Liver, nicotinic acid

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). 

Nicotinic acid has been used to treat hyperlipidemia when of the order of 1—6 g/d are required, causing dilation of blood vessels and flushing, with skin irritation. Intakes of both nicotinic acid and nicotinamide in excess of 500 mg/d can cause liver damage. 

Nicotinic acid (niacin) Liver, lean meats, cereals, legumes Energy metabolism... 

Perform liver function tests on all patients during therapy with nicotinic acid. Monitor serum transaminase levels, including ALT and AST, before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (at approximately 6-month intervals). Discontinue the drug if the transaminase levels show evidence of progression, particularly if they rise to 3 times the upper limit of normal and are persistent or if they are associated with symptoms of nausea, fever, or malaise. Consider liver biopsy if elevations persist beyond discontinuation. 

Nicotinic acid decreases formation and secretion of VLDL by the liver (mechanism III in Fig. 23.2). This action appears secondary to its ability to inhibit fatty acid mobilization from adipose tissue. Circulating free fatty acids provide the main source of fatty acids for hepatic... 

Nicotinic acid (niacin) Yes Reduces LDL Reduces VLDL Raises HDL IV Ik with fibrates severe IV with fibrates Cutaneous flush, GI distress, liver dysfunction, hyperglycemia, hyperuricemia... 

Nicotinamide (8.45) and nicotinic acid (8.46, niacin)—which have also been referred to as vitamin B3 or B5—are simple pyridine-3-carboxylic acid derivatives occurring in liver, yeast, and meat. In the form of nicotinamide-adenine dinucleotide (NAD" ) or its phosphorylated form (NADP+), nicotinamide is the most important electron carrier in intermediary metabolism. Unlike FAD, it adds a hydride ion (i.e., one pair of electrons and one hydrogen) only. 

N.A. Uncaria gambir (Hunter) Roxb. Rhyncophylline, corynoxeine, hirsutine, isorhyncophylline, nicotinic acid, catechin.297 298 299 313 Lower blood pressure, protect the liver from infection. An astringent. 

Nicotine forms a number of metabolites in the body, mainly in the liver. Approximate 75% of nicotine is oxidized to cotinine, which is the primary nicotine metabolite. Cotinine can be measured in the blood, urine, and saliva and this is used as a measure of nicotine exposure in tobacco users and in those exposed to secondhand smoke. The oxidation of nicotine also produces nicotinic acid. Nicotinic acid is vitamin B3 and has the common name niacin. Niacin deficiency results in a disease called pellagra, which is found in certain malnourished populations. Pellagras symptoms include dermatitis, diarrhea, sensitivity to light, and dementia. 

Niacin is found in unrefined and enriched grains and cereal, milk, aid lean meats, especially liver. Limited quantities of niacin can also be obtained from the metabolism of tryptophan. [Note The pathway is inefficient in that only about 1 mg of nicotinic acid is formed from 60 mg of tryptophan. Further, tryptophan is metabolized to niacin orty when there is a relative abundance of the amino acid—that is, alter the needs for protein synthesis and energy production have been met]... 

Late adverse effects include hepatic dysfunction, with altered liver function tests and hyperbilirubinemia. After prolonged use of nicotinic acid and nicotinyl alcohol, histological changes, for example parenchymal cell injury, portal fibrosis, cholangitis, cholestasis, biliary casts, and lymphocytic infiltrations around the bile ducts, have occasionally been seen. 

A starry sky liver has been reported in a patient with nicotinic acid-induced hepatitis (35). 

A 50-year-old man developed recurrent sharp lower abdominal pain and nausea, having taken modified-release nicotinic acid 500-2000 mg/day for 8 weeks for hypercholesterolemia. He had a low-grade fever, tachycardia, and hypotension. Abdominal ultrasonography showed a markedly hypoechoic liver of normal size,... 

Skin problems can be persistent in a proportion of patients, variously estimated at 10-59%, and this can severely limit adherence to therapy. The skin reaction can be ameliorated by concomitant use of non-steroidal anti-inflammatory drugs such as aspirin and indometacin (SEDA-15, 412). Transient exanthems, pruritus, and sometimes wheals are seen, as well a uniform dryness and scaling of the epidermis, brown pigmentation, and even on occasion an acanthosis nigricans-like dermatosis (15). Persistent rashes can also occur. Doses in excess of 5 g/day are routinely associated with skin manifestations and can on occasion cause liver damage, gout and ulcer formation. These reactions can be associated with nicotinic acid rather than nicotinamide, which is sometimes recommended as an alternative (37). Increased hair loss has been described. 

Niacin ia a nutritional term applied to both nicotinic acid and nicotinamide and to a mixture of the two. Their structures and those of their coenzymes are given in Table 6.1. Numerous redox reactions use NAD+ and NADP+ or NADH and NADPH. The latter are used largely in reactions designed to reductively synthesize various substances, mostly in the extramitochondrial areas of the cell. NAD+, on the other hand, is used largely in its oxidized form in catabolic redox reactions. The rat liver cytosol NADPH/NADP+ ratio is about 80, whereas its NADH/NAD+ ratio is only 8 x 10 4. Table 6.3 lists some biochemical reactions in which these cofactors participate. It shows that they are of crucial importance in the metabolism of carbohydrates, fats, and amino acids. 

Niacin (nicotinic acid) Relatively hydrophilic 15-30 Saturable liver, extensive 60-76 total dose (12% dose as unchanged drug) ... 

Acipimox is not associated with liver adverse drug reactions and should be safe to use. Niacin (nicotinic acid) has been reported to cause transient elevation in transaminases at high doses, as well as more serious... 

In the liver, there is litde utilization of preformed niacin for nucleotide synthesis. Although isolated hepatocytes will take up both vitamers from the incubation medium, they seem not to be used for NAD synthesis and cannot prevent the fall in intracellular NAD(P), which occurs during incubation. The enzymes for nicotinic acid and nicotinamide utilization are more or less saturated with their substrates at normal concentrations in the liver, and hence are unlikely to be able to use additional niacin for nucleotide synthesis. By contrast, incubation of isolated hepatocytes with tryptophan results in a considerable increase in the rate of synthesis of NAD(P) and accumulation of nicotinamide and nicotinic acid in the incubation medium. Similarly, feeding experimental animals on diets providing high intakes of nicotinic acid or nicotinamide has relatively little effect on the concentration of NAD (P) in the liver, whereas high intakes of tryptophan lead to a considerable increase. It thus seems likely that the major role of the liver is to synthesize NAD(P) from tryptophan, followed by hydrolysis to release niacin for use by extrahepatic tissues (Bender et al., 1982 McCreanor and Bender, 1986 Bender and Olufunwa, 1988). 

---