LDL niacin

Niacin (nicotinic acid) reduces the hepatic synthesis of VLDL, which in turn leads to a reduction in the synthesis of LDL. Niacin also increases HDL by reducing its catabolism. 

Deficiency of cholesterol 7ft-hydroxylase can cause elevated LDL in the heterozygous state. Homozygotes can also have elevated triglycerides, resistance to reductase inhibitors, and premature gallstones. Autosomal recessive hypercholesterolemia is due to mutations in a protein that assists in endocytosis of LDL. Niacin and ezetimibe may be useful in these disorders. 

Niacin is a vitamin that is used in high doses to treat hypercholesterolemia. Niacin acts to decrease VLDL and LDL plasma levels. Its mechanism of action is not clearly nnderstood but probably involves inhibition of VLDL secretion, which in tnm decreases the production of LDL. Niacin inhibits the release of free fatty acids from adipose tissue which leads to a decrease of free fatty acids entering the liver and decreased VLDL synthesis in the liver. This decreases the availability of VLDL for conversion to LDL (containing cholesterol esters). Niacin also increases high-density lipoprotein (HDL) (the good cholesterol ) by an nnknown mechanism. 

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. 

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). 

Reducing LDL cholesterol while substantially raising HDL cholesterol (statin + niacin) appears to reduce the risk of atherosclerotic disease progression to a greater degree than statin monotherapy. 

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

In general, niacin reduces LDL cholesterol from 5% to 25%, reduces triglycerides by 20% to 50%, and increases HDL cholesterol by 15% to 35% (Table 9-8). Niacin has been shown to reduce CHD events and total mortality31 as well as the progression of atherosclerosis when combined with a statin.31... 

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. 

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. 

Once the LDL cholesterol goal is achieved, assess non-HDL cholesterol in those with metabolic syndrome and intensify LDL-lowering therapy further or consider adding niacin or fibrate. 

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-... 

Niacin i LDL and VLDL synthesis i Triglyceride i Cholesterol i VLDL, Tldl, Thdl... 

In general, a statin plus a BAR or niacin plus a BAR provide the greatest reduction in total and LDL cholesterol. 

Niacin (11) is the most potent HDL-raising drug (20-30%) on the market, and also provides some reduction in TG and LDL-C levels. Clinical studies with niacin as monotherapy or in combination with statins have yielded marked reductions in... 

In clinical trials, the combination of niacin with lovastatin (14) afforded significant HDL elevation (30%) and reduced LDL-C (47%) and TG (41%) after 16 weeks of treatment [19]. At 52 weeks of treatment, HDL increased by 41% with this combination therapy [19]. 

Neomycin sulfate Many studies have documented lipid-lowering efficacy of neomycin. Alone, it reduced LDL cholesterol levels by 24%. Combined with niacin, it reduced LDL cholesterol levels to below the 90th percentile in 92% of patients. 

Statins Yes Reduces LDL Ila Ik with niacin Myositis, liver dysfunction, rhabdomyolysis with cerivastatin... 

Bile acid-sequestering resins Yes Reduces LDL n. Severe 11, with statin or niacin GI distress, hyperchloremic acidosis... 

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... 

LDL predominantly increased Niacin, reductase inhibitor, ezetimibe Two or three of the individual drugs... 

VLDL, LDL increased Niacin, reductase inhibitor Niacin or fibrate plus reductase inhibitor2... 

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