Vitamin B1 Deficiency Identified from Incidental Detection of Hyperlactatemia: A Case Report.

Introduction: Vitamin B1 deficiency poses a significant risk of impaired consciousness, with manifestations ranging from anorexia and fatigue to severe neurological and cardiovascular disturbances. Wernicke's encephalopathy, a neurological disorder stemming from vitamin B1 deficiency, presents as the triad of ophthalmoplegia, altered mental state, and cerebellar ataxia. However, these symptoms are not consistently present, complicating the diagnosis. In addition, subclinical vitamin B1 deficiency can progress unnoticed until severe complications arise. Studies indicate a high rate of undiagnosed cases, emphasizing the need for early detection and intervention. Case presentation: We present the case of a 65-year-old man in whom hyperlactatemia was incidentally detected, leading to the diagnosis of vitamin B1 deficiency. The patient, presenting with vertigo and vomiting, had been eating boxed lunches bought from convenience stores following the death of his wife 3 years earlier. Vertigo gradually improved with rest, but the persistence of hyperlactatemia prompted further investigation, revealing low vitamin B1 levels and high pyruvate levels. Treatment with dietary adjustments and supplements significantly improved his symptoms. Discussion: In this case, hyperlactatemia was found in a vertigo patient, revealing asymptomatic vitamin B1 deficiency. Elevated lactate is often linked with conditions like sepsis but can also stem from overlooked factors such as low vitamin B1 levels due to poor diet habits like consuming fried foods. Conclusion: This case highlights the importance of considering vitamin B1 deficiency in patients with unexplained hyperlactatemia, even in high-income countries. Early detection can prevent progression to the severe complications associated with Wernicke's encephalopathy. Proactive measurement of lactate levels in at-risk populations may facilitate early diagnosis and intervention, ultimately improving patient outcomes.

Whole blood thiamine, intravenous thiamine supplementation and delirium occurrence in the intensive care unit: retrospective cohort analyses.

BACKGROUND: Thiamine di-phosphate is an essential cofactor in glucose metabolism, glutamate transformation and acetylcholinesterase activity, pathways associated with delirium occurrence. We hypothesised that a deficiency in whole blood thiamine and intravenous thiamine supplementation could impact delirium occurrence. AIM: To establish whether a deficiency in whole blood thiamine and/or intravenous thiamine supplementation within 72 h of intensive care admission is associated with delirium occurrence. METHOD: The first dataset was secondary analysis of a previous study in an intensive care unit in the Netherlands, reported in 2017. The second dataset contained consecutive intensive care admissions 2 years before (period 1: October 2014 to October 2016) and after (period 2: April 2017 to April 2019) routine thiamine supplementation was introduced within 72 h of admission. Delirium was defined as a positive Confusion Assessment Method-Intensive Care Unit score(s) in 24 h. RESULTS: Analysis of the first dataset (n = 57) using logistic regression showed no relationship between delirium and sepsis or whole blood thiamine, but a significant association with age (p = 0.014). In the second dataset (n = 3074), 15.1% received IV thiamine in period 1 and 62.6% during period 2. Hierarchical regression analysis reported reduction in delirium occurrence in the second period; this did not reach statistical significance, OR = 0.81 (95% CI 0.652-1.002); p = 0.052. CONCLUSION: No relationship was detected between whole blood thiamine and delirium occurrence on admission, at 24 and 48 h. It remains unclear whether routine intravenous thiamine supplementation during intensive care admission impacts delirium occurrence. Further prospective randomised clinical trials are needed.

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.

Association between thiamine decrease and neuropsychiatric symptoms in gastrointestinal and hematological cancer patients receiving chemotherapy.

BACKGROUND: Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy. METHOD: We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy. RESULTS: Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p < 0.001, odds ratio = 0.040, 95% confidence interval [CI]: 0.010-0.163). The Mann-Whitney U test showed that patients with neuropsychiatric symptoms had significantly lower serum thiamine levels (19.5 ± 5.4 ng/mL, n = 39) than patients without neuropsychiatric symptoms (31.9 ± 14.2 ng/mL, n = 48) (p = 0.001). In hematological cancer patients, serum thiamine levels gradually declined after chemotherapy, with the lowest levels at 5-8 weeks (23.5 ± 7.6 ng/mL, P = 0.035 vs. 0 weeks, Wilcoxon rank sum test). CONCLUSION: Our study showed that a decrease in serum thiamine levels can be a risk factor for neuropsychiatric symptoms, and chemotherapy can lead to a decrease in serum thiamine levels.

The Effects of Genetic Mutations and Drugs on the Activity of the Thiamine Transporter, SLC19A2.

