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Listening To 5HTP

By Charles Davidson

Introduction

The chemical serotonin is important for a variety of brain functions. Its deficit is now believed to be central to the development of depression, sleep disorders, obesity and addiction. Serotonin can be produced commercially from the amino acid tryptophan in two steps or it can be obtained directly in foods such as bananas. Serotonin can also be made in the body 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. A relative deficiency of serotonin is believed to be associated with the brains perception of starvation and hunger. 5-HTP is both an appetite suppressant and an inducer of sleep. One hundred (100) milligrams of 5-HTP produces a rise in the body of serotonin levels equal to that produced from the consumption of about 10 bananas.

The 5-hydroxy L-tryptophan preparation that can be obtained from Smart Basics under the UltraPure brand is extracted from a seed that is also used in the pharmacological preparation of lectins. Lectins are pharmaceutical grade compounds that are used in blood typing for transfusions and bone marrow transplantationís.

Article

Nerve cells conduct electricity in one direction. Sensory nerves conduct electrical impulses towards the brain and spinal cord; motor nerves conduct impulses in the opposite direction. Notwithstanding the electrical nature of nerve impulses, 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 the synapse. A nerve impulse is fired when enough receptor molecules on the ìpost-synapticî nerve bind specifically to one or another class of neurotransmitter.

The level of neurological complexity is far greater in the brain than in the peripheral nervous system because of the much larger number of nerve cells and the increased diversity of neurotransmitter compounds available there. Different regions of the brain - - and different neurotransmitters -- mediate disparate processes, ranging from 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 bananas and is important for a variety of brain functions. Its deficit is now believed to be central to the development of depression, sleep disorders, obesity and addiction. Serotonin (5-hydroxytryptamine or 5-HT) can be produced commercially from the amino acid tryptophan in two steps. Serotonin can also be made in the body directly from 5-hydroxy L-tryptophan (5-HTP) which is simply, the modified amino acid.

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.

Decreased brain serotonin levels are also associated with obesity due to overeating. Drugs like dexfenfluramine (Redux), 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. 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 100 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 low calorie/high protein diet, for reasons to be explained later. 5-HTP should always be taken with adequate amounts of protein in the diet.

Serotonin levels are also increased by the intake of addictive substances, such as alcohol, tobacco, certain narcotics and caffeine. A chemical withdrawal syndrome occurs 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.

The thalamus, is the region in the brain responsible for emotions and for controlling hypothalamic 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 ìendocrine" glands in the periphery -- such as the adrenals -- to produce secondary hormones. Different emotions, situations and behaviors are frequently associated with the bodies production of different hormones.

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. Again 100 mg is effective in a large adult male. Both 5-HTP and serotonin (5-HT) are precursors to another neurotransmitter - melatonin - that also induces sleep. Melatonin, like 5-HTP 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. Its production is indirectly suppressed by light going into the eye.

Many people feel that eating a piece of toast or a banana before going to bed helps them to fall asleep. Indeed, 3 to 4 bananas actually contain about 12 mg of serotonin (the metabolite of 5-HTP). An analysis of biochemical studies indicates that the consumption of 100 mg of 5-HTP is equivalent to the consumption of 10 to 12 bananas. This observation is based on the ability of either bananas, pharmaceutical serotonin or 5-HTP to produce equivalent increases in the common urinary metabolite, 5-hydroxy indoleacetic acid (5-HIAA).

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 hormone-induced decrease in "serotonergicî activity. Conversely, pain sensitivity is markedly impaired during alcohol intoxification, which increases serotonin levels in the brain.

Over Omega century ago, the great physiologist Hans Selye observed that stress -- in both humans and in experimental animals -- resulted in an increased level of the 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 is sometimes prescribed for elderly depression for those reasons. Interestingly, the transplanting of the melatonin - producing pineal gland from young mice into old mice increased the life span of the older mice. While moderate food restriction in rodents is well known to increased lifespan, it also increases melatonin levels. Once produced in the pineal gland, melatonin enters the blood stream and circulates throughout the body. While melatonin added to the drinking water of middle-aged mice significantly increased their lifespan over that of controls, the exact mechanism of life extension by this serotonin metabolite is unknown. The consumption of low-dose 5-HTP -- a precursor to melatonin -- might then be used to mitigate some aspects of stress present during mid- life.

Potential Side-effects and Contraindication: of 5-HTP Use

Should just any person who suspects that low serotonin levels are the cause of their depression, overeating, substance abuse or insomnia consume 5-HTP? What are the contraindications of 5-HTP and is it safe for all persons? Who should not take 5-HTP? Lastly, what is the safe and appropriate daily dose of 5-HTP in persons who are otherwise healthy? These are important questions.

It is advisable that professional advice should be solicited by persons having (or suspected of having) emotional or physical conditions such as those mentioned above. Listed at the end of this article are the pre-existing conditions that contraindicate (that is, advise against) the use of 5-HTP or strongly indicate that its use should be under the guidance of a physician.

