Showing papers on "Thiamine published in 2011"

Thiamine supplementation in the critically ill.

Abstract: Purpose of reviewTo summarize the properties of thiamine and evaluate current evidence on thiamine status and supplementation, for different populations of critically ill patients.Recent findingsThiamine, in the form of thiamine pyrophosphate, is a critical co-factor in the glyocolysis and oxidative

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

Abstract: Despite the targeting of traditional risk factors for cardiovascular disease, disease burden has not been completely eliminated. Thiamine is an essential cofactor in carbohydrate metabolism and individuals with diabetes are thiamine deficient. The pathophysiology of recognised complications of thiamine deficiency is similar to that underlying atherosclerosis and the metabolic syndrome, namely oxidative stress, inflammation and endothelial dysfunction. This review examines the mechanisms by which thiamine deficiency occurs in individuals with diabetes, how this deficiency leads to hyperglycaemic-induced damage, and the effect of thiamine replacement on vascular disease, endothelial function and oxidative stress. Thiamine administration can prevent the formation of harmful by-products of glucose metabolism, reduce oxidative stress and improve endothelial function. The potential benefit of long-term replacement in those with diabetes is not yet known but may reduce cardiovascular risk and angiopathic complications.

Thiamine (Vitamin B1)

Abstract: Thiamine (vitamin B 1) was the first B vitamin to have been identified. It serves as a cofactor for several enzymes involved in energy metabolism. The thiamine-dependent enzymes are important for the biosynthesis of neurotransmitters and for the production of reducing substances used in oxidant stress defenses, as well as for the synthesis of pentoses used as nucleic acid precursors. Thiamine plays a central role in cerebral metabolism. Its deficiency results in dry beriberi, a peripheral neuropathy, wet beriberi, a cardiomyopathy with edema and lactic acidosis, and Wernicke—Korsakoff syndrome, whose manifestations consist of nystagmus, ophthalmoplegia, and ataxia evolving into confusion, retrograde amnesia, cognitive impairment, and confabulation. Patients on a strict thiamine-deficient diet display a state of severe depletion within 18 days. The most common cause of thiamine deficiency in affluent countries is either alcoholism or malnutrition in nonalcoholic patients. Treatment by thiamine supplementat...

Thiamine Pyrophosphokinase Deficiency in Encephalopathic Children with Defects in the Pyruvate Oxidation Pathway

Abstract: Thiamine pyrophosphate (TPP) is an essential cofactor of the cytosolic transketolase and of three mitochondrial enzymes involved in the oxidative decarboxylation of either pyruvate, α-ketoglutarate or branched chain amino acids. Thiamine is taken up by specific transporters into the cell and converted to the active TPP by thiamine pyrophosphokinase (TPK) in the cytosol from where it can be transported into mitochondria. Here, we report five individuals from three families presenting with variable degrees of ataxia, psychomotor retardation, progressive dystonia, and lactic acidosis. Investigation of the mitochondrial energy metabolism showed reduced oxidation of pyruvate but normal pyruvate dehydrogenase complex activity in the presence of excess TPP. A reduced concentration of TPP was found in the muscle and blood. Mutation analysis of TPK1 uncovered three missense, one splice-site, and one frameshift mutation resulting in decreased TPK protein levels.

Effect of thiamine administration on metabolic profile, cytokines and inflammatory markers in drug-naïve patients with type 2 diabetes

Abstract: To evaluate the effect of thiamine administration on metabolic profile, cytokines and inflammatory markers in drug-naive patients with type 2 diabetes mellitus (T2DM). A randomized, double-blind, placebo-controlled, pilot-scale clinical trial was carried out in 24 patients with T2DM. Twelve subjects received thiamine orally (150 mg), once daily during a fasting state for 1 month. An additional 12 patients (control group) were given placebo for the same period of time. Before and after the intervention, fasting glucose, A1C, creatinine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, very low-density lipoprotein, high-sensitive C-reactive protein, interleukin 6, tumor necrosis factor-alpha, leptin and adiponectin levels were estimated. Wilcoxon’s signed-rank and Mann–Whitney U test were used for statistical analyses. There were significant decreases in glucose (6.7 ± 1.0 mmol/l vs. 6.0 ± 1.0 mmol/l, p = 0.024) before and after the intervention, respectively, and leptin concentrations (32.9 ± 13.3 ng/ml vs. 26.9 ± 12.8 ng/ml, p = 0.027) before and after the intervention, respectively, with thiamine administration. There were no changes with the rest of the measurements. Thiamine administration for 1 month decreased glucose and leptin concentrations in drug-naive patients with T2DM.

