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Tryptophan Supplement For Sleep
Tryptophan Supplement For Sleep
A review of benefits and side effects, safety, risks L Tryptophan is an essential amino acid found in foods that contain protein such as 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. If you wish to reduce your appetite effectively and lose weight, consider an all natural herbal product that I have formulated called Diet Rx. Metabolism The figure below shows l-tryptophan converting into 5-HTP, which then readily converts into serotonin. Once serotonin is made, the pineal gland is able to convert it at night into melatonin, the sleep-inducing hormone. L-Tryptophan --> 5-Hydroxytryptophan 5-HTP --> Serotonin --> N-Acetyl-serotonin --> Melatonin Vitamin B6 is involved in the metabolism of tryptophan to serotonin. Note: LTryptophan is also metabolized to a different pathway, not all of it is converted into 5-HTP. L-Tryptophan supplement, 500mg each pill by FTH Nutraceuticals USP Pharmaceutical Grade Tryptophan source PURE L Tryptophan amino acid, this product, as determined by a Certificate of Analysis, is the highest grade available, over 99% Pure. Tryptophan is formed by a fermentation process in a lab. FTH Tryptophan is USP pharmaceutical grade, which requires a minimum of 98.5% purity.
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L-Tryptophan - 500 mg each pill Suggested use: Take one tryptophan capsule in the evening, preferably on an empty stomach, or as recommended by your health care provider. NOTE: There are some companies selling tryptophan for very cheap. They may use a low quality source or mix it with 5-HTP. This tryptophan source is of the highest 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 cognitive formula with a dozen herbs and nutrients. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support healthy: Memory and Mood Mental clarity Concentration 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 Rx include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba herb, Ginseng herb, Mucuna pruriens, and Reishi. The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Trimethylglycine, Tyrosine, and Vinpocetine.
An Alternative to Tryptophan pills 5-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 from these 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 the 5-HTP link above. Benefits Anxiety Can 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 loss The anorectic effect of increasing doses of L-tryptophan in obese patients.
Eat Weight Disord. 1997 Dec;2(4):211-5. Treatments that raise the level of tryptophan in the brain can rapidly alter the rate at which it is converted to serotonin. This paper compares the effect of 1, 2 and 3 g L-tryptophan administered 1 h before a plated meal on total food intake and carbohydrate and protein consumption in 10 obese subjects versus a lactose placebo in another 10 obese subjects. There was a progressive decrease in carbohydrate consumption in function of the tryptophan dose. These results provide further support for the view that serotoninergic mechanisms play a role in the regulation of human food intake. Dosage What 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 contents added to yogurt or juice? This product works better when taken on an empty stomach, so the contents can be mixed with water or small amount of juice and preferably without yogurt or food. The unfortunate history of L Tryptophan, safety and risks, caution and danger in past During the 1980s, consumers were using tryptophan for sleep and as an antidepressant. Tryptophan was available without a prescription until 1989 when the FDA prohibited its over-the-counter sale because a manufacturer in Japan shipped a contaminated batch to the U.S. This caused a serious illness called eosinophilia myalgia syndrome in about 1,000 individuals with serious ltryptophan side effects. Around 1995, tryptophan gradually became available by prescription through compounding pharmacies, and then since about the year 2000 tryptophan slowly and cautiously was placed on the over the counter market through a few small vitamin companies. Few large vitamin companies are selling tryptophan at this time (2007). Tryptophan side effects, caution, safety, toxicity A common tryptophan side effect from high dose use is drowsiness so it may be a good idea to take this amino acid supplement in the evening and not while driving or operating heavy machinery. Dry mouth is a less common tryptophan side 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 desired effect of many users who take this supplement for sleep. It is very rare for a tryptophan side effect to lead to confusion or disorientation. I read on a website that patients with asthma or systemic lupus erythematosus should not take tryptophan supplements, why is this?
I have not seen any studies regarding the interaction of this amino acid supplement and airway disease such as asthma or an autoimmune condition such as lupus. However, there is a possibility that elevating serotonin levels may trigger airway disease. I will await the results of studies focusing on this issue before 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. Is this common? Yes, melatonin, 5-HTP and the amino acid supplement are known to make dreams more vivid. Interaction with SSRI medications used for depression Can tryptophan be dangerous with low or moderate dose of SSRI drugs such as Prozac or Zoloft or Paxil. I would take it only under my doctors supervision. I just wanted your opinion. When taken in low dosages of 200 to 500 mg, most people are not likely to have any major untoward effects when combined with low dosages of SSRI antidepressants. However, each case is unique and some people may be very sensitive to such combinations. Tryptophan and behavior Social behaviour and mood in everyday life: the effects of tryptophan in quarrelsome 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 high scores on 2 self-report measures of trait quarrelsomeness would reduce quarrelsome behaviours and enhance agreeable behaviours when measured ecologically using an event-contingent recording method. We conducted a double-blind crossover study, in which participants took tryptophan at 3 grams a day and placebo for 15 days each and recorded how they behaved, felt and perceived others during everyday social interactions. Tryptophan supplement use significantly decreased quarrelsome behaviours and increased agreeable behaviours and perceptions of agreeableness. Men also behaved less dominantly, whereas both men and women perceived others as more dominant. Tryptophan's effects on behaviours and perceptions, while more marked in the men, were generally positive and accompanied by improved affect. Increasing serotonin in quarrelsome people may not only reduce behaviours associated with a predisposition to various mental and physical disorders but also enhance socially constructive behaviours and improve social perceptions. Tryptophan, turkey, and sleep, food content Does eating turkey make a person sleepy due to the tryptophan in turkey meat? Would eating foods high in tryptophan induce sleep?
