Nazhand A, Durazzo A, Lucarini M, Guerra F, Coêlho AG, Souto EB, Arcanjo DDR, Santini A. Beneficial Properties and Sustainable Use of a Traditional Medicinal Plant: Griffonia simplicifolia. Challenges. 2024; 15(1):14. https://doi.org/10.3390/challe15010014

Publication Date: "Published: 12 March 2024"

Peer Reviewed: Yes

Study Design: "quantitative research analysis"

Methodology: Bibliographic search using Scopus database, analysis with VOSviewer software, identification, isolation, and quantification of bioactive compounds, in vitro and in vivo studies.

Sample Size: "A total of 1386 publications, from the year 1970 to the year 2021"

Controls Used: Not specified

Dose Used: "5-HTP (5-hydroxytryptophan) at a dose of 100 mg/kg/day for nine days"

Statistical Significance Declared: "p < 0.001" for various measures in clinical trials

Adverse Events: "various unwanted effects have been reported"

Conflict of Interest: "A.N., A.D., M.L., A.G.C., E.B.S., D.D.R.A. and A.S. declare no conflicts of interest. F.G. declares that there is no commercial or financial relationships that could be construed as a potential conflicts of interest considering that she currently collaborates with Inventia Biotech, Food research centre Healthcare."

Polidori D, Sanghvi A, Seeley RJ, Hall KD. How Strongly Does Appetite Counter Weight Loss? Quantification of the Feedback Control of Human Energy Intake.Obesity (Silver Spring). 2016;24(11):2289-2295. doi:10.1002/oby.21653

Publication Date: "First published: 02 November 2016"

Peer Reviewed: Yes

Study Design: "placebo-controlled trial"

Methodology: Measured body weight and baseline characteristics in a placebo-controlled trial; calculated changes in energy intake using a validated mathematical method; analyzed data using principles from engineering control theory.

Sample Size: "153 patients treated with canagliflozin"

Controls Used: "placebo-controlled"

Dose Used: "300 mg/day canagliflozin"

Statistical Significance Declared: "mean calculated energy intake changes were within 40 kcal/day of those determined using an expensive biomarker method"

Adverse Events: Not directly stated

Conflict of Interest: "DP is a full-time employee of Janssen Research & Development, LLC. KDH reports patent pending on a method of personalized dynamic feedback control of body weight and has received funding from the Nutrition Science Initiative to investigate the effects of ketogenic diets on human energy expenditure. RJS is a paid consultant for several companies and has received research support from several companies. AS reports no conflicts of interest."

Heisler LK, Jobst EE, Sutton GM, et al. Serotonin reciprocally regulates melanocortin neurons to modulate food intake.Neuron. 2006;51(2):239-249. doi:10.1016/j.neuron.2006.06.004

Publication Date: "July 20, 2006"

Peer Reviewed: Yes

Study Design: "range of neuroanatomical, electrophysiological, transgenic, and behavioral studies"

Methodology: Electrophysiology experiments on transgenic mice expressing GFP in NPY or POMC neurons. Feeding studies in weight-matched young and obese mice.

Sample Size: "n = 16" for male C57BL/6 mice, "n = 8" per genotype for CP94253 studies, "n = 10 per genotype" for d-fen studies, "n = 10-12 per genotype" for Mc4r knockout studies

Controls Used: "wild-type littermates"

Dose Used: "4.0, 8.0, 16.0 mg/kg" for CP94253, "3.0 mg/kg" for d-fen

Statistical Significance Declared: "p < 0.05" for CP94253 reduced chow intake, "p < 0.01" for CP94253 reduced 6 hr chow mash intake in wild-type and ob/ob mice, "p < 0.001" for CP94253 reduced food intake in wild-type mice

Adverse Events: None declared

Conflict of Interest: None declared

Cangiano C, Laviano A, Del Ben M, et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients.Int J Obes Relat Metab Disord. 1998;22(7):648-654. doi:10.1038/sj.ijo.0800642

Publication Date: "accepted 2 March 1998."

