Guest guest Posted January 30, 2005 Report Share Posted January 30, 2005 Metabolism and absorption of 5-HTP JoAnn Guest Jan 29, 2005 23:03 PST ======================================================================== Metabolism and absorption of 5-HTP 5-HTP (5-hydroxytryptophan) is formed by the addition of a hydroxyl group (-OH) to the 5 carbon of the indole ring of tryptophan. Conversion of tryptophan to 5-hydroxytryptophan is catalyzed by the enzyme tryptophan hydroxylase. 5-HTP functions as the precursor for serotonin, and is converted to serotonin in a pyridoxal phosphate (vitamin B6) dependent reaction catalyzed by the enzyme L-amino acid decarboxylase.2 Synthesis of serotonin in the brain requires an adequate supply of either tryptophan or 5-HTP as precursors. The supply of tryptophan available for conversion to 5-HTP depends on a number of factors, including nutritional status and competition between tryptophan and other amino acids for transport across the blood brain barrier. Disturbances in the serotonin metabolic pathway may disrupt central nervous system functions which utilize serotonin as a neurotransmitter. Administration of 5-HTP bypasses the conversion of tryptophan to 5-HTP. 5-HTP readily crosses the blood brain barrier and becomes available for serotonin synthesis. Serotonergic neurons (nerve cells stimulated by serotonin) regulate sleep, appetite, nociception (the perception of pain), and aggressive behavior. Serotonin is metabolized to 5-HIAA (5-hydroxyindolacetic acid) which is its primary breakdown product. The concentration of 5-HIAA in cerebrospinal fluid is used as an indicator of serotonin turnover in the CNS serotonin level. Psychiatric patients have been found to have low levels of 5-HIAA in the CNS fluid, suggesting serotonin deficiency.3 5-HTP is readily absorbed by the mucosal cells of the gastrointestinal tract. The delivery of 5-HTP into general circulation is enhanced by the concomitant administration of an L-amino acid decarboxylase inhibitor such as carbidopa, which reduces the conversion of 5-HTP to serotonin in the gut and in liver. In one study using five subjects, systemic absorption of 5-HTP in combination with carbidopa averaged 69.2 percent.4 Another absorption study found that carbidopa enhanced the increase in serum 5-HTP concentration 5 to 15 fold. In this study, a single dose of 5-HTP increased the plasma level of 5-HTP only slightly, whereas 5-HIAA increased 9-20 fold. This suggests that the gut mucosa has a storage capacity for 5-HTP, and that plasma increases occur after maximum capacity is reached.5 Observed Effects of 5-HTP Administration Improves Well-Being in Depressed Persons Serotonin in the central nervous system is recognized as a causative factor in some depressed persons.6,7 A comprehensive review of seven open and seven controlled clinical studies found that oral consumption of 5-HTP improved mental and emotional status in 60 to 70 percent of depressed people. The results varied from " modest " to " marked. " 8 Dosages ranged from 50 to 300 mg daily. The accumulated evidence is inconclusive as to whether 5-HTP is more effective combined with decarboxylase inhibitors than when taken alone. Many of the early trials used the combination, and this has been a frequently used therapeutic strategy for reducing conversion of 5-HTP to serotonin outside the CNS. It is generally accepted that a large portion of absorbed 5-HTP is metabolized to serotonin in peripheral tissues before it can enter the brain. Peripheral conversion of 5-HTP to serotonin would theoretically limit the usefulness of oral 5-HTP for improving CNS functions and mental health. However, trials in which 5-HTP was given alone do show benefits. A small open trial in which 25 people were given 5-HTP either alone or with a decarboxylase inhibitor found no difference in effectiveness. Thirteen of the patients had " very good " or " good " improvement, 8 had " moderate, " and in 4 out of the twenty-five the results were judged to be " poor. " A more recent randomized double-blind study compared the efficacy of oral 5-HTP (100 mg T.I.D., without a decarboxylase inhibitor) to that of fluvoxamine, a selective serotonin reuptake inhibitor.10 (SSRIs block the reabsorption of serotonin by postsynaptic receptors, thus increasing the available supply of serotonin in the synaptic cleft.) The two were found to be equally effective, and 5-HTP was better tolerated. It should be noted