L-Tryptophan

 Main Points

  • L-Tryptophan is an essential amino acid that the body uses to produce serotonin (a neurotransmitter responsible for regulating mood).
  • Converts to 5-HTP (5-hydroxytryptophan), which is the precursor to serotonin.
  • L-Tryptophan may help promote restful sleep, calm and relaxation.
  • Oral supplementation of L-Tryptophan has a greater effect on increasing serotonin in the brain than tryptophan ingested from whole food sources.

    Name

    • L-Tryptophan (converts to 5-HTP, active serotonin precursor).

      Good Sources

      • Nuts, seeds, poultry, legumes, supplements.

          How to Take

          • A moderate dose is between 1 - 6 grams per day, though doses up to 12 grams have been studied.

              Natural Stacks Supplements Containing L-Tryptophan


                L-Tryptophan and Brain Health

                L-Tryptophan is one the nine essential amino acids, but is one of the least plentiful found in the standard American diet. It is believed to improve mood, focus, and sleep quality.

                L-tryptophan is metabolized in the liver by the rate-limiting enzyme tryptophan hydroxylase where it is then converted to 5-HTP, at which point it can then freely cross the blood-brain barrier where it is finally converted to serotonin [1]. Whereas supplemental 5-HTP can directly and freely influence serotonin production, the rate-limiting nature of L-tryptophan encourages balanced levels of serotonin.

                Serotonin is an agonist for several different serotonin receptors in the brain. Many antidepressant drugs developed over the past 30 years, known as selective serotonin re-uptake inhibitors (SSRIs), have been developed with the intention of keeping serotonin levels active in the brain by reducing the activity of the SERT protein [2].

                 

                L-Tryptophan Deficiency

                Low levels of tryptophan have been associated with poor mood [34].

                Tryptophan deficiency can be the result of chronic inflammation, in which enzymes are unregulated that inhibit serotonin production, or, deficiency can likely be the result of a diet lacking in the amino acid tryptophan [5, 6, 7].

                Additionally, deficiencies of magnesium or vitamin B6 can downregulate activity of the rate-limiting enzyme tryptophan hydroxylase which is required to convert L-Tryptophan to 5-HTP [8].

                 

                Effects on Mood

                Tryptophan is a precursor to 5-HTP which is used to produce serotonin, a neurotransmitter thought to be responsible for mood, anxiety, fear, depression, and aggression [9, 10, 11, 12].

                 

                Effects on Anxiety

                Serotonin appears to be involved with anxiety and panic attacks. Studies using a tryptophan depletion technique (thought to be a reliable method to reduce serotonin) in humans have shown that the body may be more sensitized to panic-related symptoms, reduced mood, and increased anxiety when serotonin is depleted [13, 14, 15].

                 

                Effects on Sleep

                Serotonin is broken down and then processed into melatonin via methylation [16].

                Melatonin is crucial for healthy sleep cycles and supplemental doses up to 3 mg have been shown to improve sleep quality and reduce symptoms of insomnia [17, 18]. Supplementation of melatonin has been shown to increase serotonin in animal models, and increases of melatonin from supplemental L-Tryptophan have been noted to varying degrees [19, 20].

                Seasonal affective disorder, a form of depression caused by lack of sunlight in winter months, is tied to serotonin deficiency [21]. This is possibly due to excess melatonin production from serotonin as melatonin production is controlled by light exposure and the circadian rhythms [22].

                 

                Side Effects

                Gastrointestinal effects such as nausea, heartburn, vomiting, stomach pain, and diarrhea have been reported in abnormally high doses.

