Nutraceuticals with lipid-lowering activity: do they have any effect beyond cholesterol reduction?

References

• Banegas JR, López-García E, Dallongeville J et al. Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study. Eur. Heart J. 32, 2143–2152 (2011).
   Google Scholar
• Saha S, Gerdtham UG, Johansson P. Economic evaluation of lifestyle interventions for preventing diabetes and cardiovascular diseases. Int. J. Environ. Res. Public Health 7, 3150–3195 (2010).
   Google Scholar
• King DE, Mainous AG 3rd, Matheson EM et al. Impact of healthy lifestyle on mortality in people with normal blood pressure, LDL cholesterol, and C-reactive protein. Eur. J. Cardiovasc. Prev. Rehabil. doi:10.1177/1741826711425776 (2011) (Epub ahead of print).
   Google Scholar
• Cicero AFG, Derosa G, D’Angelo A et al. Gender-specific haemodynamic and metabolic effects of a sequential training programme on overweight-obese hypertensives. Blood Press. 18, 111–116 (2009).
   Google Scholar
• Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The 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). JAMA 285, 2486–2497 (2001). ▪▪ First international guidelines on cardiovascular disease prevention citing the usefulness of dietary supplement for dyslipidemia improvement.
   Google Scholar
• Catapano AL, Reiner Z, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 217(1), 3–46 (2011). ▪▪ Latest European guidelines for dyslipidemia management, firstly including monacolins and policosanols as natural compounds potentially of interest in the management of hypercholesterolemia.
   Google Scholar
• Hasani-Ranjbar S, Nayebi N, Moradi L et al. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia: a systematic review. Curr. Pharm. Res. 16, 2935–2947 (2010).
   Google Scholar
• Houston M. The role of nutraceutical supplements in the treatment of dyslipidemia. J. Clin. Hypertens. 14(2), 121–132 (2012).
   Google Scholar
• Gunness P, Gidley MJ. Mechanisms underlying the cholesterol-lowering properties of soluble dietary fibre polysaccharides. Food Funct. 1(2), 149–155 (2010).
   Google Scholar
• Wei ZH, Wang H, Chen XY et al. Time- and dose-dependent effect of psyllium on serum lipids in mild-to-moderate hypercholesterolemia: a meta-analysis of controlled clinical trials. Eur. J. Clin. Nutr. 63, 821–827 (2009).
   Google Scholar
• Finks SW, Airee A, Chow SL et al. Key articles of dietary interventions that influence cardiovascular mortality. Pharmacotherapy 32(4), e54–e87 (2012).
   Google Scholar
• Cicero AF, Derosa G, Manca M et al. Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial. Clin. Exp. Hypertens. 29, 383–394 (2007).
   Google Scholar
• Pal S, Khossousi A, Binns C et al. The effects of 12-week psylliumfibre supplementation or healthy diet on blood pressure and arterial stiffness in overweight and obese individuals. Br. J. Nutr. 107, 725–734 (2012).
   Google Scholar
• Lattimer JM, Haub MD. Effects of dietary fiber and its components on metabolic health. Nutrients 2(12), 1266–1289 (2010).
   Google Scholar
• Mello VD, Laaksonen DE. [Dietary fibers: current trends and health benefits in the metabolic syndrome and type 2 diabetes.] Arq. Bras Endocrinol. Metabol. 53, 509–518 (2009).
   Google Scholar
• Ma Y, Hébert JR, Li W et al. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition 24(10), 941–949 (2008).
   Google Scholar
• Cicero AF, Ferroni A, Ertek S. Tolerability and safety of commonly used dietary supplements and nutraceuticals with lipid-lowering effects. Expert Opin. Drug Saf. 11(5), 753–766 (2012).
   Google Scholar
• Mechanick JI, Brett EM, Chausmer AB et al. American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals. Endocr. Pract. 9, 417–470 (2003).
   Google Scholar
• Mackay DS, Jones PJ. Plasma noncholesterol sterols: current uses, potential and need for standardization. Curr. Opin. Lipidol. 23(3), 241–247 (2012).
   Google Scholar
• Mensink RP, de Jong A, Lütjohann D et al. Plant stenols dose dependently decrease LDL cholesterol concentrations but not cholesterol standardized fat soluble antioxidant concentrations, at intakes up to 9g/d. Am. J. Clin. Nutr. 92, 24–33 (2010).
   Google Scholar
• Moruisi KG, Oosthuizen W, Opperman AM. Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects: a systematic review with meta-analysis. J. Am. Coll. Nutr. 25, 41–48 (2006).
