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DSM in Animal Nutrition & Health


Properties and Metabolism

Thiamin consists of a molecule of pyrimidine and a molecule of thiazole linked by a methylene bridge; it contains both nitrogen and sulfur atoms (Illus. 7-1). Thiamin is isolated in pure form as a white, crystalline thiamin hydrochloride. The vitamin has a characteristic sulfurous odor and a slightly bitter taste. Thiamin is very soluble in water, sparingly so in alcohol, and insoluble in fat solvents. It is very sensitive to alkali, in which the thiazole ring opens at room temperature when the pH is above 7. In a dry state, thiamin is stable at 100°C for several hours, but moisture greatly accelerates destruction, and thus it is much less stable to heat in fresh than in dry foods. Under ordinary conditions, thiamin hydrochloride is more hygroscopic than the mononitrate salt. However, both products should be kept in sealed containers.


Illustration 7-1


Substances with anti-thiamin activity are fairly common in nature and include structurally similar antagonists as well as structure-altering antagonists. The synthetic compounds pyrithiamin, oxythiamin, and amprolium (an anticoccidial) are structurally similar antagonists. Their mode of action is competitive inhibition, interfering with thiamin at different points in metabolism. Pyrithiamin blocks the esterification of thiamin with phosphoric acid, resulting in inhibition of the thiamin coenzyme cocarboxylase. Oxythiamin competitively inhibits thiamin’s binding to the carboxylase complex, blocking important metabolic reactions. Amprolium inhibits intestinal absorption of thiamin and also blocks phosphorylation of the vitamin (McDowell, 2000). Sulfur has been shown to be antagonistic to thiamin enzymes. The sulfite ion has been shown to cleave thiamin from enzymes at the methylene bridge and analytically, will imitate thiaminase. Sulfate increases thiamin-destroying activity in the rumen contents and the destructive mechanism involves thermolabile factor(s). However, the ruminal synthesis of thiamin is not affected by sulfate (Olkowski et al., 1993). Tall fescue (Festuca arundinacea Schreb.) toxicosis resembles diseases caused by elevated rumen thiaminase activity (Lauriault et al., 1990). Thiaminase activity destroys thiamin by altering the structure of the vitamin. The disease “Chastek paralysis” in foxes and other animals fed certain types of raw fish, results from a thiaminase that splits the thiamin molecule into two components, thus inactivating it. Since thiaminase is unstable to heat, the problem can be avoided by cooking the fish at 83°C for at least five minutes. Many different kinds of fish contain thiaminase, with thiamin deficiency being reported in penguins, seals, and dolphins fed primarily fish diets in zoos (Maynard et al., 1979). Thiaminase is found mainly in herrings, sprats, stints, and various carp species, a total of some 50 species, most of which live in fresh water. Wild aquatic animals apparently do not suffer thiamin deficiency even though they eat a diet primarily of fish, because fish must undergo some putrefaction to release the enzyme (Evans, 1975). In vitro and in vivoexperiments have shown that 1 kg of fish can destroy up to 25 mg thiamin. This degradation takes place within the first 30 minutes after ingestion, when still in the stomach. Certain microorganisms (bacteria and molds) and plants (bracken fern) have been shown to produce thiaminases. A disease in horses known as “bracken fern poisoning” results from antagonism to thiamin. Two types of thiaminase enzymes have been described–I and II. Thiaminase I substitutes a new base for the thiazole ring. This leads to less thiamin, but it also results in thiamin analogs consisting of the pyrimidine ring of the original thiamin and another ring from the “cosubstrate.” This thiamin analog may then be absorbed and possibly inhibit thiamin-requiring reactions (Frye et al., 1991). Thiaminase II simply cleaves the vitamin at the methylene bridge between the thiazole and the pyrimidine rings. Thiamin appears to be readily digested and released from naturally occurring sources. A precondition for normal absorption of thiamin is sufficient production of stomach hydrochloric acid. Phosphoric acid esters of thiamin are split in the intestine. The free thiamin formed is soluble in water and easily absorbed, especially in the jejunum. The mechanism of thiamin absorption is not yet fully understood, but apparently both active transport and simple diffusion are involved. At low concentrations, there is an active sodium-dependent transport of thiamin against the electrochemical potential, whereas at high concentrations, it diffuses passively through the intestinal wall. Thiamin synthesized by gut microflora in the cecum or large intestine is largely unavailable to the animal except by coprophagy. The horse can, however, absorb thiamin from the cecum. Ruminants can also absorb free thiamin from the rumen, but the rumen wall is not permeable for bound thiamin or for thiamin contained in rumen microorganisms. Specific proteins (transporters and carriers) in the cell membrane have binding sites for thiamin, allowing it to be solubilized within the cell membrane. This permits the vitamin to pass through the membrane and ultimately reach the aqueous environment on the other side (Rose, 1990; Bates, 2006). Absorbed thiamin is transported via the portal vein to the liver with the carrier plasma protein. Thiamin is efficiently transferred to the fetus.