Turkey has an amino acid called tryptophan that is involved in sleep and mood balance. However, turkey has no more tryptophan than chicken or beef. The cause of sleepiness at Thanksgiving is more likely due to consuming lots of food and drink rather than the tryptophan content in turkey. When this amino acid is ingested 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 a supplement is much more direct and effective than trying to consume this amino acid through food or turkey. Combination with St. John's wort Is 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 to learn 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 low dosages at first to know how your body reacts. Tryptophan Research studies Effect of orally administered L-tryptophan on serotonin, melatonin, and the innate immune response in the rat. Mol Cell Biochem. 2004 December. To assess the effects of external administration of L- tryptophan on the synthesis of serotonin and melatonin as well as on the immune function of Wistar rats, 300 mg 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 were collected 4 h after the administration. The accumulation of 5-hydroxytryptophan ( 5HTP ) after decarboxylase inhibition was used to measure the rate of tryptophan hydroxylation in vivo. The results showed a diurnal increase in the brain 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 4 h later. In the animals which received tryptophan during the dark period, the 5-HT declined but the 5-HT/5-HIAA ratio remained unchanged. There was also a significant increase in nocturnal circulating melatonin levels. The results indicated that the synthesis of serotonin and melatonin, as well as the innate immune response, can be modulated by oral ingestion of tryptophan. Pyridoxine, regardless of serotonin levels, increases production of 5hydroxytryptophan in rat brain. Arch Med Res. 2004 Jul-Aug. The aim of this study was to evaluate effects of pyridoxine and butylated hydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxytryptophan and serotonin. Thirty rats (30 days of age) were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxy tryptophan, and serotonin (5-HT) after intraperitoneal injections of pyridoxine HCl during 20 days and a single dose of BHT. Levels of TBARS and 5-HTP increased considerably in all vitamin- and/or BHT-treated groups, and serotonin increased partially only in B(6) with or without BHT-treated groups compared with control
group. Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-hydroxy tryptophan. Tryptophan administration increase contractility and change the ultrastructure of mice duodenum. Amino Acids. 2004 October. Serotonin is a metabolite of tryptophan. Serotonin has been shown to induce contractions in rat duodenum and ileum. We planned to investigate the in vivo effects of Tryptophan administration on duodenal contractility. Two equal groups of adult male Swiss-albino mice were used in the experiments. Controls and tryptophan treated. Duodenum tissues contractility responses to different concentration of KCl and acetylcholine (ACh) were recorded on polygraph. Body weights decreased and duodenal contractile response of ACh increased significantly by tryptophan treatment. The duodenal ultrastructural changes in tryptophan group illustrated partially loss of apical surface and fusion in microvilli. Immunohistochemical detection showed that serotonin increased by tryptophan treatment. There is a relation between duodenal contractility increased by tryptophan treatment and changes in the duodenal tissue serotonin level and ultrastructure. The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function. Psychol Med. 2003 November Dieting in healthy women results in a decrease in the availability of tryptophan, the amino-acid precursor of serotonin, for brain serotonin synthesis. This is associated with increases in the prolactin response to serotonin drug challenge suggesting a 'supersensitivity' of serotonin neuroendocrine responses. The aim of the study was to assess whether increased tryptophan intake during dieting would prevent the changes in tryptophan availability and serotonin neuroendocrine function. Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced tryptophan (1.8 g daily) or placebo in a double-blind, parallel group, design. Tryptophan supplementation failed to modify the dieting-induced reduction in fasting tryptophan availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional tryptophan did not show enhanced prolactin responses to intravenous tryptophan challenge. The decrease in tryptophan availability produced by dieting may be due to increased tryptophan metabolism rather than decreased tryptophan intake. While tryptophan treatment did not increase fasting tryptophan availability it may have modified the effect of dieting on brain serotonin function. Further studies will be needed to see if this effect of tryptophan has consequences for the effectiveness of dieting as means of weight control. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry. 2003 Nov 1;54(9):906-14.
Tryptophan degradation into kynurenine (KYN) during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy. Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFNalpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of tryptophan, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in tryptophan concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-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-alphainduced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFNalpha-mediated tryptophan depletion. Acute administration of nutritionally sourced tryptophan increases fear recognition. Psychopharmacology (Berl). 2003 Aug;169(1):104-7. The serotonin precursor tryptophan has been widely used as a nutritional supplement and antidepressant. Recently, however, the use of tryptophan has been severely restricted due to its association with the eosinophilic myalgic syndrome, an autoimmune disorder probably caused by ingestion of a contaminant produced in certain tryptophan manufacturing processes. To determine the bioavailability of a nutritional source of tryptophan obtained from milk protein and to assess whether administration of this material produced neuroendocrine and neuropsychological effects consistent with increased brain serotonin activity. We studied 24 healthy subjects who ingested approximately 1.8 g of nutritionally-sourced tryptophan or placebo in a double-blind, parallel group, design. We carried out venous sampling for amino acid and hormone estimation and performed a test of emotional processing using a facial expression recognition task. The nutritionally-sourced tryptophan caused a substantial increase in the availability of tryptophan in plasma. Relative to placebo the tryptophan material produced some evidence of an increase in plasma cortisol, and enhanced the perception of fearful and happy facial expressions. A nutritional source of tryptophan increased the availability of tryptophan for brain serotonin synthesis and produced endocrine and neuropsychological changes consistent with increased brain serotonin function. The effect of tryptophan on emotional processing may be relevant to its reported activity in primate studies of social behaviour. Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals.
