Thiamine

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Thiamine, also known as thiamin and vitamin B₁, is a vitamin – an essential micronutrient for humans and animals.<ref name="ods">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="lpi">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="medline">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is found in food and commercially synthesized to be a dietary supplement or medication.<ref name=ods/> Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.<ref name=ods/><ref name=lpi/><ref name="whitfield">Template:Cite journal</ref>

Food sources of thiamine include whole grains, legumes, and some meats and fish.<ref name=ods/> Grain processing removes much of the vitamin content, so in many countries cereals and flours are enriched with thiamine.<ref name=ods/><ref name=whitfield/> Supplements and medications are available to treat and prevent thiamine deficiency and the disorders that result from it such as beriberi and Wernicke encephalopathy.<ref name=ods/><ref name=lpi/><ref name=whitfield/> They are also used to treat maple syrup urine disease and Leigh syndrome.<ref name=drugs/> Supplements and medications are typically taken by mouth, but may also be given by intravenous or intramuscular injection.<ref name="drugs">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Thiamine supplements are generally well tolerated. Allergic reactions, including anaphylaxis, may occur when repeated doses are given by injection.<ref name=medline/><ref name=drugs/><ref name=Peds2016>Template:Cite book</ref> Thiamine is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> It is available as a generic medication, and in some countries as a non-prescription dietary supplement.<ref name=ods/><ref name=drugs/> In 2022, it was the 288th most commonly prescribed medication in the United States, with more than 500,000 prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Definition

Thiamine is one of the B vitamins and is also known as vitamin B₁.<ref name=ods/><ref name=PKIN2020B1 /><ref name="DRItext" /> It is a cation that is usually supplied as a chloride salt.<ref name=lpi/> It is soluble in water, methanol and glycerol, but practically insoluble in less polar organic solvents.<ref name="Mahan"/><ref name="ModNutr2006"/> 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.<ref name=lpi/><ref name=PKIN2020B1 />

The chemical structure consists of an aminopyrimidine and a thiazolium ring linked by a methylene bridge.<ref name=lpi/> The thiazole is substituted with methyl and hydroxyethyl side chains.<ref name=lpi/> Thiamine is stable at acidic pH, but it is unstable in alkaline solutions and from exposure to heat.<ref name="Mahan"/><ref name="ModNutr2006"/> It reacts strongly in Maillard-type reactions.<ref name="Mahan"/> Oxidation yields the fluorescent derivative thiochrome, which can be used to determine the amount of the vitamin present in biological samples.<ref>Template:Cite book</ref>

Deficiency

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} 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.<ref name=whitfield/><ref>Template:Cite book</ref> Symptoms include malaise, weight loss, irritability and confusion.<ref name=whitfield/><ref name="Mahan">Template:Cite book</ref><ref name="Combs">Template:Cite book</ref><ref>Template:Cite journal</ref>

In Western countries, chronic alcoholism is a risk factor for deficiency.<ref name=ods/><ref name=whitfield/> Also at risk are older adults, persons with HIV/AIDS or diabetes, and those who have had bariatric surgery.<ref name=ods/><ref name=whitfield/> Varying degrees of thiamine insufficiency have been associated with the long-term use of diuretics.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Biological functions

File:Thiamine monophosphate coloured.svg

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).<ref name=lpi/> They are involved in many cellular processes.<ref name=Fitzpatrick>Template:Cite journal</ref> 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.<ref name="nature.com">Template:Cite journal</ref> No physiological role is known for the monophosphate except as an intermediate in cellular conversion of thiamine to the di- and triphosphates.<ref name=Lons2006/>

Thiamine pyrophosphate

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}}

Thiamine pyrophosphate (TPP), also called thiamine diphosphate (ThDP), participates as a coenzyme in metabolic reactions, including those in which polarity inversion takes place.<ref name=lpi/><ref>Template:Cite journal</ref> Its synthesis is catalyzed by the enzyme thiamine diphosphokinase according to the reaction thiamine + ATP → TPP + AMP (EC 2.7.6.2).<ref name=lpi/> However, recent findings reveal that uridine 5′-triphosphate (UTP), rather than ATP, is the preferred substrate for TPP synthesis in cells, with TPK1 showing a ~10-fold higher affinity for UTP.<ref name="Sahu2024">Template:Cite journal</ref> 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).<ref name=lpi/> The mechanism of action of TPP as a coenzyme relies on its ability to form an ylide.<ref>Template:Cite journal</ref> Examples include:

• 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 important in carbohydrate metabolism.<ref name=lpi/> 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.<ref name=lpi/> 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.<ref name=lpi/> 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.<ref name=lpi/> In the nervous system, PDH is also involved in the synthesis of myelin and the neurotransmitter acetylcholine.<ref name="ModNutr2006">Template:Cite book</ref>