Thiamin phosphorylation can take place in most tissues, but particularly in the liver. Four-fifths of thiamin in animals is phosphorylated in the liver under the action of ATP to form the metabolically active enzyme form thiamin pyrophosphate (TPP or cocarboxylase). Of total body thiamin, about 80% is TPP, about 10% is thiamin triphosphate (TTP), and the remainder is thiamin monophosphate (TMP) and free thiamin.

Although thiamin is readily absorbed and transported to cells throughout the body, it is not stored to any great extent. The thiamin content in individual organs varies considerably and the vitamin is preferentially retained in organs with a high metabolic activity. During deficiencies, thiamin is retained in greatest quantities in major organs such as the liver, heart, brain and kidneys. Although liver and kidney tissues have the highest thiamin concentrations, approximately one-half of the total thiamin body stores are present in muscle tissue (Tanphaichir, 1976). Thiamin, however, is one of the most poorly stored vitamins. Most mammals on a thiamin-deficient diet will exhaust their body stores within one to two weeks (Ensminger et al., 1983).

Thiamin intakes in excess of current needs are rapidly excreted. Absorbed thiamin is excreted in both urine and feces, with small quantities excreted in sweat. Fecal thiamin may originate from feed, synthesis by microorganisms or endogenous sources (i.e., via bile or excretion through the mucosa of the large intestine). When thiamin is administered in large doses, urinary excretion first increases then reaches a saturation level, and with additional thiamin, the fecal concentration increases considerably (Bräunlich and Zintzen, 1976).



A principal function of thiamin in all cells is as the coenzyme cocarboxylase or TPP. The tricarboxylic acid cycle (TCA; citric acid cycle; Krebs cycle) is responsible for production of energy in the body. In this cycle, breakdown products of carbohydrates, fats and proteins are brought together for further breakdown and for synthesis. The vitamins riboflavin, pantothenic acid and niacin, as well as thiamin, play roles in the cycle. Thiamin is the coenzyme for all enzymatic decarboxylations of alpha-keto acids. Thus, it functions in the oxidative decarboxylation of pyruvate to acetate, which in turn is combined with coenzyme A (CoA) for entrance into the TCA cycle. Thiamin is essential in two oxidative decarboxylation reactions in the TCA cycle that take place in cell mitochondria and one reaction in the cytoplasm of the cells (Figure 7-1). These reactions are essential for utilization of carbohydrates to provide energy. Decarboxylation in the TCA cycle removes carbon dioxide, and the substrate is converted into the compound having the next lower number of carbon atoms:
Pyruvate -> acetyl-CoA + CO2alpha-Ketoglutaric acid -> succinyl-CoA + CO2


Figure 7-1: Thiamin as Thiamin Pyrophosphate (TPP) in the Metabolism of Carbohydrates


