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Amino Acids, Sleep, Anxiety and Depression: What Trials Show for Tryptophan, Glycine, GABA, Tyrosine and NAC

What trials and reviews show for tryptophan, glycine, GABA, tyrosine and NAC on sleep, anxiety and depression, with serotonin syndrome and medicine cautions and where to get urgent help.

Content last updated . This page has not been medically reviewed.

Urgent first

If you or someone you know is struggling or having thoughts of suicide, call or text the 988 Suicide & Crisis Lifeline at 988 (US); in life-threatening situations call 911. [1] Serotonin syndrome is a potentially life-threatening reaction in which the body has too much serotonin, most often when two or more medicines or drugs that affect serotonin are taken together. [2] Symptoms occur within minutes to hours and may include agitation, fast heartbeat, high blood pressure, hallucinations, increased body temperature and loss of coordination. [2] MedlinePlus says to contact your provider right away if you have symptoms and that untreated serotonin syndrome can be deadly. [2] In an emergency in the US, call 911.

Start here

This page is information only. Depression, anxiety disorders and long-lasting sleep trouble are medical conditions. NIMH lists existing treatments such as medications and talk therapy. [1] Do not replace or stop a prescribed medicine, especially an antidepressant, to try an amino acid. MedlinePlus advises, about serotonin syndrome medicines, not to stop taking your medicine and to talk to your health care provider about your concerns first. [2] For sleep and stress habits see Sleep Supplements and Natural Aids, Insomnia, Anxiety Disorders and Stress, Anxiety, Burnout and Depression.

How to read the evidence on this page

Labels: "limited" (few or small trials), "mixed" (trials disagree), "insufficient" (cannot conclude), "evidence of harm" and "Proper evidence not found". Many trials here used healthy volunteers or short periods; they cannot be carried over to people with a diagnosed condition. Amounts shown are study amounts, not advice.

Where each one sits

MedlinePlus lists tryptophan among the nine essential amino acids and glycine and tyrosine among the conditionally essential ones. [3] GABA is described as a non-proteinogenic amino acid. [4] 5-HTP is produced from tryptophan in the body. [5] NAC and L-theanine have their own pages.

Evidence table

Compound and questionWhat the source foundEvidence label
Tryptophan and sleepA 2022 meta-analysis (data from 4 articles analyzed) found supplementation shortened wake after sleep onset, but did not affect other sleep components [6]Limited
Tryptophan and mood in healthy adults11 randomized trials; 4 showed effects on negative and happy feelings, and the review suggested 0.14 to 3 g a day of tryptophan (study amount) could improve mood in healthy people while calling for better-designed studies [7]Limited, healthy people only
Tryptophan or 5-HTP for depressionA Cochrane review found only 2 trials (64 patients) of sufficient quality; they favored the products over placebo but were not conclusive; it noted a possible link with potentially fatal eosinophilia-myalgia syndrome not elucidated [8]Insufficient (old review, 2002)
Glycine and sleepIn a small trial, 3 g of glycine or placebo before bed during three nights of sleep restriction in healthy volunteers reduced fatigue and improved a vigilance test [9]; the researchers' review reports better subjective sleep quality in people with insomniac tendencies [10]Limited; see Glycine and Sleep
GABA (oral)A systematic review of 14 placebo-controlled studies found limited evidence for stress and very limited evidence for sleep benefits [4]Limited
Tyrosine and stressA review concluded tyrosine can enhance cognition, but only when neurotransmitter function is intact and dopamine or norepinephrine is temporarily depleted, with limited potential for clinical disorders [11]Limited, short-term stress settings
NAC and depressionA 2016 meta-analysis of 5 trials (574 people) found improved depressive symptoms [12]; a 2020 meta-analysis of 7 trials (728 people) found no improvement versus placebo [13]Mixed
NAC and anxietyA 2015 review described anxiety evidence as preliminary and needing larger studies [14]Insufficient

Notes on the table

  • L-theanine is an amino acid owned by the nootropics pages: a 2020 systematic review of 9 trials suggested 200 to 400 mg a day (study amount) may assist stress and anxiety in people exposed to stressful conditions, with larger studies needed. [15] See L-Theanine.
  • Age of the evidence: our PubMed search for tryptophan, 5-HTP and depression found only the 2001 and 2002 versions of the Cochrane review. A 2020 review also discusses the occurrence of toxic impurities in tryptophan and 5-HTP preparations. [5]
  • Sleep in general: diet and supplement reviews do not replace sleep habits and CBT-I; see CBT-I.