Peer Reviewed: Yes

Study Design: "double-blind, placebo-controlled study"

Methodology: 25 overweight non-insulin dependent diabetic outpatients were randomized to receive either 5-HTP (750 mg/d) or placebo for two weeks. Energy intake and eating behaviour were evaluated using a daily diet diary. Plasma amino acid concentrations and body weight, as well as serum glucose, insulin and glycosylated haemoglobin, were assessed.

Sample Size: "Twenty-five patients (14 male, 11 female)" "A total of twenty patients were therefore evaluated, 11 in the Placebo group and 9 in the 5-HTP group."

Controls Used: "placebo (n = 13), composed of corn starch, mannitol and magnesium stearate"

Dose Used: "5-HTP (250 mg three times/d, n = 12)"

Statistical Significance Declared: "The minimum probability level considered for statistical significance was P < 0.05." "In contrast, the oral administration of 5-HTP significantly reduced mean daily energy intake, which dropped from 8088 ± 472 kJ/d to 6388 ± 580 kJ/d during the first week (P < 0.01), and 6328 ± 528 kJ/d during the second week (P < 0.01)." "When specific macronutrient intakes were considered, we observed that in the Placebo group, macronutrient selection did not change throughout the study period. In contrast, in the 5-HTP group, carbohydrate and fat intakes declined during the second week of treatment from 263 ± 16 g/d to 196 ± 20 g/d (P < 0.01) and from 73 ± 3.2 g/d to 61 ± 4.8 g/d (P < 0.01), respectively."

Adverse Events: "Nausea was the most frequent symptom reported by patients (70% at the end of the first week of treatment)." "Nausea was an episodic and transient symptom, being less frequent during the second week of treatment (only 20% of patients reported its presence)." "In one patient only, nausea occurred during the first day of treatment and was so severe he had to withdraw from the study."

Conflict of Interest: Not declared.

Evans C, Mekhail V, Curtis J, et al. The Effects of 5-HTP on Body Composition: An 8-Week Preliminary RCT.J Diet Suppl. 2023;20(4):621-630. doi:10.1080/19390211.2022.2076760

Publication Date: "2023"

Peer Reviewed: Yes

Study Design: "placebo (PLA)-controlled, double-blind and parallel-group design."

Methodology: Subjects reported twice, data collected pre and post-treatment, instructed to maintain normal diet and exercise, used MyFitnessPal for dietary tracking, body composition measured with multi-frequency bioelectrical impedance device, statistical analysis with t-test.

Sample Size: "n = 48"

Controls Used: "placebo (n=17, six male; maltodextrin)"

Dose Used: "100 mg 5-HTP daily"

Statistical Significance Declared: "Fat mass decreased significantly post versus pre in the 5-HTP group (##p=0.02; effect size=0.12)" "The change in fat mass was significantly different between the 5-HTP and placebo group (#p=0.048; effect size=-0.645)."

Adverse Events: "Two subjects in the treatment group experienced side effects; one experienced irritability whereas another sexual dysfunction which was not clearly defined by the subject."

Conflict of Interest: "Cassandra Evans, Veronica Mekhail, Jason Curtis, Paulina Czartoryski, Jackie Kaminski, Anya Ellerbroek, Erik Bustillo, Lia Jiannine and Juan Carlos Santana have no real or perceived conflicts of interest to declare. Jose Antonio is the CEO of the ISSN, an academic nonprofit that is occasionally sponsored by companies that sell dietary supplements."

Ioannou S, Williams AL. Preliminary fMRI findings concerning the influence of 5-HTP on food selection.Brain Behav. 2016;7(1):e00594. Published 2016 Oct 28. doi:10.1002/brb3.594

Publication Date: "Received: 8 January 2016"

Peer Reviewed: Yes

Study Design: "This functional magnetic resonance imaging study"

Methodology: "Fourteen healthy male and female participants took part in the study, of which half of them received the supplement 5-HTP and the rest vitamin C (control) on an empty stomach. During the scanning session, they passively observed food (high calories, proteins, carbohydrates) and nonfood movie stimuli."

Sample Size: "Fourteen healthy male and female participants"

Controls Used: "the rest received a vitamin C tablet dissolved in orange juice"

Dose Used: "The administered dose (100 mg) did not exceed the daily recommended dose which is approximately 4 mg/kg body weight."