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 induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity. 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 testidentical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture. 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 shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive- or disinhibited response style on the continuous-performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli. These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients. Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers. Psychopharmacology (Berl). 2004 Jul 22 Disorders associated with low levels of serotonin (5-HT) are characterized by mood and cognitive disturbances. Acute tryptophan depletion is an established method for lowering 5-HT levels and an important tool to study the effects of reduced 5-HT on mood and cognition in human subjects. The University of Maastricht developed a new and inexpensive method for acute tryptophan depletion: a natural collagen protein (CP) mixture with low tryptophan content. The reductions in plasma trypotophan after taking this CP mixture were compared with the reductions achieved taking the traditional AA mixture, and effects on memory and reversal learning were studied. Fifteen healthy young volunteers participated in a double-blind, counterbalanced within-subject study. Reversal learning, verbal memory and pattern recognition were assessed at baseline and 3-4 h after taking the CP mixture. The new acute tryptophan depletion method significantly reduced plasma tryptophan by 74% and the ratio between tryptophan and the other large AAs by 82%. The placebo mixture did not change these measures. Delayed recognition reaction time on the verbal learning task was increased following acute tryptophan depletion. No other cognitive effects were found. The CP mixture was shown to be an efficient tool for lowering plasma tryptophan in humans. The validity of this method with regard to behavioral changes remains to be established in healthy, vulnerable and clinical populations.
An evening milkshake spiked with the amino acid tryptophan may help clear the morning mental fog of the sleep-deprived, preliminary research suggests. In a study of 28 healthy young adults, researchers found that accompanying an evening meal with a milkshake containing a protein powder called alphalactalbumin -- 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 a high concentration of the essential amino acid tryptophan, a protein buildingblock best known for its sleep-inducing effects. In the body, tryptophan serves as a precursor for the brain chemical serotonin, which, among other things, is thought to help regulate sleep. Tryptophan is found in foods such as beef, chicken, dairy products and, most famously, turkey -- which is often blamed for the near-coma that follows Thanksgiving dinner. In reality, however, the relatively low concentration of tryptophan in turkey and other foods is unlikely to affect the brain because it must compete with other amino acids and nutrients for absorption. In their study, Markus and his colleagues examined whether an ALAC protein powder, with its high concentration of tryptophan, could increase the ratio of tryptophan to other amino acids in participants' blood -- and whether there would be any difference in their mental alertness the next morning. The protein powder, marketed as BioPure, was supplied by Eden Prairie, Minnesotabased Davisco Foods International. Fourteen men and women with mild sleep problems, and 14 others without sleep complaints took part in two experiments on separate evenings -- one in which they consumed a tryptophan -fortified milkshake 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 and his colleagues found that participants' blood levels of tryptophan were more than twice as high on the night they dined on the supplemented milkshakes compared with the placebo milkshakes. More importantly, men and women who normally had sleep problems performed better on the mental-alertness test on the morning after having the tryptophan containing milkshakes. On the other hand, tryptophan made no difference to the performance of the 14 participants with no sleep problems. American Journal of Clinical Nutrition, May 2005. Tryptophan taken orally can convert into serotonin and melatonin Tryptophan is an amino acid available in food. A few years ago tryptophan reappeared on the market as an over the counter supplement. It's biochemistry is fascinating and quite important. It has been known for some time that in the body and brain, tryptophan gets converted into 5-hydroxy-tryptophan (5-HTP) which then converts into serotonin, a crucial brain chemical involved in mood, appetite, impulse control and sleep. Serotonin, in turn, is able to convert at night into melatonin. To confirm this knowledge, tryptophan was given to a group of rats at 8 am in the morning, and to another group of rats at 8 PM at night. Four hours after administration, researchers measured the blood and brain fluid levels of
serotonin and melatonin. During daytime administration, tryptophan raised the levels of serotonin. Interestingly, when tryptophan was given at night, serotonin levels did not increase, but melatonin levels increased significantly. Therefore, the serotonin that was generated by tryptophan administration was being converted into melatonin. Another study I came across in the January 2005 issue of the Journal of Pineal Research indicates that 5-HTP is a more potent antioxidant 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 the timing of a supplement can make a difference on how it is metabolized. Since tryptophan, 5-HTP, and melatonin are available as supplements, I have had many questions 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 a different biochemistry and would respond differently. The most reliable way to find out is by trial and error. There's really no practical blood study that can be done 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 strong influence on mood or appetite. 5-HTP has a strong influence on mood, appetite and anxiety. Tryptophan has been used for depression and sleep. L Tryptophan supplement emails Q. My doctor tried me on 5-HTP, but it made me overwhelmingly sleepy. He then tried tryptophan, to which I am responding with more energy, mental clarity, and a decrease of carbohydrate cravings. Since I thought 5-HTP was "downstream" from tryptophan on the way to becoming serotonin, what would cause this reaction? A. There are several factors that could be involved, dosage, timing, with or without 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 a lower dose of 5-HTP reduces sleepiness. A few weeks ago I had emailed you regarding bad side effects of excessive menstrual bleeding, poor control of depression when I added 5-htp and tryptophan to my Effexor treatment. I spoke to the School of Pharmacy at my local university and they advised that my heavy bleeding would have been caused by taking 5HTP, Tryptophan AND Effexor. They said this combination was too much and that I shouldn't be taking all 3. They said if I wanted to take either 5HTP or Tryptophan with Effexor, Tryptophan seems to have the best results for boosting depressive symptoms. Since I have been doing this my period this month is fine and my depression is wonderful. Seems Tryptophan with Effexor is better than 5HTP with Effexor for me. I'm only on low doses of both to avoid excess serotonin though - 500 mg Tryptophan and 75 mg Effexor / day. Just wanted to let you know that your product is in fact very good but I was not using it in the right manner or amount. It's often a matter of trial and error but thought this info may help somebody else. I don't wish my name to be made public though if you choose to use this info. Thanks for your time and a best tryptophan
product. Dear Dr. Sahelian, Thank you for your informative web site. I saw your response on 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 told this 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 reason is that we don't know too well what the long term effects are of taking a particular amino acid in high amounts. They may be beneficial, or harmful. As to the frequency of breaks or length of a break from tryptophan, this depends on each person and their individual physiology, but as a rough guideline a week off per month 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 of SSRIs so I tried Kira the German St John's Wort prescription. I am significantly better, however, I never quite went back to normal. Because on five pills a day, under my doctors supervision, I have experienced some side effects - electrical shocks 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 my dietary intake of tryptophan? Could you please give a reliable web site that lists tryptophan content of foods. I have searched and searched and found them all to be different. Perhaps there is a good book that has nutritional content of tryptophan listed. A. Tryptophan is found in foods that contain protein, however, since these foods also have other amino acids, they all compete to get in the brain and the tryptophan is not able to overwhelm the others to get in. Trying to increase brain tryptophan levels specifically through foods is not the best way to go. The best option to increase brain tryptophan levels is to take tryptophan pills or, since the real 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 into serotonin after going into the brain. Q. Is tryptophan helpful for depression? 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 or SAM-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.
