On the need to eliminate SSRIs and return to serotonin precursors

Int J Tryptophan Res. Author manuscript; available in PMC 2010 July 21.
Published in final edited form as:
Int J Tryptophan Res. 2009 March 23; 2: 45–60.

PMCID: PMC2908021
L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications
Dawn M Richard,1 Michael A Dawes,1 Charles W Mathias,1 Ashley Acheson,2 Nathalie Hill-Kapturczak,1 and Donald M Dougherty1

L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications

Other metabolic functions

Tryptophan also exerts effects on other neurotransmitters and CNS compounds. Dopamine, norepinephrine, and beta-endorphin have been shown to increase following oral dosing of tryptophan.42,5861 Through serotonin synthesis, tryptophan is also thought to be involved in modulation of the endocrine system and cortisol,60,62 as well as prolactin and growth

In the bloodstream, tryptophan competes with other large neutral amino acids (LNAA; e.g. histidine, isoleucine, leucine, methionine, phenylalanine, threonine, tyrosine, and valine) for the BBB transporter.3,35,36,71,72 Given that BBB transporter is nearly saturated at normal plasma concentrations of amino acids, it is uniquely susceptible to competitive inhibition.73 Because of the competitive transport among the LNAAs, the bioavailability of tryptophan for transport across the BBB is best expressed by the ratio of tryptophan to the sum of its competing amino acids.9,36,66,74 Therefore, changing the ratio of tryptophan to the other competing large neutral amino acids can significantly affect concentrations of brain tryptophan available for serotonin synthesis. This can be accomplished by changing plasma concentrations of tryptophan, or by changing concentrations of the CAAs, either of which affect tryptophan availability and, by extension, serotonin synthesis.7578 Although other influences, such as stress, insulin resistance, magnesium or vitamin B6 deficiency, and increasing age, can affect the rate of serotonin synthesis,79 fluctuations in the tryptophan/CAA ratio and changing tryptophan availability are the two factors most likely to affect this process.

In addition to these dietary factors that affect tryptophan’s availability for synthesis of brain serotonin, acute alcohol consumption has also been shown to decrease the tryptophan/CAA ratio by about 10% at about 30 minutes and 20%–25% at about 1.5 to 2 hours following ingestion.87,88 This decrease suggests that brain serotonin synthesis is impaired under these conditions.87,89 Where the average individual is likely to tolerate this level of serotonin depletion without undue effects on their behavior, vulnerable individuals may experience a larger depletion effect (e.g. 50% or more).90,91 This vulnerability may be due to a pre-existing condition of low or borderline serotonin function that could be further impaired by the diminished serotonin synthesis following acute alcohol consumption.88,89


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