Availability niacin

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. 

Due to the relative stability of the niacin vitamers, either acid or alkaline hydrolysis can be used to convert nicotinamide to nicotinic acid for quantitation of both vitamers as nicotinic acid (9,44). Acid hydrolysis is used to quantitate biologically available niacin. Alkaline hydrolysis releases both the biologically available and the unavailable vitamers and provides an estimate of the total niacin content. Because alkaline hydrolysis is much faster than acid hydrolysis, the latter is usually supplemented with enzymatic hydrolysis. The most common enzymes are takadiastase, papain, and clarase. On occasion, organic solvents such as methanol have been used to extract free nicotinic acid. 

Vidal-Valverde C, Reche A. Determination of available niacin in legumes and meat by high performance liquid chromatography. J Agri Food Chem 1991 39(1) 116—21. 

In the early 1900s, pellagra reached epidemic proportions in southern United States, where the diet was based primarily on corn, which is extremely low in both available niacin and in tryptophan. In 1915, 10,000 people died of the disease and, in 1917-18, there were 200,000 cases of pellagra in this country. 

Nicotinyl alcohol (3-pyridinylcarbinol, 3-pyridinemethanol) (27) has use as an antilipemic and peripheral vasodilator. It is available from either the reductions of nicotinic acid esters or preferably, the reduction of the nitrile to the amine followed by dia2otation and nucleophilic displacement. It is frequently adininistered in the form of the tartrate (Eig. 7). Nicotinic acid is frequently used as a salt in conjunction with basic dmgs such as the peripheral vasodilator xanthinol niacinate (28). Nicotinic acid and its derivatives have widespread use as antihyperlipidemic agents and peripheral vasodilators (1). 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

Some patients, in particular those with genetic forms of hypercholesterolemia (Table 9-2), will require three or more drugs to manage their disorder. Regimens using a statin, resin, and niacin were found to reduce LDL cholesterol up to 75%.42 These early studies were conducted with lovastatin, so larger reductions would be expected with the more potent statins available today. 

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-... 

Milk is an excellent source of calcium, phosphorus, riboflavin (vitamin B2), thiamine (vitamin Bl) and vitamin B12, and a valuable source of folate, niacin, magnesium and zinc (Food Standards Agency, 2002). In particular, dairy products are an important source of calcium, which is vital for maintaining optimal bone health in humans (Prentice, 2004). The vitamins and minerals it provides are all bioavailable (i.e. available for absorption and use by the body) and thus milk consumption in humans increases the chances of achieving nutritional recommendations for daily vitamins and mineral intake (Bellew et al., 2000). 

A deficiency of niacin in the diet results in the disease known as pellagra, characterized by the four D s diarrhea, dermatitis, dementia, and death. In the early years of the twentieth century in the United States, pellagra was common among poor tenant farmers and mill workers in the rural South. The diet there at that time was rich in com that contained little niacin and little available tryptophan from which to synthesize it. 

Niacin, a water-soluble vitamin vital for oxidation by living cells, functions in the body as a component of two important coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are involved in the release of energy from carbohydrate, fat, and protein, and in the synthesis of protein, fat, and pentoses for nucleic acid formation. Milk is a poor source of preformed niacin, containing about 0.08 mg per 100 g. However, milk s niacin value is considerably greater than indicated by its niacin content (Horwitt et al. 1981). Not only is the niacin in milk fully available, but the amino acid tryptophan in milk can be used by the body for the synthesis of niacin. For every 60 mg of tryptophan consumed, the body synthesizes 1 mg of niacin. Therefore, the niacin equivalents in 100 g milk equal 0.856 mg including that from pre-... 

Distribution and Sources. In plants, niacin production sites occur in leaves, germinating seeds, and shoots. In humans, niacin is not available from intestinal bacteria, but some conversion is made from tryptophan which occurs in tissues. 

Bioavailability of Niacin. Factors which cause a decrease in macm availability include (1) Cooking losses (2) bound form in corn (maize), greens, and seeds is only partially available (3) presence of oral antibiotics (4) diseases which may cause decreased absorption (5) decrease in tiyptophan conveision as in a vitamin B deficiency. Fac.tois that increase availability include (1) alkali treatment of cereals (2) storage in bver and possibly in muscle and kidney tissue and (3) increased intestinal synthesis. 

A small fraction of the niacin in niacytin may be biologically available as a result of hydrolysis by gastric acid. About 10% of the total is released as free nicotinic acid after extraction of maize or sorghum meal with 0.1 mol per L of hydrochloric acid, and Carter and Carpenter (1982) have shown that about 10% of the total niacin content of maize is biologically available to humans beings. 

The result of this is that at low rates of flux through the kynurenine pathway, which result in concentrations of aminocarhoxymuconic semialdehyde below that at which picolinate carboxylase is saturated, most of the flux will be byway of the enzyme-catalyzed pathway, leading to oxidation. There will be Utde accumulation of aminocarhoxymuconic semialdehyde to undergo nonenzymic cyclization. As the rate of formation of aminocarhoxymuconic semialdehyde increases, and picolinate carboxylase nears saturation, there will be an increasing amount available to undergo the nonenzymic reaction and onward metabolism to NAD. Thus, there is not a simple stoichiometric relationship between tryptophan and niacin, and the equivalence of the two coenzyme precursors will vary as the amount of tryptophan to be metabolized and the rate of metabolism vary. 

Despite our understanding of the biochemistry of niacin, we still cannot account for the characteristic photosensitive dermatitis in terms of the known metabolic lesions. There is no apparent relationship between reduced availability of tryptophan and niacin, and sensitivity of the skin to ultraviolet (UV) light. The only biochemical abnormalities that have been reported in the skin of pellagrins involve increased catabolism of the amino acid histidine leading to a reduction in the concentration of urocanic acid, a histidine metabolite that is the major UV-absorbing compound in normal dermis (see Figure 10.6). 

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