   Google Scholar
• Plant stanol ester consumption and arterial elasticity and endothelial function. Br. J. Nutr. 100, 603–608 (2008).
   Google Scholar
• Genser B, Silbernagel G, De Backer G et al. Plant sterols and cardiovascular disease: a systematic review and meta-analysis. Eur. Heart J. 33, 444–451 (2012).
   Google Scholar
• Chen Q, Gruber H, Swist E et al. Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of saltloading. Nutr. Metab. 7, 11 (2010).
   Google Scholar
• Lottenberg AM, Bombo RP, Ilha A et al. Do clinical and experimental investigations support an antiatherogenic role for dietary phytosterols/stanols? IUBMB Life 64(4), 296–306 (2012).
   Google Scholar
• Othman RA, Moghadasian MH. Beyond cholesterol-lowering effects of plant sterols: clinical and experimental evidence of anti-inflammatory properties. Nutr. Rev. 69, 371–382 (2011).
   Google Scholar
• Derdemezis CS, Filippatos TD, Mikhailidis DP et al. Review article: effects of plant sterols and stanols beyond low-density lipoprotein cholesterol lowering. J. Cardiovasc. Pharmacol. Ther. 15, 120–134 (2010).
   Google Scholar
• Guardamagna O, Abello F, Baracco V et al. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol. 48, 127–133 (2011).
   Google Scholar
• Moghadasian MH. Dietary phytosterols reduce cyclosporine-induced hypercholesterolemia in apolipoprotein E-knockout mice. Transplantation 81, 207–213 (2006).
   Google Scholar
• Plat J, Mensink RP. Plant stanol and sterol esters in the control of blood cholesterol levels: mechanism and safety aspects. Am. J. Cardiol. 96, 15D–22D (2005).
   Google Scholar
• Gylling H, Hallikainen M, Nissinen MJ et al. The effect of a very high daily plant stanol ester intake on serum lipids, carotenoids, and fat soluble vitamins. Clin. Nutr. 29, 112–118 (2010).
   Google Scholar
• Reinhart KM, Talati R, White CM et al. The impact of garlic on lipid parameters: a systematic review and meta-analysis. Nutr. Res. Rev. 22, 39–48 (2009).
   Google Scholar
• Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J. Nutr. 136, 736S–740S (2006).
   Google Scholar
• Ried K, Frank OR, Stocks NP. Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomized controlled trial. Maturitas 67, 144–150 (2010).
   Google Scholar
• Simons S, Wollersheim H, Thien T. A systematic review on the influence of trial quality on the effect of garlic on blood pressure. Neth. J. Med. 67, 212–219 (2009).
   Google Scholar
• Williams MJ, Sutherland WH, McCormick MP et al. Aged garlic extract improves endothelial function in men with coronary artery disease. Phytother. Res. 19, 314–319 (2005).
   Google Scholar
• Budoff MJ, Ahmadi N, Gul KM et al. Aged garlic extract supplemented with B vitamins, folic acid and l-arginine retards the progression of subclinical atherosclerosis: a randomised clinical trial. Prev. Med. 49, 101–107 (2009).
   Google Scholar
• van Doorn MB, Espirito Santo SM, Meijer P et al. Effect of garlic powder on C-reactive protein and plasma lipids in overweight and smoking subjects. Am. J. Clin. Nutr. 84, 1324–1329 (2006).
   Google Scholar
• Macan H, Uykimpang R, Alconcel M et al. Aged garlic extract may be safe for patients on warfarin therapy. J. Nutr. 136, 793S–795S (2006).
   Google Scholar
• Berginc K, Milisav I, Kristl A. Garlic flavonoids and organosulfur compounds: impact on the hepatic pharmacokinetics of saquinavir and darunavir. Drug Metab. Pharmacokinet. 25, 521–530 (2010).
   Google Scholar
• Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J. Nutr. 125, 606S–611S (1995).
   Google Scholar
• Torres N, Torre-Villalvazo I, Tovar AR. Regulation of lipid metabolism by soyprotein and its implication in diseases mediated by lipid disorders. J. Nutr. Biochem. 17, 365–373 (2006).
   Google Scholar
• Mullen E, Brown RM, Osborne TF et al. Soy isoflavones affect sterol regulatory element binding proteins (SREBPs) and SREBP-regulated genes in HepG2 cells. J. Nutr. 134, 2942–2947 (2004).
   Google Scholar
• Anderson JW, Bush HM. Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies. J. Am. Coll. Nutr. 30, 79–91 (2011).
