Melatonin improves primary progressive MS - Case Study

[Liberation]

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[CureOrBust]

"The doses of melatonin used by this patient eventually rose to 300 mg per day with no side effects being detected to date...."

These are HUGE doses. Most "neutraceuticals" I found are only around 3mg. That would mean swallowing 100 pills of a pack that probably only contains 60, every day. I think the Melatonin dose used above is well beyond the natural range as would be used by the body to perform its normal action. But hey, if it actually worked for all, hand me the pills.

and before anyone starts a self study, read the adverse events even at the usual doses of 1-3mg.
http://www.mayoclinic.org/drugs-supplem ... b-20059770

[ElliotB]

Melatonin is available in bulk for only $30 for a 100g pouch of pharmaceutical grade (pure with no fillers). This dosage seems to be the same as Biotin 100g would last about 6 months and as with Biotin should be very easy to take with water or can easily be encapsulated.

There are numerous references to seasonal lower levels of Melatonin triggering relapses on the internet, so who knows...

[NHE]

The thread was started originally in 2011 so it is likely the concept did not work.

I'm not sure where you got 2011 from. The case report was published in January 2015.
https://www.ncbi.nlm.nih.gov/pubmed/25546814

There are almost 100 papers in PubMed for melatonin and MS.
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... +melatonin

[ElliotB]

I had misread the thread date which is why I corrected my original post. There seems to have been a lot of studies with regard to MS and Melatonin with little success thus far. Perhaps this study will prove different as it is likely a much high dose than what has been used previously.

[David1949]

You can download the full text at the referenced website. It has some good info on PPMS and is relatively easy reading as MS papers go. It looks hopeful since it actually improved the patients disability from EDSS 8 to 6. As the authors point out, that type of improvement is not seen in PPMS cases, except for this case. The drawback is that the study consists of only one patient. Also the dose is well above the amount that would typically be used and it could be dangerous.

I have an appointment with my neuro in two weeks. I think I'll share this with him.

[David1949]

I wonder if they ever tested this lady's melatonin level to see if it was in a normal range? And what was the level when she was taking such huge doses? I didn't see any mention of that in the article but it seems like a logical question to ask.

[CureOrBust]

It looks hopeful since it actually improved the patients disability from EDSS 8 to 6. As the authors point out, that type of improvement is not seen in PPMS cases, except for this case

And that is one of the biggest problems with this report. It in itself, is a report of a single case. Its a big world, and there is more than a single case of where somewhere a single PPMS person has improved their EDSS. Being a single case, it is also possible the Melatonin issue was a specific medical condition of this one patient.

Now to read those almost 100 papers in PubMed for melatonin and MS...

----------- edit --------------------
I skim read the titles of the top few articles, and found this one (full text)

Multiple sclerosis: the role of melatonin and N-acetylserotonin.
... melatonin improves mitochondrial functioning ... Melatonin also inhibits demyelination and increases remyelination ...

I have not read the full article yet.

[Liberation]

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[whyRwehere]

Not melatonin, but one of my husband's doctors has been having some patients do sleep studies, and has found that improved sleep has had an effect on "walking" ability for some patients during the day. He offered this study to my husband, as we were discussing the movement/spasms of my husband's legs during the night. We are in the queue for the test...almost got a slot last week, but couldn't arrange for it at such short notice. If they find a problem and treat it, and if the treatment affects him, then I will let you know. Don't know if the treatment would be a breathing machine or melatonin, but I am pretty sure he does not sleep well and often has a bad day after a bad night.

[Liberation]

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[CureOrBust]

You can easily buy it from compounding pharmacy and do not have to bother with taking dozens of pills.

as pointed out by ElliotB above, you can purchase the powdered form in bulk; 10g for about USD$11 at the one I saw. Although, technically it would be illegal in Australia to import such quantities, without a directly corresponding script from a Dr.

[1eye]

Melatonin is available in bulk for only $30 for a 100g pouch of pharmaceutical grade (pure with no fillers). This dosage seems to be the same as Biotin 100g would last about 6 months and as with Biotin should be very easy to take with water or can easily be encapsulated.

