Effects of Oral Melatonin Supplementation on Inflammatory and Oxidative Stress Markers, Metabolic Parameters, Blood Pressure, and Sleep Quality in Patients With Stage 3 - 4 Chronic Kidney Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background: Chronic kidney disease (CKD) is a growing global health burden characterized by progressive renal decline, chronic inflammation, oxidative stress, and frequent sleep disturbances. Melatonin, an endogenous regulator of circadian rhythm with antioxidant and anti-inflammatory properties, has been proposed as a potential adjunctive therapy in CKD. Objectives: To evaluate the effects of oral melatonin supplementation on inflammatory markers, oxidative stress, metabolic parameters, blood pressure, and sleep quality in non-dialysis patients with CKD stages 3 - 4. Methods: In this randomized, double-blind, placebo-controlled clinical trial enrolled 73 non-dialysis patients with CKD stages 3 - 4 (glomerular filtration rate < 60 mL/min/1.73 m²). Participants were randomly assigned to receive either oral melatonin (3 mg/day) or matching placebo for 12 weeks. Serum levels of interleukin-1β (IL-1β), malondialdehyde (MDA), blood pressure, sleep quality, and routine biochemical parameters were measured at baseline and post-intervention. Results: After 12 weeks, no significant changes were observed in IL-1β or MDA levels in either group (P > 0.05). The MDA decreased in the melatonin group (-0.39 ± 9.36) and slightly increased in the placebo group (0.69 ± 4.93; between-group P = 0.313). Melatonin supplementation yielded a significant reduction in total cholesterol compared with placebo. Regarding sleep quality, both groups showed slight numerical changes, but the melatonin group exhibited a relatively more favorable trajectory, a smaller mean decline in PSQI score (-0.18 ± 0.84) compared with placebo (-0.69 ± 1.06; P = 0.047). Conclusions: Twelve-week melatonin supplementation did not significantly alter inflammatory or oxidative stress markers in stage 3 - 4 CKD but was well tolerated and demonstrated modest metabolic and sleep-related benefits. Larger and longer studies are warranted to clarify its clinical relevance and mechanistic pathways in this population.