The association between dietary vitamin B1 intake and constipation: a population-based study.

BACKGROUND: Numerous researches have indicated a correlation between the intake of dietary micronutrients and the occurrence of constipation. Nevertheless, the correlation between constipation and vitamin B1 remains uninvestigated. The main aim of this research was to examine the association between chronic constipation and the consumption of vitamin B1 in the diet among adult participants of the National Health and Nutrition Examination Survey (NHANES). METHODS: This study used data from the NHANES, a survey on health and nutrition conducted between 2005 and 2010. The respondents' dietary information was gathered by utilizing the 24-hour dietary records. Various statistical analyses, such as multiple logistic regression, subgroup analysis, and curve-fitting analysis, were employed to investigate the correlation between dietary intake of vitamin B1 and chronic constipation. RESULTS: In the trial, there were 10,371 participants, out of which 1,123 individuals (10.8%) were identified as having chronic constipation. Fully adjusted multiple logistic regression analyses showed that increasing dietary intake of vitamin B1 (OR = 0.87, 95% CI: 0.77-0.99) was significantly associated with a reduced risk of constipation. Following adjustment for multiple variables in Model 3, the odds ratio (OR) and 95% confidence interval (CI) for the third tertile, in comparison to the first tertile (reference group), was 0.80 (0.65, 0.99). In addition, subgroup analyses and interaction tests showed a significant inverse association between vitamin B1 intake and the prevalence of constipation, especially among men, non-hypertensive, and non-diabetic individuals (all P-values less than 0.05). CONCLUSION: This research uncovered an inverse correlation between the consumption of vitamin B1 in the diet and the occurrence of chronic constipation. One potential explanation for this phenomenon is that the consumption of vitamin B1 in one's diet is linked to the softening of stools and an augmented occurrence of colonic peristalsis. Additional extensive prospective research is required to thoroughly examine the significance of thiamine in long-term constipation.

Pre-analytical challenges from adsorptive losses associated with thiamine analysis.

Thiamine (vitamin B1) is an essential vitamin serving in its diphosphate form as a cofactor for enzymes in the citric acid cycle and pentose-phosphate pathways. Its concentration reported in the pM and nM range in environmental and clinical analyses prompted our consideration of the components used in pre-analytical processing, including the selection of filters, filter apparatuses, and sample vials. The seemingly innocuous use of glass fiber filters, glass filter flasks, and glass vials, ubiquitous in laboratory analysis of clinical and environmental samples, led to marked thiamine losses. 19.3 nM thiamine was recovered from a 100 nM standard following storage in glass autosampler vials and only 1 nM of thiamine was obtained in the filtrate of a 100 nM thiamine stock passed through a borosilicate glass fiber filter. We further observed a significant shift towards phosphorylated derivatives of thiamine when an equimolar mixture of thiamine, thiamine monophosphate, and thiamine diphosphate was stored in glass (most notably non-silanized glass, where a reduction of 54% of the thiamine peak area was observed) versus polypropylene autosampler vials. The selective losses of thiamine could lead to errors in interpreting the distribution of phosphorylated species in samples. Further, some loss of phosphorylated thiamine derivatives selectively to amber glass vials was observed relative to other glass vials. Our results suggest the use of polymeric filters (including nylon and cellulose acetate) and storage container materials (including polycarbonate and polypropylene) for thiamine handling. Losses to cellulose nitrate and polyethersulfone filters were far less substantial than to glass fiber filters, but were still notable given the low concentrations expected in samples. Thiamine losses were negated when thiamine was stored diluted in trichloroacetic acid or as thiochrome formed in situ, both of which are common practices, but not ubiquitous, in thiamine sample preparation.

Contribution of Beef to Key Nutrient Intakes and Nutrient Adequacy in Pregnant and Lactating Women: NHANES 2011-2018 Analysis.

