5 HTP: Antioxidant, Weight Loss Aid, Or Disease Producer?

2D-structure of 5-hydroxytryptophan (5-HTP; Ox...
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First a little history. 

In 1989, a load of contaminated tryptophan produced by Showa Denko made it to the U.S.  It caused eosinophilia-myalgia syndrome (EMS).  Rather than withdraw the contaminated batch, the FDA banned tryptophan.  In an extraordinary coincidence, Prozac entered the market about the same time. 

Not to be outdone, the supplement manufacturers did an end run around the ban by generating 5 hydroxy tryptophan, 5HTP, which wasn’t banned and was supposedly safer.  But a single case of the syndrome was linked to 5HTP, leading to fears that the product would be banned as well. 

Fast forward to the present.  Tryptophan quietly returned to the market without causing so much as a twitch.  5 HTP has a twenty year history with no further cases.  But every time patients talk about either they are inundated with the possibility of this syndrome.  The sydrome itself was definitively linked to contaminants within the tryptophan (study below, all studies at my website) not the tryptophan itself.  5HTP has been fed to rats in huge doses for a year without causing any problems. 

Now we’ve got studies showing that 5HTP may suppress the appetite in dieters.  (study below)  It showed almost a 70% reduction in hunger.  It also acts as an antioxidant for cell preservation.  And we’ve never had any definitive data on any dangers.  A Yale report on the initial syndrome studies shows they were seriously flawed.   

Arch Environ Contam Toxicol. 1993 Jul;25(1):134-42.

Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome.

Hill RH Jr, Caudill SP, Philen RM, Bailey SL, Flanders WD, Driskell WJ, Kamb ML, Needham LL, Sampson EJ.

SourceDivision of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Georgia 30333.


In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L-tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan. We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)


nt J Obes (Lond). 2009 Oct;33(10):1174-82. Epub 2009 Sep 15.

Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation.

Rondanelli M, Klersy C, Iadarola P, Monteferrario F, Opizzi A.

SourceSection of Human Nutrition and Dietetics, Faculty of Medicine, Endocrinology and Nutrition Unit, Department of Applied Health Sciences, Azienda di Servizi alla Persona, University of Pavia, Pavia, Italy. serv.nutrizione@asppavia.it


OBJECTIVE: To test the effect on satiety of a formulation comprising plant extracts naturally containing 5-hydroxytryptophan, delivered as sublingual spray (5HTP-Nat Exts), administered five times a day for 2 months.

DESIGN: Two-month, randomized, double-blind, placebo-controlled trial.

SUBJECTS: A total of 27 healthy, adult overweight women were randomly assigned to the treatment (14) or the placebo group (13).

MEASUREMENTS: Visual analog scales were used to assess appetite sensations every day. Moreover, the study evaluated the bioavailability of 5-hydroxytryptophan following sublingual delivery over 8 weeks, by comparing 24-h urinary excretion of 5-hydroxy-3-indoleacetic acid (5-HIAA), determined at baseline and after 2 months. Other secondary end points of the study were to compare body composition, depressive symptoms, severity of binge eating and quality of life. Finally, the study tested whether a single administration of 5HTP-Nat Exts in fasting state has an effect on amino-acid profile and on appetite ratings and whether 5HTP-Nat Exts administered before a fixed test meal has any effect on satiety.

RESULTS: The group using the 5HTP-Nat Exts experienced a significantly greater increase in their sensation of satiety over an 8-week timeframe and in fasting state following administration of 5HTP-Nat Exts than the placebo group did (AUC=305.2 (52.8) vs 236.6 (59.4), mean difference -68.7 (95% confidence interval (CI) -116.2 to -21.2), P=0.007; mean difference in Haber score change 2.5 (95% CI 0.62-3.12, P=0.007)). A difference was observed between the groups for the mean change in 5-HIAA. All the amino acids evaluated after a single administration of 5HTP-Nat Exts were found to be similar. Differences were found for the mean change in body mass index, skinfold thicknesses and hip circumference. The other parameters were found to be similar.

CONCLUSION: All these findings suggest that 5HTP-Nat Exts may be safely used to treat the problem of appetite control in overweight women during a weight loss program.



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