that 5-HTP was given in the form of enteric-coated pH-sensitive capsules which dissolve in the small intestine, thus preventing conversion of 5-HTP to serotonin in the stomach. In contrast to MAO inhibitors and SSRIs, medications which act by blocking normal physiologic functions, 5-HTP supports normal function in its role as a serotonin precursor. Correcting serotonin deficiency has been called a " functional-dimensional approach " in the treatment of depression. (continued on reverse) Improves Sleep Quality Studies have shown that 5-HTP influences the quality of sleep by increasing REM (rapid eye movement) sleep. Administration of 5-HTP in the evening prior to bedtime has been shown to increase the duration of REM sleep and decrease the amount of non-REM sleep.11,12 Helps Prevent Migraine Headaches Serotonin is known to play an important role in the pathophysiology of migraine headaches.13 Serotonin regulates a key pain control system which is activated during a migraine attack. In a placebo-controlled, double-blind cross-over study 31 people with migraine took 400 mg of 5-HTP per day. By the second month, 5-HTP reduced the frequency and severity of attacks by more than 50 percent in 52 percent of the subjects, although the results were not statistically significant. In a larger study using 124 migraine sufferers, 5-HTP for migraine prevention was compared to methysergide.14 Seventy-one percent of the subjects taking 5-HTP (600 mg per day) experienced significant reduction of intensity and duration of attacks, compared to seventy-five percent of those taking the drug. Side effects were less frequent in the 5-HTP group. Improves Clinical Parameters in Fibromyalgia Disturbances in serotonin-controlled nervous system function are believed to be a factor in fibromyalgia.15 In a 90 day open trial, 50 people with primary fibromyalgia received 100 mg of 5-HTP three times daily. Nearly 50 percent showed " good " or " fair improvements in clinical parameters such as the number of tender points, anxiety, fatigue and sleep quality. A placebo controlled, double-blind study on 50 patients produced similar significant improvements.17 5-HTP–A Free-radical Scavenger The OH group which is added to tryptophan in the formation of 5-HTP gives 5-HTP antioxidant properties.18 (Compounds such as vitamin E and flavonoids derive their free-radical quenching ability from OH groups, which donate electrons to oxidants.) 5-HTP quenches a variety of free-radicals. This is in contrast to tryptophan, which is " sensitive " to oxidation. Adverse effects of 5-HTP Oral administration of 5-HTP in clinical studies has resulted in gastrointestinal disturbances such as nausea, vomiting and diarrhea. According to a review by Byerley, et. al. these effects are tolerated by most patients and tend to lessen over time. Side effects are more marked with higher doses, and may be reduced by the use of enteric-coated, pH sensitive capsules or tablets. Scientific References: 1. Pike, R.L., Brown, M.L. Nutrition: An Integrated Approach. NY: Macmillan Pub. Co.; 1986:626-28. 2. Peters, J.C. Tryptophan nutrition and metabolism: An overview. Advances in Experimental Medicine and Biology 1991;294:345-349. 3. van Pragg, H.M. Central monoamine metabolism in depressions. I. Serotonin and related compounds. Comprehensive Psychiatry 1980;21(1):30-43. 4. Magnussen, I., Neilsen-Kudsk, F. Bioavailability and related pharmacokinetics in man of orally administered L-5-hydroxytryptophan in steady state. Acta pharmacol. et toxicol. 1980;46:257-62. 5. Magnussen, I., Jensen, T.S., Rand, J.H., Van Woert, M.H. Plasma accumulation and metabolism of orally administered single dose L-5-hydroxytryptophan in man. Acta pharmacol. et toxicol. 1981;49:184-89. 6. van Pragg, H.M. Korf, J. 5-hydroxytryptophan as an antidepressant. Journal of Nervous and Mental Disease 1974;158(5):331-37. 7. van Pragg, H.M. Management of depression with serotonin precursors. Biological Psychiatry 1981;16(3):291-310. 8. Byerley, W.F. et. al. 5-Hydroxytryptophan: A review of its antidepressant efficacy and adverse effects. Journal of Clinical Psychopharmacology 1987;7(3):127-37. 9. Zmilacher, K. Battegay, R., Gastpar, M. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Neuropsychobiology 1988;20:28-35. 10. Pšldinger, W., Calanchini, B., Schwarz, W. A functional-dimensional approach to depression: Serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81. 