   Google Scholar
• Pase MP, Grima NA, Sarris J. The effects of dietary and nutrient interventions on arterial stiffness: a systematic review. Am. J. Clin. Nutr. 93, 446–454 (2011).
   Google Scholar
• Adlercreutz H. Epidemiology of phytoestrogens. Baillieres Clin. Endocrinol. Metab. 12, 605–623 (1998).
   Google Scholar
• Ørgaard A, Jensen L. The effects of soy isoflavones on obesity. Exp. Biol. Med. 233, 1066–1080 (2008).
   Google Scholar
• Weghuber D, Widhalm K. Effect of 3 month treatment of children and adolescents with familial and polygenic hypercholesterolemia with a soy-substituted diet. Br. J. Nutr. 99, 281–286 (2008).
   Google Scholar
• Chen ST, Ferng SH, Yang CS et al. Variable effects of soy protein on plasma lipids in hyperlipidemic and normolipidemic hemodialysis patients. Am. J. Kidney Dis 46, 1099–1106 (2005).
   Google Scholar
• Hutchins AM, McIver IE, Johnston CS. Hypertensive crisis associated with high dose soy isoflovane supplementation in a post-menopausal woman; a case report. BMC Women’s Health 5, 9 (2005).
   Google Scholar
• Cambria-Kiely JA. Effect of soy milk on warfarin. Ann. Pharmacother. 36, 1893–1896 (2002).
   Google Scholar
• Anderson GD, Rosito G, Mohustsy MA et al. Drug interaction potential of soy extract and Panax ginseng. J. Clin. Pharmacol. 43, 643–648 (2003).
   Google Scholar
• Monograph. Monascus purpureus (red yeast rice). Altern. Med. Rev. 9, 208–210 (2004).
   Google Scholar
• Cicero AF, Brancaleoni M, Laghi L et al. Antihyperlipidaemic effect of a Monascus purpureus brand dietary supplement on a large sample of subjects at low risk for cardiovascular disease: a pilot study. Complem. Ther. Med. 13, 273–278 (2005).
   Google Scholar
• Keithley JK, Swanson B, Sha BE et al. A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia. Nutrition 18, 201–204 (2002).
   Google Scholar
• Gheit O, Sheashaa H, Abdelsalam M et al. Efficacy and safety of Monascus purpureus Went rice in subjects with secondary hyperlipidemia. Eur. J. Intern. Med. 20, e57–e61 (2009).
   Google Scholar
• Liu J, Zhang J, Shi Y et al. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin. Medicine 1, 4 (2006).
   Google Scholar
• Zhao SP, Liu L, Cheng YC et al. Xuezhikang, an extract of cholestin, protects endothelial function through antiinflammatory and lipid-lowering mechanisms in patients with coronary heart disease. Circulation 110, 915–920 (2004).
   Google Scholar
• Lu Z, Kou W, Du B et al. Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction. Am. J. Cardiol. 101, 1689–1693 (2008). ▪ Demostration that red yeast rice is an efficacious drug in secondary prevention of cardiovascular disease and total mortality.
   Google Scholar
• Ye P, Lu ZL, Du BM et al. Effect of xuezhikang on cardiovascular events and mortality in elderly patients with a history of myocardial infarction: a subgroup analysis of elderly subjects from the China Coronary Secondary Prevention Study. J. Am. Geriatr. Soc. 55, 1015–1022 (2007).
   Google Scholar
• Castaño G, Mas R, Fernández L et al. Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolemia. Drugs Aging 20, 153–163 (2003).
   Google Scholar
• Noa M, Más R, Lariot C. Protective effect of policosanol on endothelium and intimal thickness induced by forceps in rabbits. J. Med. Food 10, 452–459 (2007).
   Google Scholar
• Castaño G, Más R, Gámez R et al. Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. Angiology 55, 361–371 (2004).
   Google Scholar
• Sirtori CR, Galli C, Anderson JW, Sirtori E, Arnoldi A. Functional foods for dyslipidaemia and cardiovascular risk prevention. Nutr Res. Rev. 22(2), 244–261 (2009).
   Google Scholar
• Marinangeli CP, Jones PJ, Kassis AN et al. Policosanols as nutraceuticals: fact or fiction. Crit. Rev. Food Sci. Nutr. 50, 259–267 (2010).
   Google Scholar
• Guardamagna O, Abello F, Baracco V et al. The treatment of hypercholesterolemic children: efficacy and safety of a combination of red yeast rice extract and policosanols. Nutr. Metab. Cardiovasc. Dis 21, 424–429 (2011).
