Tissue Thiamine Research Articles

The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse.

The Thiamine Transporter 2 (THTR2) encoded by SLC19A3 plays an ill-defined role in the maintenance of tissue thiamine, thiamine monophosphate, and thiamine diphosphate (TDP) levels. To evaluate the impact of THTR2 on tissue thiamine status and metabolism, we expressed the human SLC19A3 transgene in the intestine of total body Slc19a3 knockout (KO) mice. Male and female wildtype (WT) and transgenic (TG) mice were fed either 17 mg/kg (1×) or 85 mg/kg (5×) thiamine hydrochloride diet, while KOs were only fed the 5× diet. Thiamine vitamers in plasma, red blood cells, duodenum, brain, liver, kidney, heart, and adipose tissue were measured. Untargeted metabolomics were performed on the brain tissues of groups with equivalent plasma thiamine. KO mice had ~two- and ~three-fold lower plasma and brain thiamine levels than WT on the 5× diet. Circulating vitamers were sensitive to diet and equivalent in TG and WT mice. However, TG had 60% lower thiamine but normal brain TDP levels regardless of diet, with subtle differences in the heart and liver. The loss of THTR2 reduced levels of nucleic acid and amino acid derivatives in the brain. Therefore, mutation or inhibition of THTR2 may alter the brain metabolome and reduce the thiamine reservoir for TDP biosynthesis.

Effects of a low-thiamine diet on reproductive traits in three populations of Atlantic salmon targeted for reintroduction into Lake Ontario

Exotic prey fishes that have high thiaminase levels are associated with a thiamine deficiency and reduced fitness in many salmonids. If sensitivity to low thiamine availability differs among the three Atlantic salmon (Salmo salar) populations targeted for reintroduction into Lake Ontario, this could substantially influence their performance. We quantified the effects of a low-thiamine diet and a control diet on tissue thiamine concentrations, survival, growth rate, and reproductive traits (sperm and egg quality) in Atlantic salmon from the three candidate source populations. Fish that consumed the low-thiamine diet had comparable growth rates but lower survival and lower muscle thiamine concentrations (26 nmol·g–1) than control fish (34 nmol·g–1). Sperm count, velocity, motility, and longevity did not differ based on diet. Embryo survival was lower for females fed the low-thiamine diet, and the low-thiamine diet was associated with significantly lower egg thiamine concentrations (11 versus 17 nmol·g–1). The effects of the low-thiamine diet did not differ among the tested populations, which suggests that source population selection is unlikely to fully overcome this potential challenge for re-establishing wild populations.

Thiamine requirement of Chinese soft‐shelled turtle,Pelodiscus sinensis(Wiegmann)

The objective of the present study was to estimate the dietary thiamine (vitamin B1) requirement of juvenile soft-shelled turtles, Pelodiscus sinensis. Eight experimental diets containing 0, 1.90, 3.63, 5.65, 7.51, 9.62, 11.37 and 13.64 mg thiamine/kg diet were fed to 160 soft-shelled turtles reared individually for 10 weeks. The turtles had an average weight of 5.33 ± 0.21 g. Among all the dietary groups, weight gain, feed utilization and tissue thiamine were the lowest in the turtles fed with a thiamine-free diet. The variables increased when dietary thiamine increased and then levelled off beyond 3.63 mg/kg diet. In contrast, plasma pyruvate and lactate concentrations in turtles decreased when dietary thiamine increased and then levelled off beyond 3.63 and 5.65 mg/kg diet respectively. Estimation using a broken-line regression model, the vitamin B1 requirement of soft-shelled turtles was 3.2 mg thiamine/kg diet based on weight gain and plasma lactate concentration. When tissue thiamine and plasma pyruvate concentrations were used as the indicators, the estimated requirement was 5.4–6.5 mg/kg diet.

