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Wikipedia

Thiamine

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body.[3][4] It is found in food and commercially synthesized to be a dietary supplement or medication.[1][5] Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.[1]

Thiamine
Skeletal formula and ball-and-stick model of the thiamine cation
Clinical data
Pronunciation/ˈθ.əmɪn/ THY-ə-min
Other namesVitamin B1, aneurine, thiamin
AHFS/Drugs.comMonograph
License data
Routes of
administration
by mouth, IV, IM[1]
Drug classvitamin
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability3.7% to 5.3% (Thiamine hydrochloride)[2]
Identifiers
  • 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol
CAS Number
  • cation: 70-16-6 Y
    67-03-8 (Cl.HCl)
  • Cl salt: 59-43-8  Y
PubChem CID
  • cation: 1130
  • Cl salt: 6042
DrugBank
  • cation: DB00152
ChemSpider
  • cation: 1098
UNII
  • cation: 4ABT0J945J
  • Cl salt: X66NSO3N35 Y
KEGG
  • cation: C00378
ChEBI
  • cation: CHEBI:18385
ChEMBL
  • cation: ChEMBL1547
CompTox Dashboard (EPA)
  • cation: DTXSID50220251
Chemical and physical data
FormulaC12H17N4OS+
Molar mass265.36 g·mol−1
3D model (JSmol)
  • cation: Interactive image
  • cation: Cc2ncc(C[n+]1csc(CCO)c1C)c(N)n2
  • cation: InChI=1S/C12H17N4OS/c1-8-11(3-4-17)18-7-16(8)6-10-5-14-9(2)15-12(10)13/h5,7,17H,3-4,6H2,1-2H3,(H2,13,14,15)/q+1 Y
  • Key:JZRWCGZRTZMZEH-UHFFFAOYSA-N

Food sources of thiamine include whole grains, legumes, and some meats and fish.[1][6] Grain processing removes much of the vitamin content, so in many countries cereals and flours are enriched with thiamine.[1] Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it include beriberi and Wernicke encephalopathy. They are also used to treat maple syrup urine disease and Leigh syndrome. Supplements and medications are typically taken by mouth, but may also be given by intravenous or intramuscular injection.[7]

Thiamine supplements are generally well tolerated. Allergic reactions, including anaphylaxis, may occur when repeated doses are given by injection.[7][8] Thiamine is on the World Health Organization's List of Essential Medicines.[9] It is available as a generic medication, and in some countries as a non-prescription dietary supplement.[7]

Definition

Thiamine is one of the B vitamins and is also known as vitamin B1.[3][4] It is a cation that is usually supplied as a chloride salt. It is soluble in water, methanol and glycerol, but practically insoluble in less polar organic solvents.[10][11] In the body, thiamine can form derivatives; the most well-characterized of which is thiamine pyrophosphate (TPP), a coenzyme in the catabolism of sugars and amino acids.[3]

The chemical structure consists of an aminopyrimidine and a thiazolium ring linked by a methylene bridge. The thiazole is substituted with methyl and hydroxyethyl side chains. Thiamine is stable at acidic pH, but it is unstable in alkaline solutions and from exposure to heat.[10][11] It reacts strongly in Maillard-type reactions.[10] Oxidation yields the fluorescent derivative thiochrome, which can be used to determine the amount of the vitamin present in biological samples.[12]

Deficiency

Well-known disorders caused by thiamine deficiency include beriberi, Wernicke–Korsakoff syndrome, optic neuropathy, Leigh's disease, African seasonal ataxia (or Nigerian seasonal ataxia), and central pontine myelinolysis.[13] Symptoms include malaise, weight loss, irritability and confusion.[10][14][15]

In Western countries, chronic alcoholism is a risk factor for deficiency. Also at risk are older adults, persons with HIV/AIDS or diabetes, and those who have had bariatric surgery.[1] Varying degrees of thiamine insufficiency have been associated with the long-term use of diuretics.[16][17]

Biological functions

 
Thiamine monophosphate (ThMP)

Five natural thiamine phosphate derivatives are known: thiamine monophosphate (ThMP), thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), adenosine thiamine diphosphate (AThDP) and adenosine thiamine triphosphate (AThTP). They are involved in many cellular processes.[18] The best-characterized form is TPP, a coenzyme in the catabolism of sugars and amino acids. While its role is well-known, the non-coenzyme action of thiamine and derivatives may be realized through binding to proteins which do not use that mechanism.[19] No physiological role is known for the monophosphate.

Thiamine pyrophosphate

 
Thiamine pyrophosphate (TPP)
 
The ylide form of TPP

Thiamine pyrophosphate (TPP), also called thiamine diphosphate (ThDP), participates as a coenzyme in metabolic reactions, including those in which polarity inversion takes place.[20] Its synthesis is catalyzed by the enzyme thiamine diphosphokinase according to the reaction thiamine + ATP → TPP + AMP (EC 2.7.6.2). TPP is a coenzyme for several enzymes 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). The mechanism of action of TPP as a coenzyme relies on its ability to form an ylide.[21] Examples include:

The enzymes transketolase, pyruvate dehydrogenase (PDH), and 2-oxoglutarate dehydrogenase (OGDH) are important in carbohydrate metabolism. The cytosolic enzyme transketolase is central to 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 the main energy transfer molecule for the cell. PDH links glycolysis to the citric acid cycle, while the reaction catalyzed by OGDH is a rate-limiting step in the citric acid cycle. In the nervous system, PDH is also involved in the synthesis of myelin and the neurotransmitter acetylcholine.[11]

Thiamine triphosphate

 
Thiamine triphosphate (ThTP)

ThTP was long considered a neurone-specific form of thiamine. It is implicated in chloride channel activation in mammals and other animals, although its precise role is not completely understood.[22] Recently, ThTP has been found in bacteria, fungi and plants, suggesting that it also has a much more general cellular role.[23] In Escherichia coli, it is implicated in the response to amino acid starvation.[24]

Adenosine derivatives

 
Adenosine thiamine diphosphate (AThDP)
 
Adenosine thiamine triphosphate (AThTP)

AThDP exists in small amounts in vertebrate liver, but its role remains unknown.[24]

AThTP is present in E. coli, where it accumulates as a result of carbon starvation. In this bacterium, AThTP may account for up to 20% of total thiamine. It also exists in lesser amounts in yeast, roots of higher plants and animal tissue.[24]

Medical uses

During pregnancy, thiamine is sent to the fetus via the placenta. Pregnant women have a greater requirement for the vitamin than other adults, especially during the third trimester. Pregnant women with hyperemesis gravidarum are at an increased risk of thiamine deficiency due to losses when vomiting.[25] In lactating women, thiamine is delivered in breast milk even if it results in thiamine deficiency in the mother.[4][26]

Thiamine is important not only for mitochondrial membrane development, but also for synaptic membrane function.[27] It has also been suggested that a deficiency hinders brain development in infants and may be a cause of sudden infant death syndrome.[22]