   Google Scholar
• Abdul MI, Jiang X, Williams KM et al. Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. Br. J. Clin. Pharmacol. 69, 508–515 (2010).
   Google Scholar
• Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother. Res. 22(8), 999–1012 (2008).
   Google Scholar
• Cicero AF, Tartagni E. Antidiabetic properties of berberine: from cellular pharmacology to clinical effects. Hosp. Pract. 40, 56–63 (2012).
   Google Scholar
• Meng S, Wang LS, Huang ZQ et al. Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin. Exp. Pharmacol. Physiol. 39, 406–411 (2012).
   Google Scholar
• Cheng F, Wang Y, Li J et al. Berberine improves endothelial function by reducing endothelial microparticles-mediated oxidative stress in humans. Int. J. Cardiol. doi:10.1016/j.ijcard.2012.03.090 (2012) (Epub ahead of print).
   Google Scholar
• Xu MG, Wang JM, Chen L et al. Berberineinduced mobilization of circulating endothelial progenitor cells improves human small artery elasticity. J. Hum. Hypertens. 22, 389–393 (2008).
   Google Scholar
• Cicero AF, Tartagni E, Ferroni A et al. Combined nutraceutical approach to postmenopausal syndrome and vascular remodeling biomarkers. J. Alt. Compl. Med. (2012) (In Press).
   Google Scholar
• Chan E. Displacement of bilirubin from albumin by berberine. Biol. Neonate 63, 201–208 (1993).
   Google Scholar
• Tan YZ, Wu AC, Tan BY et al. Study on the interactions of berberine displace other drug from their plasma proteins binding sites. Chin. Pharmacol. Bull. 18, 576–578 (2002).
   Google Scholar
• Xin HW, Wu XC, Li Q et al. The effects of berberine on the pharmacokinetics of cyclosporine A in healthy volunteers. Methods Find. Exp. Clin. Pharmacol. 28, 25–29 (2006).
   Google Scholar
• Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J. Am. Coll. Cardiol. 58(20), 2047–2067 (2011).
   Google Scholar
• Campbell F, Dickinson HO, Critchley JA et al. A systematic review of fish-oil supplements for the prevention and treatment of hypertension. Eur. J. Prev. Cardiol. doi:10.1177/2047487312437056 (2012) (Epub ahead of print).
   Google Scholar
• Pase MP, Grima NA, Sarris J. Do long-chain n-3 fatty acids reduce arterial stiffness? A meta-analysis of randomised controlled trials. Br. J. Nutr. 106, 974–980 (2011).
   Google Scholar
• Thies F, Garry JM, Yaqoob P et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477–485 (2003).
   Google Scholar
• Cicero AF, Ertek S, Borghi C. Omega-3 polyunsaturated fatty acids: their potential role in blood pressure prevention and management. Curr. Vasc. Pharmacol. 7, 330–337 (2009).
   Google Scholar
• Valagussa F, Franzosi MG, Geraci E et al. Dietary supplementation with N-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI Prevenzione trial. Lancet 354, 447–455 (1999). ▪ Large intervention trial demonstrating that low supplemented doses of omega-3 polyunsaturated fatty acids are able to significantly reduce total mortality in secondary prevention for coronary heart disease.
   Google Scholar
• Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, Perez-Jimenez F. Long chain omega-3 fatty acids and cardiovascular disease: a systematic review. Br. J. Nutr. 107(Suppl. 2), S201–S213 (2012).
   Google Scholar
• Cicero AF, De Sando V, Parini A et al. Polyunsaturated fatty acids application in internal medicine: beyond the established cardiovascular effects. Arch. Med. Sci. (2012) (In Press).
   Google Scholar
• Hooper L, Thompson RL, Harrison RA et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. Brit. Med. J. 332, 752–760 (2006). ▪▪ Milestone review on the risk–benefit ratio in the use of omega-3 polyunsaturated fatty acids as preventive nutraceuticals.
   Google Scholar
• Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am. J. Cardiol. 99, 44C–46C (2007).
   Google Scholar
• Bhupathiraju SN, Tucker KL. Coronary heart disease prevention: nutrients, foods, and dietary patterns. Clin. Chim. Acta 412(17–18), 1493–1514 (2011).
   Google Scholar
• Ramprasath VR, Jones PJ. Anti-atherogenic effects of resveratrol. Eur. J. Clin. Nutr. 64(7), 660–668 (2010).
   Google Scholar
• Tomé-Carneiro J, Gonzálvez M, Larrosa M et al. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol. Nutr. Food Res. 56(5), 810–821 (2011).
