Tryptophan is a building block for melatonin, serotonin, and endorphins.  Melatonin helps the body know when it is time to sleep and to wake up.  Serotonin is a feel-good hormone and endorphins are natural pain killers.  Our bodies make melatonin, serotonin, dopamine, and endorphins from tryptophan, so an adequate daily supply of tryptophan is required for the timely production of each.*  

Tryptophan plays a key role in the proper working of our body’s internal clock, an important determinant of the quality of our sleep, which is correlated to mortality [14].  Clinical research has also found that tryptophan may help to prevent various cancers including breast cancer and colon cancer.  Tryptophan and the byproduct serotonin hormone are essential for mood regulation; playing an important role in how we respond to anxiety and stress.  Further, tryptophan and resultant endorphins play a role in natural pain relief.

Tryptophan is an indispensable amino acid that is needed for the synthesis of many proteins that are critical for the proper functioning of the human body.  After consumption, it is transformed by the body to bioactive metabolites, including serotonin, melatonin, kynurenine, and nicotinamide (a form of vitamin B3), indole, skatole, and indoleacetic acid.  Tryptophan metabolites have significant health benefits.

Some of the health benefits associated with tryptophan include the following:

• According to the journal article Melatonin in Cancer Treatment [1]: Epidemiological and experimental studies have documented that melatonin (a tryptophan derivative) could inhibit different types of cancer in vitro and in vivo.  Results showed the involvement of melatonin in different anticancer mechanisms, inclusive of apoptosis induction (i.e., cell death); cell proliferation inhibition; tumor growth reduction and metastases inhibition; reduction in the side effects associated with chemotherapy and radiotherapy; decreasing drug resistance in cancer therapy; and augmentation of the therapeutic effects of conventional anticancer therapies.  Regarding the latter, clinical trials reveal that melatonin is an effective adjuvant (i.e., complementary) drug to all conventional therapies.  In addition, Melatonin has shown potential for the prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer, and colorectal cancer [2].

• Serotonin Production [3]: Tryptophan is a precursor to serotonin, a neurotransmitter that plays a key role in regulating mood, sleep, and appetite.  Adequate tryptophan intake can help support healthy serotonin levels, which may contribute to improved mood and overall emotional well-being. In addition, long COVID is associated with reduced circulating serotonin levels [13], possibly indicating a need for additional tryptophan consumption. 

• Depression [15]: A number of tryptophan depletion studies found that about two-thirds of people who have recently recovered from a depressive episode will relapse when given diets artificially low in tryptophan. People with a family history of depression also appear vulnerable to tryptophan depletion. And tryptophan has a secondary effect of raising serotonin levels in the brain.

• Sleep Improvement [4]: Serotonin, synthesized from tryptophan, can be further converted into melatonin, a hormone that regulates sleep-wake cycles.  Consuming foods rich in tryptophan can potentially improve sleep quality and aid in managing insomnia.

• Mood Regulation:  The hormone serotonin is linked to feelings of happiness and relaxation.  Tryptophan's role in serotonin synthesis can have a positive impact on mood regulation and may help alleviate symptoms of mild depression and anxiety.  “Low levels of serotonin are linked to depression.  The most commonly used antidepressants, the selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), work by increasing serotonin levels in the brain [5].” 

• Pain relief [6]: Tryptophan may help reduce pain by increasing the production of endorphins, a neurotransmitter that is the body's natural painkiller.

• Appetite control [7]: Tryptophan may help suppress appetite by increasing the production of serotonin.  This may be helpful for people who are trying to lose weight.

• Immunity [8]: Tryptophan is needed for the production of white blood cells, which help fight infection in the body.

In addition to these benefits, tryptophan may also be helpful for treating other conditions:

• Premenstrual syndrome (PMS) [9]: Tryptophan may help reduce symptoms of PMS, such as mood swings, fatigue, and food cravings via its role in the production of serotonin.

• Fibromyalgia [10]: Tryptophan may help reduce pain and improve sleep in people with fibromyalgia via the production of serotonin and endorphins.

• Smoking cessation [11]: Tryptophan may help reduce cravings and withdrawal symptoms in people who are trying to quit smoking per its role in the production of serotonin.

• Myopia [16][17]: Dopamine, a derivative of Tryptophan, has been found to be protective against the progression of myopia (near-sightedness).

It is important to note that more research is needed to confirm the effectiveness of tryptophan for each of these conditions.

Signs and symptoms of tryptophan deficiency include apathy, liver damage, muscle loss, skin lesions, weakness, and slowed growth in children [12].  The daily requirement for adults is 200mg of L-Tryptophan a day [12], though higher amounts are recommended to allow one to prolong exercise.  The International Journal of Sports Medicine describes tryptophan as promoting the increased tolerance to exercise pain.  The amount suggested is 1,200 mg daily in the morning plus 300 mg at night [12].  Note that excess tryptophan may require more protein uptake because of decreased absorption of other amino acids.  And, excess tryptophan supplementation may also reduce insulin production, which will raise blood sugar levels and which may be part of the mechanism that allows for the extension of exercise time.