Thiamin plays a very important role in glucose metabolism. Thiamin pyrophosphate is a coenzyme in the transketolase reaction that is part of the direct oxidative pathway (pentose phosphate cycle) of glucose metabolism occurring in the cell cytoplasm of the liver, brain, adrenal cortex and kidney, but not skeletal muscle. The pentose phosphate cycle is the only mechanism known for synthesis of ribose, which is needed for nucleotide formation. This cycle also results in the reduction of nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for reducing intermediates from carbohydrate metabolism during fatty acid synthesis. Little is known of thiamin functions in nervous tissue. However, evidence has accumulated for a specific role of thiamin in neurophysiology that is independent of its coenzyme function. The possible mechanism of action of thiamin in nervous tissue includes the following (Muralt, 1962; Cooper et al., 1963): (a) thiamin is involved in the synthesis of acetylcholine, which transmits neural impulses; (b) thiamin participates in the passive transport of sodium (Na+) to excitable membranes, which is important for the transmission of impulses at the membrane of ganglionic cells; and (c) thiamin’s role in glucose metabolism, via pentose phosphate pathways and pyruvate dehydrogenase complex, influences the efficiency of energy metabolism and synthesis of fatty acids in the nervous system. Recently, the detailed pathophysiology and biochemistry of thiamin deficiency-induced processes in the brain have been studied in human subjects, animal models, and cultured cells (Gibson and Zhang, 2002; Martin et al., 2003; Ke and Gibson, 2004). Neurodegeneration becomes apparent, initially as a reversible lesion and later irreversibly, in very specific areas of the brain, notably the submedial thalamic nucleus and parts of the cerebellum, especially the superior cerebellar vermis (Bates, 2006). 



Thiamin requirements in some species are difficult to establish because of vitamin synthesis by microflora in ruminants and most likely for all species in the lower intestine. For poultry, it is doubtful whether the amount of thiamin produced by intestinal synthesis and absorbed is large enough to make a significant contribution to body needs. Poultry species thiamin requirements generally range between 0.8 and 2.0 mg per kg (0.36 to 0.90 mg per lb) diet (NRC, 1994) while classes of Japanese quail range between 1.6 to 3.2 mg per kg (0.72 to 1.5 mg per lb) diet (Shim and Boey, 1988). Diet composition can dramatically influence thiamin requirements. Since thiamin is specifically involved in carbohydrate metabolism, level of dietary carbohydrate relative to other energy-supplying components influences thiamin requirement. The need for thiamin increases as consumption of carbohydrate increases (McDowell, 2000; Elmadfa et al., 2001). When dietary thiamin is deficient, body reserves become depleted more rapidly when animals are being maintained on a feed rich in carbohydrates than when they are receiving a diet rich in fat and protein. The “thiamin sparing” effect for fats and protein has long been known. Size, genetic factors and metabolic status affect thiamin requirements. Thiamin requirement is also proportional to size. Light poultry breeds (Leghorn) seem to have higher thiamin requirements than heavy breeds (Thornton and Schutze, 1960) and Leghorn hens deposit more thiamin in eggs than do heavy hens. As an animal ages, its need for thiamin increases because efficiency of vitamin utilization likely diminishes. Olkowski and Classen (1996), working with broilers, indicated that there are organ-specific differences in the requirement for thiamin. The heart had an increased requirement compared with the liver and brain. Maternal thiamin nutrition affects thiamin status and metabolism of the offspring (Olkowski and Classen, 1999). Maternal thiamin supplementation of the hen increased heart thiamin in broiler offspring. Thiamin requirements are obviously higher if feeds contain raw materials (e.g., fish) or additives with anti-thiamin action. Spoiled and moldy feeds may contain such antagonists or thiaminases. Chicks kept on a feed infected with Fusarium moniliforme developed polyneuritis that could be cured with thiamin injections (Fritz et al., 1973). Moldy feed analyses showed a thiamin content of less than 0.1 mg per kg (0.05 mg per lb), whereas the same feed not contaminated with Fusariumhad a thiamin content of 5.33 mg per kg (2.4 mg per lb). This antagonistic factor could be destroyed by treatment with steam. Disease conditions also result in increased thiamin requirements. When dietary thiamin is marginal, typical deficiency signs of thiamin are more likely to develop in infected animals than in normal animals. Endoparasites such as strongylids and coccidia compete with the host for thiamin contained in feed. It has been shown experimentally that infection with coccidia results in considerable reduction in thiamin blood levels. Thiamin levels found were directly correlated to infection severity (McManus and Judith, 1972). Likewise, conditions such as diarrhea and malabsorption increase the requirement.