A rare cause of megaloblastic anemia (MA) is thiamine-responsive megaloblastic anemia (TRMA), a genetic disorder caused by mutations in SLC19A2 (encoding THTR1), a thiamine transporter. The study objectives were to (1) functionally characterize selected TRMA-associated SLC19A2 variants and (2) determine whether current prescription drugs associated with drug-induced MA (DIMA) may act via inhibition of SLC19A2. Functional characterization of selected SLC19A2 variants was performed by confocal microscopy and isotopic uptake studies of [3H]-thiamine in HEK293 cells. Sixty-three drugs associated with DIMA were screened for SLC19A2 inhibition in isotopic uptake studies. Three previously uncharacterized SLC19A2 variants identified in TRMA patients exhibited disrupted localization to the plasma membrane along with near-complete loss-of-function. Ten of 63 drugs inhibited SLC19A2-mediated thiamine transport ≥ 50% at screening concentrations; however, with the exception of erythromycin, none was predicted to inhibit SLC19A2 at clinically relevant unbound plasma concentrations. Data from electronic health records revealed reduced levels of thiamine pyrophosphate (TPP) in patients prescribed erythromycin, consistent with inhibition of SLC19A2-mediated thiamine transport. Here, we confirmed the role of three SLC19A2 variants in TRMA pathology. Additionally, we report that inhibition of SLC19A2 is a potential, but uncommon mechanism for DIMA.

Relapse of rare diseases during COVID-19 pandemic: bicytopenia in an adult patient with thiamine-responsive megaloblastic anaemia.

Thiamine-responsive megaloblastic anaemia (TRMA) is a syndrome associated with megaloblastic anaemia, diabetes mellitus and sensorineural deafness, due to mutations in the SLC19A2gene, which codes for a thiamine carrier protein. Oral thiamine supplementation is the main treatment. We report the case of a 19-year-old man known for TRMA, who presented in the emergency department with bicytopenia (haemoglobin 5,4 g/dL, thrombocytes 38×109/L) revealed by dyspnea and chest pain. Investigations excluded bleeding, hemolysis, coagulopathy and iron deficiencies. A recent infection and an acute coronary syndrome have also been eliminated. We later found out that thiamine treatment had been discontinued three months before, due to general confinement in Tunisia during the COVID-19 pandemic. Parenteral administration of 100 mg of thiamine daily resulted in the recovery of haematopoiesis within three weeks.

The Relevance of Thiamine Evaluation in a Practical Setting.

Thiamine is a crucial cofactor involved in the maintenance of carbohydrate metabolism and participates in multiple cellular metabolic processes. Although thiamine can be obtained from various food sources, some common food groups are deficient in thiamine, and it can be denatured by high temperature and pH. Additionally, different drugs can alter thiamine metabolism. In addition, the half-life of thiamine in the body is between 1 and 3 weeks. All these factors could provide an explanation for the relatively short period needed to develop thiamine deficiency and observe the consequent clinical symptoms. Thiamine deficiency could lead to neurological and cardiological problems. These clinical conditions could be severe or even fatal. Marginal deficiency too may promote weaker symptoms that might be overlooked. Patients undergoing upper gastrointestinal or pancreatic surgery could have or develop thiamine deficiency for many different reasons. To achieve the best outcome for these patients, we strongly recommend the execution of both an adequate preoperative nutritional assessment, which includes thiamine evaluation, and a close nutritional follow up to avoid a nutrient deficit in the postoperative period.

Social vulnerability: The connection between psychiatric disorders and thiamine deficiency in pregnant women.

The evaluation of thiamine and its derivative phosphate esters levels in pregnant women in rural communities can contribute not only for understanding the specific characteristics of this population regarding nutritional aspects, but also for clarifying the relations of psychiatric manifestations and a vitamin deficit. In the present work we assessed sociodemographic variables, psychiatric parameters and thiamine and its derivative in the whole blood of women in a rural, low-income community in Brazil. A case-control study was done. 94 women were divided in groups using the trimesters of pregnancy as a criterion: each trimester, 1st, 2nd and 3rd had 17, 37 and 38 women, respectively. A control group of non-pregnant women (n-39) was also included. Symptoms of anxiety and depression were assessed using the HAMA Scale and Beck Inventory, respectively. The thiamine and its phosphorylated derivatives concentrations were determined in whole blood samples using the HPLC method. The results suggest that physiological mechanisms linked to the metabolic pathways of thiamine may play a role in some neurobiological substrate involved in the regulation of emotional state. Thus, social vulnerability is identified as an important factor to be considered in the evaluation of the mental health of pregnant women living in rural communities.