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 and know 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 while others prefer 5thp, and still others prefer melatonin. The best way to find out is to try each product by itself for 2 nights in a row with a break for 2 or 3 nights between 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 of other 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 feel that it's very informative and helpful in deciding the pros and cons of various treatments without the emotional "hype" that seems to be common to other alternative treatment websites. I recently read that tryptophan supplementation could have a carcinogenic effect on the liver, and for this reason, 5htp is a better treatment 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. I have a lot of information about these products, but I get mixed information from different doctors. When you have a chance, please let me know what you think about 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 when there are so many products on the market? 4. How does these products compare with some of the "normal" medicines for depressions. Is the effect the same? A. 1. 5-HTP and tryptophan supplements have not been adequately tested during pregnancy and for the time being we suggest not using them unless absolutely required. 2. 5-HTP has a more direct influence on serotonin than tryptophan. Tryptophan converts into 5-HTP which converts into serotonin. 3. It is nearly impossible for the consumer to know which product is good unless they have it tested themselves in a testing laboratory. 4. Some people respond to natural supplements better, others respond better to pharmaceutical antidepressants. For mild to moderate depression, without suicidal tendencies, we suggest using the natural options first.
I am a chronic sufferer of insomnia. Years ago I tried tryptophan and it was very effective in making sleepy and keeping asleep through the night. However, after a few days I started getting stomach cramps and I discontinued use. 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 with a small amount of food. Please tell me why there is neither tryptophan nor 5HTP in Mind Power Rx, if both tryptophan and 5HTP help with mood. 5-HTP and tryptophan can cause sedation in many people and Mind Power Rx if formulated to enhance mental alertness and concentration. Would like to know the conversion ratio for L-Tryptophan to 5-HTP please. I have been 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 enzyme varies among individuals and can be influenced by a number of factors. Tryptophan is also metabolized to a different pathway, not all of it is converted into 5-HTP. Therefore it is difficult to give a precise number for the conversion ratio since it can vary significantly among different individuals and may be affected 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 50 mg 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 first place? 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 with Sam 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 supplements since much depends on the dosage used, the timing of the supplements, and the individual 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 ltryptophan 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 optimal combination, but it is what has worked for me. Recently I began having RLS during the day. I recall taking the l-tryptophan before it was banned, but do not remember why. I just know it helped. I decided to try the l-tryptophan again, as my sleep neurologist wishes to put me on an orphan drug, Xyrem. The Xyrem would help the deep sleep. I am a little apprehensive. We have tried the dopamine agonists, Lyrica, Gabapentin, all of them. Too many side effects. Not to mention that the neurologist scoffs at such non-pharmaceutical treatments. The ltryptophan has a quick onset, but seems to only be effective for a couple of hours.
As I know of long acting amino acids like l-arginine, I tried to find such a form of the l-tryptophan and could not come up with anything. I take it with juice (carb) as suggested, along with magnesium and chromium picolinate. Are you aware of some 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
Function
Metabolism of L-tryptophan into serotonin and melatonin (left) and niacin (right). Transformed functional 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 in protein biosynthesis. In addition, tryptophan functions as a biochemical precursor for the following compounds (see also figure to the right):
y
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Serotonin (a neurotransmitter), synthesized via tryptophan hydroxylase.[9][10] Serotonin, in turn, can be converted to melatonin (a neurohormone), via N-acetyltransferase and 5hydroxyindole-O-methyltransferase activities.[11] Niacin is synthesized from tryptophan via kynurenine and quinolinic acids as key biosynthetic intermediates.[12] Auxin (a phytohormone) when sieve tube elements undergo apoptosis tryptophan is converted to auxins.[13]
The disorders fructose malabsorption and lactose intolerance causes improper absorption of tryptophan 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 the biosynthesis of tryptophan. So high levels of tryptophan prevent tryptophan synthesis through a negative 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 and rapid responses to changes in the cell's internal and external tryptophan levels.