Thiamine triphosphate

File:Thiamine triphosphate coloured.svg

Thiamine triphosphate (ThTP)

ThTP is implicated in chloride channel activation in the neurons of mammals and other animals, although its role is not well understood.<ref name=Lons2006/> ThTP has been found in bacteria, fungi and plants, suggesting that it has other cellular roles.<ref>Template:Cite journal</ref> In Escherichia coli, it is implicated in the response to amino acid starvation.<ref name="Bettendorff2021"/>

Adenosine derivatives

AThDP exists in small amounts in vertebrate liver, but its role remains unknown.<ref name="Bettendorff2021">Template:Cite journal</ref>

AThTP is present in E. coli, where it accumulates as a result of carbon starvation. In this bacterium, AThTP may account for up to Template:Percentage of total thiamine. It also exists in lesser amounts in yeast, roots of higher plants and animal tissue.<ref name="Bettendorff2021"/>

Medical uses

Template:See also 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.<ref name=ods/><ref name=lpi/> Pregnant women with hyperemesis gravidarum are at an increased risk of thiamine deficiency due to losses when vomiting.<ref>Template:Cite journal</ref> In lactating women, thiamine is delivered in breast milk even if it results in thiamine deficiency in the mother.<ref name="DRItext" /><ref name=":0">Template:Cite journal</ref>

Thiamine is important not only for mitochondrial membrane development, but also for synaptic membrane function.<ref>Template:Cite journal</ref> It has also been suggested that a deficiency hinders brain development in infants and may be a cause of sudden infant death syndrome.<ref name="Lons2006">Template:Cite journal</ref>

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<ref name=DRItext />
European Food Safety Authority
Age group	Adequate intake (mg/MJ)<ref name=EFSA>Template:Citation</ref>
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<ref name="DRItext">Template:Cite book</ref>

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.<ref name="DRItext" />

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name="DRItext" /><ref name=EFSA/>

Safety

Thiamine is generally well tolerated and non-toxic when administered orally.<ref name=drugs/> There are rare reports of adverse side effects when thiamine is given intravenously, including allergic reactions, nausea, lethargy, and impaired coordination.<ref name="EFSA" /><ref name=PKIN2020B1 />

Labeling

For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value. Since 27 May 2016, the Daily Value has been 1.2 mg, in line with the RDA.<ref name=ods/><ref name="FedReg">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Sources

Thiamine is found in a wide variety of processed and whole foods, including lentils, peas, whole grains, pork, and nuts.<ref name=ods/><ref name="usda">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A typical daily prenatal vitamin product contains around 1.5 mg of thiamine.<ref>Template:Cite journal</ref>

Food fortification

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Some countries require or recommend fortification of grain foods such as wheat, rice or maize (corn) because processing lowers vitamin content.<ref name=whitfield/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref name=FortifMap>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Synthesis

Biosynthesis

Thiamine biosynthesis occurs in bacteria, some protozoans, plants, and fungi.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref name=Caspi>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite book</ref>

File:Pyrimidine biosynthesis.svg

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

The thiazole ring is formed in a reaction catalysed by thiazole synthase (EC 2.8.1.10).<ref name=Caspi /> 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.<ref name=Begley2006>Template:Cite journal</ref>

File:Thiamine biosynthesis.svg

File:TPP riboswitch pdb-2hoj.png

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.<ref name=Caspi/>

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).<ref name=Caspi /> In most bacteria and in eukaryotes, ThMP is hydrolyzed to thiamine and then pyrophosphorylated to TPP by thiamine diphosphokinase (thiamine + ATP → TPP + AMP).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The biosynthetic pathways are regulated by riboswitches.<ref name=PKIN2020B1>Template:Cite book</ref> 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.<ref>Template:Cite journal</ref>

Laboratory synthesis

File:Thiamine synthesis.svg

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.<ref>Template:Cite journal</ref>Template:Rp<ref name=Anie>Template:Cite journal</ref>

Industrial synthesis

File:Grewe diamine.svg

Diamine used in the manufacture of thiamine

Merck & Co. adapted the 1936 laboratory-scale synthesis, allowing them to manufacture thiamine in Rahway in 1937.<ref name=Anie/> However, an alternative route using the intermediate Grewe diamine (5-(aminomethyl)-2-methyl-4-pyrimidinamine), first published in 1937,<ref>Template:Cite journal</ref> was investigated by Hoffman La Roche and competitive manufacturing processes followed. Efficient routes to the diamine have continued to be of interest.<ref name=Anie/><ref>Template:Cite journal</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name=BettendorfHandbook>Template:Cite book</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref><ref>Template:Cite journal</ref>

