Of niacin

Other Additives. Cats cannot convert tryptophan to niacin (22), or carotene to vitamin A in sufficient amounts to meet thein needs (23). These deviations, as compared with other animals, need not produce problems because added dietary sources of niacin and vitamin A provide the needs of cats. 

Both nicotinic acid and nicotinamide have been assayed by chemical and biological methods. Owing to the fact that niacin is found in many different forms in nature, it is important to indicate the specific analyte in question. For example, if biological assay procedures are used, it is necessary to indicate whether the analysis is to determine the quantity of nicotinic acid or if niacin activity is the desired result of the analysis. If nicotinic acid is desired, then a method specific for nicotinic acid should be used. If quantitation of niacin activity is the desired outcome, then all compounds (bound and unbound) which behave like niacin will assay biologically for this substance (1). 

Bioassays procedures have been developed in species such as chicks which have been fed a niacin-deficient diet. Due to the fact that, for example, tryptophan is a biological precursor of niacin, niacin can be produced from other sources (55). As a result, the tryptophan content of the diet has to be monitored carefully for accurate results. 

A deficiency of niacin also affects the nervous system. Numbness is initially observed and later, paralysis, particularly in the extremities is common. Severe cases are characteri2ed by tremor and a spastic or ataxic gait and are frequentiy associated with peripheral neuritis. Left untreated, severe thought disorders can ensue (1). 

The RDA for niacin is based on the concept that niacin coen2ymes participate in respiratory en2yme function and 6.6 niacin equivalents (NE) are needed per intake of 239 kj (1000 kcal). One NE is equivalent to 1 mg of niacin. Signs of niacin deficiency have been observed when less than 4.9 NE/239 kj or less than 8.8 NE per day were consumed. Dietary tryptophan is a rich source of niacin and the average diet in the United States contains 500—1000 mg of tryptophan. In addition, the average diet contains approximately 8—17 mg of niacin. In total, these two quantities total 16—34 NE daily. Table 5 Hsts the RDA and U.S. RDA for niacin (69). 

U.S. manufacturers of niacin and niacinamide include Nepera, Inc. and Reilly Industries, Inc. U.S. suppliers include BASF Corporation, Hoffmann-La Roche Inc., and Rhc ne-Poulenc. Western European producers and suppHers include Degussa, Rhc ne-Poulenc, BASF, Hoffmann-La Roche, and Lon2a (71). In 1995, the prices for niacin and nicotinamide were 9.75/kg and 9.25/kg, respectively (72,73). 

Pellagra is a disease caused by a deficiency of niacin (C6H5NO2) in the diet. Niacin can be synthesized in the laboratory by the side-chain oxidation of 3-methylpyridine with chromic acid or potassium permanganate. Suggest a reasonable structure for niacin. 

To a solution of 142 g (1 mol) of trans-3,3 -trimethylcyclohexenol in 400 cc of anhydrous benzene heated to 70°C is added gradually 178 g (1 mol) of niacin chloride hydrochloride. Heating is carried out under reflux conditions for 3 hours, the solution is cooled, the ester hydrochloride is filtered off and then recrystallized in an ethanol-ethyl ether mixture to obtain 227 g (80% yield) of product melting at 155°C to 157°C. 

Most foods of animal origin contain nicotinamide in the coenzyme form (high bioavialability). Liver and meat are particularly rich in highly bioavailable niacin. Most of the niacin in plants, however, occurs as nicotinic acid in overall lower concentrations and with a lower bioavailability. The major portion of niacin in cereals is found in the outer layer and its bioavailability is as low as 30% because it is bound to protein (niacytin). If the diet contains a surplus of L-tryptophan (Ttp), e.g., more than is necessary for protein synthesis, the liver can synthesize NAD from Trp. Niacin requirements are therefore declared as niacin equivalents (1 NE = 1 mg niacin = 60 mg Trp). 

NADP can be converted to nicotinic acid adenine dinucleotide phosphate (NAADP), which has distinct functions in the regulation of intracellular calcium stores. The studies of these new roles of NAD(P) in metabolism are in their early stages, but they might soon help to better understand and explain the symptoms of niacin deficiency ( pellagra) [1]. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Several different niacin formulations are available niacin immediate-release (IR), niacin sustained-release (SR), and niacin extended-release (ER).28,29 These formulations differ in terms of dissolution and absorption rates, metabolism, efficacy, and side effects. Limitations of niacin IR and SR are flushing and hepatotoxicity, respectively. These differences appear related to the dissolution and absorption rates of niacin formulations and its subsequent metabolism. Niacin IR is available by prescription (Niacor ) as well as a dietary supplement which is not regulated by the FDA.28 Currently, there are no FDA-approved niacin SR products, thus, all SR products are available only as dietary supplements. 

Loriaux SM, Deijen JB, Orlebeke JF and DeSwart JH (1985). The effect of niacin and xanthinol nicotinate on human memory in different age categories. Psychopharmacology,... 

Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

The major adverse effect of niacin treatment is intense cutaneous flushing (vasodilation), which manifests as an uncomfortable burning sensation and itchiness of the face and upper body, thereby limiting patient compliance to therapy [13]. Moreover, a short half-life, dyspepsia, hyperuricemia, and modest hyperglycemia were also reported [14-16]. 

While the precise mechanism regarding the pharmacological action of niacin remains elusive, it is known that niacin binds to GPR109A on adipocytes and decreases the hydrolysis of adipocyte TG, thereby resulting in a... 

Prior to the discovery of niacin receptors, medicinal chemistry efforts were mainly directed toward small heterocyclic carboxylic acids that are structurally similar to niacin. Systematic study of nitrogen-containing five- and six-membered heterocyclic carboxylic acids revealed that activity at GPR109A was significantly reduced for any of the variants of niacin shown in general structures (A and B) [45,46]. These heterocycles include pyrazole, isoxazole, thiazole, pyrazine, and pyrimidine. 

The principal use of niacin is for mixed hyperlipidemia or as a second-line agent in combination therapy for hypercholesterolemia. It is a first-line agent or alternative for the treatment of hypertriglyceridemia and diabetic dyslipidemia. 

In clinical trials, the combination of niacin with lovastatin (14) afforded significant HDL elevation (30%) and reduced LDL-C (47%) and TG (41%) after 16 weeks of treatment [19]. At 52 weeks of treatment, HDL increased by 41% with this combination therapy [19]. 

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