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Niacin is an old treatment to prevent coronary heart disease. It lowers bad LDL cholesterol somewhat, especially the worst type of LDL, the smallest sized particles. It also raises the good HDL cholesterol much more than the popular statins. It also lowers triglycerides, another heart disease risk factor. Niacin was the first medication for lipid cholesterol problems which was proven to extend life. It is currently being researched in combination with some of the statin medications. Regular release niacin is very inexpensive with the highest treatment dose, 3000 mg/day, costing only $7-$8 per month. In contrast, a brand-named extended release version, Niaspan, is very expensive, costing up to $325 per month. Flushing is the big problem side-effect with niacin in the high doses used to treat cholesterol problems. The standard daily value 100% dose of niacin typically found in multivitamins is only 20 mg. Niacin also causes GI upset. Fortunately, serious side-effects are very rare. A type of "flush-free" niacin, hexanicotinate, is sold by the health food industry. However, the limited research on hexanicotinate suggests that it might not have the benefits of real niacin. I like the idea of adding niacin to policosanol, if policosanol alone is inadequate. In view of the high rate of uncomfortable side-effects, niacin should be started slowly and gradually increased. Niacin Adds to Statin Benefit: In a 164 DB 20-week study with each type IIa or IIb primary hyperlipidemia patient took 4-weeks each of five phases: niacin ER (starting at 500 mg/d, increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant lovastatin dose and escalating niacin ER doses. LDL-C level reductions were greater with niacin ER/lovastatin (1500/20 mg) than with lovastatin (20 mg) (35% vs. 22%, P<.001) and with niacin ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs. 24%, P<.001). Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an additional 4% and increased HDL-C levels 8%. The maximum recommended dose (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%, triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were dose dependent and generally additive. Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses. Insull W Jr, McGovern ME, Schrott H, Thompson P, Crouse JR, Zieve F, Corbelli J. Baylor College of Medicine. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Arch Intern Med. 2004 May 24;164(10):1121-7 Extended Release Niacin Appears Best: Niacin (nicotinic acid) significantly reduces low-density lipoprotein cholesterol, triglyceride, and lipoprotein(a) levels, while increasing high-density lipoprotein cholesterol levels. Niacin is currently available in 3 formulations (immediate release, extended release, and long acting). Immediate-release niacin is generally taken 3 times a day and is associated with adverse flushing, gastrointestinal symptoms, and elevations in blood glucose levels. Long-acting niacin can be taken once daily and is associated with significantly reduced flushing, but its metabolism increases the risk of hepatotoxic effects. Extended-release niacin, also given once daily, has an absorption rate intermediate between the other formulations and is associated with fewer flushing and gastrointestinal symptoms without increasing hepatotoxic risk. New perspectives on the use of niacin in the treatment of lipid disorders. McKenney J. Virginia Commonwealth University. Arch Intern Med. 2004 Apr 12;164(7):697-705 Niacin Review: Niacin (nicotinic acid) is an effective lipid-altering agent that prevents atherosclerosis and reduces cardiovascular events. Niacin has many lipoprotein and anti-atherothrombosis effects that improve endothelial function, reduce inflammation, increase plaque stability, and diminish thrombosis. Niacin reduces the atherogenicity of low-density lipoprotein (LDL) by changing the distribution of small LDL to large LDL subclass, and the susceptibility of LDL to oxidative modification. It is the most effective agent for increasing high-density lipoprotein cholesterol. Moreover, it favorably alters high-density lipoprotein composition, increasing apolipoprotein AI relative to apolipoprotein AII. Niacin reduces blood viscosity through a variety of mechanisms, thus improving blood flow and perfusion through stenotic segments of the vasculature. Finally, niacin has cardioprotective effects that may limit ischemia-reperfusion injury. By preserving glycolysis during periods of ischemia and improving subendocardial blood flow during reperfusion, niacin can improve the functional recovery of the myocardium. Antiatherothrombotic effects of nicotinic acid. Rosenson RS. Northwestern University, Atherosclerosis. 