Tryptophan (Plasma)

- Higher urine tryptophan was noted in children with ASD;

- supplementing with B vitamins and magnesium lowered urine tryptophan.

- Inflammation can lead to higher tryptophan and lower KYN/TRP ratio.

- Higher tryptophan associated with higher BMI, glucose, antidepressants, nicotinamide.

- Lower serum tryptophan and kynurenine was correlated with higher scores on the Adult ADHD self-report scale.

- Low tryptophan levels: can result in lower serotonin production which can impact memory, cognition, sleep, and mood; was noted in depression and anxiety; methionine, phenylalanine, tyrosine levels were also lower.

- A diet rich in tryptophan and antioxidants was shown to have a positive impact on mood and cognition. A high intake of large neutral amino acids (like BCAA) can compete with tryptophan absorption.

- Modulation of tryptophan metabolism can either aggravate or prevent "inflammaging"-related diseases; age-related low-grade chronic inflammation known as inflammaging is involved in many age-related diseases.

---------------------------

Tryptophan is involved in serotonin production via vitamin B6-dependent pathways resulting in the intermediate 5-hydroxytryptophan (5-HTP).

5-HTP is often used as a supplement for serotonin formation instead of tryptophan, which can be quickly metabolized in other pathways. Serotonin is further metabolized to melatonin via methylation. Because of these downstream conversions, therapeutic administration of 5-HTP has been shown to be effective for depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

Tryptophan can be alternatively metabolized via the kynurenine pathway to produce various organic acids - kynurenic acid, quinolinic acid, and xanthurenic acid.

Two percent of dietary tryptophan is converted to niacin (vitamin B3) in the liver and deficiencies of vitamin B6, riboflavin, iron, and heme as essential cofactors for enzymes can slow the reaction rate.

Hartnup disease is a rare genetic disorder involving an inborn error of amino acid metabolism with symptoms developing in childhood. The intestines cannot properly absorb neutral amino acids and the kidney cannot properly resorb them. This leads to increased clearance of neutral amino acids in the urine, and normal or low levels in the plasma. Tryptophan deficiency is thought to account for the symptoms, since tryptophan converts to vitamin B3. This B3 deficiency causes dermatitis, a characteristic feature of Hartnup disease.

References:

- Adrych K, Smoczynski M, Stojek M, et al. Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis. World J Gastroenterol. 2010;16(35):4422-4427.

- Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alt Med Review. 1998;3(4):271-280.

- Gasperi V, Sibilano M, Savini I, Catani MV. Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. Int J Mol Sci. 2019;20(4).

- Patel AB, Prabhu AS. Hartnup disease. Indian journal of dermatology. 2008;53(1):31-32.

- Ciecierega T, Dweikat I, Awar M, Shahrour M, Libdeh BA, Sultan M. Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease. BMC Ped. 2014;14:311.

- NORD. Hartnup Disease. Rare Dis Info 2019, 2020.

- Gulati K, Anand R, Ray A. Nutraceuticals as adaptogens: their role in health and disease. In: Nutraceuticals. Elsevier; 2016:193-205.

- Wolf H, Brown RR. The effect of tryptophan load and vitamin B 6 supplementation on urinary excretion of tryptophan metabolites in human male subjects. Clin Sci. 1971;41(3):237- 248.

- Shibata K. Organ Co-Relationship in Tryptophan Metabolism and Factors That Govern the Biosynthesis of Nicotinamide from Tryptophan. J Nutr Sci Vitaminol. 2018;64(2):90-98.

- Shibata K, Shimada H, Kondo T. Effects of feeding tryptophan-limiting diets on the conversion ratio of tryptophan to niacin in rats. Biosci Biotech Biochem. 1996;60(10):1660-1666.

- Murray MF, Langan M, MacGregor RR. Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide. Nutrition. 2001;17(7- 8):654-656.

- Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Molec Psych. 2002;7(5):468- 473.

- Ramos-Chavez LA, Roldan-Roldan G, Garcia-Juarez B, et al. Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age. Ox Med Cell Longevity. 2018;2018:8604718.