There are numerous references to seasonal lower levels of Melatonin triggering relapses on the internet, so who knows...

Some fool from the Internet convinced my friend to take some minuscule amount of Biotin a whole bunch of times a day with probably more biological activity in the huge amount of filler than in the microscopic amounts of biotin.

The French trial that had some effect on progressive MS, used 300 mg. of biotin. I use about double that volume of powder, filled out with about 300 mg of rice bran filler. This stuff will not hurt me. The dose has a good effect on my lower digestion, which is improved. Taking less than this dose, you are following no medical or scientific example. You are on your own. You are a non-clinical trial with the size of one (1) subject. Nothing you are doing with biotin will prove a thing, or have any affect on anyone else.

It sounds like time for a real clinical trial on the large 300 mg dose of melatonin. I have read somewhere that human bodies can produce at most less than one milligram of melatonin. Only a trial with correct design, and of sufficient size will be of any use to anyone. Leave this to the scientists.

[NHE]

Melatonin activates the sirtuin-1 gene and enhances neruoprotection during hypoxia-ischemia. I suspect that melatonin's activity on sirtuin-1 may have played a significant role in this patient's improvement. Activation of sirtuin-1 has also been shown to have a role in preserving mitochondrial function.

Melatonin reduces endoplasmic reticulum stress and preserves sirtuin 1 expression in neuronal cells of newborn rats after hypoxia-ischemia.
J Pineal Res. 2014 Sep;57(2):192-9.

Conditions that interfere with the endoplasmic reticulum (ER) functions cause accumulation of unfolded proteins in the ER lumen, referred to as ER stress, and activate a homeostatic signaling network known as unfolded protein response (UPR). We have previously shown that in neonatal rats subjected to hypoxia-ischemia (HI), melatonin administration significantly reduces brain damage. This study assessed whether attenuation of ER stress is involved in the neuroprotective effect of melatonin after neonatal HI. We found that the UPR was strongly activated after HI. Melatonin significantly reduced the neuron splicing of XBP-1 mRNA, the increased phosphorylation of eIF2α, and elevated expression of chaperone proteins GRP78 and Hsp70 observed after HI in the brain. CHOP, which plays a convergent role in the UPR, was reduced as well. Melatonin also completely prevented the depletion of SIRT-1 induced by HI, and this effect was observed in the same neurons that over-express CHOP. These results demonstrate that melatonin reduces ER stress induced by neonatal HI and preserves SIRT-1 expression, suggesting that SIRT-1, due to its action in the modulation of a wide variety of signaling pathways involved in neuroprotection, may play a key role in the reduction of ER stress and neuroprotection observed after melatonin.

[NHE]

Here's an interesting paper cited by the authors of the above case study that describes the protective role of melatonin in mitochondria.

Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo.
J Pineal Res. 2000 May;28(4):242-8.

Melatonin displays antioxidant and free radical scavenger properties. Due to its ability with which it enters cells, these protective effects are manifested in all subcellular compartments. Recent studies suggest a role for melatonin in mitochondrial metabolism. To study the effects of melatonin on this organelle we used ruthenium red to induce mitochondrial damage and oxidative stress. The results show that melatonin (10 mg/kg i.p.) can increase the activity of the mitochondrial respiratory complexes I and IV after its administration in vivo in a time-dependent manner; these changes correlate well with the half-life of the indole in plasma. Melatonin administration also prevented the decrease in the activity of complexes I and IV due to ruthenium red (60 microg/kg i.p.) administration. At this dose, ruthenium red did not induce lipid peroxidation but it significantly reduced the activity of the antioxidative enzyme glutathione peroxidase, an effect also counteracted by melatonin. These results suggest that melatonin modulates mitochondrial respiratory activity, an effect that may account for some of the protective properties of the indoleamine. The mitochondria-modulating role of melatonin may be of physiological significance since it seems that the indoleamine is concentrated into normal mitochondria. The data also support a pharmacological use of melatonin in drug-induced mitochondrial damage in vivo.