Thiamine

Structural formula
Structure of thiamine chloride
General
Common name	Vitamin B 1
other names	Thiamine chloride Aneurine antineuritic vitamin Anti-liberifactor 3 - [(4-Amino-2-methyl-5-pyrimidinyl) methyl] -5- (2-hydroxyethyl) -4-methylthiazolium chloride
Molecular formula	C 12 H 17 ClN 4 OS (chloride) C 12 H 18 Cl 2 N 4 OS (hydrochloride)
CAS number	59-43-8 67-03-8 (hydrochloride)
ATC code	A11 DA01
Brief description	colorless powder, characteristic odor
Occurrence	see table in article text
physiology
function	Carbohydrate metabolism, coenzyme in dehydrating decarboxylation reactions (e.g. in the pyruvate dehydrogenase complex )
Daily need	1.0-1.2 mg
Consequences in case of deficiency	Muscle atrophy, heart failure, neurological disorders, beriberi , Wernicke encephalopathy
Overdose	not known
properties
Molar mass	337.27 g mol −1 (hydrochloride)
Physical state	firmly
Melting point	120–122 ° C (decomposition, chloride hydrate ) 163–165 ° C (decomposition, chloride, anhydrous) 248 ° C  (decomposition, hydrochloride)
solubility	very soluble in water (500 g l −1 )
safety instructions
Please note the restricted labeling requirements for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Hydrochloride no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
Toxicological data	214 mg kg −130 W −1 ( TD Lo ,  human , multiple routes of exposure ) 301 mg kg −1 ( LD 50 ,  mouse ,  sc )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Thiamine , vitamin B ₁ or aneurine is a water-soluble vitamin from the B complex with a weak but characteristic odor and is particularly indispensable for the functioning of the nervous system. If the vitamin B _{1 is} no longer supplied to the body for approx. 14 days, 50% of the reserves are used up.

Chemical structure

Thiamine consists of two ring systems linked by a methylene bridge: a pyrimidine and a thiazole ring .

function

Thiamine is absorbed in the intestine via the active thiamine transporter and, in high concentrations, also by diffusion. There are rare hereditary deficiency diseases of these proteins. In thiamine-responsive, megaloblastic anemia (TRMA) , mutations in the SLC19A2 gene cause the active thiamine transporter to become inoperable. As a result, the thiamine present in low concentrations in food can no longer be sufficiently absorbed. This leads to the characteristic clinical picture of TRMA with diabetes mellitus, hearing loss and megaloblastic anemia. If left untreated, TRMA leads to death. By administering a high dose of thiamine, sufficient thiamine can be absorbed via the intestine by diffusion.

Thiamine itself is not used in the body. With the help of the enzyme thiamine pyrophosphokinase , it is first converted to thiamine pyrophosphate ( TPP , also thiamine diphosphate, TDP). In this biologically active form, it is the coenzyme of pyruvate dehydrogenase E1 , α-ketoglutarate dehydrogenase , α-keto acid dehydrogenase and transketolase .

Glucose Metabolism and Mitochondria

Pyruvate is converted into acetyl-CoA in the mitochondria by means of pyruvate dehydrogenase complex (PDC) . TPP serves this enzyme complex as a coenzyme in the splitting off of CO ₂ and thus makes the aerobic utilization of glucose (and thus also other carbohydrates) possible.

If this metabolic pathway is blocked, lactate is produced from pyruvate in the cytosol through lactic acid fermentation , which is a comparatively inefficient form of energy production.

Losses in food

Thiamine is sensitive to heat, it is destroyed by boiling. It is water-soluble, so when boiling in water, some of it is lost in the cooking water. Raw fish and ferns contain the enzyme thiaminase , which breaks down and thus destroys thiamine. Preservatives from the group of sulfites (E 220 - E 228) also break down thiamine.

When making white flour (e.g. type 405) or white rice, the brown germ of the plant is removed from the rest of the seed (endosperm). However, the germ contains all of the vitamin B _{1 in} the seed, which is required to burn the carbohydrates it contains.

In contrast, whole grain flour and brown rice largely contain vitamin B ₁ .

Fortification in food

To compensate for the loss in processing, vitamin B ₁ is artificially added to flour and rice in many countries . 71 countries are now doing this with flour, including Great Britain, the USA and Canada, but not Germany.