Dietary recommendations

US National Academy of Medicine
Age group RDA (mg/day)
Infants 0–6 months 0.2*
Infants 6–12 months 0.3*
1–3 years 0.5
4–8 years 0.6
9–13 years 0.9
Females 14–18 years 1.0
Males 14+ years 1.2
Females 19+ years 1.1
Pregnant/lactating females 14–50 1.4
* Adequate intake for infants, as an RDA has yet to be established[4]
European Food Safety Authority
Age group Adequate intake
(mg/MJ)[28]
All persons 7 months+ 0.1
Neither the US National Academy of Medicine nor the European Food Safety Authority have determined the tolerable upper intake level for thiamine[4]

The US National Academy of Medicine updated the Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for thiamine in 1998. The EARs for thiamine for women and men aged 14 and over are 0.9 mg/day and 1.1 mg/day, respectively; the RDAs are 1.1 and 1.2 mg/day, respectively. RDAs are higher than EARs to provide adequate intake levels for individuals with higher than average requirements. The RDA during pregnancy and for lactating females is 1.4 mg/day. For infants up to the age of 12 months, the Adequate Intake (AI) is 0.2–0.3 mg/day and for children aged 1–13 years the RDA increases with age from 0.5 to 0.9 mg/day.[4]

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intakes (PRIs) instead of RDAs, and Average Requirements instead of EARs. For women (including those pregnant or lactating), men and children the PRI is 0.1 mg thiamine per megajoule (MJ) of energy in their diet. As the conversion is 1 MJ = 239 kcal, an adult consuming 2390 kilocalories ought to be consuming 1.0 mg thiamine. This is slightly lower than the US RDA.[29]

Neither the National Academy of Medicine nor EFSA have set an upper intake level for thiamine, as there is no human data for adverse effects from high doses.[4][28]

Safety

Thiamine is generally well tolerated and non-toxic when administered orally.[7] There are rare reports of adverse side effects when thiamine is given intravenously, including allergic reactions, nausea, lethargy, and impaired coordination.[28][3]

Labeling

For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value. Since May 27, 2016, the Daily Value has been 1.2 mg, in line with the RDA.[30][31]

Sources

Thiamine is found in a wide variety of processed and whole foods,[18] including lentils, peas, whole grains, pork, and nuts.[6][32] A typical daily prenatal vitamin product contains around 1.5 mg of thiamine.[33]

Food fortification

Some countries require or recommend fortification of grain foods such as wheat, rice or maize (corn) because processing lowers vitamin content.[34] As of February 2022, 59 countries, mostly in North and Sub-Saharan Africa, require food fortification of wheat, rice or maize with thiamine or thiamine mononitrate. The amounts stipulated range from 2.0 to 10.0 mg/kg.[35] An additional 18 countries have a voluntary fortification program. For example, the Indian government recommends 3.5 mg/kg for "maida" (white) and "atta" (whole wheat) flour.[36]

Synthesis

Biosynthesis

Thiamine biosynthesis occurs in bacteria, some protozoans, plants, and fungi.[37][38] The thiazole and pyrimidine moieties are biosynthesized separately and are then combined to form ThMP by the action of thiamine-phosphate synthase.

The pyrimidine ring system is formed in a reaction catalysed by phosphomethylpyrimidine synthase (ThiC), an enzyme in the radical SAM superfamily of iron–sulfur proteins, which use S-adenosyl methionine as a cofactor.[39][40]

 

The starting material is 5-aminoimidazole ribotide, which undergoes a rearrangement reaction via radical intermediates which incorporate the blue, green and red fragments shown into the product.[41][42]

The thiazole ring is formed in a reaction catalysed by thiazole synthase (EC 2.8.1.10).[39] The ultimate precursors are 1-deoxy-D-xylulose 5-phosphate, 2-iminoacetate and a sulfur carrier protein called ThiS. An additional protein, ThiG, is also required to bring together all the components of the ring at the enzyme active site.[43]

 
 
A 3D representation of the TPP riboswitch with thiamine bound

The final step to form ThMP involves decarboxylation of the thiazole intermediate, which reacts with the pyrophosphate derivative of phosphomethylpyrimidine, itself a product of a kinase, phosphomethylpyrimidine kinase.[39]

The biosynthetic pathways differ among organisms. In E. coli and other enterobacteriaceae, ThMP is phosphorylated to the cofactor TPP by a thiamine-phosphate kinase (ThMP + ATP → TPP + ADP).[39] In most bacteria and in eukaryotes, ThMP is hydrolyzed to thiamine and then pyrophosphorylated to TPP by thiamine diphosphokinase (thiamine + ATP → TPP + AMP).[44]

The biosynthetic pathways are regulated by riboswitches.[3] If there is sufficient thiamine present in the cell then the thiamine binds to the mRNAs for the enzymes that are required in the pathway and prevents their translation. 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 known riboswitch found in both eukaryotic and prokaryotic organisms.[45]

Laboratory synthesis

 

In the first total synthesis in 1936, ethyl 3-ethoxypropanoate was treated with ethyl formate to give an intermediate dicarbonyl compound which when reacted with acetamidine formed a substituted pyrimidine. Conversion of its hydroxyl group to an amino group was carried out by nucleophilic aromatic substitution, first to the chloride derivative using phosphorus oxychloride, followed by treatment with ammonia. The ethoxy group was then converted to a bromo derivative using hydrobromic acid. In the final stage, thiamine (as its dibromide salt) was formed in an alkylation reaction using 4-methyl-5-(2-hydroxyethyl)thiazole.[46]: 7 [47]

Industrial synthesis

 
Diamine used in the manufacture of thiamine

Merck & Co. adapted the 1936 laboratory-scale synthesis, allowing them to manufacture thiamine in Rahway in 1937.[47] However, an alternative route using the intermediate Grewe diamine (5-(aminomethyl)-2-methyl-4-pyrimidinamine), first published in 1937,[48] was investigated by Hoffman La Roche and competitive manufacturing processes followed. Efficient routes to the diamine have continued to be of interest.[47][49] In the European Economic Area, thiamine is registered under REACH regulation and between 100 and 1,000 tonnes per annum are manufactured or imported there.[50]

Synthetic analogues

Many vitamin B1 analogues, such as Benfotiamine, fursultiamine, and sulbutiamine, are synthetic derivatives of thiamine. Most were developed in Japan in the 1950s and 1960s as forms that were intended to improve absorption compared to thiamine.[51] Some are approved for use in some countries as a drug or non-prescription dietary supplement for treatment of diabetic neuropathy or other health conditions.[52][53][54]

Absorption, metabolism and excretion

In the upper small intestine, thiamine phosphate esters present in food are hydrolyzed by alkaline phosphatase enzymes. At low concentrations, the absorption process is carrier-mediated. At higher concentrations, absorption also occurs via passive diffusion.[3] Active transport can be inhibited by alcohol consumption or by folate deficiency.[10]

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-binding protein has been identified in rat serum and is believed to be a hormone-regulated carrier protein important for tissue distribution of thiamine.[14] Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.[10] Two members of the family of transporter proteins encoded by the genes SLC19A2 and SLC19A3 are capable of thiamine transport.[22] In some tissues, thiamine uptake and secretion appear to be mediated by a Na+-dependent transporter and a transcellular proton gradient.[14]

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 are present in plasma, milk, cerebrospinal fluid, and, it is presumed, all extracellular fluid. Unlike the highly phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing cell membranes. Calcium and magnesium have been shown to affect the distribution of thiamine in the body and magnesium deficiency has been shown to aggravate thiamine deficiency.[22] Thiamine contents in human tissues are less than those of other species.[14][55]

