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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 white, crystalline thiamin hydrochloride (89.2% thiamin), or thiamin mononitrate (91.9% thiamin). Thiamin has a characteristic sulfurous odor and a slightly bitter taste. Thiamin is very soluble in water, sparingly so in alcohol, and insoluble in non-polar solvents. It is very sensitive to alkali. The thiazole ring opens at room temperature when pH is greater than 7. In the 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 co-carboxylase. 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. Tall fescue (Festuca arundinacea Schreb.) toxicosis resembles diseases caused by elevated rumen thiaminase activity (Lauriault et al., 1990). Thiaminase alters the structure of the vitamin. The disease “Chastek paralysis” in foxes and other animals fed certain types of raw fish results from a thiaminase. Since thiaminase is inactivated by heat, the problem can be avoided by cooking the fish at 83°C for at least five minutes. Certain microorganisms (bacteria and molds) and plants (bracken fern) produce thiaminases and can produce toxicity in animals. Two types of thiaminase enzymes have been described. Thiaminase I substitutes a different base for the thiazole ring, which produces a thiamin analog in addition to reducing thiamin supply. The thiamin analog may then be absorbed and possibly inhibit thiamin-requiring enzyme reactions (Frye et al., 1991). In contrast, thiaminase II simply cleaves thiamin at the methylene bridge between the thiazole and the pyrimidine rings. More detailed reviews of the role of thiaminases in induced thiamin deficiency in ruminants are available (Frye et al., 1991; Harmeyer and Kollenkirchen, 1989). Thiamin appears to be readily digested and absorbed from naturally occurring sources. A precondition for normal absorption of thiamin is sufficient production of hydrochloric acid in the stomach. Phosphoric acid esters of thiamin are hydrolyzed in the small intestine. The free thiamin formed is water soluble 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 (Braunlich and Zintzen, 1976; Gubler, 1991). At low concentrations, there is an active sodium-dependent transport of thiamin against the electrochemical potential, whereas at high concentrations (>2 µM), absorption occurs by diffusion across the intestinal wall. Specific thiamin-binding proteins in the cell membrane allow thiamin to be solubilized within the cell membrane. This permits passage through the membrane for release into the aqueous environment of the cytosol (Rose, 1996). Thiamin is transported to the liver via the portal vein, bound to a carrier protein. Up to 90% of whole blood thiamin is concentrated in the erythrocytes and leukocytes (Gubler, 1991). Red blood cells and leukocytes accumulate thiamin in part due to their dependence on the pentose pathway and glycolysis.

Thiamin phosphorylation takes place in most tissues, but particularly in the liver. Eighty percent of thiamin in animals is phosphorylated in the liver by thiamin pyrophosokinase, an ATP-requiring enzyme. The metabolically active, thiamin pyrophosphate (TPP, or co-carboxylase) is formed. Of total body thiamin, about 80% is found as TPP, 10% as thiamin triphosphate (TTP) and the remaining 10% as 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, spleen and kidney. Although liver and kidney tissues have the highest thiamin concentrations, approximately one-half of the total thiamin body stores are present in muscle tissue (Tanphaichair, 1976). Thiamin, however, is one of the most poorly stored vitamins. Most mammals fed a thiamin-deficient diet will exhaust their body stores within one to two weeks (Ensminger et al., 1990).

Thiamin intakes in excess of immediate needs are rapidly excreted. Absorbed thiamin is excreted in both urine and feces, with small quantities excreted in sweat. Fecal thiamin originates 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 increases first to a saturation level, followed by a progressive increase in fecal excretion (Braunlich and Zintzen, 1976).



