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5-HTP (5-hydroxytryptophan) and Tryptophan Tryptophan hydroxylase catalyzes the first rate-limiting step of serotonin biosynthesis by converting l-tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP is then converted into serotonin. Serotonin controls a variety of functions in the human body and brain. Inadequate serotonin effect also plays a major role in depression. Serotonin is also converted into melatonin in the pineal gland where it plays a major role in the human sleep cycle. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids. Therefore, it may be taken with meals without reducing its effectiveness. Unlike tryptophan, 5-HTP cannot be diverted into niacin or protein production. Also, the therapeutic use of 5-HTP bypasses the somewhat limiting conversion of tryptophan into 5-HTP by the enzyme tryptophan hydroxylase. Consequently, serotonin is more easily produced. 5-HTP is well absorbed from an oral dose, with about 70% ending up in the bloodstream. It easily crosses the blood-brain barrier and increases brain synthesis of serotonin and melatonin. In the brain, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behavior, and pain sensation. Preliminary research has found that 5-HTP might help a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia (Birdsall TC. Altern Med Rev. 1998 Aug;3(4):271-80). Serotonin (5-hydroxytyramine) precursor 5-HTP was of added benefit for depression in three small double-blind studies when added to an anti-depressant. In two more studies by itself, it did as well as an anti-depressant, but in a sixth study, it was of no value for SSRI failures. In a 7th study, it was inferior to an anti-depressant for anxiety disorders, but better than placebo. In yet another of the add-on studies, 5-HTP by itself was no better than placebo. In summary, 5-HTP appears to be of modest benefit with a lower level of side-effects than standard anti-depressants. However, since it works via a different mechanism than anti-depressant medications, it may help some patients who are medication resistant. At 100-400 mg/day, 5-HTP has been found in double blind studies to help headaches (Pediatr Med Chir. 1984 Mar-Apr;6(2):241-5; J Neurosurg Sci. 1985 Jul-Sep;29(3):239-48; Drugs Exp Clin Res. 1987;13(7):425-33) and in just one study for fibromyalgia (J Int Med Res. 1990 May-Jun;18(3):201-9). It failed to help headaches in one trial (Headache. 2000 Jun;40(6):451-6). One double-blind study found benefits for anxiety disorders. Its impact on obsessive-compulsive disorders is unknown. Night terrors in children also improved with a single night time dose of 5-HTP. 5-HTP can be purchased without a prescription for about $13 per month (100 mg three times a day) plus shipping from www.iHerb.com . It is not covered by insurance plans. 5-HTP is promoted in a book by Michael T. Murray as a treatment for depression, insomnia, and weight loss, but I have not read the book and am doubtful of its sticking to scientifically known facts. Its claims may be exaggerated. Tryptophan can be purchased most cheaply as a powder, costing 3 grams per dollar. Most studies use 2-3 grams per day. Since the body has many other uses for tryptophan, only a minority will be manufactured by the body into 5-HTP. Also, some depressives have genetic variants of tryptophan hydroxylase, making such manufacture more difficult. In view of the cost and the past history of problems with impurities in tryptophan, 5-HTP appears more sensible to use. However, the tryptophan research is included below, since its findings support the use of 5-HTP. Depression Equal to Fluvoxamine in DB: In a 6-week study of 63 people given either 5-HTP (100 mg 3 times daily) or fluvoxamine, 50 mg 3 times daily, 5-HTP had fewer and less severe side effects than fluvoxamine. The only real complaint was occasional mild digestive distress. Poldinger 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. 