Overview
Many antidepressant drugs work by raising serotonin levels. The supplement
5-hydroxytryptophan (5-HTP) has been tried in cases of depression for a similar
reason: The body uses 5-HTP to make serotonin, so providing the body with 5-HTP
might, therefore, raise serotonin levels.
As a supplement, 5-HTP has also been proposed for the same uses as other
antidepressants, including aiding weight loss, preventing
migraine
headaches, decreasing the pain and discomfort of
fibromyalgia, improving sleep quality, and reducing
anxiety.
Sources
The supplement 5-HTP is not found in foods to any appreciable extent. For use as a supplement, it is manufactured from the seeds of an African plant called Griffonia simplicifolia.
Therapeutic Dosages
A typical dosage of 5-HTP is 100 to 300 milligrams (mg) three times daily. Once 5-HTP starts to work, it may be possible to reduce the dosage significantly and still maintain good results.
Therapeutic Uses
The primary use of 5-HTP is for depression. Several small, short-term
studies have found that it may be as effective as standard antidepressant drugs.
Because standard antidepressants are also used for insomnia and
anxiety, 5-HTP has also been suggested as a treatment for
those conditions, but there is only preliminary evidence that it works.
Similarly, antidepressant drugs are often used for migraine headaches. Some studies suggest that the regular use of 5-HTP may help reduce the frequency and severity of migraines and may help other types of headaches. Additionally, preliminary evidence suggests that 5-HTP can reduce symptoms of fibromyalgia and perhaps help a person lose weight.
Scientific Evidence
Depression. Several small studies have compared 5-HTP to standard antidepressants. The best trial was a six-week study of sixty-three people given either 5-HTP (100 mg three times daily) or an antidepressant in the Prozac family (fluvoxamine, 50 mg three times daily). Researchers found equal benefit with the supplement and with the drug. However, 5-HTP caused fewer and less severe side effects.
Migraine and other headaches. There is some evidence that 5-HTP may help prevent migraines when taken at a dosage of 400 to 600 mg daily. Lower doses may not be effective.
In a six-month trial of 124 people, 5-HTP (600 mg daily) proved just as effective as the standard drug methysergide. The most dramatic benefits observed were reductions in the intensity and duration of migraines. Because methysergide has been proven better than placebo for migraine headaches in earlier studies, the study results provide meaningful, although not airtight, evidence that 5-HTP is also effective.
Similarly good results were seen in another comparative study, using a different medication and 5-HTP (at a dose of 400 mg daily). However, in another study, 5-HTP (up to 300 mg daily) was less effective than the drug propranolol. Also, in a study involving children, 5-HTP failed to demonstrate benefit. Other studies that are sometimes quoted as evidence that 5-HTP is effective for migraines actually enrolled adults or children with many different types of headaches (including migraines).
Putting all this evidence together, it appears likely that 5-HTP can help people with frequent migraine headaches if taken in sufficient doses, but further research needs to be done. In particular, what is needed is a large double-blind study that compares 5-HTP with placebo over a period of several months.
Finally, an eight-week, double-blind, placebo-controlled trial of sixty-five people (mostly women) with tension headaches found that 5-HTP at a dose of 100 mg three times daily did not significantly reduce the number of headaches experienced; however, it did reduce participants’ need to use other pain-relieving medications.
Obesity (weight loss). The drug fenfluramine (with phentermine) made up the infamous Fen-Phen for weight loss. Although successful for weight loss, fenfluramine was later associated with damage to the valves of the heart and was removed from the market. Because fenfluramine raises serotonin levels, it seems reasonable to believe that other substances that affect serotonin might also be useful for weight reduction.
Four small, double-blind, placebo-controlled clinical trials examined
whether 5-HTP can aid weight loss. The first, a double-blind crossover study,
found that the use of 5-HTP (at a daily dose of 8 mg per kilogram of body weight)
reduced caloric intake even though the nineteen participants made no conscious
effort to eat less. Participants given placebo consumed about 2,300 calories per
day, while those taking 5-HTP ate only 1,800 calories daily. The use of 5-HTP
appeared to lead to a significantly enhanced sense of satiety after eating. In
five weeks, women taking 5-HTP effortlessly lost more than three pounds of body
weight.
A follow-up study by the same research group enrolled twenty overweight women who were trying to lose weight. Participants received either 5-HTP (900 mg per day) or placebo for two consecutive six-week periods. During the first period, there was no dietary restriction, while during the second period, participants were encouraged to follow a defined diet expected to lead to weight loss.
