Niacin status

Manson JA and Carpenter KJ (1978a) The effect of a high level of dietary leucine on the niacin status of chicks and rats. Journal of Nutrition 108,1883-8. 

Jacobson, E. L., and Jacobson, M, K. 1997). Tissue NAD as a biochemical measure of niacin status in humans. Methodf Entymol. 28D, 221-230. 

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. 

There is some interest in using the ratio of NAD/NADP in red blood cells as a convenient measure of niacin status Qacobson and Jacobson, 1997). How could this assay work Data from human studies has shown that niacin deficiency allows a decline in intracellular NAD, but a maintenance of the levels of NADP. 

At present, no blood markers are commonly used as indicators of niacin status. Most assessments of niacin nutriture have been based on measurement of the 2 urinary metabolites, N -methylnicotinamide and N -methyl-2-pyridone-5-carboxamide. Normally, adults excrete 20% to 30% of their niacin in the form of methylnicotinamide and 40% to 60% as the pyridone. An excretion ratio of pyridone to methylnicotinamide of 1.3 to 4.0 is thus normal, but latent niacin deficiency is indicated by a value below 1.0. As depletion occurs, the pyridone is absent for weeks before clinical signs are noted, and the methylnicotinamide excretion falls to a minimum at about the time that clinical signs are evident.f HPLC methods are currently the methods of choice, though some capillary electrophoresis methods have been developed. However, the measurement of 2-pyridone and N -methylnicotinamide concentrations in plasma may provide a more reliable metabolite ratio than urine measurements. A newer approach that may prove valuable is the ratio of NAD/NADP in erythrocytes and plasma tryptophan. A ratio of NAD/NADP below 1.0 would be indicative of a risk of developing niacin deficiency. ... 

Fu CS, Swendseid ME, Jacob RA, McKee RW. Biochemical markers for assessment of niacin status in... 

N -Methylnicotinamideand Ar -methyl-2-pyridone-5-carboxamide are the two metabolites that are considered sensitive measures of niacin status. 

Nicotinic acid and nicotinamide These are sometimes known by the generic term niacin. Their importance is in combination with tryptophan, as the coenzyme forms nicotinamide adenine dinucleotide (NAD + ) and nicotinamide adenine dinucleotide phosphate (NADP). HPLC is too insensitive to measure endogenous plasma levels, but the urinary metabolites N-methyl-2-pyridone-5-carboxylamide and N -methylnicotinamide can be measured to assess niacin status. Preliminary cleanup of urine by anion-exchange resins is followed by reversed-phase HPLC with UV detection. 

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. 

Kirkland, J.B., 2009. Niacin status, NAD distribution and ADP-ribose metabolism. Current Pharmaceutical Design. 15 3 11. 

Jacob, R. A., Swendseid, M.E., McKee, R.W., Fu, C.S., and Clemens, R.A., 1989. Biochemical markers for assessment of niacin status in young men urinary and blood levels of niacin metabolites. Journal of Nutrition. 119 591-598. 

Jacobson, E. L. Jacobson, M. K. Biochemical method to measure niacin status in a biological sample. U.S. Patent. 6287796, 2001 Chem. Abstr. 2001, 135, 223772. 

Preformed niacin occurs in foods either as nicotinamide (niacinamide) or as the pyridine nucleotide coenzymes derived from it, or as nicotinic acid, without the amide nitrogen, which is the form known as niacin in North America. Both nicotinamide and nicotinic acid are equally effective as the vitamin, but in large doses they exert markedly different pharmacological effects, so it is important, at least in that context, to make and maintain the distinction. In addition to the preformed vitamin, an important in vivo precursor is the amino acid L-tryptophan, obtained from dietary protein. Because the human total niacin supply, and hence niacin status, depends on the dietary tryptophan supply as well as on the amount of preformed dietary niacin and its bioavailability, it has become the accepted practice to express niacin intakes as niacin equivalents, ... 

The conversion of tryptophan to nicotinic acid in vivo is depicted in Figure 1. The rate of conversion of tryptophan to niacin and the pyridine nucleotides is controlled by the activities of tryptophan dioxygenase (known alternatively as tryptophan pyrrolase), kynurenine hydroxylase, and kynureninase. These enzymes are, in turn, dependent on factors such as other B vitamins, glucagon, glucocorticoid hormones, and estrogen metabolites, and there are various competing pathways which also affect the rate of conversion. For these reasons, a variety of nutrient deficiencies, toxins, genetic and metabolic abnormalities, etc. can influence niacin status and requirements. 

Other urinary excretion products of niacin include nicotinuric acid (nicotinoyl glycine) nicotinamide N-oxide, and trigonelline (N -methyl nicotinic acid) the latter may arise from bacterial action in the gut or from the absorption of this substance from foods. The pattern of the different turnover metabolites varies between species, between diets (depending partly on the ratio of nicotinamide to nicotinic acid in the diet), and partly with niacin status thus there are complex regulatory mechanisms to be considered. 

Whereas the measurement of B vitamin status has, in recent years, tended to focus on blood analysis, perhaps mainly because of the convenience of sample collection, the development of blood-based status analysis for niacin has lagged behind that of the other components of the B complex. Some studies have indeed suggested that the erythrocyte concentration of the niacin-derived coenzyme NAD may provide useful information about the niacin status of human subjects that a reduction in the ratio of NAD to NADP to below 1.0 in red cells may provide evidence of niacin deficiency and that a decline in plasma tryptophan levels may indicate a more severe deficiency than a decline in red cell NAD levels. These claims now need to be tested in naturally deficient human populations. The niacin coenzymes can be quantitated either by enzyme-linked reactions or by making use of their natural fluorescence in alkaline solution. 

At present, niacin status is most commonly assessed by the assay of some of the breakdown products of niacin coenzymes in the urine. Of these, -methyl nicotinamide (NMN) is the easiest to measure, because of a convenient conversion in vitro to a fluorescent product, which can then be quantitated without the need for separation. However, more definitive and reliable information can be obtained by the measurement of urinary NMN in conjunction with one or more of the urinary pyridone turnover products (N -methyl-2-pyridone-5-carboxamide and N -methyl-4-pyridone-3-carboxamide), which can be detected and quantitated by UV absorption following high-pressure liquid chromatography. The Interdepartmental Committee on Nutrition for National Defense (USA) selected the criterion of niacin deficiency in humans as an NMN excretion rate of <5.8 tmol (0.8 mg) NMN per day in 24h urine samples. 

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