Emerging role of thiamine therapy for prevention and treatment of early-stage diabetic nephropathy

Abstract: Thiamine supplementation may prevent and reverse early-stage diabetic nephropathy. This probably occurs by correcting diabetes-linked increased clearance of thiamine, maintaining activity and expression of thiamine pyrophosphate-dependent enzymes that help counter the adverse effects of high glucose concentrations-particularly transketolase. Evidence from experimental and clinical studies suggests that metabolism and clearance of thiamine is disturbed in diabetes leading to tissue-specific thiamine deficiency in the kidney and other sites of development of vascular complications. Thiamine supplementation prevented the development of early-stage nephropathy in diabetic rats and reversed increased urinary albumin excretion in patients with type 2 diabetes and microalbuminuria in two recent clinical trials. The thiamine monophosphate prodrug, Benfotiamine, whilst preventing early-stage development of diabetic nephropathy experimentally, has failed to produce similar clinical effect. The probable explanations for this are discussed. Further definitive trials for prevention of progression of early-stage diabetic nephropathy by thiamine are now required.

Chemical stability study of vitamins thiamine, riboflavin, pyridoxine and ascorbic acid in parenteral nutrition for neonatal use

Abstract: Background The objective of this work was to study the vitamins B1, B2, B6 and C stability in a pediatric formulation containing high amounts of calcium in the presence of organic phosphate, amino acids, glucose, sodium chloride, magnesium sulfate, pediatric vitamins and trace elements under different conditions using developed and validated analytical methods.

Role of thiamine in Alzheimer's disease.

Abstract: Alzheimer's disease (AD) is the most common form of dementia in elderly individuals and is associated with progressive neurodegeneration of the human neocortex. Thiamine levels and the activity of thiamine-dependent enzymes are reduced in the brains and peripheral tissues of patients with AD. Genetic studies have provided the opportunity to determine what proteins link thiamine to AD pathology (ie, transketolase, apolipoprotein E, α-1-antitrypsin, pyruvate dehydrogenase complex, p53, glycogen synthetase kinase-3β, c-Fos gene, the Sp1 promoter gene, and the poly(ADP-ribosyl) polymerase-1 gene). We reviewed the association between histopathogenesis and neurotransmitters to understand the relationship between thiamine and AD pathology. Oral thiamine trials have been shown to improve the cognitive function of patients with AD; however, absorption of thiamine is poor in elderly individuals. In the early stage of thiamine-deficient encephalopathy (Wernicke's encephalopathy), however, parental thiamine has been used successfully. Therefore, further studies are needed to determine the benefits of using parental thiamine as a treatment for AD.

Vitamin B1 (Thiamine): A Cofactor for Enzymes Involved in the Main Metabolic Pathways and an Environmental Stress Protectant

Abstract: Thiamine (vitamin B 1 ) is essential for human metabolism and is particularly important for proper brain functioning. Plants, which are the best source of this vitamin for human nutrition, synthesize thiamine in three stages. The first of these involves the independent formation of thiazole and pyrimidine moieties. In the next phase, these are coupled together to form thiamine monophosphate. The final step results in the formation of the active form of vitamin B 1 , thiamine diphosphate, which functions as a major enzymatic cofactor. The biosynthesis of thiamine is regulated through feedback inhibition by the end product of the pathway, that is, thiamine diphosphate. This regulatory mechanism involves the binding of thiamine diphosphate by mRNA elements, riboswitches (THI-BOXes). The transport of thiamine and thiamine diphosphate between plant tissues and into cell compartments determines the proper functioning of major metabolic pathways such as the acetyl-CoA synthesis, the tricarboxylic acid cycle, the pentose phosphate pathway, Calvin–Benson cycle and isoprenoid biosynthesis pathway. The recently reported activation of thiamine production in plant cells under biotic or abiotic stress conditions also suggests a non-cofactor role of this vitamin as a stress alarmone or stress protectant to enable plants to survive in unfavourable environments.