Pathophysiology, prevention, and treatment of beriberi after gastric surgery.

Beriberi is a nutritional complication of gastric surgery, caused by deficiency of vitamin B1, or thiamine. Thiamine deficiency leads to impaired glucose metabolism, decreased delivery of oxygen by red blood cells, cardiac dysfunction, failure of neurotransmission, and neuronal death. This review describes the history and pathophysiology of beriberi as well as the relationship between beriberi and nutritional deficiencies after gastric surgery. A literature review of the history and pathophysiology of beriberi and the risk factors for thiamine deficiency, particularly after gastric resection or bariatric surgery, was performed. Recommendations for nutritional follow-up post gastric surgery are based on current national guidelines. Patients may have subclinical thiamine deficiency after upper gastrointestinal surgery, and thus beriberi may be precipitated by acute illness such as sepsis or poor dietary intake. This may occur very soon or many years after gastrectomy or bariatric surgery, even in apparently well-nourished patients. Prompt recognition and administration of supplemental thiamine can decrease morbidity and mortality in patients with beriberi. Dietary education post surgery and long-term follow-up to determine nutritional status, including vitamin and mineral assessment, is recommended for patients who undergo gastric surgery.

Thiamine deficiency and oxidative stress induced by prolonged metronidazole therapy can explain its side effects of neurotoxicity and infertility in experimental animals: Effect of grapefruit co-therapy.

We aimed to explore the possible neurotoxicity and infertility mechanisms of prolonged metronidazole (MTZ) use and the effects of antioxidant grapefruit (GP) co-therapy on MTZ-induced complications. Sixty male albino Wistar rats were divided into four groups (n = 15 each). Group I (control group) received 1% dimethyl sulfoxide (27 ml/ kg/day), group II (MTZ group) received MTZ (400 mg/kg/day), group III (MTZ + GP) received MTZ (400 mg/kg/ day) plus GP juice (27 ml/kg/ day) and group IV (GP group) received GP juice (27 ml/kg) for 60 days. Semen analyses were performed. Free testosterone, gonadotrophin (follicle-stimulating hormone (FSH) and luteinizing hormone) and thiamine levels were measured. Samples of cerebellar, testicular and epididymal tissues were used for both colorimetric assays of oxidative stress markers and histopathological examinations. Significant decreases in the sperm count, percent total sperm motility, serum thiamine levels, free testosterone levels and FSH levels were observed in the MTZ and MTZ + GP groups (p < 0.05 for all parameters). Significantly higher oxidative stress levels (p < 0.05) were observed in the cerebellar and testicular tissue homogenates of these groups than in those of the control group, and associated disruptions in the cerebellar, testicular and epididymal structures were apparent compared to those of the control group. Although the GP group showed a significantly higher sperm count and significantly lower oxidative stress than the control group (p < 0.05), with histological similarity to the control group, the GP group exhibited significantly higher prolactin levels and lower free testosterone and FSH levels than the control group (p < 0.05). Oxidative stress and decreased thiamine levels could explain the MTZ-induced neurotoxicity and infertility side effects that aggravated by GP co-administration.

Subclinical thiamine deficiency identified by preoperative evaluation in an ovarian cancer patient: Diagnosis and the need for preoperative thiamine measurement.

OBJECTIVE: Although thiamine deficiency (TD) and Wernicke encephalopathy (WE) are not rare in cancer patients, the cases reported to date developed TD and/or WE after treatment had started. METHOD: From a series of cancer patients, we report a patient diagnosed with TD without the typical clinical symptoms of WE at the preoperative psychiatric examination. RESULT: A 43-year-old woman with ovarian cancer was referred by her oncologist to the psycho-oncology outpatient clinic for preoperative psychiatric evaluation. Her tumor had been growing rapidly before the referral. Although she did not develop delirium, cerebellar signs, or eye symptoms, we suspected she might have developed TD because of her 2-month loss of appetite as the storage capacity of thiamine in the body is approximately 18 days. The diagnosis of TD was supported by abnormally low serum thiamine levels. SIGNIFICANCE OF RESULTS: Cancer therapists need to be aware that thiamine deficiency may occur even before the start of cancer treatment. In cases with a loss of appetite of more than 2 weeks' duration, in particular, thiamine deficiency should be considered if the tumor is rapidly increasing, regardless of the presence or absence of delirium.

Prevalence of thiamine deficiency in older hospitalized patients.

