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By Ken Babal, C.N.
For the past 10 years, the amino acid L-tryptophan has been living in exile. Sometimes used as a sleeping pill, it was recalled from the supplement market in 1988 by the U.S. Food and Drug Administration (FDA)--but has since made a comeback. Consumers can now purchase a modified form called 5-hydroxytryptophan, or 5-HTP. Unlike the previous version that was produced by a biological fermentation process, 5HTP is derived naturally from seed pods of Griffonia simplicifolia, a West African plant with medicinal properties. Furthermore, 5-HTP may have therapeutic advantages over its predecessor. It is the next step in tryptophan metabolism and is converted to serotonin, a neurotransmitter with diverse actions in the brain.
An Essential Nutrient
Tryptophan is one of eight essential amino acids that cannot be manufactured by the body and must be obtained in food. Amino acids are the building blocks that make up various proteins in food and in body tissues including muscle, skin, hair, as well as in hormones. Proteins such as milk, cheese, eggs and meat all contain the essential amino acids. Meat, fish, eggs, dairy products, soy protein, pumpkin and sesame seeds, and lentils are the richest sources of tryptophan, the least abundant essential amino acid in foods.
In addition to their structural role, amino acids are involved in many biochemical functions that are essential to life. Each person has a distinct pattern of amino acid makeup that fluctuates with health and illness. The range of requirements may differ by as much as sevenfold for a particular amino acid.1 Providing the body with a deficient amino acid or tilting the balance can influence various systems in the body. Thus, supplements of single as well as combination amino acids have many therapeutic applications. Single amino acids such as lysine or tyrosine can be isolated and taken in a disproportionately large dose to produce a pharmacological effect. In the case of tryptophan, supplements have been used clinically for treating depression, anxiety, pain, insomnia, migraine and carbohydrate craving.
Tryptophan supplements were popular until the late 1980s when a chemical contaminant in a bad batch caused an outbreak of eosinophilia-myalgia syndrome (EMS). More than two dozen Americans died and 1,000 were afflicted. In response, FDA incorrectly concluded that tryptophan was at fault, rather than the contaminant. The agency reclassified tryptophan as an unapproved experimental drug and issued a voluntary recall except in products where small amounts were used as nutrient fortification. Although the EMS outbreak was conclusively linked to product contamination on the part of one Japanese company with a faulty laboratory filtration procedure, L-tryptophan remains banned in the United States. Today, under the 1994 Dietary Supplement Health and Education Act, food supplements and natural products cannot be arbitrarily removed from store shelves but must first be proven harmful before FDA can order a recall. The legislation makes it difficult for FDA to arbitrarily pull accessory nutrients and natural supplements such as melatonin, DHEA, GLA and Co-Q10 off the market.
The Mood Molecule
The brain chemical serotonin has been known to researchers for nearly half a century, and new research continues to demonstrate how it influences mood and emotion. Without serotonin or hundreds of other known neurotransmitters, brain cells (called neurons), could not communicate with each other to process information. This is because neurons do not touch one another but require chemical messengers to jump across a gap, known as a synapse, to stimulate receptors on adjacent cells. After the transmission, the neurotransmitter molecules are either broken down or reabsorbed.
