Disorders of Tryptophan Metabolism

One of the most infamous diseases of tryptophan metabolism is pellagra, in which there is a deficiency of tryptophan. This deficiency of tryptophan causes a deficiency of niacin (1). This disease was once common, but it has been largely eradicated due to the efforts of vitamin advocates. Vitamin supplements, if they contain niacin, prevent the disease and treat it. Tryptophan supplements were taken off of the market due to problems. Many people were getting sick from the tryptophan.

Pellagra

Dementia is one of the symptoms. Dermatitis is another. According to Ref. 1, pellagra was seen in the Mississippi Delta in the early 20th century. Dementia was seen. The diet that these unfortunates were on is described in Ref. 1. Salt pork, corn meal, and cane syrup were staples. Corn meal has very little tryptophan. Cane syrup has almost no tryptophan.

Thanks to people like Linus Pauling and Abram Hoffer, both consistent vitamin advocates, pellagra has been largely eradicated. However, alcoholics can still get it due to thier peculiar diet. Their diet is mostly carbohydrates and water. Alcoholic beverages contain almost no tryptophan. Alcoholics should take vitamins.

Patients with pellagra were often put in insane asylums. Some died. Molasses, which was a major part of their diet, has almost no tryptophan. Ref. 2 provides information on the history of this problem in America. Ref. 3 discusses the solution, which is vitamin fortification.

Schizophrenia

Strangely the excess of tryptophan has also been associated with mental symptoms. It seems that the brain needs the proper level of tryptophan to function well. Too little tryptophan is a problem, but too much tryptophan also appears to be a problem. Dr. Libuse Gilka of Canada proposed that schizophrenia is a disorder of tryptophan metabolism (4). He proposed that a diet low in certain offending amino acids should be used. This brilliant article was largely ignored in the US except by myself. He also suspected methionine.

Detroit work claimed excessive uptake of cells for tryptophan (5) in schizophrenia. Like Gilka's work, this work was largely ignored except by myself. For some reason the Detroit workers did not propose a low tryptphan diet. Their approach was to try to destroy the unknown toxic factor that caused the tryptophan to flood the cells. Their toxic factor is described in Refs. 6 & 7.

Russian Work

Russian workers confirmed the Detroit work (8).

Depression

British workers (9, 10) have reported tryptophan accumulation in platelets in depression. Many other reports have linked depression and tryptophan. At one time tryptophan was used as a therapy for depression, but there were many problems so it was taken off of the market. There have been reports of tryptophan making schizophrenia worse.

Ref. 11 by the same UK group reported "mood disturbances" related to tryptophan.

Acute Intermittent Porphyria

In this disease there are psychiatric symptoms. It seems that a key enzyme in the metabolism of tryptophan is low in this disease (12). This causes tryptophan to accumulate in the brain and cause psychiatric symptoms. Tryptophan pyrrolase breaks down tryptophan in the kynurenine pathway, which is the main pathway of tryptophan metabolism. Another pathway leads to serotonin. There is no deficiency of serotonin in this disease.

A factor that is low in porphyria is required by this enzyme. Porphyria is treated by heme, which is the factor (13, 14).

Conclusions

Ref. 15 reports that microscopy studies support a theory of amino acids flooding the brain cells in schizophrenia. This is consistent with the Detroit work and the Russian work.

Studies of the blood (16) also support this theory. It may be that tryptophan is the worst offending amino acid. In other words, tryptophan is flooding the cells at a greater rate than other amino acids in schizophrenia and depression. If all of this is true, and it appears to be true, then a diet very low in tryptophan should be considered as a treatment for psychiatric diseases. However, niacin should be given as a supplement to avoid pellagra.

References

1. Worms and Germs, Drink and Dementia: US Health, Society, and Policy in the Early 20th Century. Lynne S WilcoxPrev Chronic Dis. 2008 October; 5(4): A135. Published online 2008 September 15.

2. Goldberger J, Sydenstricker E. Pellagra in the Mississippi flood area. Public Health Rep. 1927;42:2706-2725.

3. Park YK, Sempos CT, Barton CN, Vanderveen JE, Yetley EA. Effectiveness of food fortification in the United States: the case of pellagra. Am J Public Health. 2000;90(5):727-738.

4. Acta Psychiatr Scand Suppl. 1975;258:1-83. Schizophrenia, a disorder of tryptophan metabolism. Gilka L.

5. Classically conditioned autonomic discrimination and tryptophan uptake in chronic schizophrenia. Gorham JC, Novelly RA, Ax AF, Frohman CE. Psychophysiology. 1978 Mar;15(2):158-64.

6. The effect of schizophrenic factor on liver tryptophan oxygenase. Sardesai VM, Ward V, Provido H, Frohman CE. Commun Psychopharmacol. 1977;1(5):439-46.

7. Plasma factor in schizophrenia. Frohman CE. Biol Psychiatry. 1976 Apr;11(2):251-2.

8. [Stimulating effect of schizophrenic patients' plasma on the cellular incorportation of tryptophan in vitro]Mukhin AG, Faktor MI. Zh Nevropatol Psikhiatr Im S S Korsakova. 1979;79(7):941-7. Russian.

9. Tryptophan accumulation by blood platelets of depressed patients. Wood K, Swade C, Coppen A. J Neural Transm Suppl. 1979;(15):161-3.

13. Badawy AA. The functions and regulation of tryptophan pyrrolase. Life Sci. 1977 Sep 15;21(6):755-768.

14. Badawy AA, Evans M. The effects of chemical porphyrogens and drugs on the activity of rat liver tryptophan pyrrolase. Biochem J. 1973 Dec;136(4):885-892.

15. http://www.associatedcontent.com/article/2690467/microscopy_studies_of_mental_illness.html?cat=68

10. [Indoleamine precursors in depression (author's transl)] Coppen A, Wood K. Encephale. 1979;5(5 Suppl):627-32. French.

11. Relationship between mood disturbances and free and total plasma tryptophan in postpartum women. Stein G, Milton F, Bebbington P, Wood K, Coppen A. Br Med J. 1976 Aug 21;2(6033):457.

12. Tryptophan pyrrolase, the regulatory free haem and hepatic porphyrias. Early depletion of haem by clinical and experimental exacerbators of porphyria. Badawy AA. Biochem J. 1978 Jun 15;172(3):487-94.