Project M and melatonin

Roostaei T, Sahraian MA, Hajeaghaee S, Gholipour T, Togha M, Siroos B, Mansouri S, Mohammadshirazi Z, Aghazadeh Alasti M, Harirchian MH. Impact of Melatonin on Motor, Cognitive and Neuroimaging Indices in Patients with Multiple Sclerosis.
Iran J Allergy Asthma Immunol. 2015;14(6):589-95.

A series of preclinical and clinical studies have shown the immunomodulatory effect of melatonin, especially in the state of chronic inflammation. A double-blind, randomized, parallel-group, placebo-controlled clinical trial was designed to study the tolerability and efficacy of supplemental therapy with melatonin (3 mg/day) in comparison to placebo in relapsing-remitting MS (RRMS) patients receiving once weekly interferon beta. Patients were followed up for 12 months. Primary outcomes consisted of the number of relapses, change in Extended Disability Status Scale (EDSS), and the number and volume of new T2 and gadolinium-enhancing brain lesions. Secondary outcomes included change in performance on Multiple SclerosisFunctional Composite (MSFC) as well as change in fatigue and depression. The outcomes were evaluated every three months. Twenty-six patients (13 in each group) were recruited in the study. All participants, except for one patient in the placebo group, completed the study. No patient reported serious adverse events. There was no significant difference either in primary or secondary outcomes between melatonin and placebo arm. However, a trend for beneficial effect was observed for melatonin on change in MSFC performance and the cognitive subscore of the Modified Fatigue Impact Scale (p=0.05 and 0.006, respectively, not corrected for multiple comparisons). We found no significant effect for treatment with melatonin on measures of clinical and functional disability and development of brain lesions in our small sample-size study. Studies with higher statistical power and longer follow up are needed to further evaluate the potential immunomodulatory effect of melatonin in RRMS treatment.

One of the neuros tried to get us to do some animal experiments on melatonin…projectM, but we dragged our heels and said there was already animal data and even human data, so if they wanted to do something about it, they should do it in humans rather than waste animals. 

So here we have it the nutriceutal makes no difference than beta interferon alone but with twenty six people could it ever find a difference?  Would this convince you to do a bigger study?

Will the Prof every get project M off the ground?

So why choose a neutriceutical over one of the bigger guns that have impact and really do something. Neutriceuticals have their part to play but is it wise to believe that they can really replace effective DMT. Time and time again the answer is No. 

I was talking recently to ProfG about people who refuse treatment, presumably to use safe alternative medicines and down the line time and time again, it was disaster.

 Time is Brain….Save it.

Also for the Prof here is yet more animal data. Is their any value in looking to see if it stops relapsing disease?

Chen SJ, Huang SH, Chen JW, Wang KC, Yang YR, Liu PF, Lin GJ, Sytwu HK.Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis.
Int Immunopharmacol. 2015 ;31:169-177. doi: 10.1016/j.intimp.2015.12.020. [Epub ahead of print]

Melatonin is the major product secreted by the pineal gland at night and displays multifunctional properties, including immunomodulatory functions. In this study, we investigated the therapeutic effect of melatonin in experimental autoimmune encephalomyelitis (EAE). We demonstrated that melatonin exhibits a therapeutic role by ameliorating the clinical severity and restricting the infiltration of inflammatory Th17 cells into the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Furthermore, melatonin enhances splenic interleukin (IL)-10 expression in regulatory T cells by inducing IL-27 expression in the splenic DC; it also suppresses the expression of IFN-γ, IL-17, IL-6, and CCL20 in the CNS and inhibits antigen-specific T cell proliferation. However, there were no significant differences in the percentage of splenic regulatory T cells. These data provide the first evidence that the therapeutic administration of melatonin is effective in mice with EAE and modulates adaptive immunity centrally and peripherally. Thus, we suggest that melatonin could play an adjunct therapeutic role in treating human CNS autoimmune diseases such as multiple sclerosis. Melatonin merits further studies in animals and humans.

First eh?……
Álvarez-Sánchez N, Cruz-Chamorro I, López-González A, Utrilla JC, Fernández-Santos JM, Martínez-López A, Lardone PJ, Guerrero JM, Carrillo-Vico A.Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance.Brain Behav Immun. 2015:50:101-14. doi: 10.1016/j.bbi.2015.06.021. published  in june

Experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS), is triggered by myelin-specific Th1 and Th17 cells. The immunomodulatory activities of melatonin have been shown to be beneficial under several conditions in which the immune system is exacerbated. Here, we sought to elucidate the basis of the melatonin protective effect on EAE by characterizing the T effector/regulatory responses, particularly those of the memory cell subsets. Melatonin was tested for its effect on Th1, Th17 and T regulatory (Treg) cells in the lymph nodes and CNS of immunodominant peptide of myelin oligodendrocyte glycoprotein (pMOG)-immunized and EAE mice, respectively. The capacity of melatonin to ameliorate EAE as well as modifying both T cell response and effector/regulatory balance was surveyed. T cell memory subsets and CD44, a key activation marker involved in the EAE pathogenesis, were also examined. Melatonin protected from EAE by decreasing peripheral and central Th1/Th17 responses and enhancing both the Treg frequency and IL-10 synthesis in the CNS. Melatonin reduced the T effector memory population and its pro-inflammatory response and regulated CD44 expression, which was decreased in T effector cells and increased in Tregs. The alterations in the T cell subpopulations were associated with a reduced mononuclear infiltration (CD4 and CD11b cells) of the melatonin-treated mice CNS. For the first time, we report that melatonin protects against EAE by controlling peripheral and central T effector/regulatory responses, effects that might be partially mediated by CD44. This immunomodulatory effect on EAE suggests that melatonin may represent an effective treatment option for MS.

First eh?……

Kang JC, Ahn M, Kim YS, Moon C, Lee Y, Wie MB, Lee YJ, Shin T.Melatonin ameliorates autoimmune encephalomyelitis through suppression of intercellular adhesion molecule-1.J Vet Sci. 2001 Aug;2(2):85-9.

Should we do a proper study in MS and get a real answer?

Some people call these types of comment arrogant…….

They do not comment on the validity of the work but serve to show that there is not always complete agreement and serves to show how the peer review process has its limitations  as they can not all be the first to show. This is a term used to suggest the importance of the work and if you read papers you see it often

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  • I think they should look for spinal cord injuries and nutraceuticals, in which case melatonin, since spinal cord injuries are much more difficult to decomposed … I think the role of nutraceuticals is no treatment "monotherapy" but rather aid, to act together to DMTs. I think it's the same discussion you have when looking for vitamin D, take it way assist, as an adjunct and not as a protagonist. Here in Brazil and has this "alternative monotherapy approach with high doses of vitamin D," which we have seen really are people who can stand up without outbreaks within a space 5-7 years, but some have presented very strong surge, and the process for SPMS is started or the fact consequences become irreversible even for those who remain RRMS. Probably so will Melatonin … Perhaps the right approach is the promotion of nutraceuticals as "support", not as the only option …

  • I messed up in the comment: meant that spinal cord injuries are much more difficult to be blended, remyelinate of the affected myelin sheath …

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