THIAMINE

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient for humans and animals.
Thiamine is found in food and commercially synthesized to be a dietary supplement or medication.
Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.

CAS Number: 70-16-6
IUPAC name: 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol
EC Number: 200-425-3
Molecular Formula: C12H17N4OS+

Other names: thiamine, thiamin, vitamin B1, Aneurin, Antiberiberi factor, Thiamine ion, 70-16-6, thiaminium, Betaxin, thiamine(1+), Biamine, thiamine(1+) ion, CHEBI:18385, 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol, 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium, Thiamine (Vit B1), 3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM, 4ABT0J945J, VIB, THD, UNII-X66NSO3N35, CCRIS 5823, HSDB 220, 3-((4-Amino-2-methylpyrimidin-5-yl)methyl)-5-(2-hydroxyethyl)-4-methylthiazol-3-ium, DTXSID2023648, Thiazolium, 3-((4-amino-2-methyl-5-pyrimidinyl)methyl)-5-(2-hydroxyethyl)-4-methyl-, [3H]thiamine, [3H]-thiamine, Vitamin B 1, NSC36226, [3H]vitamin B1, EINECS 200-425-3, vitaminum b1, 1sbr, 3rlb, 3-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium, ThOH, Vit B1, Thiamine HCL 100 mg, Prestwick0_000631, Prestwick1_000631, Prestwick2_000631, Prestwick3_000631, bmse000274, TimTec1_000613, CHEMBL1547, THIAMIN; VITAMIN B1, UNII-4ABT0J945J, SCHEMBL10075, BSPBio_000622, SPBio_002841, BPBio1_000686, DTXCID903648, GTPL4628, GTPL4629, SCHEMBL22129283, A11DA01, DTXSID50220251, BDBM50373877, AKOS000668650, DB00152, 2-[3-[(4-amino-2-methyl-pyrimidin-5-yl)methyl]-4-methyl-thiazol-3-ium-5-yl]ethanol, 3[(4-Amino-2-methyl-5-pyrimidinyl)-methyl]-5-(2-hydroxyethyl)-4-methylthiazolium chloride, SMP1_000084, NCGC00017013-05, NCGC00017013-06, NCGC00188957-01, NCGC00188957-02, NS00002759, C00378, Q83187, 2-(3-((4-amino-2-methyl-pyrimidin-5-yl)methyl)-4-methyl-1-thia-3-azoniacyclopenta-2,4-dien-5-yl)ethanol

Food sources of thiamine include whole grains, legumes, and some meats and fish.
Grain processing removes much of the vitamin content, so in many countries cereals and flours are enriched with thiamine.
Supplements and medications are available to treat and prevent thiamine deficiency and the disorders that result from it such as 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.

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

Definition
Thiamine is one of the B vitamins and is also known as vitamin B1.
Thiamine is a cation that is usually supplied as a chloride salt.
Thiamine is soluble in water, methanol and glycerol, but practically insoluble in less polar organic solvents.
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.

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.
Thiamine reacts strongly in Maillard-type reactions.
Oxidation yields the fluorescent derivative thiochrome, which can be used to determine the amount of the vitamin present in biological samples.

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.
Symptoms include malaise, weight loss, irritability and confusion.

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.
Varying degrees of thiamine insufficiency have been associated with the long-term use of diuretics.

Biological functions
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.
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.
No physiological role is known for the monophosphate except as an intermediate in cellular conversion of thiamine to the di- and triphosphates.

Thiamine pyrophosphate
Thiamine pyrophosphate (TPP), also called thiamine diphosphate (ThDP), participates as a coenzyme in metabolic reactions, including those in which polarity inversion takes place.
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.

The enzymes transketolase, pyruvate dehydrogenase (PDH), and 2-oxoglutarate dehydrogenase (OGDH) are important in carbohydrate metabolism.
PDH links glycolysis to the citric acid cycle.
OGDH catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO2 during the citric acid cycle.
The reaction catalyzed by OGDH is a rate-limiting step in the citric acid cycle.

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.
In the nervous system, PDH is also involved in the synthesis of myelin and the neurotransmitter acetylcholine.

