A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

J Am Board Fam Med. 2022 Jul-Aug;35(4):695-707. doi: 10.3122/jabfm.2022.04.210529.


This study aimed to help determine the effect of dietary supplements on symptom course and quality of life in patients with mild-to-moderate COVID-19 infection.

Design: We modified the Wisconsin Upper Respiratory Symptom Survey (WURSS) to conduct a 3 arm, parallel, randomized, double-blind, placebo-controlled trial, enrolling patients with mild-to-moderate symptoms of COVID-19 infection. Patients took placebo (n = 34), vitamin C 1000 mg (n = 32), or melatonin 10 mg (n = 32) orally for 14 days.

Outcomes: Ninety Eight (98 out of 104 recruited; mean age = 52 years) patients completed the study. Outcomes were calculated as differences from baseline scores on each of 2 WURSS-derived surveys and analyzed using a spline regression analysis. Regarding symptom progression, those patients taking placebo and vitamin C progressed at the same rate. When compared with those taking placebo (coefficient = -1.09 (95% confidence interval [CI] = -1.39 to -0.8) the group taking melatonin had a faster resolution of symptoms (coefficient = -0.63 [95% CI -1.02 to -0.21] P = .003). By day 14 all 3 groups had reached plateau.Quality-of-life impact analysis demonstrated that the group taking vitamin C improved at the same rate as the group taking placebo (coefficient = -0.71 (95% CI = -1.11 to -0.3)). The group taking melatonin (coefficient = -1.16 (95% CI = -1.75 to - 0.57) P < .005) had a faster improvement in quality-of-life. By day 14 all 3 groups had reached plateau.

Conclusion: Vitamin C 1000 mg once daily has no effect on disease progression. Melatonin 10 mg daily may have a statistically significant effect but it is unclear if this represents a clinically significant benefit to those with mild-to-moderate symptoms of COVID-19 infection. Further study is warranted.

Keywords: Ascorbic Acid; COVID-19; Dietary Supplements; Double-Blind Method; Melatonin; Quality of Life; Regression Analysis; Vitamin C; Vitamins; WURSS.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascorbic Acid / therapeutic use
  • COVID-19 Drug Treatment*
  • Double-Blind Method
  • Humans
  • Melatonin* / adverse effects
  • Melatonin* / therapeutic use
  • Middle Aged
  • Quality of Life
  • Vitamins / therapeutic use


  • Vitamins
  • Melatonin
  • Ascorbic Acid