Cholesterol niacin

The possibility that vitamins might have physiological functions beyond the prevention of deficiency diseases was first recognized in 1955 with the finding (8) that niacin can affect semm cholesterol levels in humans. An explosion of research (9—11) in the intervening years has been aimed at estabUshing optimal vitamin levels and anticipating the health consequences. 

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. 

A fibrate derivative or niacin should be considered in select patients with a low high-density lipoprotein (HDL) cholesterol less than 40 mg/dL (1.04 mmol/L) and/or a high triglyceride level greater than 200 mg/dL (2.26 mmol/L). In a large randomized trial in men with established CAD and low levels of HDL cholesterol, the use of gemfibrozil (600 mg twice daily) significantly decreased the risk of non-fatal myocardial infarction or death from coronary causes.78... 

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-... 

A fibrate derivative or niacin should be considered in selected patients with a low high-density lipoprotein (HDL) cholesterol (<40 mg/dL) and/ or a high triglyceride level (>200 mg/dL). 

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. 

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. 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

Niacin has been used clinically to lower serum cholesterol levels (see Chapter 23). It is used as adjunctive therapy in patients with hyperlipidemia. It is one of the drugs of first choice for patients who do not respond adequately to diet and weight loss. 

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