Biochemical Evidence Of Thiamine Deficiency Research Articles

Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos.

BackgroundIn a recent study one third of Lao patients presenting with uncomplicated Plasmodium falciparum malaria had biochemical evidence of thiamin deficiency, which was associated with a higher incidence of adverse events. Thiamin supplementation might, therefore, reduce adverse events in this population.MethodsAn exploratory, double-blind, parallel group, placebo-controlled, superiority trial of thiamin supplementation in patients of all ages with uncomplicated and severe falciparum malaria was conducted in Xepon District, Savannakhet Province, southern Laos. Patients were randomly assigned to either oral thiamin 10 mg/day for 7 days immediately after standard anti-malarial treatment then 5 mg daily until day 42, or identical oral placebo.ResultsAfter interim analyses when 630 patients (314 in thiamin and 316 in placebo groups) had been recruited, the trial was discontinued on the grounds of futility. On admission biochemical thiamin deficiency (alpha ≥ 25%) was present in 27% of patients and 9% had severe deficiency (alpha > 31%). After 42 days of treatment, the frequency of thiamin deficiency was lower in the thiamin (2%, 1% severe) compared to the placebo (11%, 3% severe) groups (p < 0.001 and p = 0.05), respectively. Except for diarrhoea, 7% in the placebo compared to 3% in the thiamin group (p = 0.04), and dizziness on day 1 (33% vs 25%, p = 0.045), all adverse events were not significantly different between the groups (p > 0.05). Clinical, haematological, and parasitological responses to treatment did not differ significantly between the two groups.ConclusionThiamin supplementation reduced biochemical thiamin deficiency among Lao malaria patients following anti-malarial drug treatment, but it did not reduce the frequency of adverse events after anti-malarial therapy or have any detected clinical or parasitological impact.Trial registrationISRCTN 85411059

Thiamin Status, Diuretic Medications, and the Management of Congestive Heart Failure

Objective To assess the prevalence of thiamin deficiency in patients with congestive heart failure who are treated with diuretics that inhibit sodium and chloride reabsorption in the thick ascending limb of the loop of Henle (loop diuretic therapy). Design A cross-sectional investigation of thiamin status of consecutive patients with congestive heart failure being treated with loop diuretic therapy. Setting Cardiology clinic of a midwestern tertiary-care medical center. Subjects Thirty-eight patients were recruited (mean age±standard deviation=55±14 years). Validation of methodology was conducted with nine age-matched control subjects. Main outcome measures Thiamin status was assessed biochemically by in vitro erythrocyte transketolase activity assay. Assessment of dietary intake of thiamin was accomplished with a semiquantitative food frequency questionnaire. Statistical analyses performed Fisher's exact test and logistic regression were used to evaluate relationships between thiamin status and variables of interest. Results Biochemical evidence of thiamin deficiency was found in 8 of 38 (21%) patients. Evidence of risk for dietary thiamin inadequacy was found in 10 of 38 patients (25%). Seven of the 8 patients with biochemical evidence of thiamin deficiency met study criteria for dietary adequacy, although quantified data suggested that only 4 of the patients achieved two thirds of the Recommended Dietary Allowance. Biochemical evidence of thiamin deficiency tended to be more common among patients with poor left ventricular ejection fractions ( P=.07). Conclusions Thiamin deficiency may occur in a substantial proportion of patients with congestive heart failure, and dietary inadequacy may contribute to increased risk. J Am DietAssoc. 1995; 95:541-544.

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy

We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months. Thirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.

Thiamin status, diuretic medications and the management of congestive heart failure

Thiamin deficiency in malnourished patients is known to have adverse cardiovascular effects: peripheral vasodilation leading to high output cardiac failure, biventricular low output failure and retention of sodium and water resulting in edema. Results from previous investigations suggest increased risk of thiamin deficiency in patients with congestive heart failure (CHF) on long term loop diuretics due to excessive urinary excretion. The purpose of this study was to assess the prevalence of thiamin deficiency in patients with CHF who are receiving loop diuretic therapy. This was a prospective investigation of thiamin status including dietary assessment and biochemical measurements via transketolase activity (TKA) with and without thiamin pyrophosphate (TPP) cofactor in consecutive patients of a cardiology clinic. Thiamin status was measured biochemically by in vitro erythrocyte TKA before and after addition of exogenous TPP. TPP effect (TPPE) was expressed as percent stimulation of TKA with exogenous TPP. Thiamin status was defined by TPPE as: normal 0–15%, mild deficiency 15–25%, severe deficiency >25%. Dietary assessment was obtained by a quantitative food frequency questionnaire of thiamin-rich foods. Adequacy of dietary intake was classified as: normal >30 servings/week, mild inadequacy 20–30 servings/week, severe inadequacy <20 servings/week. Thirty-eight patients (mean and median of 56 years; range 20–79 years); 29 males, 9 females; and 30 white, 8 nonwhite were included in the study. Inclusion criteria: 18–80, New York Heart Association class II, III, IV, left ventricular ejection fraction <40%, Lasix 80mg/day or Bumex 2mg/day, treatment with ace inhibitor, nitrate digoxin, zaroxolyn was acceptable. Measurements were compared with values obtained from nine control subjects. Logistic regression was used to evaluate relationships between thiamin status and cardiac function, clinical laboratory data, patient characteristics and confounding variables. Biochemical evidence of thiamin deficiency was found in 21% (838) of patients. Overall prevalence of dietary thiamin inadequacy was 20%. Of the eight patients with biochemical evidence of thiamin deficiency, seven had levels of dietary thiamin which appeared to meet or exceed RDA levels. Biochemical evidence of thiamin deficiency was found to be more likely to occur in males (vs. females) and nonwhites (vs. nonwhites) (p=0.005). In conclusion, thiamin deficiency may occur in one-fifth of patients with CHF in a cardiology clinic. Of this group, male and nonwhite CHF patients appear to be at highest risk for thiamin deficiency. Dietary intake of thiamin-rich foods does not appear to prevent biochemical thiamin deficiency in this population. Status of other micronutrients may also be affected by loop diuretics and deserves further study.

