Niacin effects

Niacin effectively raises high density lipoprotein (HDL) cholesterol levels. In the absence of HDL, peripheral tissues accumulate cholesterol, presumably due to lack of reverse cholesterol transport from peripheral tissues to the liver. Niacin inhibits the degradation of HDL protein by HepG2 cells, potentially by downregulating cell surface expression of the ATP synthase beta chain. 

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. 

The HMG-CoA reductase inhibitors have an additive effect when used with the bile acid sequestrants, which may provide an added benefit in treating hypercholesterolemia that does not respond to a single-drug regimen. There is an increased risk of myopathy (disorders of the striated muscle) when the HMG-CoA reductase inhibitors are administered with erythromycin, niacin, or cyclosporin a When the HMG-CoA reductase inhibitors are administered with oral anticoagulants, there is an increased anticoagulant effect. 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

Niacin ER 500, 750, 1000 mg 1000-2000 mg once Side effects include flushing, itching, gastric distress,... 

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. 

Niacin can raise uric acid levels, and in diabetics can raise blood glucose levels. However, several clinical trials have shown that niacin can be used safely and effectively in patients with diabetes.33 Due to the high cardiovascular risk of patients with diabetes, the benefits of improving the lipid profile appear to outweigh any adjustment in diabetic medication(s) that is needed.33... 

Niacin should be instituted at the lowest dose and gradually titrated to a maximum dose of 2 grams daily for ER and SR products and no more than 5 grams daily for IR products. FDA-approved niacin products are preferred because of product consistency. Moreover, niacin products labeled as no flush don t contain nicotinic acid and therefore have no therapeutic role in the treatment of lipid disorders.28 The time until maximum effect on lipids for niacins is generally 3 to 5 weeks. 

The predominant effects of fibrates are a decrease in triglyceride levels by 20% to 50% and an increase in HDL cholesterol levels by 9% to 30% (Table 9-8). The effect on LDL cholesterol is less predictable. In patients with high triglycerides, however, LDL cholesterol may increase. Fibrates increase the size and reduce the density of LDL particles much like niacin. 

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,... 

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]. 

Thus GPR109A mediates the niacin-induced antilipolysis effect in adipocytes and vasodilation effect in skin. This discovery represents significant progress in understanding the mechanism of action for niacin, but also poses a challenge to develop a therapeutic agent to separate the lipid and vasodilation effects. 

Shibata, K. and K. Iwai. 1988. Effect of dietary paraquat on the enzymes involved in tryptophan-niacin metabolism in rats. Agric. Biol. Chem. 52 1857-1858. 

Gemfibrozil reduces the synthesis of VLDL and, to a lesser extent, apolipoprotein B with a concurrent increase in the rate of removal of triglyceride-rich lipoproteins from plasma. Clofibrate is less effective than gemfibrozil or niacin in reducing VLDL production. 

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