The chemical serotonin is important for a variety of brain functions. Its deficit is now believed to be central to the development of depression, agitation, sleep disorders, obesity and addiction. Serotonin can be produced in the body from the dietary amino acid tryptophan in only two steps. Serotonin can also be made from 5-hydroxy L-tryptophan (5-HTP) which is simply, the modified amino acid obtained from plant sources.
The pharmaceutical control of brain serotonin levels is the mechanism of action of two commonly prescribed classes of drugs used in the treatment of depression and anxiety, a well known example being Prozac. A relative deficiency of serotonin is also believed to be associated with the brain's perception of starvation and hunger. For these reasons, 5-HTP has been used as an anti-depressant, as an appetite suppressant in obese persons and as an inducer of sleep.
5-HTP : A Dietary Precursor to an Important Chemical in the Brain
Notwithstanding the fact that electrical impulses travel down an individual nerve fiber, nerves communicate with each other chemically and not electrically. Nerves are classified according to their ability to either secrete or respond to various chemical compounds called neurotransmitters. (These molecules are secreted into the gap between two different nerve cells, called either the synapse or the synaptic cleft. A nerve impulse is fired when enough receptor molecules on the "post-synaptic" nerve bind specifically to one or another class of neurotransmitter that was secreted by the "pre-synaptic" nerve.) Different regions of the brain -- and different neurotransmitters -- mediate disparate processes, ranging from highly aware mental cognition to unconscious manifestations, such as hunger and sleep.
Neurotransmitters are derived from precursor chemicals found in common food substances. For example, acetylcholine is produced by nerves from choline, a chemical that can be obtained commercially from soybean lecithin. Acetylcholine is secreted by the motor nerves into the neuromuscular junction thereby, stimulating muscular contraction. The neurotransmitters GABA and norepinephrine are derived from proteins that contain the amino acids glutamate and tyrosine, respectively. Adrenaline is chemically related to norepinephrine and is used medically to restart hearts that have been arrested following a heart attack. The neurotransmitter, serotonin, is present in high levels in foods such as bananas and is important for a variety of brain functions. Serotonin, however, cannot cross the blood-brain barrier, although 5-HTP - a nutritional supplement - can enter the brain directly from the general circulation (by being transported across the blood-brain barrier).
5-HTP Helps Alleviate Depression and Reduces Aggressiveness
It is clinically significant that a deficit of serotonin is central to the development of depression, agitation, sleep disorders, obesity and addiction. For this reason, the pharmaceutical control of brain serotonin levels is the mechanism of action of two commonly prescribed classes of drugs used in the treatment of depression. Prozac is an example of a selective serotonin reuptake inhibitor (SSRI), which prevents the "presynaptic" nerve from reabsorbing serotonin that it has previously secreted. By inhibiting this normal process, Prozac causes an increase in brain serotonin levels and a non-narcotic anti-depressant effect. Another class of antidepressant drugs, the monoamine oxidase (MAO) inhibitors cause an increase in serotonin levels by preventing its degradation. Conversely, the experimental depletion of serotonin in animals -- by eliminating tryptophan from the diet -- causes an increase in aggressiveness. [Note later section entitled "5-HTP or Prozac or Both?".]
5-HTP as an Appetite Suppressant
Decreased brain serotonin levels are also associated with obesity due to overeating. Drugs like fenfluramine (Fen Phen), which increases serotonin production, are used as an appetite suppressant successfully in the treatment of common obesity. A relative deficiency of serotonin is believed to be associated with the brains perception of starvation and hunger. Tryptophan is one of the most rare of the essential amino acids - one that the body cannot produce - but one that is needed for the production of vital proteins. Consequently, the dietary depletion of tryptophan, a serotonin precursor, is an ideal homeostatic mechanism in the brain for regulating the desire for food intake.
Hunger sensation in the brain is believed to occur in the region called the hypothalamus. Opposite to the effect of food deprivation, the specific intake of carbohydrates and various sugars cause an increase in brain serotonin levels. This explains why some people are willing to eat an excess of "junk food" that entirely lacks any protein.
5-HTP -- which increases serotonin levels -- is an appetite suppressant at low doses (50 to 200 milligrams) if taken one-half hour before meals. At high doses, a common side effect of 5-HTP is nausea. During clinical trials in obese subjects, the intake of 5-HTP caused a voluntary decrease in caloric intake of both carbohydrates and fats, but not of protein. A significant loss of weight occurred, due to a voluntary decrease in caloric intake and not because of a restrictive diet. 5-HTP should also help in the adherence to a diet that is both low in calories and fat, but that is high in protein. 5-HTP should always be taken with adequate amounts of protein in the diet - not with a starvation weight loss regimen. [Note the later section entitled "5-HTP or Prozac or Both?" for a short discussion on the cardiac side effects of fenfluramine (Fen Phen) and the brain damage associated with the use of dexfenfluramine (Redux) another drug commonly prescribed to suppress appetite.]
