A perspective on the safety of supplemental tryptophan based on its metabolic fates

Journal of Nutrition

Volumn 146, Issue 12, 2016, Pages 2601S-2608S

  Fernstrom, John D ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Animals; Humans; Indoxyl 3 sulfate; Kynurenic acid; Melatonin; Microbiome; Quinolinic acid; Serotonin; Skatole; Tryptophan

Indexed keywords

5 HYDROXYINDOLE; KYNURENINE; MELATONIN; SEROTONIN; TRYPTOPHAN;

ARTICLE; DIETARY SUPPLEMENT; GASTROINTESTINAL TRACT; HUMAN; METABOLITE; MICROBIOME; NONHUMAN; PROTEIN BLOOD LEVEL; THROMBOCYTE; TRYPTOPHAN METABOLISM; BIOSYNTHESIS; METABOLISM;

DIETARY SUPPLEMENTS; HUMANS; SEROTONIN; TRYPTOPHAN;

EID: 85007004321     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.115.228643     Document Type: Article

References (79)

1. Bender DA. Biochemistry of tryptophan in health and disease. Mol Aspects Med 1983;6:101-97.
2. Bray TM, Emmerson KS. Putative mechanisms of toxicity of 3-methylindole: from free radical to pneumotoxicosis. Annu Rev Pharmacol Toxicol 1994;34:91-115.
3. Fernstrom JD. Role of precursor availability in the control of monoamine biosynthesis in brain. Physiol Rev 1983;63:484-546.
4. Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 2013;20:14-21.
5. Duerschmied D, Suidan GL, Demers M, Herr N, Carbo C, Brill A, Cifuni SM, Mauler M, Cicko S, Bader M, et al. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice. Blood 2013;121:1008-15.
6. Reiter RJ. The pineal gland. In: DeGroot LJ, editor. Endocrinology. 2nd ed. Philadelphia: Saunders; 1989. p. 240-53.
7. Stone TW, Stoy N, Darlington LG. An expanding range of targets for kynurenine metabolites of tryptophan. Trends Pharmacol Sci 2013;34:136-43.
8. Yamamoto S, Hayaishi O. Tryptophan pyrrolase of rabbit intestine: d-and l-tryptophan-cleaving enzyme or enzymes. J Biol Chem 1967;242:5260-6.
9. Zhou X, D'Agostino J, Li L, Moore CD, Yost GS, Ding X. Respective roles of CYP2A5 and CYP2F2 in the bioactivation of 3-methylindole in mouse olfactory mucosa and lung: studies using Cyp2a5-null and Cyp2f2-null mouse models. Drug Metab Dispos 2012;40:642-7.
10. Albert VR, Allen JM, Joh TH. A single gene codes for aromatic L-amino acid decarboxylase in both neuronal and non-neuronal tissues. J Biol Chem 1987;262:9404-11.
11. Invernizzi RW. Role of TPH-2 in brain function: news from behavioral and pharmacologic studies. J Neurosci Res 2007;85:3030-5.
12. Sikander A, Rana SV, Prasad KK. Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta 2009;403:47-55.
13. Morrissey JJ, Walker MN, Lovenberg W. The absence of tryptophan hydroxylase activity in blood platelets. Proc Soc Exp Biol Med 1977;154:496-9.
14. Mercado CP, Kilic F. Molecular mechanisms of SERT in platelets: regulation of plasma serotonin levels. Mol Interv 2010;10:231-41.
15. Acuñ a-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX, Reiter RJ. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 2014;71:2997-3025.
16. Bertrand PP, Bertrand RL. Serotonin release and uptake in the gastrointestinal tract. Auton Neurosci 2010;153:47-57.
17. Mawe GM, Hoffman JM. Serotonin signalling in the gut-functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol 2013;10:473-86.
18. Yuwiler A, Brammer GL, Morley JE, Raleigh MJ, Flannery JW, Geller E. Short-term and repetitive administration of oral tryptophan in normal men: effects on blood tryptophan, serotonin, and kynurenine concentrations. Arch Gen Psychiatry 1981;38:619-26.
19. Hagbom M, Istrate C, Engblom D, Karlsson T, Rodriguez-Diaz J, Buesa J, Taylor JA, Loitto VM, Magnusson KE, Ahlman H, et al. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting. PLoS Pathog 2011;7:e1002115.
20. Fernstrom JD. Effects and side effects associated with the nonnutritional use of tryptophan by humans. J Nutr 2012;142 (Suppl):2236S-44S.
21. Wyatt RJ, Engelman K, Kupfer DJ, Fram DH, Sjoerdsma A, Snyder F. Effects of L-tryptophan (a natural sedative) on human sleep. Lancet 1970;2:842-6.
22. Austin GL, Ogden LG, Hill JO. Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971-2006. Am J Clin Nutr 2011;93:836-43.
23. Panel on Macronutrients, Protein and Amino Acids. Dietary Reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. Washington (DC): National Academies Press; 2002.
24. Watts SW, Morrison SF, Davis RP, Barman SM. Serotonin and blood pressure regulation. Pharmacol Rev 2012;64:359-88.