Water-soluble vitamin levels in extended hours hemodialysis.

Abstract: Patients on extended hours (>15 h/week) hemodialysis may be at a higher risk of deficiency of water-soluble vitamins than conventional (≤15 h/week) hemodialysis patients due to their increased weekly hours of dialysis. We compared serum levels of the water-soluble vitamins in a group of extended and conventional hours hemodialysis patients. Predialysis serum levels of vitamin C, vitamin B12, thiamine, pyridoxine, and folate were measured in 52 patients: 26 extended group and 26 conventional group. Information on patient's intake of vitamin supplements and dialysis regimen was obtained. Data were log transformed due to the skewed distribution of the results. Median vitamin C levels were significantly lower in the extended group (0.30 vs. 1.14 mg/dL, P<0.001), with 7 patients having a level <0.18 mg/dL. Thiamine levels were also lower in the extended group (median 211 vs. 438.5 nmol/L, P=0.0005). However, extended patients had higher levels of pyridoxine (23.2 vs. 11.1 ng/mL, P=0.03). Vitamin B12 and folate levels were not significantly different between the groups. There was significant variability in vitamin supplement prescription in both groups, and dietary data were not obtained. This study showed a high incidence of vitamin C deficiency in extended hours hemodialysis patients, suggesting that supplementation is warranted. It also supports an ongoing role for multivitamin supplementation in conventional hemodialysis patients.

Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy

Abstract: Results of this study indicate dysfunction/deficit of intracellular active form of thiamine in diabetics which serves as a cofactor for transketolase - the key enzyme of pentose phosphate pathway which is considered one of the few potentially counterbalancing pathways opposing hyperglycemia effects. Ascertained functional thiamine deficiency in diabetes, especially when accompanied with advanced renal disease, could be potentially a critical abnormality influencing the activity of pentose phosphate pathway, development if hyperglycemia-mediated damage and diabetic complications and also target of event. pharmacologic interventions.

Thiamine seed treatment enhances LOX expression, promotes growth and induces downy mildew disease resistance in pearl millet

Abstract: Seeds of pearl millet [Pennisetum glaucum (L). R.Br.] susceptible cv. 7042S were treated with thiamine at 5, 10, 15, 20 and 25 mM concentrations and growth promotion and downy mildew resistance were tested. Seed treatment with 20 mM thiamine resulted in 72 and 70 % disease protection under greenhouse and field conditions, respectively, and enhanced vegetative and reproductive growth parameters. Analysis of lipoxygenase (LOX) activity in inoculated pearl millet seedlings at different time intervals indicated that increased LOX activity was initiated at 3 h after inoculation (hai) and maximum activity was observed at 24 hai. Northern analysis showed that LOX mRNA transcript accumulation was higher in the resistant seedlings (cv. IP18292) than in susceptible seedlings. Thiamine seed treatment induces rapid LOX gene expression and results in significant disease protection against downy mildew disease.

Effect of Vitamins on In Vitro Organogenesis of Plant

Abstract: Vitamins are necessary compounds synthesized and utilized in plants. In tissue culture media, vitamin addition is not always common; since the amount needed by plants is relatively unknown and varies. Vitamins, in combination with other media constituents, have been shown to have direct and indirect effects on callus growth, somatic growth, rooting, and embryonic development. For example, different studies have shown that thiamine is associated with cytokinin and has a role in inducing callus growth and rooting. Moreover, thiamine was essential in facilitating the production of more secondary metabolites such as proteases in pineapple. Both biotin and riboflavin play a role in callus development as well. Specifically, riboflavin exerts different effects on plant rooting either positively and negatively. Vitamin D known to cause uptake of calcium in animal tissue, exerts a similar effect in plants. In addition, vitamin D causes cell elongation and meristematic cell division. Vitamin C, known for its anti-oxidative properties, has also enhanced shoot growth and rooting.