The principal cellular function of thiamin is as the coenzyme TPP or co-carboxylase, which is required for oxidative decarboxylation of alpha-keto acids in metabolism. Thiamin is a required cofactor for two pivotal reactions of the Krebs cycle; the oxidative decarboxylations of pyruvate to acetyl-CoA, and of alpha-ketoglutarate to succinyl-CoA (Figure 7-1). The Krebs cycle (tricarboxylic acid cycle; TCA cycle; citric acid cycle) is the primary energy-producing pathway in the body. The Krebs cycle integrates catabolism of carbohydrates, fats and proteins and provides intermediates for synthesis of organic compounds. Thiamin, riboflavin, pantothenic acid, niacin and biotin play direct roles as cofactors in the Krebs cycle. The thiamin requiring reactions of the Krebs cycle are shown below:

pyruvate → acetyl-CoA + CO2,alpha-ketoglutaric acid → succinyl-CoA + CO2


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


Adapted from Bräunlich and Zintzen (1976)


Thiamin plays an important role in glucose metabolism. TPP is a coenzyme in the transketolase reaction that is part of the direct oxidative pathway (pentose phosphate cycle) of glucose. The pentose pathway occurs in the cell cytoplasm of red blood cells, liver, brain, adrenal cortex and kidney, but not in skeletal muscle. The pentose phosphate cycle is the only mechanism known for synthesis of ribose, which is required for nucleotide (RNA, DNA) formation. The pentose pathway also produces nicotinamide adenine dinucleotide phosphate (NADPH) that provides reducing equivalents for synthesis of fatty acids and other products.A more recently discovered role of thiamin is as coenzyme for the oxidative decarboxylation of iso-keto acids derived from the degradation of the branched-chain amino acids (leucine, isoleucine, valine). A dehydrogenase enzyme complex similar to pyruvate dehydrogenase has been reported (Gubler, 1991). Little is known of thiamin function in nervous tissue. However, evidence has accumulated for a specific role of thiamin in nerve transmission that is independent of its coenzyme function. Possible mechanisms of thiamin action in neural tissue include (Muralt, 1962; Cooper et al., 1963): (1) thiamin is involved in the synthesis of acetylcholine, a neurotransmitter; (2) thiamin participates in the passive transport of sodium (Na+) through nerve cell membranes, particularly in the membrane of ganglionic cells; and (3) thiamin’s role in glucose metabolism, via pentose phosphate pathways and pyruvate dehydrogenase complex, directly and indirectly 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). Additionally, there may a direct role of thiamin phosphates in generation of nerve impulses (Grubber, 1991)



Thiamin requirements are difficult to establish in ruminants because of rumen and likely, intestinal synthesis. However, synthesis in the intestine may not be important, as most of it apparently occurs in the lower intestinal tract where absorption of thiamin is limited.Animals with a functional rumen are generally considered to have no dietary thiamin requirement because of rumen microbial synthesis. Amounts of thiamin synthesized daily in the rumen (28 to 72 mg) have been reported to equal or exceed dietary intake (Breves et al., 1981). The combination of thiamin in feeds and synthesis of thiamin in the rumen meet or exceed metabolic requirements even with an estimated 48 percent destruction of dietary thiamin in the rumen (Zinn et al., 1987). However, thiamin deficiency can be produced in lambs and calves and other young ruminants that do not have a functional rumen. Thiamin-responsive polioencephalomalacia occurs in cattle and sheep with functional rumens. Acute thiamin deficiency has been produced in calves and lambs by feeding a thiamin-free diet (Drapper and Johnson, 1951; Benevenga et al. 1966). The estimated requirement for the dairy calf is 65 µg per kg (29.5 µg per lb) of body weight or 6.5 mg per kg (3.0 mg per lb) of milk replacer powder (NRC, 1989). Thiamin deficiency in the young ruminant can be produced as late as the sixth week of life. Gastrointestinal (GI) synthesis of thiamin becomes significant in calves from about the sixth week of life on, but this synthesis is still relatively poor from weaning up to five months of age (Zintzen, 1974). The GI-synthesis of thiamin is enhanced by readily fermentable carbohydrates and by nitrogen sources such as urea. Concentration of thiamin in the gastrointestinal tract, especially in the rumen, is more uniform than in feed. Thiamin synthesis appears to vary inversely with feed thiamin concentration, suggesting some type of feedback regulation of rumen thiamin synthesis (Zintzen, 1974). In steers, Miller et al. (1986a, b) reported little effect of either ration concentrate level, antibiotic or ionophore feeding on thiamin synthesis or absorption. Duodenal thiamin concentration increased with increasing thiamin intake. There was also an increase in rumen disappearance of thiamin with increasing intake.