Thiamine and its metabolites (2-methyl-4-amino-5-pyrimidine carboxylic acid, 4-methyl-thiazole-5-acetic acid, and others) are excreted principally in the urine.[3]

Interference

The bioavailability of thiamine in foods can be interfered with in a variety of ways. Sulfites, added to foods as a preservative,[56] will attack thiamine at the methylene bridge, cleaving the pyrimidine ring from the thiazole ring. The rate of this reaction is increased under acidic conditions.[14] Thiamine is degraded by thermolabile thiaminases present in some species of fish, shellfish and other foods.[10] The pupae of an African silk worm, Anaphe venata, is a traditional food in Nigeria. Consumption leads to thiamine deficiency.[57] Older literature reported that in Thailand, consumption of fermented, uncooked fish caused thiamine deficiency, but either abstaining from eating the fish or heating it first reversed the deficiency.[58] In ruminants, intestinal bacteria synthesize thiamine and thiaminases. The bacterial thiaminases are cell surface enzymes that must dissociate from the cell membrane before being activated; the dissociation can occur in ruminants under acidotic conditions. In dairy cows, over-feeding with grain causes subacute ruminal acidosis and increased ruminal bacteria thiaminase release, resulting in thiamine deficiency.[59]

From reports on two small studies conducted in Thailand, chewing slices of areca nut wrapped in betel leaves and chewing tea leaves reduced food thiamine bioavailability by a mechanism that may involve tannins.[58][60]

Bariatric surgery for weight loss is known to interfere with vitamin absorption.[61] A meta-analysis reported that 27% of people who underwent bariatric surgeries experience vitamin B1 deficiency.[62]

History

Thiamine was the first of the water-soluble vitamins to be isolated.[63] The earliest observations in humans and in chickens had shown that diets of primarily polished white rice caused beriberi, but did not attribute it to the absence of a previously unknown essential nutrient.[64][65]

In 1884, Takaki Kanehiro, a surgeon general in the Imperial Japanese Navy, rejected the previous germ theory for beriberi and suggested instead that the disease was due to insufficiencies in the diet.[64] Switching diets on a navy ship, he discovered that replacing a diet of white rice only with one also containing barley, meat, milk, bread, and vegetables, nearly eliminated beriberi on a nine-month sea voyage. However, Takaki had added many foods to the successful diet and he incorrectly attributed the benefit to increased protein intake, as vitamins were unknown at the time. The Navy was not convinced of the need for such an expensive program of dietary improvement, and many men continued to die of beriberi, even during the Russo-Japanese war of 1904–5. Not until 1905, after the anti-beriberi factor had been discovered in rice bran (removed by polishing into white rice) and in barley bran, was Takaki's experiment rewarded. He was made a baron in the Japanese peerage system, after which he was affectionately called "Barley Baron".[64]

The specific connection to grain was made in 1897 by Christiaan Eijkman, a military doctor in the Dutch East Indies, who discovered that fowl fed on a diet of cooked, polished rice developed paralysis that could be reversed by discontinuing rice polishing.[65] He attributed beriberi to the high levels of starch in rice being toxic. He believed that the toxicity was countered in a compound present in the rice polishings.[66] An associate, Gerrit Grijns, correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901: He concluded that rice contains an essential nutrient in the outer layers of the grain that is removed by polishing.[67] Eijkman was eventually awarded the Nobel Prize in Physiology and Medicine in 1929, because his observations led to the discovery of vitamins.

In 1910, a Japanese agricultural chemist of Tokyo Imperial University, Umetaro Suzuki, isolated a water-soluble thiamine compound from rice bran, which he named aberic acid. (He later renamed it Orizanin.) He described the compound as not only an anti-beriberi factor, but also as being essential to human nutrition; however, this finding failed to gain publicity outside of Japan, because a claim that the compound was a new finding was omitted in translation of his publication from Japanese to German.[63] In 1911 a Polish biochemist Casimir Funk isolated the antineuritic substance from rice bran (the modern thiamine) that he called a "vitamine" (on account of its containing an amino group).[68][69] However, Funk did not completely characterize its chemical structure. Dutch chemists, Barend Coenraad Petrus Jansen and his closest collaborator Willem Frederik Donath, went on to isolate and crystallize the active agent in 1926,[70] whose structure was determined by Robert Runnels Williams, in 1934. Thiamine was named by the Williams team as a portmanteau of "thio" (meaning sulfur-containing) and "vitamin". The term "vitamin" coming indirectly, by way of Funk, from the amine group of thiamine itself (although by this time, vitamins were known to not always be amines, for example, vitamin C). Thiamine was also synthesized by the Williams group in 1936.[71]

Sir Rudolph Peters, in Oxford, used pigeons to understand how thiamine deficiency results in the pathological-physiological symptoms of beriberi. Pigeons fed exclusively on polished rice developed opisthotonos, a condition characterized by head retraction. If not treated, the animals died after a few days. Administration of thiamine after opisthotonos was observed led to a complete cure within 30 minutes. As no morphological modifications were seen in the brain of the pigeons before and after treatment with thiamine, Peters introduced the concept of a biochemical-induced injury.[72] In 1937, Lohmann and Schuster showed that the diphosphorylated thiamine derivative, TPP, was a cofactor required for the oxidative decarboxylation of pyruvate.[73]

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External links

  • "Thiamine". Drug Information Portal. US National Library of Medicine.

