The compound, 5-hydroxytryptophan (5-HTP) is a precursor to the biosynthesis of the neurotransmitter serotonin. Synthesis of serotonin in the human body starts with the conversion of the essential amino acid L-tryptophan to 5-HTP, which is then transformed into serotonin. The pathophysiology of depression is associated with serotonin, and the research has correlated the effects of 5-HTP with an increase in serotonin at central serotonin receptors. In the central nervous system, 5-HTP can cross the blood-brain barrier and convert to serotonin without feedback inhibition.

Depression is common among individuals with the neurodegenerative disorder named Parkinson’s Disease (PD), with depressive symptoms occurring in approximately 35% of this population, which approximately fulfills 17% of the criteria for major depressive disorder. Research suggests that serotonergic dysfunction may be associated with the presence of mood disorders in PD. A double-blind, placebo-controlled, crossover, clinical trial assessed the efficacy of 5-HTP on depressive individuals with PD. The treatment consisted of 50 milligrams of 5-HTP daily for 4 weeks and evaluated outcomes based on the Beck Depression Inventory-II (BDI-II) and the Hamilton Depression Rating Scale (HDRS-21). The results showed improvement in depression scores on both scales and significant improvements when using the HDRS-21.

A recent animal study explored the association between 5-HTP, depression, and the gut microbiome. Administration of two species of the gut microbiome (Bifidobacterium longum subsp. infantis E41 and Bifidobacterium breve M2CF22M7) were shown to significantly increase the messenger RNA of tryptophan hydroxylase 1 (Tph1), which is the rate-limiting enzyme that converts tryptophan to 5-HTP. Levels of 5-HTP secretion correspondingly increased. Additionally, administration of E41 resulted in a significant increase in levels of butyrate, a short-chain fatty acid. Butyrate levels correlated significantly with the hippocampus, 5-HTP, and brain-derived neurotrophic factor levels. Furthermore, the study findings indicate that E41 and M2CF22M7 administration improved behavioral measures and neurological performance in the murine study population. This suggests that certain strains of bifidobacteria may support brain function through a 5-HTP-dependent mechanism.

Due to its role in serotonin synthesis, 5-HTP may be a supportive molecule for brain function. A recent systematic review and meta-analysis of clinical trials assessing oral supplementation with 5-HTP in individuals with depression suggestA that 5-HTP may have positive effects. Overall research indicates that 5-HTP as a supplement may play a supportive role in a healthy mood. In addition, recent studies suggest that certain microbes that contribute to the gut microbiome may play a role in 5-HTP modulation. 

By Colleen Ambrose, ND, MAT