Beyond alcoholism: Wernicke-Korsakoff syndrome in patients with psychiatric disorders.

Abstract: Wernicke encephalopathy (WE), a life-threatening disorder caused by thiamine (vitamin B1) depletion, has historically been associated with a classic triad of acute neurological symptoms: confusion, ataxia, and ophthalmoplegia. Thiamine deficiency disease can affect primarily the central and peripheral nervous systems (dry beriberi) or the cardiovascular system (wet beriberi). When thiamine deficiency affects the nervous system, ocular findings such as ophthalmoplegia and nystagmus have been described as a hallmark of the disorder, affecting about 85% of patients.1 However, only 15% to 30% of patients present with the complete WE triad,1,2 and almost 20% of patients who develop persistent confabulatory amnesia, referred to as Korsakoff syndrome, demonstrate none of the 3 findings.1 Therefore, it can be challenging to base the diagnosis solely on physical signs. Korsakoff syndrome, also called Korsakoff dementia, Korsakoff psychosis, or amnesic-confabulatory syndrome, is a life-altering, permanent neuropsychiatric condition characterized by anterograde and retrograde amnesia as well as frontal lobe dysfunction and affective disturbance.3 Korsakoff syndrome can follow an acute episode of WE, and may appear as an agitated delirium or delirium tremens. Korsakoff syndrome may affect up to 85% of patients who have suffered WE, and can result in persistent impairments ranging from mild memory deficit to stupor and coma.4,5 Confabulation and apathy are the classically reported sequelae of WE or Korsakoff syndrome. At least 60% of patients who survive WE also have residual physical impairments such as nystagmus and ataxia.6,7 A great majority of patients with acute WE and/or chronic Korsakoff syndrome (the combined disorder is termed Wernicke-Korsakoff syndrome [WKS]) are never recognized. Only 1% to 20% of cases are diagnosed clinically.5,8,9 Up to 80% are found on postmortem examination of the brain. Similarly, heart failure caused by beriberi may never be recognized, nor may thiamine deficiency’s multisystem effects. WKS most often affects people who have a nutritional deficiency related to alcoholism. However, the syndrome can result from an inadequate supply of thiamine from reduced food intake or poor nutrition of any cause.1 For example, recent attention has been given to WKS in patients who have undergone gastric bypass surgery for obesity.10,11 WKS can affect patients with immunodeficiency syndromes,8 malignancies,12 hyperemesis gravidarum, 13 liver disease,9 or hyperthyroidism.14 Similarly, WKS has been described in patients who have received prolonged parenteral nutrition12 and in patients suffering with severe anorexia nervosa.15–18 In 1 study, 30% of patients hospitalized for anorexia nervosa were found to have thiamine deficiency on admission.19 Thiamine deficiency has been found in people who subsist primarily on white polished rice.20,21 Susceptibility to WKS may also be related to a hereditary deficiency of transketolase, an enzyme involved in thiamine metabolism.22,23 WKS is even more under-recognized among malnourished patients who have psychiatric disorders, but do not abuse alcohol or suffer from anorexia nervosa. Table 1 reviews previously reported non-alcohol–induced WKS arising primarily as a consequence of psychiatric illness. TABLE 1 Prior Reports of Wernicke-Korsakoff Syndrome (WKS) in Patients With Psychiatric Conditions This report describes magnetic resonance imaging (MRI)-confirmed acute WE and clinically confirmed persistent Korsakoff syndrome in 2 patients with preexisting psychiatric disorders. Because the patients were unwilling or unable to give accurate histories, we also obtained information from family members and medical records.

Severe lactic acidosis reversed by thiamine within 24 hours.

Abstract: We report a patient with profound metabolic acidosis that resolved rapidly after thiamine infusion. Thiamine deficiency is common in malnourished patients and is afflicted with high morbidity and mortality if untreated. Intensivists should have an increased awareness of this condition and a low threshold to infuse thiamine in patients at risk, especially before intravenous nutrition with a high percentage of glucose is initiated.