thiamine, confused, with, thymine, also, known, thiamin, vitamin, vitamin, essential, micronutrient, that, cannot, made, body, found, food, commercially, synthesized, dietary, supplement, medication, phosphorylated, forms, thiamine, required, some, metabolic, . Not to be confused with Thymine Thiamine also known as thiamin and vitamin B1 is a vitamin an essential micronutrient that cannot be made in the body 3 4 It is found in food and commercially synthesized to be a dietary supplement or medication 1 5 Phosphorylated forms of thiamine are required for some metabolic reactions including the breakdown of glucose and amino acids 1 ThiamineSkeletal formula and ball and stick model of the thiamine cationClinical dataPronunciation ˈ 8 aɪ e m ɪ n THY e minOther namesVitamin B1 aneurine thiaminAHFS Drugs comMonographLicense dataUS DailyMed Thiamine US FDA ThiamineRoutes ofadministrationby mouth IV IM 1 Drug classvitaminATC codecation A11DA01 WHO Legal statusLegal statusUS OTCPharmacokinetic dataBioavailability3 7 to 5 3 Thiamine hydrochloride 2 IdentifiersIUPAC name 2 3 4 amino 2 methylpyrimidin 5 yl methyl 4 methyl 1 3 thiazol 3 ium 5 yl ethanolCAS Numbercation 70 16 6 Y 67 03 8 Cl HCl Cl salt 59 43 8 YPubChem CIDcation 1130Cl salt 6042DrugBankcation DB00152ChemSpidercation 1098UNIIcation 4ABT0J945JCl salt X66NSO3N35 YKEGGcation C00378ChEBIcation CHEBI 18385ChEMBLcation ChEMBL1547CompTox Dashboard EPA cation DTXSID50220251Chemical and physical dataFormulaC 12H 17N 4O S Molar mass265 36 g mol 13D model JSmol cation Interactive imageSMILES cation Cc2ncc C n 1csc CCO c1C c N n2InChI cation InChI 1S C12H17N4OS c1 8 11 3 4 17 18 7 16 8 6 10 5 14 9 2 15 12 10 13 h5 7 17H 3 4 6H2 1 2H3 H2 13 14 15 q 1 YKey JZRWCGZRTZMZEH UHFFFAOYSA NFood sources of thiamine include whole grains legumes and some meats and fish 1 6 Grain processing removes much of the vitamin content so in many countries cereals and flours are enriched with thiamine 1 Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it include beriberi and Wernicke encephalopathy They are also used to treat maple syrup urine disease and Leigh syndrome Supplements and medications are typically taken by mouth but may also be given by intravenous or intramuscular injection 7 Thiamine supplements are generally well tolerated Allergic reactions including anaphylaxis may occur when repeated doses are given by injection 7 8 Thiamine is on the World Health Organization s List of Essential Medicines 9 It is available as a generic medication and in some countries as a non prescription dietary supplement 7 Contents 1 Definition 2 Deficiency 3 Biological functions 3 1 Thiamine pyrophosphate 3 2 Thiamine triphosphate 3 3 Adenosine derivatives 4 Medical uses 5 Dietary recommendations 5 1 Safety 5 2 Labeling 6 Sources 6 1 Food fortification 7 Synthesis 7 1 Biosynthesis 7 2 Laboratory synthesis 7 3 Industrial synthesis 7 4 Synthetic analogues 8 Absorption metabolism and excretion 8 1 Interference 9 History 10 References 11 External linksDefinition EditThiamine is one of the B vitamins and is also known as vitamin B1 3 4 It is a cation that is usually supplied as a chloride salt It is soluble in water methanol and glycerol but practically insoluble in less polar organic solvents 10 11 In the body thiamine can form derivatives the most well characterized of which is thiamine pyrophosphate TPP a coenzyme in the catabolism of sugars and amino acids 3 The chemical structure consists of an aminopyrimidine and a thiazolium ring linked by a methylene bridge The thiazole is substituted with methyl and hydroxyethyl side chains Thiamine is stable at acidic pH but it is unstable in alkaline solutions and from exposure to heat 10 11 It reacts strongly in Maillard type reactions 10 Oxidation yields the fluorescent derivative thiochrome which can be used to determine the amount of the vitamin present in biological samples 12 Deficiency EditMain article Thiamine deficiency Well known disorders caused by thiamine deficiency include beriberi Wernicke Korsakoff syndrome optic neuropathy Leigh s disease African seasonal ataxia or Nigerian seasonal ataxia and central pontine myelinolysis 13 Symptoms include malaise weight loss irritability and confusion 10 14 15 In Western countries chronic alcoholism is a risk factor for deficiency Also at risk are older adults persons with HIV AIDS or diabetes and those who have had bariatric surgery 1 Varying degrees of thiamine insufficiency have been associated with the long term use of diuretics 16 17 Biological functions Edit Thiamine monophosphate ThMP Five natural thiamine phosphate derivatives are known thiamine monophosphate ThMP thiamine pyrophosphate TPP thiamine triphosphate ThTP adenosine thiamine diphosphate AThDP and adenosine thiamine triphosphate AThTP They are involved in many cellular processes 18 The best characterized form is TPP a coenzyme in the catabolism of sugars and amino acids While its role is well known the non coenzyme action of thiamine and derivatives may be realized through binding to proteins which do not use that mechanism 19 No physiological role is known for the monophosphate Thiamine pyrophosphate Edit Main article thiamine pyrophosphate Thiamine pyrophosphate TPP The ylide form of TPP Thiamine pyrophosphate TPP also called thiamine diphosphate ThDP participates as a coenzyme in metabolic reactions including those in which polarity inversion takes place 20 Its synthesis is catalyzed by the enzyme thiamine diphosphokinase according to the reaction thiamine ATP TPP AMP EC 2 7 6 2 TPP is a coenzyme for several enzymes 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 The mechanism of action of TPP as a coenzyme relies on its ability to form an ylide 21 Examples include Present in most species pyruvate dehydrogenase and 2 oxoglutarate dehydrogenase also called a ketoglutarate dehydrogenase branched chain a keto acid dehydrogenase 2 hydroxyphytanoyl CoA lyase transketolase Present in some species pyruvate decarboxylase in yeast several additional bacterial enzymesThe enzymes transketolase pyruvate dehydrogenase PDH and 2 oxoglutarate dehydrogenase OGDH are important in carbohydrate metabolism The cytosolic enzyme transketolase is central to 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 the main energy transfer molecule for the cell PDH links glycolysis to the citric acid cycle while the reaction catalyzed by OGDH is a rate limiting step in the citric acid cycle In the nervous system PDH is also involved in the synthesis of myelin and the neurotransmitter acetylcholine 11 Thiamine triphosphate Edit Thiamine triphosphate ThTP ThTP was long considered a neurone specific form of thiamine It is implicated in chloride channel activation in mammals and other animals although its precise role is not completely understood 22 Recently ThTP has been found in bacteria fungi and plants suggesting that it also has a much more general cellular role 23 In Escherichia coli it is implicated in the response to amino acid starvation 24 Adenosine derivatives Edit Adenosine thiamine diphosphate AThDP Adenosine thiamine triphosphate AThTP AThDP exists in small amounts in vertebrate liver but its role remains unknown 24 AThTP is present in E coli where it accumulates as a result of carbon starvation In this bacterium AThTP may account for up to 20 of total thiamine It also exists in lesser amounts in yeast roots of higher plants and animal tissue 