Thiamine triphosphate
ThTP is implicated in chloride channel activation in the neurons of mammals and other animals, although its role is not well understood.
ThTP has been found in bacteria, fungi and plants, suggesting that it has other cellular roles.
In Escherichia coli, it is implicated in the response to amino acid starvation.

Adenosine derivatives
AThDP exists in small amounts in vertebrate liver, but its role remains unknown.
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.

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.
In lactating women, thiamine is delivered in breast milk even if it results in thiamine deficiency in the mother.

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

Dietary recommendations
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.

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.

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.

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

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.

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

Food fortification
Some countries require or recommend fortification of grain foods such as wheat, rice or maize (corn) because processing lowers vitamin content.
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.
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.

Synthesis
Biosynthesis
Thiamine biosynthesis occurs in bacteria, some protozoans, plants, and fungi.
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.

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.

The thiazole ring is formed in a reaction catalysed by thiazole synthase (EC 2.8.1.10).
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.

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.

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).
In most bacteria and in eukaryotes, ThMP is hydrolyzed to thiamine and then pyrophosphorylated to TPP by thiamine diphosphokinase (thiamine + ATP → TPP + AMP).

The biosynthetic pathways are regulated by riboswitches.
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.

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.

Industrial synthesis
Merck & Co. adapted the 1936 laboratory-scale synthesis, allowing them to manufacture thiamine in Rahway in 1937.
However, an alternative route using the intermediate Grewe diamine (5-(aminomethyl)-2-methyl-4-pyrimidinamine), first published in 1937, was investigated by Hoffman La Roche and competitive manufacturing processes followed.
Efficient routes to the diamine have continued to be of interest.
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.

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.
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.

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.
Active transport can be inhibited by alcohol consumption or by folate deficiency.

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.

Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.
Two members of the family of transporter proteins encoded by the genes SLC19A2 and SLC19A3 are capable of thiamine transport.
In some tissues, thiamine uptake and secretion appear to be mediated by a Na+-dependent transporter and a transcellular proton gradient.

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.
Thiamine contents in human tissues are less than those of other species.

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.

Interference
The bioavailability of thiamine in foods can be interfered with in a variety of ways.
Sulfites, added to foods as a preservative, 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.
Thiamine is degraded by thermolabile thiaminases present in some species of fish, shellfish and other foods.

The pupae of an African silk worm, Anaphe venata, is a traditional food in Nigeria.
Consumption leads to thiamine deficiency.
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.

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.

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.

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

History
Further information: Vitamin § History
Thiamine was the first of the water-soluble vitamins to be isolated.
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.

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.
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".

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.
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.

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.

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).
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, 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.

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.
In 1937, Lohmann and Schuster showed that the diphosphorylated thiamine derivative, TPP, was a cofactor required for the oxidative decarboxylation of pyruvate.

Molar mass: 265.36 g·mol−1
XLogP3-AA: 1
Hydrogen Bond Donor Count: 2
Hydrogen Bond Acceptor Count: 5

Rotatable Bond Count: 4
Exact Mass: 265.11230735 g/mol
Monoisotopic Mass: 265.11230735 g/mol
Topological Polar Surface Area: 104Å²

Heavy Atom Count: 18
Complexity: 269
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Thiamin (thiamine), or vitamin B1, is a water-soluble vitamin found naturally in some foods, added to foods, and sold as a supplement.
Thiamin plays a vital role in the growth and function of various cells.
Only small amounts are stored in the liver, so a daily intake of thiamin-rich foods is needed.

Although symptoms of thiamin deficiency were first recorded in ancient texts of Chinese medicine, the symptoms were not connected with diet until the late 19th century.
In 1884, a Japanese physician noted very high rates of illness and death among Japanese sailors eating a limited diet of only rice for months while at sea.

When given a more varied diet with whole grains, meats, beans, and vegetables, rates of illness and death nearly disappeared.
Around the same time, two Dutch scientists observed that chickens fed white polished rice developed leg paralysis, whereas chickens fed brown unpolished rice did not.
Their observations led to the discovery of thiamin present in the outer layers of rice that were removed with polishing.

