5-HTP

1. What is 5-HTP?
5-Hydroxytryptophan (5-HTP) is an amino acid that is the intermediate step between tryptophan and the important brain chemical serotonin. There is a massive amount of evidence that suggests that low serotonin levels are a common consequence of modern living. The lifestyle and dietary practices of many people living in this stress-filled era results in lowered levels of serotonin within the brain. As a result, many people are overweight, crave sugar and other carbohydrates, experience bouts of depression, get frequent headaches, and have vague muscle aches and pain. All of these maladies are correctable by raising brain serotonin levels. The primary therapeutic applications for 5-HTP are low serotonin states as listed in Table 1.

Table 1. Conditions associated with low serotonin levels helped by 5-HTP

Depression
Obesity
Carbohydrate craving
Bulimia
Insomnia
Narcolepsy
Sleep apnea
Migraine headaches
Tension headaches
Chronic daily headaches
Premenstrual syndrome
Fibromyalgia

Although 5-HTP may be relatively new to the United States health food industry, it has been available through pharmacies for several years and has been intensely researched for the past three decades. It has been available in several European countries as a medicine since the 1970s.

What advantages does 5-HTP have over L-tryptophan?
There are many advantages of 5-HTP over L-tryptophan. First of all, because it is one step closer to serotonin, 5-HTP is more effective than L-tryptophan. 5-HTP is also inherently safer. Although L-tryptophan is safe if properly prepared and free of the contaminants linked to severe allergic reaction known as eosinophilia myalgia syndrome (EMS), L-tryptophan is still produced with the help of bacterial fermentation (a situation that lends itself to contamination). In contrast, 5-HTP is isolated from a natural source - a seed from an African plant (Griffonia simplicifolia).

Evidence that this natural source of 5-HTP does not cause EMS is provided by researchers who have been using 5-HTP for over 25 years. They state that "EMS has never appeared in the patients of ours who received only uncontaminated L-tryptophan or 5-hydroxtryptophan (5-HTP)"(1). Furthermore, researchers at the NIH studying the effects 5-HTP for various metabolic conditions have also not observed a single case of EMS nor has a case of elevated eosinophils been attributed to 5-HTP in these studies.

What effect does 5-HTP have on weight loss?
As far back as 1975, researchers demonstrated that administering 5-HTP to rats that were bred to overeat and be obese resulted in significant reduction in food intake (6). It turns out that these rats have decreased activity of the enzyme that converts tryptophan to 5-HTP and subsequently to serotonin. In other words, these rats are fat as a result of a genetically determined low level of activity of the enzyme that starts the manufacture of serotonin from tryptophan. As a result, these rats never get the message to stop eating until they have consumed far greater amounts of food than normal rats.

There is much circumstantial evidence that many humans are genetically predisposed to obesity. This predisposition may involve the same mechanism as that observed in rats genetically predisposed to obesity. In other words, many people may be predisposed to being overweight because they have a decreased conversion of tryptophan to 5-HTP and, as a result, decreased serotonin levels. By providing preformed 5-HTP, this genetic defect is bypassed and more serotonin is manufactured. 5-HTP literally turns off hunger (7).

The early animal studies that used 5-HTP as a weight loss aid have been followed by a series of three human clinical studies of overweight women, conducted at the University of Rome (8-10). The first study showed that 5-HTP was able to reduce caloric intake and promote weight loss despite the fact that the women made no conscious effort to lose weight (8). The average amount of weight loss during the five-week period of 5-HTP supplementation was a little more than 3 pounds.

The second study sought to determine whether 5-HTP helped overweight individuals adhere to dietary recommendations (9). The twelve-week study was divided into two six-week periods. For the first six weeks, there were no dietary recommendations; for the second six weeks the women were placed on a 1,200-calorie diet. As shown in Table 1, the women who took the placebo lost 2.28 pounds, while the women who took the 5-HTP lost 10.34 pounds. As in the previous study, 5-HTP appeared to promote weight loss by promoting satiety-the feeling of satisfaction-leading to fewer calories being consumed at meals. Every woman who took the 5-HTP reported early satiety.

In the third study involving 5-HTP, for the first six weeks there were no dietary restrictions, and for the second six weeks the women were placed on a 1,200-calorie-per-day diet (10). The results from this study were even more impressive than the previous studies for several reasons. The group that received the 5-HTP had lost an average of 4.39 pounds at six weeks and an average of 11.63 pounds at 12 weeks. In comparison, the placebo group had lost an average of only 0.62 pounds at six weeks and 1.87 pounds at twelve weeks. The lack of weight loss during the second six-week period in the placebo group obviously reflects the fact that the women had difficulty adhering to the diet.

Early satiety was reported by 100 percent of the subjects during the first six-week period. During the second six-week period, even with severe caloric restriction, ninety percent of the women taking 5-HTP reported early satiety. Many of the women who received the 5-HTP (300 mg three times per day) reported mild nausea during the first six weeks of therapy. However, the symptom was never severe enough for any of the women to drop out of the study. No other side effects were reported.

Wasn't the drug Redux, which raises serotonin levels, taken off the market because it caused damage to the heart valves? Is there a risk with 5-HTP doing the same?

In September 1997, the popular weight loss drug Redux and its chemical cousin fenfluramine, part of the "fen-phen" combination, were taken off the market based on a study showing that these drugs may have caused permanent damage to heart valves in as many as one-third of the people who took them. There is no evidence that 5-HTP produces these effects. Unlike Redux, 5-HTP does not raise blood serotonin levels to a significant degree nor does it block reuptake of serotonin. The point here is that 5-HTP does not disrupt the normal process of serotonin release, reabsorbtion, and elimination from the body. 5-HTP is not a synthetic drug; it is an amino acid produced naturally by your body's metabolism.

How does 5-HTP compare with melatonin in the treatment of insomnia?
5-HTP may prove to be better than melatonin. Several clinical studies have shown 5-HTP to produce good results in promoting and maintaining sleep in normal subjects as well as those experiencing insomnia (11-14). One of the key benefits with 5-HTP in the treatment of insomnia is its ability to increase sleep quality.

Has 5-HTP been studied in the treatment of depression?
Yes. In fact, there is excellent documentation that 5-HTP is an effective antidepressant agent. 5-HTP often produces very good results in patients who are unresponsive to standard antidepressant drugs. One of the more impressive studies involved 99 patients described as suffering from "therapy resistant" depression (3). These patients had not responded to any previous therapy including all available antidepressant drugs as well as electro convulsive therapy. These therapy resistant patients received 5-HTP at dosages averaging 200 mg daily but ranging from 50 to 600 mg per day. Complete recovery was seen in 43 of the 99 patients and significant improvement was noted in 8 more. Such significant improvement in patients suffering from long-standing, unresponsive depression is quite impressive prompting the author of another study to state "5-HTP merits a place in the front of the ranks of the antidepressants instead of being used as a last resort. I have never in 20 years used an agent which: (1 was effective so quickly; (2 restored the patients so completely to the persons they had been and their partners had known; [and] (3 was so entirely without side effects" (4).

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