The cause of migraine headache is believed to be related to abnormal serotonin function in blood vessels,¹ and 5-HTP (5-hydroxytryptophan, which is converted by the body into serotonin) may affect this abnormality. In one study, 40 people with recurrent migraines received either 5-HTP (200 mg per day) or methysergide (a drug used to prevent migraines) for 40 days. Both compounds reduced the frequency of migraines by about 50%.² Larger amounts of 5-HTP (600 mg per day) were also found to be as effective as medications for reducing migraine headache attacks in adults in two double-blind trials.^3,4 Migraine attacks were reduced in frequency, severity, and duration in 90% of those taking 400 mg per day of 5-HTP in a double-blind placebo-controlled trial,⁵ though another trial found no benefit of 5-HTP.⁶ In another controlled study, 400 mg of dl-5-HTP (another form of 5-HTP) led to reduced consumption of pain-killing drugs and pain scores after one to two months.⁷ Children who suffered from migraines and had problems sleeping responded well to a daily amount of 5-HTP equal to 20 mg for every 10 pounds of body weight in a controlled trial,⁸ though an earlier study showed 5-HTP had no better effect than placebo for children with migraines.⁹

5-HTP (5-hydroxytryptophan) may be helpful for tension-type headaches. A recent double-blind study of adults with chronic tension-type headaches found 300 mg per day of 5-HTP reduced the number of headache days by 36%, but this was not significantly different from the 29% reduction in the placebo group.¹⁰ (Headaches often improve significantly even when an inactive [placebo] treatment is given).¹¹ Headache severity was also similarly reduced by either 5-HTP or placebo. In this study, 5-HTP was significantly superior to placebo only in reducing the need for pain-relieving medications during headaches. Previous double-blind research studied 5-HTP in groups of patients suffering from many different types of headache, including some with tension-type headaches. Results from these studies also found substantial, but nonsignificant benefits of 5-HTP compared with placebo using either 400 mg per day in adults¹² or 100 mg per day in children.¹³

People with fibromyalgia often have low serotonin levels in their blood.^14,15,15 Supplementation with 5-HTP may increase serotonin synthesis in these cases. Both preliminary^17,18 and double-blind trials¹⁹ have reported that 5-HTP supplementation (100 mg three times per day) relieves some symptoms of fibromyalgia.

Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain.¹⁹ Supplementing with 5-HTP (5-hydroxytryptophan) may increase serotonin synthesis. Some trials using 5-HTP with people suffering from depression have shown sign of efficacy.^{20,21,22,23,24} However, much of the research was either uncontrolled or used 5-HTP in combination with antidepressant drugs. One double-blind trial found that 5-HTP was as effective as, or nearly as effective as, an antidepressant drug (fluoxetine).²⁵ Depressed people interested in considering this serotonin precursor should consult a doctor.

5-HTP is a substance that increases serotonin production and has shown antidepressant activity.²⁶ It may also be useful in the treatment of SAD, but there is currently no research testing this possibility.

A related compound that occurs naturally in the body, 5-HTP (5-hydroxytryptophan), is also converted into serotonin and might, therefore, be helpful for insomnia. In a double-blind trial of people without insomnia, supplementation with 5-HTP (200 mg at 9:15 p.m. and 400 mg at 11:15 p.m.) increased rapid-eye-movement (REM) sleep, presumably indicating improved sleep quality.²⁹ In a preliminary trial of people with fibromyalgia, supplementing with 100 mg of 5-HTP three times a day improved sleep quality.³⁰ However, additional research is needed to determine whether 5-HTP is safe and effective for people with insomnia.

In a preliminary study, 5-HTP was also found to be an effective treatment for "sleep terrors,"³¹ a common problem in children that causes sudden awakening with persistent fear or terror, screaming, sweating, confusion, and increased heart rate.

L-tryptophan is the amino acid used by the body to produce serotonin, a chemical messenger important for proper brain function. Supplementation with L-tryptophan has led to improvement in depression in many studies,^36,37 but information is limited about its effect on bipolar disorder. Case reports on two bipolar patients treated with lithium or an antidepressant drug described marked improvements when they were given 12 grams daily of L-tryptophan.^38,39 Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement,^40,41 but another double-blind, controlled study using 9.6 grams daily reported better results.⁴²

L-tryptophan is converted to 5-HTP (5-hydroxytryptophan) before it becomes serotonin in the body. In a controlled trial, 200 mg daily of supplemental 5-HTP had antidepressant effects in bipolar patients, though it was not as effective as lithium.⁴³ In a double-blind trial, patients with bipolar disorder had greater improvement with a combination of 5-HTP at 300 mg daily plus an antidepressant drug than with 5-HTP alone.⁴⁴