Increasing Thiamine Concentrations in Lake Trout Eggs from Lakes Huron and Michigan Coincide with Low Alewife Abundance

Abstract: Lake trout Salvelinus namaycush in the Laurentian Great Lakes suffer from thiamine deficiency as a result of adult lake trout consuming prey containing thiaminase, a thiamine-degrading enzyme. Sufficiently low egg thiamine concentrations result in direct mortality of or sublethal effects on newly hatched lake trout fry. To determine the prevalence and severity of low thiamine in lake trout eggs, we monitored thiamine concentrations in lake trout eggs from 15 sites in Lakes Huron and Michigan from 2001 to 2009. Lake trout egg thiamine concentrations at most sites in both lakes were initially low and increased over time at 11 of 15 sites, and the proportion of females with egg thiamine concentrations lower than the recommended management objective of 4 nmol/g decreased over time at eight sites. Egg thiamine concentrations at five of six sites in Lakes Huron and Michigan were significantly inversely related to site-specific estimates of mean abundance of alewives Alosa pseudoharengus, and successful...

The prion protein binds thiamine.

Abstract: Although highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of ~60 μM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates that the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were used to determine thiamine's interaction site, which is located between helix 1 and the preceding loop. These data, in conjunction with computer-aided docking and molecular dynamics, were used to model the thiamine-binding pharmacophore and a comparison with other thiamine binding proteins was performed to reveal the common features of interaction.

The Riboswitch Regulates a Thiamine Pyrophosphate ABC Transporter of the Oral Spirochete Treponema denticola

Abstract: Thiamine pyrophosphate (TPP), a biologically active form of thiamine (vitamin B₁), is an essential cofactor in all living systems. Microorganisms either synthesize TPP via de novo biosynthesis pathways or uptake exogenous thiamine from the environment via specific transporters. The oral spirochete Treponema denticola is an important pathogen that is associated with human periodontal diseases. It lacks a de novo TPP biosynthesis pathway and needs exogenous TPP for growth, suggesting that it may obtain exogenous TPP via a thiamine transporter. In this study, we identified a gene cluster that encodes a TPP ABC transporter which consists of a TPP-binding protein (TDE0143), a transmembrane permease (TDE0144), and a cytosolic ATPase (TDE0145). Transcriptional and translational analyses showed that the genes encoding these three proteins are cotranscribed and form an operon (tbpABC(Td)) that is initiated by a σ⁷⁰-like promoter. The expression level of this operon is negatively regulated by exogenous TPP and is mediated by a TPP-sensing riboswitch (Td(thi-)(box)). Genetic and biochemical studies revealed that the TDE0143 deletion mutant (T. denticola ΔtbpA) had a decreased ability to transport exogenous TPP, and the mutant failed to grow when exogenous TPP was insufficient. These results taken together indicate that the tbpABC(Td) operon encodes an ABC transporter that is required for the uptake of exogenous TPP and that the expression of this operon is regulated by a TPP-binding riboswitch via a feedback inhibition mechanism.

Determination of thiamine (vitamin B1) in pharmaceutical tablets and human urine by titania-based ligand-exchange hydrophilic interaction chromatography

Abstract: A new method for the determination of thiamine (vitamin B1) using high performance liquid chromatography (HPLC) on a titania-based column with UV detection has been developed. The influence of acetonitrile (MeCN) percentage in mobile phase, phosphate buffer concentration and buffer pH on the retention of thiamine were investigated. Thiamine retention on titania was ascribed to the cooperation of hydrophilic interaction and ligand-exchange. By altering the buffer concentration, the retention of thiamine on titania was easily adjusted. Isolation of thiamine in pharmaceutical tablets and human urine was achieved within 10 min. Neither complex pretreatment procedures during the sample preparation nor ion-pair reagents in the eluent were needed to retain thiamine. Hydrophobic or non-titania-affinitive interferences were weakly retained, while both the hydrophilic and titania-affinitive thiamine obtained moderate retention (retention factor k = 1.2). The method presented good linearity (R2 = 0.9997) toward thiamine in the range of 0.25–125 μg mL−1. The limit of detection (3σ) for thiamine was 75 ng mL−1. The precision (RSD) for 11 replicate detections of 5 μg mL−1thiamine was 2.3%. The recovery of spiked thiamine in vitamin B1 tablets, compound vitamin B tablets and human urine ranged from 96 to 114%. The proposed titania-based HPLC method was employed to monitor the time-dependent concentration of thiamine in human urine from a healthy volunteer after oral medication of vitamin B1 tablets. This finding is not only a supplement to the detecting methods for thiamine, but also adds new merits to titania-based stationary phase.