24 Medical uses EditSee also Prenatal vitamins During pregnancy thiamine is sent to the fetus via the placenta Pregnant women have a greater requirement for the vitamin than other adults especially during the third trimester Pregnant women with hyperemesis gravidarum are at an increased risk of thiamine deficiency due to losses when vomiting 25 In lactating women thiamine is delivered in breast milk even if it results in thiamine deficiency in the mother 4 26 Thiamine is important not only for mitochondrial membrane development but also for synaptic membrane function 27 It has also been suggested that a deficiency hinders brain development in infants and may be a cause of sudden infant death syndrome 22 Dietary recommendations EditUS National Academy of MedicineAge group RDA mg day Infants 0 6 months 0 2 Infants 6 12 months 0 3 1 3 years 0 54 8 years 0 69 13 years 0 9Females 14 18 years 1 0Males 14 years 1 2Females 19 years 1 1Pregnant lactating females 14 50 1 4 Adequate intake for infants as an RDA has yet to be established 4 European Food Safety AuthorityAge group Adequate intake mg MJ 28 All persons 7 months 0 1Neither the US National Academy of Medicine nor the European Food Safety Authority have determined the tolerable upper intake level for thiamine 4 The US National Academy of Medicine updated the Estimated Average Requirements EARs and Recommended Dietary Allowances RDAs for thiamine in 1998 The EARs for thiamine for women and men aged 14 and over are 0 9 mg day and 1 1 mg day respectively the RDAs are 1 1 and 1 2 mg day respectively RDAs are higher than EARs to provide adequate intake levels for individuals with higher than average requirements The RDA during pregnancy and for lactating females is 1 4 mg day For infants up to the age of 12 months the Adequate Intake AI is 0 2 0 3 mg day and for children aged 1 13 years the RDA increases with age from 0 5 to 0 9 mg day 4 The European Food Safety Authority EFSA refers to the collective set of information as Dietary Reference Values with Population Reference Intakes PRIs instead of RDAs and Average Requirements instead of EARs For women including those pregnant or lactating men and children the PRI is 0 1 mg thiamine per megajoule MJ of energy in their diet As the conversion is 1 MJ 239 kcal an adult consuming 2390 kilocalories ought to be consuming 1 0 mg thiamine This is slightly lower than the US RDA 29 Neither the National Academy of Medicine nor EFSA have set an upper intake level for thiamine as there is no human data for adverse effects from high doses 4 28 Safety Edit Thiamine is generally well tolerated and non toxic when administered orally 7 There are rare reports of adverse side effects when thiamine is given intravenously including allergic reactions nausea lethargy and impaired coordination 28 3 Labeling Edit For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value Since May 27 2016 the Daily Value has been 1 2 mg in line with the RDA 30 31 Sources EditThiamine is found in a wide variety of processed and whole foods 18 including lentils peas whole grains pork and nuts 6 32 A typical daily prenatal vitamin product contains around 1 5 mg of thiamine 33 Food fortification Edit Main article Food fortification Some countries require or recommend fortification of grain foods such as wheat rice or maize corn because processing lowers vitamin content 34 As of February 2022 59 countries mostly in North and Sub Saharan Africa require food fortification of wheat rice or maize with thiamine or thiamine mononitrate The amounts stipulated range from 2 0 to 10 0 mg kg 35 An additional 18 countries have a voluntary fortification program For example the Indian government recommends 3 5 mg kg for maida white and atta whole wheat flour 36 Synthesis EditBiosynthesis Edit Thiamine biosynthesis occurs in bacteria some protozoans plants and fungi 37 38 The thiazole and pyrimidine moieties are biosynthesized separately and are then combined to form ThMP by the action of thiamine phosphate synthase The pyrimidine ring system is formed in a reaction catalysed by phosphomethylpyrimidine synthase ThiC an enzyme in the radical SAM superfamily of iron sulfur proteins which use S adenosyl methionine as a cofactor 39 40 The starting material is 5 aminoimidazole ribotide which undergoes a rearrangement reaction via radical intermediates which incorporate the blue green and red fragments shown into the product 41 42 The thiazole ring is formed in a reaction catalysed by thiazole synthase EC 2 8 1 10 39 The ultimate precursors are 1 deoxy D xylulose 5 phosphate 2 iminoacetate and a sulfur carrier protein called ThiS An additional protein ThiG is also required to bring together all the components of the ring at the enzyme active site 43 A 3D representation of the TPP riboswitch with thiamine bound The final step to form ThMP involves decarboxylation of the thiazole intermediate which reacts with the pyrophosphate derivative of phosphomethylpyrimidine itself a product of a kinase phosphomethylpyrimidine kinase 39 The biosynthetic pathways differ among organisms In E coli and other enterobacteriaceae ThMP is phosphorylated to the cofactor TPP by a thiamine phosphate kinase ThMP ATP TPP ADP 39 In most bacteria and in eukaryotes ThMP is hydrolyzed to thiamine and then pyrophosphorylated to TPP by thiamine diphosphokinase thiamine ATP TPP AMP 44 The biosynthetic pathways are regulated by riboswitches 3 If there is sufficient thiamine present in the cell then the thiamine binds to the mRNAs for the enzymes that are required in the pathway and prevents their translation 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 known riboswitch found in both eukaryotic and prokaryotic organisms 45 Laboratory synthesis Edit In the first total synthesis in 1936 ethyl 3 ethoxypropanoate was treated with ethyl formate to give an intermediate dicarbonyl compound which when reacted with acetamidine formed a substituted pyrimidine Conversion of its hydroxyl group to an amino group was carried out by nucleophilic aromatic substitution first to the chloride derivative using phosphorus oxychloride followed by treatment with ammonia The ethoxy group was then converted to a bromo derivative using hydrobromic acid In the final stage thiamine as its dibromide salt was formed in an alkylation reaction using 4 methyl 5 2 hydroxyethyl thiazole 46 7 47 Industrial synthesis Edit Diamine used in the manufacture of thiamine Merck amp Co adapted the 1936 laboratory scale synthesis allowing them to manufacture thiamine in Rahway in 1937 47 However an alternative route using the intermediate Grewe diamine 5 aminomethyl 2 methyl 4 pyrimidinamine first published in 1937 48 was investigated by Hoffman La Roche and competitive manufacturing processes followed Efficient routes to the diamine have continued to be of interest 47 49 In the European Economic Area thiamine is registered under REACH regulation and between 100 and 1 000 tonnes per annum are manufactured or imported there 50 Synthetic analogues Edit Many vitamin B1 analogues such as Benfotiamine fursultiamine and sulbutiamine are synthetic derivatives of thiamine Most were developed in Japan in the 1950s and 1960s as forms that were intended to improve absorption compared to thiamine 51 Some are approved for use in some countries as a drug or non prescription dietary supplement for treatment of diabetic neuropathy or other health conditions 52 53 