Erythrocyte Transketolase Activity Research Articles

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study

BackgroundThere is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency. ObjectivesThis study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine. MethodsHospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework. ResultsThiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 μg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine. ConclusionsAlthough ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.

Race explains substantial variance in whole blood thiamine diphosphate concentrations

Deficiency for thiamine (vitamin B1), traditionally assessed via the activity of the thiamine-dependent enzyme erythrocyte transketolase, has been reported in individuals with alcohol use disorder (AUD) and in people with HIV; concentrations of the metabolically active diphosphate form, however, have yet to be reported in HIV cohorts and results in AUD are equivocal. In this cross-sectional study, samples from 170 AUD, 130 HIV, and 100 healthy control individuals were analyzed to test the hypothesis that AUD and HIV groups relative to healthy controls would show low whole blood thiamine diphosphate (TDP) concentrations related to peripheral neuropathy. TDP concentrations were not different in the 3 study groups (P = .6141) but were lower in Black (n = 172) relative to White (n = 155) individuals (P < .0001) regardless of group. In a multiple regression, race relative to diagnoses explained more than 10 times the variance in whole blood TDP concentrations (F4,395 = 3.5, P = .0086; r2 = 15.1]. Performance on a measure of peripheral neuropathy (2-point discrimination) was worse in the HIV and AUD cohorts relative to the healthy control group (P < .0001) but was not associated with TDP concentrations. These findings suggest that Black individuals carry a heightened vulnerability for low whole blood TDP concentrations, but the clinical significance and mechanisms underlying these results remain to be determined.

Association between diabetes and thiamine status - A systematic review and meta-analysis

BackgroundThiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to individuals with normal glucose metabolism. AimsWe conducted a systematic review and meta-analysis to study whether the circulating concentrations of various thiamine analytes differ between people with and those without diabetes. MethodsPubMed and the Cochrane Central Register of Controlled Trials were searched according to the study protocol. The standardized mean difference (SMD) and 95 % confidence intervals (CI) of thiamine markers between individuals with and without diabetes were used as effect size (random effects model). Subgroup analysis considered albuminuria as an additional variable. ResultsOut of the 459 articles identified, 24 full-texts were eligible for the study, 20 of which qualified for the data analysis and four were evaluated for coherence. Compared to controls, individuals with diabetes showed lower concentrations of thiamine (pooled estimate SMD [95 % CI]: −0.97 [−1.89, −0.06]), thiamine monophosphate (−1.16 [−1.82, −0.50]), and total thiamine compounds (−1.01 [−1.48, −0.54]). Thiamine diphosphate (−0.72 [−1.54, 0.11] and erythrocyte transketolase activity (−0.42 [−0.90, 0.05]) tended to be lower in persons with diabetes than in controls without reaching statistical significance. Subgroup analysis showed that individuals with diabetes and albuminuria had lower thiamine levels than the controls (−2.68 [−5.34, −0.02]). ConclusionsDiabetes is associated with lower levels of various thiamine markers, suggesting that individuals with diabetes may have higher thiamine requirements than those without diabetes, but well-designed studies are required to confirm these findings.

Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status.

Thiamine (vitamin B1) is an essential micronutrient required as a cofactor in many metabolic processes. Clinical symptoms of thiamine deficiency are poorly defined, hence biomarkers of thiamine status are important. The erythrocyte transketolase activity coefficient (ETKac) is a sensitive measure of thiamine status, but its interpretation may be confounded where the availability of the transketolase enzyme is limited. Basal ETK activity per gram of hemoglobin provides a complementary biomarker of thiamine status; however, its measurement and calculation are poorly described. Here, we describe in detail the assessment of basal ETK activity, including the calculation of path length in microplates and the molar absorption coefficient of NADH specific to the assay, and the measurement of hemoglobin in sample hemolysates. To illustrate the application of the methods, we present ETKac and basal ETK activity from women in The Gambia and UK. In conclusion, we present a clear protocol for the measurement of basal ETK activity that will permit the harmonization of methods to improve replication between laboratories.

Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275–675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.

Thiamin and riboflavin status with related enzyme activities in pulmonary tuberculosis with diabetes mellitus in Shandong province of China.

