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

Abstract

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°, 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.

Causal associations between modifiable risk factors and isolated REM sleep behavior disorder: a mendelian randomization study

“…Previous observational studies have noted that during sunnier summer months, melatonin levels are lower and last for shorter periods compared to winter ( 66 , 67 ). From the poles to the equator, with increasing sunlight intensity and duration, melatonin secretion decreases ( 68 , 69 ). This phenomenon is biochemically explained by excessive sunlight suppressing the activity of key enzymes in the synthesis pathway ( 70 , 71 ), while also activating melanopsin produced by retinal ganglion cells, thereby suppressing the synthesis and release of melatonin in the pineal gland ( 70 , 72 , 73 ).…”

Pineal gland volume loss in females with multiple sclerosis

“…A potential explanation of our study results lies in the fact that the pineal gland is connected through neural paths with the eyes and melatonin produce is suppressed by the light stimulus ( Sandyk, 1997 ). The incidence of MS is higher in geographical places with shorter daylight ( Ghareghani et al, 2023 ). This can in part potentially be explained by the suppression of melatonin produced by the excessive (artificial) light stimuli during the night.…”

“…Additionally, current studies showed a beneficial effect of melatonin as a supplement in relieving some of the MS symptoms and improving the quality of life ( Skarlis and Anagnostouli, 2020 ). Moreover, the research is being conducted on melatonin as a therapeutic option in the design of therapy regimens in MS ( Ghareghani et al, 2023 ). Pineal volume can reflect the production of melatonin, given that ca.…”

“…Multiple sclerosis has a complex pathophysiology, and numerous risk factors can contribute to its development. It is acknowledged that vitamin D regulates the immune system and helps prevent the onset and spread of autoimmune diseases ( Ghareghani et al, 2023 ). Some recent studies revealed the connection between melatonin levels and immune response and disease activity in MS patients.…”

Article Review: Multiple Sclerosis

“…The notion of the "latitude gradient" posits that there is a positive correlation between distance from the equator and multiple sclerosis risk (18). This notion has stimulated inquiries into plausible environmental stimuli, such as vitamin D insufficiency resulting from diminished sunlight exposure in regions situated at higher latitudes (22,23).…”