Niacin toxicity

Niacin is a safe drug to use and its toxicity is dose related. Niacin toxicity has been shown to manifest itself as altered mental status, nausea and vomiting (Mittal et al. 2007). Evidence shows that excess niacin can cause hepatic dysfunction with associated coagulopathy, jaundice and fulminant liver failure (Etchason et al. 1991 Fischer et al. 1991). In addition niacin overdose can cause impaired glucose control (Mittal et al. 2007). 

Most of them are generally classified as poisons. Exceptions to this rule are known. A notable one is 4-dimethyl aminopyridine (DMAP) (24), which is widely used in industry as a superior acylation catalyst (27). Quaternary salts of pyridines are usually toxic, and in particular paraquat (20) exposure can have fatal consequences. Some chloropyridines, especially polychlorinated ones, should be handled with extra care because of their potential mutagenic effects. Vinylpyridines are corrosive to the skin, and can act as a sensitizer for some susceptible individuals. Niacin (27), niacinamide (26), and some pyridinecarbaldehydes can cause skin flushing. 

Along with increasing evidence of health benefits from consumption of vitamins at levels much higher than RE) A recommendations comes concern over potential toxicity. This topic has been reviewed (19). Like all chemical substances, a toxic level does exist for each vitarnin. Traditionally it has been assumed that all water-soluble vitamins are safe at any level of intake and all fat-soluble vitamins are toxic, especially at intakes more than 10 times the recommended allowances. These assumptions are now known to be incorrect. Very high doses of some water-soluble vitamins, especially niacin and vitamin B, are associated with adverse effects. In contrast, evidence indicates that some fat-soluble micronutrients, especially vitamin E, are safe at doses many times higher than recommended levels of intake. Chronic intakes above the RDA for vitamins A and D especially are to be avoided, however. 

Niacin ER [17,18] 10-22 11 0 10-30 Skin flushing, gastrointestinal, hepatic toxicity... 

Niacin can be detected by UV, ED, or FLD. UV is a widespread technique but it needs a longer preparation step and it does not reach high sensitivity. The FLD is more sensitive but it needs a pre or postcolumn derivatization to make niacin fluorescent. Krishnan et al. [599] describe a postcol-umn derivatization using cyanogens bromide and p-aminophenol, but this method involves toxic reagents. Mawatari et al. [600], instead, propose a fast, highly specific derivatization procedure, which involves UV irradiation at 300 nm in the presence of hydrogen peroxide and copper(II) ions. 

The effects of most vitamin B overdoses have not been documented, although large dosages of pyridoxine have been reported to cause peripheral neuropathies. Ataxia and numbness of the hands and feet and impairment of the senses of pain, touch, and temperature may result. Excessive niacin intake may result in flushing, pruritus, and gastrointestinal disturbances. These symptoms are due to niacin s ability to cause the release of histamine. Large dosages of niacin can result in hepatic toxicity. 

These agents act in a complementary fashion to normalize cholesterol in patients with severe disorders involving elevated LDL. The effects are sustained, and little compound toxicity has been observed. Effective doses of the individual drugs may be lower than when each is used alone for example, as little as 1-2 g of niacin may substantially increase the effects of the other agents. 

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. 

Niacin (nicotinic acid, nicotinamide) has the active forms NAD and NADPH. It functions in electron transfer. A deficiency of niacin causes pellagra, which is characterized by der matitis, diarrhea, and dementia. There is no known toxicity for this vitamin. High doses of niacin are used to treat hyperlipidemia. 

In humans, overdosage of niacin causes a limited toxicity (1 to 4 grams/kilogram) with individual variations in sensitivity. 

McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained-vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994 271(9) 672-7. 

Abnormal accumulation in tissues and overloading of normal metabolic pathways, leading to signs of toxicity and possibly irreversible lesions. Niacin (Section 8.7.1), and vitamins A (Section 2.5.1), D (Section 3.6.1), and Bg (Section 9.6.4) are all known to be toxic in excess (see Section 1.2.4.3 for a discussion of tolerable upper levels of intake). 

Sources Shrimpton, 1997 Institute of Medicine, 1997, 1998, 2000, 2001 Scientific Committee for Food, 1993 where two figures are shown for vitamin A, the lower is for women and the higher is for men (Table 2.5). for niacin and nicotinic acid, the lower values are for sustained reiease preparations the EU upper level of 25 mg of vitamin Be was proposed by the Scientific Committee for Food Opinion, 2000 and the EU upper level of 200 xg of vitamin B12 was set because of the possible presence of inactive corrinoids in pharmaceutical preparations, not because of toxicity of the vitamin itself. 

Water soluble vitamins (Bi, B2, Be, B12, C, folacin, biotin, niacin, pantothenate) generally wash out of foods easily, and also wash out of the body relatively easily, (hence, are less easily stored in the body—an exception is vitamin B12 which is stored excellently, particularly in the liver). One may thus become depleted relatively quickly of most water soluble vitamins. Fortunately, so many foods are rich in them. Toxicity reactions, on the other hand, are more likely with fat-soluble vitamins, as they are so well-stored and are not eliminated easily from the body. 

Isoniazid may cause toxicity directly through toxic intermediates, and immunologic responses, or indirectly through the depletion of pyridoxine (vitamin Bg), and interference with several enzymes and cofactors including those needed to produce y-aminobutyric acid (GABA), nicotinamide adenine dinucleotide (NAD), and niacin (vitamin B3). 

Acute ingestions seldom require treatment. Reassurance that the niacin flush will gradually resolve over the next couple of hours should be given. In cases of chronic excessive use, the patient should be instructed to discontinue the supplement. Any toxic symptoms should be treated symptomatically. 

---