Poor nutritional status is a common finding in pulmonary tuberculosis (TB) patients with and without type 2 diabetes mellitus (T2DM), thiamin (VB-1) and riboflavin (VB-2) are coenzymes important for the activation of many enzymes involved in improving nutritional status. We aimed to investigate enzymatic activities and the associations between VB-1 and VB-2, and their relations to nutritional status in TB and TB+T2DM patients. This was a cross-sectional study that prospectively enrolled TB 40 patients with or without T2DM respectively from the Chest Hospital of Qingdao and 76 healthy controls with similar age and gender distributions were recruited from the medical center of the affiliated hospital of Qingdao Medical College. The erythrocyte transketolase activation coefficient (ETKac, for VB-1 deficiency), the glutathione reductase activation coefficient (EGRac, for VB-2 deficiency), and metabolic enzyme activities were analyzed. VB-1 and VB-2 deficiency rates were higher, and enzyme activities were lower in TB and TB+T2DM relative to control group. ETKac and EGRac were negatively correlated with enzyme activities, either with body mass index (BMI), while enzyme activities were positively associated with BMI. VB-1 and VB-2 concentrations were lower in TB patients with or without T2DM relative to controls, with concomitant reductions in the activity levels of key metabolic enzymes. Significant correlations were observed between VB-1 and VB-2 concentrations and the activity of these metabolic enzymes, they all correlated with nutrition status. VB-1 and VB-2 concentrations may thus impact metabolic enzyme activity and thereby influence nutritional status.

Thiamine deficiency in Gambian women of reproductive age.

Thiamine deficiency disorders are associated with a variety of clinical symptoms affecting the nervous and cardiovascular systems. There is growing recognition that thiamine deficiency can occur in populations well beyond the classical region of South Asia, and at‐risk populations include those who receive a large proportion of their energy from polished white rice (or other low‐thiamine staple foods) and with low dietary diversity. Reports of thiamine deficiency in West Africa over the last century have suggested that this has historically been an issue in this population, but in more recent decades, these reports have been limited to prison populations. To understand if thiamine deficiency might be an unrecognized problem in the communities of this region, erythrocyte samples collected during the wet and dry seasons from 226 women of reproductive age (mean age = 28 years old) were assessed for thiamine status by measuring the erythrocyte transketolase activity coefficient (ETKac). Overall, 35.8% of the sample was at high risk of thiamine deficiency (ETKac ≥ 1.25). Risk of thiamine deficiency was significantly higher in the wet (47.9%) compared with the dry season (22.9%) (P < 0.001). To our knowledge, this is the first report of biochemical thiamine deficiency in a free‐living population in West Africa in the 21st century and suggests that further investigation is warranted.

Thiamine (Vitamin B1) Is Often Misunderstood to Be Consumed by Excessive Carbohydrate Intake

ObjectivesThiamine acts as a coenzyme (prosthetic group) after converting to thiamine pyrophosphate in crucial metabolic enzymes of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. Theoretically, thiamine should not be consumed by an increase in the number of substrates for those enzymes. However, thiamine is often described to be consumed by excessive carbohydrate intake. Such a possible misunderstanding is assessed in the relevant literature. MethodsThe original paper (Elmadfa, et al. Int J Vitam Nutr Res 2001), which seems to mislead the reader into considering an increase in thiamine requirement for excessive carbohydrate intake, and the relevant papers were reviewed. ResultsThe original paper demonstrated that increases in carbohydrate intake from 55% to 65% and 75% of total energy caused decreases in plasma and urine concentrations of thiamine, while erythrocyte transketolase activity remained unchanged. This seems to misleadingly support the idea that excessive carbohydrate intake increases the thiamine requirement for carbohydrate metabolism. It could be interpreted as the decreases of thiamine concentrations were observed only during an adaptation period. It was reported that diabetic patients had low plasma thiamine levels in association with increased renal clearance and fractional excretion of thiamine, without a decrease in erythrocyte transketolase activity (Thornalley, et al. Diabetologia 2007). As a similar case of possible misinterpretation, a case report (Watson, et al. Ir J Med Sci 1981) demonstrated that glucose loading precipitated thiamine deficiency in malnourished patients with latent thiamine deficiency. ConclusionsFrom the relevant literature, it is inferred that excessive carbohydrate intake in people without hyperglycemia could lead to a small increase, if any, in urinary thiamine excretion, but not to an increase in thiamine requirement for glucose metabolism. Even in the academic field, it seems that thiamine is often misunderstood to be consumed by excessive carbohydrate intake. Funding SourcesNone.

