Thiamin is a water-soluble B-complex vitamin. It was the first B vitamin to be identified and one of the first organic compounds to be recognised as a vitamin in the 1930s. In fact it was through the discovery and naming of thiamin that the word 'vitamin', from the Latin “vita” = life and “amine” = nitrogen-containing compound, was coined. The notion that the absence of a substance in food could cause a disease (in this case beriberi) was a revolutionary one. Man and other primates rely on their food intake to cover their vitamin B1 requirements.
Functions
The main functions of thiamin are connected to its role as a coenzyme in the form of thiamin pyrophoshate (TPP). Coenzymes are 'helper molecules' which activate enzymes, the proteins that control the thousands of biochemical processes occurring in the body. TPP acts as a “helper molecule” in about 25 enzymatic reactions and plays an essential role in the production of energy from food in the carbohydrate metabolism as well as in the links between carbohydrate, protein and fat metabolism. It is one of the key compounds for several reactions in the breakdown of glucose to energy. Furthermore, TPP is coenzyme for the metabolism of branched-chain keto acids that are derived from branched-chain amino acids.
Another important function of thiamin is its activation of an enzyme called “transketolase”, which in turn catalyses reactions in the pentose phosphate pathway. This pathway is the basis for the production of many prominent compounds, such as ATP, GTP, NADPH and the nucleic acids DNA and RNA.
Certain non-coenzyme functions of thiamin are important for nerve tissues and muscles. Its triphosphate form (TTP) in particular plays a role in the conduction of nerve impulses, in the metabolism of the neurotransmitters acetylcholin, adrenalin, and serotonin and in aerobic metabolism.
Main functions in a nutshell:
Co-enzyme in energy metabolism
Co-enzyme for pentose metabolism as a basis for nucleic acids
Nerve impulse conduction and muscle action
Dietary sources
Thiamin is found in most foods, but mostly in small amounts. The best source of thiamin is dried brewer’s yeast. Other good sources include meat (especially pork and ham products), some species of fish (eel, tuna), whole grain cereals and bread, nuts, pulses, dried legumes and potatoes. Concerning cereal grains, the thiamin-rich bran is removed during the milling of wheat to produce white flour, and during the polishing of brown rice to produce white rice. As a consequence, enriched and fortified grain-products are common today.
Absorption and body stores
Gastrointestinal absorption of nutritional thiamin occurs in the lumen of the small intestine (mainly the jejunum) by means of a sodium and energy dependent active transport mechanism. For thiamin levels higher than 2 µmol/L, passive diffusion plays an additional role. Thiamin occurs in the human body as free thiamin and its phosphorylated forms (see Chemistry). Because thiamin has a high turnover rate (10-20 days) and is not appreciably stored in the body (approx. 1 mg/day is used up in tissues), a daily supply is required. The limited stores may be depleted within two weeks or less on a thiamin-free diet, with clinical signs of deficiency beginning shortly after. Regular intake of vitamin B1 is therefore critical. The heart, kidney, liver and brain have the highest concentrations, followed by the leukocytes and red blood cells.
Measurement
The standard way to assess thiamin status used to be to determine erythrocyte transketolase (a-ETK) activity both with and without stimulation of this enzyme by the addition of TDP cofactor. Technical difficulties led to an increasing use of direct determination of TDP in whole blood, e.g. by HPLC (High Performance Liquid Chromatography), in order to assess thiamin status. The HPLC assay is more robust and easier to perform. Thiamin status determined by this method is considered to be in good correlation with results from transketolase activation assays. Usually, whole blood concentrations are found to be between 66.5 and 200 nmol/L.
Typical serum level <75 nmol/L
Stability
Vitamin B1 is unstable when exposed to heat, alkali, oxygen and radiation. Water solubility is also a factor in the loss of thiamin from foods. About 25% of the thiamin in food is lost during the normal cooking process. Considerable amounts may be lost in thaw drip from frozen meats or in the water used to cook meats and vegetables. To preserve thiamin, foods should be cooked in a covered pan for the shortest time possible and should not be soaked in water or heated for too long. Juices and cooking water should be re-used in stews and sauces.
Interactions
Positive interactions
The presence of other B-vitamins, such as vitamins B6, B12, niacin and pantothenic acid, supports the action of thiamin. Antioxidant vitamins, such as vitamins E and C, protect thiamin by preventing its oxidation to an inactive form.
Negative interactions
A number of foods, such as coffee, tea, betel nuts (Southeast Asia) and also some cereals may act as antagonists to thiamin. Chlorogenic acid and other plant polyphenols may be responsible for this anti-thiaminic effect. It is also known that some tropical fish and African silkworms, both traditionally consumed raw in some countries, contain enzymes called “thiaminases” that break down vitamin B1. Drugs that cause nausea and lack of appetite, or which increase intestinal function or urinary excretion, decrease the availability of thiamin. Poisoning from arsenic or other heavy metals produces the neurological symptoms of thiamin deficiency. These metals act by blocking a crucial metabolic step involving thiamin in its coenzyme form.