Beef is an important source of high-quality protein and several micronutrients, including iron, zinc, and B-vitamins. The objective was to assess the association of beef intake with nutrient intake and adequacy among pregnant and lactating women using 24-h dietary recall data. Usual intakes from foods were determined with the National Cancer Institute (NCI) method and % population below Estimated Average Requirement (EAR) or above Adequate Intake (AI) were estimated. A high proportion of pregnant and lactating women had inadequate intakes for vitamin D (94%), vitamin E (82%), vitamin C (52%), and vitamin A (50%), magnesium (35%), folate (31%), zinc (25%), and vitamin B6 (22%); only 4% and 35% met AI for choline and potassium, respectively. About 67% of pregnant and lactating women were beef consumers, consuming 49 g beef/day. Beef consumers had higher intakes (p < 0.05) of energy, protein, calcium, iron, phosphorus, selenium, sodium, zinc, thiamin, riboflavin, and niacin, and a higher proportion (p < 0.05) met nutrient recommendations for protein, calcium, iron, zinc, thiamin, riboflavin, niacin, vitamin B6, and vitamin B12 compared to non-consumers. In conclusion, pregnant and lactating women generally have inadequate nutrient intakes from their diets. Beef consumers have higher intakes and adequacy for certain nutrients, many of which are inherently available in beef or in foods eaten with beef.

[Distribution of usual vitamin intake and prevalence of inadequate intake among Chinese adults in 2015].

OBJECTIVE: To estimate the usual vitamin intake and the prevalence of inadequate intakes among Chinese adults in 2015, and to provide a scientific basis for developing nutrition intervention strategies and measures for target populations. METHODS: Data was drawn from the Chinese Nutrition and Health Surveillance 2015-2017, a nationally representative cross-sectional study. The multistage stratified whole-group random sampling method was used to draw participants from 298 surveillance sites in 31 provinces(autonomous regions and municipalities). Participants with no available information or abnormal energy intake were excluded, and finally, a total of 72 231 participants aged 18 years and older were included in the current study. The dietary data of the participants were collected by the 24-hour dietary recall method combined with the condiment weighing method for three consecutive days. The National Cancer Institute method was used to estimate the distribution of the usual intake of vitamin B_1(thiamine), vitamin B_2(riboflavin), niacin, vitamin C(ascorbic acid), and vitamin E(tocopherol), and the prevalence of inadequate intake was evaluated based on estimated average requirement or adequate intake from the Chinese Dietary Reference Intakes 2023. RESULTS: The usual intake of vitamin E, vitamin C, vitamin B_1, vitamin B_2 and niacin were 27.93 mg/d, 77.67 mg/d, 0.78 mg/d, 0.62 mg/d and 13.15 mg/d, respectively. The prevalence of inadequate intake was, in descending order, vitamin B_2(95.98%), vitamin B_1(86.73%), vitamin C(63.70%), niacin(39.81%), and vitamin E(21.17%). The prevalence of inadequate vitamin E, vitamin C, vitamin B_1 and niacin intake among females was higher than among males(P<0.01). Overall, the prevalence of inadequate vitamin intake increased with age. Rural residents had a higher prevalence of inadequate intake of vitamin C, vitamin B_2 and niacin than urban residents(P<0.01). Except for vitamin E, the prevalence of inadequate intake of vitamins decreased with increasing education levels. The prevalence of inadequate intake of these five vitamins was higher among participants with lower income levels than those with middle or high income(P<0.01). Participants with normal weight had a higher prevalence of inadequate intake of vitamin E than those with overweight or obesity and had a higher prevalence of inadequate intake of vitamin C than those with obesity. However, participants with normal weight had a higher prevalence of inadequate intake of vitamin E than those with overweight or obesity, with the differences being statistically significant(P<0.01). Except for vitamin E, the prevalence of inadequate intake of vitamins decreased with increasing physical activity intensity. CONCLUSION: In 2015, the usual intake of dietary vitamins of Chinese adults was low. There are differences in usual intakes of vitamins and prevalence of inadequate vitamin intake for adults aged 18 years and above in males and females, different age groups, urban and rural areas, education levels, household income levels, body mass index and physical activity intensity.

Association of dietary intake of B vitamins with glaucoma.