5-Hydroxytryptophan Promoted for Depression: 5-HTP is the intermediate between tryptophan and serotonin. It is readily absorbed and crosses the blood-brain barrier. It is promoted for depression, binge eating with obesity, fibromyagia, chronic headaches, and insomnia. Birdsall, Altern Med Rev 8/98;3:271. Caution: L-tryptophan was pulled off market in 1990 because of an impurity after 5,000 became sick with eosinophilia myalgia, an autoimmune inflammation of connective tissue, and 40 died. 5-HTP may have similar problems, although much, much less often since 5-HTP is made from plant sources as opposed to tryptophan, which was not. I have not found any reports of any deaths and only a few developing myalgia. Of course, all anti-depressants have some side-effects. 5-HTP No Value for SSRI Failures in Small Study: Non-responders to several reuptake inhibitors, including oxaprotiline and fluvoxamine. After four unsuccessful sleep-deprivations, L-5HTP or tranylcypromine was given during four weeks in a crossover design. Of 17 patients given L-5-HTP during both treatment periods, none responded, whereas of 26 patients treated with tranylcypromine, an MAO inhibitor, 15 responded. L-5HTP in depression resistant to re-uptake inhibitors. An open comparative study with tranylcypromine. Nolen WA, van de Putte JJ, et al. Br J Psychiatry 1985 Jul;147:16-22 Clomipramine better than 5-HTP which was better than Placebo for Anxiety: A 45-patient PC DB study of anxiety disorders found 5-HTP moderately effective for anxiety measured by HCL-90 and state-trait tests but didn't do as well on depressive symptoms as clomipramine. Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. Kahn RS, Westenberg HG, et al. University Hospital, Utrecht, The Netherlands. Int Clin Psychopharmacol. 1987 Jan;2(1):33-45 5-HTP plus Chlorimipramine better than Chlorimipramine Alone: A 4-week PC DB study of 26 depressed patients with all patients on chlorimipramine 50 mg/d with or without 5-HTP 300 mg/d. Treatment of depression with L-5-hydroxytryptophan combined with chlorimipramine, a double-blind study. Nardini M, De Stefano R, et al. Int J Clin Pharmacol Res. 1983;3(4):239-50 5-HTP plus MAO Inhibitor better than 5-HTP or Placebo: In a PC DB study of 58 depressed patients, those on l-deprenyl plus 5-HTP did significantly better than the other two groups which did not differ significantly. Antidepressant potentiation of 5-hydroxytryptophan by L-deprenil in affective illness. Mendlewicz J, Youdim MB. J Affect Disord. 1980 Jun;2(2):137-46 5-HTP Equals Imipramine in DB: In a small PC DB study with 30 depressed patients, 5-HTP plus benzerazide vs. imipramine showed no difference on a variety of depression measures. 5-HTP caused gastrointestinal side-effects. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Angst J, Woggon B, Schoepf J. Arch Psychiatr Nervenkr. 1977 Oct 11;224(2):175-86 5-HTP Added Benefit to MAO Inhibitor for Depression in DB: A PC DB study of 30 hospitalized patients with endogenous depression found that the group on the MAO inhibitor plus 5-HTP improved more quickly and more fully with less postural hypotension than the group on the MAO inhibitor plus placebo. 5-Hydroxytryptophan (5-HTP) and a MAOI (nialamide) in the treatment of depressions. A double-blind controlled study. Alino JJ, Gutierrez JL, Iglesias ML. Int Pharmacopsychiatry. 1976;11(1):8-15 Depression in Elderly Helped: In a DB PC 60-day study of 50 depressed elderly (mean age, 68), those given a combination containing 3 mg of dihydroergocristine and 100 mg of levo-5-hydroxytryptophan showed significant improvements in their depressive state and psychic performance, whereas no change was observed with placebo. Effects of a levo-5-hydroxytryptophan-dihydroergocristine combination on depression and neuropsychic performance: a double-blind placebo-controlled clinical trial in elderly patients. Rousseau JJ. Clin Ther. 1987;9(3):267-72 Meta-Analysis Concludes Limited Value for Depression: In a literature search, authors found 108 studies reporting using 5-HTP or tryptophan for depression. Only two of these which covered only 64 patients were of considered scientifically adequate scientific by the authors. They concluded that there is suggestive evidence that 5-HTP does help with depression, but that the quality of the research was too insufficient to be conclusive. Tryptophan and 5-hydroxytryptophan for depression. Shaw K, Turner J, Del Mar C. University of Queensland. Cochrane Database Syst Rev. 2002;(1):CD003198. Ed: Cochrane reviews tend to be very critical and quite a number of current medical and psychiatric treatments