5-HTP, Addiction and Pain
Serotonin levels are also increased by the intake of addictive substances, such as alcohol, tobacco, certain narcotics and caffeine. Individuals attempting to kick these habits develop a chemical withdrawal syndrome when serotonin levels plummet. These results are observed in both experimental animals and in people. The above findings indicate that overeating is, in part, chemical dependency related -- by low serotonin levels -- to other chemical addictions and to depression.
Pain sensitivity increases, as well, when brain serotonin levels are low. This has been presented by some researchers as one contributing factor in pre-menstrual syndrome (PMS). Agitation, pain irritability and depression are characteristic aspects of PMS, perhaps each related to a sex hormone-induced decrease in "serotonergic" activity. Conversely, pain sensitivity is markedly impaired during alcohol intoxification, which temporarily increases serotonin levels in the brain.
5-HTP Gently Induces Sleep
Perhaps the most immediate effect of 5-HTP is its ability to induce sleep when taken on an empty stomach about one hour before going to bed. A 100 mg dose is effective in a large adult male. Both 5-HTP and serotonin (5-HT) are precursors to another neurotransmitter -- melatonin -- that also induces sleep. 5-HTP, like melatonin, can now be obtained in health food stores. Millions of people have safely taken melatonin for sleep and for eliminating jet lag. Melatonin is produced in the pineal gland deep within the brain, especially at night. Melatonin production is indirectly suppressed by light going into the eye and its levels are directly augmented by the availability of precursors, such as 5-HTP.
5-HTP, Stress Reduction and Aging
The thalamus, is the region in the brain responsible for emotions and for controlling hypothalamic - hormone related - activity. Chemical releasing factors from the hypothalamus direct the adjacent pituitary gland to produce a variety of hormones in all mammals, including man. Pituitary hormones then direct "endocrine" glands in the periphery - such as the adrenal glands and the gonads - to produce secondary hormones. Different emotions, situations and behaviors - especially stress - are frequently associated with the bodies production of different hormones.
Over ½ century ago, the great physiologist Hans Selye observed that stress -- in both humans and in experimental animals -- resulted in an increased level of the (adrenal) hormone cortisol. Cortisol is responsible for the 'fight, flight or fright" response; its elevation produces states ranging from marked wakefulness to panic. Both high cortisol levels and experimental stress reduce levels of brain serotonin. Long-term exposure to cortisol actually damages certain serotonin producing nerves in the brains of animals.
A number of factors are involved in depression in elderly individuals, exposed to a lifetime of various stresses, including an age-related decrease in brain serotonin levels. Elderly persons frequently have difficulty falling to sleep at right as well. Prozac, which raises serotonin levels, is sometimes prescribed for elderly depression for those reasons.
Interestingly, while moderate food restriction in rodents is known to increased lifespan, it also increases levels of the neurotransmitter melatonin - a metabolite of serotonin (and therefore, of 5-HTP). Additionally, melatonin added to the drinking water of middle-aged mice significantly increased their lifespan over that of controls. Furthermore, the transplanting of the melatonin - producing pineal gland from young mice into old mice increased the life span of the older mice. Therefore, the consumption of low-dose 5-HTP - a precursor to melatonin - might be used to mitigate certain aging aspects of long-term stress that begin to accumulate during mid-life.
5-HTP or Prozac or Both ?
One six week study of 69 subjects that compared another SSRI to 5-HTP found that both compounds have equal antidepressant capabilities. Moreover, 5-HTP had one-half as many moderate-to-severe side effects as the SSRI. (Also in the news recently has been reports of heart valve damage from the use of fenfluramine (Fen Phen) - another type of serotonin elevating drug in women being treated for obesity. Prozac, however, does not have this effect on the heart.)
One article which reviewed the results of 17 clinical trials which used 5-HTP - mostly for depression - concluded that "oral administration of 5-HTP. - is associated with few adverse effects". Two other facts surrounding 5-HTP are ironic vis-à-vis Prozac. For one, the efficacy of Prozac and other SSRI's are still dependent upon the brains availability or serotonin precursors like tryptophan or its derivative, 5-HTP. When patients receiving SSRI's were fed a special diet devoid of tryptophan, a relapse into depression was experienced, despite the continued presence of the SSRI. Tryptophan supplementation restored the antidepressant effects of the SSRI. On a related note, Prozac was found to be effective for anorexic individuals - who have low serotonin levels - but only once they were stabilized with a more normal weight and diet. Perhaps malnourished anorexic persons have inadequate levels of the dietary serotonin precursor - 5-HTP - so that Prozac cannot be effective.
Finally, 5-HTP is a supplemental nutrient - an amino acid - and is available without the need of a prescription. However, doses of 5-HTP greater than 200 mg per day are not recommended unless the individual is under the care of a physician.
[The studies described in this article are set forth by the author to contribute to the knowledge of the consumer of this product. The thoughts and ideas represented in this article by the author are a compilation of information found in numerous published reports known to the author at the time of writing this article and do not reflect individual studies conducted by this author.]
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