54 Absorption metabolism and excretion EditIn the upper small intestine thiamine phosphate esters present in food are hydrolyzed by alkaline phosphatase enzymes At low concentrations the absorption process is carrier mediated At higher concentrations absorption also occurs via passive diffusion 3 Active transport can be inhibited by alcohol consumption or by folate deficiency 10 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 binding protein has been identified in rat serum and is believed to be a hormone regulated carrier protein important for tissue distribution of thiamine 14 Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion 10 Two members of the family of transporter proteins encoded by the genes SLC19A2 and SLC19A3 are capable of thiamine transport 22 In some tissues thiamine uptake and secretion appear to be mediated by a Na dependent transporter and a transcellular proton gradient 14 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 are present in plasma milk cerebrospinal fluid and it is presumed all extracellular fluid Unlike the highly phosphorylated forms of thiamine ThMP and free thiamine are capable of crossing cell membranes Calcium and magnesium have been shown to affect the distribution of thiamine in the body and magnesium deficiency has been shown to aggravate thiamine deficiency 22 Thiamine contents in human tissues are less than those of other species 14 55 Thiamine and its metabolites 2 methyl 4 amino 5 pyrimidine carboxylic acid 4 methyl thiazole 5 acetic acid and others are excreted principally in the urine 3 Interference Edit The bioavailability of thiamine in foods can be interfered with in a variety of ways Sulfites added to foods as a preservative 56 will attack thiamine at the methylene bridge cleaving the pyrimidine ring from the thiazole ring The rate of this reaction is increased under acidic conditions 14 Thiamine is degraded by thermolabile thiaminases present in some species of fish shellfish and other foods 10 The pupae of an African silk worm Anaphe venata is a traditional food in Nigeria Consumption leads to thiamine deficiency 57 Older literature reported that in Thailand consumption of fermented uncooked fish caused thiamine deficiency but either abstaining from eating the fish or heating it first reversed the deficiency 58 In ruminants intestinal bacteria synthesize thiamine and thiaminases The bacterial thiaminases are cell surface enzymes that must dissociate from the cell membrane before being activated the dissociation can occur in ruminants under acidotic conditions In dairy cows over feeding with grain causes subacute ruminal acidosis and increased ruminal bacteria thiaminase release resulting in thiamine deficiency 59 From reports on two small studies conducted in Thailand chewing slices of areca nut wrapped in betel leaves and chewing tea leaves reduced food thiamine bioavailability by a mechanism that may involve tannins 58 60 Bariatric surgery for weight loss is known to interfere with vitamin absorption 61 A meta analysis reported that 27 of people who underwent bariatric surgeries experience vitamin B1 deficiency 62 History EditFurther information Vitamin History Thiamine was the first of the water soluble vitamins to be isolated 63 The earliest observations in humans and in chickens had shown that diets of primarily polished white rice caused beriberi but did not attribute it to the absence of a previously unknown essential nutrient 64 65 In 1884 Takaki Kanehiro a surgeon general in the Imperial Japanese Navy rejected the previous germ theory for beriberi and suggested instead that the disease was due to insufficiencies in the diet 64 Switching diets on a navy ship he discovered that replacing a diet of white rice only with one also containing barley meat milk bread and vegetables nearly eliminated beriberi on a nine month sea voyage However Takaki had added many foods to the successful diet and he incorrectly attributed the benefit to increased protein intake as vitamins were unknown at the time The Navy was not convinced of the need for such an expensive program of dietary improvement and many men continued to die of beriberi even during the Russo Japanese war of 1904 5 Not until 1905 after the anti beriberi factor had been discovered in rice bran removed by polishing into white rice and in barley bran was Takaki s experiment rewarded He was made a baron in the Japanese peerage system after which he was affectionately called Barley Baron 64 The specific connection to grain was made in 1897 by Christiaan Eijkman a military doctor in the Dutch East Indies who discovered that fowl fed on a diet of cooked polished rice developed paralysis that could be reversed by discontinuing rice polishing 65 He attributed beriberi to the high levels of starch in rice being toxic He believed that the toxicity was countered in a compound present in the rice polishings 66 An associate Gerrit Grijns correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901 He concluded that rice contains an essential nutrient in the outer layers of the grain that is removed by polishing 67 Eijkman was eventually awarded the Nobel Prize in Physiology and Medicine in 1929 because his observations led to the discovery of vitamins In 1910 a Japanese agricultural chemist of Tokyo Imperial University Umetaro Suzuki isolated a water soluble thiamine compound from rice bran which he named aberic acid He later renamed it Orizanin He described the compound as not only an anti beriberi factor but also as being essential to human nutrition however this finding failed to gain publicity outside of Japan because a claim that the compound was a new finding was omitted in translation of his publication from Japanese to German 63 In 1911 a Polish biochemist Casimir Funk isolated the antineuritic substance from rice bran the modern thiamine that he called a vitamine on account of its containing an amino group 68 69 However Funk did not completely characterize its chemical structure Dutch chemists Barend Coenraad Petrus Jansen and his closest collaborator Willem Frederik Donath went on to isolate and crystallize the active agent in 1926 70 whose structure was determined by Robert Runnels Williams in 1934 Thiamine was named by the Williams team as a portmanteau of thio meaning sulfur containing and vitamin The term vitamin coming indirectly by way of Funk from the amine group of thiamine itself although by this time vitamins were known to not always be amines for example vitamin C Thiamine was also synthesized by the Williams group in 1936 71 Sir Rudolph Peters in Oxford used pigeons to understand how thiamine deficiency results in the pathological physiological symptoms of beriberi Pigeons fed exclusively on polished rice developed opisthotonos a condition characterized by head retraction If not treated the animals died after a few days Administration of thiamine after opisthotonos was observed led to a complete cure within 30 minutes As no morphological modifications were seen in the brain of the pigeons before and after treatment with thiamine Peters introduced the concept of a biochemical induced injury 72 In 1937 Lohmann and Schuster showed that the diphosphorylated thiamine derivative TPP was a cofactor required for the oxidative decarboxylation of pyruvate 73 Some contributors to the discovery of thiamine Takaki Kanehiro Christiaan Eijkman Gerrit Grijns Umetaro Suzuki Casimir Funk