Thiamin requirement rises as consumption of carbohydrate does (Benevenga et al., 1966; McDowell, 2000; Elmadfa et al., 2001). When dietary thiamin is deficient, body reserves are depleted more rapidly in animals fed a high carbohydrate diet than in those fed a diet high in fat and protein. The “thiamin-sparing” effect of fat and protein has long been known. Inadequate nitrogen in the ration of lactating cows may decrease thiamin synthesis in the rumen and the amount of thiamin entering the duodenum (Breves et al., 1984).

Metabolic body size, genetics and metabolic state can affect the thiamin requirements. Infectious and parasitic diseases also increase 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. In poultry blood, thiamin is reduced in experimentally produced coccidiosis. Blood thiamin concentrations were inversely correlated to the severity of infection (McManus and Judith, 1972). Therefore circumstantial evidence suggests that young ruminants heavily infested with coccidia and being treated with amprolium should receive supplemental thiamin as a precautionary measure.

Thiamin requirements are increased if the diet contains thiaminase activity. Spoiled and moldy feeds may contain thiaminases. Fusarium molds produce thiaminase (Fritz et al., 1973). High dietary intakes of sulfur (Gooneratne et al., 1989; Kandylis, 1984), especially combined with low copper status (Olkowski et al., 1991), as well as substances in tall fescue (Festuca arundinacea) (Edwin et al., 1968; Lauriault et al., 1990) are antagonistic to thiamin, resulting in higher dietary requirements. These conditions are discussed further in the section on thiamin deficiencies.



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

The presence of active molds in feed resulted 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 uncontaminated, sound wheat (Kao and Robinson, 1973). Analyses showed a thiamin content of less than 0.1 mg per kg (0.045 mg per lb) in feed contaminated with Fusarium moniliforme, and a thiamin content of 5.33 mg per kg (2.2 mg per lb) in non-contaminated feed (Fritz et al., 1973).

The level of thiamin in grain increases with protein content, depending on species, strain and use of nitrogenous fertilizer (Zintzen, 1974). Thiamin content of hay 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 significant source of thiamin, and in a dry climate there is practically no loss in storage. Since thiamin is water soluble as well as unstable to heat, losses may occur in feed processing, although the short duration of feed processing is less detrimental than cooking (McDowell, 2000).

Thiamin sources available for addition to feed are hydrochloride and mononitrate salts. Because of its lower solubility in water, the mononitrate salt has somewhat better stability characteristics in dry products than in hydrochloride (Bauernfeind, 1969; Gadient, 1986).



In most species thiamin deficiency is expressed as a central nervous system dysfunction due to the dependence of the brain on glycolysis for energy production. Clinical signs include an apparent weakness that is usually first characterized by poor leg coordination, especially of the forelimbs, and by inability to rise and stand. The head is frequently retracted (i.e., “star-gazing”) (Illus. 7-2), and cardiac arrhythmia may occur. Affected animals may also display blindness and convulsions. Specific signs are usually accompanied by growth depression, anorexia and severe diarrhea, followed by dehydration and death (McDowell, 2000; NRC, 2000). Signs in calves can be either acute or chronic. Acutely affected calves displayed anorexia with severe diarrhea and died within 24 hours of onset. These signs appeared after two to four weeks on a low-thiamin diet (Johnson et al., 1948). Growing cattle display dullness and neural aberrations such as circling, head pressing, apparent blindness, excitability and convulsions. These symptoms may be confused with those of certain bacterial or viral diseases (e.g., clostridial infections, listeriosis, encephalitis), heavy metal poisoning (e.g., lead), hypomagnesemia or vitamin A deficiency. Mortality can be sudden and significant if animals are not treated. This condition, polioencephalomalacia (PEM) or cerebrocortical necrosis (CCN), is also observed in sheep and goats. The condition is often precipitated by feeding high grain feedlot rations or by the sudden introduction of livestock to lush pasture. Low copper status and high intakes of sulfur, especially sulfate, in feed or water are risk factors. In some instances similar symptoms arise as a result of sulfur toxicity and the production and inhalation of hydrogen sulfide gas, a neurotoxin (Kandylis, 1984).