do not satisfy their reviewers. Abnormal Tryptophan Hydroxylase-2 Gene Found in 10% of Depressed: Researchers have found a (G1463A) single nucleotide polymorphism (SNP) in the gene for the rate-limiting enzyme of neuronal serotonin synthesis, human tryptophan hydroxylase-2 (hTPH2). The functional SNP in hTPH2 replaces the highly conserved Arg441 with His, which results in approximately 80% loss of function in serotonin production when hTPH2 is expressed in PC12 cells. SNP analysis of 87 patients with unipolar major depression revealed that nine patients carried the mutant (1463A) allele, while among 219 controls, only three did. The dysfunctional SNP was not found in 60 bipolar disorder patients. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Zhang X, Gainetdinov RR, et al. Duke University. Neuron. 2005 Jan 6;45(1):11-6. Ed: This study supports the use of 5-HTP for depression, since 5-HTP is the product manufactured by the body through the use of this gene. The body then make 5-HTP into serotonin. 5-HTP Synthesis and Metabolism: The amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan. Turner EH, et al. Oregon Health and Science University, Portland, OR. Pharmacol Ther. 2005 Jul 13 Other Psychiatric Conditions Alcoholism: No Benefit Found: In a 1-year, DB PC study of 31 alcoholics, no benefit was found comparing 5-HTP to L-dopa with both accompanied by carbidopa. Pharmacologic maintenance of abstinence in patients with alcoholism: no efficacy of 5-hydroxytryptophan or levodopa. George DT, Lindquist T, et al. NIH. Bethesda. Clin Pharmacol Ther. 1992 Nov;52(5):553-60 Anxiety Helped More by SSRI, But Some by 5-HTP: In a 45-patient DB PC study of 5-HTP vs. clomipramine for anxiety disorders (DSM-III), comipramine was shown to be effective in that it induced significant improvement on all rating scales as compared to placebo. 5-HTP showed a moderate reduction of the symptomatology on the 90-item symptoms checklist (SCL-90) and the State Scale of the Spielberger State-Trait Anxiety Inventory. Clomipramine and 5-HTP differed in their efficacy in that 5-HTP did not affect the associated depressive symptomatology. Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. Kahn RS, Westenberg HG, et al. University Hospital, Utrecht, The Netherlands. Int Clin Psychopharmacol. 1987 Jan;2(1):33-45 Night Terrors: 5-HTP Helped Night Terrors in Children: In a random assignment study of 45 children with night terrors, 93% of those assigned to 20 night of 5-HTP (2 mg/kg) showed improvement vs. 29% with placebo. After 6 months, 84% were still terror-free vs. 29% of controls. L -5-Hydroxytryptophan treatment of sleep terrors in children. Bruni O, Ferri R, Miano S, Verrillo E. University of Rome "La Sapienza", Via dei Sabelli 108, 00185 Rome, Italy. Eur J Pediatr. 2004 Jul;163(7):402-7. Ed: I may be wrong on how I read this study, but I think the 5-HTP was used only 20 days and not the entire 6 months. Panic Disorder: 5-HTP Might Help Panic Attacks: In a small DB PC study of 32 volunteers given a drug that induces panic attacks (cholecystokinin-tetrapeptide (CCK-4)), 200 mg of 5-HTP given 90 minutes before the CCK-4 showed a nonsignificant reduction in panic rate (19% after 5-HTP and 44% after placebo, p = 0.13) with a trend for lower intensity of symptoms after 5-HTP (p = 0.08). The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. Maron E, Toru I, Vasar V, Shlik J. University of Tartu, Estonia. J Psychopharmacol. 2004 Jun;18(2):194-9 Panic Disorder: 5-HTP Helped Panic Patients in Experiment: The reaction of 24 panic disorder patients and 24 healthy volunteers to a 35% carbon dioxide panic challenge was assessed following administration of 200-mg of 5-HTP or placebo. L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Schruers K, van Diest R, Overbeek T, Griez E. Maastricht University, The Netherlands. Psychiatry Res. 2002 Dec 30;113(3):237-43 Non-Psychiatric Disorders Fibromyalgia Reportedly Helped by 5-HTP: In a small 50-patient Italian DB PC study, authors claim that all the clinical parameters studied were significantly improved by treatment with 5-HTP and only mild and transient side-effects were reported. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V. Sacco Hospital, Milan, Italy. J Int Med Res. 1990 May-Jun;18(3):201-9 Fibromyalgia: 5-HTP with MAO Inhibitor Helped Fibromyalgia Better than Amitriptyline: In a DB PC study of fibromyalgia sufferers of a combination of monoamine-oxidase inhibitors (MAOIs) with 5-HTP, 5-HTP alone, MAOIs alone, or the tricyclic drug amitriptyline, the combination of MAOIs with 5-HTP significantly improved fibromyalgia as determined by Visual Analogic Scale whereas the other treatments yielded poorer benefits. No subject withdrew. In two cases, transient MAO induced hypertension was associated to very dramatic emotional events. The recently shown high prevalence of migraine in the population of fibromyalgia sufferers, suggests a common ground shared by fibromyalgia and migraine. Migraine has been demonstrated to be characterized by a defect in the serotonergic and adrenergic systems. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Nicolodi M, Sicuteri F. Florence, Italy. Adv Exp Med Biol. 1996;398:373-9 Headache: 5-HTP Slight Help for Tension Headaches: In a 78-patient, 8-week DB PC study of 5-HTP 300 mg/day, there was no statistically significant change in the number of days with headache or in headache intensity in the group treated with 5-HTP. There was a significant decrease in the consumption of analgesics. During the 2 weeks after treatment, there was a significant decrease in the number of days with headache. Subjective opinion during this latter period was also favorable to 5-HTP. Five patients dropped out (1 with placebo and 4 with 5-HTP), 1 was excluded due to noncompliance, and in 7 treatment was suspended due to adverse events (3 with placebo and 4 with 5-HTP). L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society. Ribeiro CA., University of Coimbra, Portugal. Headache. 2000 Jun;40(6):451-6. Ed: The triptan family of medication is the most common treatment for acute migraine. They are 5-HTP agonists, i.e., they tend to increase the 5-HTP effect. Headache: 5-HTP Some Benefit: In a DB PC trial of 39 migraine patients, after a placebo run-in of one month, the patients received either 5-hydroxytryptophan or propranolol for 4 months. The treatment with both substances resulted in a statistically significant reduction in frequency of migraine attacks. In the propranolol group the duration of the attacks and the number of analgesics used for treatment of the attacks were significantly reduced. Although propranolol, which is considered a reference for the interval treatment of migraine, is more effective, 5-hydroxytryptophan is a possible alternative for many patients. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine. Maissen CP, Ludin HP. Kantonsspital St. Gallen. Schweiz Med Wochenschr. 1991 Oct 26;121(43):1585-90 Obesity: 5-HTP Might Help Stress Induced Overeating: In rats, 5-HTP (3-200 mg/kg ip) suppressed food intake in a dose-dependent manner in both models, but was at least eight times more effective in the stress-hyperphagia model. 5-HTP may be useful in controlling the excessive food intake sometimes generated by stress, even if given without decarboxylase inhibitors or other drugs. 5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats. Amer A, Breu J, et al. Massachusetts College of Pharmacy and Health Sciences, Boston. Pharmacol Biochem Behav. 2004 Jan;77(1):137-43 Obesity: 5-HTP Might Increase Leptin by Increasing Insulin: 5-HTP increases leptin levels which are associated with a decrease in appetite. A mouse study found evidence that 5-HTP does this by increasing insulin levels which in turn increases leptin levels. Hyperleptinemia elicited by the 5-HT precursor, 5-hydroxytryptophan in mice: involvement of insulin. Yamada J, Sugimoto Y, et al. Kobe Pharmaceutical University, Japan. Life Sci. 2003 Sep 19;73(18):2335-44 Obesity: 5-HTP Helped Obese Diabetics in Very Short, Small Study: In obese patients, brain serotonergic stimulation via orally administered 5-hydroxy-tryptophan (5-HTP), the precursor of serotonin, causes decreased carbohydrate intake and weight loss. Diabetes mellitus is associated with depressed brain serotonin, hyperphagia and carbohydrate craving. 25 overweight non-insulin dependent diabetics in a 2-week DB PC study of 5-HTP (750 mg/d) or placebo with no dietary restriction had 20 patients (nine from the 5-HTP group and 11 from the Placebo group) complete the study. Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Cangiano C, Laviano A, et al, University of Rome La Sapienza, Italy. Int J Obes Relat Metab Disord. 1998 Jul;22(7):648-54 Overdose: 5-HTP Overdoses Possible: In a study of 21 dogs with accidental 5-HTP ingestion reported to the National Animal Poison Control Center, clinical signs of toxicosis developed in 19 of 21 (90%) dogs. Neurologic signs included seizures (9 dogs), depression (6), tremors (5), hyperesthesia (5), and ataxia (4). Gastrointestinal tract signs included vomiting or diarrhea (12 dogs), signs of abdominal pain (3), and hypersalivation (2). Other clinical signs were hyperthermia (7 dogs) and transient blindness (3). Three dogs died. The minimum toxic dose was 23.6 mg/kg (10.7 mg/lb), and the minimum lethal dose was 128 mg/kg (58.1 mg/lb). Onset of signs ranged from 10 minutes to 4 hours after ingestion, and signs lasted up to 36 hours. Of 17 dogs with clinical signs of toxicosis that received treatment, 16 recovered; treatment consisted of decontamination, seizure control, thermoregulation, fluid therapy, and supportive care. Ingestion of 5-HTP in dogs can result in a potentially life-threatening syndrome resembling serotonin syndrome in humans, which requires prompt and aggressive care. 5-Hydroxytryptophan toxicosis in dogs: 21 cases (1989-1999). Gwaltney-Brant SM, Albretsen JC, Khan SA. ASPCA National Animal Poison Control Center, Urbana, IL. J Am Vet Med Assoc. 2000 Jun 15;216(12):1937-40 5-HTP Helps Elderly Rat Spatial Learning; Serotonin Deficits May be Involved in Dementia: The cholinergic hypothesis of senile dementia does not provide a sufficient explanation for age-dependent spatial learning deficits; these are observed before an appreciable reduction of cholinergic markers can be detected. Behavioral deficits similar to those observed in old rats cannot be induced in young rats by comparable cholinergic lesions but do occur following combined cholinergic/serotonergic lesions. Serotonergic raphe grafts in the hippocampus (but not in the entorhinal cortex or hypothalamus) prevent such combined lesion-induced spatial learning deficits. The behavioral deficits are associated with a reduction of hippocampal commissure feed-forward inhibition. Similar reduced inhibition is found in old rats, deficient in their performance of a spatial learning water-maze task. Finally, treating old rats with the serotonergic precursor 5-hydroxytryptophan (5-HTP) reduces the age-dependent spatial learning deficits and restores hippocampal commissure feed-forward inhibition. Serotonin may act in parallel to the cholinergic innervation of the hippocampus by affecting inhibitory interneurons but in addition it may act by modulating acetylcholine release. Acetylcholine release is modulated by serotonin and the enhancing effects of serotonin releasing drugs on dentate granule cell excitability are mediated by acetylcholine. We thus propose that a reduction of serotonergic modulation of hippocampal interneuron activity and impaired modulation of cholinergic effects in the hippocampus contribute to age-dependent cognitive deficits. Serotonin, aging and cognitive functions of the hippocampus. Richter-Levin G, Segal M. University of Haifa, Israel. Rev Neurosci. 1996 Apr-Jun;7(2):103-13 Obesity: 5-HTP Reduced Food Intake in Diabetics: In a DB PC study of 25 overweight non-insulin dependent diabetics, 5-HTP (750 mg/d) for two consecutive weeks, during which no dietary restriction was prescribed significantly decreased daily energy intake, by reducing carbohydrate and fat intake, and reduced body weight. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Cangiano C, Laviano A, et al. University of Rome La Sapienza, Italy. Int J Obes Relat Metab Disord. 1998 Jul;22(7):648-54 Obesity: 5-HTP Claimed to Help Lose Weight in Three Studies: In a 5-week DB PC crossover study of 19 obese women, 5-HTP 8 mg/kg/day led to 3 pounds of weight loss although the women made no conscious effort to lose weight. Early satiety and decreased food intake were noted. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. Ceci F, Cangiano C, et al. University of Rome La Sapienza, Italy. Obesity: Weight Loss Greater with 5-HTP: A second 12-week study for the first six weeks gave 20 obese women no dietary recommendations. For the second six weeks, the women were placed on a 1,200-calorie diet. The women who took the placebo lost 2.3 pounds, while the women who took the 5-HTP lost 10.3 pounds. 