Occurrence

According to the Federal Food Code (BLS) or Römpp Lexikon Chemie, the specified amounts of thiamine are contained per 100 g of the following foods :

food	Thiamine mg / 100 g
Brewer's yeast, organic	13.0
Wheat germ	2.01
Bee pollen	0.6 to 2.2
Sunflower seeds , fresh	1.9
Baking yeast , pressed	1.0
Soybeans , fresh	0.44
Sesame , toasted	0.4
Kamut (Khorasan wheat )	0.40
Whole grain cereals ( wheat , barley , corn , rice - not heated)	0.35-0.46
Teff (Ethiopian-Eritrean sweet grass )	0.3
Peas , green, fresh	0.3
Macadamia nuts , fresh	0.28
Pork (medium fat ), fresh	0.23
Dandelion , fresh	0.19
Oyster mushrooms , fresh	0.17
Beans, white , cooked	0.154
Oatmeal , raw	0.15
Poultry , cooked	0.11
potatoes cooked	0.07

Requirement (recommended intake)

• Infants (up to 12 months): 0.2-0.4 mg / day
• Children (1–15 years):
  • female: 0.6-1.1 mg / day
  • male: 0.6-1.4 mg / day
• Women: 1.0 mg / day
  • Pregnant women (from the 4th month): 1.2 mg / day
  • Breastfeeding: 1.4 mg / day
• Men 1.0-1.3 mg / day

In South America, thiamine is often used as a defense against mosquitoes before traveling to the Amazon region, as the mosquitoes would reject the smell. The protective effect varies from person to person and is questioned by numerous authors.

Supply situation in Germany

According to the National Consumption Study II, the median of vitamin B1 intake in all age groups is well above the recommended intake, but 21% of men and 32% of women do not achieve the recommended daily intake of vitamin B1.

Deficiency symptoms (hypovitaminosis)

See also : hypovitaminosis

As early as 1896, after returning to Europe from his Asia trip, Christiaan Eijkman stated: “White rice can be poisonous!” Before that, he had observed numerous cases of beriberi in Java , which was caused by more thorough polishing of white rice.

Symptoms:

• Disorders of the carbohydrate metabolism and nervous system (including polyneuropathy )
• Irritability and depression
• Fatigue, visual disturbances, loss of appetite, poor concentration, muscle atrophy
• Anemia
• frequent headaches
• Memory disorders ( Korsakoff syndrome ), states of confusion
• Heart failure, edema, tachycardia, low blood pressure, shortness of breath (dyspnoea)
• Decreased antibody production in infections
• disturbed energy production
• weak muscles (especially the calf muscles )
• Diseases:
  • Human: Beriberi , Wernicke encephalopathy , Strachan's syndrome
  • Animals: Cat thiamine deficiency encephalopathy , cerebrocortical necrosis , Chastek's paralysis

Alzheimer

Alzheimer's patients show a reduced utilization of glucose and oxygen in the brain, which is associated with a thiamine deficiency. The deficiency could not only be the result, but the cause of the disease. Reduced thiamine pyrophosphate levels in the blood and brain can also be used as a diagnostic criterion to differentiate between Alzheimer's disease and other forms of dementia.

Consequences of an overdose (hypervitaminosis)

See also : hypervitaminosis

Thiamine has a wide therapeutic range . Animal experiments in rats show that even a dose 100 times the daily requirement was tolerated for three generations without side effects. After administration into the muscle or into the vein, however, some extremely severe hypersensitivity reactions up to dyspnoea and shock have been described in individual cases. Because of these allergic reactions, vitamin B _{1 should} therefore only be used parenterally in exceptional cases; The oral therapy of choice for vitamin B ₁ substitution is the fat-soluble and therefore extremely tissue-penetrating thiamine prodrug benfotiamine .

history

• In 1882 the Japanese Kanehiro Takaki recognized that the beriberi disease, known in China as early as 2600 BC , can be cured with an appropriate diet (from the vitamin B range).
• In 1897, the Nobel Prize winner for medicine / physiology (Nobel Prize 1929) Christiaan Eijkman demonstrated vitamin B ₁ deficiency effects from feeding polished rice and showed that the deficiency can be remedied by feeding the silver skins ( bran ) of the rice. It was initially called anti-polyneuritis factor because of its effects on the nerves .
• Umetaro Suzuki discovered thiamine in 1910 while researching why rice bran cured beriberi sufferers. He called it aberic acid and later oryzanine.
• In 1912 Casimir Funk isolated niacin from rice bran , but mistook it for thiamine and coined the term " vitamin " because of the supposedly discovered amino group .
• In 1926 the vitamin was first described by Barend CP Jansen and Willem F. Donath isolated in crystalline form from rice bran and as a nti neur itisches Vitam in ( Aneurin called).
• In 1932, however, Windaus gave it the name thiamine because of its sulfur content, which is the only permitted name today.
• In 1936 the structure of vitamin B _{1 was} elucidated by Robert R. Williams and Rudolf Grewe at about the same time . The synthesis was carried out by Robert R. Williams and by Hans Andersag and Kurt Westphal in 1937.
• In 1952 the Japanese research group around Fujiwara discovered the fat-soluble thiamine prodrug benfotiamine, with which high thiamine levels can be achieved in the target organs.