Illustration 7-2: Thiamin Deficiency in Sheep, Opisthotonos


Courtesy of Michel Hidiroglou, Animal Research Center, Ottawa, Canada


The extensive rumen synthesis of thiamin suggests that ruminants possessing a normally functioning rumen have no absolute dietary thiamin requirement. However, thiamin deficiencies do develop in ruminants under certain conditions. In several areas in the world, a thiamin-responsive disease, which occurs sporadically in cattle, sheep and goats, is known as polioencephalomalacia (PEM), also known as cerebrocortical necrosis (CNN), cerebral necrosis and forage poisoning. The term PEM refers to a laminar softening or degeneration of grain gray matter (Brent and Bartley, 1984). Thiamin deficiency blocks the glycolytic and pentose pathways in neural tissue, leading to inflammation and necrosis. PEM affects mainly calves and young cattle between four months and two years of age and lambs, young sheep and goats between two and seven months of age. The incidence of PEM is reported to be between 1% and 20%, and mortality may reach 100%. Clinical signs in mild cases include dullness, blindness, muscle tremors, especially of the neck, and opisthotonos (“star-gazing”). Other progressive symptoms include circling, head pressing and convulsions; in severe cases, collapse within 12 to 72 hours after the onset of the disease (Illus. 7-3). In the final stages, the ears droop and the limbs and head are extended, which is a parallel of “star-gazing” in thiamin-deficient chicks. Trembling and twitching of the musculature of the ears and eyelids, weaving of the head and neck and grinding of the teeth with groaning may be observed. Without treatment, death usually occurs within a few days. The main lesions in these animals are necrotic areas in both cerebral hemispheres.


Illustration 7-3: Thiamin Deficiency in Cattle, Polioencephalomalacia


Courtesey of B. BBock, University of Florida

PEM may appear as an acute disease with high mortality or in milder forms that run a more protracted course. Not all animals in a group will be affected. It is probable that, particularly in its mild form, the condition is often not diagnosed and may in fact occur more frequently than is recognized. Clinical signs of central nervous system (CNS) disorders associated with PEM are more readily recognized than the nonspecific symptoms such as scouring, reduced growth and anorexia. However, these signs are also exhibited at later stages of thiamin deficiency (Rammell and Hill, 1986). Thornber et al. (1979) reported that lambs fed a thiamin-deficient diet may not show clinical signs of a CNS disorder for three to five weeks or longer, although depressed blood thiamin levels and other clinical signs may be observed. Without treatment, mortality is about 50% with the mild form and may be up to 100% in the acute form of PEM. The incidence and death rate are highest in young animals from two to five months of age. A number of experiments have shown that PEM can be caused by naturally occurring thiamin antagonists, reduced thiamin synthesis or increased destruction of thiamin in the rumen. Several researchers report that most field cases of PEM result from a progressive thiamin deficiency, likely the result of bacterial thiaminases in the rumen or lower intestine (Loew, 1975; Frye et al., 1991). Clinical reports indicate that high concentrate rations or sudden introduction of lush pasture results in production of rumen thiaminases and predisposes young cattle and sheep to PEM (Edwin and Lewis, 1971). There is also evidence that disruptions of rumen function by sudden diet change can result in production of anti-thiamin analogs. Thiaminases can be produced by bacterial and fungal contamination of feeds (Davies and Pill, 1968). Clostridium sporogenes and Bacillus thiaminolyticus have been isolated from the rumen of PEM-affected cattle and sheep (Loew, 1975; Cushnie et al., 1979; Haven, et al., 1983). Both organisms produce thiaminase type I. Thiaminases are found in certain plant species, such as the bracken fern. This is a special problem in Australia, where PEM occurs under pasture conditions, apparently due to grazing of certain fern species. Forage species suspected of causing PEM included Sisymbrium irio (London rocket), Capsella bursapastoris (shepherd’s pulse), Raphanus raphanistrum (wild radish) and Amaranthus blitoides (Ramos et al., 2005; McKenzie et al., 2009). In the study of Mackenzie et al. (2009), the forages causing PEM were high in sulfur (0.62% and 10.1%) which is often associated with PEM. Furazolidone at high doses produces a thiamin-responsive neuropathology including head tremors, ataxia, visual impairment and convulsions (Ali et al., 1984; Merck, 1991). The anticoccidial mode of action of amprolium is apparently through inhibition of thiamin phosphorylation. Loew and Dunlop (1972) found that high levels of amprolium (considerably above the levels needed to prevent coccidiosis) could produce the physical signs and the histological lesions of PEM. Amprolium-induced PEM produces abnormal changes in brain waves and is thiamin responsive (Itabisashi et al., 1990). Wernery et al. (1998) reported amprolium induced PEM in dromedary camels,when only a barley diet was fed and not when the camels were fed hay ad libitum. However, serum thiamin was depressed equally in both groups, indicating an interaction between amprolium and diet in producing PEM.

From Colombia, a wasting disease known as “secadera” or “drying up” (Illus. 7-4) is alleviated by thiamin injections (Mullenax, 1983). Mullenax (1983) suggested that a fungus associated with native forage produces a thiaminase. On the contrary, Miles and McDowell (1983) report that the wasting disease secadera can be successfully controlled with a highly fortified complete mineral supplement. It is possible that supplementation of this wasting disease is controlled by either thiamin or trace minerals through different mechanisms (McDowell, 1985). More recent data show an effect of copper on thiamin metabolism in cattle (Olkowski et al., 1991), suggesting that marginal copper status is a factor in PEM, and other related neural degenerative diseases (Frank et al., 1992).


Illustration 7-4: Thiamin Deficiency in Cattle. 
Wasting Disease


Wasting disease (“secadera”) of cattle in the llanos of Columbia. Animals characterized by emaciated condition even with quality available forage. This condition has been reported as thiamin deficiency since it has been alleviated with thiamin injections. However, “secadera” has also been controlled with a highly fortified complete mineral supplement. 

Courtesy of L.R. McDowell, University of Florida


High sulfur diets or water sources are associated with thiamin deficiency and PEM symptoms (Kandylis, 1984; Olkowski, 1991b; Gould, 1998; McKenzie et al., 2009). The toxicology of sulfur in ruminants has been reviewed in detail by Kandylis (1984). Gould et al. (1991) reported that in steers the highest rumen fluid sulfide concentrations coincided with the onset of clinical signs of PEM. McAllister et al. (1997) investigated a field case of PEM induced by high sulfate water and reported no reduction in blood thiamin in affected steers. Controlled studies have reported both significant reductions (Goetsch and Owens, 1987) and small reductions (Alves de Oliveira et al., 1997) in rumen thiamin production in response to high sulfate intakes. Olkowski et al. (1991b), in a large field study, reported that beef cattle consuming high sulfate water sources had reduced blood thiamin status. Several cases of PEM have occurred when gypsum (CaSO4) has been used as a feed intake-limiting factor. It would appear that the sulfate ion of gypsum, during its conversion to sulfide, must pass through sulfite, which itself may destroy thiamin or produce anti-thiamine analogs (Bartley and Brent, 1982). Feedlot cattle that received 0.72% sulfate had 50% less gain than controls and some developed PEM (Sadler et al., 1983). For sheep, high sulfur intake was shown to have a detrimental effect on in vitro polymorphonuclear leukocyte function. Thus, ruminants consuming diets or water high in sulfur may have reduced immune function and increased risk of disease (Olkowski et al., 1990). Low copper status appears to play a role in development of PEM in sheep (Olkowski et al., 1991a). High dietary sulfur and molybdenum can induce copper deficiency through formation of thiomolybdates in the rumen (Maynard et al., 1979). Thus, low dietary copper, high dietary or water sulfate and molybdenum are predisposing factors for PEM. Brassica plant species contain high levels of sulfur and can produce low copper status in ruminants (Taljaard, 1993). The symptoms of PEM are not entirely specific to thiamin deficiency although thiamin deficiency is clearly one of several causative factors, along with high concentrate diets, excess sulfur intakes and low copper status. Livestock grazing tall fescue infected by an endophyte (Acremonium coenophiatum) can suffer from tall fescue toxicosis. The symptoms resemble those caused by elevated rumen thiaminase activity, for example, PEM (Edwin et al., 1968; Lauriault et al., 1990), and are alleviated by thiamin supplementation (Dougherty et al., 