5-HTP appeared to promote weight loss by promoting satiety-the feeling of satisfaction-leading to fewer calories being consumed at meals. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Cangiano C, Ceci F, et al. University of Rome, La Sapienza, Italy. Obesity: Yet Another Report: In a third study of similar design to the above, the group who received 5-HTP lost an average of 4.4 pounds at six weeks and an average of 11.6 pounds at 12 weeks. In comparison, the placebo group had lost an average of only 0.62 pounds at six weeks and 1.87 pounds at twelve weeks. Many of the women who received the 5-HTP (300 mg three times per day) reported mild nausea during the first six weeks of therapy. However, the symptom was never severe enough for any of the women to drop out of the study. No other side effects were reported." at www.doctormurray.com. Obesity: 5-HTP Increases Leptin, Decreasing Appetite: 5-hydroxytryptophan (5-HTP) increases serum leptin levels in mice. Administration of 5-HTP causes reduced eating in rodents and humans. This study found the effect caused by increased leptin. Biol Pharm Bull 2006 Mar;29(3):557-9. PMS: 5-HTP Trapping Ability Reduced in Brain: Premenstrual dysphoria can be treated by serotonin-augmenting drugs. In a study of 8 PMS women, worsening of mood symptoms showed significant inverse associations with changes in brain 5-HTP trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria. Eriksson O, et al. University Hospital, Uppsala, Sweden. Psychiatric Res 2006 Feb 28. B-6 Pyridoxine Increases 5-HTP Production in the Brain: Results from a rat study suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-HTP. Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain. Calderon-Guzman D, Hernandez-Islas JL, et al. Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico. Arch Med Res. 2004 Jul-Aug;35(4):271-4. Ed: The 5-HTP I give some of my depressed patients contains B-6. However, there is no research proving that B-6 helps depression. It may cause problems for older adults and more research is necessary. 5-HTP Hydroxyl Scavenger; Melatonin Precursor: Hydroxyl radicals are involved in direct damage of important biomolecules. Potent radical scavengers such as vitamin C and indoles of the tryptophan family can avert the potential damage. Melatonin and its precursor 5-hydroxytryptophan (5-HTP) were compared with water-soluble vitamin C. 5-HTP showed highest hydroxyl radical scavenging effects with a 50% inhibition concentration (IC(50)) of 1.8 mum. For vitamin C an IC(50) of 12.7 mum was measured, whereas melatonin was much less efficient (IC(50) = 724 mum). 5-Hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C. Keithahn C, Lerchl A. International University Bremen, Germany. J Pineal Res. 2005 Jan;38(1):62-6 Eosinophilia-Myalgia Syndrome from Contaminants: Eosinophilia-myalgia syndrome-like symptoms have been associated with ingestion or exposure to 5-HTP. A HPLC-UV analysis of EMS-implicated 5-HTP revealed the presence of peak X, described as case-implicated. These researchers report that peak X is actually a family of contaminants with the same molecular weight (234 Da) and similar HPLC retention times. They said that all eight samples of commercially available 5-HTP analyzed by HPLC-MS contained three or more contaminants of the peak X family. Mayo Clinic, Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan. Klarskov K, Johnson KL, et al. Adv Exp Med Biol 1999;467:461-8. Most Recent Research Says Serious Side-Effects Very Rare: The use of L-tryptophan (L-Trp) 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-Trp from a single manufacturer. 