Suspected thiamine deficiency presenting as peripheral neuropathy among peripartum women in a hospital in rural Assam: A neglected public health problem

Context: A single case of thiamine deficiency seen in a population reflects a public health problem which is preventable and easily treatable. Aim: This article describes suspected thiamine deficiency among peripartum women in a rural population in Assam presenting as clinically overt peripheral polyneuropathy. Materials and Methods: A retrospective review of the clinical presentation and electrodiagnostic features of peripartum women presenting with peripheral polyneuropathy during a 6-month period, showing improvement in clinical symptoms after administration of thiamine. Results: The clinical profile of 24 peripartum women described is consistent with features of thiamine deficiency presenting with peripheral polyneuropathy and/or cardiopathy. Of the patients followed up after thiamine supplementation, 90% (18) reported either improvement of neurological deficits or improvement in nerve conduction studies after an average of 10 days. Predominant use of polished rice, thiamine poor diet and habitual use of tea, betel nut, and fermented fish are observed to have precipitated the disease. Limitations of the study include the lack of biochemical measurement of tissue thiamine stores in patients. Conclusions: The observations made among peripartum women in this population assumes public health importance as thiamine deficiency is a preventable and easily treatable illness. There is an urgent need to initiate prospective studies including population surveys to conclusively prove the existence of clinically overt thiamine deficiency in this rural population and its likely causes so that effective public health strategies can be formulated to prevent the morbidity associated with this clinical entity.

Effects of feeding high dietary thiaminase to sub-adult Atlantic salmon from three populations

Abstract Salmonids consuming high thiaminase-containing prey fishes can develop debilitating thiamine deficiencies. Historically, salmonids within the Laurentian Great Lakes consumed low thiaminase-containing prey fishes. Currently, however, salmonids are consuming introduced high thiaminase-containing prey fishes, which may be an impediment to the persistence of native species. Here, we examined the effects of feeding high thiaminase on sub-adult (two-year-old) Atlantic salmon ( Salmo salar ) from three populations (LaHave, Sebago, and Saint-Jean) that are being used for reintroduction into Lake Ontario. The thiaminase diet, mimicking the current high thiaminase concentrations of prey fishes, was produced by mixing natural bacterial thiaminase into prepared feed. After 6 months of feeding fish the thiaminase diet, we found significant drops in thiamine in red blood cells, white muscle, and liver tissues in all three populations as compared to fish fed a control diet. Additionally for liver tissue, we found a higher reduction in thiamine for the LaHave population relative to the Sebago and Saint-Jean populations. Although the salmon fed the thiaminase diet had no change in survival or growth after 8 months, the salmon had lower swimming performance than fish fed a control diet. There were also trends for lower body condition, a less streamlined body shape, and less yellow body pigmentation when fed the thiaminase diet. The changes in these latter traits may indicate the onset of a thiamine deficiency and could negatively impact Atlantic salmon survival in the lake.

Neurohistopathological findings of the effects of amprolium on the brain and spinal cord changes in the a animal model: An experimental study

The aim of the study was to evaluate the polioencephalomalacia induced with amprolium in goats: pathologic changes of the central nervous system. Eight apparently healthy goats of 6 to 9 weeks of age were drenched with amprolium (200 mg/kg body weight) till the development of clinical signs. Three goats of the same age group were drenched with tap water only and these served as controls. Amprolium drenched goats were allowed to die after the onset of clinical signs and control goats were euthanised after the death of amprolium fed goats. At the time of development of typical clinical signs of cerebrocortical necrosis (CCN) the goats were killed and necropsied and a complete histopathologic examination was performed. At necropsy of the four goats, large necrotic lesion was found in the cerebral cortex, and tissue thiamine levels decreased significantly, especially in cerebrum and cerebellum. However, the brain as a whole in all experimental animals, exhibited moderate to severe congestion, oedema and numerous small yellowish foci of varying sizes scattered on the surface of the cerebral hemispheres.Microscopic changes in the brain were limited to gray matter structures of cerebral and cerebellar cortex, caudal colliculi of mid brain, thalamus, cerebellum and spinal cord. There was shrinkage of neurons, perivascular and pericellular edema, necrosis of neurons, satellitosis, glial nodule, gliosis, middle laminar necrosis and deep laminar edema. Blood vessel walls were thickened due to hypertrophy and hyperplasia of endothelial and adventitial cells. Swollen and prominent capillary epithelium, satellitosis, presence of ghost cells, gliosis and perivascular cuffing were also observed but only in some of the animals. In the cerebellar cortex, there was degeneration of Purkinje cells. The caudal colliculi of mid brain showed bilateral malacia. To the best of our knowledge, these researchers questioned the hypothesis that the amprolium could be the major factor causing polioencephalomalacia. This is the first documentation of Amprolium-Induced cerebrocortical necrosis on goat in Iran.

Neurohistopathological Findings of the Effects of Amprolium on the Brain and Spinal Cord Changes in the a Animal Model

The aim of the study was to evaluate the polioencephalomalacia induced with amprolium in goats: pathologic changes of the central nervous system. Eight apparently healthy goats of 6 to 9 weeks of age were drenched with amprolium (200 mg/kg body weight) till the development of clinical signs. Three goats of the same age group were drenched with tap water only and these served as controls. Amprolium drenched goats were allowed to die after the onset of clinical signs and control goats were euthanised after the death of amprolium fed goats. At the time of development of typical clinical signs of Cerebrocortical Necrosis (CCN) the goats were killed and necropsied and a complete histopathologic examination was performed. At necropsy of the four goats, large necrotic lesion was found in the cerebral cortex, and tissue thiamine levels decreased significantly, especially in cerebrum and cerebellum. However, the brain as a whole in all experimental animals, exhibited moderate to severe congestion, oedema and numerous small yellowish foci of varying sizes scattered on the surface of the cerebral hemispheres. Microscopic changes in the brain were limited to gray matter structures of cerebral and cerebellar cortex, caudal colliculi of mid brain, thalamus, cerebellum and spinal cord. There was shrinkage of neurons, perivascular and pericellular edema, necrosis of neurons, satellitosis, glial nodule, gliosis, middle laminar necrosis and deep laminar edema. Blood vessel walls were thickened due to hypertrophy and hyperplasia of endothelial and adventitial cells. Swollen and prominent capillary epithelium, satellitosis, presence of ghost cells, gliosis and perivascular cuffing were also observed but only in some of the animals. In the cerebellar cortex, there was degeneration of Purkinje cells. The caudal colliculi of mid brain showed bilateral malacia. To the best of our knowledge, these researchers questioned the hypothesis that the amprolium could be the major factor causing polioencephalomalacia. This is the first documentation of Amprolium-Induced cerebrocortical necrosis on goat in Iran.

Impact of Thiamine Deficiency on T‐cell Dependent and T‐cell Independent Antibody Production in Lake Trout

Lake trout Salvelinus namaycush on thiamine-replete and thiamine-depleted diets were evaluated for the effects of thiamine status on in vivo responses to the T-dependent antigen trinitophenol (TNP)-keyhole limpet hemocyanin (TNP-KLH), the T-independent antigen trinitrophenol-lipolysaccaharide (TNP-LPS), or Dulbecco's phosphate-buffered saline (DPBS; negative control fish). Plasma antibody concentrations were evaluated for possible differences in total anti-TNP activity as well as differences in response kinetics. Associations between anti-TNP activity and muscle and liver thiamine concentrations as well as ratios of muscle-to-liver thiamine to anti-TNP activity were also examined. Thiamine-depleted lake trout that were injected with TNP-LPS exhibited significantly more anti-TNP activity than thiamine-replete fish. The depleted fish injected with TNP-LPS also exhibited significantly different response kinetics relative to thiamine-replete lake trout. No differences in activity or kinetics were observed between the thiamine-replete and -depleted fish injected with TNP-KLH or in the DPBS negative controls. Anti-TNP activity in thiamine-depleted lake trout injected with TNP-KLH was positively associated with muscle thiamine pyrophosphate (thiamine diphosphate; TPP) concentration. A negative association was observed between the ratio of muscle-to-liver TPP and T-independent responses. No significant associations between anti-TNP activity and tissue thiamine concentration were observed in the thiamine-replete fish. We demonstrated that thiamine deficiency leads to alterations in both T-dependent and T-independent immune responses in lake trout.