While some neurotransmitters have an excitatory effect on the nervous system, others, such as serotonin, produce an inhibitory effect that soothes, calms and gives rise to feelings of contentment. Some serotonin is converted by the pineal gland into melatonin, the hormone that helps determine our sleep/wake cycle. Specifically, serotonin deficiency has been implicated in depression, uncontrollable appetite, obsessive-compulsive disorder, autism, bulimia, social phobias, premenstrual syndrome, anxiety and panic, migraines, schizophrenia and extreme violence. 2
Studies during the early 1980s by Richard Wurtman of the Massachusetts Institute of Technology, in Cambridge, showed that serotonin concentration in the brain is directly related to dietary intake of tryptophan. This was the first accepted demonstration that a single amino acid derived from the diet is capable of affecting neuronal biochemistry.3
Recognition of serotonin's critical role in brain chemistry has created a boom in the development of patented drugs that target the neurotransmitter. Among them are the popular antidepressants ElavilTM, ProzacTM and ZoloftTM; powerful appetite suppressants ReduxTM and fenfluramine; and the antipsychotic drug clozapine. Prozac is one of several antidepressants classified as selective serotonin reuptake inhibitors, or SSRIs. These drugs prevent circulating serotonin from being reabsorbed by nerve endings for later use. They are called selective SRIs because they affect only serotonin, whereas tricyclic antidepressants (e.g., Elavil) are designed to prevent reabsorption of several neurotransmitters, including serotonin. Some drugs, such as Redux and fenfluramine, go a step further and stimulate nerve endings to release extra serotonin into the synapse.
Popular as they may be, these drugs have not been without serious complications. In September 1997, manufacturers of the weight-reduction drug ReduxTM and its close chemical cousin fenfluramine (an agent that comprises half of the drug mix popularly known as fen/phen) recalled the product when it was discovered that as many as 30 percent of patients using it could develop heart valve abnormalities.4 Before the drugs were even approved, both manufacturers and FDA were aware of other possible adverse effects such as primary pulmonary hypertension, a potentially fatal lung condition.
The FDA tryptophan ban may be forcing people to take dangerous and expensive drugs to achieve the same results as the amino acid. Fortunately, the ban does not apply to the recently introduced 5-HTP and has had the unforeseen benefit of spurring a closer examination of the extensive tryptophan research. A recent statistic shows there are nearly 5,000 papers referencing 5-HTP that can be accessed via the Internet.5
Eric Braverman, M.D., and Carl Pfeiffer, M.D., Ph.D., of the Brain Bio Center in Princeton, N.J., report that 5-HTP is comparable to clomipramine (a tricyclic antidepressant that is used for obsessive-compulsive disorder) and that the two, when given concurrently, are superior to either compound given separately.6
In one study, 5-HTP was compared to fluvoxamine, an SSRI.7 In a double-blind, multi-center study by Swiss and German psychiatric researchers, subjects diagnosed with depression were given either 100 mg of 5-HTP three times per day or 150 mg of fluvoxamine three times per day. The subjects were evaluated at zero, two, four and six weeks using standard depression rating scales. They were also asked to evaluate how well they felt. Beginning at week two and continuing through week six, both treatment groups experienced a significant and nearly equal reduction in depression. At week four, 15 of 36 patients treated with 5-HTP and 18 of 33 patients treated with fluvoxamine had improved by at least 50 percent, according to evaluation scores. When the numbers were totaled, researchers found the mean percentage improvement from baseline to the final assessment was greater for the patients treated with 5-HTP. Although not statistically significant, the number of treatment failures was higher (17 percent) in the fluvoxamine group than in the 5-HTP group (6 percent). Adverse side effects from both treatments were rare and generally mild, usually occurring during the first few days of treatment and then disappearing.
Although tryptophan may have antidepressant properties, there is more data available to suggest 5-HTP is efficacious in treating depressed patients. In one study, researchers administered 5-HTP (50 to 300 mg) to 107 patients with endogenous depression and found that 74 patients (69 percent) were either cured or showed marked improvement.8 (A 50 mg capsule of 5-HTP is generally regarded as the equivalent of 500 mg L-tryptophan.)
It has been reported that 5-HTP treatment is statistically superior to placebo in treating a small number of patients with endogenous depression.9 However, researchers recommend additional placebo-controlled investigations of 5-HTP and depression in which larger numbers of subjects are studied for at least six weeks.10
Obesity And Insomnia
An Italian double-blind, crossover study concluded that 5-HTP could be safely used as an obesity treatment.11 In the study, 19 obese female subjects were given either 5-HTP (8 mg/kg/day) or placebo for five weeks, during which time patients were not prescribed any dietary restrictions. It was found that 5-HTP administration promoted a decrease in appetite and carbohydrate intake that resulted in significant weight loss (approximately 5 percent) during the period, compared to no significant change in body weight with the placebo-controlled subjects.
