Regular articleNiacin and cholesterol: role in cardiovascular disease (review)
Section snippets
Background
Nicotinic acid (Niacin, Vitamin B3) is a water soluble vitamin. The major metabolic role of niacin is that it serves as a precursor for two essential coenzymes, Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Both NAD and NADP can be reduced to NADH and NADPH, respectively, and these coenzymes participate in oxidation-reduction reactions catalyzed by dehydrogenase and oxidoreductase enzymes. These NAD/NADP linked enzyme systems are involved in
Lipid profile and CHD
Disorders in lipid (e.g., cholesterol and triglycerides) and lipoprotein metabolism are major established independent risk factors in the development and progression of atherosclerotic CHD. Lipid-carrying proteins, termed as lipoproteins, are classified as 3 major classes, including very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). VLDL carries mainly triglycerides, and cholesterol is carried mainly in LDL, and to a lesser extent in HDL
Niacin as a lipid-regulating agent and its effect on atherosclerotic CHD
The use of niacin as a pharmacologic agent has been reported as early as 1955 by Altshul, Hoffer and Stephen [23], and currently it is a widely used agent in the treatment of dyslipidemia [24], [25]. In pharmacologic doses (1-3 g/day), niacin reduces concentrations of total plasma cholesterol, apolipoprotein (apo) B, triglyceride, VLDL, LDL, and Lp(a), and increases HDL levels (reviewed in 25). Niacin is the most potent available lipid-regulating agent to increase HDL levels. Because of these
Mechanism of action of niacin on triglyceride and apo B metabolism
There are mainly two mechanisms by which niacin influences plasma lipids and the secretion of apo B bearing lipoproteins including VLDL particles in the liver. VLDL is precursor to subsequent catabolic products including VLDL remnants, intermediate density lipoproteins (IDL), and LDL. Lp(a) is essentially LDL with a polypeptide linkage of apo B to apo(a). These include: 1) modulation of triglyceride lipolysis in adipose tissue, and 2) modulation of triglyceride synthesis resulting in increased
Role of niacin in HDL metabolism
As discussed earlier, niacin is the most effective pharmacologic agent to increase HDL levels. HDL are a complex class of lipoproteins with hydrophobic core of cholesterol esters and triglycerides and an outer hydrophilic layer of apolipoproteins, phospholipids and unesterified cholesterol. Apo AI and apo AII are the major proteins of HDL (accounting for approximately 70% and 20% of protein mass respectively). The liver and intestine are major organs for synthesis and secretion of HDL and its
Conclusions
A brief outline of the mechanisms of action of niacin on triglyceride, VLDL/LDL, and HDL metabolic processes is shown in Fig. 1. The ability of niacin to reduce triglyceride and VLDL/LDL secretion may involve modulation of specific events in adipocytes and hepatocytes. Firstly, niacin can decrease the mobilization of fatty acids from adipose tissue by inhibiting the hormone-sensitive lipase-mediated lipolysis of triglycerides. Secondly, niacin by directly inhibiting hepatic microsomal
Acknowledgements
This work has been supported, in part, by Veterans Affairs Merit Review Program, The Southern California Institute for Education and Research, and Kos Pharmaceuticals.
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