Tryptophan Supplement for Sleep

8/6/2019 Tryptophan Supplement for Sleep

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Tryptophan supplement for sleep, mood, and stress by Ray Sahelian, M.D. Areview of benefits and side effects, safety, risks

L Tryptophan is an essential amino acid found in foods that contain protein suchas turkey. It is able to convert into 5-HTP (5-hydroxy-tryptophan), and then to

serotonin. Serotonin is involved in mood, appetite, sleep and impulse control. Ifyou wish to reduce your appetite effectively and lose weight, consider an allnatural herbal product that I have formulated called Diet Rx.

MetabolismThe figure below shows l-tryptophan converting into 5-HTP, which then readilyconverts into serotonin. Once serotonin is made, the pineal gland is able toconvert it at night into melatonin, the sleep-inducing hormone.

L-Tryptophan --> 5-Hydroxytryptophan 5-HTP --> Serotonin --> N-Acetyl-serotonin--> Melatonin

Vitamin B6 is involved in the metabolism of tryptophan to serotonin. Note: L-Tryptophan is also metabolized to a different pathway, not all of it is convertedinto 5-HTP.

L-Tryptophan supplement, 500mg each pill by FTH NutraceuticalsUSP Pharmaceutical GradeTryptophan sourcePURE L Tryptophan amino acid, thisproduct, as determined by aCertificate of Analysis, is the highest

grade available, over 99% Pure.

Tryptophan is formed by afermentation process in alab. FTH Tryptophan is USP

pharmaceutical grade, which requires a minimum of 98.5% purity.

Click here to learn more about this Tryptophan product, Mind Power Rxfor brain enhancer, Diet Rx for appetite suppression, Good Night Rx for

deeper sleep, Eyesight Rx for clearer vision, Mind Power Rx brainenhancer, or to sign up to a FREE newsletterSubscribe to a FREE Supplement Research Update newsletter. Once or twice amonth you will receive an email with a review of several studies on supplementsand natural medicine topics. We discuss natural ways to treat depression, reduceappetite, improve mood, sleep better, and reduce anxiety.


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L-Tryptophan - 500 mg each pill

Suggested use: Take one tryptophan capsule in the evening, preferably on anempty stomach, or as recommended by your health care provider.

NOTE: There are some companies selling tryptophan for very cheap. They mayuse a low quality source or mix it with 5-HTP. This tryptophan source is of thehighest quality and purity and possibly the best raw material source available.

Mind Power Rx - formulated by Ray Sahelian, M.D.

This mind and mood enhancing product is a sophisticated cognitiveformula with a dozen herbs and nutrients. It combines a delicatebalance of brain circulation agents and neurotransmitter precursorswith powerful natural brain chemicals that support healthy:

Memory and MoodMental clarityConcentration

Alertness & Focus

Why use all the individual herbs and nutrients separately -- at great expense --when you can take this excellent combination? The herbs in Mind Power Rxinclude: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba herb, Ginseng herb,Mucuna pruriens, and Reishi. The nutrients and vitamins in Mind Power Rxinclude Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol,Methylcobalamin, Trimethylglycine, Tyrosine, and Vinpocetine.

An Alternative to Tryptophan pills5-HTP is also available over the counter. 5-HTP is extracted from griffonia seeds,which come from an African shrub-tree grown in Ghana and the Ivory Coast.There are several European pharmaceutical companies that extract 5-HTP fromthese seeds. For a complete discussion of the clinical uses of 5-HTP, cautions,side effects, and how to combine it with other nutrients to support mood, see the5-HTP link above.

Benefits

AnxietyCan tryptophan be of benefit for anxiety and panic disorder related symptoms?

Some people find this amino acid supplement to be useful for anxiety reduction,however, how well it helps to reduce panic disorder is still not clear.

Weight lossThe anorectic effect of increasing doses of L-tryptophan in obese patients.


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Eat Weight Disord. 1997 Dec;2(4):211-5.Treatments that raise the level of tryptophan in the brain can rapidly alter the rateat which it is converted to serotonin. This paper compares the effect of 1, 2 and 3g L-tryptophan administered 1 h before a plated meal on total food intake andcarbohydrate and protein consumption in 10 obese subjects versus a lactose

placebo in another 10 obese subjects. There was a progressive decrease incarbohydrate consumption in function of the tryptophan dose. These resultsprovide further support for the view that serotoninergic mechanisms play a rolein the regulation of human food intake.

DosageWhat is generally the dose of tryptophan that is taken to see the positive effects?

Most people find 500 mg or 1000 mg taken in the evening to be helpful.

I have trouble swallowing pills, can the capsules be opened and the contentsadded to yogurt or juice?

This product works better when taken on an empty stomach, so the contentscan be mixed with water or small amount of juice and preferably without yogurt orfood.

The unfortunate history of L Tryptophan, safety and risks, caution and danger inpastDuring the 1980s, consumers were using tryptophan for sleep and as anantidepressant. Tryptophan was available without a prescription until 1989 whenthe FDA prohibited its over-the-counter sale because a manufacturer in Japanshipped a contaminated batch to the U.S. This caused a serious illness calledeosinophilia myalgia syndrome in about 1,000 individuals with serious l-tryptophan side effects.

Around 1995, tryptophan gradually became available by prescription throughcompounding pharmacies, and then since about the year 2000 tryptophan slowlyand cautiously was placed on the over the counter market through a few smallvitamin companies. Few large vitamin companies are selling tryptophan at thistime (2007).

Tryptophan side effects, caution, safety, toxicityA common tryptophan side effect from high dose use is drowsiness so it may bea good idea to take this amino acid supplement in the evening and not whiledriving or operating heavy machinery. Dry mouth is a less common tryptophanside effect. Other less common l-tryptophan side effects include nausea,dizziness, and loss of appetite.

A beneficial l-tryptophan side effect is drowsiness since that is the desiredeffect of many users who take this supplement for sleep. It is very rare for atryptophan side effect to lead to confusion or disorientation.

I read on a website that patients with asthma or systemic lupus erythematosusshould not take tryptophan supplements, why is this?


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I have not seen any studies regarding the interaction of this amino acidsupplement and airway disease such as asthma or an autoimmune conditionsuch as lupus. However, there is a possibility that elevating serotonin levels maytrigger airway disease. I will await the results of studies focusing on this issuebefore coming to a firmer conclusion. A search on Medline for "tryptophan

asthma" and "tryptophan autoimmune or lupus" reveals no human clinical trials.

I have taken tryptophan some time ago, and it caused me to have nightmares. Isthis common?

Yes, melatonin, 5-HTP and the amino acid supplement are known to makedreams more vivid.

Interaction with SSRI medications used for depressionCan tryptophan be dangerous with low or moderate dose of SSRI drugs such asProzac or Zoloft or Paxil. I would take it only under my doctors supervision. I justwanted your opinion.

When taken in low dosages of 200 to 500 mg, most people are not likely to haveany major untoward effects when combined with low dosages of SSRIantidepressants. However, each case is unique and some people may be verysensitive to such combinations.

