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.

2. 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)". 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.

3. 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. 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.

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. 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. 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. 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. 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.

4. 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. One of the key benefits with 5-HTP in the treatment of insomnia is its ability to increase sleep quality.

5. What is fibromyalgia and how does 5-HTP help?

Fibromyalgia is a recently recognized disorder regarded as a common cause of chronic musculoskeletal pain and fatigue. Fibromyalgia is a relatively common condition estimated to affect about 4% of the general population. Diagnosis requires fulfillment of all three major criteria and four or more minor criteria.

Major criteria

Generalized aches or stiffness of at least three anatomic sites for at least three months.

Six or more typical, reproducible tender points.

Exclusion of other disorders which can cause similar symptoms.

Minor criteria

* Generalized fatigue

* Chronic headache

* Sleep disturbance

* Neurological and psychological complaints

* Joint swelling

* Numbing or tingling sensations

* Irritable bowel syndrome

* Variation of symptoms in relation to activity, stress, and weather changes

The history of the development of 5-HTP as an effective treatment for fibromyalgia began with studies on the drug fenclonine. This drug blocks the enzyme which converts tryptophan to 5-HTP and as a result blocks serotonin production. During the late 1960s and early 1970s, it was thought that increased serotonin formation may promote migraine headaches (the opposite of what was later proved, i.e., increasing serotonin levels reduce migraine headache occurrence). The researchers discovered that providing headache sufferers with fenclonine resulted in very severe muscle pain. This effect was exactly opposite of what was expected, but led to some important advances in the understanding of fibromyalgia--a way to induce its severe symptoms of (as well as symptoms nearly identical to EMS, the condition caused by contaminated L-tryptophan). The researchers also discovered that migraine sufferers reacted to the drug much more than non-headache sufferers. In fact, in most normal subjects fenclonine produced no fibromyalgia. These occurrences highlight just how sensitive migraine sufferers are to low serotonin levels.

6. Can 5-HTP be taken with St. John's wort extract?

Yes. In fact, the two seem to work very well together. St. John's wort extract has been shown in over 25 double-blind studies to be as or more effective than antidepressant drugs in the treatment of mild to moderate depression. In more severe cases, I recommend using 5-HTP along with St. John's wort. Be sure to use the St. John's wort extract standardized for 0.3% hypericin. The dosage for this extract is typically 300 mg three times per day. When using it in combination with 5-HTP I recommend 50-100 mg of 5-HTP and 150-300 mg of St. John's wort extract three times daily.

7. 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. 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; 3 was so entirely without side effects".

8. Are there any studies where 5-HTP was compared directly to antidepressant drugs?

Yes, there are several. 5-HTP is equal to or better than standard antidepressant drugs and the side effects are much less severe. The study with the most significance was one that compared to fluvoxamine, a "selective serotonin re-uptake inhibitor" like Prozac, Paxil, and Zoloft. In the study, subjects received either 5-HTP (100 mg) or fluvoxamine (50 mg) three times daily for 6 weeks. The percentage decrease in overall depression scores was slightly better in the 5-HTP group (60.7% vs. 56.1%). More patients responded to 5-HTP than fluvoxamine and 5-HTP was quicker acting than the fluvoxamine.

The real advantage of 5-HTP in this study was the low rate of side effect. Here is how the physicians described the differences among the two groups:

"Whereas the two treatment groups did not differ significantly in the number of patients sustaining adverse events, the interaction between the degree of severity and the type of medication was highly significant: fluvoxamine predominantly produced moderate to severe, oxitriptan [5-HTP] primarily mild forms of adverse effects."

The most common side effects with 5-HTP were nausea, heartburn, and gastrointestinal problems (flatulence, feelings of fullness, and rumbling sensations). These side effects were rated as being very mild to mild. In contrast, most of the side effects experienced in the fluvoxamine group were of moderate to severe intensity.

9. How does 5-HTP benefit headache sufferers?

Because chronic headache sufferers have low levels of serotonin in their tissues, some researchers refer to migraine and chronic headaches as a "low serotonin syndrome". There have been several clinical studies with 5-HTP in headaches, both migraine and tension headaches, that have showed excellent results. In particular, the use of 5-HTP in the prevention of migraine headache offers considerable advantages over drug therapy. Although a number of drugs have been shown to be useful in the prevention of migraine headaches, all of them carry significant side effects. In contrast, 5-HTP is very safe.

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