Tryptophan Research
43 peer-reviewed studies · Evidence score: 8/10
Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis
Cheng YC et al. • Psychological medicine (2025)
This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.
- Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response.
- This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.
- Further research warranted to confirm findings
The Tryptophan Catabolite or Kynurenine Pathway in a Major Depressive Episode with Melancholia, Psychotic Features and Suicidal Behaviors: A Systematic Review and Meta-Analysis
Almulla AF et al. • Cells (2022)
Patients with affective disorders with melancholic and psychotic features and suicidal behaviors showed normal IDO enzyme activity but a lowered availability of plasma/serum TRP to the brain, which is probably due to other processes such as low albumin levels.
- Severe patients showed significant lower (p < 0.0001) TRP (standardized mean difference, SMD = -0.517, 95% confidence interval, CI: -0.735; -0.299) and TRP/CAAs (SMD = -0.617, CI: -0.957; -0.277) levels with moderate effect sizes, while no significant difference in CAAs were found.
- Kynurenine (KYN) levels were unaltered in severe MDD/BD phenotypes, while the KYN/TRP ratio showed a significant increase only in patients with psychotic features (SMD = 0.224, CI: 0.012; 0.436).
- Quinolinic acid (QA) was significantly increased (SMD = 0.358, CI: 0.015; 0.701) and kynurenic acid (KA) significantly decreased (SMD = -0.260, CI: -0.487; -0.034) in severe MDD/BD.
Kynurenine metabolite changes in individuals with alcohol use disorder: A systematic review and meta-analysis
Wang Z et al. • Drug and alcohol dependence (2023)
Our results suggested a shift in the tryptophan metabolism to the kynurenine pathway and a down-regulation of the potentially neuroprotective kynurenic acid in individuals with AUD.
- The peripheral blood levels of kynurenine (SMD = 0.58; p = 0.004) along with the ratio of kynurenine and tryptophan (SMD = 0.73; p = 0.002) were higher in individuals with AUD, while kynurenic acid levels (SMD = -0.81; p = 0.003) were reduced in individuals with AUD compared to controls.
- Our results suggested a shift in the tryptophan metabolism to the kynurenine pathway and a down-regulation of the potentially neuroprotective kynurenic acid in individuals with AUD.
- Further research warranted to confirm findings
Tryptophan Dietary Intake, Serotonin, and Depression: A Systematic Review and Meta-Analysis
Kikuchi AM et al. • Nutrients (2021)
Higher tryptophan intake was inversely associated with depression risk.
- Higher tryptophan intake associated with lower depression prevalence
- Dose-response relationship observed between tryptophan and serotonin markers
- Both dietary and supplemental tryptophan showed mood-related benefits
Antidepressants for smoking cessation
Hughes JR et al. • The Cochrane database of systematic reviews (2014)
The antidepressants bupropion and nortriptyline aid long-term smoking cessation.
- There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76).
- There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78).
- There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit.
The Tryptophan Catabolite or Kynurenine Pathway in Alzheimer's Disease: A Systematic Review and Meta-Analysis
Almulla AF et al. • Journal of Alzheimer's disease : JAD (2022)
AD is characterized by TRP depletion but not by an overactivity of the TRYCAT pathway.
- Moreover, we also found a significant increase in the central nervous system (CNS), brain, and cerebrospinal fluid kynurenic acid (KA)/KYN ratio but not in peripheral blood, as well as a significant decrease in plasma KA and xanthurenic acid in the CNS and blood.
- AD is characterized by TRP depletion but not by an overactivity of the TRYCAT pathway.
- IDO-induced production of neurotoxic TRYCATs is not a key factor in the pathophysiology of AD.
Effects of L-Tryptophan on Sleep: A Systematic Review
Sutanto CN et al. • Nutrients (2022)
L-tryptophan supplementation at doses >= 1g improved overall sleep quality, particularly in subjects with existing sleep difficulties.
- Doses of 1g or more consistently improved sleep quality outcomes
- Benefits most pronounced in individuals with existing sleep disturbances
- Tryptophan supplementation reduced sleep onset latency across multiple trials
Differential Metabolites in Osteoarthritis: A Systematic Review and Meta-Analysis
Liao Z et al. • Nutrients (2023)
This meta-analysis examined the effects of Acetyl-L-Carnitine.
- In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts.
- Among them, 37 metabolites appeared more than twice.
