells (PBMCs) of PCOS women with RT-PCR method. After the 12-week intervention, compared with the placebo, magnesium and zinc co-supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (- 1.6 +/- 2.4 vs. + 0.1 +/- 0.7 mg/L, P = 0.001) and protein carbonyl (PCO) (- 0.14 +/- 0.28 vs. + 0.02 +/- 0.07 mmol/mg protein, P = 0.002) and significantly increased plasma total antioxidant capacity (TAC) levels (+ 60.7 +/- 69.4 vs. - 1.5 +/- 141.5 mmol/L, P = 0.03). Results of RT-PCR demonstrated that compared with the placebo, magnesium and zinc co-supplementation downregulated gene expression of interleukin-1 (IL-1) (P = 0.007) and tumor necrosis factor alpha (TNF-alpha) (P = 0.03) in PBMCs of subjects with PCOS. Overall, magnesium and zinc co-supplementation, compared with the placebo, for 12 weeks among PCOS women had beneficial effects on serum hs-CRP, plasma PCO, TAC, and gene expression of IL-1 and TNF-alpha. Clinical trial registration number: IRCT201706075623N121.