Related

Tryptophan · Tyrosine · GABA Supplements

Frequently asked questions

Do amino acids help depression?

Evidence is limited. A Cochrane review of tryptophan and 5-HTP found only two adequate trials and called the evidence not conclusive. [8] NAC trials are mixed. [12][13]

Can I take tryptophan or 5-HTP with an antidepressant?

Ask a doctor or pharmacist first. Tryptophan is listed among agents reported in serotonin syndrome, and serotonin syndrome is a potentially life-threatening reaction when serotonin-acting medicines are combined. [16][2]

Does glycine help sleep?

A small trial and the researchers' own review report better subjective sleep quality in people with insomniac tendencies, and less daytime fatigue after restricted sleep. [10][9] Larger independent trials were not found in what we read.

Does oral GABA calm anxiety or help sleep?

A systematic review found limited evidence for stress and very limited evidence for sleep. [4]

Is NAC proven for anxiety?

No. A 2015 review called anxiety evidence preliminary. [14]

More details: evidence, limits and cautions

The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.

Safety and interactions
  • Serotonin syndrome: tryptophan is listed among serotonin-acting agents that have been reported in serotonin syndrome, alone or with monoamine oxidase inhibitors. [16] A 5-HTP review highlights eosinophilia-myalgia syndrome and serotonin syndrome as the safety issues. [17] Anyone taking antidepressants (SSRIs, SNRIs, MAOIs), triptans or other serotonin-acting medicines must ask a doctor or pharmacist before using tryptophan, 5-HTP or similar products. See Tryptophan, 5-HTP and Serotonin Syndrome and 5-HTP.
  • NAC: in the 2020 meta-analysis NAC caused more gastrointestinal adverse events than placebo (risk ratio 1.79). [13] See NAC Evidence.
  • Medicines in general: see Medication Interactions.
  • Pregnancy, breastfeeding and children: the sources we read give no safety data for these groups for the products above; ask a clinician; see Pregnancy and Breastfeeding and Children and Teens.
  • Kidney, liver, surgery: ask first; see Supplements Before Surgery.
  • Quality: see Quality Testing and Certifications.
References
  1. NIMH (US National Institutes of Health). Depression. Read 2026-10-23.
  2. MedlinePlus (US National Library of Medicine). Serotonin syndrome. Review date 4/13/2026. Read 2026-10-23.
  3. MedlinePlus (US National Library of Medicine). Amino acids. Review date 1/21/2025. Read 2026-10-23.
  4. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Frontiers in Neuroscience 2020 (PubMed abstract). Read 2026-10-23.
  5. 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. International Journal of Molecular Sciences 2020 (PubMed abstract). Read 2026-10-23.
  6. The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression. Nutrition Reviews 2022 (PubMed abstract). Read 2026-10-23.
  7. A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning. Journal of Dietary Supplements 2021 (PubMed abstract). Read 2026-10-23.
  8. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database of Systematic Reviews 2002 (PubMed abstract). Read 2026-10-23.
  9. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology 2012 (PubMed abstract). Read 2026-10-23.
  10. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of Pharmacological Sciences 2012 (PubMed abstract). Read 2026-10-23.
  11. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review. Journal of Psychiatric Research 2015 (PubMed abstract). Read 2026-10-23.
  12. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. Journal of Clinical Psychiatry 2016 (PubMed abstract). Read 2026-10-23.
  13. N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials. Psychopharmacology 2020 (PubMed abstract). Read 2026-10-23.
  14. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neuroscience & Biobehavioral Reviews 2015 (PubMed abstract). Read 2026-10-23.
  15. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. Plant Foods for Human Nutrition 2020 (PubMed abstract). Read 2026-10-23.
  16. Serotonin syndrome. Neurology 1995 (PubMed abstract, case report with background). Read 2026-10-23.
  17. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacology & Therapeutics 2006 (PubMed abstract). Read 2026-10-23.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.