Proposed link between paralytic syndrome and thiamine deficiency in Swedish gulls not substantiated

Although Balk et al. (1) demonstrated decreased levels of thiamine in Swedish birds, the claim that thiamine deficiency causes the idiopathic neurologic syndrome seen is not substantiated by the evidence that these authors provide. The authors rely heavily on behavioral abnormalities in sick birds to corroborate their argument. However, many of the clinical signs described are shared by other diseases, including botulism and neurotropic viral infections. Postmortem examination and thorough diagnostic testing (apparently not done) are essential to rule out such etiologies. Furthermore, the authors present no evidence for lower tissue thiamine levels in paralyzed gulls compared with those not showing signs, an expected outcome in thiamine deficiency (2).

Severe thiamine deficiency complicated by weight loss protects against renal ischaemia-reperfusion injury in rats.

Injury due to reperfusion after prior ischaemia (IRI) is an important cause of delayed graft function after renal transplantation [1]. Studies in dogs and rats suggest that thiamine is protective against IRI in heart and brain [2–4]. It has been argued that many organs, including kidneys are deficient in thiamine at the moment of transplantation [4]. We aimed to investigate the effect of severe tissue thiamine deficiency on ischaemia-reperfusion injury in rat kidneys.

Metabolic and structural role of thiamine in nervous tissues.

In the literature, previous descriptions of the role of thiamine (B1 vitamin) focused mostly on its biochemical functions as a coenzyme precursor of some key enzymes of the carbohydrate metabolism. This report reviews recent developments on the metabolic and structural role of thiamine, e.g., the coenzyme and noncoenzyme functions of the vitamin. Taking into account analysis of our experimental data relating to the effects of thiamine deficiency on developing central nervous system (CNS) and data available in literature, we seek to establish a clear difference between the metabolic and structural role of thiamine. Our experimental data indicate that the specific and nonspecific effects express two diametrically diverse functions of thiamine in development: the nonspecific effects show up the metabolic consequences of thiamine deficiency resulting in apoptosis and severe cellular deficit; inversely, the specific effects announced the structural consequences of thiamine deficiency, described as cellular membrane damage, irregular and ectopic cells. The review highlights the existence of noncoenzyme functions of this vitamin through its interactions with biological membranes.

PATHOLOGY, PHYSIOLOGIC PARAMETERS, TISSUE CONTAMINANTS, AND TISSUE THIAMINE IN MORBID AND HEALTHY CENTRAL FLORIDA ADULT AMERICAN ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS)

An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B(1)) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities.

Tissue thiamine deficiency as potential cause of delayed graft function after kidney transplantation: Thiamine supplementation of kidney donors may improve transplantation outcome

Delayed graft function is an important medical problem after renal transplantation. It occurs in approximately 30% of cases, and is not only associated with more prolonged and complicated hospitalisation, but also with earlier graft loss on the long-term. Delayed graft function is the consequence of acute tubular necrosis caused by ischaemia-reperfusion injury, with insufficiently opposed toxic effects of reactive oxygen species and insufficient ATP regeneration. An optimal tissue thiamine status is pivotal for scavenging of reactive oxygen species and regeneration of ATP. There are several reasons to suppose that tissue thiamine availability is suboptimal in donor kidneys prior to reperfusion in transplantation. These reasons include a high prevalence of untreated thiamine deficiency at admission of donors to intensive care units, quick exhaustion of body thiamine stores during periods of non-feeding or inappropriate feeding during hospital stays of donors, and loss of the water-soluble vitamin into water-based organ preservation solutions. We therefore hypothesize that a suboptimal tissue thiamine status is a cause of delayed graft function after renal transplantation, and that it can be prevented with thiamine supplementation.

The Effect of Thiamine Injection on Upstream Migration, Survival, and Thiamine Status of Putative Thiamine‐Deficient Coho Salmon

