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 by-products should be kept in sealed containers.
Substances with antithiamin 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. Thiaminases are found in high concentrations in raw fish, shellfish, bacteria, yeast and fungi. Cooking destroys thiaminases. 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 vivo experiments 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; Bales, 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 + CO2
alpha-ketoglutaric acid —> succinyl-CoA + CO2
Figure 7-1: Thiamin as Thiamin Pyrophosphate (TPP) in the Metabolism 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 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 of 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 due to endogenous vitamin synthesis by intestinal microflora. Diets containing starch rather than sucrose favor intestinal synthesis, and the practice of coprophagy (dogs) can markedly influence dietary requirements for this vitamin. For dogs and cats, however, 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.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 (Benevenga et al., 1966; McDowell, 2000; Elmadfa et al., 2001). When thiamin is deficient, body reserves become depleted more rapidly when animals are maintained on a feed rich in carbohydrates than when they receive a diet rich in fat and protein. The “thiamin-sparing” effect of fats and protein has long been known. Dogs receiving diets with high fat levels required lower levels of thiamin to meet their thiamin needs than did dogs receiving low-fat diets (Arnold and Elvehjem, 1939). Excess intake of carbohydrate foods such as potatoes, bread and possibly certain grains can increase the thiamin requirement.
Size, genetic factors and metabolic status affect thiamin requirements. Periods of increased metabolism (e.g., fever, elevated muscular activity, pregnancy and lactation) can also increase thiamin requirements (Marks, 1975). Infectious and parasitic diseases 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 food. It has been shown experimentally with poultry that infection with coccidia results in considerable reduction in thiamin blood levels. Thiamin blood levels were found to be directly correlated to infection severity (McManus and Judith, 1972). Likewise, conditions such as diarrhea and malabsorption increase the requirement.
Thiamin requirements are higher if feeds contain raw ingredients (e.g., fish) or additives with anti-thiamin activity. 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). A malady dubbed “spiking syndrome” in broilers results in a high mortality. 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). High dietary intakes of sulfur as well as substances in tall fescue (Festuca arundinacea Schreb.) are antagonistic to thiamin, resulting in higher requirements (Edwin et al., 1968; Lauriault et al., 1990).
According to NRC (2006) the thiamin requirements of puppies are 1.38 mg per kg (0.63 mg per lb) of diet while adult dogs at maintenance, in late gestation and at peak lactation require 2.25 mg per kg (1.02 mg per lb) of diet. Ralston Purina (1987) suggests 40 µg per kg (18.2 µg per lb) of diet for puppies and 10 µg per kg (4.5 µg per lb) for adult dogs. A higher thiamin recommendation is made by the Association of American Feed Control Officials (AAFCO, 2007) of 1.0 mg per kg (0.45 mg per lb) of diet for all classes of dogs.
Cats have a higher requirement for thiamin compared to dogs and other species. According to the NRC (2006) the dietary thiamin requirement for kittens is 5.5 mg per kg (2.50 mg per lb) of diet, for adult cats at maintenance is 5.6 mg per kg (2.55 mg per lb) of diet and for cats in late gestation or peak lactation it is 6.3 mg per kg (2.86 mg per lb) of diet. AAFCO (2007) recommend 5 mg thiamin per kg (2.27 mg per lb) of diet as the minimal requirement for growth, with this recommendation also apparently adequate for gestation and lactation (Corbin, 1995). An additional recommendation would be 5 mg thiamin per kg (2.27 mg per lb) of diet for kittens and 1.5 mg per kg (0.68 mg per lb) of diet for adults (Ralston Purina, 1987).
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. The richest sources are whole grains, yeast and liver (especially pork liver). 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. Whole 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) (Marks, 1975). Wheat germ ranks next to yeast in thiamin concentration. 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 several varieties of sorghum and pigeonpea (40% to 70%) and lower in rice and chickpea (10% to 40%), and 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 (Kau and Robinson, 1973). Moldy feed analyses showed a thiamin content of less than 0.1 mg per kg (0.045 mg per lb), whereas the same feed not contaminated with Fusarium moniliforme had a thiamin content of 5.33 mg per kg (2.2 mg per lb). The antagonistic factor could be destroyed by treatment with steam (Fritzet al., 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).