Absorption, metabolism and excretion

In the upper small intestine, thiamine phosphate esters present in food are hydrolyzed by alkaline phosphatase enzymes.<ref>Template:Cite book</ref> At low concentrations (<2 μmol l−1), the absorption process is carrier-mediated.<ref name="Laird"/> At higher concentrations, absorption also occurs via passive diffusion.<ref name="Laird"/><ref name=PKIN2020B1/> Active transport can be inhibited by alcohol consumption or by folate deficiency.<ref name="Mahan"/>

The majority of thiamine in serum is circulating bound to albumin,<ref name="Laird">Template:Cite book</ref> with over (Template:Percentage) in erythrocytes (red blood cells),<ref name="Laird"/> and is delivered to cells with high metabolic needs—particularly those in the brain, liver, pancreas, heart, and skeletal and smooth muscles, including cardiac muscle cells.<ref name=whitfield/> 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.<ref name="Combs"/> Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.<ref name="Mahan"/><ref name="Laird"/> Two members of the family of transporter proteins encoded by the genes SLC19A2 and SLC19A3 are capable of thiamine transport.<ref>Template:Cite book</ref><ref name="Laird"/><ref name=Lons2006/> In some tissues, thiamine uptake and secretion appear to be mediated by a Na⁺-dependent transporter and a transcellular proton gradient.<ref name="Combs"/>

Human storage of thiamine is about 25 to 50 mg,<ref name=ods/><ref name="pmid30281514"/> with the greatest concentrations in liver,<ref name=ods/><ref name="uptake"/> skeletal muscle, heart, brain, and kidneys.<ref name="pmid30281514">Template:Cite journal</ref><ref name="uptake">Template:Cite book</ref> 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.<ref name=Lons2006/> Thiamine contents in human tissues are less than those of other species.<ref name="Combs"/><ref>Template:Cite journal</ref> The half-life of thiamine content stored in tissues of human body is about 9-18 days,<ref name="pmid30281514"/> while after intake in high doses, the half-life of thiamine in circulating blood is about one to 12 hours.<ref name=whitfield/> Additionally, thiamine pyrophosphate derived from pyrimidines supports lipid synthesis and adipogenesis, highlighting its role in energy storage and cellular differentiation.<ref name=lpi/><ref name="Sahu2024"/>

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.<ref name=PKIN2020B1/>

Interference

The bioavailability of thiamine in foods can be interfered with in a variety of ways. Sulfites, added to foods as a preservative,<ref>Template:Cite book</ref> 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.<ref name="Combs"/> Thiamine is degraded by thermolabile thiaminases present in some species of fish, shellfish and other foods.<ref name="Mahan"/> The pupae of an African silk worm, Anaphe venata, is a traditional food in Nigeria. Consumption leads to thiamine deficiency.<ref>Template:Cite journal</ref> 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.<ref name="Vimokesant1975">Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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.<ref name="Vimokesant1975"/><ref>Template:Cite journal</ref>

Bariatric surgery for weight loss is known to interfere with vitamin absorption.<ref>Template:Cite journal</ref> A meta-analysis reported that Template:Percentage of people who underwent bariatric surgeries experience vitamin B₁ deficiency.<ref>Template:Cite journal</ref>

History

Template:See Thiamine was the first of the water-soluble vitamins to be isolated.<ref name=Suzuki/> 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.<ref name="McCollum"/><ref name=Eijkman1897/>

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.<ref name="McCollum">Template:Cite book</ref> 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".<ref name="McCollum"/>

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.<ref name=Eijkman1897>Template:Cite journal</ref> 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.<ref name="Nobel">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref> 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.<ref name=Suzuki>Template:Cite journal</ref> 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).<ref>Template:Cite journal</ref><ref>Template:Cite journal 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."</ref> 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,<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> In 1937, Lohmann and Schuster showed that the diphosphorylated thiamine derivative, TPP, was a cofactor required for the oxidative decarboxylation of pyruvate.<ref>Template:Cite journal</ref>

• Some contributors to the discovery of thiamine
• Takaki Kanehiro.jpg

  Takaki Kanehiro

• Eijkman.jpg

  Christiaan Eijkman

• Portrait of Gerrit Grijns Wellcome M0010254.jpg

  Gerrit Grijns

• Umetarosuzuki-pre1943.jpg

  Umetaro Suzuki

• Casimir Funk 01.jpg

  Casimir Funk

• Rudolph Albert Peters.jpg

  Rudolph Peters