Thiamine (vitamin B1) is found in many foods and is used to treat low thiamine, beriberi, certain nerve diseases, and Wernicke-Korsakoff syndrome (WKS).

Thiamine is required by our bodies to properly use carbohydrates. It also helps maintain proper nerve function.
Thiamine's found in foods such as yeast, cereal grains, beans, nuts, and meat. It's often used in combination with other B vitamins, and is found in many vitamin B complex products.

People take thiamine for conditions related to low levels of thiamine, including beriberi and inflammation of the nerves (neuritis).
Thiamine's also used for digestive problems, diabetic nerve pain, heart disease, and other conditions, but there is no good scientific evidence to support these other uses.

Thiamine is a primary alcohol that is 1,3-thiazol-3-ium substituted by (4-amino-2-methylpyrimidin-5-yl)methyl, methyl and 2-hydroxyethyl groups at positions 3, 4 and 5, respectively.
Thiamine has a role as a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite.
Thiamine is a primary alcohol and a vitamin B1.
Thiamine is a conjugate base of a thiamine(2+).

Thiamine or thiamin, also known as vitamin B1, is a colorless compound with the chemical formula C12H17N4OS.
Thiamine is soluble in water and insoluble in alcohol.
Thiamine decomposes if heated.
Thiamine was first discovered by Umetaro Suzuki in Japan when researching how rice bran cured patients of Beriberi.

Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation.
Thiamine plays an important role in helping the body convert carbohydrates and fat into energy.
It is essential for normal growth and development and helps to maintain proper functioning of the heart and the nervous and digestive systems.
Thiamine cannot be stored in the body; however, once absorbed, the vitamin is concentrated in muscle tissue.

Thiamine is a heat-labile and water-soluble essential vitamin, belonging to the vitamin B family, with antioxidant, erythropoietic, mood modulating, and glucose-regulating activities.
Thiamine reacts with adenosine triphosphate (ATP) to form an active coenzyme, thiamine pyrophosphate.

Thiamine pyrophosphate is necessary for the actions of pyruvate dehydrogenase and alpha-ketoglutarate in carbohydrate metabolism and for the actions of transketolase, an enzyme that plays an important role in the pentose phosphate pathway.
Thiamine plays a key role in intracellular glucose metabolism and may inhibit the action of glucose and insulin on arterial smooth muscle cell proliferation.
Thiamine may also protect against lead toxicity by inhibiting lead-induced lipid peroxidation.

Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, which cannot be made in the body.
Thiamine is found in food and commercially synthesized to be a dietary supplement or medication.
Food sources of thiamine include whole grains, legumes, and some meats and fish.
Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine.

Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy.
Other uses include the treatment of maple syrup urine disease and Leigh syndrome.
They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.

Thiamine supplements are generally well tolerated.
Allergic reactions, including anaphylaxis, may occur when repeated doses are given by injection.
Thiamine is required for metabolism including that of glucose, amino acids, and lipids.
Thiamine is on the World Health Organization's List of Essential Medicines.
Thiamine is available as a generic medication, and as an over-the-counter drug.

Chemistry
Thiamine is a colorless organosulfur compound.
Its 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 soluble in water, methanol, and glycerol and practically insoluble in less polar organic solvents.

Thiamine is a cation and is usually supplied as its chloride salt.
The amino group can form additional salts with further acids.
Thiamine is stable at acidic pH, but is unstable in alkaline solutions and from exposure to heat.
Thiamine reacts strongly in Maillard-type reactions

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, ready for the final stage in which thiamine (as its dibromide salt) was formed in an alkylation reaction using 4-methyl-5-(2-hydroxyethyl)thiazole.

Functions
Thiamine 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.
Five natural thiamine phosphate derivatives are known: thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), adenosine thiamine triphosphate (AThTP) and adenosine thiamine diphosphate (AThDP).
While the coenzyme role of thiamine diphosphate is well-known and extensively characterized, the non-coenzyme action of thiamine and derivatives may be realized through binding to a number of recently identified proteins which do not use the catalytic action of thiamine diphosphate.