Individual evidence

1. ↑ ^{a b c d e} entry on thiamine. In: Römpp Online . Georg Thieme Verlag, accessed on April 19, 2016.
2. ↑ ^{a b c d} Entry on thiamine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ↑ ^{a b} Data sheet Thiamine hydrochloride from Sigma-Aldrich , accessed on June 25, 2017 ( PDF ).
4. ↑ Zhongguo Yaoxue Zazhi. In: Chinese Pharmaceutical Journal. Vol. 30, 1995, p. 407.
5. ↑ ET ANGELAKOS, ER LOEW: Histamine toxicity in mice and rats following treatment with histaminase inhibitors. In: Journal of Pharmacology and Experimental Therapeutics . Volume 119, Number 3, March 1957, pp. 444-451, PMID 13417100 .
6. ↑ Thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural hearing loss. In: Orphanet (Rare Disease Database).
7. ↑ Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky: Campbell Biology . 10th edition. Benjamin-Cummings Pub Co, 2014, ISBN 978-0-13-404462-0 , pp. 894 .
8. ↑ Michael M. Cox, Albert L. Lehninger: Lehninger principles of biochemistry . WH Freeman and Company, 2013, ISBN 978-1-4292-3414-6 , pp. 567-569 .
9. ↑ Lisa A. Urry, Michael L. Cain (Michael Lee), Steven Alexander Wasserman, Peter V. Minorsky, Rob Jackson: Campbell biology . 10th edition. ISBN 978-0-321-77565-8 , pp. 178-179 .
10. ↑ Entry on sulfur dioxide. In: Römpp Online . Georg Thieme Verlag, accessed on February 8, 2016.
11. ↑ Rich in vitamins: flour for the world. on: muehlenchemie.de
12. ↑ EW HERBERT, JT VANDERSLICE, MEIS-HSIA HUANG, DJ HIGGS: LEVELS OF THIAMINE AND ITS ESTERS IN BEE COLLECTED POLLEN USING LIQUID CHROMATOGRAPHY AND ROBOTICS . In: Apidology . tape 18 , no. 2 , 1987, pp. 129-136 , doi : 10.1051 / apido: 19870203 ( apidologie.org [accessed August 9, 2017]).
13. ↑ Vanilda Aparecida Soares de Arruda, Aline Aparecida Santos Pereira, Leticia M. Estevinho, Ligia Bicudo de Almeida-Muradian: Presence and stability of B complex vitamins in bee pollen using different storage conditions . In: Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association . tape 51 , January 2013, p. 143–148 , doi : 10.1016 / j.fct.2012.09.019 , PMID 23022013 .
14. ↑ ^{a b c d e f g} DGE : The reference values ​​for nutrient intake: thiamine (vitamin B1)
15. ↑ Max Rubner Institute , Federal Research Institute for Nutrition and Food (Ed.): National Consumption Study II . Results report, part 2. Karlsruhe 2008, p. 113 ff . ( bund.de [PDF]).
16. ↑ Christiaan Eijkman: Beriberi and Vitamin B1. Retrieved February 4, 2017 . 
17. ↑ Gary E. Gibson, Joseph A. Hirsch, Pasquale Fonzetti, Barry D. Jordan, Rosanna T. Cirio: Vitamin B1 (thiamine) and dementia . In: Annals of the New York Academy of Sciences . tape 1367 , no. 1 , March 1, 2016, p. 21-30 , doi : 10.1111 / nyas.13031 , PMID 26971083 , PMC 4846521 (free full text).
18. ^ Gary E. Gibson, Joseph A. Hirsch, Rosanna T. Cirio, Barry D. Jordan, Pasquale Fonzetti: Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes . In: Molecular and Cellular Neurosciences . tape 55 , July 1, 2013, p. 17-25 , doi : 10.1016 / j.mcn.2012.09.001 , PMID 22982063 , PMC 3609887 (free full text).
19. ^ Lack of Vitamin B1 May Lead to Alzheimer's. Retrieved February 6, 2017 . 
20. ↑ Xiaoli Pan, Guoqiang Fei, Jingwen Lu, Lirong Jin, Shumei Pan: Measurement of Blood Thiamine Metabolites for Alzheimer's Disease Diagnosis . In: EBioMedicine . tape 3 , January 1, 2016, p. 155–162 , doi : 10.1016 / j.ebiom.2015.11.039 , PMID 26870826 , PMC 4739421 (free full text).
21. ↑ Casimir Funk: The etiology of the deficiency diseases. Beri-beri, polyneuritis in birds, epidemic deopsy, scurvy, experimental scurvy in animals, infantile scurvy, ship beri-beri, pellagra. In: Journal of State Medicine. 20, 1912, pp. 341-368.
22. ↑ Karim Bschir: Science and Reality Mohr Siebeck, Tübingen 2012 ISBN 978-3-16-151934-5 pp. 14-15

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !