Subclinical Thiamine Deficiency Research Articles

Exploring the impact of age, and body condition score on erythrocytic B1-Dependent transketolase activity in cats: A comprehensive analysis of thiamine status

One of the key factors influencing aging and morbidity is the overall antioxidant status and regenerative capacity. In examining contributors to the antioxidant status, we analyzed the thiamine status in felines and the influence of age, gender, and body condition score. We measured erythrocytic B1-dependent specific transketolase (STKT) activity, an enzyme in the pentose phosphate pathway, in a group of 60 sexually intact, healthy, and specific pathogen-free felines (44 females, 16 males, aged 1–17 years) with thiamine diphosphate (TDP; 0.3 and 3 mM) and without it. Only two parameters (STKT activity with and without 0.3 mM TDP) decreased with age. After adjusting for age, statistical thresholds were established using these and other age-independent parameters, identifying 15 felines with subclinical thiamine deficiency. The red blood cell proteomics analysis revealed that the pentose phosphate shunt, glycolysis, and oxidative stress response were the most affected pathways in deficient felines, confirming the above diagnosis. Age emerged as the primary factor associated with thiamine deficiency, supported by the enrichment of neurodegenerative diseases with a proteotoxicity component; five young-adult felines showed marginal or acute B1 deficiency, and six were adult-mature with a more chronic deficiency, possibly linked to cognitive decline, all with an underweight to ideal body condition scores. Only three senior-adult felines were deficient and overweight-obese. Detecting thiamine deficiency emphasizes the need for more accurate reference values, the establishment of advanced preventive or therapeutic measures to enhance the well-being of aging companion animals, and potential extensions to human health, particularly concerning cognitive function.

Basal Ganglia Disease Mimicking Acute Encephalitis Syndrome Among Infants of Bodo Tribe, Assam

We conducted a review of hospital records of infants with acute encephalitis syndrome with bilateral symmetrical basal ganglia infarcts, between 2011-2015, at a single center in Assam. Thiamine (as part of multivitamin injection) was used in the treatment of 23 infants and not used in 27; Only 1 (3.7%) infant died in the former group and 20 infants (86.9%) died in the latter [RR (95% CI) 0.04 (0.006,0.29); P<0.001). Two infants on follow-up had normal development, both in the thiamine group. The study suggests the possibility of subclinical thiamine deficiency, mitochondrial diseases, or SLC19A3 gene mutation in this population.

Whole Blood Thiamine in Organ Donors After the Neurologic Determination of Death.

Metabolic resuscitation of organ donors and the attenuation of oxidative stress incurred by organs following brain death and transplantation have the potential to improve organ yield and allograft function. Thiamine (vitamin B1) is a vital coenzyme in both energy metabolism and the production of antioxidants that has not been studied in the donor population. To determine the frequency of subclinical thiamine deficiency in brain-dead organ donors and its correlation with demographics, length of hospitalization, donor management, lactic acidosis, and the requirement for vasoactive support. Prospective cohort study of brain-dead donors managed at a single organ procurement organization's organ recovery facility. A total 64 donors were enrolled; 24 donors had thiamine levels drawn upon arrival and 40 donors had levels drawn at the time of organ procurement. Whole blood thiamine levels were inversely correlated with the time from death (P = .007) and 20% (8/40) of donors had levels below the normal range at the time of organ procurement. Demographic features of the donor were not associated with thiamine levels although longer hospital stays prior to death were associated with lower levels (P < .05). The presence and resolution of lactic acidosis was not associated with whole blood thiamine level. Higher thiamine levels were associated with earlier discontinuation of vasoactive support (P = .04). Whole blood thiamine deficiency was not uncommon at the time of organ procurement. Thiamine may be associated with the requirement for hemodynamic support.

Subclinical thiamine deficiency identified by pretreatment evaluation in an esophageal cancer patient

Despite the fact that both thiamine deficiency (TD) and Wernicke encephalopathy (WE) have been observed to some degree in cancer patients, such cases of TD and/or WE reported to date have all been diagnosed after the initiation of treatment. We here report a case of TD that presented without the commonly accepted triad of WE symptoms based on a total nutritional evaluation prior to the onset of treatment for cancer. The patient was a 71-year-old man with esophageal cancer who was referred to the oncology outpatient clinic for evaluation to determine the treatment plan. Although he did not present with delirium, cerebellar signs, or ocular symptoms, TD was suspected based on a reduction in appetite lasting 2 months as thiamine stores in the body are depleted in as few as 18 days. Blood findings showed a marked decline in serum thiamine level supported, which the diagnosis of TD. This case revealed the existence of a cancer patient with subclinical TD prior to the onset of treatment for cancer. Due to the fact that TD can occur without the characteristic symptoms as in this case, we believe it is important that total nutritional evaluation of cancer patients always be considered.

