Ice-in-veins 5HTP Aberrations

Summary

Specific points of metabolic aberrations appear in a man using high doses of 5-hydroxytryptophan for sleep.

This content was created by the Metametrix Institute

History

This patient is a 57- year-old man who is intent on preserving his health. He reports a frequent sensation of ice in his veins. He has mild tachycardia, and, after snow shoveling exertion, he had elevated blood pressure for two days. He also reports difficulty with headaches after drinking wine with dinner, which he would like to enjoy as he has in the past. He complains of chronic insomnia, and his major quest is to be able to drink wine and sleep soundly. Impaired sulfite clearance is an explanation of the reaction to wine, so the physician has placed the patient on supplemental glutathione, mixed amino acids, taurine, and other detoxification regimens. The patient has been using supplemental arginine (500 mg bid), phenylalanine (500 mg AM), tyrosine (500 mg PM), vitamins A, E, and Coenzyme Q10. He has also been using 1500 mg L-tryptophan at bedtime for sleep.

Age

57

Gender

Male

Description of Results

We first note the imbalanced high level of L-tryptophan in plasma that is consistent with a loading of 5-HTP. Otherwise, there is a suspiciously high Arg/Cit ratio, indicating possible difficulty with nitric oxide production. (Arg -NOS-> Cit + NO)

Erythrocyte mineral concentrations are unremarkable.

There is a suggestion of excess membrane polyunsaturated fatty acid levels in the finding of elevated lipid peroxides in the presence of above normal levels of serum antioxidant vitamin concentrations. The PUFA problem is confirmed by the plasma fatty acid profile that shows high GLA and AA with relatively balanced EPA. The finding of low DHA indicates that dietary flax oil or other ALA sources are the major contributor to the n-3 fatty acids rather than fish oils that would be supplying DHA as well as EPA.

Dramatic influence of high L-Trp supplementation is found in the Organix profile where the tryptophan metabolites xanthurenate and kynurenate are extremely elevated. These markers of vitamin B6 adequacy occur in the kynurenin pathway where hepatic clearance of L-Trp is via conversion to nicotinate and other oxidized products. Since the patient has been using multi-vitamin supplementation for some time, the indication is that the kynurenin pathway is simply overloaded to the point of spilling of multiple intermediates.

Note that serotonin turnover is still low, as evidenced by the low 5-HIA (#25). Also, something is causing a severe elevation of p-hydroxyphenyllactate (and presumably its methyl ester that exerts cell regulator and apoptotic control function). Also, there may be mild mitochondrial energetic disruption giving some elevation of lactate and succinate.
Follow-up testing:  Results from ADMA testing show normal levels, allowing us to rule out that source of inhibition in nitric oxide synthesis.

Recommendations

Stop the high dose L-tryptophan at bed time, increase L-arginine to 1 gm tid. Do follow up testing of plasma amino acids with asymmetric dimethylarginine (ADMA) assay added to look for increased production of this suspected inhibitor of nitric oxide synthase. Stop supplementation of GLA dietary oil sources. Start a course of vitamin C at bowel tolerance to help lower the HPLA levels.

Other Comments

When the kynurenate/quinolinate ratio reaches 10:1 one begins to wonder about suppression of hippocampal NMDA receptors. This is the corollary of the more frequently encountered low Kyn/Quin ratio where the NMDA agonist action of Quin can lead to insomnia and neruodegenerative depression. Such a case of extreme intake of L-tryptophan complicates the normal interpretation of elevated xanthurenate as a marker of vitamin B6 deficiency. It is still possible that raising B6 intake to high enough levels can alleviate the metabolic congestion in the kynurenin pathway.