This cross-sectional study investigated the association between glaucoma and B vitamin dietary intake. A total of 5025 enrolled individuals participated in self-reported glaucoma questionnaire and 3264 participated in International Society Geographical and Epidemiological Ophthalmology (ISGEO) criteria. In self-reported glaucoma, the risk of having self-reported glaucoma was lower in the third quartile of vitamin B1 intake (odds ratio [odds ratio [OR] 0.63, 95% confidence interval [CI] 0.40-0.97), and P trend (P trend = 0.004) for vitamin B12 was significant; in males, the third quartile of vitamin B1 intake (OR 0.44, 95% CI 0.24-0.83) and the fourth quartile of vitamin B2 intake (OR 0.39, 95% CI 0.17-0.89) were associated with a lower risk. In glaucoma based on ISGEO criteria, the increase of niacin intake (OR 0.94, 95% CI 0.89-0.99) was negatively associated with the odds of self-reported glaucoma. After sex-stratified analysis, the third quartile of vitamin B6 intake (OR 0.21, 95% CI 0.08-0.60) in males were associated with reduced odds of glaucoma. The restricted cubic spline analysis revealed a nonlinear association of vitamin B2 (p for nonlinearity = 0.04) and B9 (p for nonlinearity = 0.024) intake with glaucoma diagnosed by ISGEO criteria in females.

In Vitro and In Silico Studies on Cytotoxic Properties of Oxythiamine and 2'-Methylthiamine.

It is important to search for cytostatic compounds in order to fight cancer. One of them could be 2'-methylthiamine, which is a thiamine antimetabolite with an additional methyl group at the C-2 carbon of thiazole. So far, the cytostatic potential of 2'-methylthiamine has not been studied. We have come forward with a simplified method of synthesis using commercially available substrates and presented a comparison of its effects, as boosted by oxythiamine, on normal skin fibroblasts and HeLa cancer cells, having adopted in vitro culture techniques. Oxythiamine has been found to inhibit the growth and metabolism of cancer cells significantly better than 2'-methylthiamine (GI50 36 and 107 µM, respectively), while 2'-methylthiamine is more selective for cancer cells than oxythiamine (SI = 180 and 153, respectively). Docking analyses have revealed that 2'-methylthiamine (ΔG -8.2 kcal/mol) demonstrates a better affinity with thiamine pyrophosphokinase than thiamine (ΔG -7.5 kcal/mol ) and oxythiamine (ΔG -7.0 kcal/mol), which includes 2'-methylthiamine as a potential cytostatic. Our results suggest that the limited effect of 2'-methylthiamine on HeLa arises from the related arduous transport as compared to oxythiamine. Given that 2'-methylthiamine may possibly inhibit thiamine pyrophosphokinase, it could once again be considered a potential cytostatic. Thus, research should be carried out in order to find the best way to improve the transport of 2'-methylthiamine into cells, which may trigger its cytostatic properties.

[Influence of chronic immobilization stress on vitamin status in rats fed different diets].