                 

                References

                1. Birdsall, T. C. (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative medicine review: a journal of clinical therapeutic, 3(4), 271-280.
                2. Kristensen, A. S., Andersen, J., Jørgensen, T. N., Sørensen, L., Eriksen, J., Loland, C. J., ... & Gether, U. (2011). SLC6 neurotransmitter transporters: structure, function, and regulation. Pharmacological reviews, 63(3), 585-640.
                1. Coppen, A., Eccleston, E. G., & Peet, M. (1973). Total and free tryptophan concentration in the plasma of depressive patients. The Lancet, 302(7820), 60-63.
                2. Cowen, P. J., Parry-Billings, M., & Newsholme, E. A. (1989). Decreased plasma tryptophan levels in major depression. Journal of affective disorders, 16(1), 27-31.
                3. Taylor, M. W., & Feng, G. S. (1991). Relationship between interferon-gamma, indoleamine 2, 3-dioxygenase, and tryptophan catabolism. The FASEB Journal, 5(11), 2516-2522.
                4. Myint, A. M., & Kim, Y. K. (2003). Cytokine–serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Medical hypotheses, 61(5), 519-525.
                5. Babcock, T. A., & Carlin, J. M. (2000). Transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor α in interferon-treated epithelial cells. Cytokine, 12(6), 588-594.
                6. Green, A. R., Aronson, J. K., Curzon, G., & Woods, H. F. (1980). Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan. British journal of clinical pharmacology, 10(6), 603-610.
                7. Young, S. N., & Leyton, M. (2002). The role of serotonin in human mood and social interaction: insight from altered tryptophan levels. Pharmacology Biochemistry and Behavior, 71(4), 857-865.
                8. Homberg, J. R. (2012). Serotonergic modulation of conditioned fear. Scientifica, 2012.
                9. Alekseyenko, O. V., & Kravitz, E. A. (2014). Serotonin and the search for the anatomical substrate of aggression. Fly, 8(4), 200-205.
                10. Piszczek, L., Piszczek, A., Kuczmanska, J., Audero, E., & Gross, C. T. (2015). Modulation of anxiety by cortical serotonin 1A receptors. Frontiers in behavioral neuroscience, 9.
                11. Park, S. B., Coull, J. T., McShane, R. H., Young, A. H., Sahakian, B. J., Robbins, T. W., & Cowen, P. J. (1994). Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology, 33(3), 575-588.
                12. Cleare, A. J., & Bond, A. J. (1995). The effect of tryptophan depletion and enhancement on subjective and behavioural aggression in normal male subjects. Psychopharmacology, 118(1), 72-81.
                13. Klaassen, T., Klumperbeek, J., Deutz, N. E., van Praag, H. M., & Griez, E. (1998). Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge. Psychiatry research, 77(3), 167-174.
                14. Axelrod, J., & Weissbach, H. (1960). Enzymatic O-methylation of N-acetylserotonin to melatonin. Science, 131(3409), 1312-1312.
                15. Van Geijlswijk, I. M., Mol, R. H., Egberts, T. C., & Smits, M. G. (2011). Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomniaPsychopharmacology216(1), 111-120.
                16. Luthringer, R., Muzet, M., Zisapel, N., & Staner, L. (2009). The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomniaInternational clinical psychopharmacology24(5), 239-249.
                17. Kollmann, M. T., Locher, M., Hirche, F., Eder, K., Meyer, H. H. D., & Bruckmaier, R. M. (2008). Effects of tryptophan supplementation on plasma tryptophan and related hormone levels in heifers and dairy cows. Domestic animal endocrinology34(1), 14-24.
                18. Miguez, J. M., Martin, F. J., & Aldegunde, M. (1994). Effects of single doses and daily melatonin treatments on serotonin metabolism in rat brain regions. Journal of pineal research, 17(4), 170-176.
                19. Gupta, A., Sharma, P. K., Garg, V. K., Singh, A. K., & Mondal, S. C. (2013). Role of serotonin in seasonal affective disorder. European review for medical and pharmacological sciences, 17(1), 49-55.
                20. Rosenthal, N. E., Sack, D. A., Jacobsen, F. M., James, S. P., Parry, B. L., Arendt, J., ... & Wehr, T. A. (1985). Melatonin in seasonal affective disorder and phototherapy. Journal of neural transmission. Supplementum, 21, 257-267.

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