Thiamine Status of Supplemented, Lactating Mothers in Rural Cambodia: A Randomized Controlled Trial

ObjectivesThiamine deficiency is a cause of infant morbidity and mortality throughout Southeast and South Asia. Maternal intake influences human milk thiamine concentrations, thus mother’s intake must be improved to combat infant deficiency. However, the dose of supplemental thiamine required by lactating mothers is unknown. We aimed to estimate the maternal oral thiamine dose required to optimize milk thiamine concentrations, and to investigate the impact of various doses on thiamine status biomarkers. MethodsThis was a double-blind, four-parallel arm randomized controlled dose-response trial. At 2 weeks postpartum, healthy mothers were randomized to consume one capsule daily for 22 weeks, containing either 0 mg (placebo, n = 83), 1.2 mg (estimated average requirement, n = 86), 2.4 mg (n = 81), or 10 mg (n = 85) thiamine. Human milk total thiamine, whole blood thiamine diphosphate, and erythrocyte transketolase activity coefficient (ETKac) were assessed. An Emax curve, estimated using a non-linear least squares model, was plotted for human milk. Linear mixed-effects models were used to test for differences between treatment groups for milk and blood biomarkers. ResultsA maternal supplemental dose of 2.35 (95% CI 0.58, 7.01) mg/d was estimated to reach 90% of the maximum average human milk total thiamine concentration of 191 μg/L. The mean (SD) milk thiamine concentration was significantly higher in all intervention groups (183 (91), 190 (105), and 206 (89) μg/L, for 1.2, 2.4, and 10 mg, respectively) compared to placebo (153 (85) μg/L; p < 0.0001), and did not differ from each other. Blood biomarkers followed similar group trends, except for infant ETKac, where only the 10 mg (mean [SD]: 1.18 [0.10]) and placebo (1.12 [0.06]) groups differed significantly (p = 0.003). ConclusionsWhile an estimated maternal dose of 2.35 (0.58, 7.01) mg/d was required to reach a milk thiamine concentration of 191 μg/L in Emax dose analyses, group comparisons suggest a daily dose of 1.2 mg/d is sufficient to improve maternal biomarkers to levels similar to higher doses (2.4 and 10 mg/d) and consistent with thiamine-replete populations. However, a higher maternal dose of 10 mg/d was required to improve infant ETKac status compared to other dose groups. Funding SourcesBill & Melinda Gates Foundation, The New York Academy of Sciences.

The relation between acute changes in the systemic inflammatory response and circulating thiamine and magnesium concentrations after elective knee arthroplasty

Thiamine diphosphate (TDP) and magnesium are co-factors for key enzymes in human intermediary metabolism. However, their role in the systemic inflammatory response (SIR) is not clear. Therefore, the aim of the present study was to examine the relation between acute changes in the SIR and thiamine and magnesium dependent enzyme activity in patients undergoing elective knee arthroplasty (a standard reproducible surgical injury in apparently healthy individuals). Patients (n = 35) who underwent elective total knee arthroplasty had venous blood samples collected pre- and post-operatively for 3 days, for measurement of whole blood TDP, serum and erythrocyte magnesium, erythrocyte transketolase activity (ETKA), lactate dehydrogenase (LDH), glucose and lactate concentrations. Pre-operatively, TDP concentrations, erythrocyte magnesium concentrations, ETKA and plasma glucose were within normal limits for all patients. In contrast, 5 patients (14%) had low serum magnesium concentrations (< 0.75 mmol/L). On post-operative day1, both TDP concentrations (p < 0.001) and basal ETKA (p < 0.05) increased and serum magnesium concentrations decreased (p < 0.001). Erythrocyte magnesium concentrations correlated with serum magnesium concentrations (rs = 0.338, p < 0.05) and remained constant during SIR. Post-operatively 14 patients (40%) had low serum magnesium concentrations. On day1 serum magnesium concentrations were directly associated with LDH (p < 0.05), WCC (p < 0.05) and neutrophils (p < 0.01). Whole blood TDP and basal ETKA increased while serum magnesium concentrations decreased, indicating increased requirement for thiamine and magnesium dependent enzyme activity during SIR. Therefore, thiamine and magnesium represent potentially modifiable therapeutic targets that may modulate the host inflammatory response. Erythrocyte magnesium concentrations are likely to be reliable measures of status, whereas serum magnesium concentrations and whole blood TDP may not.ClinicalTrials.gov: NCT03554668.

An Unusual Case of Thiamine Deficiency in a Total Parenteral Nutrition-Dependent Child Secondary to Munchausen by Proxy

An Unusual Case of Thiamine Deficiency in a Total Parenteral Nutrition-Dependent Child Secondary to Munchausen by Proxy

Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status.

