Glycine Side Effects: What Is Known and Who Should Be Careful

Glycine is the simplest amino acid and a common ingredient in sleep, collagen and recovery products. Because the body makes it and food supplies several grams a day, it is often assumed to be risk-free. In practice the safety record is good, but there are dose-related effects and a few groups who should be cautious. Here is what our editorial team found in the literature.

Glycine in brief

Glycine is a non-essential amino acid, meaning the body can synthesise it, mainly from serine. It is a building block of collagen, where it makes up roughly a third of the amino acid residues, and it is needed to make glutathione, creatine and haem.

In the nervous system glycine has two roles. In the spinal cord and brainstem it is an inhibitory neurotransmitter. In the brain it also acts as a co-agonist at NMDA glutamate receptors, which is why it has been studied in psychiatry as well as for sleep.

Supplement interest in the UK mainly concerns sleep. Japanese studies from the 2000s gave around 3 g before bed and reported better subjective sleep quality and less daytime fatigue. Animal work suggests glycine lowers core body temperature slightly, which may help sleep onset.

Glycine is sold in the UK as a food supplement, either as a sweet-tasting powder or in capsules, and it also appears in blends with magnesium (magnesium glycinate). It is not on the WADA Prohibited List.

Side effects at commonly used doses

At the 3 g dose used in sleep studies, adverse effects reported in trials were few and mild. The most common complaint in supplement users is a soft stool or mild stomach upset, particularly when glycine is taken on an empty stomach.

Some people notice daytime drowsiness, especially if they take glycine in the morning or combine it with other sleep aids. This is consistent with its intended effect. It is sensible not to drive or operate machinery until you know how it affects you.

• nausea or a feeling of fullness;
• loose stools or mild diarrhoea;
• drowsiness or a "heavy" feeling the next morning in some people;
• occasional headache, reported anecdotally rather than consistently in trials.

Because glycine tastes sweet, people sometimes use it as a sugar replacement in drinks. This can quietly push daily intake much higher than intended. If you add it to coffee or tea several times a day, count those grams too.

If side effects appear, the simplest fixes are to reduce the amount, split it into two portions or take it with food. Persistent symptoms suggest the supplement is not right for you, and it is reasonable simply to stop.

What happens at high doses

Much higher intakes have been studied in schizophrenia research, where glycine was used as an add-on to boost NMDA receptor activity. In those trials, adults took around 0.8 g per kilogram of body weight daily, often more than 50 g, for several weeks under medical supervision.

At these levels gastrointestinal effects became more noticeable, mainly nausea and occasional vomiting, but serious toxicity was not a prominent finding. These doses are many times higher than anything sensible for sleep or recovery and should not be copied outside a clinical trial.

Glycine is metabolised partly in the liver and kidneys, and the breakdown releases ammonia and carbon dioxide. In healthy people this is handled easily. In those with severe liver or kidney disease, an additional amino acid load deserves a conversation with a doctor first.

A rare inherited disorder, non-ketotic hyperglycinaemia, causes toxic accumulation of glycine. It is diagnosed in infancy and is not relevant to healthy adults, but it explains why glycine is not considered inert in every context.

Interactions and groups who should take care

The most important known interaction involves clozapine, an antipsychotic used for treatment-resistant schizophrenia. A small trial by Potkin and colleagues found that adding high-dose glycine to clozapine was associated with worse symptoms, so anyone taking clozapine should avoid glycine supplements unless their psychiatrist agrees.

For pregnancy and breastfeeding there is no evidence of harm from normal dietary glycine, but there are also no good trials of supplements. The cautious UK approach is to avoid non-essential supplements unless a midwife or doctor recommends them.

Glycine is sometimes combined with melatonin, magnesium or herbal products in "sleep stacks". Melatonin is a prescription-only medicine in the UK, so blends containing it bought online may not meet UK rules and may contain unexpected amounts.

Quality is a further consideration. Pure glycine is cheap to produce, so adulteration is uncommon, but buying from manufacturers that publish independent batch testing reduces the risk of contamination, particularly for tested athletes.

Using glycine sensibly

If you want to try glycine for sleep, the evidence supports around 3 g taken 30–60 minutes before bed. Starting with a smaller amount and taking it with a light snack or drink can reduce stomach upset.

Give it a fair but limited trial, for example two to three weeks, and judge the effect honestly. Sleep supplements have strong placebo effects, and a sleep diary or wearable data can help you decide whether it is genuinely helping.

Remember that basic sleep hygiene usually matters more: a regular schedule, a cool and dark bedroom, limiting caffeine after midday and avoiding heavy training late in the evening. Glycine is at most a modest addition to these measures.

Persistent insomnia, loud snoring or breathing pauses during sleep, and excessive daytime sleepiness are reasons to see a GP rather than to keep experimenting with supplements, because they can indicate conditions such as sleep apnoea.

Conclusions of the editorial team

Glycine has a good safety profile at the doses typically used for sleep. Side effects are usually mild and digestive, with drowsiness being an expected effect rather than a warning sign.

Very high intakes used in psychiatric research cause more stomach problems and are unsuitable for self-use. The clozapine interaction is the clearest reason for some people to avoid glycine altogether.

People with significant kidney or liver disease, pregnant or breastfeeding women and anyone taking sedating medication should seek professional advice first. For everyone else, a short trial at around 3 g before bed is a reasonable, low-risk experiment.

Our editorial team has also covered magnesium forms and sleep, how caffeine timing affects recovery, and the evidence on collagen supplements for joints, which may interest readers exploring glycine.

References

1. Inagawa K, Hisaki T, Suzuki M, et al. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 2006;4(1):75–77.
2. Yamadera W, Inagawa K, Chiba S, et al. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 2007;5(2):126–131.
3. Bannai M, Kawai N, Ono K, et al. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61.
4. Kawai N, Sakai N, Okuro M, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015;40(6):1405–1416.
5. Heresco-Levy U, Javitt DC, Ermilov M, et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999;56(1):29–36.
6. Potkin SG, Jin Y, Bunney BG, Costa J, Gulasekaram B. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry. 1999;156(1):145–147.
7. 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.