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.

Infantile Thiamine Deficiency: New Insights into an Old Disease

The wide spectrum of clinical presentation in infantile thiamine deficiency is difficult to recognize, and the diagnosis is frequently missed due to the lack of widespread awareness, and non-availability of costly and technically demanding investigations. The topic was searched by two independent researchers using online databases of Google scholar and PubMed. We considered the related studies published in the last 20 years. The terms used for the search were 'thiamine', 'thiamine deficiency', 'beri-beri', 'B-vitamins','micronutrients', 'malnutrition', 'infant mortality'. 'Wernicke's syndrome','Wernicke's encephalopathy', and 'lactic acidosis'. In the absence of specific diagnostic tests, a low threshold for a therapeutic thiamine challenge is currently the best approach to diagnose infantile thiamine deficiency in severe acute conditions. The practical approach is to consider thiamine injection as a complementary resuscitation tool in infants with severe acute conditions; more so in presence of underlying risk factors, clinically evident malnutrition or where a dextrose-based fluid is used for resuscitation. Further, as persistent subclinical thiamine deficiency during infancy can have long-term neuro-developmental effects, reasonable strategy is to treat pregnant women suspected of having the deficiency, and to supplement thiamine in both mother and the baby during breastfeeding. Health care professionals in the country need to be sensitized to adopt a high level of clinical suspicion for thiamine deficiency and a low threshold for the administration of thiamine, particularly when infantile thiamine deficiency is suspected.

Overcoming the Current Challenges of Thiamine Deficiency Disorders (P10-091-19)

ObjectivesThiamine deficiency (the “forgotten scourge of Southeast Asia”) remains a pressing public health challenge as infantile beriberi, the most commonly fatal thiamine deficiency disorder (TDD), often results in death within hours of clinical presentation if left untreated.Objective was to assess the global prevalence, burden of disease, and consequences of thiamine deficiency. MethodsAn expert committee of public health professionals, physicians, neurologists, biochemists and nutritionists was assembled by the Sackler Institute for Nutrition Science. Two technical consultations were held to compile current knowledge on thiamine and identify gaps. Experts presented research findings and participated in discussions to determine the best biomarkers of thiamine status, estimate global prevalence of thiamine deficiency, and devise strategies to improve thiamine status in deficient populations. ResultsTDD remain prevalent in Southeast Asia, 45% of infant deaths during the first six months are attributable to beriberi in parts of Cambodia, and it is the second most common cause of infant deaths between 28 days and 1 year of age in Myanmar. However, the issue is not contained to SEA: 24 published outbreaks of thiamine deficiency were identified in locations, such as Kashmir, Kiribati and some West African countries. Growing evidence also suggests that sub-clinical thiamine deficiency may have lasting impacts on cognitive development and psychomotor functions. ConclusionsSeveral gaps in knowledge impair the ability to address the wide spectrum of TDD, including the lack of an accepted case definition of TDD, poor understanding of biomarkers, unknown status in large regions of the world. Factors triggering clinical disease, and the ability of prophylactic interventions to prevent TDD are also poorly understood. The committee commissioned several studies to address the gaps in knowledge, and to develop control and prevention programs in affected countries. It also proposed a case definition of thiamine deficiency disorders and clinical guidelines for empirical treatment of suspected TDD. The presentation will highlight the work of the expert group and ongoing studies. Funding SourcesBill & Melinda Gates Foundation.

