Medical Research on Tryptophan

"Degradation of tryptophan, resulting in lower blood levels and impaired cerebral production and release of serotonin, is enhanced by inter alia inflammation, pregnancy and stress in all species investigated, including humans. Consequently, tryptophan may not only serve as a nutrient, but also as a bona fide signalling amino acid. Humans suffering from inflammatory and other somatic diseases accompanied by low tryptophan levels, exhibit disturbed social behaviour, increased irritability and lack of impulse control, rather than depression." (1)

Introduction

There have been many theories involving serotonin, an important metabolite of tryptophan. However, niacin is also an important metabolite of tryptophan, and there may be other important metabolites. There are many metabolites of tryptophan, but some are not completely understood yet. One theory is that serotonin is abnormal in depression (1).

Interferon (INF)

This cytokine is used as a treatment for various diseases. It stimulates the immune system. Unfortunately it produces adverse behavioral symptoms as a side effect (2). It is known to degrade tryptophan into kynurenine and other metabolites in the kynurenine pathway of tryptophan degradation.

Psychiatric Drugs

Unfortunately there have been terrible problems with psychiatric drugs (3) including obesity and other metabolic problems. The obesity can be treated by diet. "Antidepressants" are toxic to the liver (4, 5).

Unfortunately weight gain caused by the drugs (6, 7) is a risk factor for hypertension, diabetes, and other diseases.

Depression

There is a cytokine theory for depression (8). This reference favors "pharmacological treatment", but I favor the use of alternative medicine due to the terrible side effects drugs. Alternative medicine is cheaper and safer.

Anorexia

Ref. 9 implicates cytokines in anorexia.

Schizophrenia

Ref. 12 reports a possible genetic basis for schizophrenia.

Tryptophan

Ref. 13 associates tryptophan with weight gain in a study on pigs. What is not clear is whether tryptophan has anything to do with the weight gain caused by psychiatric drugs (14). This article that I have written is the most devastating attack on psychiatric drugs I have ever written. It is a very strong support for orthomolecular psychiatry, which uses therapeutic nutrition.

There is evidence (15) that tryptophan metabolism is abnormal in irritable bowel syndrome.

Conclusions

Refs. 16-18 provide more information on mental health. Ref. 19 provides a mouse model of depression. It claims that depression was caused in mice by increased tryptophan metabolism in the kynurenine pathway. Whether or not this is an accurate model of human depression is not clear, but it could be.

References

1. Tryptophan as an evolutionarily conserved signal to brain serotonin: Molecular evidence and psychiatric implications. Russo S, Kema IP, Bosker F, Haavik J, Korf J. World J Biol Psychiatry. 2009;10(4):258-268.

2. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, Spivey JR, Saito K, Miller AH. Mol Psychiatry. 2009 Nov 17.

3. Baptista T, Kin NM, Beaulieu S, de Baptista EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 2002;35:205-219.

4. Davis M. Hepatotoxicity of antidepressants. Int. Clin. Psychopharmacol. 1991;6:97-103.

5. Himmerich H, Kaufmann C, Schuld A, Pollmächer T. Elevation of liver enzyme levels during psychopharmacological treatment is associated with weight gain. J. Psychiatr. Res. 2005;39:35-42.

6. Himmerich H, Schuld A, Haack M, Kaufmann C, Pollmächer T. Early prediction of changes in weight during six weeks of treatment with antidepressants. J. Psychiatr. Res. 2004;38:485-489.

7. Hinze-Selch D, Deuschle M, Weber B, Heuser I, Pollmächer T. Effect of coadministration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts, plasma levels of cytokines and body weight. Psychopharmacology. 2000;149:163-169.

8. O'Brien SM, Scott LV, Dinan TG. Cytokines abnormalities in major depression and implications for pharmacological treatment. Hum. Psychopharmacol. 2004;19:397-403.

9. Plata-Salamán CR. Brain mechanisms in cytokine-induced anorexia. Psychoneuroendocrinology. 1999;24:25-41. 1998 Curt P. Richter Award.

10. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmächer T. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen. Psychiatry. 2001;58:445-452.

11. Selim K, Kaplowitz N. Hepatotoxicity of psychotropic drugs. Hepatology. 1999;29:1347-1351.

12. Wang S, Sun CE, Walczak CA, Ziegle JS, Kipps BR, Goldin LR, Diehl SR. Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22. Nat. Genet. 1995;10:41-46.

13. Zhang H, Yin J, Li D, Zhou X, Li X. Tryptophan enhances ghrelin expression and secretion associated with increased food intake and weight gain in weanling pigs. Domest. Anim. Endocrinol. 2007;33:47-61.

14. Zimmermann U, Kraus T, Himmerich H, Schuld A, Pollmächer T. Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients. J. Psychiatr. Res. 2003;37:193-220.

15. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. Clarke G, Fitzgerald P, Cryan JF, Cassidy EM, Quigley EM, Dinan TG. BMC Gastroenterol. 2009 Jan 20;9:6.

16. www.associatedcontent.com/article/2408396/paranoia_theory_and_treatments.html

17. www.associatedcontent.com/article/2408348/obsessivecompulsive_disorder_symptoms.html

18. www.associatedcontent.com/article/2412558/inborn_errors_of_metabolism.html

19. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. J.C. O'Connor, M.A. Lawson, C. André, M. Moreau, J. Lestage, N. Castanon, K.W. Kelley, and R. Dantzer. Mol Psychiatry. Author manuscript; available in PMC 2009 November 1.