Tryptophan: Sleep, Gut Health, and Mood Benefits
By Adin Smith, MS | Posted June 15, 2022
- Estimated reading time 10 minutes
Tryptophan is an essential amino acid you must obtain through your diet. Animal and plant-based proteins contain the best tryptophan sources. However, the brain can absorb slightly more tryptophan from plant-based proteins.[1]Sutanto CN, et al. Association Between Dietary Protein Intake and Sleep Quality in Middle-Aged and Older Adults in Singapore. Front Nutr. 2022 Mar 9;9:832341.
Tryptophan plays a role in producing serotonin, melatonin, niacin (vitamin B3), and many other compounds essential to health.
Serotonin is a neurotransmitter that helps regulate mood and cognition, sleep, memory, appetite, and blood clotting.[2]Sanner JE, Frazier L. The role of serotonin in depression and clotting in the coronary artery disease population. J Cardiovasc Nurs. 2011 Sep-Oct;26(5):423-9. It is also involved in pain perception, sexual function, temperature regulation, and gastrointestinal function, with possible protective effects on bone density.[3]Terry N, et al. Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance. Handb Exp Pharmacol. 2017;239:319-342. The highest serotonin concentrations exist in the gut, with smaller amounts in the central nervous system and in platelets (the cells responsible for preventing bleeding).
Melatonin is a hormone that helps regulate the sleep-wake cycle and is vital in mediating immune responses.[4]Tordjman S, et al. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr Neuropharmacol. 2017;15(3):434-443. Additionally, melatonin exists in mitochondria (the powerhouse of the cell responsible for energy production), where it helps maintain energy balance.[5]Tan DX, et al. Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics. Int J Mol Sci. 2016;17(12):2124. [6]Cipolla-Neto J, et al. Melatonin, energy metabolism, and obesity: a review. J Pineal Res. 2014 May;56(4):371-81.
Tryptamine is a monoamine alkaloid found in trace amounts in the gastrointestinal tract, brain, neurons, and platelets.[7]National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/Tryptamine. Accessed May 27, 2022. It plays a role as a neuromodulator, helping balance serotonin’s excitatory and inhibitory functions.[8]Jones RS. Tryptamine: a neuromodulator or neurotransmitter in mammalian brain? Prog Neurobiol. 1982;19(1-2):117-39. Tryptamine may also act as a neurotransmitter that binds to receptors unrelated to serotonin function.
Kynurenine is the first molecule participating in a cascade of reactions called the kynurenine pathway (KP).[9]Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res. 2017;10. When tryptophan enters the KP, it gets transformed into kynurenine and numerous related derivatives necessary for regulating immune responses and neurological functioning. One of the most familiar compounds produced in the KP is niacin.
Niacin, or vitamin B3, is a generic term for nicotinic acid and nicotinamide—the main dietary precursors to the coenzymes nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP.[10]Ansari HR, Raghava GP. Identification of NAD interacting residues in proteins. BMC Bioinformatics. 2010 Mar 30;11:160. NAD and NADP are cofactors involved in catalyzing over 400 enzymatic reactions essential to cellular integrity and energy metabolism.
Some tryptophan food sources
| Food (cooked) | Serving | L-Tryptophan (mg) *† |
|---|---|---|
Chicken | 3 oz | 226-343 |
Beef | 3 oz | 113-318 |
Turkey | 3 oz | 247-290 |
Tuna | 3 oz | 243-285 |
Salmon | 3 oz | 210-285 |
Tofu (raw) | 3 oz | 82-200 |
Oats | 1 cup | 33-150 |
Skim Milk | 8 oz | About 106 |
Egg | 1 | 70-77 |
Cheddar Cheese | 1 oz | 80-91 |
Bread (wheat) | 1 slice | About 19 |
Semisweet Chocolate | 1 ounce | About 18 |
Banana | 1 medium | About 11 |
Deficiency
Tryptophan deficiency is rare because most people consume around 1000 mg per day, which is much more than the amount required for nitrogen balance. The Estimated Average Requirement (EAR) for tryptophan is 4 milligrams per kilogram (kg) each day. For instance, the EAR for a 70 kg adult would equate to about 280 milligrams per day.[11]Lieberman HR, Agarwal S, et al. Tryptophan Intake in the US Adult Population Is Not Related to Liver or Kidney Function but Is Associated with Depression and Sleep Outcomes. J Nutr. 2016 … Continue reading [12]Richard DM, et al. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009;2:45-60.
