5-HTP And The Serotonin Connection
5-HTP And The Serotonin Connection

The amino acid tryptophan, present in protein foods, plays a role in a number of biochemical reactions in the body. Some tryptophan becomes protein, some is converted into niacin (vitamin B3) and some enters the brain to become the neurotransmitter serotonin. Serotonin, a key brain chemical, is responsible for producing, among other things, a feeling of calm and well-being. Three decades of research connects various states of depression and anxiety with altered amounts of serotonin.

In the 1970s and 1980s tryptophan became a popular nutritional supplement because of its role as a precursor to serotonin. Tryptophan proved to be remarkably effective at alleviating symptoms of depression, but in 1989 the Food and Drug Administration (FDA) banned the retail sale of tryptophan after a contaminated batch from a single Japanese manufacturer caused a serious condition known as eosinophilia-myalgia syndrome (EMS). Although tryptophan itself was not clearly implicated in causing EMS, FDA has steadfastly maintained its ban. Fortunately, another substance has come to light as a natural precursor to serotonin: 5-hydroxytryptophan (5-HTP). Derived from the seed pods of Griffonia simplicifolia, a West African plant, 5-HTP is a close relative of tryptophan and part of the metabolic pathway that leads to serotonin production:

tryptophan —> 5-HTP —> serotonin

The diagram illustrates, simply, that 5-HTP is a more immediate precursor to serotonin than tryptophan is. This means 5-HTP is more directly linked to the production of serotonin than is tryptophan.

So how effective is 5-HTP? Numerous clinical trials have studied the efficacy of 5-HTP for treating depression. One compared 5-HTP to the antidepressant drug fluvoxamine and found 5-HTP to be equally effective. [1] Researchers used the Hamilton Depression Rating Scale and a self-assessment scale to gauge the effectiveness of the two medications. Both scales revealed a gradual reduction in depressive symptoms through time with both medications. Perhaps the most convincing evidence, however, comes from scientists who examined research from around the world on the use of 5-HTP in treating depression. One such researcher, writing in Neuropsychobiology, sums up the findings this way: "Of the 17 reviewed studies, 13 confirm that 5-HTP has true antidepressant properties." [2]

The effective dose of 5-HTP appears to be between 50 and 500 mg daily. [3] Used in combination with other antidepressant substances, however, the effective dose may be even lower. Research shows that some people respond better to lower doses, so I recommend beginning at the low end of the dose range and increasing as necessary. Side effects associated with therapeutic doses of 5-HTP are rare. When they do occur, they are usually limited to mild gastrointestinal complaints. [4] Compare this to the litany of possible side effects from antidepressant drugs: sedation, fatigue, blurry vision, urine retention, constipation, palpitations, EKG changes, insomnia, nausea, vomiting, diarrhea and mild to severe agitation. [5]

Researchers looking for other applications for 5-HTP found positive results in fibromyalgia treatment, [6] weight loss in obese individuals [7] and a reduction in occurrence of migraine headaches. [8] Because so many conditions may be affected by serotonin function, it is not surprising to see such a wide range of therapeutic possibilities for 5-HTP.

It appears that 5-HTP may be one of the most helpful natural substances to be discovered in recent years. As with most treatments, the following words of caution apply: 5-HTP may not be appropriate for all types of depression and may not be compatible with all types of medication. Consultation with a health care practitioner is strongly advised.

By David Wolfson, N.D., a physician, nutrition educator and writer as well as a consultant to the natural products industry.


  1. Poldinger W, et al. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.
    Psychopathology 1991;24:53-81.

  2. Zmilacher K, et al. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression.
    Neuropsychobiology 1988;20:28-35.

  3. van Praag H. Management of depression with serotonin precursors.
    Biol Psychiatry 1981;16:291-310.

  4. Byerley W, et al. 5-hydroxytryptophan: a review of its antidepressant efficacy and adverse effects.
    J Clin Psychopharmacol 1987;7:127.

  5. Physician's Desk Reference. 49th ed. Montvale, NJ: Medical Economics Data Production Company; 1995.

  6. Caruso I, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.
    J Int Med Res 1990;18:201-9.

  7. Cangiano C, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan.
    Am J Clin Nutr 1992;56:863-7.

  8. Maissen CP, et al. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine.
    Schweiz Med Wochenschr 1991;121:1585-90.

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