Obviously, individuals who are already under medical treatment using drugs which alter serotonin metabolism should not take 5-HTP unless under the supervision of the prescribing physician. Anti-depressants, weight-loss drugs and L-dopa (used in the treatment of Parkinsonís disease) are examples of types of drugs that might contraindicate unsupervised use at the same time as 5-HTP. An expanded list of possibly contraindicated drugs are also included at the end of this article.

As a nutritional supplement in most individuals 5-HTP can safely be consumed at a dosage of up to 100 milligrams (mg) per day. Recall that 100 mg of 5-HTP produces, in the body, a rise in the blood (plasma) concentration of serotonin equivalent to the amount that is produced from the consumption of about 10 bananas. Much higher doses of several hundred to nearly 3000 mg per day of 5-HTP have been used in the treatment of severe muscular (myoclonic) contractions. As will be described, a particular side effect can occur in certain susceptible individuals

It is important to note that in persons experiencing certain underlying medical conditions (mentioned below), long-term elevations of serotonin have been associated with the deposition of connective tissue (fibrosis) in the heart. muscles, skin, and blood vessels. A predisposition to a heart disease called endomyocardial fibrosis (EMP) exists among chronically malnourished populations who consume low protein/high carbohydrate diets rich in serotonin-containing foods (such as bananas, plantain or cassavas). This indicates that persons on a weight loss program who use 5-HTP should be on a high protein/low carbohydrate diet.

Another factor in the development of fibrosis is the simultaneous presence of both high levels of serotonin and another tryptophan metabolite that is not derived from 5-HTP, but that is toxic. The level of this toxic metabolite was highly elevated in 1 out of 8 people who developed fibrosis of the skin (scleroderma) after long-term treatment with 5-HTP for myoclonic contractions. Conditions such as AIDS, cancer, aging and autoimmune diseases frequently cause an elevation in the level of this toxic tryptophan metabolite. Persons with these conditions (and those listed at the end of this article) should, therefore, not consume 5-HTP unless under the guidance of a physician.

Vitamin B-6 is a cofactor for the enzyme that degrades toxic tryptophan metabolites. Since B-6 is also needed by the enzyme that converts 5-HTP into serotonin, this vitamin should regularly be taken on the same day as 5-HTP, but at least 6 hours before 5-HTP consumption. This preliminary use of B-6 before 5-HTP both helps to prevent the accumulation of toxic tryptophan metabolites and delays somewhat the rise in plasma levels of serotonin (from 5-HTP). No additional B-6 is needed beyond that obtained in a typical B-vitamin pill or a minimum of 10 mg per day

Alcohol effects the metabolism of 5-HTP. Therefore, persons who have taken 5-HTP should not drink alcohol within six (6) hours of its use. Persons with liver damage should not use 5-HTP. For example, those who are chronic alcoholics, or intravenous drug users, or who have cirrhosis, hepatitis or parasitic infections should not use 5- HTP. Experimental 5-HTP use in animals -- at the same time that liver toxic drugs were administered -- produced heart fibrosis. 5-HTP administration alone did not produce this effect. Malnourished African persons who consume serotonin-rich foods and have heart fibrosis also probably have liver damage induced by chronic viral hepatitis and parasites like malaria. Therefore, drugs which damage the liver -- and probably effect tryptophan metabolism -- such as cancer chemotherapies and powerful antibiotics should not be used at the same time as 5-HTP.

Since serotonin is involved in the constriction of blood vessels and the clotting of blood by platelets, it should not be used in persons at risk of heart disease or strokes or who have high blood pressure. Its use in elderly persons should be under the supervision of a physician, especially those individuals receiving L-dopa for Parkinson's disease. Persons with severe allergies should not use 5-HTP. It should not be taken by persons who have previously experienced either flushing of the skin or diarrhea with it use. If nausea is induced by 5-HTP, the dosage should be reduced or, if symptoms persist, its use discontinued entirely.

The effect of 5-HTP on fetuses and in pregnant women has not been investigated clinically, therefore its use during pregnancy is contraindicated. Lastly, persons driving an automobile or operating machinery should not consume 5-HTP within six hours prior to that activity. 5-HTP can potentate the effects of certain tranquilizing drugs and alcohol.

One of the titles of this article ìListening to 5-HTP" is a parody of the title of the book ìListening to Prozacî. The author of "Listening to Prozac" generally extols the virtues of selective serotonin reuptake inhibitor drugs, like Prozac, especially underscoring their marked improvement over previously developed types of anti- depressants. Yet ironically, 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. 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-#-vis Prozac. For one, the efficacy of Prozac and other SSRIís are still dependent upon the brains availability or serotonin precursors like tryptophan or its derivative, 5-HTP. When patients receiving SSRIís 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. Finally, 5-HTP is an amino acid and is available without a prescription.

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. In addition, the information described in the article do not reflect individual studies conducted by this author.