11. Zarcone, V.P. Hoddes, E., Smythe, H. Oral 5-hydroxytryptophan effects on sleep. in Serotonin and Behavior, edited by Barchas, J., Usidin, E., NY: Academic Press; 1973:499-505. 12. Wyatt, R.J., et. al. Effects of 5-hydroxytryptophan on the sleep of normal human subjects. Electroencephalography and Clinical Neurophysiology 1971;30:505-09. 13. De Benedittis, G., Massei, R. 5-HT precursors in migraine prophylaxis: A double-blind cross-over study with L-5-hydroxytryptophan versus placebo. The Clinical Journal of Pain 1986;2:123-129. 14. Titus, F., D‡valos, A., Alom, J., Codina, A. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine. Eur. Neurol. 1986;25:327-29. 15. Nicolodi, M., Sicuteri, F. Fibromyalgia and migraine, two faces of the same mechanism. Recent Advances in Tryptophan Research, Vol. 398, edited by Filippini, G.A., et. al., NY: Plenum Press; 1996:373-79. 16. Puttini, P.S., Caruso, I. Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90 day open study. The Journal of International Medical Research 1992;20:182-89. 17. Caruso, I., Puttini, P.S., Cazzola, M., Azzolini, V. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. The Journal of International Medical Research 1990;18:201-09. 18. Simic, M.G. Al-Sheikhly, M. Jovanovic, S.V. Inhibition of free radical processes by antioxidantsÐtryptophan and 5-hydroxytrytophan. Bibl Nutra Dieta 1989;43:288-96. http://www.willner.com/References/webref58.html ===================================================================== 5-HTP Honest Information --- 5-HTP Honest Information by Ray Sahelian, M.D., http://www.raysahelian.com/5-htp.html best selling author of 5-HTP: Nature's Serotonin Solution 5-HTP (5-hydroxytryptophan or 5-hydroxy-l-tryptophan) is a natural supplement that converts in the brain into serotonin. Serotonin is an important brain chemical involved in mood, behavior, appetite, and sleep. Serotonin is also involved in impulse control. For instance, low serotonin levels may lead to addictive behavior such as gambling or other habits with weak will power. Serotonin is known as 5-HT, or 5-hydroxytryptamine, and is found in many places in the body particularly the brain, gastrointestinal system, and blood cells. 5-HTP is best absorbed on an empty stomach. 5-HTP Properties -- Appetite, Sleep, Mood, Stress Some people who take 5-HTP notice better mood balance, decrease in appetite, reduced anxiety, better impulse control, and better sleep. I have come across some individuals who find themselves more alert rather than in a relaxed, sleepy state of mind with 5-HTP. Some find that 5-HTP helps curb appetite with better weight control. This nutrient could be used temporarily for appetite suppression while other lifestyle and dietary changes are being incorporated regarding a life long plan for keeping weight off. Not everyone notices the appetite suppressing effect from 5-HTP. A study in rodents indicates that 5-HTP may be useful in controlling the excessive food intake sometimes generated by stress. 5-HTP may be temporarily helpful in conditions that normally require prescription antidepressants, anti-anxiety agents, sleeping pills, and weight loss drugs. 5-HTP may also be helpful in some individuals with migraine headaches and fibromyalgia. 5-HTP reduces the severity of a panic attack which may indicate that panic attacks may partly be due to low serotonin levels. Amount Per Capsule: 5-HTP - 50 mg Vitamin C - 30 mg Vitamin E - 10 iu Vitamin C and Vitamin E added as antioxidants Laboratory tested. The certificate of analysis says this product actually has 113% of its actual content which means it has 56 mg of 5-HTP. There is no Peak X or any unwanted substances, only pure 5-HTP. Plus: Subscribe to our free Supplement Research Update newsletter. Once or twice a month we email a brief abstract of several studies on supplements and natural medicine topics and their practical interpretation by Ray Sahelian, M.D. We occasionally discuss 5-HTP. A message regarding the safe use of 5-HTP 5-HTP was introduced to the over the counter market in 1994. Our understanding of 5-HTP's clinical role and its safety is still fuzzy. We don't know as much as we should about the effects of chronic 5-HTP use. Therefore, until we learn more, the idea is to take 5-HTP in the minimum effective dosage and to avoid its prolonged use. I tell my patients who use 5-HTP to take frequent breaks (the frequency and length of breaks varies since each person is unique). During these breaks, other