Thiamine deficiency in alcoholics with normal body mass index

Background: Ethanol consumption leads to nutritional deficiency due to various causes. Well known theoretical as well as literature supports the hypothesis on dietary factors, metabolic derangement and alcohol per se produces empty calories. In this study completed in 2000 go hand in hand with the earlier observations and the available literature after 2000. Nutritional deficiency in turn leads to Alcoholic brain damage which is reversible if identified early. Among the nutritional deficiency Thiamine deficiency (Vitamin B6) appears as the most common findings across the studies.Aim: To find out the nutritional deficiency in otherwise normal healthy males who consume alcohol amounting to dependence.Materials and Methods: In this study, 40 males who were moderate drinkers, diagnosed as Alcohol dependence syndrome according to ICD-10 DCR-criteria with no indicators of overt nutritional deficiency on clinical assessment by ICMR Scale, Biochemical assessment and anthropometric assessment were included for the study. All the study subjects were subjected to detailed diet history by 24 hours recall, clinical assessment, biochemical investigations, anthropometric assessment along with demographic data and drinking history.Results: All the samples were clinically healthy and the BMI was 19.4 which fall under normal BMI. Anorexia was the predominant clinical symptom (45 percent). Biochemical and anthropometric assessment were within normal limits for an average Indian Males. But, serum Pyrophosphate was 318.47 mmol per litre (Normal value is 0.08 to 0.16 mmol per litre), which is an indirect indicator of thiamine deficiency.Conclusion: Though very preliminary and cross sectional analysis, sub-clinical thiamine deficiency was found in this study and corroborate with the previous observations. Hence, thiamine supplementation of all the drinkers irrespective of the clinical and biochemical nutritional deficiency will prevent at large both acute and chronic alcoholic brain damage.

Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs.

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month‐specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high‐risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing.

Subtype Presentation and Prevalence of Subclinical Thiamine Deficiency in Morbidly Obese Individuals Seeking Bariatric Surgery

Introduction: In the past 20 years, the prevalence of obesity has risen to 35% of adults in the US. Preoperative biochemical studies have reported a 6%-29% prevalence of low whole blood thiamine levels in the morbidly obese. In our prior study of individuals seen for GI consultation after gastric bypass surgery, 18% had thiamine deficiency, and 41% of deficient individuals had gastrointestinal manifestations. The hypothesis of this study is that symptoms of subclinical thiamine deficiency are common in morbidly obese individuals seeking bariatric surgery. Methods: This is a retrospective evaluation of morbidly obese individuals with no history of prior bariatric surgery who underwent preoperative GI consultation in a large, urban community teaching hospital from 2013 to 2014. Men with 15 or more drinks (1 drink = 14 g of alcohol) weekly or women with 8 or more drinks weekly were excluded. Patient charts were reviewed to record the symptoms of thiamine deficiencies including gastrointestinal (abdominal pain, nausea/emesis, or constipation), cardiologic (dyspnea on exertion, palpitations, or lower extremity edema), neurologic (blurred vision, nystagmus, ataxia, or paresthesias), or psychiatric (aggressive behavior or psychosis). Patient demographics were also recorded. Thiamine deficiency is defined by consistent clinical symptoms and either: A. a low whole blood thiamine level or B. resolution of an individual's clinical symptoms after receiving oral or intramuscular thiamine. Results: Among the 138 individuals, the mean age was 46 years (range: 18 to 75 years). The mean body mass index was 47.9 kg/m2 (range: 35 to 102); 84% were women and 16% were men. At evaluation, 11% of these individuals were taking a multivitamin supplement. Twenty-three out of 138 individuals (16.7%) fulfilled the dual criteria for thiamine deficiency: 6 patients (26%) had consistent GI symptoms, 17 patients (73%) had cardiac manifestations, 14 patients (61%) had neurological manifestations, and 1 patient (4%) had a psychiatric manifestation. Conclusion: Symptoms of subclinical thiamine deficiency are common in morbidly obese individuals seen for bariatric surgery. The results of this study support prior preoperative biochemical studies of thiamine deficiency in the morbidly obese. Dietary intake may be both an origin for obesity as well as an origin for thiamine deficiency. GI physicians should consider thiamine deficiency when evaluating morbidly obese patients who have consistent gastrointestinal symptoms.

Interactions between chronic ethanol consumption and thiamine deficiency on neural plasticity, spatial memory, and cognitive flexibility.

Many alcoholics display moderate to severe cognitive dysfunction accompanied by brain pathology. A factor confounded with prolonged heavy alcohol consumption is poor nutrition, and many alcoholics are thiamine deficient. Thus, thiamine deficiency (TD) has emerged as a key factor underlying alcohol-related brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can progress into Wernicke-Korsakoff syndrome and these disorders have a high prevalence among alcoholics. Animal models are critical for determining the exact contributions of ethanol (EtOH)- and TD-induced neurotoxicity, as well as the interactions of those factors to brain and cognitive dysfunction. Adult rats were randomly assigned to 1 of 6 treatment conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH over 6months; severe pyrithiamine-induced TD (PTD-moderate acute stage); moderate PTD (PTD-early acute stage); moderate PTD followed by CET (PTD-CET); moderate PTD during CET (CET-PTD); and pair-fed (PF) control. After recovery from treatment, all rats were tested on spontaneous alternation and attentional set-shifting. After behavioral testing, brains were harvested for determination of mature brain-derived neurotrophic factor (BDNF) and thalamic pathology. Moderate TD combined with CET, regardless of treatment order, produced significant impairments in spatial memory, cognitive flexibility, and reductions in brain plasticity as measured by BDNF levels in the frontal cortex and hippocampus. These alterations are greater than those seen in moderate TD alone, and the synergistic effects of moderate TD with CET lead to a unique cognitive profile. However, CET did not exacerbate thalamic pathology seen after moderate TD. These data support the emerging theory that subclinical TD during chronic heavy alcohol consumption is critical for the development of significant cognitive impairment associated with ARBD.

Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study

Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in long-term thiamine deficiency, which may further compromise cardiac function. This study evaluated the effect of high dose thiamine supplementation in heart failure patients. Nine patients with diuretic treatment for symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive thiamine (300mg/day) or placebo for 28days. After a wash-out of 6weeks, the patients crossed-over to a second treatment period. The primary outcome was a change in LVEF. Mean age was 56.7±9.2years (range 44.9-75.4years). Baseline LVEF was similar for both treatment groups (29.5% in the thiamine group and 29.5% in the placebo group, P=0.911). After 28days of thiamine treatment, the LVEF increased to 32.8% which was significantly (P=0.024) different from the LVEF in the placebo group (28.8%). This corresponds to a treatment effect for LVEF of 3.9% in absolute terms. This study suggests that thiamine supplementation has beneficial effects on cardiac function in patients with diuretic drugs for symptomatic chronic heart failure. Subclinical thiamine deficiency is probably an underestimated issue in these outpatients.

Clinically Unapparent Infantile Thiamin Deficiency in Vientiane, Laos

BackgroundBeriberi occurs in Vientiane, Lao PDR, among breastfed infants. Clinical disease may be the tip of an iceberg with subclinical thiamin deficiency contributing to other illnesses. Thiamin treatment could improve outcome.Methodology/Principal FindingsA cohort of 778 sick infants admitted during one year without clinical evidence of beriberi were studied prospectively and erythrocyte transketolase assays (ETK) performed. Biochemical thiamin deficiency was defined both in terms of the activation coefficient (α>31%) and basal ETK activity <0.59 micromoles/min/gHb. Of the 778 infants, median (range) age was 5 (0–12) months, 79.2% were breastfed, 5.1% had α>31% and 13.4 % basal ETK<0.59 micromoles/min/gHb. Infants ≥2 months old had a higher frequency of biochemical markers of thiamin deficiency. Mortality was 5.5% but, among infants ≥2 months old, mortality was higher in those with basal ETK<0.59 micromoles/min/gHb (3/47, 6.4%) than in those with basal ETK≥0.59 micromoles/min/gHb (1/146, 0.7%) (P = 0.045, relative risk = 9.32 (95%CI 0.99 to 87.5)). Multivariate regression analysis indicated that infant age ≥2 months and fewer maternal years of schooling were independently associated with infant basal ETK<0.59 micromoles/min/gHb.Conclusions/SignificanceClinically unapparent thiamin deficiency is common among sick infants (≥2 months old) admitted to hospital in Vientiane. This may contribute to mortality and a low clinical threshold for providing thiamin to sick infants may be needed.

Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition?

Despite modern pharmacologic agents in the therapy of heart failure, the prevalence of heart failure is increasing worldwide. In the vitamin B1 deficiency disease beriberi, cardiac symptoms may represent the central feature. Two new studies confirmed that all diuretics lead to increased urinary thiamin excretion depending on the urinary flow rate. In a subject at risk, such as an elderly patient, chronic diuretic treatment may lead to a subclinical thiamin deficiency. Whether subclinical thiamin nutriture is a modulator of the prevalence and/or severity of heart failure is not known; however, it seems to be plausible from the metabolic point of view.

Wernicke-Enzephalopathie bei chronischer gastropankreatischer Erkrankung mit Pylorusstenose

The acute symptomatology of Wernicke's syndrome was observed in a 17-year-old female patient and a 48-year-old male patient. They were both affected by chronic gastropancreatic disease with pyloric stenosis and showed already subclinical thiamine deficiency. Symptoms occurred within 4 weeks of an infusion regime rich in carbohydrates. Parenteral administration of high doses of thiamine (200 mg/d and 360 mg/d) led to clear-cut regression of symptoms. Due to the unfavourable prognosis of Wernicke's encephalopathy prophylactic administration of thiamine in a daily dosage of 50-100 mg is recommended in patients with chronic intestinal disease and parenteral nutrition.

