Thiamin status

Thiamin that is not bound to plasma proteins is rapidly filtered at the glomerulus. Diuresis increases the excretion of the vitamin, and patients who are treated with diuretics are potentially at risk of thiamin deficiency. Some of the diuretics used in the treatment of hypertension may also inhibit cardiac (and other tissue) uptake of thiamin, thus further impairing thiamin status, which may be a factor in the etiology of heart failure (Suter and Vetter, 2000). 

Thiamine status is influenced by the diet and by a variety of other factors, including its bioavailability in food products, ethanol consumption, the presence of antithiamine factors in the diet as well as folate and protein status. Ingested thiamine is fairly well absorbed, rapidly converted to phosphorylated forms, stored poorly, and excreted in the urine in a variety of hydrolyzed and oxidized products (TanPhaichitr et al., 1999). 

The most reliable method for assessing thiamin status involves the measurement of red blood cell transketolase. This enzyme is measured with and without the addition of TPP to the enzyme assay mixtures. In dietary thiamin deficiency, synthesis of transketolasc continues, but conversion of the apoet zyme to the holoenzyme in the cell is inhibited, resulting in the accumulation of the enzyme in the apoenzyme form. Addition of TPP to cell homogenates results in the conversion of apoenzyme to holoenzyme. This conversion can easily be detected by enzyme assays. The amount of shmulation of enzyme activity by the added TPP is used to assess thiamin status. A deficiency is indicated by a shmulation of over 20%, The TPP-dependent stimulation, using red blood cells from normal subjects, ranges from 0 to 15%. 

At one time it was thought that plasma pyruvate levels could be used to assess thiamin status. Plea.se rat Inna li .c this test. State how it would work. Then eKplain how the test could be influenced by factors other than thiamin status. (Sec Chong, 1970.)... 

Methylcobalamin, 516 5-Melhyl-cytosine, deaminatitm, 894 Methylglyoxal, 836 Methylmalonic acid (MMA), 434, 522 MethylmalcHiy. CoA, 434, 517, 518 Mevalonic acid, 327, 328 Mg-ATP complex, 795-796 Micelles, 25,27-29 MLcroaulophagy, 444 Microbiological assays, 508 biotin determination, 541 folate status by, 509 thiamin status, 607 Microcytic anemia, 5H Microsomal ethanol-oxidizing system, 247 Microvilli, 58 Milk... 

Schiano TD, Klang MG, Quesada E, Scott F, Tao Y, Shike M. Thiamine status in patients receiving long-term home parenteral nutrition. Am J Gastroenterol 1996 91(12) 2555-9. 

Thiamin status has been assessed by direct tests involving the measurement of thiamin levels in the blood or urine. The vitamin can be assayed by the thiochrome method or by microbiological assays. The disadvantage of these methods is that thiamin levels in normal individuals can vary greatly. The test organism used for microbiological assays may be Lactobacillus viridescens or Lactobacillus fermenti. 

Historically, assessment of thiamine status was by animal bioassay (the correction of bradycardia in thiamine-deficient rats) and later by microbiological assays using the fungus Phycomyces hlakesleeanus, yeast fermentation, or bacteria of the Staphylococcus, Streptococcus, or Lactobacillus species. Some bacterial microbiological assays are still in use in the food industry. Early chemical methods were often based upon the production of a fluorophore, thiochrome, when thiamine is oxidized with ferricyanide in alkaline solution, a property that is used in some modern chromatographic methods. 

Determination of the urinary excretion of thiamine in a 4-hour specimen, especially with comparison of excretion before and after a test load, is helpful in differentiating among extremes of thiamine status. However, as with most assessments based on amount of water-soluble vitamins in urine, excretion can be influenced considerably by dietary intake, absorption, and other factors. Measurements of certain urinary metabolites, notably thiamine acetic acid, have also been suggested as reflecting thiamine status. ... 

Baines M, Davies G. The evaluation of erythrocyte thiamin diphosphate as an indicator of thiamin status in man, and its comparison with erythrocyte transketolase activity measurements. Ann Clin Biochem 1988 25 (Pt 6) 698-705. 

Boros LG. Population thiamine status and varying cancer rates between western, Asian and African countries. Anticancer Res 2000 20 2245-8. 

Frank T, et al. Assessment of thiamin status in chronic renal failure patients, transplant recipients and hemodialysis patients receiving a multivitamin supplementation. Int J Vitam Nutr Res 2000 70 159-166. 

Briggs, M. H., and Briggs, M., Thiamine status and oral contraceptives. Contraception 11, 151-154 (1975). 

Brady, J.A., Rock, C.L., and Horneffer, M.R. (1995). Thiamin status, diruretic medications, and the management of congestive heart failure. J. Am. Diet. Aiioc. 95 541-544. 

Standard methods for assessment of thiamine status used to be determination of erythrocyte transketolase (a-ETK) activity (EC 2.2.1.1) with and without stimulation of this enzyme by addition of TDP cofactor (TOP TK effect). A TDP TK effect >15% is considered to show some degree of deficiency, whereas values >22% are considered to indicate severe deficiency. Technical difficulties, including standardization of the assay, instability of the enzyme during storage, and various conditions possibly influencing apoenzyme concentrations led to an increasing use of direct determination of TDP in whole blood, e.g., by HPLC in order to assess thiamine status. The HPLC assay is more robust and easier to perform. Thiamine... 

