Can glycine improve sleep, reduce depression, or reduce nighttime urinary frequency?

Answer:

Glycine is a non-essential amino acid (meaning that it can be made in the body and is not required from the diet) that acts as a neurotransmitter.

Several small clinical trials (generally supported by Ajinomoto, which sells glycine) have evaluated the effects of glycine supplementation for improving sleep and for reducing nighttime urinary frequency in people with overactive bladder, chronic prostatitis, and/or bladder pain syndrome/interstitial cystitis.

Health benefits of glycine

Sleep and fatigue
A study among eleven men and women with self-reported "unsatisfactory sleep," found that 3 grams of glycine taken one hour before bedtime significantly improved self-reported sleep quality and shortened the time it took to fall asleep (as measured by brain wave, heart rate and breathing monitors) compared to placebo (Yamadera, Sleep Biologic Rhythms 2007). Two other very small studies, each conducted among 10 to 15 Ajinomoto employees, found that 3 grams of glycine taken one hour before bedtime improved self-reported sleep quality and/or decreased next-day fatigue (Inagawa, Sleep Biologic Rhythms 2006; Bannai, Front Neurol 2012). No adverse events were reported.

Overactive bladder and chronic prostatitis
A study in Japan among 16 men and four women (average age 67) with mild to moderate overactive bladder, chronic prostatitis and/or bladder pain syndrome/interstitial cystitis found that 3 grams of glycine taken twice daily for one month modestly reduced nighttime urinary urgency and frequency (but not during the day), and slightly improved overall scores on an assessment of overactive bladder symptoms (a decrease of about 1 point on a 15-point scale) and self-reported "vitality" compared to placebo. In addition, glycine supplementation slightly reduced the amount of time it took to fall asleep and modestly decreased bladder pain as well as and systolic and diastolic blood pressure compared to baseline, but these improvements were not statistically significant compared to placebo (Sugaya, J Complement Integr Med 2021).

Depression
There is speculation that glycine may be beneficial for depression, although this has not been proven. The speculation stems from test-tube studies and animal research (Sutton, eLife 2018; Laboute, Science 2023) and an observational study showing that people with major depressive disorder have lower blood levels of glycine compared to healthy controls (Altamura, Eur Neuropsychopharmacol 1995). A clinical study among 22 people with treatment-resistant schizophrenia found that supplementing with very high-doses of glycine (starting at 4 grams daily and increased to 40 to 90 grams daily over about 2 weeks) for a total of 6 weeks slightly improved depression symptoms compared to placebo (Heresco-Levy, Arch Gen Psychiatry 1999). There do not appear to be any studies evaluating glycine supplementation in people without schizophrenia who have depression.

Glycine safety, side effects, and drug interactions

There are no reported side effects of glycine when taken at the doses used in these studies, or in doses of up to 60 grams/day for up to six weeks (Javitt, Int J Neuropsychopharmacol 2001).

Be aware that glycine might potentially worsen symptoms in some people with schizophrenia taking antipsychotic medication clozapine (Clozaril) (Potkin, Am J Psychiatry 1999).