Urine riboflavin excretion

Riboflavin status is assessed by (1) determination of urine riboflavin excretion, (2) a functional assay using the activation coefficient of stimulation of the enzyme glutathione reductase by FAD, or (3) direct measurement of riboflavin or its metabolites in plasma or erythrocytes. The advantages and disadvantages of functional or direct methods have been discussed in the section on thiamine. 

Kon and his co-workers have shown that the amount of the vitamins made available by starch refection in rats is reduced when 0.5% sulfonamides are included in the diet (Coates et al., 1946 Ford et al., 1953). There is a reduction in the amounts of thiamine and riboflavin in the tissues and excreted in the feces, and of riboflavin excreted in the urine. 

Little is known of the catabolism of riboflavin in humans, but riboflavin is a normal constituent of the urine. Therefore, all the excess vitamin could be excreted without breakdown of the molecule. The vitamin is not stored consequently, administration of excessive doses of riboflavin is accompanied by increased excretion in the urine. Riboflavin is also excreted in the milk, and the riboflavin concentration in milk reflects the vitamin intake. 

Urine. The sensitive determination of riboflavin excreted into urine is of interest because it seems to be a good means for monitoring dietary intake of the vitamin. The flavin content in urine can establish the vitamin B2 status of an individual and it can be used as an index of the relative bioavailability of vitamin... 

In foods vitamin B2 occurs free or combined both as FAD and FMN and complexed with proteins. Riboflavin is widely distributed in foodstnffs, but there are very few rich sources. Only yeast and liver contain more than 2mg/100g. Other good sources are milk, the white of eggs, fish roe, kidney, and leafy vegetables. Since riboflavin is continuously excreted in the urine, deficiency is qnite common when dietary intake is insufficient. The symptoms of deficiency are cracked and red lips, inflammation of the lining of the month and tongue, mouth ulcers, cracks at the comer of the mouth, and sore throat. Overdose of oral intake present low toxicity, probably explained by the limited capacity of the intestinal absorption mechanism [417]. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

When taken up by the body, riboflavin is converted into its coenzyme forms (Chapter 25) and any excess is quickly excreted in the urine. Urine also contains smaller amounts of metabolites. The ribityl group may be cut by the action of intestinal bacteria acting on riboflavin before it is absorbed. The resulting 10-hydroxyethyl flavin may sometimes be a major urinary product.c d The related 10-formylmethyl flavin is also excreted,0 as are small amounts of 7a- and 8a- hydroxyriboflavins, apparently formed in the body by hydroxylation. These may be degraded farther to the 7a- and 8a- carboxylic acids of lumichrome (riboflavin from which the ribityl side chain is totally missing).6 A riboflavin glucoside has also been found in rat urine.f... 

Today, biochemical deficiency of riboflavin is accepted in the absence of clinical signs of deficiency. Biochemical signs of deficiency include change in the amount of the vitamin which is excreted in the urine, or change in the level of activity of a red blood cell (erythrocyte) enzyme, which is known as the erythrocyte glutathione reductase. Requirements for the vitamin are defined as that amount which will prevent both clinical and biochemical signs of deficiency. 

About 7% of dietary riboflavin is covalently bound to proteins (mainly as riboflavin-8-a-histidine or riboflavin-8-a-cysteine). The riboflavin-amino acid complexes released by proteolysis are not biologically available although they are absorbed from the gastrointestinal tract, they are excreted in the urine (Chia et al., 1978). 

Intestinal bacterial cleavage of the ribityl side chain results in the formation of 10-hydroxyethylflavin (an oxidation product of lumifiavin), lumichrome, and 7- and 8-carboxy-lumichromes, which are also excreted in the urine. Some of the lumichromes detected in urine may result from photolysis of riboflavin in the circulation. 

Riboflavin is absorbed by the gut and enters the bloodstream, where close to half of it is loosely bound to serum albumin. The main site of absorption is the ileum. As might be expected, when large doses (20- 60 mg) of riboflavin are eaten, much of the dose is promptly excreted in the urine (Zempleni et ai, 1996). The FAD CO factors based on riboflavin are called flavins enzymes using flavins as a cofactor are called flavopioteins. 

The vitamin is commercially available as riboflavin, riboflavin S-phosphate. and riboflavin S-phosphate sodium. The phosphate esters are used commercially only in multivitamin preparations, and they are hydrolyzed before absorption occurs. Ab.sorption occurs through an active transport. system in which riboflavin is phosphorylated by the intestinal mucosa during absorption. Food and bile enhance absorption. Riboflavin is distributed widely in the body, with limited stores in the liver, spleen, heart, and kidneys. Conversion to FAD occurs primarily in the liver. FMN and FAD circulate primarily protein bound. Only small amounts ( 9%) are excreted in the urine unchanged. Larger amounts can be found after administration of large doses. 

The human body cannot store riboflavin, so it is excreted in the urine. For this reason, it is not dangerous to consume large doses of riboflavin, although the consumption of large amounts of the vitamin serves no biological purpose. 