While thiamine deficiency is usually associated with the Wernicke-Korsakoff syndrome, thiamine status is also important in the elderly. 

Though the classic syndrome is not apparent, uncontrolled studies have indicated improvement in the confusion of older patients with thiamine replacement (Mitra, 1971). In two groups of older orthopedic patients studied by Older and Dickerson (1982), thiamine levels were correlated with clinical confusion and sleepiness. The stress of major surgery led to consistent deterioration of thiamine status. While alcoholics with Wer-nicke-Korsakoff syndrome respond poorly to therapy, nutritionally depleted prisoners showed good memory deficit response to thiamine (Lishman, 1981). Perhaps in the alcoholics, recurrent subclinical deficiency led to permanent structural pathology, whereas the prisoners and elderly were subject to only one episode. If this was the case, more vigorous attempts at dietary supplementation should be made to prevent development of the full-blown syndrome. 

Gangolf, M., Czerniecki, J., Radermecker, M., Detry, O., Nisolle, M., Jouan, C., Martin, D., Chantraine, F., Lakaye, B., Wins, P., Grisar, T., and Bettendorlf, L., 2010a. Thiamine status in humans and content of phosphorylated thiamine derivatives in biopsies and cultured cells. PLoS One. 5 el3616. 

Levels of excreted thiamine in urine have been measured using various techniques, including the trichrome method (based on the oxidation of thiamine) (Bessey et al. 1952), microbiological assay using Lactobacillus viridescens (Sauberlich et al. 1979), and high performance liquid chromatography (HPLC) (Roser et al. 1978). Urinary assessment of thiamine status presents several... 

ETK based methods, once considered the most reliable means of assessing thiamine status, are now considered inadequate because they only provide an indirect measure. Because transketolase activity requires thiamine, decreased transketolase activity is presumed to be due to a decrease in thiamine. However, other factors may decrease transketolase activity including decreased enzymatic binding and decreased enzyme synthesis as has been demonstrated in diseases such as diabetes (Friedrich 1988) and liver dysfunction (Feimelly et al. 1967). ETK based methods have also been criticized as unreliable, insensitive, and subject to poor precision (Bailey et al. 1994). 

The most accurate way to measure thiamine status is to quantify the biologically active form of thiamine, thiamine diphosphate, in whole blood or isolated red blood cells. 

Erythrocyte transketolase activity was the classic method to assess thiamine status. Two samples of blood are incubated with excess substrate for the pentose phosphate pathway to one is also added excess thiamine diphosphate while the other serves as the control. The amount of substrate remaining and product formed are quantified, and any enhancement in activity resulting from the added thiamine diphosphate indicates that the sample was originally deficient in thiamine to some extent. 

Cromer, B.A., Wyatt, D.T., Brandstaetter, L.A., Spadone, S., and Sloan, H.R., 1989. Thiamine status in urban adolescents effects of race. Journal of Pediatric Gastroenterology and Nutrition. 9 502 506. 

Nichols, H.K., and Basu, T.K., 1994. Thiamin status of the elderly dietary intake and thiamin pyrophosphate response. Journal of the American College of Nutrition. 13 57-61. 

O Rourke, N.P., Bunker, V.W., Thomas, A.J., Finglas, P.M., Bailey, A.L., and Clayton, B.E., 1990. Thiamine status of healthy and institutionalized elderly subjects analysis of dietary intake and biochemical indices. Age and Ageing. 19 325-329. 

Ortega, R.M., Lopez-Sobaler, A.M., Andres, P., Rodriguez-Rodriguez, E., Aparicio, A., and Bermejo, L.M., 2009. Increasing consumption of breakfast cereal improves thiamine status in overweight/obese women following a hypocaloric diet. International Journal of Food Science Nutrition. 60 69-79. 

Pepersack, T., Garbusinski, J., Robberecht, J., Beyer, L, Willems, D., and Fuss, M., 1999. Clinical relevance of thiamine status amongst hospitalized elderly patients. Gerontology. 45 96-101. 

Nutritional status assessment for thiamine is generally carried out by assaying the total thiamine in whole blood or erythrocytes, or by measuring the activity of erythrocyte transketolase before and after incubation with exogenous thiamine pyrophosphate. The latter serves as the sensitive index of thiamine nutritional status (Brin 1980). In addition to the enzymatic test, a measure of urinary thiamine in relation to dietary intake has been the basis for balance studies to assess the adequacy of intake. When thiamine excretion is low, a larger portion of the test dose is retained, indicating a tissue s need for thiamine. A high excretion indicates tissue saturation. In the deficient state, excretion drops to zero. Plasma pyruvate and lactate concentrations have also been used to assess thiamine status. 

Serum pyruvate normal thiamine status 62% low thiamine no symptoms 38% (ETK-A >20% serum pyruvate > 79 gmol/L) and gross clinical thiamine deficiency (w = 6) Barry 1985... 

Oxidized glutathione (GSSG) is reduced back to active GSH by glutathione reductase, which uses NADPH as the reducing agent. Glutathione reductase is a flavin-dependent enzyme, and its activity, or its activation after incubation with FAD, can be used as an index of vitamin status (section 11.7.4.1), in the same way as activation of transketolase by thiamin diphosphate can be used as an index of thiamin status (section 11.6.4.1). 

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