25. Sved AF, Van Itallie CM, Fernstrom JD. Studies on the antihypertensive action of L-tryptophan. J Pharmacol Exp Ther 1982;221:329-33.
26. Fregly MJ, Sumners C, Cade JR. Effect of chronic dietary treatment with L-tryptophan on the maintenance of hypertension in spontaneously hypertensive rats. Can J Physiol Pharmacol 1989;67: 656-62.
27. Diaz J, Ni W, Thompson J, King A, Fink GD, Watts SW. 5-Hydroxytryptamine lowers blood pressure in normotensive and hypertensive rats. J Pharmacol Exp Ther 2008;325:1031-8.
28. Price LH, Charney DS, Heninger GR. Effects of trazodone treatment on serotonergic function in depressed patients. Psychiatry Res 1988;24:165-75.
29. Wingrove J, Bond AJ, Cleare AJ. Tryptophan enhancement/depletion and reactions to failure on a cooperative computer game. Neuropsychopharmacology 1999;21:755-64.
30. Feltkamp H, Meurer KA, Godehardt E. Tryptophan-induced lowering of blood pressure and changes of serotonin uptake by platelets in patients with essential hypertension. Klin Wochenschr 1984;62: 1115-9.
31. Wurtman RJ, Axelrod J, Phillips LS. Melatonin synthesis in the pineal gland: control by light. Science 1963;142:1071-3.
32. Ganguly S, Coon SL, Klein DC. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res 2002;309:127-37.
33. Yaga K, Reiter RJ, Richardson BA. Tryptophan loading increases daytime serum melatonin levels in intact and pinealectomized rats. Life Sci 1993;52:1231-8.
34. Huether G, Poeggeler B, Reimer A, George A. Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. Life Sci 1992;51:945-53.
35. Hajak G, Huether G, Blanke J, Blömer M, Freyer C, Poeggeler B, Reimer A, Rodenbeck A, Schulz-Varszegi M, Ruther E. The influence of intravenous L-tryptophan on plasma melatonin and sleep in men. Pharmacopsychiatry 1991;24:17-20.
36. Jahnke G, Marr M, Myers C, Wilson R, Travlos G, Price C. Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol Sci 1999;50:271-9.
37. Ogden CL, Fryar CD, Carroll MD, Flegal KM. Mean body weight, height, and body mass index, United States 1960-2002. Advance Data from Vital and Health Statistics. No. 347. Hyattsville (MD): National Center for Health Statistics; 2004.
38. Keszthelyi D, Troost FJ, Masclee AAM. Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function. Neurogastroenterol Motil 2009;21:1239-49.
39. Schwarcz R. The kynurenine pathway of tryptophan degradation as a drug target. Curr Opin Pharmacol 2004;4:12-7.
40. Kolodziej LR, Paleolog EM, Williams RO. Kynurenine metabolism in health and disease. Amino Acids 2011;41:1173-83.
41. Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunol Cell Biol 2003;81:247-65.
42. Shimizu T, Nomiyama S, Hirata F, Hayaishi O. Indoleamine 2, 3-dioxygenase: purification and some properties. J Biol Chem 1978;253: 4700-6.
43. Yoshida R, Nukiwa T, Watanabe Y, Fujiwara M, Hirata F, Hayaishi O. Regulation of indoleamine 2, 3-dioxygenase activity in the small intestine and the epididymis of mice. Arch Biochem Biophys 1980;203: 343-51.
44. Collingridge GL, Lester RA. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 1989;41:143-210.
45. Moroni F, Cozzi A, Sili M, Mannaioni G. Kynurenic acid: a metabolite with multiple actions and multiple targets in brain and periphery. J Neural Transm 2012;119:133-9.
46. Guillemin GJ. Quinolinic acid, the inescapable neurotoxin. FEBS J 2012;279:1356-65.
47. Chen Y, Brew BJ, Guillemin GJ. Characterization of the kynurenine pathway in NSC-34 cell line: implications for amyotrophic lateral sclerosis. J Neurochem 2011;118:816-25.
48. Beagles KE, Morrison PF, Heyes MP. Quinolinic acid in vivo synthesis rates, extracellular concentrations, and intercompartmental distributions in normal and immune-activated brain as determined by multipleisotope microdialysis. J Neurochem 1998;70:281-91.
49. Chen Y, Gilles JG. Kynurenine pathway metabolites in humans: disease and healthy states. Int J Tryptophan Res 2009;2:1-19.
50. During MJ, Freese A, Heyes MP, Swartz KJ, Markey SP, Roth RH, Martin JB. Neuroactive metabolises of L-tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid effect of tryptophan loading. FEBS Lett 1989;247:438-44.
51. Swartz KJ, During MJ, Freese A, Beal MF. Cerebral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors. J Neurosci 1990;10:2965-73.
52. Vécsei L, Miller J, MacGarvey U, Beal MF. Kynurenine and probenecid inhibit pentylenetetrazol-and NMDLA-induced seizures and increase kynurenic acid concentrations in the brain. Brain Res Bull 1992;28: 233-8.