Food egg, white, dried spirulina, dried cod, atlantic, dried soybeans, raw Pepita cheese, Parmesan caribou sesame seed cheese, cheddar sunflower seed pork, chop turkey chicken beef salmon lamb, chop perch, Atlantic egg wheat flour, white
baking chocolate, unsweetened milk rice, white oatmeal, cooked potatoes, russet banana
[edit] Metabolites
A metabolite of tryptophan, 5-Hydroxytryptophan (5-HTP), has been suggested as a treatment for epilepsy[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 of heart 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 the blood-brain barrier and in addition is rapidly decarboxylated to serotonin (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 monoamine oxidase, 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 bottle contains.[40]
As 5-HTP is usually converted to serotonin before it can reach the brain, elevating blood serotonin 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 dopa decarboxylase inhibitor such as Carbidopa, which slows its conversion to serotonin, allowing more of supplement to reach the brain.[citation needed]
Thiamine
From Wikipedia, the free encyclopedia Jump to: navigation, search For the similarly-spelled nucleobase, see thymine.
Thiamine chloride
CAS number
MeSH SMILES
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Thiamine
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InChI key
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Properties Molecular formula Molar mass Melting point Hazards Main hazards Allergies C12H17N4OS+Cl-.HCl 337.27 248-260 C (hydrochloride salt)
(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 or thiamin or vitamin B1 (pronounced / a . m n/ THYE- -min), and named as the "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 was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are involved in many cellular processes. The best-characterized form is thiamine pyrophosphate
(TPP), a coenzyme in the catabolism of sugars and amino acids. In yeast, TPP is also required in the first step of alcoholic fermentation. All living organisms use thiamine in their biochemistry, but it is synthesized in bacteria, fungi, and plants. Animals must obtain it from their diet, and, thus, for them it is a vitamin. Insufficient intake in birds produces a characteristic polyneuritis, and in mammals results in a disease called beriberi affecting the peripheral 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 thiamine deficiency leads to the specific symptoms observed (see below). New thiamine phosphate derivatives have recently been discovered,[3] emphasizing the complexity of thiamine metabolism and the need for more research in the field. Thiamine derivatives with improved pharmacokinetics have been discovered and are to be considered more effective in alleviating the symptoms of thiamine deficiency and other thiamine-related conditions such as impaired glucose metabolism in diabetes. These compounds include allithiamine, prosultiamine, fursultiamine, benfotiamine, and sulbutiamine, among others.
Contents
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1 History: The discovery of vitamins and the biochemical lesion 2 Biosynthesis 3 Nutrition o 3.1 Occurrence in foods o 3.2 Reference Daily Intake and high doses o 3.3 Antagonists 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 5 Thiamine phosphate derivatives and function o 5.1 Thiamine monophosphate o 5.2 Thiamine diphosphate o 5.3 Thiamine triphosphate o 5.4 Adenosine thiamine triphosphate o 5.5 Adenosine thiamine diphosphate 6 Deficiency o 6.1 Beriberi o 6.2 Alcoholic brain disease o 6.3 Thiamine deficiency in poultry
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6.4 Thiamine deficiency in ruminants 6.5 Idiopathic paralytic disease in wild birds 6.6 Analysis and diagnostic testing 7 Genetic diseases 8 Research o 8.1 Understanding the mechanism by which thiamine deficiency leads to selective neuronal 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 9 See also 10 References 11 External links
o o o
lead to the pathological-physiological symptoms of beriberi. Indeed, feeding the pigeons upon polished 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 at the 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 of pyruvate,[11] (a reaction now known to be catalyzed by pyruvate dehydrogenase), the mechanism of action of thiamine in the cellular metabolism seemed to be elucidated. At present, this view seems to be oversimplified: Pyruvate dehydrogenase is only one of several enzymes requiring thiamine diphosphate as a cofactor; moreover, other thiamine phosphate derivatives have been discovered 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 by proton substitution on position 2 of the thiazolium ring was elucidated by Ronald Breslow in 1958.[12]
[edit] Biosynthesis
Complex thiamine biosynthetic pathways occur in bacteria, some protozoans, plants and fungi.[13][14] The thiazole and pyrimidine 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 other enterobacteriaceae ThMP may be phosphorylated to the cofactor ThDP 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 synthesise thiamine. 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 no thiamine 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 most highly 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 thiamine than 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. In the US, processed flour must be enriched with thiamine mononitrate (along with niacin, ferrous iron, 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), and eggs.[2] Thiamine hydrochloride (Betaxin) is a (when by itself) white, crystalline hygroscopic foodadditive 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, and carbohydrate reactions.[16][17]
available of adverse effects from consumption of excess thiamine by ingestion of food and supplements. 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 foods usually 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 under acidic conditions. Thiamine is degraded by thermolabile thiaminases (present in raw fish and shellfish[1]). Some thiaminases are produced by bacteria. Bacterial thiaminases are cell surface enzymes 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. These compounds 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 thiamine antagonists.[2]
Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.[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 thiamine transporter that is dependent on Na+ and a transcellular proton gradient.[2]
[edit] Excretion
Thiamine and its acid metabolites (2-methyl-4-amino-5-pyrimidine carboxylic acid, 4-methylthiazole-5-acetic acid and thiamine acetic acid) are excreted principally in the urine.[22]
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
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 a key player in the pentose phosphate pathway, a major route for the biosynthesis of the pentose sugars deoxyribose and ribose. The mitochondrial PDH and OGDH are part of biochemical pathways that result in the generation of adenosine triphosphate (ATP), which is a major form of energy for the cell. PDH links glycolysis to the citric acid cycle, while the reaction catalyzed by OGDH 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] 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, the nervous 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 diet high in thiaminase-rich foods (raw freshwater fish, raw shellfish, ferns) and/or foods high in antithiamine factors (tea, coffee, betel nuts)[27] and by grossly impaired nutritional status associated with 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 that this may be linked to some of the complications that can occur.[29][30]
Well-known syndromes caused by thiamine deficiency include beriberi and Wernicke-Korsakoff syndrome, diseases also common with chronic alcoholism.