Tryptophan and behaviorSocial behaviour and mood in everyday life: the effects of tryptophan inquarrelsome individuals.J Psychiatry Neurosci. 2006 July. aan het Rot M, Moskowitz DS, Pinard G, Young SN.Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal,Quebec.

We hypothesized that increasing brain serotonin in healthy individuals with highscores on 2 self-report measures of trait quarrelsomeness would reducequarrelsome behaviours and enhance agreeable behaviours when measuredecologically using an event-contingent recording method. We conducted adouble-blind crossover study, in which participants took tryptophan at 3 grams aday and placebo for 15 days each and recorded how they behaved, felt andperceived others during everyday social interactions. Tryptophan supplementuse significantly decreased quarrelsome behaviours and increased agreeablebehaviours and perceptions of agreeableness. Men also behaved less dominantly,whereas both men and women perceived others as more dominant. Tryptophan'seffects on behaviours and perceptions, while more marked in the men, weregenerally positive and accompanied by improved affect. Increasing serotonin inquarrelsome people may not only reduce behaviours associated with apredisposition to various mental and physical disorders but also enhancesocially constructive behaviours and improve social perceptions.

Tryptophan, turkey, and sleep, food contentDoes eating turkey make a person sleepy due to the tryptophan in turkey meat?Would eating foods high in tryptophan induce sleep?


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Turkey has an amino acid called tryptophan that is involved in sleep and moodbalance. However, turkey has no more tryptophan than chicken or beef. Thecause of sleepiness at Thanksgiving is more likely due to consuming lots of foodand drink rather than the tryptophan content in turkey. When this amino acid isingested as part of a protein food, there are a number of additional amino acids in

the protein that compete with crossing the blood brain barrier. Hence, taking asupplement is much more direct and effective than trying to consume this aminoacid through food or turkey.

Combination with St. John's wortIs St John's wort herb okay to take with tryptophan pill? I read these interact.

Much depends on the dosage used and the person taking them. It is best tolearn how each one works by itself before combining. Some people take the St.John's wort in the morning and the tryptophan pill in the evening. Use lowdosages at first to know how your body reacts.

Tryptophan Research studiesEffect of orally administered L-tryptophan on serotonin, melatonin, and the innateimmune response in the rat.Mol Cell Biochem. 2004 December.To assess the effects of external administration of L- tryptophan on the synthesisof serotonin and melatonin as well as on the immune function of Wistar rats, 300mg of the amino acid were administered either during daylight (08:00) or at night(20:00) for 5 days. Brain, plasma, and peritoneal macrophage samples werecollected 4 h after the administration. The accumulation of 5-hydroxytryptophan( 5HTP ) after decarboxylase inhibition was used to measure the rate oftryptophan hydroxylation in vivo. The results showed a diurnal increase in thebrain 5HTP, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindolacetic acid(5-HIAA) of the animals which had received tryptophan at 08:00 and were killed 4h later. In the animals which received tryptophan during the dark period, the 5-HTdeclined but the 5-HT/5-HIAA ratio remained unchanged. There was also asignificant increase in nocturnal circulating melatonin levels. The resultsindicated that the synthesis of serotonin and melatonin, as well as the innateimmune response, can be modulated by oral ingestion of tryptophan.

Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain.

Arch Med Res. 2004 Jul-Aug.The aim of this study was to evaluate effects of pyridoxine and butylatedhydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxy-tryptophan and serotonin. Thirty rats (30 days of age) were used in the survey,measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxytryptophan, and serotonin (5-HT) after intraperitoneal injections of pyridoxine HClduring 20 days and a single dose of BHT. Levels of TBARS and 5-HTP increasedconsiderably in all vitamin- and/or BHT-treated groups, and serotonin increasedpartially only in B(6) with or without BHT-treated groups compared with control


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Tryptophan degradation into kynurenine (KYN) during immune activation maycontribute to development of depressive symptoms during interferon (IFN)-alphatherapy. Twenty-six patients with malignant melanoma were randomly assignedin double-blind fashion to receive either placebo or paroxetine, beginning 2weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-

alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alphatreatment, measurements of tryptophan, KYN, and neopterin (a marker of immuneactivation), were obtained, along with structured assessments of depression,anxiety, and neurotoxicity. Among antidepressant-free patients, patients whodeveloped major depression exhibited significantly greater increases in KYN andneopterin concentrations and more prolonged decreases in tryptophanconcentrations than did nondepressed, antidepressant-free patients. Moreover, inantidepressant-free patients, decreases in tryptophan correlated with depressive,anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms.The results suggest that reduced tryptophan availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or

neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated tryptophan depletion.

Acute administration of nutritionally sourced tryptophan increases fearrecognition.Psychopharmacology (Berl). 2003 Aug;169(1):104-7.The serotonin precursor tryptophan has been widely used as a nutritionalsupplement and antidepressant. Recently, however, the use of tryptophan hasbeen severely restricted due to its association with the eosinophilic myalgicsyndrome, an autoimmune disorder probably caused by ingestion of acontaminant produced in certain tryptophan manufacturing processes. Todetermine the bioavailability of a nutritional source of tryptophan obtained frommilk protein and to assess whether administration of this material producedneuroendocrine and neuropsychological effects consistent with increased brainserotonin activity. We studied 24 healthy subjects who ingested approximately1.8 g of nutritionally-sourced tryptophan or placebo in a double-blind, parallelgroup, design. We carried out venous sampling for amino acid and hormoneestimation and performed a test of emotional processing using a facialexpression recognition task. The nutritionally-sourced tryptophan caused asubstantial increase in the availability of tryptophan in plasma. Relative toplacebo the tryptophan material produced some evidence of an increase inplasma cortisol, and enhanced the perception of fearful and happy facialexpressions. A nutritional source of tryptophan increased the availability oftryptophan for brain serotonin synthesis and produced endocrine andneuropsychological changes consistent with increased brain serotonin function.The effect of tryptophan on emotional processing may be relevant to its reportedactivity in primate studies of social behaviour.

Lowering of serotonin by rapid tryptophan depletion increases impulsiveness innormal individuals.


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Psychopharmacology (Berl). 2002 Dec;164(4):385-91. Epub 2002 Oct 12.Reduced serotonergic activity has been associated with impulsive behavior;however, intervention studies have been scarce. To examine whether inducedlowering of serotonin (5-HT) levels would increase behavioral measures ofimpulsivity. Twenty-four healthy young males ingested a mixture of the essential

amino acids except for tryptophan in a balanced, randomized, double-blind,placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophanwas expected to be at the lowest point. The plasma concentrations of 23 aminoacids were measured at baseline and 5 h after the ingestion of the amino acidmixture. The intervention led to a dramatic fall in free and total plasma tryptophan,and the tryptophan /large neutral amino acids ratio. This in turn has been shownto lower the level of 5-HT in the central nervous system. The tryptophan depletionresulted in a statistically significant more impulsive- or disinhibited responsestyle on the continuous-performance test-identical pairs when the subjects weresolving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer

correct responses and a decreased ability to discriminate between stimuli. Theseresults indicate that a rapid lowering of tryptophan increases impulsiveness anddecreases discriminating ability in normal individuals. The effect of 5-HTdepletion on discriminating ability in this study was similar to that previouslyreported in depressed patients.