PURPOSE: Despite some reports of high prevalence of thiamine deficiency in elderly people, the reported prevalence is controversial mainly due to the methods used in assessing thiamin concentrations. In this study, we sought to investigate the prevalence of vitamin B1 deficiency, using the high-performance liquid chromatography (HPLC) method, among older hospitalized patients. PATIENTS AND METHODS: This cross-sectional study retrospectively analyzed the results of routine measurements of vitamin B1 of 238 older patients who were consecutively hospitalized to a geriatric acute care ward. Whole blood vitamin B1 concentrations were measured using the HPLC method at hospital admission, and the whole blood vitamin B1 level of <20 ng/mL was considered as deficiency. RESULTS: Of 238 patients, with a mean age of 82.1±7.1 years, 63% of patients were women. In total, the mean whole blood vitamin B1 level was 66.1±24.8 ng/mL (range 29.5-215 ng/mL), indicating no vitamin B1 deficiency in the entire population. In addition, no significant differences in the mean whole blood vitamin B1 concentrations between sexes were observed (P=0.356). CONCLUSION: This study indicates that the mean whole blood vitamin B1 concentrations using the HPLC method were within the normal range in older hospitalized patients suggesting that thiamine deficiency appears to be rather uncommon among these patients.

Thiamine status in end-stage chronic kidney disease patients: a single-center study.

BACKGROUND: Reportedly, thiamine deficiency, resulting from malnutrition and long-term diuretic therapy, is observed in patients with chronic kidney disease (CKD). The risk of thiamine deficiency might be enhanced, especially in end-stage CKD patients. Here, we assessed thiamine status in incident dialysis patients. METHODS: This study was a single-center cross-sectional study which included 288 consecutive patients initiated into dialysis between April 2013 and March 2017 at our hospital. Thiamine status was evaluated by high-performance liquid chromatography of whole blood samples. We evaluated the association between blood thiamine concentration and other clinical parameters. RESULTS: Of the 288 patients, 21 patients receiving thiamine supplementation at the time of dialysis initiation and 26 patients without blood thiamine measurements were excluded. In 30 patients (12.4%), blood thiamine concentration was lower than the lower limit of normal (21.3 ng/mL; dotted line). Blood thiamine concentration correlated with age, body mass index, and Barthel index (BI) score (p = 0.008, 0.012 and 0.009, respectively). Stepwise multivariate regression analysis indicated that BI scores were independent risk factors for thiamine deficiency (ß coefficients = 0.169, p = 0.013). CONCLUSIONS: The proportion of end-stage CKD patients with low blood thiamine concentration is high. Low physical function (low BI score) is an independent risk factor of thiamine deficiency. Clinicians should be aware of thiamine deficiency in end-stage CKD patients, especially those with low physical function.

Stabilization of the hypoxia-inducible transcription Factor-1 alpha (HIF-1α) in thiamine deficiency is mediated by pyruvate accumulation.

Vitamin B1, or thiamine is a critical enzyme cofactor required for metabolic function and energy production. Thiamine deficiency (TD) is common in various diseases, and results in severe neurological complications due to diminished mitochondrial function, oxidative stress, excitotoxicity and inflammation. These pathological sequelae result in apoptotic cell death in both neurons and astrocytes in distinct regions, in particular the thalamus and mammillary bodies. Comparable histological injuries in patients with hypoxia/ischemia (H/I) have also been described, suggesting a congruency between the cellular responses to these stresses. Analogous to H/I, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α) even without changes in physiological oxygen levels. However, the mechanism of HIF-1α stabilization in TD is currently unknown. Using a pyruvate assay, we have demonstrated that TD induces pyruvate accumulation in mouse primary astrocytes which correlates to an increase in HIF-1α expression. Additionally, we utilized an enzymatic assay for pyruvate dehydrogenase to demonstrate a reduction in catalytic activity during TD due to lack of available thiamine pyrophosphate cofactor, resulting in the observed pyruvate accumulation. Finally, a pyruvate kinase inhibitor which limited pyruvate accumulation was utilized to demonstrate the role of pyruvate accumulation in HIF-1α stabilization during TD. These results reveal that stabilization of HIF-1α protein in TD centralizes on pyruvate accumulation in mouse primary astrocytes due to metabolic disruption of PDH.

Re-emergence of thiamine deficiency disease in the Pacific islands (2014-15): A case-control study.

