Kidneys thiamin excretion

There is no evidence of any toxic effect of high intakes of thiamin, although high parenteral doses have been reported to cause respiratory depression in animals and anaphylactic shock in human beings. Hypersensitivity and contact dermatitis have been reported in pharmaceutical workers handling thiamin. As noted in Section 6.2, absorption of dietary thiamin is limited, and no more than about 2.5 mg (10 /.tmol) can be absorbed from a single dose free thiamin is rapidly filtered by the kidneys and excreted. 

PAM Cl is rapidly and almost completely excreted unchanged by the kidneys 80% to 90% of an intramuscular or intravenous dose is excreted in 3 hours,146 probably by an active tubular excretory mechanism (its renal clearance is close to that of p-aminohippurate147), with a half-time of about 90 minutes.146 Both clearance and amount excreted are decreased by heat, exercise, or both.148 Thiamine also decreases excretion (presumably by blocking tubular excretion), prolongs the plasma half-life, and increases the plasma concentration for the duration of thiamine activity147 150 some151 question the therapeutic benefit of thiamine, however. 

There are only a few studies concerning the degradation and elimination of thiamin in animals. Most excess thiamin is eliminated as such by the kidneys. In a couple of older studies (Neal and Pearson 1964 Pearson et al. 1966), radioactive thiamin was administered in rats and the urines were analysed. Several radioactive degradation products of thiamin (2-methyl-4-amino-5-pyrimidine carboxylic acid and 4-methyl-thiazole-5-acetic acid), resulting from the cleavage between the thiazole and the pyrimidine moieties, were excreted in the urine. Other products were also detected but not identified. No enzymes specifically involved in thiamin degradation in mammals have been identified. 

Thiamin is the least stored of all the vitamins. The adult human body contains approximately 30 mg. Of the thiamin stored in the body, about 80% is thiamin pyrophosphate, about 10% is thiamin triphosphate, and the remainder is thiamin monophosphate. The liver, kidneys, heart, brain, and skeletal muscles have somewhat higher concentrations than the blood. If the diet is deficient, tissues are depleted of their normal content of the vitamin ini to 2 weeks, so fresh supplies are needed regularly to provide for maintenance of tissue levels. Body tissues take up only as much thiamin as they need with the need increased by metabolic demand (fever, increased muscular activity, pregnancy, and lactation) or by composition of the diet (carbohydrate increases the need for thiamin, while fat and protein spare thiamin). Because thiamin is water soluble, most of the vitamin not required for day-to-day use is excreted in the urine. This means that the body needs a regular supply, and that unneeded intakes are wasted. With a well-balanced diet, approximately 0.1 mg is normally excreted every 24 hours. However, the amount excreted in the urine decreases as the intake becomes inadequate and increases as the intake exceeds body needs because of this, the most widely used biochemical method to assess thiamin status in individuals is the measurement of the vitamin in the urine. 

Likewise, in most other tissues, there is very little free thiamin and it is mostly present as TDP (90%) in coenzymes bound to respective enzymes and a smaller amount of TTP (10%) in nervous tissues. The concentration of thiamin in specific tissues is on the order of 2-3 pg/g for heart muscle 1 pg/g for brain, liver, and kidney and 0.5 pg/g in skeletal muscle. Thiamin supplements can increase these concentrations slightly and prolonged febrile illnesses are likely to reduce them. Thiamin is mainly excreted intact in the urine but there are small amounts of thiochrome (Figure 2) and other thiazole and pyrimidine metabolites. A linear relationship exists between intake and excretion of thiamin until intake falls to an amount approaching minimum requirements when excretion decreases rapidly indicating a renal conservation mechanism. 

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