Important Considerations for Treatment with Dietary Supplement versus Prescription Niacin Products

References

• . Baigent C, Keech A, Kearney PM, ; Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–1278
   PubMed Web of Science ®Google Scholar
• . Colhoun HM, Betteridge DJ, Durrington PN, . Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–696
   PubMed Web of Science ®Google Scholar
• . Downs JR, Clearfield M, Weis S, . Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279(20):1615–1622
   PubMed Web of Science ®Google Scholar
• . Neil HA, DeMicco DA, Luo D, ; CARDS Study Investigators. Analysis of efficacy and safety in patients aged 65–75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care. 2006;29(11):2378–2384
   PubMed Web of Science ®Google Scholar
• . Sacks FM, Pfeffer MA, Moye LA, . The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–1009
   PubMed Web of Science ®Google Scholar
• . Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions. J Vasc Surg. 2007;45(4):645–654; discussion 653–654
   PubMed Web of Science ®Google Scholar
• . Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339(19):1349–1357
   PubMed Web of Science ®Google Scholar
• . Shepherd J, Cobbe SM, Ford I, ; West of Scotland Cornary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. 1995. Atheroscler Suppl. 2004;5(3):91–97
   PubMed Web of Science ®Google Scholar
• . Fruchart JC, Sacks F, Hermans MP, . The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am J Cardiol. 2008;102( 10 suppl):1K–34K
   PubMed Web of Science ®Google Scholar
• . Cannon CP. High-density lipoprotein cholesterol and residual cardiometabolic risk in metabolic syndrome. Clin Cornerstone. 2007;8( suppl 6):S14–S23
   PubMedGoogle Scholar
• . National cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–3421
   PubMed Web of Science ®Google Scholar
• . Chapman MJ. Beyond the statins: new therapeutic perspectives in cardiovascular disease prevention. Cardiovasc Drugs Ther. 2005;19(2):135–139
   PubMed Web of Science ®Google Scholar
• . Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world–a growing challenge. N Engl J Med. 2007;356(3):213–215
   PubMed Web of Science ®Google Scholar
• . Barter P, Gotto AM, LaRosa JC, . HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301–1310
   PubMed Web of Science ®Google Scholar
• . Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol. 2003;18(4):278–285
   PubMed Web of Science ®Google Scholar
• . Cannon CP. Combination therapy in the management of mixed dyslipidaemia. J Intern Med. 2008;263(4):353–365
   PubMed Web of Science ®Google Scholar
• . Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986;256(20):2835–2838
   PubMed Web of Science ®Google Scholar
• . Gordon DJ, Probstfield JL, Garrison RJ, . High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79(1):8–15
   PubMed Web of Science ®Google Scholar
• . Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA. 2007;298(7):786–798
   PubMed Web of Science ®Google Scholar
• . Marcil M, O'Connell B, Krimbou L, Genest J Jr. High-density lipoproteins: multifunctional vanguards of the cardiovascular system. Expert Rev Cardiovasc Ther. 2004;2(3):417–430
   PubMedGoogle Scholar
• . McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med. 2004;164(7):697–705
   PubMedGoogle Scholar
• . Davidson MH, Toth PP. High-density lipoprotein metabolism: potential therapeutic targets. Am J Cardiol. 2007;100(11 A):n32–n40
   Web of Science ®Google Scholar
• . Clarke R, Peden JF, Hopewell JC, ; PROCARDIS Consortium. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518–2528
   PubMed Web of Science ®Google Scholar
• . Kathiresan S. Lp(a) lipoprotein redux–from curious molecule to causal risk factor. N Engl J Med. 2009;361(26):2573–2574