Bibliography

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2. Wurtman RJ and Wurtman JJ. Brain serotonin, carbohydrate-craving obesity and depression. (Review. Obesity Research. 3 Suppl. 4:4775-4805 (1995).

3. Delgado PL, Price LU and others. Serotonin and the biology of depression. Effects of tryptophan depletion in drug-free depressed patients. Arch. Gen. Psych.. 51(11)865- 74(1994).

4. Benkelfat C. Ellenbogen MA and others. Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders. Arch. Gen Psych.. 51(9)687-97 (1994).

5. Ryan ND, Birmaher B. and others, Neuroendocrine Response to L-5- Hydroxytryptophan Challenge in Prepupertal Major Depression. Arch, Gen. Psych. 49(11)1:843-51(1992).

6. Stokes PE. The potential role of excessive cortisol induced by HPA hyperfunction in the pathogenesis of depression. [Review]. European Neuropsychopharmacology. 5 Suppl.:77-82 (1995).

7. Cangiano C, Ceci, F, Cascino A and others. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Amer. Clin Nutr.. 56:863-7 (1992).

8. Haleem JD, Yasmeen A and others. 24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain; implications for caffeine-induced depression. Life Sciences. 57(19):PL285-92 (1995).

9. Adams WK Keirer SW and Badia-Elder N. Tryptophan deficiency and alcohol consumption in rats as a model for disadvantaged human populations; a preliminary study. Medical Anthropology. 16(2):175-91 (1995).

10. Menkes BB, Coates DC and Fawcett JP. Acute tryptophan depletion aggravates premenstrual syndrome. Journal of Affective Disorders. 32(1 ):37-44(1994).

11. Shea-Moore MM, Thomas DP and Mench JA. Decreases in aggression in tryptophan-supplemented broiler breeder males are not due to increases in blood niacin levels. Poultry Science. 75(3)370-4. (1996).

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16. Van Woert MH, Rosenbaum D and others. Long-term therapy of monoclonus and other neurological disorders with L-5-hydroxytryptophan and carbadopa. N. Engl. J. Med.. 296:70-75 (1977).

17. Sternberg, EM, Van Woert MH, and others. Development of scleroderma-like illness during therapy with 5-hydroxytryptophan and carbadopa. New England Journal of Medicine. 303:782-7(1980)

18. Stachow A and others. 5-Hydroxytryptarnine and tryptomine pathways in scleroderma. Brit. J. Derm. 97:147-155 (1997).

19. Ratnavel RC, Burrows NP and Pye RJ. Scleroderma and the Carcinoid Syndrome. Clin. Exp. Derm..19:83-5 (1994).

20. Mckinney B and Crawford MA. Fibrosis in guinea pig hearts produced by plantain diet. Lancet. 2:880-2 (1965).

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Contraindications to 5-HTP use or conditions under which 5-HTP use should only be under the supervision of a physician are:

Cardiovascular Diseases (high blood pressure, post-stroke, post-heart attack); Extremely Elderly Persons; those with Parkinsons; Disease, Cancer or Autoimmune Diseases (Scleroderma, Rheumatoid Arthritis, Multiple Sclerosis, Lupus); Lung Diseases; Chronic Alcoholism; Liver diseases (hepatitis or cirrhosis); parasitic infection; AIDS; Anorexia Nervosa; Low protein Diets; Allergies (severe); Myalgia (persistent pain and weakness of the muscles); Peripheral Neuropathy (pain weakness of the muscles); Rash or Flushing; Edema; Nausea; Diarrhea; Sickle cell anemia; hemophilia; Pregnancy

Concurrent drug use: 5-HTP should not be used if taking: Anti-depressant drugs; Monoamine oxidase inhibitors; Selective Serotonin Reuptake Inhibitors (SSRI's e.g., Prozac); Tricyclic medications; Weight Loss medications (i.e., dextenfluramine); Anti-parkinson medications (e.g., L-dopa); Barbiturates and other tranquilizing drugs; Antihistamines and cold medications; Alcoholic beverages; Intravenous (illegal I.V.) drugs; Cancer chemotherapy or antibiotic medications.

Warning: Dosages of 5-hydroxy L-tryptophan (5-HTP) greater than 100 milligrams per day should be taken only under the guidance of a physician. 5-HTP use at doses greater than 100 mg per day should be taken with the prescription drug carbadopa to prevent excessive levels of serotonin production in the peripheral blood circulation. 5-HTP can increase the effect of tranquilizing drugs and can impair the ability to drive an automobile.

Warning: Dosages of 5-hydroxy L-tryptophan (5-HTP) greater than 100 milligrams per day should be taken only under the guidance of a physician. 5-HTP use at doses greater than 100 mg per day should be taken with the prescription drug carbadopa to prevent excessive levels of serotonin production in the peripheral blood circulation. 5- HTP can increase the effect of tranquilizing drugs and can impair the ability to drive an automobile.

Please call, write or e-mail your experiences with 5-hydroxy L-tryptophan (5-HTP), positive or negative, to us. Thank You.




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