When comparing thiamin deficiency signs among 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 all mammals, the brain covers its energy requirement chiefly by the degradation of glucose. Therefore, it is dependent on biochemical reactions in which thiamin plays a key role. Because of the body’s limited storage of thiamin, clinical signs of deficiency appear in a shorter time after exposure to a thiamin-deficient diet than for most other vitamins.
Thiamin deficiency may result from inadequate intake of thiamin, attributable to foods with low-thiamin content or processing losses, or high intake of thiamin antagonists. The processing conditions used to prepare commercial pet foods are destructive to thiamin. However, this anticipated loss is overcome by adding synthetic thiamin before processing (Hand et al., 2010).
Numerous reports of thiamin deficiency in cats and, less frequently, dogs exist in the literature. In these, the dietary deficiency was attributed to destruction of thiamin by heat during cooking or processing (Loew et al., 1970; Read et al., 1977; Baggs et al., 1978; Hoffmann-La Roche, 1981) or by thiaminase-containing fish (Smith and Proutt, 1944; Jubb et al., 1956; Houston and Hulland, 1988) or other antagonist such as amprolium and sulfur dioxide (Studdert and Labuc, 1991; McDowell, 2000; Hazlett et al., 2005; Malik and Sibraa, 2005; Singh et al., 2005).
The deficiency expresses itself clinically as anorexia (lack of appetite) and neurological disorders (especially of the postural mechanism), followed ultimately by weakness, heart failure and death. The induction of thiamin deficiency will determine clinical effects. An acute deficiency will produce severe neurological clinical signs and involve the brain, while chronic deficiency will involve changes in the peripheral nerves and myocardium. Because of its water-soluble nature and the body’s limited capacity to store thiamin, clinical signs due to thiamin deficiency may be observed after a relatively short period of ingestion of a thiamin-deficient diet.
Diagnosis of thiamin deficiency in dogs and cats is made based on clinical signs and the dietary history of the animal. 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, sick animals react so promptly to treatment with thiamin (sometimes within hours) that early treatment with thiamin is used for confirming the diagnosis of deficiency.
Biochemical changes associated with thiamin deficiency include reduced blood, urine and tissue thiamin contents, dramatic elevation of blood pyruvate and lactate, and markedly reduced transketolase activity (Bräunlich and Zintzen, 1976). Thiamin concentrations in blood and urine are decreased with a deficiency. Brin (1969) was able to show that blood (particularly the red cell) transketolase activity is a reliable index of the availability of coenzyme thiamin pyrophosphate (TPP), and thus correlated well with the degree of deficiency in animals. Transketolase is an excellent indicator in that it is useful in detecting 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. The in vitro measurement of erythrocyte transketolase stimulation by TPP (Noel et al., 1971; Read, 1979) has been used to diagnose thiamin deficiency in the dog and cat (Baggs et al., 1978; Deady et al., 1981a, b). However, a decrease in the concentration of TPP in the blood of rats has been shown to precede changes in transketolase activity (Warnock et al., 1978) and may be a superior test for both dogs and cats.
