A Fascinating Compound

A Lowdown on Glycine and it's Benefits

I’ve been fascinated by and tracking glycine for a while. For newer readers, I have covered some of the lenses I used for decision making when it comes to things like glycine. In essence; beyond the research on it’s benefits, which is of course the starting point, it’s safe, relatively cheap and low downside. With this as context, it becomes quite a low bar for me to try something and likewise write about it. *This is an opportune time to remind you that all of my articles are informational only, and that I am a doctor NOT YOUR doctor - speak to your healthcare practitioners before making health decisions.

A recent systematic review, did a great job in summarising the research in the space, elaborating on the fact that glycine’s research is in its infancy in healthy populations but there is certainly promise there. Figure 2 in the paper is particularly interesting with respect to a research summary.

If glycine sounds familiar to you, it is probably because I mentioned it a while back as part of “GlyNAC” which is the combination of glycine and N-Acetyl Cysteine, a very popular supplement in the longevity space.

What is Glycine

Originally isolated from hydrolysates of protein in 1820, it is named for its sweet taste derived from Greek word “glykys.”
Glycine is the smallest amino acid, and as many readers would know, amino acids are the building blocks for peptides and proteins (multiple amino acids makes a peptide and proteins are bigger chains still - the line is technically 50, 2-50 amino acids make a peptide whereas beyond 50 amino acids is considered a protein). Many folks would have heard of essential and non-essential amino acids, with glycine being the latter - meaning it can be synthesised in the body provided there are the correct building blocks present for this.

What Does Glycine Do?

Glycine, being an amino acid, is crucial for many different purposes. Of particular interest is that it is one of three amino acids used to make glutathione (the body’s master antioxidant), one of three amino acids used to make creatine and constitutes a significant portion (25% +) of the amino acids in collagen.

Additionally glycine can help lower blood glucose and serves functions as a neurotransmitter in the CNS, in the immune system and other metabolic functions.

Below you can see a summary of some of the effects of glycine.

From Aguayo-Cerón et al

Glycine and Sleep

One of the initial reasons I became interested in glycine is for sleep. Specifically due to the undeniably essential role that sleep plays in health and performance. Of course when it comes to sleep, as with all things, it is important to start with the big rocks first. That said once these are addressed then things like supplements may be worth investigating to further improve sleep. There are no shortage of supplements that can aid in sleep, or at least have claims to this effect, some with better profiles than others in my eyes - back to the lenses and the fact that glycine is cheap and low downside/risk (at high doses it can cause gastrointestinal upset - along with everything else really).

Mechanism of Action

Despite the research on the efficacy of glycine in its sleep promoting benefits being quite consistent, the mechanism of action is less widely known. There is some research suggesting a peripheral vasodilation, contributing to a cooling like effect helping improve sleep. That said, if this was the sole mechanism research would more likely point to improved sleep onset rather than improve sleep more generally. There is also evidence suggesting glycine plays a role in receptors in the brain which can contribute to sleep.
Like most things, it is probably a combination of these two factors and others we are yet to elucidate.

Dietary Sources

Astute readers would probably be thinking; sounds interesting but also as though I can get enough of this from food, or at least the components of which, for it to be synthesised (and this is a valid viewpoint).

Sources of glycine in the diet speak to the role it plays in the body (remember it is 25%+ of the amino acids in collagen), which is to say that it is highest in animal meats, nuts and beans. Of course, one can supplement with it (more on this later) and as mentioned it is a significant portion of other supplements such as creatine and collagen - remembering it is a non-essential meaning the body can synthesise it from enough dietary building blocks.
A fairly extensive list of dietary sourced that can be filtered is here.

Interestingly, the above linked systematic review, suggests that dietary intake may be insufficient;

“Nutritional studies have highlighted that the amount of glycine available in humans and animals is inadequate to satisfy metabolic requirements, suggesting the need for dietary glycine supplementation”

Which, quite honestly, surprised me initially.