Thiamine diphosphate
No physiological role is known for ThMP. ThPP is physiologically relevant.
Its synthesis is catalyzed by the enzyme thiamine diphosphokinase according to the reaction thiamine + ATP → ThDP + AMP.
ThDP 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).
- Present in most species
- pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase (also called α-ketoglutarate dehydrogenase)
- branched-chain α-keto acid dehydrogenase
- 2-hydroxyphytanoyl-CoA lyase
- transketolase
- Present in some species:
- pyruvate decarboxylase (in yeast)
- 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-limiting 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.

Thiamine triphosphate
ThTP was long considered a specific neuroactive form of thiamine, playing a role in chloride channels in the neurons of mammals and other animals, although this is not completely understood.
However, it was shown that ThTP exists in bacteria, fungi, plants and animals suggesting a much more general cellular role.
In particular in E. coli, it seems to play a role in response to amino acid starvation.

Adenosine thiamine triphosphate
AThTP is present in Escherichia coli, where it accumulates as a result of carbon starvation.
In E. coli, AThTP may account for up to 20% of total thiamine.
Thiamine also exists in lesser amounts in yeast, roots of higher plants and animal tissue.

Adenosine thiamine diphosphate
AThDP exists in small amounts in vertebrate liver, but its role remains unknown.

Biosynthesis
Thiamine biosynthesis occurs in bacteria, some protozoans, plants, and fungi.
The thiazole and pyrimidine moieties are biosynthesized separately and then combined to form thiamine monophosphate (ThMP) by the action of thiamine-phosphate synthase (EC 2.5.1.3).

The pyrimidine ring system is formed in reaction EC 4.1.99.17 catalysed by phosphomethylpyrimidine synthase, an enzyme in the radical SAM superfamily of iron–sulphur proteins, which use S-adenosyl methionine as a cofactor.

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.

The thiazole ring is formed in reaction EC 2.8.1.10 catalysed by thiazole synthase.
The ultimate precursors are 1-deoxy-D-xylulose 5-phosphate, 2-iminoacetate and a sulphur carrier protein called ThiS.
These are assembled by the action of an additional protein component, ThiG.

The final step to form ThMP involves decarboxylation of the thiazole intermediate, which reacts with the pyrophosphate derivative of the phospho methyl pyrimidine, itself a product of a kinase, phosphomethylpyrimidine kinase, via reaction EC 2.7.4.7.

The biosynthetic pathways may differ among organisms.
In E. coli and other enterobacteriaceae, ThMP may be phosphorylated to the cofactor thiamine diphosphate (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, which may then be pyrophosphorylation to ThDP by thiamine diphosphokinase. (thiamine + ATP → ThDP + AMP, EC 2.7.6.2)

The biosynthetic pathways are regulated by riboswitches.
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 (or ThDP), is the only riboswitch identified in both eukaryotic and prokaryotic organisms.

Industrial synthesis
Benfotiamine, fursultiamine, sulbutiamine and others listed at Vitamin B1 analogues are synthetic derivatives of thiamine, some of which are approved for use in some countries as a drug or non-prescription dietary supplement for treatment of diabetic neuropathy and other health conditions.

Medical uses
Prenatal supplementation
Women who are pregnant or lactating require more thiamine due to thiamine being preferentially sent to the foetus and placenta, especially during the third trimester.
For lactating women, thiamine is delivered in breast milk even if it results in thiamine deficiency in the mother.

Thiamine is important for not only mitochondrial membrane development, but also synaptosomal membrane function.
Thiamine has also been suggested that thiamine deficiency plays a role in the poor development of the infant brain that can lead to sudden infant death syndrome (SIDS).

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.
AI and UL are defined the same as in the United States.
For women (including those pregnant or lactating), men and children the PRI is 0.1 mg thiamine per megajoule (MJ) of energy consumed.
As the conversion is 1 MJ = 239 kcal, an adult consuming 2390 kilocalories should be consuming 1.0 mg thiamine.
This is slightly lower than the U.S. RDA.
The EFSA reviewed the same safety question and also reached the conclusion that there was not sufficient evidence to set a UL for thiamin

Sources
Thiamine is found in a wide variety of processed and whole foods.
Whole grains, legumes, pork, fruits, and yeast are rich sources.

