Excretion of riboflavin

Fig. 10 Urinary excretion of riboflavin (A, B) and ascorbic acid (C, D) in humans as a function of oral dose. Graphs A and C illustrate the nonlinear dependence of absorption on dose, which is suggestive of a saturable specialized absorption process. Graphs B and D represent an alternative graph of the same data and illustrate the reduced absorption efficiency as the dose increases. (Graphs A and C based on data in Ref. 39 and graphs B and D based on data in Ref. 40.)...

Horwitt, M. K., Harvey, C. C., Hills, 0. W. Liebert, E. (1950) Correlation of urinary excretion of riboflavin with dietary intake and symptoms of ariboflavinosis. J. Nutr. 41, 247-64. 

There is no evidence of any significant storage of riboflavin in addition to the limited absorption, any surplus intake is excreted rapidly thus, once metabolic requirements have been met, urinary excretion of riboflavin and its metabolites reflects intake until intestinal absorption is saturated. In depleted animals, the maximum growth response is achieved with intakes that give about 75% saturation of tissues, and the intake to achieve tissue saturation is that at which there is quantitative urinary excretion of the vitamin. 

Under normal conditions, about 25% of the urinary excretion of riboflavin is as the unchanged vitamin, with a small amount as a variety of glycosides of riboflavin and its metabolites. Riboflavin-8-a-histidine andriboflavin-8-a-cysteine arising from the catabofism of enzymes in which the coenzyme is covalently bound are excreted unchanged. 

Table 7.2 Urinary Excretion of Riboflavin Metabolites % of Total ...

The phenothiazines, such as chlorpromazine, used in the treatment of schizophrenia, the tricyclic antidepressant drugs such as imipramine and amitryp-tUine, antimalarials such as quinacrine, and the anticancer agent adriamycin are structural analogs of riboflavin (see Figure 7.6) and inhibit flavokinase. In experimental animals, administration of these drugs at doses equivalent to those used clinically results in an increase in the EGR activation coefficient (Section 7.5.2) and increased urinary excretion of riboflavin, with reduced tissue concentrations of riboflavin phosphate and FAD, despite feeding diets providing more riboflavin than is needed to meet requirements (Pinto et al., 1981). 

Clinical signs of riboflavin deficiency are seen at intakes below about 1 mg per day. At intakes below about 1.1 mg per day, there is very little urinary excretion of riboflavin thereafter, as intake increases, there is a sharp increase in excretion. Up to about 2.5 mg per day, there is a linear relationship between intake and excretion. At higher levels of intake, excretion increases sharply, reflecting active renal secretion of excessive vitamin (Section 7.2.5). 

Indices of Vitamin E Nutritional Status Reference Intakes of Vitamin K Indices of Thiamin Nutritional Status Reference Intakes of Thiamin Tissue Flavins in the Rat Urinary Excretion of Riboflavin Metabolites... 

Rats fed a riboflavin-deficient diet with 10% glucose lost weight. When, however, the glucose was replaced with sorbitol, the rats grew well for the duration of the experiment and developed no signs of deficiency (Medley and Yudkin, 1959). Haenel et al. (19.59) showed that the urinary excretions of riboflavin in rats was increased when their diets contained 10% or 20% sorbitol. 

In a small study of children on PHT, their mean urinary excretion of riboflavin was low, i.e. 14% of dietary intake. This may indicate riboflavin deficiency (Lewis et at. 1998). Patients on inducer AEDs (PHT, PB, PRD and CBZ) have low plasma riboflavin (Apeland et at. 2003 Krause et at. 1988). Low plasma riboflavin may indicate increased risk of vitamin B2 deficiency. Furthermore, patients with low plasma riboflavin also have elevated plasma flavin nucleotides (Apeland et at. 2003). 

The urinary excretion of riboflavin is decreased in human deficiency, both in 24-hr. periods and after administration of test doses of riboflavin. Because of the close relationship between retention of riboflavin and retention of protein, excretion data must be interpreted with caution. In starvation and in conditions associated with negative nitrogen balance, riboflavin excretion is increased. 

Riboflavin and riboflavin phosphate that are not bound to plasma proteins are filtered at the glomerulus. Renal tubular resorption of riboflavin is saturated at normal plasma concentrations. There is also active tubular secretion of the vitamin urinary excretion of riboflavin after high doses can be two- to threefold greater than the glomerular filtration rate. 

The amormt of absorbed riboflavin that can remain within the body and the circulation (in blood plasma) is strictly regulated by glomerular and tubular filtration and tubular reabsorption in the kidneys. The latter is an active, saturable, sodium-dependent transport process, with characteristics similar to those of active transport in the gastrointestinal tract. It is responsible for the very sharp and characteristic transition between minimal urinary excretion of riboflavin at low intakes, and a much higher level of excretion, proportional to intake, at higher intakes. This transition point has been extensively used to define and to measure riboflavin status and requirements (see below), and to permit studies of intestinal absorption in vivo (see above). Excretion of riboflavin is affected by some chemicals (such as boric acid, which complexes with it), and by certain diseases and hormone imbalances. 

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