1991). Response to supplemental thiamin was found to be greater when cattle grazing endophyte-infected tall fescue were exposed to heat stress (Lauriault et al., 1990). Results suggest that oral thiamin supplementation may alleviate tall fescue toxicosis of beef cattle during hot weather. An earlier study (Fontenot et al., 1988) found that in cattle grazing fescue moderately infected by endophytes, supplemental thiamin did not have any beneficial effect. Diagnosis of thiamin deficiency initially depended upon recognition of the clinical signs in live animals, followed by confirmatory brain histopathology or clinical response to thiamin administration (Rammell and Hill, 1986). Moreover, affected animals react so promptly to treatment with thiamin (sometimes within hours) that early treatment with thiamin is used to confirm the diagnosis of PEM. Biochemical changes indicating that PEM is associated with thiamin deficiency include reduced blood, urine and tissue thiamin concentrations, dramatic elevation of blood pyruvate and lactate, and markedly reduced erythrocyte transketolase activity (Braunlich and Zintzen, 1976; Karapinar et al., 2010). Brin (1969) showed that blood transketolase activity (particularly in the red cells) is a reliable index of the availability of coenzyme TPP, and thus is well correlated with the degree of deficiency in animals. Transketolase activity is an excellent indicator of a marginal thiamin deficiency. The best transketolase assay for assessing thiamin deficiency is based on the so-called TPP effect, which is the percentage increase in transketolase activity following addition of excess TPP to the sample. Values of 120% to 250% have been reported for animals diagnosed as having PEM (Edwin et al., 1979). Benevenga et al. (1966) performed a classical experiment on thiamin deficiency in Holstein calves fed a purified diet. Deficiency symptoms appeared 27 to 48 days after initiation of a thiamin-free diet. Anorexia, heart arrhythmia, respiratory distress, lacrimation and grinding of teeth were clinical symptoms. Blood pyruvate and lactate levels were elevated, hemoglobin and PCV depressed and, activities of several liver enzymes were reduced 30% to 50%. Re-feeding thiamin relieved all symptoms.Zintzen (1974) concludes that PEM can be definitely established if the following four situations exist:

  1. Case history: Animals maintained on high energy feeds rich in soluble carbohydrates died after showing central nervous system disorders.
  2. Biochemical evidence: Blood pyruvate has steeply increased and the activity of erythrocyte-transketolase has been reduced.
  3. Diagnostic therapy: Animals thought to have PEM will react promptly to early treatment with thiamin.
  4. Pathological changes: Necropsy shows typical pathological, anatomical changes, i.e., bilateral cortical necrosis in the brain.


Seasonal trends have been associated with PEM, which may be due to increased metabolic demands of gestation, lactation and growth, or changes in rumen microbial populations. Additionally, feeding of high-concentrate, low-fiber rations may induce PEM. Polioencephalomalacia generally occurs in feedlot cattle about three weeks after a diet change. Thiamin deficiency in both chronic ruminal acidosis and acute ruminal lactic acidosis may occur because of inadequate synthesis of thiamin. Furthermore, a decrease in ruminal pH may result in the release of bacterial thiaminases. Research suggests that PEM is associated with lactic acid acidosis and with the adaptation to high-grain rations. Oltjen et al. (1962) reported that thiamin in the rumen is decreased by a reduction in rumen pH; a low ruminant pH is characteristic of cattle fed high-concentrate diets. However, this effect was not observed in vitro using rumen simulation techniques (Alves de Oliveira et al., 1997).

