The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis

Brain Behav Immun. 2013 Aug:32:180-5. doi: 10.1016/j.bbi.2013.04.010. Epub 2013 May 7.


Background: Multiple sclerosis (MS) incidence is higher in geographic regions with less sunlight exposure. Both vitamin D and melatonin are essential mediators of the effect of sunlight in health, and as such are candidates to play a key role in MS. We hypothesized that vitamin D and melatonin may have related influences in patients with MS.

Methods: In a randomized, double blind study of 40 IFN-β treated MS patients, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. Serum 25-hydroxy-vitamin-D (25-OH-D) and nighttime urine melatonin metabolite, 6-sulphatoxy-melatonin (6-SMT), were measured at baseline, 3 months and 1 year from enrolment.

Results: After 3 months supplementation, 25-OH-D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group. After 1 year, a decrease in 25-OH-D levels, accompanied by an increase of urine nighttime 6-SMT were observed in the high dose group. Percent change in serum 25-OH-D was significantly and negatively correlated with percent change in urine 6-SMT after 3 months and between 3 months to 1 year. 25-OH-D levels by the end of the study were significantly and negatively correlated to BMI.

Conclusions: Melatonin secretion is negatively correlated with alterations in serum 25-OH-D in IFN-β treated patients with MS. The finding suggests that melatonin should be considered as a potential mediator of vitamin D neuro-immunomodulatory effects in patients with MS.

Publication types

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

MeSH terms

  • Adult
  • Cholecalciferol / blood
  • Data Interpretation, Statistical
  • Depression / psychology
  • Dietary Supplements
  • Female
  • Humans
  • Hydroxycholecalciferols / blood
  • Male
  • Melatonin / analogs & derivatives
  • Melatonin / metabolism*
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • Multiple Sclerosis, Relapsing-Remitting / psychology
  • Vitamin D / administration & dosage
  • Vitamin D / therapeutic use*
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*


  • Hydroxycholecalciferols
  • Vitamins
  • Vitamin D
  • Cholecalciferol
  • 6-sulfatoxymelatonin
  • Melatonin