Prior to this 1989 study, another study provided evidence that the high quantity of carbohydrate-rich snacks frequently consumed by obese people can be diminished by treatments aimed at either enhancing serotonin release (fenfluramine) or increasing its synthesis (tryptophan).12
Serotonin's inhibitory functions in the brain prevent excess nervous stimulation at night so sleep can occur. Serotonin also is a growth hormone releaser. Growth hormone, which normally reaches peak levels during sleep, is crucial for growth and repair as well as stimulation of the immune system. These growth hormone peaks are frequently absent or smaller in elderly and obese people.13
People formerly took tryptophan as a sleep aid. It appears 5-HTP produces similar effects. A French study found that 100 mg of 5-HTP resulted in significant improvement in people described as "mildly insomniac."14
A great deal of published data indicates that 5-HTP is safe and produces relatively few adverse effects. Side effects have been known to include headache, nasal congestion, nausea and constipation. As a nutritional supplement, up to 100 mg/day is reasonable for most individuals and should be taken apart from meals.
Because of competition among amino acids, dietary protein intake should be adequate, especially if larger doses of 5-HTP are taken. However, persons taking prescription drugs, particularly to alter mood or induce weight loss, should be extremely cautious. It is likely that 5-HTP potentiates the effects of such medications. Combining 5-HTP with other drugs should be done only with the consent and supervision of a physician. There also are some medical conditions in which serotonin or tryptophan metabolites become elevated. The effect of 5-HTP on fetuses and in pregnant women has not been studied; therefore, its use during pregnancy is contraindicated. Since 5-HTP may cause drowsiness, it should not be used while driving a car or operating heavy machinery.
Ken Babal, C.N., is a consulting nutritionist and a member of the board of directors for the Society of Certified Nutritionists. Babal is the author of the recently released book Maitake: King Of Mushrooms (Keats Good Health Guide, 1997).
1. Davis, D. "Nutritional Needs and Biochemical Diversity." In Medical Applications of Clinical Nutrition: 41-45. J. Bland, editor, Keats Publishers, New Canaan, Conn., 1983.
2. Lemock, M. "The Mood Molecule." Time Magazine, 74, Sept. 29, 1997.
3. Braverman, E. & Pfeiffer, C. The Healing Nutrients Within: 59. New Canaan, Conn.: Keats Pub., 1987.
4. Lemock, M, op. cit., 76.
5. Dean, W. & Morgenthaler, J. "5-HTP Facts and Fiction." Life Enhancement, 19, March 1997.
6. Braverman, E. & Pfeiffer, C., op. cit., 66.
7. 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, 24: 53-81, 1991.
8. Sano, I. "L-5-hydroxytryptophan (L-5HTP) therapie." Folia Psychiatr Neurol Jpn: 26: 7-17, 1972.
9. Van Praag, H.M. "Studies in the mechanism of action of serotonin precursors in depression." Psychopharmacol Bull: 20: 599-600, 1984.
10. Byerley, W.F., et al. "5-Hydroxytryptophan: A Review of Its Antidepressant Efficacy and Adverse Effects." J Clin Psychopharmacol: 7: 127-137, 1987.
11. Ceci, F., et al., "The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects." J Neural Transm: 76: 109-117, 1989.
12. Wurtman, R., et al. "Carbohydrate craving in obese people: suppression by treatments affecting serotonergic neurotransmission." Int J Eating Dis: 1: 2-15, 1981.
13. Pearson, D. & Shaw, S. Life Extension: 794. New York: Warner Books, 1982.
14. Sourlairac, A., et al. "Action du 5-hydroxytryptophane, precurseur de la serotonine, sur les troubles du sommeil." Ann Med-Psychol: 135: 792-798, 1977
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