Thiamin deficiency in dogs results from animals consuming diets where marginal thiamin concentrations have been destroyed in food processing or thiaminases are sufficiently high in the diet. A group of sled dogs that were fed a diet consisting of frozen, uncooked carp developed clinical signs of thiamin deficiency after a six-month period. The addition of oatmeal, a dry dog food, and 100 mg of thiamin daily to the affected dogs resulted in complete recovery within two months (Houston and Hulland, 1988). Thiamin deficiency was diagnosed in dogs being fed fresh minced meat, which contained sulphur dioxide as a preservative and less than 0.5 mg per kg (0.23 mg per lb) thiamin. Thiamin in the meat and in added dietary ingredients, including a supplementary vitamin mixture, was destroyed by the sulphur dioxide (Studdert and Labu, 1991). Singh et al. (2005) described the thiamin deficiency in two adult dogs and seven-week-old puppies consuming a diet of sulphite preserved meat. The history for the older dog was inappetence, weight loss and vomiting that rapidly progressed to signs of multifocal intracranial disease including mental dullness, paresis and seizures. Magnetic resonance imaging revealed, bilaterally symmetrical hyperintensity of the caudate nucleus and rostral colliculi. The other four dogs also exhibited rapidly progressive multifocal central nervous system signs including ataxia, paresis, decreased muscle tone and seizures. Both of the older dogs made rapid recoveries with thiamin supplementation. Euthanasia and necropsy of a puppy revealed malacia of multiple brainstem nuclei and edema of the cerebral cortex. These findings were consistent with thiamin deficiency.Pathological changes due to thiamin deficiency predominantly involve the nervous system and heart. The pattern of pathological changes depends on the period of induction; acute deficiencies tend to involve the brain and produce severe neurological signs, whereas chronic deficiencies produce pathological changes in the heart and peripheral nerves (Read, 1979).
Read and Harrington (1981) induced clinical signs of thiamin deficiency in young beagles by feeding a diet containing 20 to 30 µg thiamin per kg (9.1 to 13.6 µg per lb) of diet. They reported three phases of disease: an initial phase where dogs appeared healthy but grew suboptimally, lasting 18 ± 8 days; an intermediate stage of variable duration (59 ± 37 days) of anorexia, loss of body weight and coprophagy; and either a short period of neurological illness or sudden death. The terminal period, which in most dogs was abrupt and short (8 ± 6 days), consisted of either a neurological syndrome or sudden, unexpected death. The neurological syndrome was characterized by anorexia, vomiting, central nervous system depression, paraparesis (partial paralysis of lower extremities), sensory ataxia, torticollis (twisting of neck), circling, tonic-clonic convulsions (relaxation alternating with spasms), profound muscular weakness and recumbency (Read and Harrington, 1981; NRC, 2006).
A prominent clinical sign of thiamin deficiency in dogs is anorexia. This progresses after a few days to ataxia with possible vomiting. These signs continue to tonic convulsions and can eventually lead to death of the animal. Dogs sometimes show cardiac hypertrophy (enlargement) with slowing of the heart rate and signs of congestive heart failure including labored breathing and edema. Read (1979) described the cardiac lesion as nonspecific multifocal myocardial necrosis, and suggested primary vascular damage may be involved. Brain lesions include symmetrical necrosis of the gray matter (Read et al., 1977), and histologically the reported peripheral neuropathy is characterized by diffuse bilateral myelin degeneration and axonal disintegration (Voegtlin and Lake, 1919; Street et al., 1941b; Read, 1979; Garosi et al., 2003).
Of all the domestic animals, the cat is most often reported to be clinically thiamin deficient (Illus. 7-2). This might well be expected as domesticated cats often consume fish, with the possibility of thiaminase being present in many cat foods (NRC, 2006). Cats appear to be more susceptible because of their high requirement for this vitamin in the diet and because of the tendency of pet owners to feed cats unconventional diets (Smith and Proutt, 1944; Loew et al., 1970). Most cases have been the result of feeding cats diets that contained a large proportion of raw fish (Smith and Proutt, 1944; Jarrett, 1970). Experimental studies with cats have produced signs of thiamin deficiency within 23 to 40 days of consuming diets composed solely of raw carp or raw salt-water herring (Smith and Proutt, 1944). The subcutaneous administration of thiamin to affected cats resulted in recovery in all cases. Thiamin deficiency in cats (also dogs) has been associated with feeding meat preserved with sulfur dioxide (Studdert and Labuc, 1991; Malik and Sibraa, 2005; Singh et al., 2005).