2003 Nov;171(1):87-96 Niacin Can Help Reduce LDL and Reduce Heart Disease: In the 160-patient HATS study of stable coronary atherosclerosis, a combination of simvastatin and niacin reduced LDL cholesterol from 132 to 75 mg/dL, decreased coronary stenosis and reduced cardiovascular events by 90% over a 3-year period compared to placebo controls. BG Brown et al, N Engl J Med 2001; 345:1583. Niacin Side-Effects Common, But Niacin Helps Even at Low Dosage: In a DB PC study of 66 healthy adults, 33 on niacin (100%) and 1 on placebo (3%) flushed. Mean time to flushing was 18.2 min; mean duration of flushing was 75.4 min. Other adverse effects occurred commonly in the niacin group: chills (51.5% vs. 0%), generalized itching (75% vs. 0%), gastrointestinal upset (30% vs. 3%), and cutaneous tingling (30% vs. 0%). Six participants did not tolerate the adverse effects of niacin. In the Coronary Drug Project, patients randomized to receive niacin had a decrease in nonfatal recurrent myocardial infarction during the 6 year study and an 11% reduction in all-cause mortality nine years after termination of the trial [J Am Coll Cardiol 1986, 8:1245 Even Extended Release Niacin Has Flushing Problem: In a DB PC study of a lovastatin/niacin ER vs. lovastatin alone, 11% dropped out due to niacin flushing with dose of niacin at 1000-2000/day. A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extended-release and lovastatin. Hunninghake DB, McGovern ME, Koren M, Brazg R, Murdock D, Weiss S, Pearson T. Clin Cardiol. 2003 Mar;26(3):112-8 Niacin Niaspan Raises HDL and Lowers Triglycerides: In a 148-patient DB PC study of diabetics, 1000-1500 mg/day of extended release niacin had only a 4% drop out rate due to flushing. HDL-C was raised 19% and 24% for the two doses and triglycerides were decreased 13% and 28%. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Grundy SM, Vega GL, McGovern ME, Tulloch BR, Kendall DM, Fitz-Patrick D, Ganda OP, Rosenson RS, Buse JB, Robertson DD, Sheehan JP; Diabetes Multicenter Research Group. Hexanicotinate with Inositol Has no Niacin Flush, But...: A niacin preparation from www.puritan.com and elsewhere uses inositol to eliminate flushing and reduce GI discomfort, but I have not found any studies or reports on this. Niacin 20 mg is the daily value and the amount in most multivitamins. The amount used to lower cholesterol is much higher: 1000-2000 mg/day. Time-release formulations also reduce discomfort but still caused 10% of patients to discontinue niacin due to flushing in one study (Am J Cardiol. 2002 Mar 15;89(6):672-8). (Immediate release niacin 500 mg tabs cost around $0.05, time-release 500 mg tabs $0.08, and no flush 500 mg for $0.09-0.10, Niaspan time-release 500 mg. tabs $1.58!). Ed: I don't know if inositol would reduce the flush of niacin. Hexanicotinate has a small amount of research which, unfortunately, suggests that it may not have the benefits of regular niacin. Niacin Helped High Cholesterol Patients with Reduced Heart Attacks and Death: In the 6-year 1969 DB PC Coronary Drug Project, 1119 men, aged 30-64, were randomized to niacin and 2789 to placebo. Although side-effects interfered with adherence to the niacin, it was the most effective agent in achieving cholesterol-lowering (10% overall); other agents in the trial were clofibrate, dextrothyroxine, and conjugated equine estrogens. After 6 years, the niacin group had a statistically significantly lower incidence of definite, non-fatal heart attacks. In an extended follow-up after 12 years for the men who were still alive at the end of treatment and active follow-up in the trial in 1975 (827 in the niacin group and 2008 in placebo groups), in the group previously randomized to niacin, there were 69 (11%) fewer deaths than were expected on the basis of mortality in the placebo group (P = 0.0004). Mayo Clinic. Coronary drug project: experience with niacin. Coronary Drug Project Research Group. Berge KG, Canner PL. Eur J Clin Pharmacol. 1991;40 Suppl 1:S49-51 Niacin + Cholestipol Better than Lovastativ + Cholestipol: In a DB PC 2.5-year study of 146 men with high levels of apolipoprotein B, both lovastatin 20 mg/day plus cholestipol three times a day and niacin 1 g four times a day plus cholestipol showed much better coronary artery lesion results and had fewer cardiac events. Even though the difference was sizable, because of the small number of patients in the study, the difference was not quite statistically significant. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Niacin Helped Diabetic and Nondiabetic: In a 1-year DB PC study of 468 patients, niacin up to 3 g/day resulted increased HDL-C by 29% and decreased triglycerides by 26% and low-density lipoprotein cholesterol (LDL-C) by 9% with no difference between diabetic and non-diabetic patients. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. Elam MB, Hunninghake DB, Davis KB, Garg R, Johnson C, Egan D, Kostis JB, Sheps DS, Brinton EA. Univ. Tenn. JAMA. 2000 Sep 13;284(10):1263-70 Immediate Release Niacin As Good As Niaspan: In a DB PC study of 223 adults, those on Niaspan 1.5 g at bedtime had virtually identical lipid results and side-effects compared to those on regular niacin 500 mg three times a day. High dose niacin 1000 mg three times a day roughly doubled the beneficial effects. Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). However, flushing severity was slightly greater with Niaspan. Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Knopp RH, Alagona P, Davidson M, Goldberg AC, Kafonek SD, Kashyap M, Sprecher D, Superko HR, Jenkins S, Marcovina S. Metabolism. 1998 Sep;47(9):1097-104 |
1255]. In other randomized trials, the combination of niacin and lovastatin reduced cardiovascular risk in patients with coronary artery disease [Am J Cardiol 2002, 89:672