   PubMed Web of Science ®Google Scholar
• . Chapman MJ, Huby T, Nigon F, Thillet J. Lipoprotein (a): implication in atherothrombosis. Atherosclerosis. 1994;110( suppl):S69–S75
   PubMed Web of Science ®Google Scholar
• . Chapman MJ, Redfern JS, McGovern ME, Giral P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010;126(3):314–345
   PubMed Web of Science ®Google Scholar
• . Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation. 2000;102(10):1082–1085
   PubMed Web of Science ®Google Scholar
• . McKenney JM, McCormick LS, Schaefer EJ, Black DM, Watkins ML. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Am J Cardiol. 2001;88(3):270–274
   PubMed Web of Science ®Google Scholar
• . Jafri H, Karas RH, Kuvin JT. Effects of niacin on LDL particle number. Clin Lipidology. 2009;4(5):565–571
   Web of Science ®Google Scholar
• . Canner PL, Berge KG, Wenger NK, . Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245–1255
   PubMed Web of Science ®Google Scholar
• . Brown G, Albers JJ, Fisher LD, . Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323(19):1289–1298
   PubMed Web of Science ®Google Scholar
• . Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987;257(23):3233–3240
   PubMed Web of Science ®Google Scholar
• . Cashin-Hemphill L, Mack WJ, Pogoda JM, Sanmarco ME, Azen SP, Blankenhorn DH. Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. JAMA. 1990;264(23):3013–3017
   PubMed Web of Science ®Google Scholar
• . Taylor AJ, Villines TC, Stanek EJ, . Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361(22):2113–2122
   PubMed Web of Science ®Google Scholar
• . Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin. 2006;22(11):2243–2250
   PubMed Web of Science ®Google Scholar
• . Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110(23):3512–3517
   PubMed Web of Science ®Google Scholar
• . Villines TC, Stanek EJ, Devine PJ, . The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol. 2010;55(24):2721–2726
   PubMed Web of Science ®Google Scholar
• . McCormack PL, Keating GM. Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. Drugs. 2005;65(18):2719–2740
   PubMed Web of Science ®Google Scholar
• . National Academy of Sciences, Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998
   Google Scholar
• . Jacobson TA. A “hot” topic in dyslipidemia management—“how to beat a flush”: optimizing niacin tolerability to promote long-term treatment adherence and coronary disease prevention. Mayo Clin Proc. 2010;85(4):365–379
   PubMed Web of Science ®Google Scholar
• . Piepho RW. The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol. Am J Cardiol. 2000;86(12 A):35L–40L
   PubMedGoogle Scholar
• . Miller ON, Hamilton JG, Goldsmith GA. On the mechanism of action of nicotinic acid in lowering serum lipids. Am J Clin Nutr. 1962;10:285–296
   PubMed Web of Science ®Google Scholar
• . . Council for Responsible NutritionHathcock JN, ed. Niacin: nicotinic acid and nicotinamide. In: Vitamin and Mineral Safety. 2nd ed. Washington, DC: Council for Responsible Nutrition; 2004
   Google Scholar
• . Niacor (niacin) [package insert]. Minneapolis, MN: Upsher-Smith Laboratories, Inc; 2008
   Google Scholar
• . Benyo Z, Gille A, Bennett CL, Clausen BE, Offermanns S. Nicotinic acid-induced flushing is mediated by activation of epidermal langer-hans cells. Mol Pharmacol. 2006;70(6):1844–1849
   PubMed Web of Science ®Google Scholar
• . Kamanna VS, Ganji SH, Kashyap ML. The mechanism and mitigation of niacin-induced flushing. Int J Clin Pract. 2009;63(9):1369–1377
   PubMed Web of Science ®Google Scholar
• . Oberwittler H, Baccara-Dinet M. Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment. Int J Clin Pract. 2006;60(6):707–715