Ultrastructural pathology of Baltic salmon, Salmo salar L., yolk sac fry with the M74 syndrome

The ultrastructural pathology in liver, brain, skeletal and cardiac muscle of Baltic salmon yolk sac fry with the M74 syndrome is described. In the clinical stage of disease, the main pathological findings in the liver were a depletion of glycogen, condensation of nuclear chromatin, hydropic degeneration of mitochondria and a dilation of the bile canaliculi. In the terminal stage, additional findings were lipid accumulation and myelin whorls in the cytoplasm. The rough endoplasmic reticulum (RER) was degranulated and vesiculated and in some individuals, it formed concentric membranous whorls. Mitochondria showed several additional lesions, such as matrix densities, pleomorphism and cristae abnormalities. Skeletal myocytes were degenerated, and intracellular lipid accumulation was seen in the myocardium. In the brain, an increased frequency of cells exhibiting pyknosis or karryorhexis was recorded. The cytoplasm of these cells formed an amorphous mass of moderate density. The evaluation of brain and skeletal muscle was complicated by sporadic occurrence of pathological findings in the reference material, i.e. clinically healthy Baltic salmon yolk sac fry. As these yolk sac fry are suspected to have a subclinical thiamine deficiency, reference material in future studies should include salmon yolk sac fry from Atlantic populations or originating from reared broodstock.

Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot study

Malignancy associated primary thiamine deficiency has been documented in several experimental tumours, sporadic clinical case reports, and in a number of patients with fast growing haematological malignancies.Thiamine status was assessed...

The response to treatment of subclinical thiamine deficiency in the elderly

The significance of subclinical thiamine deficiency in the elderly was determined by assessing response to thiamine supplementation in a randomized double-blind, placebo-controlled trial. Thirty-five of 222 people aged > or = 65 y had two concentrations of erythrocyte thiamine pyrophosphate (TPP) < 140 nmol/L 3 mo apart and 41 other people had the first, but not the second, TPP concentration below this value. Both groups were randomly assigned in a double-blind trial to oral thiamine (10 mg/d) or a placebo. All subjects randomly assigned to receive thiamine showed increases in TPP concentrations compared with control subjects. Only the subjects with persistently low TPP concentrations showed subjective benefits from treatment with improvements in quality of life (measured on a visual analogue scale; P = 0.02) and decreases in systolic blood pressure (P = 0.05) and weight (P < 0.01) when compared with subjects given placebo. There was a trend toward benefits in sleep and energy (P = 0.07). We conclude that a low TPP concentration on two occasions is a better predictor of response to treatment than an isolated measurement. Quality of life was enhanced by providing thiamine supplements. Blood pressure and weight were lower after thiamine supplementation.

Natural establishment of thiaminase activity in the alimentary tract of newborn lambs and effects on thiamine status and growth rates.

Thiaminase activity was detected in the faeces of lambs at 2 to 5 days of age. Levels of activity increased for 10 days and then declined over the next 3 to 4 weeks. Decreased erythrocyte transketolase activity indicated thiamine insufficiency in lambs with high thiaminase activity. Mean growth rates were 17% less in lambs with high thiaminase activity than in lambs with zero or low thiaminase activity. Bacillus thiaminolyticus was the only organism isolated which produced thiaminase. Treatment of newborn lambs with intramuscular injections of sulphadoxine did not prevent them from excreting thiaminase in their faeces. It is proposed that oral thiamine supplementation of lambs at 2 to 3 weeks of age may be the most appropriate prevention and treatment for subclinical thiamine deficiency of the cause described.

The course of idiopathic dilated cardiomyopathy in New Zealand.

The course of dilated cardiomyopathy in New Zealand was studied in 72 cases that were followed up for less than or equal to 10 years after cardiac catheterisation and coronary angiography. Eighty one per cent were male and 86% were white; the remainder were Maori. The mean age of patients at the time of investigation was 50 X 15 years. Most patients were unskilled labourers. The commonest presenting symptom was dyspnoea and the commonest physical sign was cardiomegaly. Mean survival time from first hospital presentation was 85 months; half the deaths were sudden. Factors predicting a poor survival included cardiomegaly, age, arrhythmias, cigarette smoking, and subclinical thiamine deficiency. The syndrome of dilated cardiomyopathy in New Zealand appears to be identical with that seen in other European populations.