To aid with adequate micronutrient intake, pregnant women are often advised to take a daily prenatal multivitamin.
While micronutrient compositions vary among different vitamins, a typical prenatal vitamin contains around 1.5 mg of thiamine.

Antagonists
Thiamine in foods can be degraded in a variety of ways. Sulfites, which are added to foods usually as a preservative, will attack thiamine at the methylene bridge in the structure, cleaving the pyrimidine ring from the thiazole ring.
The rate of this reaction is increased under acidic conditions.
Thiamine is degraded by thermolabile thiaminases (present in raw fish and shellfish).
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 acidic 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.

Absorption, metabolism and excretion
Thiamine phosphate esters in food are hydrolyzed to thiamine by intestinal alkaline phosphatase in the upper small intestine. At low concentrations, the absorption process is carrier-mediated.
At higher concentrations, absorption also occurs via passive diffusion.
Active transport can be inhibited by alcohol consumption or by folate deficiency.

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 (TBP) has been identified in rat serum and is believed to be a hormone-regulated carrier protein important for tissue distribution of thiamine.

Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.
About 80% of intracellular thiamine is phosphorylated and most is bound to proteins.
Two members of the SLC gene family of transporter proteins coded by the genes SLC19A2 and SLC19A3 are capable of the thiamine transport.
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.

Human storage of thiamine is about 25 to 30 mg, with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys.
ThMP and free (unphosphorylated) thiamine is present 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.
Thiamine contents in human tissues are less than those of other species.

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.

Deficiency
Non-specific signs of thiamine deficiency include malaise, weight loss, irritability and confusion.
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.

In Western countries, chronic alcoholism is a secondary cause.
Also at risk are older adults, persons with HIV/AIDS or diabetes, and persons who have had bariatric surgery.
Varying degrees of thiamine deficiency have been associated with the long-term use of high doses of diuretics.

History
Further information: Vitamin § History
Thiamine was the first of the water-soluble vitamins to be isolated, in 1910.
Prior to that, observations in humans and in chickens had shown that diets of primarily polished white rice caused a disease "beriberi", but did not attribute it to the absence of a previously unknown essential nutrient.

In 1884, Takaki Kanehiro, a surgeon general in the Japanese navy, rejected the previous germ theory for beriberi and hypothesized that the disease was due to insufficiencies in the diet instead.
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 substances at the time.

The Navy was not convinced of the need for so expensive a 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 by making him a baron in the Japanese peerage system, after which he was affectionately called "Barley Baron".

The specific connection to grain was made in 1897 by Christiaan Eijkman, a military doctor in the Dutch Indies, who discovered that fowl fed on a diet of cooked, polished rice developed paralysis, which could be reversed by discontinuing rice polishing.
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.

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.
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, first isolated a water-soluble thiamine compound from rice bran and named it as aberic acid (He renamed it as Orizanin later).

He described the compound is not only anti beri-beri factor but also essential nutrition to human in the paper, however, this finding failed to gain publicity outside of Japan, because a claim that the compound is a new finding was omitted in translation from Japanese to German.
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).

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, whose structure was determined by Robert Runnels Williams, in 1934.

Thiamine was named by the Williams team as "thio" or "sulfur-containing vitamin", with the term "vitamin" coming indirectly, by way of Funk, from the amine group of thiamine itself (by this time in 1936, vitamins were known to not always be amines, for example, vitamin C).
Thiamine was synthesized in 1936 by the Williams group.

Thiamine was first named "aneurin" (for anti-neuritic vitamin).
Sir Rudolph Peters, in Oxford, introduced thiamine-deprived pigeons as a model for understanding how thiamine deficiency can 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 animals died after a few days.
Administration of thiamine at the stage of opisthotonos led to a complete cure within 30 minutes.
As no morphological modifications were observed in the brain of the pigeons before and after treatment with thiamine, Peters introduced the concept of a biochemical lesion.

