Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial

•This study evaluated the effects of melatonin on PD.•Melatonin improved some clinical symptom in PD.•Melatonin decreased hs-CRP, insulin and HOMA-IR, and elevated TAC in patient with PD.•Melatonin down-regulated TNF-α, PPAR-γ and LDLR in patients with PD. This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (β −2.33; 95% CI, −3.57, −1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (β −1.82; 95% CI, −3.36, −0.27; P = 0.02), Beck Depression Inventory (BDI) (β −3.32; 95% CI, −5.23, −1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (β −2.22; 95% CI, −3.84, −0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (β −0.94 mg/L; 95% CI, −1.55, −0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (β 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (β 77.08 μmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (β −1.79 μIU/mL; 95% CI, −3.12, −0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (β −0.47; 95% CI, −0.80, −0.13; P = 0.007), total- (β −13.16 mg/dL; 95% CI, −25.14, −1.17; P = 0.03) and LDL- (β −10.44 mg/dL; 95% CI, −20.55, −0.34; P = 0.04) compared with the placebo. Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.