[edit] Beriberi
Beriberi is a neurological and cardiovascular disease. The three major forms of the disorder are dry beriberi, wet beriberi, and infantile beriberi.[22]
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Dry beriberi is 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] Wet beriberi is associated with mental confusion, muscular wasting, edema, tachycardia, cardiomegaly, and congestive heart failure in addition to peripheral neuropathy.[1] Infantile beriberi occurs 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]
Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine. Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure. Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.[36] 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.
The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency. Ethanol per 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 in patients 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.<[28] Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed; particularly poor brain functionality, although in more severe cases, Wernicke-Korsakoff syndrome leaves permanent damage. (See delirium tremens.)
Oxidation of thiamine derivatives to fluorescent thiochromes by potassium ferricyanide under alkaline conditions
A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte Transketolase Activation Assay). Thiamine, as well as its phosphate derivatives, can also be detected directly in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent thiochrome derivatives (Thiochrome Assay) and separation by highperformance liquid chromatography (HPLC).[46][47][48] In recent reports, a number of Capillary Electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as potential alternative techniques for the determination and monitoring of thiamine in samples.[49]
Other disorders in which a putative role for thiamine has been implicated include subacute necrotizing encephalomyelopathy, opsoclonic cerebellopathy (a paraneoplastic syndrome), and Nigerian seasonal ataxia. In addition, several inherited disorders of ThDP-dependent enzymes have been reported,[55] which may respond to thiamine treatment.[28]
[edit] Research
Research in the field mainly concerns the mechanisms by which thiamine deficiency leads to neuronal death in relation to Wernicke Korsakoff Psychosis. Another important field concerns the understanding of the molecular mechanisms involved in ThDP catalysis. More recently, research has been devoted to the understanding of the possible non-cofactor roles of other derivatives such as ThTP and AThTP.
[edit] Understanding the mechanism by which thiamine deficiency leads to selective neuronal death
Experimentally induced beriberi polyneuropathy in chickens may be a good model for studying these forms of neuropathy in view of diagnosis and treatment.[56] From studies using rat models, a link between thiamine deciency and colon carcinogenesis was suggested.[57] Rat model is used also in research of Wernicke's encephalopathy.[58] Thiamine deprived mice are a classic model of systemic oxidative stress, used in research of Alzheimers disease.[59]
[edit] References
1. ^ a b c d e f Mahan LK, Escott-Stump S, editors. Krause's food, nutrition, & diet therapy. 10th ed. Philadelphia: W.B. Saunders Company; 2000 2. ^ a b c d e f g h Combs, G. F. Jr. The vitamins: Fundamental Aspects in Nutrition and Health. 3rd Edition. Ithaca, NY: Elsevier Academic Press; 2008 3. ^ a b c Bettendorff L, Wirtzfeld B, Makarchikov AF, Mazzucchelli G, Frdrich M, Gigliobianco T, Gangolf M, De Pauw E, Angenot L and Wins P (2007). "Discovery of a natural thiamine adenine nucleotide". Nature Chem. Biol. 3: 211 212. doi:10.1038/nchembio867. 4. ^ McCollum EV. A History of Nutrition. Cambridge, MA: Riverside Press, Houghton Mifflin; 1957. 5. ^ Eijkman, C. (1897). Eine Beriberihnliche Krankheit der Hhner. Virchows Arch. Pathol. Anat. 148: 523. 6. ^ Grijns, G. (1901) Over polyneuritis gallinarum. I. Geneesk. Tijdscht. Ned. Ind. 43, 3-110 7. ^ Jansen, B.C.P. and Donath, W.F. (1926) On the isolation of antiberiberi vitamin. Proc. Kon. Ned. Akad. Wet. 29: 1390-1400. 8. ^ Williams, R.R. and Cline, J.K. (1936). Synthesis of vitamin B1. J. Am. Chem. Soc. 58: 1504-1505. 9. ^ Carpenter KJ. Beriberi, white rice, and vitamin B: a disease, a cause, and a cure. Berkeley, CA: University of California Press; 2000 10. ^ Peters, R.A. (1936). The biochemical lesion in vitamin B1 deficiency. Application of modern biochemical analysis in its diagnosis. Lancet 1: 1161-1164. 11. ^ Lohmann, K. and Schuster, P. (1937). Untersuchungen ber die Cocarboxylase. Biochem. Z. 294, 188-214. 12. ^ Breslow R (1958). "On the mechanism of thiamine action. IV.1 Evidence from studies on model systems". J Am Chem Soc 80: 3719 3726. doi:10.1021/ja01547a064. 