The work of Haenel et al. (1959), which has been mentioned several times, showed that rats given diets with 20% sorbitol excreted more thiamine, riboflavin, pyridoxine, and niacin in the urine. This confirms that sorbitol can increase the supply of all these substances to the animal. 

Being a water-soluble vitamin, when riboflavin intake is higher than tissue requirements, the excess is excreted in the urine, mainly as free riboflavin (6(U90%) or other metabolites, such as 7-hydroxymethylriboflavin (3-7%), 8a-sulfonylriboflavin (2-15%), 10-hydroxyethylflavin (17%), 8-hydroxy-methylriboflavin (1 %), riboflavinyl peptide ester (up to 5%), with traces of lumiflavin and, sometimes, the 10-formylmethyl- and carboxylmethylflavins (Figure 6.6). 

The kidneys are the organs for the elimination of riboflavin from mammalian organisms, maintaining the vitamin homeostasis. Riboflavin passes through the glomeruli and is transported by the tubules, where secretion or reabsorption takes place, depending on riboflavin plasma concentration. Finally, excretion is in the urine. 

Riboflavin is excreted in the urine, the output varjdng with the intake and the degree to which tissue stores are saturated. In normal persons, values range from 150 to 2000 /xg. daily. 

Pyridoxine deficiency has been induced by administration of desoxy-pyridoxine to adults receiving a diet low in B complex vitamins. Seborrheic skin lesions developed about the eyes, nose, and mouth, and cheilosis, glossitis, and stomatitis were observed. Although these findings resemble those commonly seen in riboflavin and niacin deficiency, healing was dependent on administration of pyridoxine. The deficient subjects excreted large amounts of xanthurenic acid in the urine after a test dose of tryptophan, but ability to convert tryptophan to niacin was unimpaired. 

Riboflavin is excreted in the urine, and some people seem to excrete more than others on the same intake. It is produced by some bacteria and destroyed by others. Human requirements for riboflavin have not been definitely established. The U.S. Allowance for a moderately active man (optimal maximal ) is 1.8 mg. daily in Canada 1.5 mg. daily is recommended for 160 lb. body weight. There is thus not much spread suggested by available evidence in the requirement for riboflavin, even on these two bases. Studies by Horwitt et al. (1950) suggest that minimal requirements for the prevention of clinical lesions in the adult male lie between 0.65 mg. and 0.75 mg. daily. Requirements for riboflavin are altered by exercise and also by the use of antibiotics. 

Estimates of riboflavin requirements are based on depletion/repletion studies to determine the minimum intake at which there is significant excretion of the vitamin. In deficiency there is virtually no excretion of the vitamin as requirements are met, so any excess is excreted in the urine. On this basis the minimum adult requirement for riboflavin is 0.5-0.8 mg/day. At intakes between 1.1 and 1.6mg/day urinary excretion rises sharply because tissue reserves are saturated. 

Within the mammalian cells, most of the riboflavin is converted to FAD and FMN (Fig. 5). Flavins are mainly excreted in human urine in the form of riboflavin and some catabolites, including 8a- and 7a-hydroxyriboflavin (18). 

Water soluble vitamins are generally not stored in the body, or are stored only for a limited time and the excess is excreted in the urine. Lipophilic vitamins are stored mainly in the Hver. The reserve capacity, defined as the time during which the need for the vitamin is covered by the organism reserves, is the longest for corrinoids (3-5 years) and vitamin A (1-2 years). The reserve capacity for folacin is 3-4 months, for vitamins C, D, E and K, riboflavin, pyridoxine and niacin it is 2-6 weeks, and for thiamine, pantothenic acid and biotin it is only 4-10 days. Reserve capacity is affected by the history of vitamin intake, the metabolic need for the vitamin and the health status of the individual. 

The body has limited capacity for storing riboflavin, although higher concentrations are found in the liver and kidneys than in other tissues. So, day-to-day tissue needs must be supplied by the diet Excretion is primarily via the urine, with the amount excreted related to uptake. When the intake is high, urinary excretion is high when the intake is low, excretion is low. Some riboflavin is excreted in the feces. All mammals secrete riboflavin in their milk. 

Role of Riboflavin. Riboflavin deficiency has been found to produce abnormaUties in the metabolism of tryptophan (307-311). The deficiency leads to an increased excretion in the urine of kynurenine, anthranilic acid, and kynurenic acid and its conjugates (308, 309). In liver and kidney slices riboflavin deficiency leads to a decrease in indolepyruvic acid accumulation and an increase in the production of kynurenic acid and anthranilic acid from L-kynurenine (310, 311). The deficiency was also found to... 

In experimental animals a deficiency of riboflavin impairs normal growth and causes symptoms of the skin. In man the principal symptoms of ariboflavinosis are dermatitis ( pellagra sine pellagra ), cheilosis (changes around the lips), and disorders of the eyes. The nutritional supply of the vitamin is adequate in general. Excessive amounts of riboflavin in the body are excreted in urine. 

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