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Answering Common 5-HTP Questions


The amino acid 5-hydroxytryptophan (5-HTP) 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. Examples of low serotonin states include:

• Depression

• Obesity

• Carbohydrate craving

• Bulimia

• Sleep issues (i.e., insomnia, narcolepsy and sleep apnea)

• Headaches (i.e., migraine, tension and chronic daily)

• Premenstrual syndrome

• Fibromyalgia

What Clinical 5-HTP Research Exists?

Clinical studies have demonstrated excellent results for all of the conditions linked to low serotonin levels. In fact, in head-to-head comparison studies, 5-HTP has outperformed antidepressant drugs and recent studies have shown it to be quite helpful in reducing appetite and promoting weight loss in overweight subjects. Most commercially available 5-HTP is isolated from a natural source—a seed from an African plant (Griffonia simplicifolia).

How Does Tryptophan Compare to 5-HTP?

There really is no comparison between L-tryptophan and 5-HTP. The reason is that tryptophan must be converted to 5-HTP before it is metabolized to serotonin. This conversion is impaired in many people especially if they have either high cortisol due to stress, insulin resistance or are lacking in key nutrients like B6 and magnesium. In addition, tryptophan requires active transport into the brain and competes with other amino acids for this transport site. In contrast, 5-HTP easily crosses the blood-brain barrier. As a result, detailed studies show that while only three percent of an oral dose of tryptophan is converted to serotonin, more than 70 percent of an oral dose of 5-HTP is converted to serotonin. In addition to increasing serotonin levels, 5-HTP causes an increase in endorphins and other neurotransmitters.

The antidepressive effects of 5-HTP were compared with tryptophan in the early 1970s with 5-HTP producing much better results. In fact, tryptophan was only slightly better than a placebo. In one study, 45 subjects with depression were given tryptophan (5 g/day), 5-HTP (200 mg/day) or a placebo. The patients were matched in clinical features (e.g., age, sex) and severity of depression. The main outcome measure was a rating scale called the Hamilton Depression Scale (HDS), the most widely used assessment tool in clinical research on depression. The HDS score is determined by having the test subject complete a series of questions in which he or she rates the severity of symptoms on a numerical basis, as follows:

• 0—not present

• 1—present but mild

• 2—moderate

• 3—severe

• 4—very severe

Symptoms assessed by the HDS include depression, feelings of guilt, insomnia, gastrointestinal symptoms and other bodily symptoms of depression (e.g., headaches, muscle aches, heart palpitations) and anxiety. The HDS is popular in research because it provides a good assessment of the overall symptoms of depression. The following table shows the results of the study.

How Effective is 5-HTP in Helping Weight Loss?

5-HTP can be very helpful with weight loss, especially in reducing excessive carbohydrate consumption. More than three decades ago, researchers demonstrated that administering 5-HTP to rats that were genetically bred to overeat and be obese resulted in a significant reduction in food intake. Further research revealed that these rats have decreased activity of the enzyme (tryptophan hydroxylase), which converts tryptophan to 5-HTP, itself subsequently converted 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 don’t get the message to stop eating until they have consumed far greater amounts of food than normal rats.

Circumstantial evidence indicates that many humans are genetically predisposed to obesity. This predisposition may involve the same mechanism as rats genetically predisposed to obesity (i. e., 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.

The early animal studies with 5-HTP as a weight-loss aid have been followed by a series of four human clinical studies in overweight women. These studies show that 5-HTP was able to reduce calorie intake and promote satiety. The average amount of weight loss during the five to six week period of 5-HTP supplementation averaged between 1 and 1.5 pounds per week even in overweight women that made no conscious effort to lose weight.

What is the Best Way to Take 5-HTP?

For customers seeking the benefits of 5-HTP, be sure to offer them entericcoated capsules or tablets (pills prepared in a manner so that they will not dissolve in the stomach), or 5-HTP in chewable tables. If 5-HTP acts in the stomach, it will produce significant nausea. For depression, weight loss, headaches and fibromyalgia, the dosage should be started at 50 mg three times per day. If the response is inadequate after two weeks, increase the dosage to 100 mg three times per day. For insomnia, take 50 to 150 mg 30 to 45 minutes before retiring. Start with the lower dose for at least three days before increasing dosage. 5-HTP can be taken with food, but if your customer is taking it for weight-loss benefits, it should be taken 20 minutes before meals.

Does 5-HTP Cause Daytime Sleepiness/Tiredness?

No. In double-blind, placebo-controlled studies, 5-HTP produced no greater reports of daytime sleepiness than the placebo.

Can 5-HTP Be Used With Antidepressant Drugs?

Although 5-HTP has been shown to work very well with antidepressant drugs in clinical trials, the best recommendation is for retailers to caution customers against taking 5-HTP until they consult with their doctor. It is theoretically possible for serotonin levels to get too high. The result is a condition known as the “serotonin syndrome,” which is characterized by confusion, fever, shivering, sweating, diarrhea and muscle spasms.

That being said, with a doctor’s supervision, 5-HTP can be used in conjunction with antidepressant drugs. The typical dosage schedule is to begin with a dosage of 5-HTP at 50 mg three times daily; after one month, the dosage of the antidepressant drug can be cut in half. If satisfactory response is achieved after the next month, the dosage of 5- HTP can be increased to 100 mg three times daily and discontinue the medication.

Again, a physician must supervise any change in the dosage of a prescription medication.

Are There Any Contraindications for 5-HTP?

• Do not use 5-HTP during pregnancy or lactation.

• Do not use 5-HTP in Parkinson’s disease unless the drug Sinemet.

• Do not use 5-HTP if you have sceleroderma (linked to a defect in tryptophan metabolism).

• Do not use 5-HTP with the drugs methysergide and cyproheptadine.

Is 5-HTP Safe for Long-Term Use?

Yes. Some people with a genetic defect in the conversion of tryptophan to 5- HTP require lifelong supplementation. Just to be safe, long-term continual use of 5-HTP should be monitored by regular (every year) eosinophil determination. This determination is part of a standard laboratory blood test known as a complete blood count (CBC).

Michael T. Murray, ND, is widely regarded as one of the world’s leading authorities on natural medicine. He is a graduate, former faculty member and serves on the Board of Regents of Bastyr University in Seattle, WA. The author of more than 30 books on health nutrition, Murray is also director of product development and education for Natural Factors Nutritional Products. For more information, visit www.doctormurray.com.