13. ^ Webb ME, Marquet A, Mendel RR, Rebeille F & Smith AG (2007) Elucidating biosynthetic pathways for vitamins and cofactors. Nat Prod Rep 24, 988-1008. 14. ^ Begley TP, Chatterjee A, Hanes JW, Hazra A & Ealick SE (2008) Cofactor biosynthesis still yielding fascinating new biological chemistry. Curr Opin Chem Biol 12, 118-125. 15. ^ Switching the light on plant riboswitches. Samuel Bocobza and Asaph Aharoni Trends in Plant Science Volume 13, Issue 10, October 2008, Pages 526-533 doi:10.1016/j.tplants.2008.07.004 16. ^ Skylabs Inc. "Thiamine Hydrochloride Information." 2007. 17. ^ [1] 18. ^ Thiamine's Mood-Mending Qualities, Richard N. Podel, Nutrition Science News, January 1999. 19. ^ McGuire, M. and K.A. Beerman. Nutritional Sciences: From Fundamentals to Foods. 2007. California: Thomas Wadsworth. 20. ^ Hayes KC, Hegsted DM. Toxicity of the Vitamins. In: National Research Council (U.S.). Food Protection Committee. Toxicants Occurring Naturally in Foods. 2nd ed. Washington DCL: National Academy Press; 1973. 21. ^ Bettendorff L., Mastrogiacomo F., Kish S. J., and Grisar T. (1996). "Thiamine, thiamine phosphates and their metabolizing enzymes in human brain". J. Neurochem. 66 (1): 250 258. doi:10.1046/j.1471-4159.1996.66010250.x. PMID 8522961. 22. ^ a b c d Tanphaichitr V. Thiamin. In: Shils ME, Olsen JA, Shike M et al., editors. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999 23. ^ Butterworth RF. Thiamin. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006 24. ^ Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P, Grisar T and Bettendorff L (2003). "Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to
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mammals". Cell. Mol. Life Sci 60 (7): 1477 1488. doi:10.1007/s00018-003-3098-4. PMID 12943234. ^ Lakaye B, Wirtzfeld B, Wins P, Grisar T and Bettendorff L (2004). "Thiamine triphosphate, a new signal required for optimal growth of Escherichia coli during amino acid starvation". J. Biol. Chem. 279 (17): 17142 17147. doi:10.1074/jbc.M313569200. PMID 14769791. ^ a b c Frdrich M., Delvaux D., Gigliobianco T., Gangolf M., Dive G., Mazzucchelli G., Elias B., De Pauw E., Angenot L., Wins P. and Bettendorff L. (2009). "Thiaminylated adenine nucleotides chemical synthesis, structural characterization and natural occurrence FEBS J.". FEBS Journal 276 (12): 3256 3268. doi:10.1111/j.1742-4658.2009.07040.x. PMID 19438713. ^ "Thiamin", Jane Higdon, Micronutrient Information Center, Linus Pauling Institute ^ a b c d e Butterworth RF. Thiamin. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006. ^ Thornalley PJ (2005). "The potential role of thiamine (vitamin B(1)) in diabetic complications". Curr Diabetes Rev 1 (3): 287 98. doi:10.2174/157339905774574383. PMID 18220605. ^ Diabetes problems 'vitamin link', BBC News, Tuesday, 7 August 2007 ^ Maurice V, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. 2nd ed. Philadelphia: FA Davis, 1989. ^ Martin, PR, Singleton, CK, Hiller-Sturmhofel, S (2003). "The role of thiamine deficiency in alcoholic brain disease". Alcohol Research and Health 27 (2): 134 142. PMID 15303623. ^ a b Kril JJ (1996). "Neuropathology of thiamine deficiency disorders". Metab Brain Dis 11 (1): 9 17. doi:10.1007/BF02080928. PMID 8815394. ^ Butterworth RF, Gaudreau C, Vincelette J et al. (1991). "Thiamine deficiency and wernicke's encephalopathy in AIDS". Metab Brain Dis 6 (4): 207 12. doi:10.1007/BF00996920. PMID 1812394. ^ Harper C. (1979). "Wernicke s encephalopathy, a more common disease than realised (a neuropathological study of 51 cases)". J Neurol Neurosurg Psychol 42 (3): 226 231. doi:10.1136/jnnp.42.3.226. PMID 438830. ^ Butterworth RF (1993). "Pathophysiologic mechanisms responsible for the reversible (thiamine-responsive) and irreversible (thiamine non-responsive) neurological symptoms of Wernicke's encephalopathy". Drug Alcohol Rev 12 (3): 315 22. doi:10.1080/09595239300185371. PMID 16840290. ^ Rindi G, Imarisio L, Patrini C (1986). "Effects of acute and chronic ethanol administration on regional thiamin pyrophosphokinase activity of the rat brain". Biochem Pharmacol 35 (22): 3903 8. doi:10.1016/0006-2952(86)90002-X. PMID 3022743. ^ McCollum EV A History of Nutrition. Cambridge, MA: Riverside Press, Houghton Mifflin; 1957. ^ Merck Veterinary Manual, ed 1967, pp 1440-1441. ^ R.E. Austic and M.L. Scott, Nutritional deficiency diseases, in Diseases of poultry, ed. by M.S. Hofstad, Iowa State University Press, Ames, Iowa, USA ISBN 0-8138-0430-2, p. 50. ^ The disease is described more carefully here: merckvetmanual.com ^ National Research Council. 1996. Nutrient Requirements of Beef Cattle, Seventh Revised Ed. Washington, D.C.: National Academy Press. ^ Polioencephalomalacia: Introduction, Merck Veterinary Manual ^ Polioencephalomacia: Introduction, "ACES Publications" ^ a b Balk L, Hgerroth PA, Akerman G, Hanson M, Tjrnlund U, Hansson T, Hallgrimsson GT, Zebhr Y, Broman D, Mrner T, Sundberg H. (2009). Wild birds of declining European species are dying from a thiamine deficiency syndrome. Proc Natl Acad Sci U S A. 106:12001 12006. PMID 19597145 doi:10.1073/pnas.0902903106