The influence of a stress factor, widespread in modern conditions, on the vitamin status has not been studied enough. At the same time, the negative stress impact can be aggravated against the background of unhealthy nutrition, which in turn affects the vitamin status of the organism. In this regard, the goal of the research was to evaluate the effect of chronic restrict stress on the vitamin supply in rats fed a diet with adequate and increased content of fat, sugar and cholesterol. Material and methods. The experiment was carried out on 37 growing male Wistar rats (initial body weight of 45±5 g) divided into 4 groups. Animals of the 1st (control) and the 2nd groups received a complete semi-synthetic diet (CSSD) (20% protein, 10% fat, 58% carbohydrates in the form of starch, 384 kcal/100 g) for 92 days. The levels of all vitamins and mineral elements in the rats' diets were adequate for growing rats. Rats of the 3rd and the 4th groups were fed a high-calorie, high-fat high-carbohydrate diet (HFHCD) (20% protein, 28% fat, 2% cholesterol, 18% carbohydrates in the form of starch, 20% sucrose, 511 kcal/100 g). Animals of groups 2 and 4 were subjected to daily 90-minute immobilization. The concentration of vitamins A (retinol and retinol palmitate) and E (α-tocopherol) in the blood serum and liver were determined by high-performance liquid chromatography, vitamins B1 and B2 in the liver and urine, as well as riboflavin in the blood serum and 4-pyridoxic acid (4-PA) in urine were determined by fluorimetric methods. Biochemical parameters of blood serum were determined on a biochemical analyzer; the total content of fat, triglycerides (TG) and cholesterol (CH) was determined in the liver. Results. Replacing CSSD with HFHCD, both under restraint stress and without, was accompanied by an increase in liver weight by 1.8-2.0 fold, in its fat content by 2.6-3.3 fold, cholesterol by 32.6-35.3 fold and TG - by 33.0-57.6 fold (p=<0.001). An increase in alanine aminotransferase (ALT) activity by 1.7-2.0 fold (p=<0.01), in low-density lipoprotein (LDL) cholesterol level by 5.4 fold (p=<0.05) and the atherogenic coefficient by 2.5 fold (p<0.01) as well as a decrease in creatinine and urea level (p=<0.05) in blood serum were revealed. Immobilization was accompanied by a decrease in body weight, liver and liver fat in rats fed both CSSD and HFHCD (p<0.05), but didn't affect the blood serum biochemical parameters, with the exception of an increase in ALT activity. If the activity of alkaline phosphatase (ALP) did not change during immobilization of rats fed the CSSD, then in animals fed the high-calorie diet it decreased by 37.5% (p=<0.05 from the control) under its increase against the background of restrict stress by 78.7% (p=<0.01) compared to the indicator of rats of the 3rd group. Immobilization of rats treated with CSSD was accompanied by an increase in both absolute serum α-tocopherol level and concentration correlated with the level of cholesterol and triglycerides by 26.0-57.5% (p<0.05), with a simultaneous decrease in its content in the liver per 1 g of wet tissue by 22.1% (p=0.041) relative to the indicators of intact animals. Immobilization reduced the level of retinol palmitate in the liver by 2.3 times (p<0.01), but did not affect retinol level in the blood serum. At the same time, indicators of B vitamin status (the content of vitamins B1 and B2 in the liver per 1 g of wet tissue and per organ, blood serum riboflavin level, urinary excretion of riboflavin and 4-PA) did not change, with the exception of thiamine urinary excretion, which reduced compared to the control by 38.8%. In rats fed HFHCD, immobilization had no additional effect on the supply with vitamins A and E. The content of vitamins B1 and B2 in the liver in terms of the whole organ was reduced by 14.0-26.7% relative to the indicator in animals of the 3rd group, not subjected to chronic stress, only due to differences in liver weight in animals of these groups. Conclusion. The data obtained indicate that chronic stress has a negative effect on the vitamin status of the body, worsening the supply with vitamins A, E and B1, and substantiate the feasibility of studying the mechanisms of this effect in order to develop effective vitamin complexes for the treatment and prevention of diseases caused by long-term stress.

[Influence of the rat diet enrichment with oat ß-gucans on the assimilation of B group vitamins, mineral elements and lipid metabolism].

Despite the widespread use of oat ß-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. The purpose of the study was to evaluate the effect of including oat bran with a high content of ß-glucans (ß-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of ß-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with ß-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. Results. Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of ß-glucans in the diet. At the same time, against the background of the presence of ß-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with ß-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. Conclusion. The presence of ß-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.

High-dose oral thiamine versus placebo for chronic fatigue in patients with primary biliary cholangitis: A crossover randomized clinical trial.