Vitamin B1 (thiamine) is an essential nutrient that acts as a cofactor for a number of metabolic processes, particularly in energy metabolism. Symptoms of classic thiamine deficiency are recognized as beriberi, although clinical symptoms are nonspecific and recognition of subclinical deficiency is difficult. Therefore, reliable biomarkers of thiamine status are required. Thiamine diphosphate is a cofactor for transketolase, including erythrocyte transketolase (ETK). The ETK activity assay as an indirect, functional marker of thiamine status has been used for over 50 years. The ETK activity assay provides a sensitive and specific biomarker of thiamine status; however, there is a lack of consensus over the cutoffs for deficiency, partly due to a lack of assay harmonization. Here, we provide a step‐by‐step protocol for the measurement of ETK activity and the calculation of the ETK activity coefficient, including detailed explanations of equipment and chemicals required and guidance for quality control procedures. Harmonization of the protocol will provide the basis for the development of internationally recognized cutoffs for thiamine insufficiency. The establishment of quality control materials and a quality assurance scheme are recommended to provide reliability. This will ensure that the ETK activity assay remains an important method for the assessment of thiamine status.

Thiamine status and lactate concentration in sepsis: A prospective observational study.

Thiamine is an essential co-factor for aerobic metabolism. Both thiamine deficiency and sepsis may be associated with hyperlactatemia and hypotension. We assessed the relationship between thiamine compounds, lactate concentrations and clinical outcomes in septic patients.We undertook a prospective observational single-center study. Erythrocyte levels of total thiamine, free thiamine, thiamine mono, di and triphosphate (TMP, TDP, and TTP respectively), the erythrocyte transketolase activity (ETKA) and the effect of thiamine diphosphate on ETKA were measured in septic patients by high performance liquid chromatography and correlated with arterial lactate. Vital status at the end of intensive care unit stay was recorded.Overall, 28 patients suffering from sepsis were included. Median (interquartile range [IQR]) age was 60 [44-77.3] years, 15 (53.6%) patients were male, median [IQR] simplified acute physiology score II was 40 [27-50]. There was no correlation between total thiamine and lactate levels (P = .33). There was no correlation between free thiamine (P = .81), TMP (P = .71), TDP (P = .31), TTP (P = .86), and lactate levels in our population. There was no correlation between ETKA (P = .58) or the effect of TDP on ETKA (P = .40) and lactate concentration. Total thiamine and TDP concentration were significantly higher in intensive care unit (ICU) survivors than in nonsurvivors (P = .03 and P = .03). The effect of TDP on ETKA was significantly higher in nonsurvivors compared to survivors (P = .04).We found no correlation between thiamine compounds and lactate concentration in sepsis. Thiamine deficiency in sepsis may be associated with ICU-mortality.

Erythrocyte transketolase deficiency in patients suffering from Crohn's disease.

Aim of the study was to assess the possible vitamin B1 deficiency in relation to the exacerbation of Crohn's disease (CD) in adult patients. Forty-nine Crohn's disease (CD) patients with different disease activity (The Crohn's Disease Activity Index-CDAI) were included in the study. Anthropometrical and biochemical parameters, i.e., high sensitive C-reactive protein, were assessed. The spectrophotometric method was used to measure the transketolase activity (TK) in erythrocytes. The normalized transketolase activity ratio (NTKZ) and the percentage of activation with thiamine pyrophosphate (%TPP) were also evaluated. The mean values of BMI were close to cut-off: 18.5 kg/m2, indicating a poor nutritional status in CD patients. The patients with moderate-to-severe active CD had a statistically significant higher value of CDAI and hsCRP concentrations compared to those being in the asymptomatic remission or at the mildly active stage of the disease. The level of NTKZ and %TPP were statistically different between the analyzed groups, showing the deficit of vitamin B1 in the group of moderate-to-severe active CD patients (Mean ± SD; NTKZ: 1.99 ± 0.87 vs. 1.54 ± 0.62 U/g Hb; % of TPP: 0.15 ± 0.78 vs. 54.90 ± 38.80). Vitamin B1 deficiency is part of the Crohn's disease manifestation in moderate-to-severe active patients.

Prevalence of and factors associated with thiamin deficiency in obese Thai children.