5-HTP has since become a popular dietary supplement in lieu of the removal of L-Trp from the market. Because of its chemical and biochemical relationship to L-Trp, 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-Trp, 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. Safety of 5-hydroxy-L-tryptophan. Das YT, Bagchi M, et al. ISSI Laboratories Inc., Piscataway, NJ. Toxicol Lett. 2004 Apr 15;150(1):111-22. Ed: Patients and physicians must be alert to possible side-effects. Drawing a CBC (complete blood count) should muscle soreness develop is wise. However, all anti-depressant medications have significant rates of side-effects and unresolved depression has a markedly elevated mortality rate, primarily from suicides and a doubling of the rate of heart attacks. Only a handful of cases of EMS have ever been reported with 5-HTP. The only mention of outcome which I have seen was that in two of the cases the symptoms resolved shortly after the medication was discontinued. Alpha-Lactalbumin Affects Memory: Depression is associated with reduced brain serotonin (5-hydroxytryptamine; 5-HT) function and with cognitive dysfunctions. A diet rich in alpha-lactalbumin protein increases the ratio tryptophan /large neutral amino acids, and to improve cognitive functioning in individuals with high neuroticism scores. In DB PC crossover study of 23 recovered depressed patients and 20 healthy controls, meals rich in alpha-lactalbumin vs. casein protein found alpha-lactalbumin protein had no effect on mood, but improved abstract visual memory and impaired simple motor performance. These effects were independent of history of depression. Diet rich in {alpha}-lactalbumin improves memory in unmedicated recovered depressed patients and matched controls. Booij L, et al. Leiden University, the Netherlands. J Psychopharmacol. 2005 Sep 20 Tryptophan Tryptophan Reportedly Helped Insomnia: Deoiled gourd seed (a rich source of tryptophan-22 mg tryptophan/1 g protein) was combined with glucose, a carbohydrate that reduces serum levels of competing LNAAs which was then compared to pharmaceutical grade tryptophan with carbohydrate as well as carbohydrate alone. In a 3-week DB PC study of 57 adults, protein source tryptophan with carbohydrate and pharmaceutical grade tryptophan, but not carbohydrate alone, resulted in significant improvement on subjective and objective measures of insomnia. Protein source tryptophan versus pharmaceutical grade tryptophan as an efficacious treatment for chronic insomnia. Hudson C, et al. Biosential Inc.,Toronto. . Nutr Neurosci. 2005 Apr;8(2):121-7 Tryptophan Caused Increased Morning Alertness and Improved Sleep: Brain uptake of the serotonin precursor tryptophan is dependent on nutrients that influence the availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp:LNAA). In a DB PC study of 14 mild insomniacs and 14 normals, evening consumption of alpha-lactalbumin protein with an enriched tryptophan content of 4.8 g/100 g caused a 130% increase in Trp:LNAA before bedtime (P = 0.0001) and modestly but significantly reduced sleepiness (P = 0.013) and improved brain-sustained attention processes (P = 0.002) the following morning. Only in poor sleepers was this accompanied by improved behavioral performance (P = 0.05). Evening intake of alpha-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention. Markus CR, et al. University of Maastricht, Netherlands. . Am J Clin Nutr. 2005 May;81(5):1026-33. Ed: Authors attribute the benefit to increasing serotonin via the conversion of tryptophan into 5-HTP to serotonin (and to melatonin). Tryptophan Helped Aggression: Serotonin decreases aggression, and increases affiliative and dominant behaviors in animals. In a 12-day DB PC cross-over study 100 healthy adults, when taking tryptophan (1 g after each meal), the adults had a significant decrease in quarrelsome behaviors and a significant increase in dominant behaviors. Tryptophan, serotonin and human social behavior. Moskowitz DS, et al. McGill University. . Adv Exp Med Biol. 2003;527:215-24. Same study: Neuropsychopharmacology. 2001 Aug;25(2):277-89. Obesity: Tryptophan Supplement Didn't Help Weight Loss: In a 3-week DB PC study of 50 women on a 1000 calorie per diet weight loss diet, those taking 1.8 g/day of tryptophan did no better. Psychol Med. 2003 Nov;33(8):1381-6. Obesity: Possible Effect: In a DB PC study of 20-40 obese women, increasing doses of tryptophan 1 hour before a meal decreased the number of calories consumed: 1188 (1 g); 1031 (2 g: p < 0.05) and 1016 (3g: p < 0.05) vs. 1294 calories for placebo. Eat Weight Disord. 