Brewer’s yeast is the richest known natural source of thiamin. Cereal grains and their by-products, soybean meal, cottonseed meal and peanut meal are relatively rich sources of thiamin. Since the vitamin is present primarily in the germ and seed coats, by-products containing the latter are richer than the whole kernel, while highly milled flour is very deficient. While rice may contain 5 mg per kg (2.3 mg per lb) thiamin with much lower and higher concentrations for polished rice (0.3 mg per kg; 0.14 mg per lb) and rice bran (23 mg per kg; 10.5 mg per lb), respectively (Marks, 1975). Wheat germ ranks next to yeast in thiamin concentration. Reddy and Pushpamma (1986) studied the effects of one year of storage and insect infestation on the thiamin content of feeds. Thiamin losses were high in several varieties of sorghum and pigeonpea (40% to 70%) and lower in rice and chickpea (10% to 40%). Insect infestation caused further loss.

The presence of molds in feeds can result in substantial nutrient loss, including thiamin (Cook, 1990). The content of thiamin was reduced from 43% to 50% for two cultivars of wheat infested with Aspergillus flavus compared to the uncontaminated sound wheat (Kao and Robinson, 1973).

The level of thiamin in grain rises as the level of protein rises; it depends on species, strain, and use of nitrogenous fertilizers (Zintzen, 1974). The content in hays decreases as plants mature and is lower in cured than in fresh products. The thiamin concentration is correlated with leafiness and greenness as well as protein content. In general, good quality hay is a substantial source, and in a dry climate there is practically no loss in storage. Since thiamin is water soluble as well as unstable to heat, in certain cooking operations large losses result (McDowell. 2000).

Thiamin sources available for addition to feed are the hydrochloride and mononitrate salts. Because of its lower solubility in water, the mononitrate salt has somewhat better stability characteristics in dry products than the hydrochloride (Bauernfeind. 1969).



Poultry are more susceptible to neuromuscular effects of thiamin deficiency than most mammals. In chickens and turkeys, there is a loss of appetite, emaciation, impairment of digestion, a general weakness, opisthotonos or stargazing and frequent convulsions, with polyneuritis as an extreme clinical sign. Deficient birds can rapidly detect and discriminate against feeds that do not provide the vitamin (Hughes and Wood-Gush, 1971) and are high in carbohydrate content (Thornton and Shutze, 1960). The classic disease of polyneuritis in birds represents a late stage of thiamin deficiency resulting from a peripheral neuritis, perhaps caused by accumulation of intermediates of carbohydrate metabolism. Comparing thiamin deficiency signs in various species, it is seen that disorders affecting the central nervous system are the same in all species. This is explained by the fact that, in animals, the brain covers its energy requirement chiefly by the degradation of glucose and is therefore dependent on biochemical reactions in which thiamin plays a key role. In turkeys, thiamin deficiency also resulted in tissue alteration of amino acids, decreased concentration of epinephrine and ATP and increased serotonin in the brain of birds (Remus and Firman, 1989; 1990; 1991a, b). In addition to neurological disease conditions, the other main group of disorders involves cardiovascular damage.Of all nutrients, a deficiency of thiamin has the most marked effect on appetite. Animals consuming a low-thiamin diet soon show severe anorexia, lose all interest in food and will not resume eating unless given thiamin. If the deficiency is severe, thiamin must be force fed or injected to induce animals to resume eating. Early signs of thiamin deficiency are lethargy and head tremors. Chicks fed very low thiamin (0.4 mg per kg; 0.18 mg per lb) survived for only seven to 10 days, apparently only a few days after the supply of thiamin in the yolk sac was exhausted (Gries and Scott, 1972). Some chicks developed nervous disorders, apathy and tremor as early as the third or fourth day of life. These signs increased in severity up to ataxia, inability to stand, and high-grade opisthotonos or twisting of the neck. Severity of the spasms increased when the chicks were frightened. Chicks that showed these high-grade nervous disorders died within a few hours. Cardiac abnormalities have also been reported in acutely thiamin-deficient chicks (Sturkie et al., 1954). A paralysis of the crop, manifested as delayed emptying, accompanies the general neuropathy of experimental thiamin deficiency in chicks (Naidoo, 1956). Deficiency in pigeons results in crop voiding (vomiting). In mature chickens, polyneuritis (Illus. 7-2) is observed approximately three weeks after they are fed a thiamin-deficient diet (Scott et al., 1982). As the deficiency progresses, paralysis of the muscles occurs, beginning with the flexors of the toes and progressing upward, affecting the extensor muscles of the legs, wings and neck. The chicken sits on its flexed legs and draws back the head in a stargazing (opisthotonos) position. Retraction of the head is due to paralysis of the anterior neck muscles. At this stage, the chicken soon loses the ability to stand or sit upright and falls to the floor, where it may lie with the head still retracted.