   PubMed Web of Science ®Google Scholar
• . Thakkar RB, Kashyap ML, Lewin AJ, Krause SL, Jiang P, Padley RJ. Acetylsalicylic acid reduces niacin extended-release-induced flushing in patients with dyslipidemia. Am J Cardiovasc Drugs. 2009;9(2):69–79
   PubMed Web of Science ®Google Scholar
• . Kalogeromitros D, Makris M, Chliva C, Aggelides X, Kempuraj D, Theoharides TC. A quercetin containing supplement reduces niacin-induced flush in humans. Int J Immunopathol Pharmacol. 2008;21(3):509–514
   PubMed Web of Science ®Google Scholar
• . Maccubbin D, Bays HE, Olsson AG, . Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Int J Clin Pract. 2008;62(12):1959–1970
   PubMed Web of Science ®Google Scholar
• . Goldberg A, Alagona P Jr, Capuzzi DM, . Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol. 2000;85(9):1100–1105
   PubMed Web of Science ®Google Scholar
• . Morgan JM, Capuzzi DM, Guyton JR. A new extended-release niacin (Niaspan): efficacy, tolerability, and safety in hypercholesterolemic patients. Am J Cardiol. 1998;82(12 A):29U–34U; discussion 39U–41U
   Google Scholar
• . Grundy SM, Vega GL, McGovern ME, ; Diabetes Multicenter Research Group. 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. Arch Intern Med. 2002;162(14):1568–1576
   PubMedGoogle Scholar
• . Canner PL, Furberg CD, Terrin ML, McGovern ME. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2005;95(2):254–257
   PubMed Web of Science ®Google Scholar
• . Miller M. Niacin as a component of combination therapy for dyslipidemia. Mayo Clin Proc. 2003;78(6):735–742
   PubMed Web of Science ®Google Scholar
• . Capuzzi DM, Morgan JM, Brusco OA Jr, Intenzo CM. Niacin dosing: relationship to benefits and adverse effects. Curr Atheroscler Rep. 2000;2(1):64–71
   PubMedGoogle Scholar
• . ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. American Society of Health-System Pharmacists. Am J Health Syst Pharm. 1997;54(24):2815–2819
   PubMed Web of Science ®Google Scholar
• . Mills E, Prousky J, Raskin G, . The safety of over-the-counter niacin. A randomized placebo-controlled trial [ISRCTN18054903]. BMC Clin Pharmacol. 2003;3:4
   PubMedGoogle Scholar
• . Clofibrate and niacin in coronary heart disease. JAMA. 1975;231(4):360–381
   PubMed Web of Science ®Google Scholar
• . Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. 2007;99(6 A):22C–31C
   PubMed Web of Science ®Google Scholar
• . Niaspan (niacin tablet, extended release) [package insert]. North Chicago, IL: Abbott Laboratories; 2007
   Google Scholar
• . Joy TR, Hegele RA. Narrative review: statin-related myopathy. Ann Intern Med. 2009;150(12):858–868
   PubMed Web of Science ®Google Scholar
• . Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother. 2002;36(2):288–295
   PubMed Web of Science ®Google Scholar
• . US Food and Drug Administration. Overview of dietary supplements. http://www.fda.gov/Food/DietarySupplements/ConsumerInformation/ucm110417.htm. Accessed September 10, 2010
   Google Scholar
• . Dietary Supplement Health and Education Act of 1994. http://www.health.gov/dietsupp/ch1.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. FDA 101: dietary supplements. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm050803.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. Adverse Event Reporting System (AERS). http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. Adverse drug experience reporting. http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm082056.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. Claims that can be made for conventional foods and dietary supplements. http://www.fda.gov/Food/LabelingNutrition/LabelClaims/ucm111447.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. Major issues and recommendations related to the labeling of dietary supplements. http://www.health.gov/dietsupp/ch3.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. Guidance for industry: evidence-based review system for the scientific evaluation of health claims – final. http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm073332.htm. Accessed September 10, 2010