Not getting enough dietary tryptophan is typically associated with malnutrition and several other vitamin and mineral deficiencies. For instance, pellagra is the most studied condition caused by insufficient intake of tryptophan or niacin.[13]Pellagra. MedlinePlus.gov. Accessed on Jun 12th, 2022. Symptoms include dermatitis, dementia, diarrhea, abdominal pain, and loss of appetite.
Some factors linked to low tryptophan status include:
- COVID-19
- Aging [14]de Bie J, Guest J, Guillemin GJ, Grant R. Central kynurenine pathway shift with age in women. J Neurochem. 2016 Mar;136(5):995-1003.
- Obesity [15]Cussotto S, et al. Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation. Front Immunol. 2020;11:557.
- Cognitive impairment [16]Ramos-Chávez, L A et al. Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age. Ox med cell long. 2018.
- Depression [17]Islam MR, Ali S, et al. Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder. BMC Psychiatry. 2020 Jun 24;20(1):333.
- Sarcopenia (loss of muscle mass and function) [18]Dai M, Lin T, Yue J, Dai L. Signatures and Clinical Significance of Amino Acid Flux in Sarcopenia: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021 Sep 13;12:725518.
- Elevated inflammatory markers [19]Murr C, Grammer TB, Kleber ME, Meinitzer A, März W, Fuchs D. Low serum tryptophan predicts higher mortality in cardiovascular disease. Eur J Clin Invest. 2015 Mar;45(3):247-54.
- Excessive alcohol consumption [20]Badawy AA. Tryptophan metabolism in alcoholism. Adv Exp Med Biol. 1999;467:265-74.
- Gastrointestinal conditions such as carcinoid syndrome (symptoms related to small tumors in the digestive tract, appendix, and bronchial tubes in the lungs). [21]Carcinoid Syndrome. STATPEARLS. Accessed June, 2022.
Tryptophan Benefits
1. Sleep
Before tryptophan can provide its sleep-promoting effects, it must compete with other large neutral amino acids (LNAAs) for entry into the brain.
LNAAs competing with tryptophan include:
- Leucine, isoleucine, and valine
- Phenylalanine and tyrosine
- Threonine
- Methionine
- Histidine
Vegetarian proteins have a higher tryptophan/LNAA ratio than animal proteins, suggesting that a vegetarian diet may increase brain tryptophan over an omnivorous diet. Another way to increase this ratio is through supplementation.
Taking tryptophan capsules for promoting sleep appears to be most helpful in people with mild insomnia or gene variants affecting serotonin function.[22]Schneider-Helmert D, Spinweber CL. Evaluation of L-tryptophan for treatment of insomnia: a review. Psychopharmacology (Berl). 1986;89(1):1-7.
In a randomized, double-blind placebo-controlled crossover trial, researchers selected individuals with gene variations affecting serotonin metabolism to evaluate differences in the sleep-promoting effects of tryptophan.[23]van Dalfsen JH, et al. The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the sleep-promoting effects of tryptophan. J Psychopharmacol. 2019;33(8):948-954. Subjects were genotyped and randomly assigned to receive 1000 mg of tryptophan or placebo capsules each night before bed for one week, then switched treatments for another week.
After trial completion, sleep efficiency improvements were apparent in all subjects taking tryptophan regardless of genetic variation. Additional benefits among people with a specific gene variant called 5-HTTLPR had improvements in subjective sleep quality and the number of nighttime awakenings.
