5-HTP

Authors:

Massimo E Maffei

Findings:

This review covers the natural occurrence (e.g., Griffonia simplicifolia), chemical analysis, synthesis, biosynthesis (via TPH), and biotechnological production (metabolic engineering in E. coli, yeast) of 5-HTP. It discusses physiological effects observed in animal studies and human clinical trials, including potential benefits for depression, anxiety, sleep disorders, obesity, migraine, and other conditions. The review also addresses the toxicology of 5-HTP, including serotonin syndrome and the historical issue of toxic contaminants in preparations.

Participants:

The review discusses studies involving various animal models (mice, rats, guinea pigs, snails, rabbits, cats, dogs, sheep, cows, fetal lambs) and human participants, including healthy volunteers, depressed patients (adults, children, women with SSRI/SNRI resistance), patients with anxiety/panic disorders, schizophrenic boys, mongoloid infants, children with sleep terrors, subjects with romantic stress, migraine sufferers, patients with ataxia, fibromyalgia patients, patients with dementia of the Alzheimer’s type (DAT), Parkinson’s disease (PD) patients, patients with myoclonus (posthypoxic intention, palatal, cherry red spot, spinal segmental), obese adult females, and dogs with toxicosis.

Dosage:

Specific dosages mentioned include: doses above 100mg associated with vomiting/nausea; 50 mg daily used in a trial for depression in Parkinson's disease; administration at 4-hour intervals studied for prolactin release; 1.5–3 mg intracisternally studied in rabbits. Dose-dependent effects (e.g., tremors, wet dog shakes) were noted in rats. Combination treatments with other drugs (nialamide, L-deprenil, carbidopa, creatine) are also mentioned.

Study Quality Assessment:

This is a review article. It describes its search strategy (Web of Science 1985–2020, PubMed 1940–2020, selecting 195 papers from 816). It discusses human clinical trials, mentioning methodologies like 'double-blind controlled study', 'open trial study', 'open-label pilot study', 'double-blind comparison', 'double-blind study', 'double-blind, randomized, placebo-controlled study', 'single-center, randomized, double-blind, placebo-controlled, cross-over trial'. Analytical methods discussed include HPLC, mass spectrometry (MS), capillary electrophoresis (CE), NMR, electrochemical sensors. Toxicological concerns regarding contaminants (e.g., peak X, peak E, peak UV5, peak AAA) in tryptophan and 5-HTP preparations linked to eosinophilia–myalgia syndrome (EMS) are mentioned.

All Effects:

Authors:

Jane Turner, Kelly A Shaw

Findings:

Available evidence from two small trials suggests 5-HTP and tryptophan were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% CI 1.28-13.15). However, the evidence quality is insufficient to be conclusive, and further studies are needed to evaluate efficacy and safety before widespread use can be recommended, especially given the existence of proven alternatives and unresolved safety concerns.

Participants:

Adults with unipolar depression or dysthymia (total N=64 across two included trials).

Study Quality Assessment:

Systematic Review (Cochrane Database Syst Rev). Searched multiple databases (Medline, Psychlit, Embase, Cochrane registers). Selection criteria: randomized trials vs placebo. Data extracted independently by three reviewers. Trial quality scored according to risk of bias. Limitations: Only two trials (N=64) met quality criteria; evidence deemed of insufficient quality to be conclusive. Potential safety concern (Eosinophilia-Myalgia Syndrome) mentioned as not elucidated.

Findings:

5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of L-tryptophan in serotonin biosynthesis. Its intestinal absorption does not require a transport molecule.

Findings:

The meta-analysis found a depression remission rate of 0.65 (95% CI, 0.55-0.78) based on 13 studies, supported by questionnaire results showing a large effect size (Hedges' g = 1.11; 95% CI, 0.53-1.69). However, results showed significant heterogeneity due to methodological variability, and the included studies were generally considered weak, often lacking placebo controls.

Participants:

depressed patients

Dosage:

Methodological variability in 5-hydroxytryptophan dosage was noted, but specific dosages were not detailed in the abstract.

Study Quality Assessment:

Systematic review and meta-analysis (PRISMA guidelines used, pre-registered on PROSPERO: CRD42018104415). Included 13 investigations in review, 7 in meta-analysis. Limitations noted: Methodological variability (treatment duration, type of depression, experimental design, 5-hydroxytryptophan dosage), heterogeneity (I2 = 76%, τ2 = 0.379), overall weakness of current studies (few include placebo groups, assessed via OHAT tool).

Findings:

In one preliminary study (N=25), 50mg daily 5-HTP significantly improved depressive symptoms compared to placebo over 4 weeks, but did not reduce apathy symptoms. In another preliminary study (N=12), 50mg daily 5-HTP significantly improved levodopa-induced dyskinesias over 4 weeks.

Participants:

Study 1 ('Efficacy and safety of 5-hydroxytryptophan on depression and apathy...'): N=25 individuals with Parkinson’s disease. Study 2 ('Efficacy and safety of 5-Hydroxytryptophan on levodopa-induced motor complications...'): N=12 Parkinson’s patients diagnosed with levodopa-induced dyskinesias and motor fluctuations.

Dosage:

50 mg of 5-HTP daily over a period of 4 weeks (used in both studies mentioned).

Study Quality Assessment:

Two small, preliminary studies mentioned. Both described as single-center, randomized, double-blind, placebo-controlled cross-over trials. Limitations mentioned: small sample size, need for larger studies, longer treatment duration, and different doses recommended for corroboration.