   Google Scholar
• . National Institutes of Health. Dietary supplements: background information. http://ods.od.nih.gov/factsheets/dietarysupplements.asp. Accessed September 10, 2010
   Google Scholar
• . Troppmann L, Gray-Donald K, Johns T. Supplement use: is there any nutritional benefit? J Am Diet Assoc. 2002;102(6):818–825
   PubMedGoogle Scholar
• . American Heart Association. Cholesterol-lowering drugs. http://www.americanheart.org/presenter.jhtml?identifier=4510. Accessed September 10, 2010
   Google Scholar
• . Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med. 1994;121(4):252–258
   PubMed Web of Science ®Google Scholar
• . McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA. 1994;271(9):672–677
   PubMed Web of Science ®Google Scholar
• . Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2005;45(2):185–197
   PubMed Web of Science ®Google Scholar
• . Swanson Vitamins. Flush-free niacin. http://www.swansonvitamins.com/SWU080/ItemDetail. Accessed September 10, 2010
   Google Scholar
• . Sundown Natural. Flush free niacin 500 mg capsules. http://www.sundownnaturals.com/products/product.aspx?UPC=030768037871. Accessed September 10, 2010
   Google Scholar
• . Nature's Bounty. Niacin. http://www.naturesbounty.com/vf/labels/001976NB.pdf. Accessed September 10, 2010
   Google Scholar
• . Schiff. Niacin (flush free). http://www.schiffvitamins.com/product_detail.asp?id=15#. Accessed September 10, 2010
   Google Scholar
• . Puritan's Pride. Flush Free Niacin 1000 mg. http://www.puritan.com/niacin-b-3–362/flush-free-niacin-inositol-nicotinate-1000-mg-015482?NewPage=1#product. Accessed September 10, 2010
   Google Scholar
• . Source Naturals. No-Flush Niacin. http://www.sourcenaturals.com/products/GP1447/. Accessed September 10, 2010
   Google Scholar
• . Meyers CD, Carr MC, Park S, Brunzell JD. Varying cost and free nicotinic acid content in over-the-counter niacin preparations for dyslipidemia. Ann Intern Med. 2003;139(12):996–1002
   PubMed Web of Science ®Google Scholar
• . Poon IO, Chow DS, Liang D. Dissolution profiles of nonprescription extended-release niacin and inositol niacinate products. Am J Health Syst Pharm. 2006;63(21):2128–2134
   PubMed Web of Science ®Google Scholar
• . Dorner G, Fischer FW. [On the modification of serum lipids and lipoproteins by the hexanicotinic acid ester of m-inositol]. Arzneimittelforschung. 1961;11:110–113
   PubMedGoogle Scholar
• . Welsh AL, Ede M. Inositol hexanicotinate for improved nicotinic acid therapy. Preliminary report. Int Rec Med. 1961;174:9–15
   PubMedGoogle Scholar
• . Agusti R, Jordan C, Aste H, Tapia F. [Effect of hexanicotinate of meso-inositol in patients with primary hyperlipidemia (author's transl)]. Rev Invest Clin. 1978;30(4):327–335
   PubMedGoogle Scholar
• . Kruse W, Kruse W, Raetzer H, . Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives. Eur J Clin Pharmacol. 1979;16(1):11–15
   PubMed Web of Science ®Google Scholar
• . Ziliotto GR, Lamberti G, Wagner A, Cima L, Genco G. [Comparative studies of the response of normolipemic and dyslipemic aged subjects to 2 forms of delayed-action nicotinic acid polyesters. Pentaerythrotol tetranicotinate and inositol hexanicotinate. Results of a controlled cross-over trial]. Arch Sci Med (Torino). 1977;134(4):359–394
   PubMedGoogle Scholar
