Hot or Not? 5-HTP for Hot Flashes

Abstract & Commentary

By Russell H. Greenfield, MD, Editor

Synopsis: The single author of this small pilot study concludes that 50 mg of 5-HTP taken three times a day for 4 weeks is ineffective against menopausal hot flashes. The paper is disappointing in many ways, however, and readers might question whether the actual reason behind the trial was indeed to test 5-HTP.

Source: Freedman R. Treatment of menopausal hot flashes with 5-hydroxytryptophan. Maturitas 2010;65:383-385.

The lone researcher behind this study employed double-blind, placebo-controlled methodology to evaluate the effects of 5-hydroxytryptophan (5-HTP) on hot flashes in 24 postmenopausal women who reported at least 6 hot flashes per day. Subjects were recruited through local newspaper advertisements, received $300 for participating, and were randomized to receive either 5-HTP or placebo. Treatment outcome was measured using a miniature electronic hot flash recorder that measures chest wall humidity, defining a hot flash as a change in relative humidity of at least 3%/min. At study initiation subjects were to wear the recorder continuously for one week, removing it only when bathing, and then return it at which time they were given bottles of either 5-HTP (50 mg) or placebo to be taken three times a day for 3 weeks. At the start of the fourth week subjects again donned the recorder continuously for 7 days, this time while also taking their assigned pills. Pre- and post-treatment hot flash recorder readings were then compared. Of note, subjects were not asked about hot flash frequency.

The author reports no significant effects of 5-HTP on hot flash incidence compared with placebo. Pre- and post-treatment 24-hour hot flash frequency was 23.8/18.5 in the active group and 22.8/22.6 in the placebo group, respectively. No P values were noted, though a power analysis statement was made.

The author concludes that 50 mg of 5-HTP provided three times daily over 4 weeks does not reduce menopausal hot flashes significantly as measured objectively with an electronic recorder.

Commentary

At face value, one might assume this article adds salient information to the discourse on appropriate management of hot flashes, but a thorough review makes that stance at least debatable. The problems go beyond those methodological in nature, which include the small sample size (again, it was a pilot trial), short duration of intervention, and lack of control for differences in ambient temperature or levels of physical activity. The oft-cited recommended dosage range for 5-HTP of 150-300 mg/day comes with a paucity of supportive data. Looming large, however, are persistent questions regarding the safety of 5-HTP that linger in the aftermath of now remote case reports on the associated development of eosinophilia myalgia syndrome, though many experts believe these episodes were probably due to the presence of contaminants.1,2

In an interesting twist, hot flash occurrence was determined objectively with the use of a recorder that was reportedly validated in a small 2007 study. Therein lies a potential rub, however. The lone researcher and author of this trial is also the president and CEO of the company making the monitor, and a patent is pending. To be sure, objective methods of hot flash measurement could add important information, since data are likely lost when subjects are simply queried on hot flash frequency or asked to record such occurrences in a diary (still, it would have been interesting in this trial to see what the subjects had to say about their response to the given agents). In addition, the placebo effect might be lessened, although objective indications of a hot flash might not always be indicative of a bothersome subjective sensation of one.

Hot flashes are the most common symptom associated with menopause and can negatively impact quality of life in significant ways. Extrapolation of animal data led to the conclusion that increasing brain serotonin levels might help ameliorate menopausal hot flashes, and some studies using SSRIs support this approach. Tryptophan is a precursor of serotonin, so exploring the use of 5-HTP in this setting makes sense. But the current study does not answer the question of its potential utility.

Not a small amount of space in the article is devoted to the recorder itself, and concerns of bias cannot be comfortably dispelled. Was this trial designed to test the safety and effectiveness of 5-HTP against menopausal hot flashes or to help validate the usefulness of the author's invention? One might offer the benefit of the doubt to the former, but the latter issue gnaws. The results of this trial do little to answer the question of the place of 5-HTP, if any, in the treatment of menopausal hot flashes.

References

1. Michelson D, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5- hydroxytryptophan. J Rheumatol 1994;21:2261-2265.

2. Klarskov K, et al. Eosinophilia-myalgia syndrome case-associated contaminants in commercially avail- able 5-hydroxytryptophan. Adv Exp Med Biol 1999; 467:461-468.