Statistical Significance Declared: "The following second-level comparisons were made which are reported at p < .001 (uncorrected) due to the limited number of participants (cluster activation surviving FWE correction at p < .05 are also indicated where possible)."

Adverse Events: Not reported in the study

Conflict of Interest: Not declared in the study

Amer A, Breu J, McDermott J, Wurtman RJ, Maher TJ. 5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats.Pharmacol Biochem Behav. 2004;77(1):137-143. doi:10.1016/j.pbb.2003.10.011

Publication Date: "Available online 29 November 2003." 

Peer Reviewed: Yes 

Study Design: "placebo-controlled, double-blind clinical trial." 

Methodology: Intraperitoneal injections, oral administration, blood sample analysis, food intake measurement. 

Sample Size: "four groups of male Sprague–Dawley rats (n=14)", "seven groups of rats (n=6–8)", "six healthy female subjects". 

Controls Used: "vehicle control condition", "placebo-controlled". 

Dose Used: "5-HTP (3–200 mg/kg ip)", "oral 5-HTP (1.2–2.0 mg/kg)", "5-HTP (8 mg/kg/day)", "5-HTP (900 mg/day)", "5-HTP (750 mg/day)". 

Statistical Significance Declared: "F(3,52)=13.84, 12.63, and 11.17 (all P<.001)", "F(3,12)=12.29, P<.001; F(3,12)=6.52, P<.05; F(3,12)=6.06, P<.05", "F(7,58)=12.16, P<.001", "F(3,20)=21.31, P<.001", "F(3,20)=9.12, P<.001", "r2=.8098, F(1,22)=93.68, P<.001", "F(5,30)=7.22 and 7.58 (all P<.001)". 

Adverse Events: "transient increases in plasma serotonin levels", "clinical findings similar to those seen in the carcinoid syndrome." 

Conflict of Interest: "These studies were supported in part by an NIH grant (MO1 RR0008) to the MIT Clinical Research Center, an NIMH grant (MH-28783), and a grant from the Center for Brain Sciences and Metabolism Charitable Trust."

Jacobsen JPR, Krystal AD, Krishnan KRR, Caron MG. Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale.Trends Pharmacol Sci. 2016;37(11):933-944. doi:10.1016/j.tips.2016.09.001

Publication Date: "Available online 28 September 2016"

Peer Reviewed: Yes

Study Design: "Review."

Methodology: Review of clinical trials and preclinical data, adjunctive treatment with 5-HTP in conjunction with SSRIs, evaluation of safety and efficacy in humans and animals.

Sample Size: "Most trials have used 5-HTP monotherapy, but, as noted above, 5-HTP may be more relevant as an adjunctive, augmentation therapy."

Controls Used: "Placebo versus clomipramine 225 mg (tricyclic) versus HTP 200 mg versus clomipramine + 5-HTP (N = 10, all groups)."

Dose Used: "Adjunct 5-HTP SR will be 500–2000 mg per day."

Statistical Significance Declared: "Nialamide + 5-HTP superior (P < 0.05) to nialamide at day 15."

Adverse Events: "The worst reported adverse event was diarrhea. Transient hypomania in 1/3; ‘no significant side-effects’. Nausea was the most common adverse events. Few adverse effects."

Conflict of Interest: "J.P.R.J. and M.G.C. are inventors on US patents pertaining to the adjunct 5-HTP SR method-of-treatment, and hold stock in Evecxia Inc., a company founded to develop a 5-HTP SR drug. A.D.K. and R.R.K. serve on the Evecxia Scientific Advisory Board."