Participants receiving placebo did not lose weight during either period. However, those receiving 5-HTP lost about 2 percent of their initial body weight during the no-diet period and an additional 3 percent while on the diet. Thus, a woman with an initial weight of 170 pounds lost about 3.5 pounds after six weeks of using 5-HTP without dieting and another 5 pounds while dieting. Once again, participants taking 5-HTP experienced quicker satiety.
Similar benefits were seen in a double-blind study of fourteen overweight women given 900 mg of 5-HTP daily. Finally, a double-blind, placebo-controlled study of twenty overweight people with type 2 diabetes found that the use of 5-HTP (750 mg per day) without intentional dieting resulted in about a 4.5-pound weight loss in two weeks. The use of 5-HTP reduced carbohydrate intake by 75 percent and fat intake to a lesser extent.
Fibromyalgia. Antidepressants are the primary conventional treatment for fibromyalgia, a little-understood disease characterized by painful and tender muscles, fatigue, and disturbed sleep. One study suggests that 5-HTP also may be helpful for fibromyalgia. In this double-blind trial, fifty persons with fibromyalgia were given either 100 mg of 5-HTP or placebo three times daily for one month. Those receiving 5-HTP experienced significant improvements in all symptom categories, including pain, stiffness, sleep patterns, anxiety, and fatigue.
Anxiety. An eight-week, double-blind, placebo-controlled study compared 5-HTP and the drug clomipramine in forty-five people suffering from anxiety disorders. The results showed that 5-HTP was effective, but clomipramine was more effective.
Safety Issues
No significant adverse effects have been reported in clinical trials of 5-HTP. Side effects appear to be generally limited to short-term, mild digestive distress and possible allergic reactions.
One potential safety issue with 5-HTP involves an interaction with a medication
used for Parkinson’s disease: carbidopa. Several reports suggest that the
combination can create skin changes similar to those that occur in the disease
scleroderma.
According to several reports, dogs that have consumed excessive amounts of
5-HTP have developed signs of excess serotonin. In humans, this so-called
serotonin syndrome includes such symptoms as confusion, agitation, rapid heart
rate, high blood pressure, muscle jerks, loss of coordination, sweating,
shivering, and fever; rapid breathing, coma, and death are possible. Serotonin
syndrome might also occur if 5-HTP is combined with drugs that raise serotonin
levels, such as selective serotonin reuptake inhibitors (including Prozac),
other antidepressants, or the pain medication tramadol.
There are some reasons for concern that 5-HTP could increase the risk of “infantile spasms” (technically, massive myoclonic seizure disorder) in developmentally disabled children. Although safety in children in general has not been proven, children have been given 5-HTP in studies without any apparent harmful effects. Safety in pregnant or nursing women and those with liver or kidney disease has not been established.
Peak X. One report in 1998 raised a potential safety concern with 5-HTP. Researchers discovered evidence of an unidentified substance called peak X in a limited number of 5-HTP products.
Peak X has a frightening history involving a supplement related to 5-HTP: tryptophan. The body turns tryptophan into 5-HTP, and the two supplements have similar effects in the body. Until the late 1980s, tryptophan was widely used as a sleep aid. However, it was taken off the market when thousands of people using tryptophan developed a disabling and sometimes fatal blood disorder called eosinophilia myalgia. Peak X, introduced through a manufacturer’s mistake, is thought to have been the cause, although not all experts agree.
Despite this one report, it seems unlikely that 5-HTP could present the same risk as tryptophan. It is manufactured completely differently; peak X has not been seen again in 5-HTP samples, and no epidemic of eosinophilia myalgia has occurred with 5-HTP use.
Important Interactions
Persons should not take 5-HTP, except on a physician’s advice, if also taking
prescription antidepressants (including selective serotonin reuptake inhibitors,
monoamine
oxidase inhibitors, or tricyclics), the pain drug tramadol,
or migraine drugs in the triptan family (such as sumatriptan). One also should
avoid taking the Parkinson’s disease medication carbidopa at the same time as
5-HTP; the two together could cause skin changes similar to those that develop in
the disease scleroderma.
Bibliography
Cangiano, C., et al. “Effects of Oral 5-Hydroxy-Tryptophan on Energy Intake and Macronutrient Selection in Non-insulin-Dependent Diabetic Patients.” International Journal of Obesity and Related Metabolic Disorders 22 (1998): 648-654.
Das, Y. T., et al. “Safety of 5-Hydroxy-L-Tryptophan.” Toxicology Letters 150 (2004): 111-122.
Ribeiro, C. A. F. “L-5-Hydroxytryptophan in the Prophylaxis of Chronic Tension-Type Headache.” Headache 40 (2000): 451-456.
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