PEM has caused significant economic losses in tropical countries, not only in feedlots where high-grain diets are fed, but also where high levels of molasses are fed. When molasses is provided ad libitum together with diets containing little crude fiber, a disease referred to as “molasses toxicity” or “molasses drunkenness” appears (Losada et al., 1971). Clinical signs of this condition closely resemble PEM, and some studies completed in Cuba have suggested that thiamin treatment, together with additional roughage, may be an effective cure. Mella et al. (1976) induced PEM by feeding a molasses-urea diet to cattle.


Fortification Considerations

The thiamin content of most common feeds is sufficient to exceed thiamin requirements of most species by three to four times, based on normal feed intakes (Brent, 1985). Under normal feeding and management conditions, and in the absence of anti-metabolites, thiamin deficiency should theoretically not occur in either young or adult ruminants. Nevertheless, utilization of available thiamin in feedstuffs may be limited and may also be impaired by thiamin antagonists. Likewise, high sulfur intakes pose a risk for PEM. Thiamin supplementation should be considered for ruminant animals that may potentially develop PEM as a result of consuming high-concentrate diets or high-sulfate water. Grazing ruminants normally would not receive supplemental thiamin unless evidence is provided that consumed pastures contain antagonists. An example would be thiamin supplementation for livestock grazing potentially toxic tall fescue pastures during midsummer when toxicosis is likely to be severe. Thiamin may be supplied to cattle at the daily rate of 1 g per head (Lauriault et al., 1990; Dougherty et al., 1991). Johnson and Krautmann (1989) reported that feeding 500 mg of thiamin per head per day for the first 30 days that cattle are in the feedyard reduced the effects of thermal stress. Although little information is available on the direct addition of thiamin to finishing cattle diets,Brethour (1972) reported that in two trials, a combination of thiamin and sodium carbonate supplement increased feed intake by 5% and daily gain by 8%. In a third trial, thiamin administered alone produced an intermediate response to calves immediately after weaning. Supplemental thiamin at 956 mg per day was not beneficial to stressed beef steers or heifers in two experiments (Silzell and Kegley, 1998). Goetsch and Owens (1987) reported that feeding 1,000 mg per day supplemental thiamin to steers markedly reduced rumen organic matter digestion and total tract digestion of starch and crude protein. Therefore, 1,000 mg per day may be excessive supplementation for cattle not suffering obvious thiamin deficiency symptoms. Recently, a series of three experiments tested the effects of supplemental thiamin in lactating dairy cows (Shaver, 1999). Cows were fed rations with varying proportions of alfalfa silage and corn silage, supplemented with corn-soy or corn byproduct grain mixtures. Thiamin, as thiamin mononitrate, was fed at 150 mg per day in the first trial and 300 mg per day in the latter two trials. There was a significant trend toward increased milk production in the first two experiments, while in the third trial thiamin decreased milk fat percentage and yield. Supplemental dietary thiamin, 150 to 300 mg per day, increased milk and component yields when dietary concentrations of neutral and acid detergent fiber were lower and non-fiber carbohydrate was higher than recommended (Shaver and Bal, 2000). Thiamin status may be marginal under certain conditions in high producing dairy cows. Subclinical deficiencies of thiamin can result in reduced synthesis of other B-vitamins because certain rumen bacteria require thiamin for growth. Mathison (1986) reported a feedlot trial in which a significant response to supplemental thiamin was observed and transketolase activity was numerically reduced in the controls. Thiamin did not increase gain in two subsequent trials, although bloat apparently was reduced in one trial. In a concomitant field survey, conducted in Alberta, 2.7% of 645 beef cattle sampled were marginal in plasma thiamin pyrophosphate (TPP), the coenzyme for transketolase. In acute PEM, 1,000 mg per day of injected thiamin is indicated until the animals resume eating, then 500 mg per day can be supplemented in the diet for 7 to 14 days (Mathison, 1986). If treated promptly by parenteral injection of thiamin 2.2 mg per kg (1 mg per lb) of bodyweight, the condition can be reversed (NRC, 2000). Feeding 4 to 6 mg of thiamin per kg (1.8 to 2.7 mg per lb) of diet has been suggested to help prevent subclinical thiamin deficiency in animals fed high-grain rations.