- Further research warranted to confirm findings
Metabolomics on depression: A comparison of clinical and animal research
Wang Y et al. • Journal of affective disorders (2024)
This systematic review delineated metabolic biomarkers and pathways related to depression in the murine and clinical samples, providing opportunities for early diagnosis of MDD and the development of novel diagnostic targets.
- This systematic review delineated metabolic biomarkers and pathways related to depression in the murine and clinical samples, providing opportunities for early diagnosis of MDD and the development of novel diagnostic targets.
- Published in Journal of affective disorders (2024)
- Further research warranted to confirm findings
The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis
Tosti G et al. • Nutrients (2023)
The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.
- There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48-1.37; I2 = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50-1.55; I2 = 63%), and NMSC (RR 0.82, 95% CI 0.61-1.12; I2 = 63%).
- The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.
- Further research warranted to confirm findings
The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome
Wang S et al. • Nutrients (2023)
Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.
- In order to identify the role of altered intestinal tryptophan metabolism in IBD pathogenesis, a meta-analysis of the transcriptome was performed to identify differentially expressed genes involved in the tryptophan metabolism pathways in intestinal biopsies of IBD as compared to non-IBD controls.
- Moreover, a systematic review of the metabolome was performed to identify the concurrent changes in tryptophan metabolites.
- Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.
Genetic polymorphism involved in major depressive disorder: a systemic review and meta-analysis
Suktas A et al. • BMC psychiatry (2024)
At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly.
- A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78-2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77-1.64; P = 0.56).
- At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly.
- These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction.
A systematic review and meta-analysis of proteomic and metabolomic alterations in anaphylaxis reactions
Gallizzi AA et al. • Frontiers in immunology (2024)
Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions.
- Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions.
- These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis.
- Further research warranted to confirm findings
A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning
Kikuchi AM et al. • Journal of dietary supplements (2021)
In order to estimate the optimum amount of TRP intake more accurately, further studies need to be conducted with more appropriate settings of intake period, intake frequency, and intake method.
- This suggests that TRP intake may be an effective approach to decrease anxiety and increase positive mood in healthy individuals.
- On the other hand, the effectiveness of TRP for aggressive feelings was not recognized.
- Reviewing these 11 RCTs, we concluded that taking 0.14-3 g of TRP per day in addition to the usual meal can be expected to improve the mood of healthy individuals.
The role of tryptophan and its derivatives in musculoskeletal pains: A systematic review and meta-analysis
De La Torre Canales G et al. • Journal of oral rehabilitation (2024)
The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain.
- The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain.
- Published in Journal of oral rehabilitation (2024)
- Further research warranted to confirm findings
Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis
Hebbrecht K et al. • Frontiers in immunology (2021)
The TRYCAT pathway appears to be downregulated in BD patients.
- Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls.
- The TRYCAT pathway appears to be downregulated in BD patients.
- There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
Antidepressants for neuropathic pain
Saarto T et al. • The Cochrane database of systematic reviews (2005)
Antidepressants are effective for a variety of neuropathic pains.
- Amitriptyline has an NNT of 2 (95%CI 1.7 to 2.5) RR 4.1(95%CI 2.9-5.9) for the achievement of at least moderate pain relief.
- For diabetic neuropathy the NNT for effectiveness was 1.3 (95%CI 1.2 to 1.5) RR 12.4(95%CI 5.2-29.2) (five studies); for postherpetic neuralgia 2.2 (95%CI 1.7 to 3.1), RR 4.8(95%CI 2.5-9.5)(three studies).
- The number needed to harm(NNH) for major adverse effects defined as an event leading to withdrawal from a study was 16 (95%CI: 10-45).
The serotonin theory of depression: a systematic umbrella review of the evidence
Moncrieff J et al. • Molecular psychiatry (2023)
This meta-analysis examined the effects of Tryptophan.
- The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.
- Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.© 2022.
- Further research warranted to confirm findings
The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression
Sutanto CN et al. • Nutrition reviews (2022)
Trp supplementation, especially at ≥1 g can help improve sleep quality.
- Trp supplementation, especially at ≥1 g can help improve sleep quality.
- Published in Nutrition reviews (2022)
- Further research warranted to confirm findings
Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis
Plitman E et al. • Schizophrenia bulletin (2017)
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- Standardized mean differences (SMDs) were calculated to determine differences in KYNA levels between groups.
- The influences of patients' age, antipsychotic status (%medicated), and sex (%male) on study SMDs were assessed through a meta-regression.
- Patients' age, %medicated, and %male were each positively associated with study SMDs.