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Anxiety, depression, and obesity are an unholy trinity of ill health in the modern age, each reinforcing the other. Now, a well- researched nutritional supplement called 5-HTP (5-hydroxy-L-tryptophan) appears to have something to offer sufferers of each malady. According to noted researcher Michael Murray, N.D., "Numerous double-blind studies have shown 5-HTP to be as effective as antidepressant drugs, but it is better tolerated and is associated with fewer and much milder side effects." 5-HTP has been available since 1995. It is made in the lab, or, more commonly, extracted from an African tree (Griffonia simplicia). The body converts tryptophan, an amino acid (protein compound) found in food, into 5-HTP, which is used to make serotonin—an important brain chemical regulating mood, behavior, appetite, and sleep.
Dr. Ray Sahelian, M.D., author of "5-HTP: Nature's Serotonin Solution," believes 5-HTP holds a great deal of promise. As he has said, "5-HTP helps control appetite, improve mood, and reduce anxiety. However, consumers must be cautious. Few long-term studies are available to determine 5-HTP's safety. Until we learn more about this interesting supplement, I recommend that consumers not continuously use 5-HTP longer than three months without a break." Sahelian also recommends physician supervision, and has observed that uncommon side effects from 5-HTP can include nausea, daytime sleepiness, and nightmares.
Safety of 5-HTP. At the beginning of September, researchers reported finding unidentified chemicals other than 5-HTP in several 5-HTP products. We've posted a press release from a supplement industry trade association (NNFA), plus the Mayo Clinic's press release and a US FDA bulletin on the issue. If we suspect any product may be unsafe, we will withdraw it from sale. To date, the U.S. Food & Drug Administration (FDA) has not removed 5-HTP from the market.
How Does 5-HTP Work? What explains the apparent mood-elevating, relaxing effects of 5-HTP? Key to each of these conditions are imbalances in monoamine neurotransmitters, with low levels of serotonin being a known factor in depression, obesity, and anxiety. (Serotonin is a monoamine compound, chemically related to amino acid derivatives like 5-HTP.) In addition, 5-HTP increases levels of endorphin and other neurotransmitters, deficiencies of which are associated with depression.
5-HTP versus L-Tryptophan: The body uses an amino acid called L-tryptophan to manufacture serotonin, which is why it has been a popular insomnia remedy, supported by clinical evidence. But until recently, non-prescription sale of L-tryptophan was severely restricted, following an incident in which a contaminated, bacterially manufactured batch from Japan produced a serious illness (eosinophilia-myalgia syndrome or EMS) in over 1,500 consumers, killing 38. (Pure L-tryptophan is perfectly safe, and is even has therapeutic benefit in treating EMS.)
Compared with L-tryptophan, 5-HTP is one step closer to serotonin in the body's manufacturing process. In addition, far more 5-HTP is converted to serotonin (70% versus 1-3%), because the body uses a large percentage of dietary L-tryptophan to make therapeutically irrelevant compounds (e.g., kynurenine, vitamin B3). These differences make dietary 5-HTP far more efficient than L-tryptophan at boosting serotonin levels in the brain. In addition, consumption of L-tryptophan produces potentially toxic, carcinogenic compounds, especially under the very conditions (stress, anxiety) for which people have used L-tryptophan. And, 5-HTP is extracted from an African herb (Griffonia simplicifolia), making it inherently safer than a synthetically produced compound like L-tryptophan.
5-HTP and Depression: The latest so-called miracle antidepressants, like Prozac, Zoloft and Paxil, work by blocking the degradation of serotonin after it has performed its chief job, to bridge nerve synapses (gaps between nerve cells). These drugs, called SSRIs (serotonin-selective re-uptake inhibitors) produce significant adverse side effects, and cannot work well unless the body is producing adequate levels of serotonin in the first place.
To date, there has been one controlled clinical trial comparing 5-HTP to an SSRI drug, in this case fluvoxamine (Luvox, which is very similar to, but perhaps more effective than Prozac). The participants receiving 5-HTP were judged to have enjoyed slightly better, faster, relief than those who received fluvoxamine, and a greater percentage of them had a positive response to 5-HTP. Note: One study showed that despite having increased serotonin levels, one in five patients who responded positively to 5-HTP relapsed after one month, probably because levels of other monamines decreased. These patients responded to supplementation with the amino acid tyrosine.