AbstractA diet containing a high proportion of alewives Alosa pseudoharengus results in a thiamine deficiency that has been associated with high larval salmonid mortality, known as early mortality syndrome (EMS), but relatively little is known about the effects of the deficiency on adults. Using thiamine injection (50 mg thiamine/kg body weight) of ascending adult female coho salmon Oncorhynchus kisutch on the Platte River, Michigan, we investigated the effects of thiamine supplementation on migration, adult survival, and thiamine status. The thiamine concentrations of eggs, muscle (red and white), spleen, kidney (head and trunk), and liver and the transketolase activity of the liver, head kidney, and trunk kidney of fish injected with thiamine dissolved in physiological saline (PST) or physiological saline only (PS) were compared with those of uninjected fish. The injection did not affect the number of fish making the 15‐km upstream migration to a collection weir but did affect survival once fish reached the upstream weir, where survival of PST‐injected fish was almost twice that of controls. The egg and liver thiamine concentrations in PS fish sampled after their upstream migration were significantly lower than those of uninjected fish collected at the downstream weir, but the white muscle thiamine concentration did not differ between the two groups. At the upper weir, thiamine levels in the liver, spleen, head kidney, and trunk kidney of PS fish were indistinguishable from those of uninjected fish (called “wigglers”) suffering from a severe deficiency and exhibiting reduced equilibrium, a stage that precedes total loss of equilibrium and death. For PST fish collected at the upstream weir, total thiamine levels in all tissues were significantly elevated over those of PS fish. Based on the limited number of tissues examined, thiamine status was indicated better by tissue thiamine concentration than by transketolase activity. The adult injection method we used appears to be a more effective means of increasing egg thiamine levels than immersion of eggs in a thiamine solution.

Cell Biology of the Human Thiamine Transporter-1 (hTHTR1): INTRACELLULAR TRAFFICKING AND MEMBRANE TARGETING MECHANISMS

The human thiamine transporter hTHTR1 is involved in the cellular accumulation of thiamine (vitamin B1) in many tissues. Thiamine deficiency disorders, such as thiamine-responsive megaloblastic anemia (TRMA), which is associated with specific mutations within hTHTR1, likely impairs the functionality and/or intracellular targeting of hTHTR1. Unfortunately, nothing is known about the mechanisms that control the intracellular trafficking or membrane targeting of hTHTR1. To identify molecular determinants involved in hTHTR1 targeting, we generated a series of hTHTR1 truncations fused with the green fluorescent protein and imaged the targeting and trafficking dynamics of each construct in living duodenal epithelial cells. Whereas the full-length fusion protein was functionally expressed at the plasma membrane, analysis of the truncated mutants demonstrated an essential role for both NH(2)-terminal sequence and the integrity of the backbone polypeptide for cell surface expression. Most notably, truncation of hTHTR1 within a region where several TRMA truncations are clustered resulted in intracellular retention of the mutant protein. Finally, confocal imaging of the dynamics of intracellular hTHTR1 vesicles revealed a critical role for microtubules, but not microfilaments, in hTHTR1 trafficking. Taken together, these results correlate hTHTR1 structure with cellular expression profile and reveal a critical dependence on hTHTR1 backbone integrity and microtubule-based trafficking processes for functional expression of hTHTR1.

Thiamin requirement of juvenile abalone, Haliotis discus hannai Ino

Juvenile abalone, Haliotis discus hannai Ino, of initial weight 0.55±0.02 g, were fed with experimental diets with graded levels of thiamin–HCl (0, 9.8, 18.9, 37.2, 75.9, 150.4 and 309.5 mg/kg diet) for 16 weeks. Thiamin–HCl and other water-soluble vitamins were microencapsulated with sodium alginate by an emulsion coacervation process prior to supplementation. To estimate the thiamin requirement of abalone and to evaluate the thiamin status in this animal, weight gain (WG), daily increment in shell length (DISL), tissue thiamin, thiamin pyrophosphate (TPP), thiamin monophosphate (TMP), transketolase (TKA) and thiamin pyrophosphate effect (TPP-effect) both in viscera and muscle were measured. Except for TMP, all parameters mentioned above responded significantly to the change of dietary thiamin levels in a broken line model. However, growth (WG and DISL), TPP concentrations and TPP-effect both in viscera and muscle were found to be the most sensitive indicators. Based on broken line analyses, the thiamin requirement to satisfy maximum growth was estimated to be 51 mg/kg diet, and the dietary thiamin levels to maximize visceral TPP content and TPP-effect of H. discus hannai were estimated to be 61 and 58 mg/kg diet, respectively.