*Warning, nerdy digression* - It also made me reflect on whether essential or non-essential amino acids were ‘more important’ to the body (perhaps non-essential amino acids are more essential to the body because if they aren’t present they are synthesised signifying their importance) remembering that the nomenclature is about whether they are essential to eat because the essentials cannot be synthesised - it’s not to do with importance metabolically.

Supplementation

As mentioned early in this piece, glycine has a sweet taste, and as such can be used for this purpose - perhaps limiting use of other sweeteners (a swap that almost everyone would consider a dietary improvement). That said, it is less sweet than things like sucrose (table sugar) or artificial sweeteners so don’t anticipate a straight swap without some sacrifice of taste.

Generally a dose of 3-5g, with meals is suggested by most resources. This probably largely reflects its role in management of blood glucose. This is also the same dose suggested for sleep.

It is available as a powder and in tablet form - obviously if you are substituting it in as a sweetener, you’d opt for the powder. Also, if you are using tablets - it ends up being quite a few to get a 3-5g dose.

Final Thoughts

As the title of this piece suggests, I am fascinated by glycine (it’s strongest evidence may be in helping those with schizophrenia). I’ve written this before, but usually people’s (also mine) BS meters are triggered by claims of panaceas and multi-potent substances, and this case is no different. The research is probably a little bit early and, as summarised in the systematic review, at a high risk of bias. Having said that, and as touched on in the beginning of the article, my lenses of decision making certainly made me open to it - and as such I have been using glycine, mostly for sleep to good effect (or at least good placebo).

If you do decide to try glycine, do let me know what you think/find either in the comments on Substack or replying to the email.

References

1. Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi: 10.1155/2017/1716701. Epub 2017 Mar 1. Erratum in: Oxid Med Cell Longev. 2022 Feb 23;2022:9857645. doi: 10.1155/2022/9857645. PMID: 28337245; PMCID: PMC5350494.

2. Aguayo-Cerón KA, Sánchez-Muñoz F, Gutierrez-Rojas RA, Acevedo-Villavicencio LN, Flores-Zarate AV, Huang F, Giacoman-Martinez A, Villafaña S, Romero-Nava R. Glycine: The Smallest Anti-Inflammatory Micronutrient. Int J Mol Sci. 2023 Jul 8;24(14):11236. doi: 10.3390/ijms241411236. PMID: 37510995; PMCID: PMC10379184.

3. Brosnan JT, da Silva RP, Brosnan ME. The metabolic burden of creatine synthesis. Amino Acids. 2011 May;40(5):1325-31. doi: 10.1007/s00726-011-0853-y. Epub 2011 Mar 9. PMID: 21387089.

4. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013 May;1830(5):3143-53. doi: 10.1016/j.bbagen.2012.09.008. Epub 2012 Sep 17. PMID: 22995213; PMCID: PMC3549305.

5. Inagawa, K., Hiraoka, T., Kohda, T. et al. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol. Rhythms 4, 75–77 (2006). https://doi.org/10.1111/j.1479-8425.2006.00193.x

6. Yamadera, W., Inagawa, K., Chiba, S. et al. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol. Rhythms 5, 126–131 (2007). https://doi.org/10.1111/j.1479-8425.2007.00262.x

7. Bannai M, Kawai N, Ono K, Nakahara K, Murakami N. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61.

8. Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, Takeda T, Bannai M, Nishino S. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015 May;40(6):1405-16. doi: 10.1038/npp.2014.326. Epub 2014 Dec 23. PMID: 25533534; PMCID: PMC4397399.

9. Koopman R, Caldow MK, Ham DJ, Lynch GS. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):237-242. doi: 10.1097/MCO.0000000000000383. PMID: 28375879.

10. Soh J, Raventhiran S, Lee JH, Lim ZX, Goh J, Kennedy BK, Maier AB. The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review. Geroscience. 2024 Feb;46(1):219-239. doi: 10.1007/s11357-023-00970-8. Epub 2023 Oct 18. PMID: 37851316; PMCID: PMC10828290.