Riboflavin urinary excretion

E. The patient has demonstrated a deficiency in riboflavin (urinary excretion of less than 30 pg/mg creatinine is considered clinically deficient). Riboflavin is a component of the cofactor FAD (flavin adenine dinucleotide), which is required for the conversion of succinate to fumarate by succinate dehydrogenase. 

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.)...

Najjar and co-workers58 found on diets furnishing only 60 to 90 ig. of riboflavin per day that the urinary excretion (human) was about twice the intake, and the fecal excretion was about 5 to 6 times the intake. This indicates that for certain individuals on certain diets synthesis of riboflavin by intestinal organisms is sufficient to take care of the entire riboflavin needs. The authors conclude that riboflavin may not be a dietary essential in all cases. If this finding is valid, it certainly points to the probability that human needs vary widely because riboflavin deficiencies in human beings have been observed a great many times on many different types of diets. 

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). 

Two methods of assessing riboflavin status are generally used urinary excretion of the vitamin and its metabolites, and activation of EGR. Criteria of riboflavin adequacy are shown in Table 7.5. 

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). 

On the basis of depletion/repletion studies, the minimum adult requirement for riboflavin is 0.5 to 0.8 mg per day. In population studies, values of the EGR activation coefficient <1.3 are seen in subjects whose habitual intake of riboflavin is 1.2 to 1.5 mg per day. At intakes between 1.1 to 1.6 mg per day urinary excretion rises sharply, suggesting that tissue reserves are saturated. On the basis of such studies, reference intakes (see Table 7.6) are in the range of 1.2 to 1.6 mg per day (Bates, 1987a, 1987b). 

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... 

One of the rare studies of the excretion of tryptophan metabolites, both spontaneous and after load, by patients with hematological disorders, is the work of Altman and Miller (A4). They reported an elevated urinary excretion of anthranilic acid in 9 children with an unusual congenital anemia referred to as erythrogenesis imperfecta (A4). Oral administration of 1.6 g L-tryptophan to one patient led to increased urinary excretion of anthranilic acid as well as other intermediary metabolites of tryptophan. Massive doses of riboflavin per os during 30 days caused no change in the hematological status, but there appeared to be a decrease in the amount of anthranilic acid excreted. 

Urinary excretions of nicotinic acid metabolites and 2-pyridone, as well as of 4-pyridoxic and xanthurenic acids were determined in 15 South African Bantu pellagrins before and after tryptophan administration (P13). Red blood cell riboflavine levels and serum glutamic-oxalacetic transaminase levels were also measured. The authors discussed the apparent inability of the pellagra patients to convert tryptophan to nicotinic acid as indicated by their low excretion of nicotinic acid metabolites before and after tryptophan load. The possibility that the subjects were also suffering from a riboflavine deficiency was also discussed. 

Morrison A, Chapman D, Campbell J. Further studies on the relation between in vitro disintegration time of tablets and the urinary excretion rates of riboflavin. J Am Pharm Assoc 1959 48 634-637. 

Urinary excretion of hydroxykynurenine, rather than its phosphate, is not surprising in view of the widespread occurrence of phosphatases in many organs including the kidney. Riboflavin might therefore be concerned with a phosphorylative rather than a purely oxidative function, and the increased xanthurenic acid excretion in riboflavin deficiency can be plausibly explained on this basis (142). It is of interest that in Knox s early work on the quinine-oxidizing system of liver (477) the partially purified enzyme which hydroxylated quinolines appeared to be a flavo-protein. 

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. 

Watson and Yudkin (1959) investigated the urinary excretion of thiamine, riboflavin, and niacin (as JV-methylniacinamide) in one subject... 

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