- 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.
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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.
- 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.
Low levels of essential amino acids may indicate a poor-quality diet, or maldigestion due to deficient digestive peptidase activity or pancreatic dysfunction. Because some dietary tryptophan is converted to niacin, tryptophan-deficient diets have been associated with lower niacin production. Interestingly, niacin administration increased plasma tryptophan by 40%.
Clinically, low serum tryptophan levels have been shown to correlate with depressive symptoms and cognitive impairment.
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- 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.
Elevated tryptophan may be seen in high protein diets or supplementation. Stress, insulin resistance, magnesium or vitamin B6 deficiency, and increasing age can all inhibit the conversion of tryptophan to 5-HTP and elevate tryptophan. Lack of nutrient cofactors (vitamin B6, riboflavin, iron, and heme) in several other tryptophan pathways can also contribute to elevations.
Lastly, glutaric aciduria is a rare inborn error of metabolism characterized by elevated tryptophan.
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1-Methylhistidine, 1-Methylhistidine (Plasma), 2-,3-, and 4-Methylhippuric acid, 2-Methylhippuric Acid, 2-Methylsuccinic Acid, 3,4-Dihydroxyhydrocinnamic Acid, 3,5-Dihydroxybenzoic Acid, 3-Methylhistidine, 3-Methylhistidine (Plasma), 3-Phenylpropionylglycine, 4-Hydroxybenzoic Acid, 4-Hydroxyphenylacetic Acid, 4-Hydroxyphenylpyruvic Acid, 5-Hydroxyindoleacetic Acid, 8-Hydroxy-2'-deoxyguanosine, a-Hydroxybutyric Acid, a-Keto-b-methylvaleric Acid, a-Ketobutyric Acid, a-Ketoglutaric Acid, a-Ketoisocaproic Acid, a-Ketoisovaleric Acid, a-Aminoadipic Acid, a-Aminoadipic Acid (Plasma), Adipic Acid, Alanine, Alanine (Plasma), Aldosterone, Anserine (Plasma), Anthranilic Acid, Arabinitol, Arginine, Arginine (Plasma), Arginosuccinic Acid, Arginosuccinic Acid (Plasma), Asparagine, Asparagine (Plasma), Aspartic Acid (Plasma), b-Hydroxybutyric Acid, b-Hydroxyisovaleric Acid, b-Alanine, b-Alanine (Plasma), Benzoic Acid, Benzoylform, Branched Chain Alpha-Keto Organic Acids, Carnosine, Carnosine (Plasma), cis-Aconitic Acid, Citric Acid, Citrulline, Citrulline (Plasma), Cortisol, Cortisone, Creatinine, Cystathionine, Cystathionine (Plasma), Cystine, Cystine (Plasma), D-Lactic Acid, Equol, Ethanolamine, Ethanolamine (Plasma), Ethylmalonic Acid, Formiminoglutamic Acid, Fructose, Fumaric Acid, g-Aminobutyric Acid, g-Aminobutyric Acid (Plasma), Glucaric Acid, Glucose, Glutamic Acid, Glutamic Acid (Plasma), Glutamine, Glutamine (Plasma), Glutamine / Glutamate Ratio, Glutamine / Glutamate Ratio (Plasma), Glutaric Acid, Glycine, Glycine (Plasma), Glycylproline, Glycylproline (Plasma), Hexanoylglycine, Hippuric Acid, Histidine, Histidine (Plasma), Homocitrulline (Plasma), Homocystine, Homocystine (Plasma), Homogentisic Acid, Homovanillic Acid, Hydroxykynurenine, Hydroxyproline, Hydroxyproline (Plasma), Indoleacetic Acid, Isocitric Acid, Isoleucine/allo-Isoleucine, Isoleucine/allo-Isoleucine (Plasma), KT Ratio, KT Ratio (Plasma), Kynurenic Acid, Kynurenine, Kynurenine (Plasma), Lactic Acid, Leucine, Leucine (Plasma), Lysine, Lysine (Plasma), Malic Acid, Mandelic Acid, Methionine, Methionine (Plasma), Methylmalonic Acid, Microalbumin, Ornithine, Ornithine (Ornithine transcarbamylase), Ornithine (Plasma), Orotic Acid, Oxalic Acid, pH, Phenylacetic Acid, Phenylalanine, Phenylalanine (Plasma), Phosphate, Phosphoethanolamine, Phosphoethanolamine (Plasma), Picolinic Acid, Pimelic Acid, Proline, Proline (Plasma), Pyridoxic Acid, Pyroglutamic Acid, Pyruvic Acid, Quercetin, Quinolinic Acid, Sarcosine, Sarcosine (Plasma), Sebacic Acid, Serine, Serine (Plasma), Suberic Acid, Suberylglycine, Succinic Acid, Sulfocysteine, Sulfocysteine (Plasma), Tartaric Acid, Taurine, Taurine (Plasma), Threonine, Threonine (Plasma), Total Branched Chain Amino Acids, Total Branched Chain Amino Acids (Plasma), Tryptophan, Tryptophan (Plasma), Tyrosine, Tyrosine (Plasma), Valine, Valine (Plasma), Vannilylmandelic Acid, Xanthurenic Acid