When Lohman and Schuster (1937) showed that the diphosphorylated thiamine derivative (thiamine diphosphate, ThDP) was a cofactor required for the oxydative decarboxylation of pyruvate, 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.
Lastly, the mechanism by which the thiamine moiety of ThDP exerts its coenzyme function by proton substitution on position 2 of the thiazole ring was elucidated by Ronald Breslow in 1958.

Thiamin (thiamine), or vitamin B1, is a water-soluble vitamin found naturally in some foods, added to foods, and sold as a supplement. Thiamin plays a vital role in the growth and function of various cells.
Only small amounts are stored in the liver, so a daily intake of thiamin-rich foods is needed.

Food Sources
Thiamine is found naturally in meats, fish, and whole grains. Thiamine is also added to breads, cereals, and baby formulas.
-Fortified breakfast cereals
-Pork
-Fish
-Beans, lentils
-Green peas
-Enriched cereals, breads, noodles, rice
-Sunflower seeds
-Yogurt

Thiamine is found in many foods and is used to treat low thiamine, beriberi, certain nerve diseases, and Wernicke-Korsakoff syndrome (WKS).
Thiamine is required by our bodies to properly use carbohydrates.
Thiamine also helps maintain proper nerve function. It's found in foods such as yeast, cereal grains, beans, nuts, and meat.
It's often used in combination with other B vitamins, and is found in many vitamin B complex products.

People take thiamine for conditions related to low levels of thiamine, including beriberi and inflammation of the nerves (neuritis).
It's also used for digestive problems, diabetic nerve pain, heart disease, and other conditions, but there is no good scientific evidence to support these other uses.

Uses & Effectiveness
Effective for Thiamine deficiency.
Taking thiamine by mouth helps prevent and treat thiamine deficiency.
A brain disorder caused by low levels of thiamine (Wernicke-Korsakoff syndrome).
Taking thiamine by IV helps decrease the risk and symptoms of Wernicke-Korsakoff syndrome (WKS), which is related to low levels of thiamine.
Thiamine is often seen in people with alcohol use disorder.

Therapeutic Function
Enzyme cofactor vitamin, Antineuritic

General Description
Thiamine, the preferred name for vitamin B1, holds a prominent place in the history of vitamin discovery because beriberi, the disease resulting from insufficient thiamine intake, was one of the earliest recognized deficiency diseases.

Biological Activity
Some earlier designations for this substance included aneurin, antineuritic factor, antiberiberi factor, and oryzamin. Thiamine is metabolically active as thiamine pyrophosphate (TPP).
TPP functions as a coenzyme which participates in decarboxylation of α-keto acids.

Thiamine or thiamin, also known as vitamin B1, is a colorless compound with the chemical formula C12H17N4OS. Thiamine is soluble in water and insoluble in alcohol.
Thiamine decomposes if heated.
Thiamine was first discovered by Umetaro Suzuki in Japan when researching how rice bran cured patients of Beriberi.

Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation.
Thiamine plays an important role in helping the body convert carbohydrates and fat into energy.
Thiamine is essential for normal growth and development and helps to maintain proper functioning of the heart and the nervous and digestive systems.
Thiamine cannot be stored in the body; however, once absorbed, the vitamin is concentrated in muscle tissue.

Thiamine is a natural product found in Matteuccia struthiopteris, Chlorella vulgaris, and other organisms with data available.

Use and Manufacturing
Prevention and treatment of vitamin B1 deficiency
Medicine, nutrition, enriched flours.
Isolated usually as the chloride
Available as thiamine hydrochloride and thiamine mononitrate

Thiamine, also known as vitamin B1, is one of the eight essential B vitamins.
Thiamine plays a key role in several important health functions, and not getting enough of it can lead to thiamine deficiency.
This deficiency is known as beriberi if it’s severe and chronic.

What is thiamine (B1)?
Thiamine is a vitamin your body needs for growth, development, and cellular function, as well as converting food into energy.

Like the other B vitamins, thiamine is water-soluble.
That means that it dissolves in water and isn’t stored in your body, so you need to consume it on a regular basis.
In fact, your body can only store around 20 days’ worth of thiamine at any given time.