Deficiency
Marginal thiamin deficiency may manifest itself in such vague symptoms as fatigue, insomnia, irritability and lack of concentration, anorexia, abdominal discomfort, constipation and loss of appetite. When there is not enough thiamin, the overall decrease in carbohydrate metabolism and its interconnection with amino acid metabolism has severe consequences. The two principal thiamin deficiency diseases are “beriberi” and “Wernicke-Korsakoff syndrome”.
Beriberi, which translated into English means “I can't, I can't”, manifests itself primarily in disorders of the nervous and cardiovascular systems. Unfortunately this serious disease is still common in parts of southeast Asia, where polished rice is a staple food and thiamin enrichment programs are not fully in place. Many other countries fortify rice and other cereal grains to replace the nutrients lost in processing.
The disease exists in three forms:
dry beriberi, a polyneuropathy with severe muscle wasting
wet beriberi, which in addition to neurologic symptoms is characterised by cardiovascular manifestations, edema and ultimately heart failure
infantile beriberi, which occurs in breast-fed infants whose nursing mothers are deficient in thiamin. Symptoms of vomiting, convulsions, abdominal distention and anorexia appear quite suddenly and may be followed by death from heart failure.
The “Wernicke-Korsakoff syndrome” (cerebral beriberi) is the thiamin deficiency disease seen most often in the Western world. It is frequently associated with chronic alcoholism in conjunction with limited food consumption. Symptoms include confusion, paralysis of eye motor nerves, abnormal oscillation of the eyes, psychosis, confabulation, and impaired retentive memory and cognitive function. The syndrome is also seen occasionally in people who fast, have chronic vomiting (hook worm) or have gross malnutrition due to e.g., AIDS or stomach cancer. If treatment of amnesic symptoms is delayed, the memory may be permanently impaired. Recent evidence suggests that oxidative stress plays an important role in the neurologic pathology of thiamin deficiency.
The development of vitamin B1 deficiency can be caused by:
Alcoholic disease
Inadequate storage and preparation of food
Increased demand due to pregnancy and lactation, heavy physical exertion, fever and stress, or adolescent growth
Inadequate nutrition
high carbohydrate intake (e.g., milled or polished rice, sweeties)
regular heavy consumption of tea and coffee (Tannin = antithiamin)
Thiamin is specific in the prevention and treatment of beriberi and other manifestations of vitamin B1 deficiency (e.g. Wernicke-Korsakoff, peripheral neuritis). The dosage range is from 100 mg daily in mild deficiency states to 200-300 mg in severe cases. Thiamin administration is often beneficial in neuritis accompanied by excessive alcohol consumption or pregnancy. With alcoholic and diabetic polyneuropathies, the therapeutic dose is most often in the range of 10-100 mg/daily. When alcoholism has led to delirium tremens, large doses of vitamin B1, together with other vitamins should be given by slow injection. Large doses of thiamin (100-600 mg daily) have been advocated in the treatment of such diverse conditions as lumbago, sciatica, trigeminal neuritis, facial paralysis and optic neuritis. However, the response to such treatment has been variable.
Recommended Dietary Allowance (RDA)
Because thiamin facilitates energy utilisation, requirements are tied to energy intake, which can be very much dependent on activity levels. For adults, the RDA is 0.5 mg per 1000 kcal, which amounts to a range of 1.0-1.1 mg per day for women and 1.2-1.5 mg for men, based on an average caloric intake. An additional 0.4-0.5 mg per day are recommended during pregnancy and lactation. Children's needs are lower: 0.3-0.4 mg/day (infants) and 0.7-1.0 mg/day (children), depending on the age and caloric intake of the child.
Safety
Thiamin has been found to be well tolerated in healthy people, even at very high oral doses (up to 200 mg/day). Due to its very broad safety margin for oral administration and long history of safe use, none of the official regulatory authorities has defined a safe upper limit for this vitamin. The only reaction found in humans is of the hypersensitivity type. In the vast majority of cases these have occurred after injection of thiamin in patients with a history of allergic reactions. For parenteral administration, the doses that produced these reactions varied from 5 to 100 mg, though most of them occurred at the higher end of this range.
Supplements and food fortification
Thiamin is mostly formulated in combination with other B-vitamins (B-complex) or included in multivitamin supplements. Fortification of white flour, cereals, pasta, beverages and rice began in the United States during the second World War (1939-1945), with other countries quickly following suit. Fortification of staple foods has virtually eradicated the B-vitamin deficiency diseases in developed nations.
Industrial production
Chemical synthesis of thiamin is a complicated process, involving some 15-17 different steps. Although commercial production of thiamin was first accomplished in 1937, the production did not develop on a broad scale until the 1950s, when demand rose sharply because of food fortification.