Effects of a novel method of acute tryptophan depletion on plasma tryptophanand cognitive performance in healthy volunteers.Psychopharmacology (Berl). 2004 Jul 22Disorders associated with low levels of serotonin (5-HT) are characterized bymood and cognitive disturbances. Acute tryptophan depletion is an establishedmethod for lowering 5-HT levels and an important tool to study the effects ofreduced 5-HT on mood and cognition in human subjects. The University ofMaastricht developed a new and inexpensive method for acute tryptophandepletion: a natural collagen protein (CP) mixture with low tryptophan content.The reductions in plasma trypotophan after taking this CP mixture werecompared with the reductions achieved taking the traditional AA mixture, andeffects on memory and reversal learning were studied. Fifteen healthy youngvolunteers participated in a double-blind, counterbalanced within-subject study.Reversal learning, verbal memory and pattern recognition were assessed atbaseline and 3-4 h after taking the CP mixture. The new acute tryptophandepletion method significantly reduced plasma tryptophan by 74% and the ratiobetween tryptophan and the other large AAs by 82%. The placebo mixture did notchange these measures. Delayed recognition reaction time on the verbal learningtask was increased following acute tryptophan depletion. No other cognitiveeffects were found. The CP mixture was shown to be an efficient tool for loweringplasma tryptophan in humans. The validity of this method with regard tobehavioral changes remains to be established in healthy, vulnerable and clinicalpopulations.


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An evening milkshake spiked with the amino acid tryptophan may help clear themorning mental fog of the sleep-deprived, preliminary research suggests. In astudy of 28 healthy young adults, researchers found that accompanying anevening meal with a milkshake containing a protein powder called alpha-lactalbumin -- which delivers a high concentration of tryptophan -- seemed to

improve morning alertness among participants who had mild sleep problems."Good" sleepers, on the other hand, showed no such benefit. Alpha-lactalbumin,or A-LAC, is a protein derived from the whey component of milk. It contains ahigh concentration of the essential amino acid tryptophan, a protein building-block best known for its sleep-inducing effects. In the body, tryptophan serves asa precursor for the brain chemical serotonin, which, among other things, isthought to help regulate sleep. Tryptophan is found in foods such as beef,chicken, dairy products and, most famously, turkey -- which is often blamed forthe near-coma that follows Thanksgiving dinner. In reality, however, the relativelylow concentration of tryptophan in turkey and other foods is unlikely to affect thebrain because it must compete with other amino acids and nutrients for

absorption. In their study, Markus and his colleagues examined whether an A-LAC protein powder, with its high concentration of tryptophan, could increase theratio of tryptophan to other amino acids in participants' blood -- and whetherthere would be any difference in their mental alertness the next morning. Theprotein powder, marketed as BioPure, was supplied by Eden Prairie, Minnesota-based Davisco Foods International. Fourteen men and women with mild sleepproblems, and 14 others without sleep complaints took part in two experimentson separate evenings -- one in which they consumed a tryptophan -fortifiedmilkshake with dinner and later for a snack, and one in which they had "placebo"milkshakes that did not contain the A-LAC supplement. The next morning,participants took a computerized test that measured their mental reaction times,while electrodes placed on their scalps recorded their brain activity. Markus andhis colleagues found that participants' blood levels of tryptophan were more thantwice as high on the night they dined on the supplemented milkshakes comparedwith the placebo milkshakes. More importantly, men and women who normallyhad sleep problems performed better on the mental-alertness test on the morningafter having the tryptophan containing milkshakes. On the other hand, tryptophanmade no difference to the performance of the 14 participants with no sleepproblems. American Journal of Clinical Nutrition, May 2005.

Tryptophan taken orally can convert into serotonin and melatoninTryptophan is an amino acid available in food. A few years ago tryptophanreappeared on the market as an over the counter supplement. It's biochemistry isfascinating and quite important. It has been known for some time that in the bodyand brain, tryptophan gets converted into 5-hydroxy-tryptophan (5-HTP) whichthen converts into serotonin, a crucial brain chemical involved in mood, appetite,impulse control and sleep. Serotonin, in turn, is able to convert at night intomelatonin. To confirm this knowledge, tryptophan was given to a group of rats at8 am in the morning, and to another group of rats at 8 PM at night. Four hoursafter administration, researchers measured the blood and brain fluid levels of


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serotonin and melatonin. During daytime administration, tryptophan raised thelevels of serotonin. Interestingly, when tryptophan was given at night, serotoninlevels did not increase, but melatonin levels increased significantly. Therefore,the serotonin that was generated by tryptophan administration was beingconverted into melatonin. Another study I came across in the January 2005 issue

of theJournal of Pineal Research

indicates that 5-HTP is a more potentantioxidant than Vitamin C.My comments: First, this study confirms again that levels of 5-HTP, serotonin,

and melatonin can be influenced by supplements. Second, it shows that thetiming of a supplement can make a difference on how it is metabolized. Sincetryptophan, 5-HTP, and melatonin are available as supplements, I have had manyquestions over the years asking which one is best to take for depression, sleep,anxiety, or appetite control. This is difficult to answer since each person has adifferent biochemistry and would respond differently. The most reliable way tofind out is by trial and error. There's really no practical blood study that can bedone to determine which supplement someone will respond to, and in what

dosage. As a rule, melatonin is most helpful for sleep and does not have a stronginfluence on mood or appetite. 5-HTP has a strong influence on mood, appetiteand anxiety. Tryptophan has been used for depression and sleep.

L Tryptophan supplement emailsQ. My doctor tried me on 5-HTP, but it made me overwhelmingly sleepy. He thentried tryptophan, to which I am responding with more energy, mental clarity, anda decrease of carbohydrate cravings. Since I thought 5-HTP was "downstream"from tryptophan on the way to becoming serotonin, what would cause thisreaction?

A. There are several factors that could be involved, dosage, timing, with orwithout food, etc. Also, tryptophan does not completely metabolize into 5-HTP,some of it is channeled in different metabolic pathways. You may try to see if alower dose of 5-HTP reduces sleepiness.

A few weeks ago I had emailed you regarding bad side effects of excessivemenstrual bleeding, poor control of depression when I added 5-htp andtryptophan to my Effexor treatment. I spoke to the School of Pharmacy at mylocal university and they advised that my heavy bleeding would have beencaused by taking 5HTP, Tryptophan AND Effexor. They said this combination wastoo much and that I shouldn't be taking all 3. They said if I wanted to take either5HTP or Tryptophan with Effexor, Tryptophan seems to have the best results forboosting depressive symptoms. Since I have been doing this my period thismonth is fine and my depression is wonderful. Seems Tryptophan with Effexor isbetter than 5HTP with Effexor for me. I'm only on low doses of both to avoidexcess serotonin though - 500 mg Tryptophan and 75 mg Effexor / day. Justwanted to let you know that your product is in fact very good but I was not usingit in the right manner or amount. It's often a matter of trial and error but thoughtthis info may help somebody else. I don't wish my name to be made publicthough if you choose to use this info. Thanks for your time and a best tryptophan


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product.

Dear Dr. Sahelian, Thank you for your informative web site. I saw your responseon your web site about stopping the tryptophan frequently, and need more info:What happens if you don't stop periodically? How long should tryptophan be

taken before stopping? How long should it be stopped for? I have never been toldthis before and wonder if that is why the tryptophan has stopped working for me?As with many supplements, particularly amino acids, somehow the body and

brain get used to the effects, so that is one reason to take breaks. Another reasonis that we don't know too well what the long term effects are of taking a particularamino acid in high amounts. They may be beneficial, or harmful. As to thefrequency of breaks or length of a break from tryptophan, this depends on eachperson and their individual physiology, but as a rough guideline a week off permonth seems reasonable.

Q. I have experienced the worst 8 months of my life thanks to my first extreme

bout of depression and anxiety at 38. I have been unable to tolerate a number ofSSRIs so I tried Kira the German St John's Wort prescription. I am significantlybetter, however, I never quite went back to normal. Because on five pills a day,under my doctors supervision, I have experienced some side effects - electricalshocks in my hands and feet when cool and thick, tingling sensations in my brain.It is all worth it though! Could I perhaps decrease my dose and increase mydietary intake of tryptophan? Could you please give a reliable web site that liststryptophan content of foods. I have searched and searched and found them all tobe different. Perhaps there is a good book that has nutritional content oftryptophan listed.

A. Tryptophan is found in foods that contain protein, however, since thesefoods also have other amino acids, they all compete to get in the brain and thetryptophan is not able to overwhelm the others to get in. Trying to increase braintryptophan levels specifically through foods is not the best way to go. The bestoption to increase brain tryptophan levels is to take tryptophan pills or, since thereal goal is to increase serotonin levels, taking 5-HTP is another option.

Q. Why don't they sell serotonin pills?A. Serotonin is not able to easily cross the blood brain barrier, hence either

tryptophan or 5-hydroxy-trytophan are good options since they convert intoserotonin after going into the brain.

Q. Is tryptophan helpful fordepression?A. Some people who have a shortage of serotonin may benefit from it for

depression, others may be helped by St. John's wort, still others by 5-HTP orSAM-e or pharmaceutical drugs.

Q. I understand tryptophan is found in turkey. What other food source have it?A. Any food with protein will have tryptophan, and turkey, meat, chicken, fish,

dairy, eggs, all have this substance.


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Q. Is l tryptophan powder available for sale?Yes, l tryptophan powder is sold, but it is difficult to make an accurate

measurement of the appropriate dosage. I prefer use a tryptophan capsule andknow exactly how much I'm taking.

Q. How does tryptophan compare to 5-HTP as far as sleep?A. This is a good question. Some people prefer tryptophan for sleep whileothers prefer 5thp, and still others prefer melatonin. The best way to find out is totry each product by itself for 2 nights in a row with a break for 2 or 3 nightsbetween each supplement trial.

Q. Can you get enough tryptophan from food to fight depression?A. I don't think so. Tryptophan is needed by itself in the blood stream to easily

cross the blood brain barrier and enter the brain and convert into serotonin.While tryptophan is found in food such as meat and poultry, there are tons ofother amino acids present in these foods that would interefere with the pure

tryptophan effect needed to fight depression.

Q. Thanks for your informative website on alternative medical treatments. I feelthat it's very informative and helpful in deciding the pros and cons of varioustreatments without the emotional "hype" that seems to be common to otheralternative treatment websites. I recently read that tryptophan supplementationcould have a carcinogenic effect on the liver, and for this reason, 5htp is a bettertreatment option to increase serotonin levels in the brain.

A. We have not seen any reports that tryptophan use leads to harm to the liver.

Q. I am a freelance journalist from Sweden. I am doing research on 5-Htp and L

Tryptophan and had a few questions that I hope you might have the answers to. Ihave a lot of information about these products, but I get mixed information fromdifferent doctors. When you have a chance, please let me know what you thinkabout the following questions:1. Are 5-HTP and tryptophan safe before and during pregnancy?2. Which of these two products are most effective to raise seratonin levels?3. How can you know that you will get good 5-Htp or tryptophan product whenthere are so many products on the market?4. How does these products compare with some of the "normal" medicines fordepressions. Is the effect the same?

A. 1. 5-HTP and tryptophan supplements have not been adequately testedduring pregnancy and for the time being we suggest not using them unlessabsolutely required. 2. 5-HTP has a more direct influence on serotonin thantryptophan. Tryptophan converts into 5-HTP which converts into serotonin. 3. It isnearly impossible for the consumer to know which product is good unless theyhave it tested themselves in a testing laboratory. 4. Some people respond tonatural supplements better, others respond better to pharmaceuticalantidepressants. For mild to moderate depression, without suicidal tendencies,we suggest using the natural options first.


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I am a chronic sufferer of insomnia. Years ago I tried tryptophan and it was veryeffective in making sleepy and keeping asleep through the night.However, after a few days I started getting stomach cramps and I discontinueduse. Are stomach cramps possible from tryptophan use?

5-HTP causes stomach cramps more frequently than tryptophan, but tryptophan

can cause GI symptoms, too. Lowering the dose could be of help or taking it witha small amount of food.

Please tell me why there is neither tryptophan nor 5HTP in Mind Power Rx, if bothtryptophan and 5HTP help with mood.

5-HTP and tryptophan can cause sedation in many people and Mind Power Rx ifformulated to enhance mental alertness and concentration.

Would like to know the conversion ratio for L-Tryptophan to 5-HTP please. I havebeen told anywhere from 5-1 to 10-1.

Tryptophan hydroxylase is the rate-limiting enzyme for serotonin production

and involves the conversion of tryptophan to 5-HTP. The activity of this enzymevaries among individuals and can be influenced by a number of factors.Tryptophan is also metabolized to a different pathway, not all of it is convertedinto 5-HTP. Therefore it is difficult to give a precise number for the conversionratio since it can vary significantly among different individuals and may beaffected within the same person by a number of factors including diet, time of day,stress, medications, etc. But a rate of 5 to 1 or 10 to 1 seems reasonable since 50mg of 5-HTP often has a similar affect as 500 mg of tryptophan in most people.

If tryptophan converts to melatonin, then why not start with melatonin in the firstplace? I successfully manage my depression with Sam E (200mg once a week),

but have been having some trouble with sleep recently. If I use tryptophan withSam E, will I risk too much seratonin? Maybe I should go straight to melatonin?The effects of tryptophan slightly overlap with those of melatonin but they are

not the same. There are no easy answers in regards to combining supplementssince much depends on the dosage used, the timing of the supplements, and theindividual person's overall health and biochemistry.