   Google Scholar
• Mollace V, Sacco I, Janda E et al. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies. Fitoterapia 82(3), 309–316 (2011).
   Google Scholar
• Cesar TB, Aptekmann NP, Araujo MP, Vinagre CC, Maranhão RC. Orange juice decreases low-density lipoprotein cholesterol in hypercholesterolemic subjects and improves lipid transfer to high-density lipoprotein in normal and hypercholesterolemic subjects. Nutr. Res. 30(10), 689–694 (2010).
   Google Scholar
• Gorinstein S, Caspi A, Libman I, Katrich E, Lerner HT, Trakhtenberg S. Fresh Israeli jaffa sweetie juice consumption improves lipid metabolism and increases antioxidant capacity in hypercholesterolemic patients suffering from coronary artery disease: studies in vitro and in humans and positive changes in albumin and fibrinogen fractions. J. Agric. Food Chem. 52(16), 5215–5222 (2004).
   Google Scholar
• Demonty I, Lin Y, Zebregs YE et al. The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J. Nutr. 140(9), 1615–1620 (2010).
   Google Scholar
• Aviram M, Rosenblat M, Gaitini D et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin. Nutr. 23(3), 423–433 (2004).
   Google Scholar
• Davidson MH, Maki KC, Dicklin MR et al. Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease. Am. J. Cardiol. 104(7), 936–942 (2009).
   Google Scholar
• Prasad K. Tocotrienols and cardiovascular health. Curr. Pharm. Des. 17(21), 2147–2154 (2011).
   Google Scholar
• Baliarsingh S, Beg ZH, Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis 182(2), 367–374 (2005).
   Google Scholar
• Chin SF, Ibahim J, Makpol S et al. Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: a randomized controlled study. Nutr. Metab. 8(1), 42 (2011).
   Google Scholar
• Ried K, Fakler P. Protective effect of lycopene on serum cholesterol and blood pressure: meta-analyses of intervention trials. Maturitas 68(4), 299–310 (2011).
   Google Scholar
• McEneny J, Wade L, Young IS et al. Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals. J. Nutr. Biochem. doi:10.1016/j.jnutbio.2012.03.015 (2012) (Epub ahead of print).
   Google Scholar
• Xaplanteris P, Vlachopoulos C, Pietri P et al. Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects. Nutr. Res. 32(5), 390–394 (2012).
   Google Scholar
• Slevin M, Ahmed N, Wang Q, McDowell G, Badimon L. Unique vascular protective properties of natural products: supplements or future main-line drugs with significant anti-atherosclerotic potential? Vasc. Cell 4(1), 9 (2012).
   Google Scholar
• Houston MC, Fazio S, Chilton FH et al. Nonpharmacologic treatment of dyslipidemia. Prog. Cardiovasc. Dis. 52, 61–94 (2009).
   Google Scholar
• Ros E. Health benefits of nut consumption. Nutrients 2(7), 652–682 (2010).
   Google Scholar
• Trimarco B, Benvenuti C, Rozza F et al. Clinical evidence of efficacy of red yeast rice and berberine in a large controlled study versus diet. Med. J. Nutr. Metab. 4, 133–140 (2011).
   Google Scholar
• Cicero AFG, De Sando V, Izzo R et al. Effect of a combined nutraceutical containing Orthosiphon stamineus effect on blood pressure and metabolic syndrome components in hypertensive dyslipidaemic patients: a randomized clinical trial. Complement. Ther. Clin. Pract. 18(3), 190–194 (2012).
   Google Scholar
• Affuso F, Mercurio V, Ruvolo A et al. A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome. World J. Cardiol. 4, 77–83 (2012).
   Google Scholar
• Pirro M, Del Giorno R, Lupattelli G et al. Nutraceutical combination (red yeast rice, berberine and policosanols) improves aortic stiffnes in low-moderate risk hypercholesterolemic patients. Nutr. Res. (2012) (In Press).
   Google Scholar
• Yokoyama M, Origasa H, Matsuzaki M et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 369(9567), 1090–1098 (2007). ▪▪ First outcome study clearly showing the additive effect of a nutraceutical and a statin in reducing the cardiovascular disease risk in primary prevention.
   Google Scholar
• Lin X, Racette SB, Lefevre M et al. Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans. Circulation 124(5), 596–601 (2011).
   Google Scholar
• Eussen SR, Rompelberg CJ, Klungel OH, van Eijkeren JC. Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/stanols in humans. Lipids Health Dis. 10, 187 (2011).
   Google Scholar