Illustration 7-2: Thiamin Deficiency, Abnormal Posture
For thiamin-deficient cats, anorexia and sometimes vomiting occur within two weeks of ingestion of a thiamin-deficient diet and are followed by the sudden development of neurological disorders, including abnormal posture (Illus. 7-2), ataxia and seizures, culminating in progressive weakness and death. Affected cats often show ventroflexion of the head when suspended by the rear legs or somersaulting when the cat leaps (Everett, 1944; Jubb et al., 1956). The impaired vestibulolocular reflexes observed include decreased nystagmus (eyeball movement) time and an impaired or slow pupillary light reflex (Negrin et al., 2010). Affected kittens also have dilated pupils. Postural abnormalities are likely to develop and may include a spastic gait and curling up when lifted, or a head tilt. Seizures or abnormal behavior, dilated pupils, stupor or opisthotonos (spasms where head and heels bend backwards) may also be observed (Shell, 1995). Untreated cats that develop extensor rigidity, subside to coma, and can die within 48 hours of the appearance of these terminal signs.
Electrocardiographic changes due to thiamin deficiency have been described (Toman et al., 1945). These included bradycardia, which developed as early as the second week. Tachycardia was less frequent and seen later. Disorders in heart rate regularity and impulse formation responded promptly to thiamin treatment. Cats affected with thiamin deficiency may exhibit spontaneous seizures, which may be accompanied by brief periods of tachycardia followed by severe bradycardia (Toman et al., 1945; NRC, 2006). A number of pathological changes of the central nervous system have been described. In acute cases, bilateral symmetrical hemorrhages of the brain in the periventricular gray matter have been recorded. A one year old intact male African lion fed only beef muscle meat was evaluated for episodes of hypermetric ataxia, generalized weakness and tonic-clonic front limb movements. Clinical signs resolved completely 9 days after instituting oral thiamine (3 mg per kg per day or 1.36 mg per lb per day) and a completely nutritional diet (DiGesualdo et al., 2005).
Depending on the severity of the case, deficiency signs in cats can be alleviated by the administration of thiamin; however, the hemorrhages that occur in the periventricular gray matter of the brain because of thiamin deficiency can permanently affect the animal. It has been found that cats who have recovered from experimentally induced thiamin deficiency have significantly greater difficulty in learning or remembering maze tasks (Ralston Purina, 1987).
The thiamin content of most common feeds should be three to four times greater than requirements for most species (Brent, 1985). However, this would not be true for cats, mink, fox, and other carnivores, which have a higher requirement for the vitamin. Under normal feeding and management conditions, and in the absence of antimetabolites, thiamin deficiency should theoretically not occur in either dogs or cats. Nevertheless, utilization of available thiamin in feedstuffs may be limited and may also be impaired by thiamin antagonists. Under certain conditions a thiamin inadequacy in pet diets may be created. Thiamin is very unstable in heat under neutral and alkaline pH conditions. Test shows that while no destruction occurs in 1% 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. Pet 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 temperatures for all animal feeds in order to control Salmonella organisms and increase digestibility, which leads to increased thiamin degradation (Ward, 2005).
Clinical cases of thiamin deficiency in cats and dogs have been associated with feeding of either canned commercial foods or raw fish. With cats, it should be remembered that cats like fish and that tinned cat foods often contain fish. The quantity of thiaminase may be sufficient to destroy even thiamin added to the food as a supplement (Bräunlich and Zintzen, 1976). Five cases of thiamin deficiency in cats prompted a Canadian group of researchers (Loew et al.,1970) to investigate tinned cat foods bought on the open market. They found that not only fish-based foods, but also foods based on liver, beef and poultry meat contained extremely low concentrations of thiamin and were responsible for the occurrence of the thiamin deficiency signs. Multifocal intracranial disease was reported for cats fed commercially available diets (Marks et al., 2011). The neurological disease was reversible with thiamin administration.