Thiamine deficiency and wernicke's encephalopathy in AIDS

Several neuropathological reports in the last 5 years have described brain lesions characteristic of Wernicke's Encephalopathy in patients with AIDS. Using the erythrocyte transketolase activation assay, we now report biochemical evidence of thiamine deficiency in 9/39 (23%) of patients with AIDS or AIDS-related complex. In no cases was there history of alcohol abuse nor were there clinical signs of Wernicke's Encephalopathy. Thiamine deficiency in these patients most likely results from the cachexia and catabolic state characteristic of AIDS. In view of (i) the confirmed neuropathological evidence of Wernicke's Encephalopathy in AIDS patients, (ii) the significant thiamine deficiency in these patients and (iii) the difficulties of clinical diagnosis of Wernicke's Encephalopathy, it is recommended that dietary thiamine supplementation be initiated in all newly diagnosed cases of AIDS or AIDS-related complex.

Thiamine deficiency in the critically ill

There have been recent reports of hospitalised patients developing clinical thiamine deficiency, combined with much debate on the optimal supplementation of thiamine for the parenterally fed patient, particularly in the intensive therapy environment. We performed a retrospective study on 158 patients admitted to the Intensive Care Unit who required nutritional support. Patients who survived had significantly higher body thiamine status than those who died (p less than 0.01). There was no difference between serum albumin concentrations of the two groups. Twenty percent of the patients had biochemical evidence of thiamine deficiency and the mortality rate in these patients was 72% as compared with 50% mortality overall. Follow-up results suggest that current levels of thiamine supplementation are insufficient for critically ill intravenously fed patients. We suggest that patients be given a loading dose of 50-250 mg thiamine on admission to the Intensive Care Unit.

Thiamin status in normal and malnourished children in Jamaica.

Thiamin status has been measured using the erythrocyte transketolase (EC 2.2.1.1) assay in twenty-eight normal children and in twenty-five severely-malnourished children throughout the course of recovery. Subclinical thiamin deficiency was found in 7% of the normal children and 36% of the malnourished children on admission. There was no significant association between thiamin status and oedema, stunting or wasting, history of breast-feeding, pattern of weaning, age or sex. Five malnourished children, who died, all had a normal thiamin status on admission; however, two developed biochemical evidence of thiamin deficiency preterminally.

Erythrocyte transketolase activity in alcoholic liver disease.

Erythrocyte transketolase activity and its stimulation in vitro by the addition of thiamine pyrophosphate (TPP effect) was measured in 64 normally nourished alcoholics with well-compensated liver disease and in 20 control subjects. Biochemical evidence of thiamine deficiency as judged by low transketolase activity was found in 19 alcoholics (29.7%). In 5 of these 19 patients the TPP effect was abnormally high, indicating depleted thiamine stores. IN the other 13 patients the TPP effect was either normal or low, suggesting a deficiency or an inability to use the transketolase apoenzyme, probably as a result o long-standing thiamine deficiency or the presence of liver disease. a further eight patients (12.5%) had normal transketolase activity but a low TPP effect, perhaps reflecting failure of hte coenzyme TPP to recombine with the transketolase apoenzyme in the presence of normal thiamine stores. There was no relationship between transketolase activity and the daily alcohol consumption, the duration of alcoholism, or the histological severity of the liver disease. Thiamine should be given routinely to alcoholics even if their diet appears adequate and their liver disease is minimal or well compensated.