Obesity is a state that results from excessive energy consumption, and obese people often have micronutrient deficiencies. The objective of this study was to investigate the prevalence of and factors associated with thiamin deficiency in obese Thai children. This cross-sectional study was conducted at Faculty of Medicine Siriraj Hospital, Mahidol University during 2014 to 2017. Children aged 7-15 years old with exogenous obesity were recruited. Symptoms and signs of thiamin deficiency were evaluated. Erythrocyte transketolase activity was measured by thiamin pyrophosphate effect (TPPE), with ≥15% indicating thiamin deficiency. Dietary consumption from a 5-day food diary and food frequency questionnaire was calculated by INMUCAL software. Other medical complications of obesity were also evaluated. One hundred and twenty-four subjects (81 males and 43 females) were enrolled, with a mean age of 10.9 years. Fifty-two subjects had abnormal TPPE for an overall prevalence of thiamin deficiency of 42%. Manifestations of thiamin deficiency included numbness, weakness, and calf muscle cramping. TPPE test results were correlated with at least one symptom or a sign of thiamin deficiency (p<0.01). The thiamin-deficient group tended to have higher proportion of morbid obesity and larger waist circumferences than thiamin-sufficient group. The thiamindeficient group tended to consume less thiamin in relation to energy intake than the thiamin-sufficient group (p=0.057). Items of foods consumed were statistically indistinguishable between groups. The results of this study revealed a 42% prevalence of thiamin deficiency among obese Thai children, and most of those cases were subclinical.

The effect of thiamine and/or magnesium supplementation on thiamine, magnesium, lactate and erythrocyte transketolase activity in patients presenting to the emergency department with alcohol withdrawal syndrome

The effect of thiamine and/or magnesium supplementation on thiamine, magnesium, lactate and erythrocyte transketolase activity in patients presenting to the emergency department with alcohol withdrawal syndrome

The relationship between circulating concentrations of thiamine, magnesium, lactate and erythrocyte transketolase activity (ETKA) in patients presenting with alcohol withdrawal syndrome

The relationship between circulating concentrations of thiamine, magnesium, lactate and erythrocyte transketolase activity (ETKA) in patients presenting with alcohol withdrawal syndrome

Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women.

Background: Traditionally, vitamin B1 status is assessed by a functional test measuring erythrocyte transketolase (ETK) activity or direct measurement of erythrocyte thiamine diphosphate (eThDP) concentration. However, such analyses are logistically challenging, and do not allow assessment of vitamin B1 status in plasma/serum samples stored in biobanks. Using a multiplex assay, we evaluated plasma concentrations of thiamine and thiamine monophosphate (TMP), as alternative, convenient measures of vitamin B1 status. Methods: We investigated the relationships between the established biomarker eThDP and plasma concentrations of thiamine and TMP, and compared the response of these thiamine forms to thiamine fortification using samples from 196 healthy Cambodian women (aged 18–45 years.). eThDP was measured by high performance liquid chromatography with fluorescence detection (HPLC-FLD) and plasma thiamine and TMP by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Plasma thiamine and TMP correlated significantly with eThDP at baseline and study-end (p < 0.05). Among the fortification groups, the strongest response was observed for plasma thiamine (increased by 266%), while increases in plasma TMP (60%) and eThDP (53%) were comparable. Conclusions: Plasma thiamine and TMP correlated positively with eThDP, and all thiamine forms responded significantly to thiamine intervention. Measuring plasma concentrations of thiamine forms is advantageous due to convenient sample handling and capacity to develop low volume, high-throughput, multiplex assays.

Treatment of rats with the JAK-2 inhibitor fedratinib does not lead to experimental Wernicke’s encephalopathy

Recent clinical trials suggest that patients with myelofibrosis can develop Wernicke’s encephalopathy (WE) when treated with fedratinib, a specific Janus kinase-2 (JAK-2) inhibitor. To investigate this issue, we have examined (1) if fedratinib can produce or alter the course of this disorder, (2) its effects on thiamine-dependent enzyme activity and thiamine status, and (3) its influence on the uptake of thiamine. Animals administered fedratinib for 28days at a comparable dose used to treat human cases of myelofibrosis showed no evidence of clinical signs of thiamine deficiency (TD). Rats treated with a combination of fedratinib and TD exhibited no neurological differences in their progress to the symptomatic stage when compared to thiamine-deficient animals only. Treatment with the JAK-2 inhibitor did not compromise erythrocyte transketolase activity, and thiamine status was not affected in a major way unlike animals with TD. In addition, treatment of cultured astrocytes with fedratinib did not diminish the uptake of thiamine into these cells. Our findings suggest that treatment with fedratinib does not lead to or alter the progress of TD, and do not support the notion that administration of this JAK-2 inhibitor directly results in the development of WE due to inhibition of thiamine transport. Known adverse effects of fedratinib involving compromised gastrointestinal function may be an important indirect contributing factor to previously reported cases of WE in patients with myelofibrosis.