Melatonin in ASD: a review

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kulkulkan
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Melatonin in ASD: a review

Postby kulkulkan » Fri Nov 21, 2014 5:27 pm

The lead author was also doing a clinical trial to see dosage dependent effect of supplementing melatonin in ASD - for efficacy beyond just sleep (not published yet). Very promising. Although serum serotonin levels (which are often found to be high in ASD) don't correlate to ASD severity, melatonin levels have been shown to correlate to severity in couple of studies.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821628/

Int J Mol Sci. 2013 Oct 14;14(10):20508-42. doi: 10.3390/ijms141020508.
Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives.
Tordjman S1, Najjar I, Bellissant E, Anderson GM, Barburoth M, Cohen D, Jaafari N, Schischmanoff O, Fagard R, Lagdas E, Kermarrec S, Ribardiere S, Botbol M, Fougerou C, Bronsard G, Vernay-Leconte J.
Author information
Abstract
Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.

HeatherWig
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Joined: Sun Nov 16, 2014 6:07 pm

Re: Melatonin in ASD: a review

Postby HeatherWig » Sun Nov 23, 2014 5:12 pm

This is a very interesting study!
I have been using melatonin as a natural sleep aid for many months.
As a mother to be with MTHFR c667t I am always trying to stay up to date regarding the latest studies and nutritional interventions. I have done quite a bit of reading that mothers with the MTHFR gene are likely to pass it onto their child and this is a risk factor for ASD. I am no expert on the subject, just learn what I can from others.

kulkulkan
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Joined: Tue Mar 13, 2012 1:37 pm

Re: Melatonin in ASD: a review

Postby kulkulkan » Mon Nov 24, 2014 1:54 pm

MTHFR is certainly one risk factor but that is a common mutation and if pregnant, methyl folate is better than synthetic folic acid.

Santosg
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Re: Melatonin in ASD: a review

Postby Santosg » Wed Nov 26, 2014 10:35 pm

Melatonin has a number of functions. It can increase longevity in many organisms. Most interesting, from an ASD perspective, is that it is a very effective chelator. I think that many of its benefits for ASD, beyond sleep, rests precisely in this capacity.

kulkulkan
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Joined: Tue Mar 13, 2012 1:37 pm

Re: Melatonin in ASD: a review

Postby kulkulkan » Wed Nov 26, 2014 11:39 pm

Technically melatonin is not a chelator as it doesn't have a di thiol group but it is a very powerful antioxidant that can raise intracellular glutathione (which is a weak chelator), activate nrf2 pathway and can cross membranes including BBB. We have started using melatonin with each AC round for that reason and it has been studied together with DMSA to show more efficacy.

I think equally relevant for ASD is that it is a powerful anti inflammatory (inhibits cox-2) and it can increase or restore serotonin, GABA, and oxytocin levels in brain (one ASD rat model study). It likely also reduces glutamate and increases glutamine.

It is almost the perfect antioxidant except it puts you to sleep, so hard to use during the day. I think night time dosing is still great as it frees up the burden ahead for ASMT enzyme during the day (which is shown to be lower in ASD).

Just need to be careful with long term dosing (even though there is no feedback mechanism regulating it and it is a terminal antioxidant). For people who use it for sleep daily, I have heard stories that it stopped working over time. We do pulse dosing on the weekends only now (typically during AC round) and thinking about increasing melatonin dosage and/or frequency.

Need to find something like melatonin for daytime.

noelm
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Joined: Tue Jun 21, 2011 2:50 pm

Re: Melatonin in ASD: a review

Postby noelm » Sun Nov 30, 2014 7:39 am

Its a good literature survey.

Although the authors primarily focused on Autistic traits, I believe, they missed out on a major piece and that is autoimmune conditions. Unless they study adults with autism and their predisposition towards autoimmune diseases (or review those articles), I believe it is still incomplete.
There is a good evidence that melatonin stimulates lot of cytokines that play a major role in exacerbation of autoimmune diseases, like rheumatoid arthritis and lupus. In that case, melatonin supplementation may not be a good idea.
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HeatherWig
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Joined: Sun Nov 16, 2014 6:07 pm

Re: Melatonin in ASD: a review

Postby HeatherWig » Thu Dec 11, 2014 12:48 am

kulkulkan wrote:MTHFR is certainly one risk factor but that is a common mutation and if pregnant, methyl folate is better than synthetic folic acid.

This is how I understand it as well. I am actually looking at a supplement complex right now that has a form of folate called quatrefolic, I believe it is the patented name for the form of 5-MTHF though. It also contains B12 in the form of methylcobalamin so it seems they took individuals with MTHFR into consideration.


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