Foods rich in tryptophan include turkey, chicken, eggs, dairy products, nuts, seeds, soy products, and certain seafood.  Plants and legumes generally only contain trace amounts of tryptophan [12].  Additionally, individual responses to tryptophan can vary, and its benefits are best achieved as part of a balanced diet that supports overall health.  If you are considering tryptophan supplements for specific health purposes, it is advisable to consult a healthcare professional before making any changes to your diet or supplementation regimen.

In summary, tryptophan is an essential amino acid, which is a key building block for serotonin, melatonin, endorphins, and other metabolites, which help to improve sleep, enhance mood, reduce pain, and decrease cancer risk.

* It is also possible to get melatonin and serotonin from food and supplements, but we prefer to let the body's intelligence decide how much of each metabolite to make from tryptophan.  Exercise, which provides many health benefits, stimulates the increased production of endorphins in the body.

References

[1]   Talib WH, Alsayed AR, Abuawad A, Daoud S, Mahmod AI. Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities. Molecules. 2021 Apr 25;26(9):2506. doi: 10.3390/molecules26092506. PMID: 33923028; PMCID: PMC8123278.

[2]  Li, Y.; Zhou, Y. Melatonin for the prevention and treatment of cancer. Oncotarget 2017, 8, 39896–39921.

[3]   Friedman M. Analysis, Nutrition, and Health Benefits of Tryptophan. Int J Tryptophan Res. 2018 Sep 26;11:1178646918802282. doi: 10.1177/1178646918802282. PMID: 30275700; PMCID: PMC6158605.

[4]   Sutanto CN, Loh WW, Kim JE. The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression. Nutr Rev. 2022 Jan 10;80(2):306-316. doi: 10.1093/nutrit/nuab027. PMID: 33942088.

[5]   Watson, S., Serotonin: The natural mood booster, Harvard Health Publishing, 20 July 2021, https://www.health.harvard.edu/mind-and-mood/serotonin-the-natural-mood-booster.

[6]   Samuel Seltzer, Russell Stoch, Richard Marcus, Eric Jackson, Alteration of human pain thresholds by nutritional manipulation and L-tryptophan supplementation, PAIN®, Volume 13, Issue 4, 1982, Pages 385-393, ISSN 0304-3959, https://doi.org/10.1016/0304-3959(82)90007-0.  (https://www.sciencedirect.com/science/article/pii/0304395982900070)

[7]   Greenblatt, J., Controlling Appetite With Amino Acid Supplements, Psychiatry Redefined eNewsletter, https://www.psychiatryredefined.org/controlling-appetite-with-amino-acids/, accessed on 11 August 2023.

[8]   Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunol Cell Biol. 2003 Aug;81(4):247-65. doi: 10.1046/j.1440-1711.2003.t01-1-01177.x. PMID: 12848846.

[9]  Rapkin AJ, Reading AE, Woo S, Goldman LM. Tryptophan and neutral amino acids in premenstrual syndrome. Am J Obstet Gynecol. 1991 Dec;165(6 Pt 1):1830-3. doi: 10.1016/0002-9378(91)90040-x. PMID: 1750482.

[10]  M. Nicolodi, F. Sicuteri, Fibromyalgia and Migraine, Two Faces of the Same Mechanism: Serotonin as the Common Clue for Pathogenesis and Therapy, Part of the Advances in Experimental Medicine and Biology book series (AEMB, Volume 398), 1996.

[11]  Bowen DJ, Spring B, Fox E. Tryptophan and high-carbohydrate diets as adjuncts to smoking cessation therapy. J Behav Med. 1991 Apr;14(2):97-110. doi: 10.1007/BF00846173. PMID: 1880796.

[12] Braverman et al., The Healing Nutrients Within: Facts, Findings, and New Research on Amino Acids, 2003. 

[13] Wong et al., Serotonin reduction in post-acute sequelae of viral infection, Cell, October 16, 2023, DOI:https://doi.org/10.1016/j.cell.2023.09.013. 

[14] Windred et al., Sleep regularity is a stronger predictor of mortality risk than sleep duration: A prospective cohort study, Oxford University Press on behalf of Sleep Research Society, 2023.

[15] Thompson, J., The Cause of Depression Is Probably Not What You Think, Quanta Magazine, 26 January 2023. 

[16] Richard, DM et al., L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications, International Journal of Tryptophan Research 2009:2 45–60.

[17] Zhou, X et al., Dopamine Signaling and Myopia Development: What Are the Key Challenges, Prog Retin Eye Res. 2017 Nov; 61: 60–71, Published online 2017 Jun 7. doi: 10.1016/j.preteyeres.2017.06.003.