I am a medical doctor. I wrote you a while back about my sleep disorders. RLS,PLMD, no deep sleep, REM sleep disorder. I believe I had asked about l-tryptophan and deep sleep. I have been on a "cocktail" of Clonazepam, Flexeril,and Vicodin for the RLS for many years (Vicodin added later). Not an optimalcombination, but it is what has worked for me. Recently I began having RLSduring the day. I recall taking the l-tryptophan before it was banned, but do notremember why. I just know it helped. I decided to try the l-tryptophan again, asmy sleep neurologist wishes to put me on an orphan drug, Xyrem. The Xyremwould help the deep sleep. I am a little apprehensive. We have tried the dopamineagonists, Lyrica, Gabapentin, all of them. Too many side effects. Not to mentionthat the neurologist scoffs at such non-pharmaceutical treatments. The l-tryptophan has a quick onset, but seems to only be effective for a couple of hours.


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As I know of long acting amino acids like l-arginine, I tried to find such a form ofthe l-tryptophan and could not come up with anything. I take it with juice (carb) assuggested, along with magnesium and chromium picolinate. Are you aware ofsome sort of long acting l-tryptophan supplement?

I am not aware of long acting tryptophan supplements.

Some people misspell this amino acid as tryptophane or triptophan


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Function

Metabolism of L-tryptophan into serotonin and melatonin (left) and niacin (right). Transformedfunctional groups after each chemical reaction are highlighted in red.

For many organisms (including humans), tryptophan is an essential amino acid. This means that

it cannot be synthesized by the organism and therefore must be part of its diet. Amino acids,including tryptophan, act as building blocks inprotein biosynthesis. In addition, tryptophan

functions as a biochemicalprecursorfor the following compounds (see also figure to the right):

y Serotonin (a neurotransmitter), synthesized via tryptophan hydroxylase.[9][10]Serotonin,

in turn, can be converted to melatonin (a neurohormone), viaN-acetyltransferase and 5-

hydroxyindole-O-methyltransferase activities.[11]

y Niacin is synthesized from tryptophan via kynurenine and quinolinic acids as key

biosynthetic intermediates.[12]

y Auxin (aphytohormone) when sieve tube elements undergo apoptosis tryptophan is

converted to auxins.[13]


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The disorders fructose malabsorption and lactose intolerance causes improper absorption oftryptophan in the intestine, reduced levels of tryptophan in the blood

[14]and depression.

[15]

In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a repressor

protein, which binds to the trp operon.[16]

Binding of this repressor to the tryptophan operon

prevents transcription of downstream DNA that codes for the enzymes involved in thebiosynthesis of tryptophan. So high levels of tryptophan prevent tryptophan synthesis through anegative feedback loop and, when the cell's tryptophan levels are reduced, transcription from the

trp operon resumes. The genetic organisation of the trp operon thus permits tightly regulated andrapid responses to changes in the cell's internal and external tryptophan levels.

[edit] Dietary sources

Tryptophan is a routine constituent of most protein-based foods or dietary proteins. It isparticularly plentiful in chocolate, oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs,

fish,poultry, sesame, chickpeas, sunflower seeds,pumpkin seeds, spirulina, andpeanuts.[17]

Despite popular belief that turkey has a particularly high amount of tryptophan, the amount oftryptophan in turkey is typical of most poultry.

[18]

Tryptophan (Trp) Content of Various Foods[18][19]

FoodProtein

[g/100g of food]

Tryptophan

[g/100g of food]

Tryptophan/Protein

[%]

egg, white, dried 81.10 1.00 1.23

spirulina, dried 57.47 0.93 1.62

cod, atlantic, dried 62.82 0.70 1.11

soybeans, raw 36.49 0.59 1.62

Pepita 33.08 0.57 1.72

cheese, Parmesan 37.90 0.56 1.47

caribou 29.77 0.46 1.55

sesame seed 17.00 0.37 2.17

cheese, cheddar 24.90 0.32 1.29

sunflower seed 17.20 0.30 1.74

pork, chop 19.27 0.25 1.27

turkey 21.89 0.24 1.11

chicken 20.85 0.24 1.14

beef 20.13 0.23

salmon 19.84 0.22 1.12

lamb, chop 18.33 0.21 1.17

perch, Atlantic 18.62 0.21 1.12

egg 12.58 0.17 1.33

wheat flour, white 10.33 0.13 1.23


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baking chocolate,

unsweetened12.9 0.13 1.23

milk 3.22 0.08 2.34

rice, white 7.13 0.08 1.16

oatmeal, cooked 2.54 0.04 1.16

potatoes, russet 2.14 0.02 0.84

banana 1.03 0.01

[edit] Use as a dietary supplement

For some time, tryptophan has been available in health food stores as a dietary supplement.Many people found tryptophan to be a safe and reasonably effective sleep aid, probably due to its

ability to increasebrain levels ofserotonin (a calming neurotransmitterwhen present in moderatelevels)

[20]and/ormelatonin (a sleep-inducing hormone secreted by thepineal gland in response

to darkness or low light levels).[21][22]

Clinical research has shown mixed results with respect to tryptophan's effectiveness as a sleepaid, especially in normal patients.

[23][24][25]Furthermore tryptophan has shown some effectiveness

for treatment of a variety of other conditions typically associated with low serotonin levels in thebrain

[26]such aspremenstrual dysphoric disorder

[27]and seasonal affective disorder.

[28][29]In

particular, tryptophan has shown considerable promise as an antidepressant alone[30]

and as an"augmenter" of antidepressant drugs.

[30][31]However, the reliability of these clinical trials has

been questioned.[32][33]

[edit] Metabolites

A metabolite of tryptophan, 5-Hydroxytryptophan (5-HTP), has been suggested as a treatmentforepilepsy

[34]and depression, although clinical trials are regarded inconclusive and lacking.

[35]

Due to the conversion of 5-HTP into serotonin by the liver, there may be a significant risk ofheart valve disease from serotonin's effect on the heart.

[36][37]In Europe, 5-HTP is prescribed

with carbidopa to prevent the conversion of 5-HTP into serotonin until it reaches the brain.[38]

Since 5-HTP readily crosses theblood-brain barrierand in addition is rapidly decarboxylated toserotonin (5-hydroxytryptamine or 5-HT),

[39]it may be useful for the treatment of depression.

However, serotonin has a relatively short half-life since it is rapidly metabolized by monoamineoxidase, and therefore is likely to have limited efficacy. It is marketed in Europe for depression

and other indications under the brand names Cincofarm, Tript-OH and Optimax (UK).

In the United States, 5-HTP does not require a prescription, as it is covered under the Dietary

Supplement Act. Since the quality of dietary supplements is now regulated by the U.S. Food and

Drug Administration there is now a guarantee that the label accurately depicts what the bottlecontains.