BACKGROUND & AIMS: Fatigue has high negative impact on many patients with primary biliary cholangitis (PBC) and treatment options are limited. Recently we showed favorable effects of four weeks of high-dose thiamine treatment on fatigue in patients with inflammatory bowel disease. We aimed to investigate the effect and safety of high-dose (600-1800 mg daily) oral thiamine treatment on chronic fatigue in patients with PBC. METHODS: Randomized, double-blinded, placebo-controlled crossover trial including patients with severe PBC-related fatigue. Participants were allocated 1:1 to either group 1) 4 weeks of high-dose thiamine, 4 weeks of washout, and 4 weeks of placebo; or group 2) 4 weeks of placebo, washout, and high-dose thiamine, respectively. Fatigue severity was quantified using the fatigue subscale of the PBC-40 questionnaire. The primary outcome was a fatigue reduction of ≥ 5 points after 4 weeks of high-dose thiamine treatment. RESULTS: We enrolled 36 patients; 34 completed the study. The overall mean reduction in fatigue was 5.0 points (95% CI: 2.5 to 7.5; p < 0.001) for the combined group 1 and group 2. Crossover analysis showed a mean increase in fatigue of 0.3 points (95% CI: -4.2 to 3.8) after high-dose thiamine treatment compared to a 1.4 points (95% CI: 6.2 to -3.4) mean reduction after placebo (p = 0.55). Only mild and transient adverse events were recorded. CONCLUSION: Four weeks of high-dose oral thiamine treatment in patients with PBC was well tolerated and safe. However, high-dose thiamine was not superior to placebo in reducing PBC-related fatigue. TRIAL REGISTRATION: The trial was registered in the ClinicalTrials.gov (NCT04893993) and EudraCT (2020-004935-26).

Altered Mental Status and Cardiac Failure Due to Thiamine Deficiency in an Overweight Teen.

We describe an overweight but otherwise previously healthy 17-year-old female who presented with altered mental status and rapidly progressive weakness. She was ultimately diagnosed with Wernicke encephalopathy and wet beriberi resulting from severe thiamine deficiency. She required admission to the pediatric ICU because of hypoventilation with progressive weakness and worsening encephalopathy and was found to have impaired cardiac function as assessed by echocardiography. Her heart function and encephalopathy improved on initiation of thiamine repletion. She remained in inpatient rehabilitation for 10 months but still remained weak at discharge. Thiamine deficiency is not commonly considered in the United States as a diagnosis other than in patients with severe alcohol use disorder. However, thiamine may be depleted in as little as 2 weeks if nutrition is inadequate. In such a setting, thiamine deficiency is an important etiology to consider early in the pediatric patient with altered mentation especially because it can be readily and safely treated.

Thiamine as a metabolic resuscitator after in-hospital cardiac arrest.

INTRODUCTION: Elevated lactate is associated with mortality after cardiac arrest. Thiamine, a cofactor of pyruvate dehydrogenase, is necessary for aerobic metabolism. In a mouse model of cardiac arrest, thiamine improved pyruvate dehydrogenase activity, survival and neurologic outcome. AIM: To determine if thiamine would decrease lactate and increase oxygen consumption after in-hospital cardiac arrest. METHODS: Randomized, double-blind, placebo-controlled phase II trial. Adult patients with arrest within 12 hours, mechanically ventilated, with lactate ≥ 3 mmol/L were included. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. Thiamine 500 mg or placebo was administered every 12 hours for 3 days. The primary outcome of lactate was checked at baseline, 6, 12, 24, and 48 hours, and compared using a linear mixed model, accounting for repeated measures. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase, and mortality. RESULTS: Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis. There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88) or any secondary outcomes. In those with randomization lactate > 5 mmol/L, mortality was 92% (11/12) with thiamine and 67% (8/12) with placebo (p = 0.32). In those with randomization lactate ≤ 5 mmol/L mortality was 17% (1/6) with thiamine and 67% (4/6) with placebo (p = 0.24). There was a significant interaction between randomization lactate and the effect of thiamine on survival (p = 0.03). CONCLUSIONS: In this single center trial thiamine had no overall effect on lactate after in-hospital cardiac arrest.

Transposon sequencing reveals metabolic pathways essential for Mycobacterium tuberculosis infection.