Animals with clinical signs of thiamin deficiency and (or) other indicators of insufficiency (i.e., reduced transketolase activity) should be rapidly treated with thiamin at therapeutic doses. Since thiamin deficiency causes anorexia, injection of the vitamin is preferred to the oral route in severe deficiency. Clinical signs in calves weighing less than 50 kg were prevented with 0.65 mg of thiamin hydrochloride per kg (0.30 mg per lb) of liquid diet fed at 10% of live weight (65 µg per kg or 29.5 µg per lb live weight) (Johnson et al., 1948). Treatment levels of thiamin for intravenous or intramuscular administration, for three-day periods, have been recommended for lambs and calves (100 to 400 mg per day) and for sheep and cattle (500 to 2,000 mg per day) (Zintzen, 1974).

For general maintenance following the treatment of mild cases of PEM, or as a prophylactic measure when a herd is at risk, 5 to 10 mg of thiamin should be added per kg (2.3 to 4.5 mg per lb) of dry feed. Feeds should be supplemented with thiamin such that animals receive 100 to 500 mg daily. Likewise, roughage should be added to the daily diet at the rate of 1.5% of body weight. Smith (1979) has suggested an oral dose of 6.6 to 11 mg per kg (3 to 5 mg per lb) body weight, repeated every six hours for 24 hours, for PEM therapy in goats.

The administration of thiamin to PEM animals generally produces rapid results, sometimes within hours. Where recognition of the disease has been delayed and irreversible necrosis has already developed in the brain, treatment with thiamin may be useless. The prognosis for recumbent animals is generally poor. Although treatment usually improves the condition of such animals, relapses and permanent damage are probable since irreversible changes will have occurred in the central nervous system.

Without doubt, PEM is the most important thiamin deficiency disease in ruminants. However, it is noteworthy that thiamin can also be used effectively as supportive treatment of the metabolic disorders rumen acidosis and ketosis (Harmeyer and Kollenkirchen, 1989). Even though treatment with thiamin can be therapeutically successful, it does not follow that a deficiency of thiamin contributes to the etiology of these two diseases (Zintzen, 1974).

If treated promptly by parenteral injection of thiamin (2.2 mg per kg (1 mg per lb) of bodyweight, the condition can be reversed (NRC, 2000). Thiamin sources available for addition to feed are the hydrochloride and mononitrate salts. Because of its lower solubility in water, the mononitrate is preferred for addition to premixes. The mononitrate has somewhat better stability characteristics in dry products than the hydrochloride (Bauernfeind, 1969).

Stability of thiamin in premixes should be monitored. More than 50% of the thiamin was destroyed in vitamin-mineral premixes after one month at room temperature (Verbeeck, 1975). When thiamin was stored in premixes without minerals, no losses were encountered when kept at room temperature for six months. Choline in addition to trace minerals accelerates degradation of thiamin in premixes.

In concentrate diets, 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, 90% destruction occurs under the same conditions at pH 7, and 100% destruction in 15 minutes at pH 9. 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 Salmonellaorganisms and increase digestibility and are using steam pelleting, prepelleting conditioners and feed expanders, which lead to increased vitamin degradation (Ward, 2005).


Vitamin Safety

Large oral doses of thiamin are not toxic, and usually the same is true of parenteral administration. Dietary intakes of thiamin up to 1,000 times the requirement are apparently safe for most animal species (NRC, 1987). The effects of excessive intakes of thiamin have not been studied in ruminants (NRC, 1987).