[40]


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As 5-HTP is usually converted to serotonin before it can reach the brain, elevating bloodserotonin levels greatly, it may cause diarrhea and heart problems, while only slightly increasing

brain serotonin. Therefore, 5-HTP is more effectively used when in conjunction with a dopadecarboxylase inhibitor such as Carbidopa, which slows its conversion to serotonin, allowing

more of supplement to reach the brain.[citation needed]


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Thiamine

From Wikipedia, the free encyclopedia

Jump to: navigation, search

For the similarly-spelled nucleobase, see thymine.

Thiamine chloride

IUPAC name[hide]

2-[3-[(4-Amino-2-methyl-pyrimidin-5-yl)methyl]-4-methyl-

thiazol-5-yl] ethanol

Other names[hide]

Aneurine hydrochloride, thiamin

Identifiers

CAS number

59-43-8 (Cl-)

, 67-03-

8 (Cl-.HCl

hydrochloride)

PubChem 6042

ChemSpider 5819

UNII X66NSO3N35


20/35

MeSH Thiamine

SMILES

[show]

InChI

[show]

InChI key

[show]

Properties

Molecular formula C12H17N4OS+Cl

-.HCl

Molar mass 337.27

Melting point 248-260 C(hydrochloride salt)

Hazards

Main hazards Allergies

(what is this?) (verify)

Except where noted otherwise, data are given for materials

in their standard state (at 25 C, 100 kPa)

Infobox references

Thiamine orthiamin orvitamin B1 (pronounced /a.mn/THYE--min), and named asthe "thio-vitamine" ("sulfur-containing vitamin") is a water-soluble vitamin of the B complex.

First named aneurin for the detrimental neurological effects of its lack in the diet, it waseventually assigned the generic descriptor name vitamin B1. Itsphosphate derivatives are

involved in many cellular processes. The best-characterized form is thiamine pyrophosphate


21/35

(TPP), a coenzyme in the catabolism ofsugars and amino acids. In yeast, TPP is also required inthe first step ofalcoholic fermentation.

All living organisms use thiamine in their biochemistry, but it is synthesized inbacteria, fungi,

andplants. Animals must obtain it from their diet, and, thus, for them it is a vitamin. Insufficient

intake in birds produces a characteristicpolyneuritis, and in mammals results in a disease calledberiberi affecting theperipheral nervous system (polyneuritis) and/or the cardiovascular system,with fatal outcome if not cured by thiamine administration.

[1]In less severe deficiency,

nonspecific signs include malaise, weight loss, irritability and confusion.[2]

There is still much work devoted to elucidating the exact mechanisms by which thiaminedeficiency leads to the specific symptoms observed (see below). New thiamine phosphate

derivatives have recently been discovered,[3]

emphasizing the complexity of thiaminemetabolism and the need for more research in the field.

Thiamine derivatives with improvedpharmacokinetics have been discovered and are to be

considered more effective in alleviating the symptoms of thiamine deficiency and otherthiamine-related conditions such as impaired glucose metabolism in diabetes. These compoundsinclude allithiamine,prosultiamine, fursultiamine,benfotiamine, and sulbutiamine, among others.

Contents

[hide]

y 1 History: The discovery of vitamins and the biochemical lesion

y 2 Biosynthesis

y 3 Nutrition

o 3.1 Occurrence in foods

o 3.2 Reference Daily Intake and high doses

o 3.3 Antagonists

y 4 Absorption and transport

o 4.1 Absorption

o 4.2 Bound to serum proteins

o 4.3 Cellular uptake

o 4.4 Tissue distribution

o 4.5 Excretion

y 5 Thiamine phosphate derivatives and function

o 5.1 Thiamine monophosphate

o 5.2 Thiamine diphosphateo 5.3 Thiamine triphosphate

o 5.4 Adenosine thiamine triphosphate

o 5.5 Adenosine thiamine diphosphate

y 6 Deficiency

o 6.1 Beriberi

o 6.2 Alcoholic brain disease

o 6.3 Thiamine deficiency in poultry


22/35

o 6.4 Thiamine deficiency in ruminants

o 6.5 Idiopathic paralytic disease in wild birds

o 6.6 Analysis and diagnostic testing

y 7 Genetic diseases

y 8 Research

o

8.1 Understanding the mechanism by which thiamine deficiency leads to selectiveneuronal death

o 8.2 Catalytic mechanisms in thiamine diphosphate-dependent enzymes

o 8.3 Non-cofactor roles of thiamine derivatives

o 8.4 Persistent carbenes

y 9 See also

y 10 References

y 11 External links

[edit] History: Thediscovery of vitamins and the

biochemical lesion

Thiamine was the first of the water-soluble vitamins to be described,[1]

leading to the discoveryof more such trace compounds essential for survival and to the notion ofvitamin. Chinese

medical texts referred to beriberi (a thiamine deficiency disease) as early as 2700 BC.[4]

It wasnot until AD 1884 that Kanehiro Takaki (18491920), a surgeon general in the Japanese navy,

rejected the previous germ theory and attributed the disease to insufficient diet. Switching diet onnavy ships, he discovered that substituting white rice with brown barley rice will eliminate

beriberi (he was nicknamed "Barley Baron" after obtaining peerage). However, he incorrectlyattributed the benefit to nitrogen intake as vitamin was unknown substance at the time.

In 1897, Christiaan Eijkman (18581930), a military doctor in the Dutch Indies, discovered thatfowl fed on a diet of cooked, polished rice developed paralysis, which could be reversed by

discontinuing rice polishing.[5]

He attributed that to a nerve poison in the endosperm of rice, fromwhich the outer layers of the grain gave protection to the body. Eijkman was awarded theNobel

Prize in Physiology and Medicine in 1929, because his observations led to the discovery ofvitamins. An associate, Gerrit Grijns (18651944), correctly interpreted the connection between

excessive consumption of polished rice and beriberi in 1901: He concluded that rice contains anessential nutrient in the outer layers of the grain that is removed by polishing.

[6]

In 1911, Casimir Funkisolated an antineuritic substance from rice bran that he called a

"vitamine" (on account of its containing an amino group). Dutch chemists, Barend CoenraadPetrus Jansen (18841962) and his closest collaboratorWillem Frederik Donath (18891957),

went on to isolate and crystallize the active agent in 1926,[7] whose structure was determined byRobert Runnels Williams (18861965), a US chemist, in 1934. Thiamine (sulfur-containing

vitamin) was synthesized in 1936 by the same group.[8]

It was rst named "aneurin" (for anti-neuritic vitamin).[9]

SirRudolph Peters, in Oxford,

introduced thiamine-deprived pigeons as a model for understanding how thiamine deficiency can


23/35

lead to the pathological-physiological symptoms of beriberi. Indeed, feeding the pigeons uponpolished rice leads to an easily recognizable behavior of head retraction, a condition called

opisthotonos. If not treated, the animal will die after a few days. Administration of thiamine atthe stage of opithotonos will lead to a complete cure of the animal within 30 min. As no

morphological modifications were observed in the brain of the pigeons before and after treatment

with thiamine, Peeters introduced the concept of biochemical lesion

[10]

When Lohman and Schuster (1937) showed that the diphosphorylated thiamine derivative

(thiamine diphosphate, ThDP) was a cofactor required for the oxydative decarboxylation ofpyruvate,[11] (a reaction now known to be catalyzed bypyruvate dehydrogenase), the mechanism

of action of thiamine in the cellular metabolism seemed to be elucidated. At present, this viewseems to be oversimplified: Pyruvate dehydrogenase is only one of several enzymes requiring

thiamine diphosphate as a cofactor; moreover, other thiamine phosphate derivatives have beendiscovered since then, and they may also contribute to the symptoms observed during thiamine

deficiency.