• . El-Enein AMA, Hafez YS, Salem H, Abdel M. The role of nicotinic acid and inositol hexaniocotinate as anticholesterolemic and antilipemic agents. Nutrition Reports International. 1983;28:899–911
   Google Scholar
• . Norris RB. “Flush-free niacin”: dietary supplement may be “benefit-free”. Prev Cardiol. 2006;9(1):64–65
   PubMedGoogle Scholar
• . Keenan JM. Sustained-release nicotinic acid vs inositol hexanicotinate for the treatment of dyslipidemia [Abstract P153]. Arterioscler Thromb Vasc Biol. 2008:e-61–e-62
   Google Scholar
• . Aronov DM, Keenan JM, Akhmedzhanov NM, Perova NV, Oganov RY, Kiseleva NY. Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia. Arch Fam Med. 1996;5(10):567–575
   PubMedGoogle Scholar
• . Keenan JM, Bae CY, Fontaine PL, . Treatment of hypercholesterolemia: comparison of younger versus older patients using wax-matrix sustained-release niacin. J Am Geriatr Soc. 1992;40(1):12–18
   PubMed Web of Science ®Google Scholar
• . Keenan JM, Fontaine PL, Wenz JB, Myers S, Huang ZQ, Ripsin CM. Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia. Arch Intern Med. 1991;151(7):1424–1432
   PubMedGoogle Scholar
• . Knopp RH, Retzlaff BM, Fish B, . The SLIM Study: Slo-Niacin(R) and Atorvastatin Treatment of Lipoproteins and Inflammatory Markers in Combined Hyperlipidemia. J Clin Lipidol. 2009;3(3):167–178
   PubMed Web of Science ®Google Scholar
• . Brown BG, Zhao XQ, Chait A, . Simvastatin and niacin, anti-oxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345(22):1583–1592
   PubMed Web of Science ®Google Scholar
• . Coppola A, Brady PG, Nord HJ. Niacin-induced hepatotoxicity: unusual presentations. South Med J. 1994;87(1):30–32
   PubMed Web of Science ®Google Scholar
• . Dalton TA, Berry RS. Hepatotoxicity associated with sustained-release niacin. Am J Med. 1992;93(1):102–104
   PubMed Web of Science ®Google Scholar
• . Etchason JA, Miller TD, Squires RW, . Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin. Mayo Clin Proc. 1991;66(1):23–28
   PubMed Web of Science ®Google Scholar
• . Lawrence SP. Transient focal hepatic defects related to sustained-release niacin. J Clin Gastroenterol. 1993;16(3):234–236
   PubMed Web of Science ®Google Scholar
• . US Food and Drug Administration. Code of Federal Regulations Title 21. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=314.80. Accessed September 10, 2010
   Google Scholar
• . Knopp RH, Alagona P, Davidson M, . Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism. 1998;47(9):1097–1104
   PubMed Web of Science ®Google Scholar
• . Simcor (simvastatin/niacin extended-release) [package insert]. North Chicago, IL: Abbott Laboratories; 2010
   Google Scholar
• . Advicor (lovastatin/niacin extended-release) [package insert]. North Chicago, IL: Abbott Laboratories; 2010
   Google Scholar
• . Devine PJ, Turco MA, Taylor AJ. Design and rationale of the ARBITER 6 trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)-6-HDL and LDL Treatment Strategies in Atherosclerosis (HALTS). Cardiovasc Drugs Ther. 2007;21(3):221–225
   PubMed Web of Science ®Google Scholar
• . Alsheikh-Ali AA, Karas RH. The safety of niacin in the US Food and Drug Administration adverse event reporting database. Am J Cardiol. 2008;101(8 A):9B–13B
   PubMed Web of Science ®Google Scholar
• . American Heart Association. Cholesterol medications. http://www.americanheart.org/presenter.jhtml?identifier=3044771#four. Accessed September 10, 2010
   Google Scholar
• . American Pharmacists Association. American Heart Associations updates niacin guidelines. http://www.pharmacist.com/AM/Template.cfm?Section=Home2&TEMPLATE=/CM/ContentDisplay.cfm&CONTENTID=11154. Accessed February 12, 2010
   Google Scholar