Thiamin is readily destroyed by heat, especially under neutral or alkaline conditions, and extensive losses may occur in canned cat and dog foods during processing and storage (Baggs et al., 1978). Losses of 74% of thiamin have been reported for some canned dog foods due to retorting and storage for 14 days (Hoffmann-La Roche, 1981). Up to 90% of thiamin in natural ingredients may be lost as a result of processing. Therefore, thiamin supplementation is common in pet foods. Since naturally occurring clinical cases of thiamin deficiency in dogs and cats attributed to thermal destruction of thiamin in meat have been reported, intake of thiamin should, therefore, be calculated from analyses of diets taken at the time of consumption.
This destruction of thiamin has important implications in the feeding of cats and dogs, as sulfur dioxide-treated meat can induce a thiamin-deficient state when fed alone or mixed with thiamin-replete commercial pet foods. Although legislation in many countries prohibits the use of sulfur dioxide in human foods, nutritionists and producers should be aware of the health risks that these treated meats pose to cats and dogs (Studdert and Labuc, 1991).
For pet foods, thiamin is a particularly important vitamin from the aspect of dietary formulation because it is progressively destroyed by cooking and various antagonists, particularly thiaminases, which are found in a number of foods, particularly raw fish. Thiaminases are themselves inactivated by heat so the maintenance of an adequate thiamin intake must take all of these various factors into consideration. For commercially prepared dog and cat foods, the normal practice is to supplement with a large enough quantity before processing so that even if particularly serious losses occur, the amount remaining in the finished product will still meet or exceed the dietary recommendations.
Treatment of dogs and cats with thiamin deficiency includes elimination of raw fish or other antagonists from the diet, feeding a well-balanced, commercial pet food, and thiamin therapy. Thiamin should be administered intravenously or subcutaneously at a dose of 75 to 100 mg twice daily until neurological signs subside (Loew et al., 1970; Case et al., 1995). Oral thiamin supplementation should also be administered for several months following the initial clinical episode (Houston and Hulland, 1988). In most affected pets, these clinical signs will decrease within several days. However, if severe neurological damage has occurred, the pet may never make a full recovery. A permanent intolerance of physical exercise and some degree of persistent ataxia occasionally occurs in animals that have recovered from thiamin deficiency (Case et al., 1995).
Most commercial therapeutic diets designed for animals with cardiac disease contain increased levels of water-soluble vitamins to offset potential urinary losses. For example, dogs and cats receiving furosemide have increased urinary loss of water-soluble vitamins. Humans treated with furosemide have developed thiamin deficiency (Freeman et al., 1998).
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 observed in premixes without minerals, no losses were encountered when kept at room temperature for six months. When the minerals were supplied as sulfates, the losses of thiamin were greatly increased. After six months, only 27% of the thiamin hydrochloride activity remained in a vitamin premix that also contained choline and trace minerals (Gadient, 1986).
Thiamin ingested in large amounts orally is not toxic, and usually the same is true of parenteral doses. Dietary intakes of thiamin up to 1,000 times the requirement are apparently safe for most animal species (NRC, 1987). There are no reports of toxicity in cats resulting from excessive oral intakes of thiamin but intravenous thiamin in high doses can cause neuromuscular and cardiovascular damage (Freye and Agoutin, 1978). Lethal intravenous injections of thiamin administered to dogs have been reported to be 50 to 125 mg per kg (22.7 to 56.8 mg per lb) of body weight (Smith et al., 1947; 1948) and 350 mg per kg (159.1 mg per lb) of body weight (Gubler, 1991). Vasodilation, fall in blood pressure, bradycardia, respiratory arrhythmia and depression result when animals are given thiamin in large doses intravenously. In dogs, an oral dose of 100 to 115 µg of thiamin per kg (45.5 to 52.3 µg per lb) body weight per day appeared safe (Noel et al., 1971).
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