5-HTP and Obesity: Three placebo-controlled clinical studies indicate that 5-HTP can be effective in producing weight loss in overweight women, probably by producing feelings of satiety. Participants taking 5-HTP lost 3-5 times as much weight as those who were taking a placebo.
5-HTP and Insomnia: In clinical studies, 5-HTP decreased symptoms of insomnia, probably because it increases vital REM sleep and deep-sleep stages 3 and 4.
5-HTP and Headaches: Clinical research shows that 5-HTP is as effective as pharmaceutical drugs in reducing symptoms of migraine headaches, presumably because of its serotonin-boosting properties.
Selected 5-HTP
References
Poldinger 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.
Carney MWP et al. Red cell folate concentrations in psychiatric patients. J Affective
Disorders. 1990;19:207-13.
Cangiano C et al. Eating behavior and adherence to dietary prescriptions in obese adult
subjects treated with 5-hydroxytryptophan. AM J Clin Nutr. 1992;56:863-67.
5-HTP Safety: The
Supplement Industry Speaks
In a letter to the editor published September 1, 1998 in the journal Nature
Medicine, Mayo Clinic researchers claimed to have discovered a potentially harmful
contaminant in several products containing the amino acid 5-hyroxy-L-tryptophan (5-HTP), a
widely used dietary supplement.
According to the National Nutritional Foods Association (NNFA), a trade association for the natural products industry, the letter contains more speculation than fact. "My concerns about this article are far greater than any concerns I have about the safety of 5- HTP," said Michael Q. Ford, NNFA's executive director. "Even a cursory review of this letter raises serious questions about the conclusions reached by the researchers and their impartiality. It's more politics than science."
The numerous concerns raised by Ford include the following
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The authors cite two cases of EMS "associated" with 5-HTP use, "most recently" in 1991 (reported in 1994) and the other "as far back as 1980." They use data from the former as the benchmark against which to measure potential EMS risk in the current samples of 5-HTP. In fact, these two cases represent the only connections reported in the literature of a link between EMS and 5-HTP, and both are inconclusive. In the words of the authors of the 1994 article, "The role of 5-HTP in the eosinophilia of this patient is (thus) uncertain."
The authors allege that they have discovered a chemical structure called "peak x," which represents contamination in 5-HTP and can cause EMS. To verify this, NNFA supplier members had various batches of 5-HTP tested by independent laboratories using the same methodology as the Mayo Clinic researchers. While these laboratories were able to identify a distinct peak, none has been able to replicate the Mayo Clinic's findings that this peak is the same or similar to the contaminant found in L-tryptophan.
The authors concede that "one possible reason" no new cases of EMS-like symptoms have been reported in connection with 5-HTP is due to the low dosage recommendations on the label. Yet they state, "since the intake of supplements is not medically supervised," higher dosages are bound to be consumed. Unless one is a patient in a hospital under close supervision, it is highly unlikely that ingestion of any substance — food, medication or supplements — would ever be supervised by a medical professional.
The authors quote, but do not identify, Richard Wurtman as saying 5-HTP is "another accident (epidemic) waiting to happen" Wurtman is a physician whose company, Interneuron Inc. holds the patent on Redux, a product banned by the FDA last year for causing heart defects. Redux is a serotonin generator; an effect 5-HTP has been reported to induce, raising serious questions about Wurtman's vested interests and bias.
At the end of their letter, the authors thank several people and institutions, among them Dateline NBC "for supplying commercial preparations" of 5-HTP. It is incredible that an institution with the reputation of the Mayo Clinic would allow such a questionable procedure as obtaining samples from a television newsmagazine for use in testing. Ford said his own association employs the rigorous chain-of-custody procedure sanctioned by the Drug Enforcement Agency in testing commercial samples of member products. That a scientific institute would not use a similar protocol raises serious questions of ethics and bias.
"Clearly, all involved – the researchers, FDA, Dateline NBC and Wurtman — had a vested interest in a negative outcome in testing 5-HTP," Ford said. "But in the end, any link between alleged contamination of 5-HTP and L-tryptophan remains unproven. This isn't good science and it certainly shouldn't be news."
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