Illustration 7-2: Thiamin Deficiency, Polyneuritis


Courtesy of M.L. Scott, Cornell University


Acutely deficient pigeons developed vomiting, emaciation, leg weakness, and opisthotonos, the last of which appears between seven and 12 days after beginning the thiamin-free diet (Swank, 1940). Chronic deficiency due to a diet partially inadequate in thiamin resulted in leg weakness but no opisthotonos. Evidence of cardiac failure was also noted. The lesions produced in thiamin-deficient pigeons are reported to be identical to those found in Wernicke’s polioencephalitis in humans (Lofland et al., 1963). Pheasant mycotoxin-induced polyneuritis was eliminated within hours after intraperitoneal injection of thiamin (Cook, 1990). In the thiamin-deficient turkey, the onset of anorexia was rapid; by the fourth day, deficient birds had significantly lower feed consumption (Remus and Firman, 1990). For chickens with thiamin deficiency, body temperature drops to as low as 36°C (97°F) and respiratory rate progressively decreases (Scottet al., 1982). There is adrenal gland hypertrophy that apparently results in tissue edema, particularly in the skin. Atrophy of genital organs also occurs in chickens affected with chronic thiamin deficiency, being more pronounced in the testes than in the ovaries. The heart shows a slight degree of atrophy. The hen transfers thiamin to the egg in proportion to dietary content (Polin et al., 1963; NRC, 1994; Peŕeg-Vendrell et al., 2003b). Inadequate thiamin to the breeder flock will result in high mortality of embryos prior to hatching and chicks that do hatch express polyneuritis (Polin et al., 1962; Charles et al., 1972).


