5htp (5 htp) Hydroxytryptophan (hydroxy tryptophan) Studies

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The Serotonin Solution
This article first appeared in the March 1997 issue of Vitamin Research News reprinted by permission from Pat Whittington of Vitamin Research Products

by James South

Serotonin is one of the ten or so major brain neurotransmitters; there are perhaps 100 minor neurotransmitters. Neurotransmitters are the biochemicals nerve cells use to "talk" to each other. There are an estimated 10-100 billion neurons in the human brain and each neuron may connect to thousands of other neurons. Yet, when these interconnecting neurons do not quite touch each other, there is a microscopic gap between them called the "synaptic gap." As a burst of electric current travels down the length of a neuron, it releases a packet of neurotransmitter molecules which are stored at the edge of the synaptic gap. These neurotransmitters then diffuse across the synaptic gap and "plug in" to the receptor sites of the next neuron, like keys fitting into locks. When a sufficient number of molecules have "plugged in" to the corresponding receptors of the next neuron, this neuron then discharges a burst of electricity down its cell membrane surface, repeating the process with neurons to which it connects. Thus, neurons use electricity to propagate a signal down the length of their own cell structure, but use chemical neurotransmitter molecules to signal other neurons. When there are inadequate numbers of neurotransmitters to activate other neurons, various brain circuits become under or overactive due to lack of communication between nerve cells.

Studies with humans and animals have shown that serotonin nerve circuits promote feelings of well being, calm, personal security, relaxation, confidence, and concentration.(15) Serotonin neural circuits also help counterbalance the tendency of brain dopamine and noradrenalin (two other major neurotransmitters) to encourage overarousal, fear, anger, tension, aggression, violence, obsessive-compulsive actions, overeating, anxiety and sleep disturbances.(15) Unfortunately, neuroscience has also discovered that many people suffer from various degrees of brain serotonin deficiency, leading to a host of mental, emotional and behavioral problems. To understand why brain serotonin deficiency is becoming ever more common in modern society, it is necessary to look at how the brain makes serotonin.

Serotonin Function
Serotonin (also called "5HT"), dopamine, and noradrenaline are the three main "monoamine" neurotransmitters. They are each made from one specific amino acid. Serotonin is made from the amino acid tryptophan while dopamine and noradrenaline are made from the amino acid tyrosine. While other cells outside the brain such as blood platelets and some intestinal lining cells make and/or use serotonin, all serotonin used by brain cells must be made within the neurons. Due to the blood-brain barrier, serotonin cannot be "imported" from outside the brain. The blood-brain barrier serves as a protection device to prevent toxins from entering the brain, yet this protection comes at a price. Even friendly molecules needed by the brain, such as amino acids, are limited in their access to the brain. Nutrients are ferried through the blood-brain barrier by transport molecules, like passengers on a bus. This creates a special bottleneck for serotonin. Serotonin itself cannot pass through the blood-brain barrier, while its precursor tryptophan must share its transport "bus" with five other amino acids leucine, isoleucine, valine, tyrosine and phenylalanine. In any normal diet, animal protein-based or vegetarian tryptophan is the least plentiful of all 20 food amino acids. Thus, tryptophan is typically outnumbered as much as 7-9:1 in its competition to secure its transport through the blood-brain barrier into the brain. Eating a high protein diet in an attempt to increase dietary tryptophan (a typical diet provides only 1-1.5 grams/day) only increases its competition even more. Ironically, the only dietary strategy that increases brain tryptophan supply is to eat a high carbohydrate, low protein diet. When large amounts of carbs are eaten, the body secretes large amounts of the hormone insulin to lower the ensuing high blood sugar. Insulin also clears most of the five amino acids from the blood that compete with tryptophan for a ride to the brain. Tryptophan then has the "bus" to itself, allowing plenty of tryptophan to reach the brain. (10)

This strategy is instinctively known and practiced by many Americans who eat large amounts of carbs such as candy, cake, pie, bread, chips, ice cream, etc. They do this when they are feeling stressed, depressed, or anxious. The increased brain serotonin this produces lowers arousal and anxiety which promotes a (temporary) sense of well-being and security. This strategy comes at a price. The same insulin which enhances brain serotonin also enhances the conversion of the fats, carbs, and aminos cleared from the blood into stored body fat! Hence the carb addiction / overfat-serotonin connection. (10)

Tryptophan v. 5-HTP
In the 1970's, the American health food industry began providing an alternative method of getting more tryptophan to the brain with tryptophan supplements. Some people found that 500 - 3000 mg of supplementary tryptophan daily provided sufficient support. Yet, in 1989 the FDA removed tryptophan from the American health food market due to an ailment called eosinophilia myalgia (EMS) caused by a single batch of contaminated tryptophan from a single Japanese producer. To this day, the FDA shows no signs of allowing tryptophan back on the market. If the FDA were to re-approve tryptophan for general use, would it still be the best natural non-drug way to deal with the serotonin deficiency syndrome? For several reasons, the answer is "No."

It is generally accepted that only about 1% or less of dietary/supplementary tryptophan ever enters the brain. The rest is used to make various body proteins; some is converted into vitamin B-3 at a cost of 60 mg tryptophan to make one mg B-3; some is converted by other body cells into serotonin for their needs; and some may be broken down through the kynurenine pathway. A liver enzyme, tryptophan pyrrolase, converts tryptophan into kynurenine, which may then be converted to hydroxykynurenine (3-OH-K), xanthurenic acid (XA), and hydroxyanthranilic acid (3-OH-AA) for urinary excretion. Unfortunately, 3-OH-K, XA and 3-OH-AA are all known to cause liver damage and bladder cancer.(16) It may not be pure chance or coincidence that nature has arranged tryptophan to be the least plentiful amino in our diets. Furthermore, there are at least two known factors which significantly increase liver pyrrolase activity, dramatically enhancing production of these toxic metabolites. The first is the stress hormone cortisol.(13) Cortisol, produced by the adrenal glands, is the "state-of-siege" stress hormone. It is released in response to unremitting stress which we can neither fight nor flee. Cortisol is known to be elevated frequently in the very conditions, such as depression, insomnia and obesity(13), for which tryptophan /serotonin might be useful. Thus, taking tryptophan supplements while under elevated cortisol-stress conditions might supply little extra to the brain for serotonin synthesis, yet dramatically raise toxic 3-OH-K, XA and 3-OH-AA levels.

The second factor known to increase liver pyrrolase activity is increased intake of tryptophan. The kynurenine pathway is the major degradation pathway for tryptophan in the human body, and higher tryptophan intake automatically induces higher pyrrolase activity.(13) This explains why studies using tryptophan as an antidepressant frequently find moderate doses more effective than high doses, and why van Praag noted in 1981 that "L-tryptophan was found to be effective in [only] five of the ten double-blind comparative studies."(5)

Fortunately, a safe alternative to both tryptophan and drugs (such as Prozac) is now available in the U.S. without a prescription. This substance is L-5-Hydroxytryptophan (5-HTP). 5-HTP is not produced by bacterial fermentation (as was the tainted tryptophan) nor chemical synthesis but is extracted from the seeds of the Griffonia plant.

Recommended Dosage
The recommended dose of 5HTP for most people is 33-100 mg, three times a day, 20 minutes before meals.

Click here to read more from Dr. Michael T. Murray, Author of 5-HTP: The Natural Way to Boost Serotonin.

Click here for 6 steps to healthy sleep by Dr. David Williams.

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