Fortunately, thiamine is naturally found in a variety of foods and added to others via fortification.
It’s also commonly added to multivitamins or taken as an individual supplement or as part of a vitamin B complex.

Some of the best places to find thiamine in your diet include foods like:
enriched white rice or egg noodles
fortified breakfast cereal
pork
trout
black beans
sunflower seeds
acorn squash
yogurt
many commercial bread varieties
corn
Not getting enough thiamine can lead to thiamine deficiency, which can happen in as little as 3 weeks and affect your heart, nervous system, and immune system.
True thiamine deficiency is rare among healthy individuals with adequate access to thiamine-rich foods.

In highly industrialized countries, most people who experience true thiamine deficiency are experiencing other health conditions or procedures.
Thiamin (vitamin B-1) helps the body generate energy from nutrients.
Also known as thiamine, thiamin is necessary for the growth, development and function of cells.

Most people get enough thiamin from the food they eat.
Foods rich in thiamin include yeast, legumes, pork, brown rice, as well as fortified foods, such as breakfast cereals.
However, heating foods containing thiamin can reduce thiamin content.
Thiamin can also be taken as a supplement, typically orally.

There are high concentrations of Vitamin B1 in the outer layers and germ of cereals, as well as in yeast, beef, pork, nuts, whole grains, and pulses.
Fruit and vegetables that contain it include cauliflower, liver, oranges, eggs, potatoes, asparagus, and kale.
Other sources include brewer’s yeast and blackstrap molasses.
Breakfast cereals and products made with white flour or white rice may be enriched with vitamin B.

In the United States, people consume around half of their vitamin B1 intake in foods that naturally contain thiamin, while the rest comes from foods that are fortified with the vitamin.
Heating, cooking, and processing foods, and boiling them in water, destroy thiamin. As vitamin B1 is water-soluble, it dissolves into cooking water. White rice that is not enriched will contain only one tenth of the thiamin available in brown rice.

The National Institutes of Health (NIH) Office of Dietary Supplements (ODS) note that one serving of fortified breakfast cereal provides 1.5 milligramsTrusted Source (mg) of thiamin, which is more than 100 percent of the daily recommended amount.
One slice of whole wheat bread contains 0.1 mg, or 7 percent of the daily requirement.
Cheese, chicken, and apples contain no thiamin.
Humans need a continuous supply of vitamin B1, because it is not stored in the body. Thiamine should be part of the daily diet.

Benefits
Vitamin B1, or thiamin, helps prevent complications in the nervous system, brain, muscles, heart, stomach, and intestines.
Thiamine is also involved in the flow of electrolytes into and out of muscle and nerve cells.
Thiamine helps prevent diseases such as beriberi, which involves disorders of the heart, nerves, and digestive system.

Uses in medicine
Patients who may receive thiamin to treat low levels of vitamin B1 include those with peripheral neuritis, which is an inflammation of the nerves outside the brain, or pellagra.
People with ulcerative colitis, persistent diarrhea, and poor appetite may also receive thiamin.
Those who are in a coma may be given thiamin injections.
Some athletes use thiamin to help improve their performance. Thiamine is not a prohibited substances for athletes in the U.S.

Other conditions in which thiamin supplements may help include:
-AIDS
-canker sores
-cataracts
-glaucoma and other vision problems
-cerebellar syndrome, a type of brain damage
-cervical cancer
-diabetic pain
-stress
-heart disease
-kidney disease in patients with diabetes type 2
-motion sickness
-a weakened immune system.

Thiamine is found in foods such as cereals, whole grains, meat, nuts, beans, and peas.
Thiamine is important in the breakdown of carbohydrates from foods into products needed by the body.
Thiamine is used to treat or prevent vitamin B1 deficiency.
Thiamine injection is used to treat beriberi, a serious condition caused by prolonged lack of vitamin B1.

Thiamine taken by mouth (oral) is available without a prescription.
Injectable thiamine must be given by a healthcare professional.
Thiamine may also be used for purposes not listed in this medication guide.