Biochemical evidence of thiamin deficiency in young Ghanaian children

Detailed biochemical studies for nutritional status were carried out on 146 Ghanaian children ages 6 months to 6 years over a 2-year period. Study children comprised three main groups: severe protein-calorie malnutrition; mild to moderate protein-calorie malnutrition and apparently healthy children. Erythrocyte transketolase activity and the percentage of erythrocyte transketolase pyrophosphate effect were also determined. In the first year of the study elevated percentage of transketolase pyrophosphate effect indicative of thiamin deficiency was found in all three of the above-mentioned groups, with the most widespread deficiency in the normal groups. In year 2, repeat studies of the severely malnourished group after 2 weeks of nutritional therapy with the administration of vitamin capsules, which included thiamin, resulted in the normalization of transketolase pyrophosphate effect. Apoenzymc activity was comparable in all groups studied. There were no obvious clinical signs of thiamin deficiency, although sensory testing was not performed. A relatively large number of children with high percentage of transketolase pyrophosphate effect also had serum folic acid deficiency. This evidence of widespread biochemical thiamin deficiency is indicative of an at-risk population among young children for clinical thiamin deficiency. Further studies are needed to identify whether the problem is inadequate thiamin intake, destruction of thiamin by thiaminases or food preparation methods, or malabsorption of thiamin.

Red blood cell transketolase activity and the effect of thiamine supplementation in patients with chronic liver disease.

Biochemical evidence of thiamine deficiency was found in 58% of patients with chronic liver disease, the incidence being higher in alcoholic than in non-alcoholic patients. Daily supplementation with high doses of thiamine hydrochloride (200 mg/day) for one week restored levels of thiamine pyrophosphate (TPP), the active co-enzyme form of thiamine, to normal in all cases. Such supplementation also stimulated synthesis of the TPP dependent enzyme transketolase. Because of the essential role of TPP as a co-factor in intermediary metabolism, it is concluded that high doses of thiamine should be included in the routine nutritional management of patients with severe chronic liver disease.

Thiamine Status in Alcoholism

Summary :Thiamine status in alcoholism. Beverley Wood, Kerry J. Breen and D. G. Penington, Aust. N.Z. J. Med., 1977, 7, pp. 475–484. The erythrocyte transketolase assay was used to seek biochemical evidence of thiamine deficiency in 265 alcoholic persons attending an inner city Australian hospital. Fifty patients were found to have recent vitamin therapy and were excluded from further study. Wernicke's encephalopathy was diagnosed in 24 subjects (11.3%). The thiamine pyrophosphate (TPP) effect was elevated in only 13 of the 24 patients with Wernicke's encephalopathy; a much closer correlation was observed with erythrocyte transketolase activity which was depressed in 21 persons with this diagnosis. Low erythrocyte transketolase activity (32.6%) was more frequently seen than an elevated TPP effect (24-7%) in the overall group of 215 subjects. Of 47 patients with a low erythrocyte transketolase activity which failed to return to normal after the addition of TPP in vitro, only ten patients had liver disease. Twelve patients with Wernicke's encephalopathy studied following thiamine hydrochloride in vivo showed complete biochemical response despite the presence of biopsy proven severe liver disease in two patients and the lack of response of low erythrocyte transketolase activity to TPP in vitro in eleven of the twelve patients. Fiftyfive patients were studied before and after thiamine in vivo. Seventeen of these subjects had severe liver disease but only two of the 17 had low ETKA which failed to respond to TPP in vitro; both responded biochemically to thiamine hydrochloride in vivo. In the remaining 38 patients without evidence of severe liver disease, 14 had low ETKA which failed to return to normal with TPP in vitro; three of these failed to respond biochemically to thiamine hydrochloride in vivo. These data indicated that apparent deficiency of erythroc yte apotransketolase was infrequently linked with the presence of liver disease and that liver disease did not appear to interfere with the biochemical response to thiamine in vivo. Urinary thiamine excretion measured in 79 subjects did. not correlate with any means of expression of the transketolase assay or with clinical thiamine deficiency. It was concluded that the TPP effect was frequently misleading in subjects with gross thiamine deficiency (Wernicke'S encephalopathy) and it was suggested that erythrocyte transketolase activity may be the best parameter to use in assessing thiamine status with the erythrocyte transketolase assay. Finally, it is postulated that severe thiamine deficiency per se may lead to deficiency of erythrocyte apotransketolase which has been previously ascribed to liver damage.

Carbohydrate metabolism and nutritional state in multiple sclerosis

An investigation was undertaken into the nutrition and carbohydrate metabolism of ten patients suffering from multiple sclerosis who subsisted on diets of their own choice. The general level of nutrition was poor, intake of fat and protein was low in both sexes, and the carbohydrate intake was low in women. Thiamine and niacin of the diet appeared adequate. The observed patterns of abnormal glucose tolerance tests corresponded to those seen in starvation and could be rectified by glucose feeding. One case of diabetes mellitus became apparent after glucose feeding. There was no biochemical evidence of thiamine deficiency in these patients subsisting on poor diets. There was evidence of temporary thiamine deficiency in one patient after extra loading with glucose. Glucose tolerance curves, following the administration of thiamine and cocarboxylase, respectively, were of a similar pattern. Cocarboxylase and thiamine were found to be of no therapeutic value.