53. Gál EM, Sherman AD. L-Kynurenine: its synthesis and possible regulatory function in brain. Neurochem Res 1980;5:223-39.
54. Gill SS, Pulido OM. Glutamate receptors in peripheral tissues: current knowledge, future research, and implications for toxicology [review]. Toxicol Pathol 2001;29:208-23.
55. Luzzi S, Zilletti L, Franchi-Micheli S, Gori AM, Moroni F. Agonists, antagonists and modulators of excitatory amino acid receptors in the guinea-pig myenteric plexus. Br J Pharmacol 1988;95:1271-7.
56. Moroni F, Pellegrini-Giampietro DE, Alesiani M, Cherici G, Mori F, Galli A. Glycine and kynurenate modulate the glutamate receptors in the myenteric plexus and in cortical membranes. Eur J Pharmacol 1989;163:123-6.
57. Shannon HE, Sawyer BD. Glutamate receptors of the N-methyl-daspartate subtype in the myenteric plexus of the guinea pig ileum. J Pharmacol Exp Ther 1989;251:518-23.
58. Kaszaki J, Palasthy Z, Erczes D, Racz A, Torday C, Varga G, Vecsei L, Boros M. Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs. Neurogastroenterol Motil 2008;20:53-62.
59. Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski WA. Micromolar concentration of kynurenic acid in rat small intestine. Amino Acids 2008;35:503-5.
60. Keszthelyi D, Troost FJ, Jonkers DM, van Donkelaar EL, Dekker J, Buurman WA, Masclee AA. Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine? Am J Clin Nutr 2012;95:603-8.
61. Keszthelyi D, Troost FJ, Jonkers DM, Kruimel JW, Leue C, Masclee AAM. Decreased levels of kynurenic acid in the intestinal mucosa of IBS patients: relation to serotonin and psychological state. J Psychosom Res 2013;74:501-4.
62. Moffett JR, Blinder KL, Venkateshan CN, Namboodiri MAA. Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs. Cell Tissue Res 1998;293:525-34.
63. Yokoyama MT, Carlson JR. Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole. Am J Clin Nutr 1979;32:173-8.
64. Bryan GT. Quantitative studies on the urinary excretion of indoxyl sulfate (indican) in man following administration of L-tryptophan and acetyl-L-tryptophan. Am J Clin Nutr 1966;19:105-12.
65. Schroeder JC, DiNatale BC, Murray IA, Flaveny CA, Liu Q, Laurenzana EM, Lin JM, Strom SC, Omiecinski CJ, Amin S, et al. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 2010;49:393-400.
66. Murray IA, Patterson AD, Perdew GH. Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer 2014;14:801-14.
67. Cheng Y, Jin UH, Allred CD, Jayaraman A, Chapkin RS, Safe S. Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes. Drug Metab Dispos 2015;43:1536-43.
68. Sallée M, Dou L, Cerini C, Poitevin S, Brunet P, Burtey S. The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: a new concept to understand cardiovascular complications of chronic kidney disease. Toxins (Basel) 2014;6:934-49.
69. Miyazaki T, Aoyama I, Ise M, Seo H, Niwa T. An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF-1 in uraemic rat kidneys. Nephrol Dial Transplant 2000;15:1773-81.
70. Sidransky H. Tryptophan and carcinogenesis: review and update on how tryptophan may act. Nutr Cancer 1997;29:181-94.
71. Benevenga NJ, Steele RD. Adverse effects of excessive consumption of amino acids. Annu Rev Nutr 1984;4:157-81.
72. Sainio EL, Pulkki K, Young SN. L-Tryptophan: biochemical, nutritional and pharmacological aspects. Amino Acids 1996;10:21-47.
73. National Cancer Institute. Bioassay of L-tryptophan for possible carcinogenicity. Washington (DC): US Government Printing Office; 1978 NIH DHEW Publication No.: 78-1321
74. Yost GS. Mechanisms of 3-methylindole pneumotoxicity. Chem Res Toxicol 1989;2:273-9.
75. Karlin DA, Mastromarino AJ, Jones RD, Stroehlein JR, Lorentz O. Fecal skatole and indole and breath methane and hydrogen in patients with large bowel polyps or cancer. J Cancer Res Clin Oncol 1985;109:135-41.
76. Suyama Y, Hirayama C. Serum indole and skatole in patients with various liver diseases. Clin Chim Acta 1988;176:203-6.
77. Regal KA, Laws GM, Yuan C, Yost GS, Skiles GL. Detection and characterization of DNA adducts of 3-methylindole. Chem Res Toxicol 2001;14:1014-24.
78. Nichols WK, Mehta R, Skordos K, Mace K, Pfeifer AMA, Carr BA, Minko T, Burchiel SW, Yost GS. 3-Methylindole-induced toxicity to human bronchial epithelial cell lines. Toxicol Sci 2003;71:229-36.
79. Michael AF, Drummond KN, Doeden D, Anderson JA, Good RA. Tryptophan metabolism in man. J Clin Invest 1964;43:1730-46.