2. Gut health
Once tryptophan reaches the small and large intestine, about 4-6% transforms into small molecules essential to gastrointestinal function.[24]Gao J, et al. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Front Cell Infect Microbiol. 2018 Feb 6;8:13. [25]Taleb S. Tryptophan Dietary Impacts Gut Barrier and Metabolic Diseases. Front Immunol. 2019;10:2113. For instance, gut bacteria can transform tryptophan into specific molecules that stimulate the secretion of antimicrobial peptides—important molecules for eliminating unwanted microorganisms such as certain fungi, parasites, bacteria, and viruses.
The gut barrier is a single layer of protective cells that lines the lower digestive tract, responsible for inhibiting pathogens, toxins, or other foreign substances from entering the blood and causing harm. Experimental studies show that bacterial tryptophan metabolites bind to receptors in the gut responsible for maintaining intestinal barrier function.[26]Scott SA, et al. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2020;117(32):19376-19387.
Most of the body’s serotonin (95%) is found in the gut, where it triggers peristalsis, the wave-like contractions responsible for moving food down your digestive tract. To support healthy serotonin production in the digestive tract, promote normal gut motility, and proper food transit time, consuming at least the recommended daily amount of tryptophan is necessary.
3. Mood
Researchers commonly evaluate the effect of tryptophan on mood by having participants ingest a tryptophan-free amino acid drink. Such studies have consistently shown that tryptophan elimination has a mood-lowering effect, especially in people with depression or those with a family history of mental disorders.[27]Young SN. Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects. J Psychiatry Neurosci. 2013 Sep;38(5):294-305.
Other studies suggest that dietary patterns may impact your state of mind. For instance, to determine the relationship between diet and mood, researchers analyzed tryptophan intake and metabolism, plus mood scores in participants aged 36-85 with or without mild or moderate depression symptoms.[28]Chojnacki C, et al. Tryptophan Intake and Metabolism in Older Adults with Mood Disorders. Nutrients. 2020;12(10):3183. Published 2020 Oct 18.
After analysis, researchers found that older adults with depression consumed significantly less daily tryptophan than individuals without such symptoms. Furthermore, older individuals had increased markers of tryptophan breakdown (depletion) compared to younger adults.
In summary, older adults with psychiatric problems have an increased need for tryptophan yet consume significantly fewer amounts.
Safety and side effects
In 1989, tryptophan supplements were linked to a life-threatening illness called eosinophilia-myalgia syndrome (EMS). A case-control study later traced the cause of EMS to contaminants in a tryptophan product made by a Japanese company, Showa Denko.[29]Back EE, et al. Risk factors for developing eosinophilia myalgia syndrome among L-tryptophan users in New York. J Rheumatol. 1993 Apr;20(4):666-72. Since then, no reported EMS cases have emerged from tryptophan use in research and clinical trials. However, as observed in some human studies, its use may come with the following occasional or rare side effects.[30]Fernstrom JD. Effects and side effects associated with the non-nutritional use of tryptophan by humans. J Nutr. 2012 Dec;142(12):2236S-2244S. [31]Holeček M. Side effects of amino acid supplements. Physiol Res. 2022;71(1):29-45.
- Fatigue or drowsiness
- Nausea, dizziness, tremors
- Sweating, palpitations, dry mouth
- Serotonin syndrome—a rare condition where serotonin overstimulation results from combining tryptophan with two or more serotonin-enhancing drugs (e.g., Citalopram (Celexa) and Fluoxetine (Prozac)—both SSRIs, or MAO inhibitors like phenelzine (Nardil) and selegiline (Emsam).
Conclusion
Some people may benefit from additional dietary tryptophan to help compensate for specific health factors, medications, infections, or medical conditions that cause reductions in tryptophan.
Compared to animal proteins, plant-based protein sources contain a higher proportion of tryptophan relative to other large neutral amino acids. Thus, vegetarian diets containing fewer competing amino acids may better support brain tryptophan entry.
Although tryptophan supplementation is generally safe, certain people may be vulnerable to side effects, especially those already taking a serotonin-acting drug.
References
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