BACKGROUND: From late 2014 multiple atolls in Kiribati reported an unusual and sometimes fatal illness. We conducted an investigation to identify the etiology of the outbreak on the most severely affected atoll, Kuria, and identified thiamine deficiency disease as the cause. Thiamine deficiency disease has not been reported in the Pacific islands for >5 decades. We present the epidemiological, clinical, and laboratory findings of the investigation. METHODOLOGY/PRINCIPAL FINDINGS: We initially conducted detailed interviews and examinations on previously identified cases to characterize the unknown illness and develop a case definition. Active and passive surveillance was then conducted to identify additional cases. A questionnaire to identify potential risk factors and blood samples to assay biochemical indices were collected from cases and asymptomatic controls. Thiamine hydrochloride treatment was implemented and the response to treatment was systematically monitored using a five-point visual analogue scale and by assessing resolution of previously abnormal neurological examination findings. Risk factors and biochemical results were assessed by univariate and multivariate analyses. 69 cases were identified on Kuria (7% attack rate) including 34 confirmed and 35 unconfirmed. Most were adults (median age 28 years [range 0-62]) and 83% were male. Seven adult males and two infants died (13% case fatality rate). Resolution of objective clinical signs (78%) or symptoms (94%) were identified within one week of starting treatment. Risk factors included having a friend with thiamine deficiency disease and drinking kava; drinking yeast alcohol reduced the risk of disease. Higher chromium (p<0·001) but not thiamine deficiency (p = 0·66) or other biochemical indices were associated with disease by univariate analyses. Chromium (p<0·001) and thiamine deficiency (p = 0·02) were associated with disease by multivariate analysis. CONCLUSIONS/SIGNIFICANCE: An outbreak of thiamine deficiency disease (beriberi) in Kiribati signals the re-emergence of a classic nutritional disease in the Pacific islands after five decades. Although treatment is safe and effective, the underlying reason for the re-emergence remains unknown. Chromium was highly and positively correlated with disease in this study raising questions about the potential role of factors other than thiamine in the biochemistry and pathophysiology of clinical disease.

Effect of blood thiamine concentrations on mortality: Influence of nutritional status.

OBJECTIVE: To test the hypothesis that low blood thiamine concentrations in malnourished critically ill children are associated with higher risk of 30-d mortality. METHODS: Prospective cohort study in 202 consecutively admitted children who had whole blood thiamine concentrations assessed on admission and on days 5 and 10 of intensive care unit (ICU) stay. The primary outcome variable was 30-d mortality. Mean blood thiamine concentrations within the first 10 d of ICU stay, age, sex, malnutrition, C-reactive protein concentration, Pediatric Index of Mortality 2 score, and severe sepsis/septic shock were the main potential exposure variables for outcome. RESULTS: Thiamine deficiency was detected in 61 patients within the first 10 d of ICU stay, 57 cases being diagnosed on admission and 4 new cases on the 5th d. C-reactive protein concentration during ICU stay was independently associated with decreased blood thiamine concentrations (P = 0.003). There was a significant statistical interaction between mean blood thiamine concentrations and malnutrition on the risk of 30-d mortality (P = 0.002). In an adjusted analysis, mean blood thiamine concentrations were associated with a decrease in the mortality risk in malnourished patients (odds ratio = 0.85; 95% confidence interval [CI]: 0.73-0.98; P = 0.029), whereas no effect was noted for well-nourished patients (odds ratio: 1.03; 95% CI: 0.94-1.13; P = 0.46). CONCLUSIONS: Blood thiamine concentration probably has a protective effect on the risk of 30-d mortality in malnourished patients but not in those who were well nourished.

Burning mouth syndrome: results of screening tests for vitamin and mineral deficiencies, thyroid hormone, and glucose levels-experience at Mayo Clinic over a decade.

BACKGROUND: Burning mouth syndrome (BMS) is a disorder characterized by chronic mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral deficiencies may have a role in BMS, but data regarding the prevalence and relevance of hematinic deficiencies are conflicting. We aimed to determine the frequency of specific laboratory abnormalities in patients with BMS. METHODS: We retrospectively reviewed the results of screening blood tests in patients with BMS at our institution between January 2003 and December 2013. RESULTS: Among 659 patients with BMS, the most common decreased values or deficiencies were vitamin D3 (15%), vitamin B2 (15%), vitamin B6 (5.7%), zinc (5.7%), vitamin B1 (5.3%), thyrotropin (TSH) (3.2%), vitamin B12 (0.8%), and folic acid (0.7%). Laboratory values for fasting blood glucose and TSH were increased in 23.7% and 5.2%, respectively. CONCLUSIONS: In patients with symptoms of BMS, our results suggest it is reasonable to screen for fasting blood glucose, vitamin D (D2 and D3 ), vitamin B6 , zinc, vitamin B1 , and TSH. Deficiencies of vitamin B12 and folic acid were rare (<1% abnormal).