1997 Dec;2(4):211-5. Tryptophan Depletion Causes Depression, Irritability: Studies show that acute tryptophan depletion (ATD), by administration of an amino acid drink lacking tryptophan, can produce clinically significant depressive symptoms in subjects who have recovered from major depression. This is more likely in female patients who have had suicidal ideation, recurrent depression, and treatment with specific serotonin reuptake inhibitors. Am J Geriatr Psychiatry. 2005 Jul;13(7):607-15. Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals. Psychopharmacology (Berl). 2002 Dec;164(4):385-91 Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder. Argyropoulos SV, et al. Psychopharmacology Unit, University of Bristol. Biol Psychiatry. 2004 Oct 1;56(7):503-9. Depression: Didn't Helped SSRI as Add-On: In a DB PC study, 2-4 g/day didn't add to the benefit of fluoxetine 20 mg/day except some possible 1st week acceleration of benefit. J Psychiatry Neurosci. 2000 Sep;25(4):337-46 Depression: Add-on Benefit to MAO Inhibitors: Work done in the 1960s and 1970s demonstrated that tryptophan has a robust augmenting effect when used with the older monoamine oxidase inhibitors. Coppen A, Shaw DM, Farrell JP. Potentiation of the antidepressant effect of monoamine oxidase inhibitors by tryptophan. Lancet 1963;79-81; Pare CMB. Potentiation of monoamine oxidase inhibitors by tryptophan. Lancet 1963;527-8; Glassman AH, Platman SR. Potentiation of a monoamine oxidase inhibitor by tryptophan. J Psychiatr Res 1969;7:83-8; Ayuso Gutierrez JL, Lopez-Ibor Alino JJ. Tryptophan and an MAOI (Nialamide) in the treatment of depression. Int Pharmacopsychiatry 1971;6:92-7. Depression: Tryptophan Helped Depression: In the largest study of tryptophan used with a tricyclic antidepressant, placebo was compared with amitriptyline alone, tryptophan (3 g per day) alone, and amitriptyline plus tryptophan in patients with mild to moderate depressive disorder in a 12-week, double-blind protocol. Based on Hamilton Depression Scale scores, the 3 active treatments were equivalent in their effect, and all significantly better than placebo. Other work suggests that tryptophan added to clomipramine may have beneficial effects. Thomson J, Rankin H, Ashcroft GW, Yates CM, McQueen JK,Cummings SW. The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. Psychol Med 1982;12:741-51. Depression: Sometimes Tryptophan Didn't Help: However, several negative studies of tryptophan augmentation of tricyclics have also been published: Wålinder J, Skott A, Carlsson A, Nagy A, Roos BE. Potentiation of the antidepressant action of clomipramine by tryptophan. Arch Gen Psychiatry 1976;33:1384-9. Hale AS, Procter AW, Bridges PK. Clomipramine, tryptophan and lithum in combination for resistant endogenous depression: seven case studies. Br J Psychiatry 1987;151:213-7; Shaw DM, MacSweeney DA, Hewland R, Johnson AL. Tricyclic antidepressants and tryptophan in unipolar depression. Psychol Med 1975;5:276-8; Lopez-Ibor Alino JJ, Ayuso Gutierrez JL, Montejo Iglasias ML. Tryptophan and amitriptyline in the treatment of depression: a double blind study. Int Pharmacopsychiatry 1973;8:145-51; Chouinard G, Young SN, Annable L, Sourkes TL. Tryptophannicotinamide, imipramine and their combination in depression. Acta Psychiatr Scand 1979;59:395-414. Tryptophan Hydroxylase Polymorphism Less Responsive to Citalopram, But Tryptophan Restored Responsiveness: Polymorphism of tryptophan hydroxylase is associated with less synthesis of brain 5-HT in DBA/2J and BALB/c than in C57BL/6J and 129/Sv mice. Using the forced swimming test, citalopram reduced immobility time in C57BL/6J and 129/Sv mice but had no such effect in DBA/2J and BALB/c mice. The drug reduced accumulation of 5-hydroxytryptophan (5-HTP), an indicator of 5-HT synthesis, in C57BL/6J and 129/Sv mice but much less in DBA/2J and BALB/c mice. Pretreatment with tryptophan raised 5-HTP accumulation and reinstated the antidepressant-like effect of citalopram in DBA/2J and BALB/c mice, whereas pharmacological inhibition of 5-HT synthesis prevented the effect of citalopram in C57BL/6J and 129/Sv mice. L-Tyrosine No Benefit from L-Tyrosine in DB: 65 patients with Major Depression Disorder were treated in a 4 week DB PC study with 100 mg/kg/d L-tyrosine vs. imipramine 2.5 mg/kg/d or placebo. Univ. Ariz. Tyrosine for depression: a double-blind trial. Gelenberg AJ, Wojcik JD, et al. J Affect Disord. 1990 Jun;19(2):125-32 |