Excretion Of Thiamine Research Articles

Effect of Chronic Ethanol Administration on Thiamin Metabolism in the Rat

The effect of chronic alcohol administration on the absorption, excretion and metabolism of thiamin in the rat has been examined. In ethanol-fed rats receiving a marginal daily intake of thiamin (10 microgram/day) by stomach tube or by intraperitoneal injection, less of the vitamin and its metabolites were excreted in the urine as compared to controls administered the same diet except that sucrose replaced the energy represented by ethanol. More of the oral dose of thiamin was excreted in the feces of the ethanol-fed as compared to control rats. These data support previous reports of decreased adsorption of thiamin from the gut in animals exposed to ethanol. The studies in which the thiamin was administered by intraperitoneal injection also indicate an effect of ethanol on thiamin excretion in the urine which appears not to be related to absorption of the vitamin from the gut. An examination reveals no difference in the level of thiamin and its metabolites in the tissues of ethanol-fed as compared to control rats receiving thiamin by stomach tube. Thus, the decreased absorption of thiamin from the gut in the ethanol-fed rats seems to be balanced by a decreased excretion in the urine leading to a comparable accumulation of the vitamin in the tissues as controls.

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.

Preliminary clinical and anthropometric findings from the first Health and Nutrition Examination Survey, USA, 1971–1972

Eight percent of Negroes between the ages of 45 to 59 had hepatomegaly. Tongue signs and absent knee and ankle jerks were more prevalent in Negroes ages 45 to 74; they also had lower urinary excretion of thiamine and riboflavin than Whites. Bowed legs and knock knees were more frequent in Negroes ages 1 to 17 and Negro women 18 to 44. Prevalence of bleeding, swollen gums was highest in Negroes ages 45 to 59. Both grade I and II goiter were more prevalent in Negroes at all ages except men 18 to 59. Chvostek's sign indicating possible calcium deficiency was more frequent in Negroes at all ages with two exceptions. Major anthropometric findings will also be presented.

Biochemical assessment of the nutritional status of low-income pregnant women of Mexican descent

Biochemical parameters of nutritional status were investigated in 300 women of Mexican descent during the first and second trimesters of pregnancy. Blood samples were obtained from the women during clinic visits, and measurements were made of serum iron, hemoglobin, hematocrit, serum protein, and transferrin saturation. Additionally, the nutritional status of seven vitamins was determined either by direct assay of the vitamin levels in blood or by measurement of erythrocyte enzyme stimulation. Thiamin and riboflavin were also determined in causal urine samples. Very few women, 8% or less, were classified as being low or deficient in hemoglobin, serum protein, iron, transferrin saturation, vitamin C, carotene, vitamin A, or vitamin B12. Thirty-one percent had low or deficient hematocrit values according to the guidelines used. Folic acid was the most prevalent vitamin deficiency, with 69% of the women having low or deficient serum levels. Based on the erythrocyte enzyme stimulation tests, 22% of the women were low or deficient in thiamin, 29% were low or deficient in riboflavin, and 9% were deficient in pyridoxine. None of the women had a low urinary excretion of thiamin, but 8% had excretion values of riboflavin below the acceptable level. Fewer deficiencies of thiamin and serum folic acid were observed in women taking vitamin and mineral supplements than in those who were not.

Effect of oral contraceptive agents on nutrients: II. Vitamins

Clinical, biochemical and nutritional data were collected from a large population of women using oral contraceptive agents. Higher incidence of abnormal clinical signs related to malnutrition were observed in the lower (B) as compared to the higher (A) socioeconomic groups, and also in the nonsupplemented groups as compared to the supplemented groups in the B subjects. As a rule the intake of oral contraceptive agent subjects of vitamin A, C, B6 and folic acid did not differ from that of the controls As expected, subjects from the supplemented groups had higher intake of vitamin A, C, B6, thiamin, riboflavin and folic acid, and A groups had higher intake of vitamin C, B6, riboflavin and folic acid. Increased plasma vitamin A and decreased carotene levels were observed in oral contraceptive agent users. In general oral contraceptive agents had little or no effect on plasma ascorbic acid. Urinary excretion of both thiamin and riboflavin in subjects using oral contraceptive agents were lower in A groups. Erythrocyte folate and plasma pyridoxal phosphate was decreased in A groups due to oral contraceptive agents. Subjects who took supplements had higher levels of plasma vitamin A, ascorbic acid and folate. But urinary thiamin and riboflavin were higher only in group A subjects who took supplements.