Javelle F, Lampit A, Bloch W, Häussermann P, Johnson SL, Zimmer P. Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis.Nutr Rev. 2020;78(1):77-88. doi:10.1093/nutrit/nuz039

Publication Date: "2020"

Peer Reviewed: Yes

Study Design: "Randomized and nonrandomized human controlled trials Cohorts Cross-sectional studies Case-series studies"

Methodology: "MEDLINE (via PubMed) and Google Scholar were searched from inception to May 2018 for studies assessing the behavioral effects of 5-hydroxytryptophan in people with depression, using the following search query: (tryptophan metabolite [Title/Abstract] OR oxitriptan [Title/Abstract] 2-amino-3–(5-hydroxy-1H-indol-3-yl)propanoic acid [Title/Abstract] OR 5 hydroxtryptophan [Title/Abstract] OR 5HTP [Title/Abstract] OR 5-HTP [Title/Abstract] OR 5-hydroxytryptophan [Title/Abstract]) AND (Depression [Title/Abstract] OR Depressive [Title/Abstract] OR Depressed [Title/Abstract]). The species filter 'humans' was applied to this search."

Sample Size: "Thirteen studies met all the eligibility criteria and were included in the systematic review (Figure 2). Yet, 6 of these studies used only expert clinical evaluation and/or did not report depressive scores from a validated scale; therefore only 7 investigations were included in the full statistical analysis."

Controls Used: "Studies without placebo were included in the meta-analysis (but rated with high possibility of bias)."

Dose Used: "5-HTP dosage and treatment length varied not only between, but also within, studies, which interfered with the inclusion of these study characteristics as moderators in the statistical analysis."

Statistical Significance Declared: "The average Hedge’s g was found to be large (1.11; 95%CI, 0.53–1.69)."

Adverse Events: "Both supplements exert only minor side effects (eg, upset stomach, headaches, and fatigue when overdosed)."

Conflict of Interest: "The authors have no relevant interests to declare."

Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor.Altern Med Rev. 1998;3(4):271-280.

Publication Date: "1998"

Peer Reviewed: Yes

Study Design: "double-blind, multicenter study design"

Methodology: Subjects received either 100 mg of 5-HTP three times per day, or 150 mg of fluvoxamine three times daily. Evaluated at 0, 2, 4, and 6 weeks, using four evaluation tools: the Hamilton Rating Scale for Depression, a patient-performed self-assessment, the investigator’s assessment of severity, and a global clinical impression.

Sample Size: "36 subjects"

Controls Used: "fluvoxamine"

Dose Used: "100 mg of 5-HTP three times per day"

Statistical Significance Declared: "significant weight loss in both the first period (99.7 ± 5.9 kg vs. 98.0 ± 5.0 kg, p<0.03) and the second period (98.0 ± 5.0 vs. 94.7 ± 5.1 kg, p<0.02)"

Adverse Events: "Some patients may initially experience mild nausea." "80 percent of the subjects initially reported experiencing some nausea." "Serotonin syndrome is characterized by agitation, confusion, delirium, tachycardia, diaphoresis, and blood pressure fluctuations." "Two cases of EMS-like symptoms have been described in patients taking 5-HTP."

Conflict of Interest: None stated

Quattrocchi T, Micali E, Gentile A, La Ferrera EG, Barbaro L, Ciarcià S, Corrado F, Di Costa M, Fazio R, Licenziato R, Marcazzò A, Minniti R, Riccobene R, Russello CM, Cancellieri F. Effects of a phyto complex on well-being of climacteric women. J Obstet Gynaecol Res. 2015;41(7):1093-1098. doi:10.1111/jog.12659

Publication Date: "First published: 06 February 2015"

Peer Reviewed: Yes

Study Design: "observational multicenter study"

Methodology: Conducted in 12 Sicilian menopause centers. Enrolled 151 women aged 42-67 in spontaneous or surgical menopause for at least 12 months, reporting climacteric symptoms. Used Greene Climacteric Scale (GCS) and Beck Depression Inventory (BDI) at T0 and T6, with interim evaluations at T1 and T3 on five GCS symptoms. Each woman received the phyto complex for 180 days.

Sample Size: "151 women aged 42–67 years"

Controls Used: No randomized placebo-controlled group

Dose Used: "two tablets a day for the first 15 days, then one tablet a day, for a total of 180 days"

Statistical Significance Declared: "P < 0.05 value is considered statistically significant."

Adverse Events: "None of the women enrolled reported the onset of genital bleeding or pelvic pain."

Conflict of Interest: "All authors declare that there is no financial support or relationships that may pose a potential conflict of interest."