Effect of Dietary Amprolium on Tissue Thiamin and Cayuga Syndrome in Atlantic Salmon

Broodfish of Atlantic salmon Salmo salar were fed either thiamin-deficient diets fortified with 0.05% and 0.1% amprolium chloride (Amp, a thiamin antagonist) or thiamin-sufficient diets (0% Amp and ASD2-30, a U.S. Fish and Wildlife Service open-formula feed) for 6 months before spawning. We observed Cayuga syndrome (CS) only in the fry produced from broodfish fed the amprolium diets. The percent fry mortality due to CS was less than 1% in the 0.05% Amp group and was more than 3% in the 0.1% Amp group. Free thiamin was the predominant form of thiamin in the eggs of all broodfish; concentrations were two orders of magnitude greater than that of thiamin pyrophosphate (TPP) and thiamin monophosphate (TMP). Free thiamin was greatest in eggs of broodfish fed the thiamin-sufficient diets. Total thiamin and TMP in red blood cells (RBCs) of broodfish fed the thiamin-deficient diets were reduced to the initial levels by the end of the study. Levels of free thiamin in RBCs were similar in all treatment groups at spawning, as were levels of TPP. Amprolium feeding significantly reduced total thiamin levels in heart, liver, and muscle but not in kidney. Except for thiamin found in eggs, TPP was the predominant form of thiamin in all the other tissues, whereas free thiamin was the least predominant. The data support the hypothesis that thiamin deficiency may cause Cayuga syndrome in Atlantic salmon sac fry. The low incidence of the syndrome in this study may be due to the short duration of the feeding trial or to the low levels of amprolium added to the diets.

Thiamine in excitable tissues: reflections on a non-cofactor role.

Thiamine in excitable tissues: reflections on a non-cofactor role.

Nutritional and metabolic characterization of a thiamine-deficient rat model.

The effects of a thiamine-deficient diet on plasma and tissue vitamin concentrations and on whole-body glucose metabolism were assessed. Male Sprague-Dawley rats (175 to 200 g body weight) fed a thiamine-deficient (TD) or nutritionally complete purified diet were used for plasma thiamine mononitrate and monophosphate and for red blood cell and tissue thiamine pyrophosphate (TPP) determinations weekly for up to 5 weeks. Additional rats were used for assessment of basal glucose kinetics by using a primed constant infusion of [3-3H]glucose. Plasma thiamine mononitrate levels decreased 60% at 1 week and were undetectable after 5 weeks on the diet. Plasma thiamine monophosphate decreased 80% after 1 week on the TD diet, and levels were undetectable after 4 weeks on the diet. Red blood cell TPP in the TD group decreased progressively with time: 54% at 1 week, 86% at 3 weeks, and 92% at 5 weeks. At 1 and 4 weeks, the decrease in tissue TPP was significant in the liver (65% and 89%, respectively), gut (52% and 94%, respectively), spleen (40% and 60%, respectively), and skeletal muscle (37% and 76%, respectively), with the brain (7% and 84%, respectively) showing the slowest initial rate of depletion. The TD diet did not alter plasma glucose concentrations, but it increased plasma lactate by 75% and plasma pyruvate by 50% to 75%. Rates of hepatic glucose production and peripheral glucose utilization were not different between the control and TD rats at 2 weeks, but they were 25% higher in the TD rats after 6 weeks on the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of an Oral Drug Formulation for Dichloroacetate and Thiamine

Dichloroacetate (DCA) is an investigational drug for the treatment of several metabolic and cardiovascular disorders. Hitherto, it has been used mostly in intravenous, short term treatment regimens. Chronic administration of the drug may be toxic, due in part to the depletion of tissue thiamine stores. We therefore developed a stable liquid preparation of the sodium salt of DCA and thiamine HCl suitable for chronic oral administration. The DCA-thiamine mixture is formulated as a palatable solution containing glycerol, sodium benzoate and aspartame in phosphate buffer at pH 3.5. A thermally accelerated decomposition study of the oral DCA formulation revealed a shelf-life of about 5 years at 4°C and about 156 days at 25°C. The stability was also followed for 1 year at its storage condition of 4°C and it was found to be stable at least for 1 year, which is its current recommended storage time. A new high performance liquid chromatographic method was developed to quantitate DCA, thiamine, aspartame and sodium...