Thiamine and thiamine pyrophosphate in obsese patients during partial and total fasting (author's transl)

The development of vitamin B1 (thiamine) deficiency was investigated in 17 obese patients in the course of a 1000 calory diet or during total fasting for a fortnight. Compared with normal persons no changes of concentrations of total thiamine, TPP, and pyruvate in the blood; thiamine excretion in the urine, or activiation coefficient of the eryhrocyte transketolase (alphaETK) were observed during the reducing diet. However, during a fortnight's total fasting all values decreased significantly to those of thiamine deficiency. The thiamine pyrophosphate (TPP) levels in the blood dropped from the 1st to the 14th day, whereas the alphaETK rose accordingly and the pyruvate levels showed a delayed rise. Total thiamine content of the blood and thiamine excretion in the urine only showed significantly different values when comparing the 1st and the 14th day. There was no dependency of thiamine excretion on urinary output. Clinical symptoms of thiamine deficiency could be demonstrated in no case.

Biochemical assessment of thiamin status in patients with neurosis.

The thiamin status of 65 patients with neurosis was studied soon after their admission to the psychiatric department; 49 healthy persons were also studied. In comparison with the control group, the patients with neurosis had a twice as low thiamin excretion and a 22% lower erythrocyte transketolase (p less than 0.001), while their blood pyruvate and pyruvate excretions were 31-38% higher (p less than 0.001).

The Effect of the Determination of the Basal Metabolism of College Women on their Urinary Excretion of Thiamine

The Effect of the Determination of the Basal Metabolism of College Women on their Urinary Excretion of Thiamine

Erratum to : The Effect of the Determination of the Basal Metabolism of College Women on their Urinary Excretion of Thiamine

Erratum to : The Effect of the Determination of the Basal Metabolism of College Women on their Urinary Excretion of Thiamine

Biological activities of -ketovinyl thioether type thiamines and related compounds.

β-Ketovinyl thioether type thiamines and the related compounds have been examined on thiamine activity as well as thiamine liberation in vitro and in vivo. Sixteen compounds showed more or less vitamin activity, of which the most active ones were BD 108 and BD 81 with about 70% of the activity of thiamine HCI, while BD 101 and BD 142 showed no activity. BD 99, BD 108, and BD 112 with higher thiamine activity were converted into thiamine by incubation with glutathione. Urinary excretions of thiamine was significantly increased following intraperitoneal injection of these derivatives. A correlation was recognized between thiamine activity and urinary excretion of thiamine.

Thiamin, riboflavin, and pyridoxine excretion during acute starvation and calorie restriction

Daily excretion of thiamin and vitamin B6in micrograms per gram creatinine were in the low-to-deficient ranges established by the ICNND during the calorie restriction period, indicating rapid depletion of body stores. Although riboflavin excretion decreased during the latter days of calorie restriction (studies I and II), these values remained in the high range of acceptability. The elevated excretions of riboflavin are indicative of adequate reserves and catabolism of body protein for use as energy, or both. These data suggest that under conditions of calorie restriction, the daily minimal allowances of vitamins B1, B2, and B6are influenced by the calorie, vitamin, and protein intakes, the degree of negative nitrogen balance, and the subsequent protein catabolism.

Transketolase Activity and Urinary Excretion of Thiamin in the Assessment of Thiamin-Nutrition Status of Indians

Transketolase Activity and Urinary Excretion of Thiamin in the Assessment of Thiamin-Nutrition Status of Indians

Metabolism of Thiamine and Thiamine Tetrahydrofurfuryl Disulfide to 4-Methylthiazole-5-Acetic Acid in Conventional and Germfree Rats under Various Dosing Conditions

The urinary excretion of thiamine and 4-methylthiazole-5-acetic acid was studied in both conventional and germfree rats under various dosing conditions of thiazole-2-14C-labeled thiamine or thiamine tetrahydrofurfuryl disulfide. The urine was fractionated by Amberlite CG-50 chromatography and the thiazole acid was determined by the isotope dilution method. Thiamine, in an oral dose larger than 1.5 mg/rat, was predominantly excreted in the urine after conversion to the thiazole acid, whereas most of the injected thiamine was eliminated unchanged. The thiamine moiety of thiamine tetrahydrofurfuryl disulfide was also converted to the thiazole acid upon oral ingestion but less was excreted as the thiazole acid and more as the unchanged thiamine, comparing with the administration of thiamine. Time course study on the urinary metabolite pattern showed that most of the thiazole acid was excreted during the first 3 hours after oral ingestion of both vitamins. The thiazole acid was also identified as a metabolite of thiamine in germfree rats and there was no essential difference in the urinary metabolite pattern between conventional rats and germfree ones. This finding indicates that intestinal microflora are not primarily responsible for the conversion of thiamine to the thiazole acid in the rat.

