Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.
Farez MF, Mascanfroni ID, Méndez-Huergo SP, Yeste A, Murugaiyan G, Garo LP, Balbuena Aguirre ME, Patel B, Ysrraelit MC, Zhu C, Kuchroo VK, Rabinovich GA, Quintana FJ, Correale J.Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.Cell. 2015 Sep 10;162(6):1338-1352. doi: 10.1016/j.cell.2015.08.025
We have all heard about vitamin D and the influence of vitaminD but one of the Profs in the lab came up to me a quite a few years ago and said that may be melatonin was an influence. This is produced when we sleep in response to the dark, is important in MS.
Project M was born and he asked, could we look at the effect of melatonin in EAE.
However as it had already been done in EAE a few times and even in MS already.Why do it again in EAE? and Why didn’t they just do something in MS, rather than waste animals, so heels were well and truly dragged..sorry Prof..
Anyway the Prof gets their wish and I’m off the hook as this paper looks at the effect of melatonin.
It reports that relapses are associated with low melatonin levels, which varies with the seasons (is ice cream also?) and then they show that melatonin has some capacity to inhibit EAE by blocking Th17 and promoting regulatory cells.
They use daily 5mg/kg, so that is 350mg in human doses and about 350 1mg tablets a day, which is a bit above the nutriceutical dose. Will it work to inhibit MS, maybe, more trials are needed.
You can’t buy melatonin in the chemists in UK but it is in supermarkets in the US and 1 tablet is part of my lack of jet lag routine and so one pot would last me years…
Where is the hard evidence it works…..there is none…
Maybe Project M will be tried in MS but what is the dose?. This is the key with translating all nutriceuticals because at the dose used in animals you will be rattling, especially with all those biotin tabs too.