Monday, 14 September 2015

Melatonin and seasonal variability of MS.

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

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.


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.

15 comments:

  1. I read about this study on melatonin ... I at least thought the issue of climate seasonality influence on the production of melatonin, the participants appeared to have improved the symptoms of MS in autumn and winter, while another study on the production of vitamin D in the body has shown that it is obviously lower in these seasons ... I could have a relationship the route of action of Melatonin with Vitamin D? Anyway I always had insomnia even before a day "dream" of having MS, then melatonin supplements taken in the days that insomnia is "at its peak" always helped me to relax and sleep. In fact I think it is not even insomnia but my biological clock that is "inverted"...Anyway Anyway I even buy over the Internet ... But is this question of dose, to sleep I only take 1 tablet 30 minutes before bedtime and low-dose ...

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  2. Could melatonin have some part in progressive MS? I have felt much better during the summer and rubbish in winter the last couple of years, with a lot of "temporary symptoms". I wondered if it might be a vD slump, but last winter I was taking vD supplements. Who knows if it has anything to do with melatonin, is the answer I suppose...

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  3. I sleep better after taking 10.000 ui/day VitD3.

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  4. I think MSDoctors should learn more about neuropharmacology. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001211/

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  5. Melatonin and brain inflammaging
    http://www.ncbi.nlm.nih.gov/pubmed/25697044

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  6. What about the mouse to human dose difference
    What does this mean for people who want to try melatonin
    What is the suggested dose as per the trial?

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    1. The mouse dose is so far above the human dose one wonders if it would do anything if a human dose was tested in mouse. We get a lot of amazing science proving the hypothesis but seldom do we see a dose response.

      I am not going to start suggesting relevant doses because truth is I have no idea

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    2. Maybe just good sleep hygiene, time outdoors in natural light and a good diet would be as good as anything?

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    3. I think you raise some good points. Bedroom with dark or blackout curtains. Switching off screens a few hours before bed and catching the angel train (going to bed early).

      Magnesium and calcium are involved in melatonin production. Foods which assist melatonin production include toms, bananas, turmeric, ginger, rice, corn and oats.

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  7. It is important that we get adequate exposure to light in daytime hours, as inadequate exposure can distrupt natural melatonin cycles.

    Common melatonin inhibiting drugs include NSAIDs, anti anxiety meds, steroids, some anti depressants and if at all possible avoid taking these in the few hours before bed.

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  8. You mentioned Biotin. What do you use it for?

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  9. Perhaps MS in the future will be treated with DMT's and also elements of how SAD (seasonal affective disorder) is. With CBT for understanding how the seasons impact on MS.

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  10. B vitamins can interfere with the production of melatonin I have been reading. Especially B12, so would be better to take B vitamins in the morning or lunchtime and not near bedtime.

    I take B1, B12 and B complex so will be changing to taking all these with breakfast. I did try biotin too but found I had increased activity at night (foot spasms) so stopped taking it.
    Perhaps that's why I had the foot spasms at night as was taking biotin sometimes near bedtime?

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