Finally, the mechanism by which the thiamine moiety of ThDP exerts its coenzyme function byproton substitution on position 2 of the thiazolium ring was elucidated by Ronald Breslow in

1958.[12]

[edit] Biosynthesis


24/35

A 3D representation of the TPP riboswitch with thiamine bound

Complex thiamine biosynthetic pathways occur in bacteria, some protozoans, plants andfungi.

[13][14]The thiazole andpyrimidine moieties are synthesized separately and then assembled

to form ThMP by thiamine-phosphate synthase (EC 2.5.1.3). The exact biosynthetic pathways

may differ among organisms. In E. coli and otherenterobacteriaceae ThMP may bephosphorylated to the cofactorThDP by a thiamine-phosphate kinase (ThMP + ATP ThDP +ADP, EC 2.7.4.16). In most bacteria and in eukaryotes, ThMP is hydrolyzed to thiamine, that

may then be pyrophosphorylated to ThDP by thiamine diphosphokinase (thiamine + ATP ThDP + AMP, EC 2.7.6.2).

The biosynthetic pathways are regulated by riboswitches in all organisms that synthesisethiamine. If there is sufficient thiamine present in the cell then the thiamine binds to the mRNA

encoding genes required in the pathway preventing the translation of the enzymes. If there is nothiamine present then there is no inhibition, and the enzymes required for the biosynthesis are

produced. The specific riboswitch, the TPP riboswitch, is the only riboswitch identified in both

eukaryotic and prokaryotic organisms.

[15]

[edit] Nutrition

[edit] Occurrence in foods

Thiamine is found in a wide variety of foods at low concentrations. Yeast and pork are the mosthighly concentrated sources of thiamine. In general, cereal grains are the most important dietary

sources of thiamine, by virtue of their ubiquity. Of these, whole grains contain more thiaminethan refined grains, as thiamine is found mostly in the outer layers of the grain and in the germ

(which are removed during the refining process). For example, 100 g of whole-wheat flour

contains 0.55 mg of thiamine, while 100 g of white flour contains only 0.06 mg of thiamine. Inthe US, processed flour must be enriched with thiamine mononitrate (along with niacin, ferrousiron, riboflavin, and folic acid) to replace that lost in processing.

Some other foods rich in thiamine are oatmeal, flax, and sunflower seeds,brown rice, whole

grain rye, asparagus, kale, cauliflower,potatoes, oranges, liver(beef, pork and chicken), andeggs.

[2]

Thiamine hydrochloride (Betaxin) is a (when by itself) white, crystalline hygroscopic food-additive used to add a brothy/meaty flavor to gravies or soups. It is a natural intermediary

resulting from a thiamine-HCl reaction, which precedes hydrolysis and phosphorylation, before

it is finally employed (in the form of TPP) in a number of enzymatic amino, fatty acid, andcarbohydrate reactions.

[16][17]

[edit] Reference Daily Intake and high doses

The RDA in most countries is set at about 1.4 mg. However, tests on female volunteers at dailydoses of about 50 mg have claimed an increase in mental acuity.

[18]There are no reports


25/35

available of adverse effects from consumption of excess thiamine by ingestion of food andsupplements. Because the data is inadequate for a quantitative risk assessment, no Tolerable

Upper Intake Level (UL) can be derived for thiamine.

[edit] Antagonists

Thiamine in foods can be degraded in a variety of ways. Sulfites, which are added to foodsusually as a preservative,

[19]will attack thiamine at the methylene bridge in the structure,

cleaving the pyrimidine ring from the thiazole ring.[2]

The rate of this reaction is increased underacidic conditions. Thiamine is degraded by thermolabile thiaminases (present in raw fish and

shellfish[1]

). Some thiaminases are produced by bacteria. Bacterial thiaminases are cell surfaceenzymes that must dissociate from the membrane before being activated; the dissociation can

occur in ruminants under acidotic conditions. Rumen bacteria also reduce sulfate to sulfite,therefore high dietary intakes of sulfate can have thiamine-antagonistic activities.

Plant thiamine antagonists are heat-stable and occur as both the ortho- and para-hydroxyphenols.

Some examples of these antagonists are caffeic acid, chlorogenic acid, and tannic acid. Thesecompounds interact with the thiamine to oxidize the thiazole ring, thus rendering it unable to be

absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamineantagonists.

[2]

[edit] Absorption and transport

[edit] Absorption

Thiamine is released by the action of phosphatase and pyrophosphatase in the upper smallintestine. At low concentrations, the process is carrier mediated and at higher concentrations,

absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum (itis inhibited by alcohol consumption and by folic deficiency).

[1]Decline in thiamine absorption

occurs at intakes above 5 mg.[20]

The cells of the intestinal mucosa have thiaminepyrophosphokinase activity, but it is unclear whether the enzyme is linked to active absorption.The majority of thiamine present in the intestine is in the pyrophosphorylated form ThDP, but

when thiamine arrives on the serosal side of the intestine it is often in the free form. The uptakeof thiamine by the mucosal cell is likely coupled in some way to its

phosphorylation/dephosphorylation. On the serosal side of the intestine, evidence has shown thatdischarge of the vitamin by those cells is dependent on Na

+-dependent ATPase.

[2]

[edit] Bound to serum proteins

The majority of thiamine in serum is bound to proteins, mainly albumin. Approximately 90% of

total thiamine in blood is in erythrocytes. A specific binding protein called thiamine-bindingprotein (TBP) has been identified in rat serum and is believed to be a hormonally regulated

carrier protein that is important for tissue distribution of thiamine.[2]

[edit] Cellular uptake


26/35

Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passivediffusion.

[1]About 80% of intracellular thiamine is phosphorylated and most is bound to proteins.

In some tissues, thiamine uptake and secretion appears to be mediated by a soluble thiaminetransporter that is dependent on Na+ and a transcellular proton gradient.[2]

[edit] Tissuedistribution

Human storage of thiamine is about 25 to 30 mg with the greatest concentrations in skeletal

muscle, heart, brain, liver, and kidneys. ThMP and free (unphosphorylated) thiamine is present inplasma, milk, cerebrospinal fluid, and likely all extracellular fluids. Unlike the highly

phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing cellmembranes. Thiamine contents in human tissues are less than those of other species.