46. ^ Bettendorff L, Peeters M., Jouan C., Wins P., and Schoffeniels E. (1991) Determination of thiamin and its phosphate esters in cultured neurons and astrocytes using an ion-pair reversedphase high-performance liquid chromatographic method. Anal. Biochem. 198: 52-59. 47. ^ Losa R, Sierra MI, Fernndez A, Blanco D, Buesa JM. (2005) Determination of thiamine and its phosphorylated forms in human plasma, erythrocytes and urine by HPLC and fluorescence detection: a preliminary study on cancer patients.J Pharm Biomed Anal. 37:1025-1029. 48. ^ Lu J, Frank EL. (2008) Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem. 2008 May;54(5):901-906. 49. ^ Shabangi M, Sutton JA. Separation of thiamin and its phosphate esters by capillary zone electrophoresis and its application to the analysis of water-soluble vitamins. Journal of Pharmaceutical and Biomedical Analysis 2005; 38:1:66-71. 50. ^ Slater, PV (1978). "Thiamine Responsive Megaloblastic Anemia with severe diabetes mellitus and sensorineural deafness (TRMA)". The Australian nurses' journal 7 (11): 40 3. PMID 249270. 51. ^ Kopriva, V; Bilkovic, R; Licko, T (Dec 1977). "Tumours of the small intestine (author's transl)". Ceskoslovenska gastroenterologie a vyziva 31 (8): 549 53. ISSN 0009-0565. PMID 603941. 52. ^ Beissel, J (Dec 1977). "The role of right catheterization in valvular prosthesis surveillance (author's transl)". Annales de cardiologie et d'angeiologie 26 (6): 587 9. ISSN 0003-3928. PMID 606152. 53. ^ Online 'Mendelian Inheritance in Man' (OMIM) 249270 54. ^ Butterworth RF. Pyruvate dehydrogenase deficiency disorders. In: McCandless DW, ed. Cerebral Energy Metabolism and Metabolic Encephalopathy. Plenum Publishing Corp.; 1985. 55. ^ Blass JP. Inborn errors of pyruvate metabolism. In: Stanbury JB, Wyngaarden JB, Frederckson DS et al., eds. Metabolic Basis of Inherited Disease. 5th ed. New York: McGraw-Hill, 1983. 56. ^ Djoenaidi W, Notermans SL, Gabrels-Festen AA, Lilisantoso AH, Sudanawidjaja A (1995). "Experimentally induced beriberi polyneuropathy in chickens". Electromyogr Clin Neurophysiol 35 (1): 53 60. PMID 7737017. 57. ^ Bruce WR, Furrer R, Shangari N, O Brien PJ, Medline A, Wang Y (2003). "Marginal dietary thiamin de ciency induces the formation of colonic aberrant crypt foci (ACF) in rats". Cancer Lett 202 (2): 125 129. doi:10.1016/j.canlet.2003.08.005. PMID 14643441. 58. ^ Langlais PJ (1995). "Pathogenesis of diencephalic lesions in an experimental model of Wernicke's encephalopathy". Metab Brain Dis 10 (1): 31 44. doi:10.1007/BF01991781. PMID 7596327. 59. ^ Frederikse PH, Zigler SJ Jr, Farnsworth PN, Carper DA (2000). "Prion protein expression in mammalian lenses". Curr Eye Res 20 (2): 137 43. doi:10.1076/0271-3683(200002)20:2;1D;FT137. PMID 10617916. 60. ^ Kale S, Ulas G, Song J, Brudvig GW, Furey W & Jordan F (2008) Efficient coupling of catalysis and dynamics in the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex.Proc Natl Acad Sci U S A. 105, 1158-1163 61. ^ Kluger R & Tittmann K (2008) Thiamin diphosphate catalysis: enzymic and nonenzymic covalent intermediates. Chem Rev 108, 1797-1833 62. ^ Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P, Grisar T & Bettendorff L (2003) Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals. Cell Mol Life Sci 60, 1477-1488. 63. ^ Bettendorff L. and Wins P. (2009). "Thiamin diphosphate in biological chemistry : new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors". FEBS J. 276 (11): 2917 2925. doi:10.1111/j.1742-4658.2009.07017.x. PMID 19490098.
"Branched-Chain Amino Acid Metabolism" at ncbi.nlm.nih.gov Thiamin deficiency in poultry Type of vitamin B1 could treat common cause of blindness [hide]
v d e
Vitamins (A11)
A Retinol -Carotene Tretinoin -Carotene
D Fat soluble
D2 (Ergosterol, Ergocalciferol) D3 (7-Dehydrocholesterol, Previtamin D3, Cholecalciferol, 25-hydroxycholecalciferol, Calcitriol (1,25dihydroxycholecalciferol), Calcitroic acid)
D4 (Dihydroergocalciferol) D5 D analogues (Dihydrotachysterol, Calcipotriol, Tacalcitol, Paricalcitol)
E Tocopherol (Alpha, Beta, Gamma, Delta) Tocotrienol Tocofersolan Naphthoquinone Phylloquinone (K1) Menatetrenone (K2) Menadione (K3) Menadiol (K4)
B Water soluble
B1 (Thiamine) B2 (Riboflavin) B3 (Niacin, Nicotinamide) B5 (Pantothenic acid, Dexpanthenol, Pantethine) B6 (Pyridoxine, Pyridoxal phosphate, Pyridoxamine)
B7 (Biotin) B9 (Folic acid, Dihydrofolic acid, Folinic acid) B12 (Cyanocobalamin, Hydroxocobalamin, Methylcobalamin, Cobamamide) Choline
M: NUT
drug(A8/11/12)