Rudolph PetersReferences Edit a b c d e f Thiamin Fact Sheets for Health Professionals Office of Dietary Supplements 11 February 2016 Archived from the original on 30 December 2016 Retrieved 30 December 2016 Smithline HA Donnino M Greenblatt DJ February 2012 Pharmacokinetics of high dose oral thiamine hydrochloride in healthy subjects BMC Clinical Pharmacology 12 1 4 doi 10 1186 1472 6904 12 4 PMC 3293077 PMID 22305197 a b c d e f g Bettendorff L 2020 Thiamine In Marriott BP Birt DF Stallings VA Yates AA eds Present Knowledge in Nutrition Eleventh Edition London United Kingdom Academic Press Elsevier pp 171 88 ISBN 978 0 323 66162 1 a b c d e f g Institute of Medicine 1998 Thiamin Dietary Reference Intakes for Thiamin Riboflavin Niacin Vitamin B6 Folate Vitamin B12 Pantothenic Acid Biotin and Choline Washington DC The National Academies Press pp 58 86 ISBN 978 0 309 06554 2 Archived from the original on 16 July 2015 Retrieved 29 August 2017 Thiamine MedlinePlus Drug Information medlineplus gov Retrieved 30 April 2018 a b Thiamin Micronutrient Information Center Linus Pauling Institute Oregon State University 2013 Retrieved 2 February 2022 a b c d American Society of Health System Pharmacists Thiamine Hydrochloride Drugsite Trust Drugs com Retrieved 17 April 2018 Kliegman RM Stanton B 2016 Nelson Textbook of Pediatrics Elsevier Health Sciences p 322 ISBN 9781455775668 There are no cases of adverse effects of excess thiamine A few isolated cases of puritis World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO a b c d e f g Mahan LK Escott Stump S eds 2000 Krause s food nutrition amp diet therapy 10th ed Philadelphia W B Saunders Company ISBN 978 0 7216 7904 4 a b c Butterworth RF 2006 Thiamin In Shils ME Shike M Ross AC Caballero B Cousins RJ eds Modern Nutrition in Health and Disease 10th ed Baltimore Lippincott Williams amp Wilkins Bettendorff L Wins P 2013 Biochemistry of Thiamine and Thiamine Phosphate Compounds Encyclopedia of Biological Chemistry pp 202 9 doi 10 1016 B978 0 12 378630 2 00102 X ISBN 9780123786319 McCandless D 2010 Thiamine Deficiency and Associate Clinical Disorders New York NY Humana Press pp 157 9 ISBN 978 1 60761 310 7 a b c d e Combs Jr GF 2008 The Vitamins Fundamental Aspects in Nutrition and Health 3rd ed Ithaca NY Elsevier Academic Press ISBN 978 0 12 183493 7 Smith TJ Johnson CR Koshy R Hess SY Qureshi UA Mynak ML Fischer PR August 2021 Thiamine deficiency disorders a clinical perspective Annals of the New York Academy of Sciences 1498 1 9 28 Bibcode 2021NYASA1498 9S doi 10 1111 nyas 14536 PMC 8451766 PMID 33305487 Katta N Balla S Alpert MA July 2016 Does Long Term Furosemide Therapy Cause Thiamine Deficiency in Patients with Heart Failure A Focused Review The American Journal of Medicine 129 7 753 e7 753 e11 doi 10 1016 j amjmed 2016 01 037 PMID 26899752 Gomes F Bergeron G Bourassa MW Fischer PR August 2021 Thiamine deficiency unrelated to alcohol consumption in high income countries a literature review Annals of the New York Academy of Sciences 1498 1 46 56 doi 10 1111 nyas 14569 PMC 8451800 PMID 33576090 a b Fitzpatrick TB Chapman LM August 2020 The importance of thiamine vitamin B1 in plant health From crop yield to biofortification The Journal of Biological Chemistry 295 34 12002 13 doi 10 1074 jbc REV120 010918 PMC 7443482 PMID 32554808 Mkrtchyan G Aleshin V Parkhomenko Y Kaehne T Di Salvo ML Parroni A et al July 2015 Molecular mechanisms of the non coenzyme action of thiamin in brain biochemical structural and pathway analysis Scientific Reports 5 12583 Bibcode 2015NatSR 512583M doi 10 1038 srep12583 PMC 4515825 PMID 26212886 Boluda CJ Junca C Soto E de la Cruz D Pena A 13 December 2019 Umpolung in reactions catalyzed by thiamine pyrophosphate dependent enzymes Ciencia Ambiente y Clima in Spanish 2 2 27 42 doi 10 22206 cac 2019 v2i2 pp27 42 ISSN 2636 2333 S2CID 213836801 Ciszak EM Korotchkina LG Dominiak PM Sidhu S Patel MS June 2003 Structural basis for flip flop action of thiamin pyrophosphate dependent enzymes revealed by human pyruvate dehydrogenase The Journal of Biological Chemistry 278 23 21240 21246 doi 10 1074 jbc M300339200 PMID 12651851 a b c d Lonsdale D March 2006 A review of the biochemistry metabolism and clinical benefits of thiamin e and its derivatives Evidence Based Complementary and Alternative Medicine 3 1 49 59 doi 10 1093 ecam nek009 PMC 1375232 PMID 16550223 Makarchikov AF Lakaye B Gulyai IE Czerniecki J Coumans B et al July 2003 Thiamine triphosphate and thiamine triphosphatase activities from bacteria to mammals Cellular and Molecular Life Sciences 60 7 1477 88 doi 10 1007 s00018 003 3098 4 PMID 12943234 S2CID 25400487 a b c Bettendorff L November 2021 Update on Thiamine Triphosphorylated Derivatives and Metabolizing Enzymatic Complexes Biomolecules 11 11 1645 doi 10 3390 biom11111645 PMC 8615392 PMID 34827643 Oudman E Wijnia JW Oey M van Dam M Painter RC Postma A May 2019 Wernicke s encephalopathy in hyperemesis gravidarum A systematic review European Journal of Obstetrics Gynecology and Reproductive Biology 236 84 93 doi 10 1016 j ejogrb 2019 03 006 hdl 1874 379566 PMID 30889425 S2CID 84184482 Butterworth RF December 2001 Maternal thiamine deficiency still a problem in some world communities The American Journal of Clinical Nutrition 74 6 712 3 doi 10 1093 ajcn 74 6 712 PMID 11722950 Kloss O Eskin NA Suh M April 2018 Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure Biochemistry and Cell Biology 96 2 169 77 doi 10 1139 bcb 2017 0082 hdl 1807 87775 PMID 28915355 a b c Tolerable Upper Intake Levels For Vitamins And Minerals PDF European Food Safety Authority 2006 archived PDF from the original on 16 March 2016 Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products Nutrition and Allergies PDF 2017 Archived PDF from the original on 28 August 2017 Federal Register May 27 2016 Food Labeling Revision of the Nutrition and Supplement Facts Labels FR page 33982 PDF Archived PDF from the original on 8 August 2016 Daily Value Reference of the Dietary Supplement Label Database DSLD Dietary Supplement Label Database DSLD Archived from the original on 7 April 2020 Retrieved 6 February 2022 Thiamin content per 100 grams select food subset abridged list by food groups United States Department of Agriculture Agricultural Research Service USDA Branded Food Products Database v 3 6 4 1 17 January 2017 Archived from the original on 2 February 2017 Retrieved 27 January 2017 Kominiarek MA Rajan P November 2016 Nutrition Recommendations in Pregnancy and Lactation The Medical Clinics of North America 100 6 1199 215 doi 10 1016 j mcna 2016 06 004 PMC 5104202 PMID 27745590 What nutrients are added to flour and rice in fortification Food Fortification Initiative 2021 Retrieved 8 October 2021 Map Count of Nutrients In Fortification Standards Global Fortification Data Exchange Retrieved 11 October 2021 Direction under Section 16 5 of Foods Safety and Standards Act 2006 regarding Operationalisation of Food Safety amp Standards Fortification of Foods Regulations 2017 relating to standards for fortification of food PDF Food Safety amp Standards Authority of India FSSAI 19 May 2017 Retrieved 1 February 2022 Webb ME Marquet A Mendel RR Rebeille F Smith AG October 2007 Elucidating biosynthetic pathways for vitamins and cofactors Natural Product Reports 24 5 988 1008 doi 10 1039 b703105j PMID 17898894 Begley TP Chatterjee A Hanes JW Hazra A Ealick SE April 2008 