Catabolism of 14C-Thiazole-labeled Oxythiamine and Its Effects on Thiamine Catabolism in the Rat

The metabolism of oxythiamine and its effects on thiamine metabolism were studied. Three groups of six rats each were injected daily with 40 μg 14C-thiamine, 40 μg 14C-thiamine + 80 μg oxythiamine, or 40 μg thiamine + 80 μg 14C-oxythiamine. Injections were continued for 8 to 20 weeks after which time the urinary excretions of thiamine and oxythiamine metabolites were studied. Under these conditions oxythiamine was less susceptible to destruction by opening of the thiazole ring than was thiamine. Oxythiamine was poorly retained by the rat tissue but enhanced the excretion of thiamine. Injection of somewhat higher oxythiamine-to-thiamine ratios (4:1, 6:1) resulted in a decrease in the amount of 14CO2 generated from thiamine and the urinary excretion of thiamine and its metabolites. Higher ratios (8:1, 10:1) had less effect. Oxythiamine yielded only about half as many urinary metabolites as thiamine. One product of oxythiamine metabolism appears to be thiamine itself but the amount converted is extremely low and is of no apparent benefit to the rat.

Catabolism of 14C-Labeled Thiamine by the Rat as Influenced by Dietary Intake and Body Thiamine Stores

Whether the rate of thiamine catabolism is influenced by the extent of body stores was investigated. Three groups of weanling rats were injected with 8, 40, or 100 µg 14C-thiazole thiamine until their stores were considered to be in equilibrium with intake. The excretion of urinary thiamine (with Lactobacillus viridescens), urinary thiamine metabolites (radioactivity) and 14CO2 was measured. The magnitude of the excretion of 14CO2 correlated well both with thiamine intake and thiamine levels in liver, kidney and muscle. No correlation, however, was observed with brain thiamine levels. The excretion of thiamine metabolites in urine showed an excellent correlation with intake but urinary thiamine per se was a poor index of intake. The excretion of urinary radioactivity after a single injection of radioactive thiamine gave some insight into body stores but under these conditions, 14CO2 was not detected. Because a stoichiometric relationship between caloric intake and thiamine metabolism was not observed, it is suggested that the destruction of thiamine does not occur primarily during its participation in energy-yielding reactions.

Biochemical Alterations in Thiamine Deficiency—Their Interpretation

In evaluating thiamine nutritional states, it would appear justified to determine, whenever feasible, not only thiamine excretion in the urine, but also erythrocyte transketolase activity. Determination of an appropriate thiamine-dependent enzyme system reflects the metabolism of the vitamin at the cellular and molecular level. Urinary thiamine levels can provide information as to the adequacy of the dietary intakes, but do not necessarily evaluate accurately a marginal deficiency. Determinatons for pyruvic acid and other metabolites in blood or urine can provide evidence of a thiamine insufficiency, particularly when clinical signs are evident. Determinations of free thiamine in plasma do not necessarily reflect a direct relationship to the level in the blood and tissues. Erythrocyte or leukocyte thiamine values apparently show a more direct relationship to tissue content. It is for this reason that erythrocyte transketolase activity appears to provide information as to tissue reserves of thiamine and reflects a direct functional evaluation at the cellular level. Consequently, the transketolase activity assay makes it possible to differentiate with reasonable accuracy between hypovitaminosis and a sufficient thiamine intake, as well as between hypovitaminosis and avitaminosis thiamine. Biochemical changes may precede clinical manifestations of a disease situation. Such changes may have prognostic value. Other biochemical changes, such as lowered urine or plasma levels of thiamine may indicate only low nutrient intakes and not reflect any metabolic abnormalities. However, plasma or urine thiamine levels of a certain critical level, if continued without increased dietary intakes and concomitant plasma or urinary increases, would lead to metabolic abnormalities detected by other biochemical means. Clinical manifestations may still not occur at this state of the deficiency. In other instances, biochemical changes occur simultaneously with clinical manifestations. Such tests perhaps could be improved in sensitivity in order to detect earlier existence of deficiency alterations. However, even so, such tests can corroborate a tentative clinical diagnosis. Not all biochemical tests that may be developed for the clinical laboratory can be used for nutritional survey work, for numerous reasons, including technical, physical, and economical. Nevertheless, an attempt should be made to devise methods that may receive as broad an application and use as possible. Undoubtedly, the transketolase activity assay procedure could be developed into a more routine test with further study. In certain instances, particularly where endemic vitamin B1 deficiency occurs, physical performance and mental performance evaluations need to be incorporated into the biochemical tests in an attempt to enhance the sensitivity and specificity of the methods. Early detection by biochemical means appears essential in infantile beriberi in order to employ corrective measures before death ensues.

