Niacin vitamin excretion

Niacin (vitamin B3) is converted in the body to the amide, which is incorporated into niacinamide adenine dinucleotide (NAD). It is excreted in the urine unmodified and as several metabolites. 

Vitamins are a chemically and functionally inhomogeneous group of biomolecules. As a gross classification distinction is usually made between (1) fat-soluble and (2) water-soluble vitamins. Owing to their insolubility in water the fat-soluble vitamins A, D, E, and K can be accumulated in fat tissue and excessive intake causes hypervitaminoses. The water-soluble vitamins - vitamin Bj, vitamin B2, niacin, vitamin Bg, folic acid, pantothenic acid, biotin, vitamin B12, and ascorbic acid - can generally only be stored in a small amount and intake exceeding actual need is excreted in the urine. 

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. 

Vitamins and Minerals. Milk is a rich source of vitamins and other organic substances that stimulate microbial growth. Niacin, biotin, and pantothenic acid are required for growth by lactic streptococci (Reiter and Oram 1962). Thus the presence of an ample quantity of B-complex vitamins makes milk an excellent growth medium for these and other lactic acid bacteria. Milk is also a good source of orotic acid, a metabolic precursor of the pyrimidines required for nucleic acid synthesis. Fermentation can either increase or decrease the vitamin content of milk products (Deeth and Tamime 1981 Reddy et al. 1976). The folic acid and vitamin Bi2 content of cultured milk depends on the species and strain of culture used and the incubation conditions (Rao et al. 1984). When mixed cultures are used, excretion of B-complex vita-... 

It is clear from Equation (19.4) that saturated fat, not cholesterol, is the single most important factor that raises serum cholesterol. Some cases of hyperlipoproteinemia type IV (high VLDL) respond to low-carbohydrate diets, because the excess of VLDL comes from intestinal cells, where it is produced from dietary carbohydrate. Resins, such as cholestyramine and cholestipol, bind and cause the excretion of bile salts, forcing the organism to use more cholesterol. Lovastatin decreases endogenous cholesterol biosynthesis (see later), and niacin (nicotinic acid) apparently decreases the production of VLDL and, consequently, LDL. It also results in an HDL increase. Antioxidants that inhibit the conversion of LDL to oxidized LDL have also been used with some success. These are high doses of vitamin E and the drug probucol. 

Kelsay J, Miller LT, and Linkswiler H (1968b) Effect of protein intake on the excretion of quinolinic acid and niacin metabolites by men during vitamin Bg depletion. Journal of Nutrition 94,27-31. 

That nongrowing animals require niacin implies that it is lost from the body either as intact niacin or as a modified or breakdown product of the vitamin. An amount of niacin equivalent to nearly 90% of our daily intake is excreted in the forms of N-methyl-2-p)nidone-5urinary metabolites can be used to assess niacin status. Loss of the normal quantity in the urine each day indicates that the supply in the diet is adequate. In humans, the healthy adult excretes 4 to 6 mg of N-methyl-nicoti-namide per day. An abnormally low level indicates that the dietary intake is not adequate. Measurement of urinary niacin metabolites has proven useful in determining the amoimt of niacin available in a variety of foods. The body s ability to use niacin in different foods may vary even if the foods contain identical quantities of the vitamin. One contributing factor to the low availability of niacin is the occurrence of the vitamin in the "bound form," as mentioned earlier. Excretion of normal levels of pyridone, for example, depends not only on normal absorption of the vitamin from the diet, but also on its conversion to NAD or NADP, followed by catabolism to the metabolite. 

Niacin (nicotinic acid pyridine-3-carboxylic acid) and nicotinamide are precursors of NAD+ and NADP+ (Figure 38-19). Niacin occurs in meat, eggs, yeast, and whole-grain cereals in conjunction with other members of the vitamin B group. Little is known about absorption, transport, and excretion of niacin and its coenzyme forms. A limited amount of niacin can be synthesized in the body from tryptophan, but it is not adequate to meet metabolic needs. 

If the dietary levels of niacin and tryptophan are insufficient, the condition known as pellagra results. The symptoms of pellagra are dermatitis, diarrhea, dementia, and, finally, death. In addition, abnormal metabolism of tryptophan occurs in a vitamin B6 deficiency. Kynurenine intermediates in tryptophan degradation cannot be cleaved because kynureninase requires PLP derived from vitamin B6. Consequently, these intermediates enter a minor pathway for tryptophan metabolism that produces xanthurenic acid, which is excreted in the urine. 

Fig. 39.19. Degradation of tryptophan. One of the ring carbons produces formate. The nonring portion forms alanine. Kynurenine is an intermediate, which can be converted to a number of urinary excretion products (e.g., xanthurenate), degraded to CO2 and acetyl CoA, or converted to the nicotinamide moiety of NAD and NADP, which also can be formed from the vitamin niacin.

The status of niacin in relation to most other vitamins is different as it can be synthesized by humans to some extend from tryptophan. Body status determination has been based on the determination of urinary excretion of niacin metabolites, predominately N-methyl-2-pyridone-5-carboxylamide and N-methyl-nicotinamide. The ratio of these compounds has been used as indicator of niacin status. Recent studies suggest that the determination of the two niacin-derived coenzymes, NAD and NADP, in erythrocytes, and their ratio are more reliable indicators of niacin status. However, a broadly accepted and easy to use determination method does not seem to exist. 

Tsuji, T., Fukuwatari, T., Sasaki, S., and Shibata, K., 2010. Urinary excretion of vitamin Bl, B2, B6, niacin, pantothenic acid, folate, and vitamin C correlates with dietary intakes of free-living elderly, female Japanese. Nutrition Research. 30 171-178. 

Hydroxyanthranilic Acid. Since kynurenic and xanthurenic acids were eliminated as being precursors of nicotinic acid because tracer experiments showed that the alanyl side chain was lost prior to the formation of the vitamin, it appeared plausible to assume that 3-hydroxyanthranilic acid was an intermediate immediately following 3-hydroxykynurenine. In support of this, it has been found that it can replace niacin in the diet of the rat, but its activity is of the order of tryptophan rather than that of niacin. Furthermore, feeding 3-hydroxyanthranilic acid yields an increased urinary excretion of N -methyl nicotinamide. ... 

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. 

K Shibata, H Taguchi, Y Sakakibara. Comparison of the urinary excretion of niacin and its metabolites in various mammals. Vitamins (Japan) 63 369-372, 1989. 

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. 

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