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Depression, 5HTP and L-Tryptophan: Laboratory Markers Matter

Posted Apr 04 2010 12:00am

Depression Treatment History
Consider the typical progression of a patient with : They usually go through periods of poor appetite and limited food intake, and they systematically show decreases in average stomach acid output. So, their intake and digestive capacity become deteriorated. At the same time, they are placed on SSRI therapy that increases their demand for serotonin production. The major catabolic end product from serotonin metabolism is (5-HIA), which is mainly excreted in urine. {The important point here: 5-HIA [some call it 5-HIAA], the breakdown product from serotonin metabolism, can be measured accurately in the laboratory.}

The Details of Deterioration
The typical patient who has been placed on will show levels of 5-HIA that are ~2 times the upper 95% reference limit, or 4-5 times the mean [the breakdown values are significantly elevated in the urine]. That means that the percentage of dietary that is flowing into the serotonin pathway is now more like 4-5 times the usual ~10%. Tryptophan as a limiting amino acid, meaning that the amounts found in foods are relatively small in proportion to the other amino acids. When the cells of human tissues need to be replaced, synthesis of thousands of proteins comes to a halt the moment tryptophan is not available.

Organ Reserve Matters
Thus, patients with long term major depression can have serious difficulty with maintenance of organ reserve. So, which organs will most quickly show the effects of inadequate ability to maintain reserve? Is it not those that have the greatest turnover and routine demands? And, does that not take us straight to the gut and ? The parietal cells that make , the enterocytes that line the inner surface of the small intestines, and the pancreatic cells that must produce many grams of digestive enzymes daily, lose their ability to keep up with demand.

Treatment Failure: Deeper Cellular Consequences
Thus, it is no wonder that the progression of patients with major depression is so often a downward spiral as more and more drugs are used with less and less efficacy because the ability of their bodies to reverse the major organ reserve loss becomes more and more restricted. The energetic demands of the parietal cells cannot be met because they can’t crank up the rate of mitochondrial enzyme production. The massive daily loss of enterocytes is not matched by new formation of cells at the base of the villi because they can’t supply amino trytophanyl-t-RNA at sufficient rates for ribosomal of everything from calbindin to glutathione-S-transferase. The absence of L-tryptophan alone can produce all of these effects. And, no additional amounts of any other amino acids will help, because the protein synthesis process ceases the moment the ribosome fails to receive a single tryptophan for insertion.

What To Do Next
So, are you going to recommend therapy with large doses of tryptophan for patients on typical SSRI therapy for major depression? No, because you may induce the dangerous serotonin syndrome. This is one of the most challenging nutritional intervention decisions that you will face. A solution that has merit for your investigation is the use of customized free-form amino acid supplement powders based on plasma amino acid profile results. Because of the presence of the full spectrum of amino acids, the large neutral amino acids limit the rate at which blood tryptophan is transferred across the . Many clinicians are learning that their patients with major depression (and the frequently accompanying condition of chronic fatigue) respond very positively to this intervention.

Outcome Over Time
Once their organ reserves are restored, they can stop the free-form supplements and go back to dietary protein, or, for an interval, use isolated whey or other superior protein supplements.

Comments on 5-HTP Supplementation
What about the use of 5-HTP as an alternative therapy to support brain serotonin? It can help with mood stabilization. But, does it help with protein synthesis? No, because the conversion of tryptophan to 5-hydroxytryptophan (serotonin) is not a reversible process. So it serves only to slightly spare the loss of tryptophan. What is needed is a consistent increase in available L-tryptophan to drive protein synthesis everywhere, and allow the organ reserve capacity to be rebuilt, -  turning the course of the degenerative spiral towards rebuilding of health.

Ed Note
I’m very pleased to share with you this first guest post at CorePsych Blog, written by Dr Richard Lord, Chief Science Officer at Metametrix Laboratories - and teaches at the Metametrix Institute. For those interested in further understanding Laboratory Evaluations see Dr Lord and Dr Bralley’s book linked below. These three YouTube videos on Autism will provide an excellent window into Dr Lord’s engaging personality and deep insights into specific measurements for treating Autism. I strongly recommend you follow this link over to his presentations on file at Metametrix .

Dr Richard Lord
- Received his BS in Chemistry from Georgia State University, and his PhD in Biochemistry from the University of Texas in 1970. Postdoctoral and staff fellowships were completed at the Clayton Foundation Biochemical Institute (oligopeptide properties), the University of Arizona (insulin self-association), and the National Institutes of Health – Institute of Arthritis and Metabolic Diseases (human thyroid-binding globulin). He served as clinical laboratory director at Horizon Laboratories from 1974-1981, then, for the next eight years, Dr. Lord was Professor and Chairman in the Department of Chemistry for Life University where he was instrumental in the initiation and design of a BS degree in Nutritional Science. Dr. Lord joined Metametrix in 1989 where he currently fills the role of Chief Science Officer.

In addition to co-authoring and editing the books, Laboratory Evaluations in Molecular Medicine and Laboratory Evaluations for Integrative and Functional Medicine , Dr. Lord also publishes technical articles, lectures live at the Applying Laboratory Evaluations to Improve Clinical Outcome Seminars , and consults with health professionals regarding clinical applications of testing for metabolites and toxicants. Dr. Lord has participated in Think Tanks on Orthomolecular Medicine, Environmental Medicine and Autism.

Thanks Richard for this excellent review [emphasis with italics and subheadings my own],

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