Alterations in Liver Enzyme Activities and Blood and Urine Metabolite Levels during the Onset of Thiamine Deficiency in the Dairy Calf

A combination of physiological, clinical and enzymatic criteria was used to characterize the onset of thiamine deficiency in male Holstein calves fed a purified diet lacking thiamine. Deficiency symptoms appeared between 27 and 48 days after eliminating thiamine from the diet and 24 to 45 days after thiamine excretion had decreased to below 0.05 mg/day. Concomitantly with the appearance of overt deficiency symptoms, blood pyruvate and lactate levels increased from 1 and 15 mg/100 ml to 5 and 100 mg/100 ml, respectively; urinary pyruvate excretion increased from 15 mg/day to over 50 mg/day. Average blood hemoglobin and hematocrit levels were significantly depressed, 16 and 22%, respectively. The activities of transketolase and anaerobic pyruvate dehydrogenase decreased to 50 and 30% of control values. Aldolase activity increased at the time of the clinical symptoms relative to that of controls, whereas malic enzyme, isocitrate dehydrogenase, and glucose-6-phosphate dehydrogenase activities apparently were not altered. Refeeding thiamine corrected all the deficiency symptoms.

Some Preliminary Biochemical Findings in Junior High School Children in Syracuse and Onondaga County, New York

Some Preliminary Biochemical Findings in Junior High School Children in Syracuse and Onondaga County, New York

Reversal of selective toxicity of (-)-alpha-lipoic acid by thiamine in thiamine-deficient rats.

INTRAPERITONEAL injection of (±)-α-lipoic acid has been reported to be toxic to thiamine-deficient rats1. Development of the toxic effect was prevented by simultaneous injection of 100 µg of thiamine hydrochloride. It was also noticed that (±)-α-lipoic acid, unlike neopyrithiamine, had no effect on thiamine excretion. The toxicity of (±)-α-lipoic acid to thiamine-deficient rats therefore could not be related to the depletion of the thiamine reserves present in the organs of thiamine-deficient animals. Obviously, the results obtained from the use of the racemic form of lipoic acid could not reveal whether both or one of the isomers had been responsible for the toxic effects in the deficient animals. In order to clarify the relative toxicity of the isomers of lipoic acid in thiamine-deficient rats, the experiments were repeated with the natural and unnatural isomers of α-lipoic acid. The preparation of pure (+)-α-lipoic acid was accomplished from (+)-6,8-dichlorooctanoic acid (−)-ephedrine salt2. However, the (−)-α-lipoic acid was found to be contaminated with 15–20 per cent of the dextro-rotatory enantiomorph2. Therefore, the pure (−)-α-lipoic acid was synthesized from the purified (−)-6,8-dichlorooctanoic acid (+)-ephedrine salt. This was obtained after converting a sample of (−)-6,8-dichlorooctanoic acid (−)-ephedrine salt into the (+)-ephedrine salt. (The (−)-6,8-dichlorooctanoic acid (−)-ephedrine salt was generously supplied by Dr. W. J. Wayne of Du Pont.)

Excretion of Thiamine and its Metabolites in the Urine of Young Adult Males Receiving Restricted Intakes of the Vitamin

Eight young men consuming a 2800-kcal diet consisting of 80 g protein, 100 g fat and 400 g carbohydrate and providing 0.11 to 0.18 mg thiamine/day, developed clinical symptoms of thiamine deficiency in 9 to 27 days. Thiamine excreted in the urine decreased to less than 50 µg/day at the sixth day and to undetectable levels by the eighteenth day of depletion. Low-level repletion (0.54 to 0.61 µg/day) for 12 days failed to produce detectable levels of thiamine in the urine. Red blood cell transketolase activity declined with progressive thiamine deficiency and returned to normal levels with low-level repletion. The excretion of the pyrimidine and thiazole moieties of thiamine as metabolites of the vitamin appeared to increase above the levels found with the use of a diet with sufficient thiamine (about 2 mg/day), and was reduced to control levels following low-level repletion. The pyrimidine moiety in the deficient individual appears to be further catabolized. There appears to be a body store of thiamine which is utilized during a period of deficient intake. Serum cholesterol, nonesterified fatty acids, blood phospholipids, creatinine and hematocrit did not change appreciably during thiamine deficiency. The biochemical pattern for thiamine deficiency in human adults is described.