Fortification Considerations

Thiamin is found in most feedstuffs, but in widely differing concentrations. The thiamin content of most common feeds should be three to four times greater than requirements for most species (Brent, 1985). For poultry consuming typical diets (e.g., corn-soybean meal), thiamin is one of the vitamins least likely to be deficient. Although thiamin levels supplied by feedstuffs in the ration are generally considered adequate for poultry, thiamin deficiency and inadequacy have been observed in poultry under commercial production conditions. Field experience and research showed that although the amounts of thiamin supplied by feedstuffs in practical corn-soybean rations met the minimum requirement for broilers, adding supplemental thiamin and (or) biotin to these rations improved growth rate and feed conversion (Wagstaff, 1978). Increasing supplemental thiamin to levels that exceed NRC requirements and current industry averages has been reported to decrease mortality in turkeys (Cook, 1992). Drying and processing can lower the concentrations of available thiamin in feedstuffs because thiamin is heat labile. Utilization of available thiamin in feedstuffs may be limited and may also be impaired by thiamin antagonists; therefore it is common practice to add supplemental thiamin to poultry feeds to replace thiamin loss during processing and storage. Thiamin supplementation is greatly modified if diets contain anti-thiamin substances, such as thiaminases from fish or moldy feed. In addition, of the several water-soluble vitamins analyzed, two cultivars of corn were found to experience substantial declines only in thiamin (Kao and Robinson, 1972). Anti-thiamin substances present in some feedstuffs and weeds, such as oxythiamin, should be considered. Non-nutrient substances intentionally added to diets are sometimes of concern, such as the coccidiostat amprolium, a thiamin antimetabolite. A mild thiamin deficiency from amprolium added to a standard commercial hen feed caused a reduction in feed intake and egg laying performance and an increase in the mortality of embryos and chicks. These phenomena could be prevented or effectively counteracted by high thiamin doses in the feed. At recommended levels, apparently, amprolium does not interfere with the thiamin metabolism of the chicken (Scott et al., 1982). Other thiamin antagonists, such as the free bisulfite, may be present in feeds and reduce free thiamin activity. It has been reported that use of high-moisture barley treated with sulfur dioxide resulted in destruction of 61% of dietary thiamin (Gibson et al., 1987). Treatment of feed ingredients with sulfur dioxide inactivates thiamin.

A malady dubbed “spiking syndrome” in broilers caused a sharp rise in mortality at about 14 days of age. Some nutritionists feel that this problem may be associated with fusaria mycotoxins, although the exact cause is not clearly defined. Increased levels of thiamin ameliorate the rise in mortality, and it is suggested that when either corn quality is poor or mycotoxin levels and/or mold counts are high, thiamin should be increased by 1.11 to 1.65 mg per kg (0.50 to 0.75 mg per lb) in the starter feed (Coelho, 1996).

Thiamin sources available for addition to feed are the hydrochloride and mononitrate forms. Because of its lower solubility in water, the mononitrate is preferred for addition to dry premixes. The mononitrate form has somewhat better stability characteristics in dry products than the hydrochloride (Bauernfeind, 1969).

Stability of thiamin in feed premixes can be a problem. More than 50% of the thiamin was destroyed in premixes after one month at room temperature (Verbeeck, 1975). When thiamin was in premixes without minerals, no losses were encountered when kept at room temperature for six months. However, vitamin premixes that contain choline and trace minerals will experience problems with instability.

Under certain conditions a thiamin inadequacy for a poultry feed may be created. Thiamin is very unstable to heat under neutral and alkaline pH conditions. Tests show that while no destruction occurs in 1 percent HCl during 7 hours at 100°C, over 90% destruction occurs under the same conditions at pH 7, and 100% destruction in 15 minutes at pH 9. Poultry diets, and especially pelleted diets, should not contain alkaline salts in sufficient quantities to produce an alkaline reaction in the feed (Leeson and Summer, 2001). In recent years, feed manufacturers have increased pelleting temperatures for all animal feeds in order to control Salmonella organisms and increase digestibility and are using steam pelleting, prepelleting conditioners and feed expanders, which lead to increased vitamin degradation (Ward, 2005).

A discussion has arisen on removal of vitamin and trace mineral supplementation from poultry and other species’ diets some time prior to slaughter. Skinner et al. (1992) reported that removal of vitamins and trace minerals from broiler diets did not impact performance. In contrast, Teeter and Deyhim (1993) detected reduced performance and carcass variables when the same period was examined. Deyhim et al. (1996) withdrew vitamin and trace minerals for 21 days in broiler diets during heat stress and found 23% less thiamin in the Pectoralis major muscles. Such effects have the potential to affect consumer perception of poultry meat as wholesome and should be considered when vitamin withdrawal is being contemplated.


Vitamin Safety

Thiamin in large amounts orally is not generally toxic and usually the same is true of parenteral doses (NRC, 1987). In chickens, it takes some 700 times the requirement level of thiamin in order to induce toxicity. Signs of toxicity are blockage of nerve transmissions and labored breathing, with death usually occurring due to respiratory failure.