Cofactor biosynthesis still yielding fascinating new biological chemistry Current Opinion in Chemical Biology 12 2 118 25 doi 10 1016 j cbpa 2008 02 006 PMC 2677635 PMID 18314013 a b c d Caspi R 14 September 2011 Pathway superpathway of thiamine diphosphate biosynthesis I MetaCyc Metabolic Pathway Database Retrieved 1 February 2022 Holliday GL Akiva E Meng EC Brown SD Calhoun S et al 2018 Atlas of the Radical SAM Superfamily Divergent Evolution of Function Using a Plug and Play Domain Radical SAM Enzymes Methods in Enzymology Vol 606 pp 1 71 doi 10 1016 bs mie 2018 06 004 ISBN 9780128127940 PMC 6445391 PMID 30097089 Chatterjee A Hazra AB Abdelwahed S Hilmey DG Begley TP November 2010 A radical dance in thiamin biosynthesis mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase Angewandte Chemie 49 46 8653 6 doi 10 1002 anie 201003419 PMC 3147014 PMID 20886485 Mehta AP Abdelwahed SH Fenwick MK Hazra AB Taga ME Zhang Y et al August 2015 Anaerobic 5 Hydroxybenzimidazole Formation from Aminoimidazole Ribotide An Unanticipated Intersection of Thiamin and Vitamin B Biosynthesis Journal of the American Chemical Society 137 33 10444 7 doi 10 1021 jacs 5b03576 PMC 4753784 PMID 26237670 Begley TP February 2006 Cofactor biosynthesis an organic chemist s treasure trove Natural Product Reports 23 1 15 25 doi 10 1039 b207131m PMID 16453030 Caspi R 23 September 2011 Pathway superpathway of thiamine diphosphate biosynthesis III eukaryotes MetaCyc Metabolic Pathway Database Retrieved 14 November 2022 Bocobza SE Aharoni A October 2008 Switching the light on plant riboswitches Trends in Plant Science 13 10 526 33 doi 10 1016 j tplants 2008 07 004 PMID 18778966 Tylicki A Lotowski Z Siemieniuk M Ratkiewicz A February 2018 Thiamine and selected thiamine antivitamins biological activity and methods of synthesis Bioscience Reports 38 1 doi 10 1042 BSR20171148 PMC 6435462 PMID 29208764 a b c Eggersdorfer M Laudert D Letinois U McClymont T Medlock J Netscher T Bonrath W December 2012 One hundred years of vitamins a success story of the natural sciences Angewandte Chemie 51 52 12960 90 doi 10 1002 anie 201205886 PMID 23208776 Todd AR Bergel F 1937 73 Aneurin Part VII A synthesis of aneurin Journal of the Chemical Society Resumed 364 doi 10 1039 JR9370000364 Jiang M Liu M Huang H Chen F 2021 Fully Continuous Flow Synthesis of 5 Aminomethyl 2 methylpyrimidin 4 amine A Key Intermediate of Vitamin B1 Organic Process Research amp Development 25 10 2331 7 doi 10 1021 acs oprd 1c00253 S2CID 242772232 Substance Infocard echa europa eu Retrieved 11 May 2022 Bettendorff L 2014 Chapter 7 Thiamine In Zempleni J Suttie JW Gregory JF Stover PJ eds Handbook of vitamins 5th ed Hoboken CRC Press pp 267 324 ISBN 9781466515574 Zaheer A Zaheer F Saeed H Tahir Z Tahir MW April 2021 A Review of Alternative Treatment Options in Diabetic Polyneuropathy Cureus 13 4 e14600 doi 10 7759 cureus 14600 PMC 8139599 PMID 34040901 McCarty MF Inoguchi T 2008 11 Targeting Oxidant Stress as a Strategy for Preventing Vascular Complications of Diabetes and Metabolic Syndrome In Pasupuleti VK Anderson JW eds Nutraceuticals glycemic health and type 2 diabetes 1st ed Ames Iowa Wiley Blackwell IFT Press p 213 ISBN 9780813804286 Lonsdale D September 2004 Thiamine tetrahydrofurfuryl disulfide a little known therapeutic agent Medical Science Monitor 10 9 RA199 203 PMID 15328496 Bettendorff L Mastrogiacomo F Kish SJ Grisar T January 1996 Thiamine thiamine phosphates and their metabolizing enzymes in human brain Journal of Neurochemistry 66 1 250 8 doi 10 1046 j 1471 4159 1996 66010250 x PMID 8522961 S2CID 7161882 McGuire M Beerman KA 2007 Nutritional Sciences From Fundamentals to Foods California Thomas Wadsworth Nishimune T Watanabe Y Okazaki H Akai H 2000 Thiamin is decomposed due to Anaphe spp entomophagy in seasonal ataxia patients in Nigeria J Nutr 130 6 1625 8 doi 10 1093 jn 130 6 1625 PMID 10827220 a b Vimokesant SL Hilker DM Nakornchai S Rungruangsak K Dhanamitta S December 1975 Effects of betel nut and fermented fish on the thiamin status of northeastern Thais Am J Clin Nutr 28 12 1458 63 doi 10 1093 ajcn 28 12 1458 PMID 803009 Pan X Nan X Yang L Jiang L Xiong B September 2018 Thiamine status metabolism and application in dairy cows a review Br J Nutr 120 5 491 9 doi 10 1017 S0007114518001666 PMID 29986774 S2CID 51606809 Vimokesant S Kunjara S Rungruangsak K Nakornchai S Panijpan B 1982 Beriberi caused by antithiamin factors in food and its prevention Ann N Y Acad Sci 378 1 123 36 Bibcode 1982NYASA 378 123V doi 10 1111 j 1749 6632 1982 tb31191 x PMID 7044221 S2CID 40854060 Nunes R Santos Sousa H Vieira S Nogueiro J Bouca Machado R et al March 2022 Vitamin B Complex Deficiency After Roux en Y Gastric Bypass and Sleeve Gastrectomy a Systematic Review and Meta Analysis Obes Surg 32 3 873 91 doi 10 1007 s11695 021 05783 2 PMID 34982396 S2CID 245655046 Bahardoust M Eghbali F Shahmiri SS Alijanpour A Yarigholi F et al September 2022 B1 Vitamin Deficiency After Bariatric Surgery Prevalence and Symptoms a Systematic Review and Meta analysis Obes Surg 32 9 3104 12 doi 10 1007 s11695 022 06178 7 PMID 35776243 S2CID 250149680 a b Suzuki U Shimamura T 1911 Active constituent of rice grits preventing bird polyneuritis Tokyo Kagaku Kaishi 32 4 7 144 6 335 58 doi 10 1246 nikkashi1880 32 4 a b c McCollum EV 1957 A History of Nutrition Cambridge Massachusetts Riverside Press Houghton Mifflin a b Eijkman C 1897 Eine Beriberiahnliche Krankheit der Huhner A disease of chickens which is similar to beriberi Archiv fur Pathologische Anatomie und Physiologie und fur Klinische Medicin 148 3 523 532 doi 10 1007 BF01937576 S2CID 38445999 The Nobel Prize and the Discovery of Vitamins nobelprize org Grijns G 1901 Over polyneuritis gallinarum On polyneuritis gallinarum Geneeskundig Tijdschrift voor Nederlandsch Indie Medical Journal for the Dutch East Indies 41 1 3 11 Funk C December 1911 On the chemical nature of the substance which cures polyneuritis in birds induced by a diet of polished rice The Journal of Physiology 43 5 395 400 doi 10 1113 jphysiol 1911 sp001481 PMC 1512869 PMID 16993097 Funk C 1912 The etiology of the deficiency diseases Beri beri polyneuritis in birds epidemic dropsy scurvy experimental scurvy in animals infantile scurvy ship beri beri pellagra Journal of State Medicine 20 341 68 The word vitamine is coined on p 342 It is now known that all these diseases with the exception of pellagra can be prevented and cured by the addition of certain preventative substances the deficient substances which are of the nature of organic bases we will call vitamines and we will speak of a beri beri or scurvy vitamine which means a substance preventing the special disease Jansen BC Donath WF 1926 On the isolation of antiberiberi vitamin Proc Kon Ned Akad Wet 29 1390 400 Williams RR Cline JK 1936 Synthesis of Vitamin B1 Journal of the American Chemical Society 58 8 1504 5 doi 10 1021 ja01299a505 Peters RA 1936 The biochemical lesion in vitamin B1 deficiency Application of modern biochemical analysis in its diagnosis Lancet 230 5882 1161 4 doi 10 1016 S0140 6736 01 28025 8 Lohmann K Schuster P 1937 Untersuchungen uber die Cocarboxylase Biochem Z 294 188 214 External links Edit Thiamine Drug Information Portal US National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Thiamine amp oldid 1128370058, wikipedia, wiki, book, books, library,

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