Tryptophan Depletion and Mood Disorders

Some interesting work in this area has been reported by Israeli scientists (1). One of the original theories involved serotonin. However, other theories have been proposed (2). One theory is that a toxic metabolite of tryptophan poisons the brain in mental disorders (3). There is also an immune system theory for depression (4, 5).

The Cytokine Theory

"When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people." Dantzer et al (5)

The authors correlate this theory with abnormal tryptophan metabolism.

"Immunotherapy alters the clinical biochemistry of patients; the most revealing sign is a pronounced reduction in plasma levels of tryptophan⁵⁶, which correlates with the patients' depression scores 3 weeks into the treatment. Tryptophan is an essential amino acid that is actively transported into the brain for the synthesis of serotonin." Dantzer et al (5)

I have included their Ref. 56 as my Ref. 6. Ref. 6 reports a side effect of cancer treatment. This side effect is depression for the cytokine treatment. This side effect is associated with possible increased transport of tryptophan into the cells causing decreased serum tryptophan and increased tryptophan metabolism. Ref. 7 also supports this theory, which is a good one.

My own theory is that stress is involved in depression. Some of these facts have been known for a long time (8).

Tryptophan In Foods

The following foods are high in tryptophan (9):

Bananas, beans, brewer's yeast, brown rice bran, caseinate, cottage cheese, dairy products, dates, eggs, fish, lactalbumin, legumes, meat, milk, nuts, peanuts, protein (hydrolysis), seafood, seeds, soy, turkey, whey, whole grains.

These foods should be avoided on a low-tryptophan diet. This diet can be used for tryptophan depletion.

There have been some tryptophan depletion experiments using an amino acid mixture devoid of tryptophan. This mixture was similar to unflavored gelatin, which has no tryptophan. Unfortunately the experimenters added a lot of sugar to the mixture to make it palatable. This sugar would enhance the brain uptake of tryptophan since insulin would be released. Because of this mistake the research was questionable.

Conclusions

Mental diseases appear to be errors in tryptophan metabolism where tryptophan floods the brain cells. This causes adverse changes in brain energy metabolism. The brain is supposed to burn glucose for fuel, but it can also burn amino acids in an emergency. It appears that a diet very low in tryptophan might help. This is called "tryptophan depletion".

References

1. Isr J Psychiatry Relat Sci. 2010;47(1):46-55. The biology of tryptophan depletion and mood disorders. Toker L, Amar S, Bersudsky Y, Benjamin J, Klein E.

2. Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch HWM, Leonard BE. Kynurenine pathway in major depression: Evidence of impaired neuroprotection. J Affect Disord. 2007;98:143-151. doi: 10.1016/j.jad.2006.07.013. [PubMed] [Cross Ref]

3. Kim JP, Choi DW. Quinolinate neurotoxicity in cortical cell culture. Neurosci. 1987;23:423-432. doi: 10.1016/0306-4522(87)90066-2.

4. Barry S, Clarke G, Scully P, Dinan TG. Kynurenine pathway in psychosis: evidence of increased tryptophan degradation. J Psychopharmacology. 2009;23:287-294. doi: 10.1177/0269881108089583.

5. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46-56.

6. Mol Psychiatry. 2002;7(5):468-73. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R.

7. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24-31. An excellent review of the clinical features of cytokine-induced depression and its possible mechanisms.

8. Renault PF, et al. Psychiatric complications of long-term interferon alfa therapy. Arch Intern Med. 1987;147:1577-1580.

9. www.orthomolecular.org.