[2][21]

[edit] Excretion

Thiamine and its acid metabolites (2-methyl-4-amino-5-pyrimidine carboxylic acid, 4-methyl-

thiazole-5-acetic acid and thiamine acetic acid) are excreted principally in the urine.[22]

[edit] Thiamine phosphatederivatives and function

Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated

thiamine derivatives. There are four known natural thiamine phosphate derivatives: thiaminemonophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine

pyrophosphate (TPP), thiamine triphosphate (ThTP), and the recently discovered adenosinethiamine triphosphate (AThTP) and adenosine thiamine diphosphate (AThDP).

[edit] Thiaminemonophosphate

There is no known physiological role of ThMP.

[edit] Thiaminediphosphate

The synthesis ofthiamine diphosphate (ThDP), also known as thiamine pyrophosphate (TPP) orcocarboxylase, is catalyzed by an enzyme called thiamine diphosphokinase according to the

reaction thiamine + ATP ThDP + AMP (EC 2.7.6.2). ThDP is a coenzyme for severalenzymes that catalyze the transfer of two-carbon units and in particular the dehydrogenation

(decarboxylation and subsequent conjugation with coenzyme A) of 2-oxoacids (alpha-keto acids).

Examples include:

y Present in most species

o pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase (also called -ketoglutarate

dehydrogenase)

o branched-chain -keto acid dehydrogenase

o 2-hydroxyphytanoyl-CoA lyase

o transketolase


27/35

y Present in some species:

o pyruvate decarboxylase (in yeast)

o several additional bacterial enzymes

The enzymes transketolase,pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase

(OGDH) are all important in carbohydrate metabolism. The cytosolic enzyme transketolase is akey player in thepentose phosphate pathway, a major route for the biosynthesis of the pentose

sugarsdeoxyribose and ribose. The mitochondrial PDH and OGDH are part of biochemicalpathways that result in the generation ofadenosine triphosphate (ATP), which is a major form of

energy for the cell. PDH links glycolysis to the citric acid cycle, while the reaction catalyzed byOGDH is a rate-limting step in the citric acid cycle. In the nervous system, PDH is also involved

in the production of acetylcholine, a neurotransmitter, and for myelin synthesis.[23]

[edit] Thiamine triphosphate

Thiamine triphosphate (ThTP) was long considered a specific neuroactive form of thiamine.

However, recently it was shown that ThTP exists inbacteria, fungi,plants and animalssuggesting a much more general cellular role.[24]

In particular in E. coli, it seems to play a role in

response to amino acid starvation.[25]

[edit] Adenosine thiamine triphosphate

Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recentlybeen discovered in Escherichia coli where it accumulates as a result of carbon starvation.

[3]In E.

coli, AThTP may account for up to 20 % of total thiamine. It also exists in lesser amounts inyeast, roots of higher plants and animal tissue.

[26]

[edit] Adenosine thiaminediphosphate

Adenosine thiamine diphosphate (AThDP) or thiaminylated adenosine diphosphate exists in

small amounts in vertebrate liver, but its role remains unknown.[26]

[edit] Deficiency

Thiamine derivatives and thiamine-dependent enzymes are present in all cells of the body, thus, a

thiamine deficiency would seem to adversely affect all of the organ systems. However, thenervous system and the heart are particularly sensitive to thiamine deficiency, because of their

high oxidative metabolism.

Thiamine deficiency can lead to severe fatigue of eyes and myriad problems including

neurodegeneration, wasting, and death. A lack of thiamine can be caused by malnutrition, a diethigh in thiaminase-rich foods (raw freshwater fish, raw shellfish, ferns) and/or foods high in anti-

thiamine factors (tea, coffee,betel nuts)[27]

and by grossly impaired nutritional status associatedwith chronic diseases, such as alcoholism, gastrointestinal diseases, HIV-AIDS, and persistent

vomiting.[28] It is thought that many people with diabetes have a deficiency of thiamine and thatthis may be linked to some of the complications that can occur.

[29][30]


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Well-known syndromes caused by thiamine deficiency includeberiberi and Wernicke-Korsakoffsyndrome, diseases also common with chronic alcoholism.

[edit] Beriberi

Beriberi is a neurological and cardiovascular disease. The three major forms of the disorder aredry beriberi, wet beriberi, and infantile beriberi.[22]

y Dry beriberiis characterized principally by peripheral neuropathy consisting of symmetric

impairment of sensory, motor, and reflex functions affecting distal more than proximal limb

segments and causing calf muscle tenderness.[28]

y Wet beriberiis associated with mental confusion, muscular wasting, edema, tachycardia,

cardiomegaly, and congestive heart failure in addition to peripheral neuropathy.[1]

y Infantile beriberioccurs in infants breast-fed by thiamin-deficient mothers (who may show no

sign of thiamine deficiency). Infants may manifest cardiac, aphonic, or pseudomeningitic forms

of the disorder. Infants with cardiac beriberi frequently exhibit a loud piercing cry, vomiting, and

tachycardia.[22]

Convulsions are not uncommon, and death may ensue if thiamine is not

administered promptly.[28]

Following thiamine treatment, rapid improvement occurs, in general, within 24 hours.[22]

Improvements of peripheral neuropathy may require several months of thiamine treatment.[31]

[edit] Alcoholic brain disease

Nerve cells and other supporting cells (such as glial cells) of the nervous system require thiamine.Examples of neurologic disorders that are linked to alcohol abuse include Wernickes

encephalopathy (WE, Wernicke-Korsakoff syndrome) and Korsakoffs psychosis (alcohol

amnestic disorder) as well as varying degrees of cognitive impairment.

[32]

Wernickes encephalopathy is the most frequently encountered manifestation of thiamine

deficiency in Western society,[33]

though it may also occur in patients with impaired nutritionfrom other causes, such as gastrointestinal disease,

[33]those with HIV-AIDS, and with the

injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation.

[34]This is a striking neuro-psychiatric disorder characterized by

paralysis of eye movements, abnormal stance and gait, and markedly deranged mentalfunction.

[35]

Alcoholics may have thiamine deficiency because of the following:

y Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of

thiamine.

y Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is

disturbed during acute alcohol exposure.

y Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.[36]

y Impaired thiamine utilization:Magnesium, which is required for the binding of thiamine to

thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption.


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The inefficient utilization of any thiamine that does reach the cells will further exacerbate the

thiamine deficiency.

y Ethanolper se inhibits thiamine transport in the gastrointestinal system and blocks

phosphorylation of thiamine to its cofactor form (ThDP).[37]

Korsakoff Psychosis is, in general, considered to occur with deterioration of brain function inpatients initially diagnosed with WE.

[38]. This is an amnestic-confabulatory syndrome

characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and

decreased spontaneity and initiative.

Documents

Tryptophan Supplement for Sleep