• . US Food and Drug Administration. Prescription drugs and over-the-counter (OTC) drugs: questions and answers. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/QuestionsAnswers/ucm100101.htm. Accessed September 10, 2010
   Google Scholar
• . US Food and Drug Administration. Postmarket requirements and commitments. http://www.fda.gov/Drugs/InformationOnDrugs/ucm142931.htm. Accessed September 10, 2010
   Google Scholar
• . US Pharmacopeia. The regulation of dietary supplements. www.usp.org/pdf/EN/USPVerified/dietarySupplementRegulation.pdf. Accessed September 10, 2010
   Google Scholar
• . Davignon J, Roederer G, Montigny M, . Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol. 1994;73(5):339–345
   PubMed Web of Science ®Google Scholar
• . Morgan JM, Capuzzi DM, Baksh RI, . Effects of extended-release niacin on lipoprotein subclass distribution. Am J Cardiol. 2003;91(12):1432–1436
   PubMed Web of Science ®Google Scholar
• . Goldberg AC. Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. Am J Cardiol. 1998;82(12 A):35U–38U; discussion 39U–41U
   Google Scholar
• . Kuvin JT, Rämet ME, Patel AR, Pandian NG, Mendelsohn ME, Karas RH. A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol: enhanced vasorelaxation and increased endothelial nitric oxide synthase expression. Am Heart J. 2002;144(1):165–172
   PubMed Web of Science ®Google Scholar
• . Brown BG, Bardsley J, Poulin D, . Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. Am J Cardiol. 1997;80(2):111–115
   PubMed Web of Science ®Google Scholar
• . Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA. 1990;264(6):723–726
   PubMed Web of Science ®Google Scholar
• . King JM, Crouse JR, Terry JG, Morgan TM, Spray BJ, Miller NE. Evaluation of effects of unmodified niacin on fasting and postprandial plasma lipids in normolipidemic men with hypoalphalipoproteinemia. Am J Med. 1994;97(4):323–331
   PubMed Web of Science ®Google Scholar
• . Elam MB, Hunninghake DB, Davis KB, . 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. JAMA. 2000;284(10):1263–1270
   PubMed Web of Science ®Google Scholar
• . Mostaza JM, Schulz I, Vega GL, Grundy SM. Comparison of pravastatin with crystalline nicotinic acid monotherapy in treatment of combined hyperlipidemia. Am J Cardiol. 1997;79(9):1298–1301
   PubMed Web of Science ®Google Scholar
• . Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med. 1994;154(1):73–82
   PubMedGoogle Scholar
• . Wink J, Giacoppe G, King J. Effect of very-low-dose niacin on high-density lipoprotein in patients undergoing long-term statin therapy. Am Heart J. 2002;143(3):514–518
   PubMed Web of Science ®Google Scholar
• . O'Kane MJ, Trinick TR, Tynan MB, Trimble ER, Nicholls DP. A comparison of acipimox and nicotinic acid in type 2b hyperlipidaemia. Br J Clin Pharmacol. 1992;33(4):451–453
   PubMed Web of Science ®Google Scholar
• . O'Keefe JH Jr, Harris WS, Nelson J, Windsor SL. Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol. 1995;76(7):480–484
   PubMed Web of Science ®Google Scholar
• . Vacek JL, Dittmeier G, Chiarelli T, White J, Bell HH. Comparison of lovastatin (20 mg) and nicotinic acid (1.2 g) with either drug alone for type II hyperlipoproteinemia. Am J Cardiol. 1995;76(3):182–184
   PubMed Web of Science ®Google Scholar
• . Lavie CJ, Mailander L, Milani RV. Marked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease. Am J Cardiol. 1992;69(12):1083–1085
   PubMed Web of Science ®Google Scholar
• . Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999;79(4):1193–1226
   PubMed Web of Science ®Google Scholar
• . Yiu KH, Cheung BM, Tse HF. A new paradigm for managing dyslipidemia with combination therapy: laropiprant + niacin + simvastatin. Expert Opin Investig Drugs. 2010;19(3):437–449
   PubMed Web of Science ®Google Scholar