Melatonin and vitamin D, two sides of the same coin, better to land on its edge to improve multiple sclerosis

Previous studies revealed a latitudinal gradient of multiple sclerosis (MS) prevalence, increasing by moving from the equator to the poles. The duration and quality of an individual's exposure to sunlight vary with latitude. Skin exposure to sunlight activates vitamin D synthesis, while light absence, as perceived by the eyes, activates melatonin synthesis in the pineal gland. Vitamin D or melatonin deficiency/insufficiency or overdose can occur at any latitude due to specific lifestyles and diets. Moving away from the equator, especially beyond 37 degrees, decreases vitamin D while raising melatonin. Furthermore, melatonin synthesis increases in cold habitats like northern countries. Since melatonin's beneficial role was shown in MS, it is expected that northern countries whose individuals have higher endogenous melatonin should show a lower MS prevalence; however, these are ranked with the highest scores. In addition, countries like the United States and Canada have uncontrolled over-the-counter usage. In high latitudes, vitamin D deficiency and a higher MS prevalence persist even though vitamin D is typically compensated for by supplementation and not sunlight. Recently, we found that prolonged darkness increased MS melatonin levels, mimicking the long-term increase in northern countries. This caused a reduction in cortisol and increased infiltration, inflammation, and demyelination, which were all rescued by constant light therapy. In this review, we explain melatonin and vitamin D's possible roles in MS prevalence. The possible causes in northern countries are then discussed. Finally, we suggest strategies to treat MS by manipulating vitamin D and melatonin, preferably with sunlight or darkness, not supplements.

Automated summary

Previous studies have shown that the prevalence of multiple sclerosis (MS) increases as one moves from the equator to the poles. This is due to variations in exposure to sunlight, which activates vitamin D synthesis, and absence of light, which activates melatonin synthesis. Deficiencies or excesses in vitamin D or melatonin can occur at any latitude due to specific lifestyles and diets. Northern countries with higher melatonin levels were expected to have lower MS prevalence, but this is not the case. Vitamin D deficiency and a higher MS prevalence persist in high latitudes even with supplementation. Darkness increases MS melatonin levels, causing negative effects that can be alleviated by light therapy. This review discusses the roles of melatonin and vitamin D in MS prevalence, possible causes in northern countries, and suggests strategies to treat MS using sunlight or darkness instead of supplements.