forms of therapy could be substituted. As of now, and after years of 5-HTP sold to the public, I am not aware of any reports in the medical literature of anyone who has encountered life threatening or other serious side effects from the use of 5-HTP. 5-HTP Dosage Some studies have used dosages of 300 mg a day for depression, but I consider any 5-HTP dose above 50 mg a high dose. Most 5-HTP products on the market are sold in 50 and 100 mg capsules. Some people do well with 20 to 50 mg, while others may temporarily require 100 mg or more. I'm not aware of 5-HTP products on the market that are less than 50 mg. Those who do well with small doses can open a capsule and take a portion mixed with water. 5-HTP is best absorbed on an empty stomach. Medical supervision is recommended if high doses of 5-HTP are required to treat a particular condition. I don't recommend the routine use of daily intake doses greater than 100 mg since there's the possibility of nausea or nightmares. Also, we still don't know if there are any long term side effects if people take high doses for many years. 5-HTP enhances dreams and makes them more vivid. Safety of 5-HTP-- as discussed in the April 2004 issue of Toxicology Letters 5-Hydroxy-L-tryptophan (5-HTP) is the immediate precursor in the biosynthesis of 5-hydroxy-tryptamine (5-HT; serotonin) from the essential amino acid L-tryptophan. The use of L-Tryptophan as a dietary supplement was discontinued in 1989 due to an outbreak of eosinophilia-myalgia syndrome (EMS) that was traced to a contaminated synthetic L-Tryptophan from a single manufacturer. 5-HTP has since become a popular dietary supplement in lieu of the removal of L-Tryptophan from the market. Because of its chemical and biochemical relationship to L-Tryptophan, 5-HTP has been under vigilance by consumers, industry, academia and government for its safety. However, no definitive cases of toxicity have emerged despite the worldwide usage of 5-HTP for last 20 years, with the possible exception of one unresolved case of a Canadian woman. Extensive analyses of several sources of 5-HTP have shown no toxic contaminants similar to those associated with L-Tryptophan, nor the presence of any other significant impurities. A minor chromatographic peak (peak X) reported in some 5-HTP samples lacks credibility due to chromatographic artifacts and infinitesimal concentrations, and has raised undue speculations concerning its chemistry and toxicity. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004 Apr 15;150(1):111-22. ISSI Laboratories Inc., 515 Blue Ridge Avenue, Piscataway, NJ 08854, USA. Biochemistry of 5-HTP The figure below shows tryptophan converting into 5-HTP, which then readily converts into serotonin. Once serotonin is made, the pineal gland is able to convert it at night into melatonin, the sleep-inducing hormone. Vitamin B6 is involved in the process of serotonin formation. Tryptophan, 5-HTP, and melatonin are available for sale as supplements. Tryptophan* â 5-HTP â Serotonin â N-Acetyl-serotonin â Melatonin *Note: Tryptophan is also metabolized on a different pathway, not all of it is converted into 5-HTP. Figure 13.2 from the book Mind Boosters: Conversion of Tryptophan into 5-HTP, Serotonin and Melatonin. ==================================================================== Drug Interactions: 5-HTP (5-Hydroxytryptophan) --- 5-Hydroxytryptophan Also indexed as: 5-HTP Drug Interactions Certain medicines interact with 5-hydroxytryptophan: Some interactions may increase the need for 5-hydroxytryptophan (), other interactions may be negative () and indicate 5-hydroxytryptophan should not be taken without first speaking with your physician or pharmacist, others may require further explanation (). Refer to the individual drug article for specific details about an interaction. Note: the following list only includes the generic or class name of a medicine—to find a specific brand name, use the Safetychecker index. Carbidopa Carbidopa/Levodopa Fluoxetine Fluvoxamine Paroxetine Selegiline Sertraline Sibutramine Sumatriptan Tramadol Venlafaxine Zolmitriptan Zolpidem www.healthnotes.com --- JoAnn Guest mrsjo- DietaryTi- www.geocities.com/mrsjoguest/Genes AIM Barleygreen " Wisdom of the Past, Food of the Future " http://www.geocities.com/mrsjoguest/Diets.html The all-new My – Get yours free! Quote Link to comment Share on other sites More sharing options...
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