New drugs are needed to shorten and simplify treatment of tuberculosis caused by Mycobacterium tuberculosis. Metabolic pathways that M. tuberculosis requires for growth or survival during infection represent potential targets for anti-tubercular drug development. Genes and metabolic pathways essential for M. tuberculosis growth in standard laboratory culture conditions have been defined by genome-wide genetic screens. However, whether M. tuberculosis requires these essential genes during infection has not been comprehensively explored because mutant strains cannot be generated using standard methods. Here we show that M. tuberculosis requires the phenylalanine (Phe) and de novo purine and thiamine biosynthetic pathways for mammalian infection. We used a defined collection of M. tuberculosis transposon (Tn) mutants in essential genes, which we generated using a custom nutrient-rich medium, and transposon sequencing (Tn-seq) to identify multiple central metabolic pathways required for fitness in a mouse infection model. We confirmed by individual retesting and complementation that mutations in pheA (Phe biosynthesis) or purF (purine and thiamine biosynthesis) cause death of M. tuberculosis in the absence of nutrient supplementation in vitro and strong attenuation in infected mice. Our findings show that Tn-seq with defined Tn mutant pools can be used to identify M. tuberculosis genes required during mouse lung infection. Our results also demonstrate that M. tuberculosis requires Phe and purine/thiamine biosynthesis for survival in the host, implicating these metabolic pathways as prime targets for the development of new antibiotics to combat tuberculosis.

[Analysis on vitamin B_1 and vitamin B_2 proficiency testing assessment in China disease control and prevention system].

OBJECTIVE: To evaluate the detection ability of vitamin B_1 and vitamin B_(2 )in rice flour in the laboratories of disease control and prevention system, by conducting the proficiency testing(PT)activity. METHODS: Before the vitamin B_1 and vitamin B_2 quality control samples were distributed to the laboratories of disease control and prevention system, the uniformity and stability of samples were analyzed by one-way ANOVO respectively. High performance liquid chromatography(HPLC) method was required to determine vitamin B_1(GB 5009.84-2016: determination of vitamin B_1 in food, first method as reference). HPLC method was also required to determine vitamin B_2(GB 5009.85-2016: determination of vitamin B_2 in food, first method as reference). Robust statistics analysis of proficiency testing result was conducted to evaluate laboratory testing ability through Z score. RESULTS: A total of 43 laboratories completed the proficiency testing. In all of the laboratories participated in the determination of vitamin B_(1 )and vitamin B_2, the total satisfactory rate of vitamin B_1 was 88.4%, while vitamin B_2 was 86.0%. CONCLUSION: The ability of vitamin B_1 and vitamin B_2 detection in disease control and prevention system in China is better than expected, and the testing ability of a few laboratory needs to be improved.

Thiamine as a metabolic resuscitator after out-of-hospital cardiac arrest.

INTRODUCTION: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients. METHODS: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality. RESULTS: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.

The relationship between thiamin, folic acid and cognitive function in a rat model of uremia.

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2'-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Elevated liver enzymes and fasting glucose levels correlate with neuropathy in patients diagnosed with alcohol use disorder independently of the blood thiamine levels.

AIMS: Chronic alcohol consumption is well known to cause peripheral neuropathy, affecting both small and large nerve fibers. The aim of this study was to correlate biochemical and neurophysiological findings and investigate possible biomarkers and risk factors for pathogenetic mechanisms of neuropathy in patients diagnosed with alcohol use disorder (AUD). METHODS: Ninety patients diagnosed with AUD were enrolled in this prospective study over a period of 3 years. Serum biochemical parameters, as well as thiamine blood levels, were determined upon admission. Every subject was assessed by clinical neurological examination, followed by Nerve Conduction Studies, Quantitative Sensory Testing, and Sympathetic Skin Response. Fifty age and gender-matched patients without a diagnosis of AUD were used as the control group. RESULTS: Peripheral neuropathy was diagnosed in 54 patients (60%). Among them, pure large fiber neuropathy was found in 18 patients, pure small fiber neuropathy in 12 patients, and both large and small fiber neuropathy was diagnosed in 24 patients. Elevated liver enzymes and fasting glucose levels upon admission were significantly correlated with neuropathy. Lower blood thiamine levels (than reference) were found in seven patients and were not correlated with neuropathy. CONCLUSIONS: Our study suggests that alcohol-related liver dysfunction and hyperglycemia may contribute as risk factors of peripheral neuropathy in patients diagnosed with AUD, while blood thiamine levels do not correlate with neuropathy. Moreover, we suggest that liver enzymes and the De Ritis ratio could be potentially used as biomarkers for the incidence and severity of alcohol-related neuropathy.