Wednesday 26 September 2012

Glycine as a sleep aid?

Sleeping beauty @ Paul Whiteley
When it comes to sleep and autism, or more specifically suggestions on how to improve sleeping patterns and sleep duration in cases of childhood autism, one compound crops up time and time again: melatonin.

I've talked about melatonin quite a bit on this blog; running through the current evidence for effect (here) and also speculatively discussing some of the ways and means that melatonin is made (here) and where the various findings on alterations in levels of the stuff in cases of autism might be derived from. 

All very interesting for the 'miracle' that is melatonin, bearing in mind that even melatonin supplementation might have a downside for some (including some pretty important drug interactions).

Having said all that, and again pronouncing my mantra: no medical advice given or intended, I was very interested to hear about another area of possible interest specifically with sleep in mind, supplementation with the amino acid glycine.

I don't know if you know or not but I'm a bit of a fan of amino acid chemistry and the myriad of ways that amino acids influence our health - somatic and psychiatric - and wellbeing. I've tended to focus quite a bit on the aromatic amino acids (tryptophan, tyrosine, phenylalanine) simply because of the various important links that have been made with for example serotonin (5-HT) chemistry and the in-born errors of metabolism such as PKU. I was also very interested in the whole branched-chain amino acids and rare cases of autism connection made quite recently.

Glycine is a little bit different in that it is categorised as a non-essential amino acid (i.e. the body can make the stuff itself); the body being capable of synthesising glycine from another amino acid serine (see here for a really small and complicated picture of how this happens).

The University of Wikipedia(!) reports that glycine is, quite importantly, also an inhibitory neurotransmitter; a point included in this overview by Bowery & Smart* (full-text) who also discuss the links with another important inhibitory neurotransmitter, GABA (see recent post). Mention of the words 'inhibitory' and 'GABA' immediately get me thinking about the sleep connection to glycine based on what an inhibitory neurotransmitter like GABA (and its receptors) has been suggested to be able to do.

Believe it or not, there is actually some peer-reviewed literature on the potential usefulness of glycine supplementation with sleep in mind. This paper by Bannai & Kawai** (full-text) is as good as any in outlining this fact, together with some speculation on the mode of action being linked to a lowering of body temperature normally experienced during sleep. Indeed the lead author, Makoto Bannai, seems to be quite interested in the whole glycine-sleep area as per another article*** suggesting that glycine supplementation might also cut down on perceived "daytime sleepiness and fatigue induced by acute sleep restriction" during a placebo-controlled trial. I hasten to add that this effect seemed independent of any findings related to melatonin.

Appreciating that quite a bit more research might need to be done on glycine and the link with sleep, I can't help but wonder whether glycine might also show some favour in cases of autism with sleeping issues. I stress that I am not advocating this or any other position without the appropriate medical advice and guidance. In view however of the speculations on glycine and body temperature - something also noted in cases of autism - and some very, very soft evidence on glycine supplementation and peripheral features like hyperactivity (here), one has to at least wonder whether more investigation is warranted.

Indeed bearing in mind that products such as dimethylglycine (DMG) and trimethylglycine (TMG) have already been discussed with autism in mind, could there be a greater effect over just altering stomach pH and the delivery of methyl groups to a potentially hypomethylating population?

To finish, somebody that I used to know? I dunno him but maybe you do.


* Bowery NG. & Smart TG. GABA and glycine as neurotransmitters: a brief history. British Journal of Pharmacology. 2006; 147: S109-S119.

** Bannai M. & Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of Pharmacological Sciences. 2012; 118: 145-148.

*** Bannai M. et alThe effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology. 2012; 3: 61.

---------- Bannai M, & Kawai N (2012). New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of pharmacological sciences, 118 (2), 145-8 PMID: 22293292


  1. Great article, Paul. Glycine is also helpful for restoring intestinal barrier integrity. Seems like a win-win for autism.

  2. Thanks Chris.

    Glycine being one of the simplest of the amino acids is starting to make some waves both from the inhibitory neurotransmitter point of view and also with its other potential applications in mind.

    Insofar as the permeability connection, its probably not in the same league as glutamine for example:
    but it's relations with for example the purines (and onwards nucleic acids) make it a valuable asset in biochemical terms.

  3. It certainly makes me sleepy. It's also a main component of collagen, which we don't seem to get as much of nowadays in our diet, unless you make bone broths.

    About aminos like tyrosine, it seems that one can take it to boost dopamine and attentiveness for a while, until the body shifts to maintain homeostasis. Perhaps the solution is to find substances that block (for example) dopamine for a period so that the body responds by making more dopamine or more receptors. I'm thinking of the way low dose naltrexone purportedly works on opioid receptors.

  4. Thanks Stephen. I'd never really thought about bone broth and glycine content to be honest but it makes sense that glycine would be abundent.
    As for the LDN... watch this space.


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