Does early treatment prevent deafness in thiamine-responsive megaloblastic anaemia syndrome?

Abstract: Thiamine-responsive megaloblastic anaemia (TRMA; OMIM 249270) syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anaemia, and sensorineural deafness. Progressive hearing loss is one of the cardinal findings of the syndrome and is known to be irreversible. Whether the deafness in TRMA syndrome can be prevented is not yet known. Here, we report a four-month-old female infant diagnosed with TRMA syndrome at an early age. There was no hearing loss at the time of diagnosis. The patient's initial auditory evoked brainstem response measurements were normal. Although she was given thiamine supplementation regularly following the diagnosis, the patient developed moderate sensorineural hearing loss at 20 months of age, indicating that early diagnosis and treatment with oral thiamine (100 mg/day) could not prevent deafness in TRMA syndrome. It would be premature to draw general conclusions from one case, but we believe that further patient-based observations can shed light on the pathophysiology of this rare syndrome as well as prediction of its prognosis.

Thiamine and its derivatives in the regulation of cell metabolism

Abstract: For over 70 years thiamine (vitamin B1) has aroused the interest of biologists, biochemists and medical doctors because of its multilateral participation in key biochemical and physiological processes. The thiamine molecule is composed of pyrimidine and thiazole rings which are linked by a methylene bridge. It is synthesized by microorganisms, fungi and plants, whereas animals and humans have to obtain it from food. There are several known forms of vitamin B1 inside cells: free thiamine, three phosphate esters (mono-, di-, and triphosphate), and the recently found adenosine thiamine triphosphate. Thiamine has a dual, coenzymatic and non-coenzymatic role. First of all, it is a precursor of thiamin diphosphate, which is a coenzyme for over 20 characterized enzymes which are involved in cell bioenergetic processes leading to the synthesis of ATP. Moreover, these enzymes take part in the biosynthesis of pentose (required for the synthesis of nucleotides), amino acids and other organic compounds of cell metabolism. On the other hand, recent discoveries show the non-coenzymatic role of thiamine derivatives in the process of regulation of gene expression (riboswitches in microorganisms and plants), the stress response, and perhaps so far unknown signal transduction pathways associated with adverse environmental conditions, or transduction of nerve signals with participation of thiamine triphosphate and adenosine thiamine triphosphate. From the clinical point of view thiamine deficiency is related to beri-beri, Parkinson disease, Alzheimer disease, Wernicke-Korsakoff syndrome and other pathologies of the nervous system, and it is successfully applied in medical practice. On the other hand, identifying new synthetic analogues of thiamine which could be used as cytostatics, herbicides or agents preventing deficiency of vitamin B1 is currently the major goal of the research. In this paper we present the current state of knowledge of thiamine and its derivatives, indicating the participation of these compounds in the regulation of cell metabolism at both the coenzymatic and non-coenzymatic level.

Adenosine Thiamine Triphosphate (AThTP) Inhibits Poly(ADP-Ribose) Polymerase-1 (PARP-1) Activity

Abstract: Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus. Deficiency of cellular nicotinamide adenine dinucleotide (NAD+) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions. Adenosine thiamine triphosphate (AThTP) exists in small amounts in mammals; however, the function(s) of this metabolite remains unresolved. The structure of AThTP resembles NAD+. Recent experimental studies demonstrate beneficial impacts of high-dose thiamine treatment of diabetic complications. These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1. We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity. AThTP inhibited the PARP-1 activity at 10 μM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site. The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.