Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients

Abstract

Introduction

Statins are at the forefront of strategies to manage dyslipidemia, although they are not always well tolerated. At 6–7 months after the drug was supplied, discontinuation rates averaged 30%. Alternate agents to statins have been studied. Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations. However, there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients. The purpose of this study was to examine the efficacy, safety, and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins.

Methods

This study was performed as a randomized, prospective, parallel group, single-blind study. Patients were included in the study if they had high total cholesterolemia, high low-density lipoprotein cholesterol (LDL-C), >75 years of age, statin-intolerant, and were refusing other pharmaceutical treatments for hypercholesterolemia. At the baseline visit, eligible patients were randomized to either nutraceutical-combined pill (containing berberine 500 mg, policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg) or placebo, and the first dose was dispensed. The efficacy, safety, and tolerability of the proposed treatment were fully assessed after 3, 6, and 12 months of treatment.

Results

Out of 106 consecutive patients screened, 80 eligible patients were randomized to receive either nutraceutical-combined pill (40 patients) or placebo (40 patients). No patients were lost and no deaths occurred during the follow-up. There was a statistically significant reduction in total cholesterolemia (−20%), LDL-C (−31%), and insulin resistance (−10%) with nutraceutical treatment. No significant changes were detected for plasma high-density lipoprotein cholesterol (HDL-C). Furthermore, no statistical differences were found between baseline and end-study safety parameters. Medication compliance and tolerability were high.

Conclusion

In this study the authors have demonstrated that combined nutraceuticals significantly reduce cholesterolemia and achieved acceptable plasma LDL-C levels in elderly hypercholesterolemic patients who were previously statin-intolerant. Combined nutraceuticals is also safe and well tolerated in these patients.

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References

  1. 1.

    American Heart Association 2011. Heart and Stroke Statistical Update. Available at: http://www.heart.org/HEARTORG/General/Heart-and-Stroke-Association-Statistics_UCM_319064_SubHomePage.jsp. Last accessed November 7, 2011.

  2. 2.

    Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326: 1419. Erratum in: BMJ. 2003;327:586. BMJ. 2006;60:823.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Yusuf S, Hawken S, Ounpuu S, et al. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–952.

    PubMed  Article  Google Scholar 

  4. 4.

    Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths Prospective Studies Collaboration Lancet. 2007;70:1829–1839.

    Google Scholar 

  5. 5.

    Kronmal RA, Cain KC, Omenn GS. Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993;153:1065–1073.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Vaughan CJ, Gotto AM Jr. Update on statins: 2003. Circulation. 2004;110:886–892.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Afilalo J, Duque G, Steele R, et al. Statins for secondary prevention in elderly patients. J Am Coll Cardiol. 2008;51:37–45.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289:1682–1690.

    Google Scholar 

  9. 9.

    Thompson PD, Clarkson PM, Rosenson RS. National Lipid Association Statin Safety Task Force Muscle Safety Expert Panel. An assessment of statin safety by muscle experts Am J Cardiol. 2006;97:69C–76C.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288:462–467.

    PubMed  Article  Google Scholar 

  11. 11.

    Heeschen C, Hamm CW, Laufs U, et al. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Investigators. Withdrawal of statins increases event rates in patients with acute coronary syndromes. For the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Investigators. Circulation. 2002;105:1446–1452.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Thomas MK, Narang D, Lakshmy R, et al. Correlation between inflammation and oxidative stress in normocholesterolemic coronary artery disease patients ‘on’ and ‘off’ atorvastatin for short time intervals. Cardiovasc Drugs Ther. 2006;20:37–44.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Kalra EK. Nutraceutical — definition and introduction. AAPS PharmSci. 2003;5:E25.

    PubMed  Article  Google Scholar 

  14. 14.

    Cicero AFG, Rovati L, Setnikar I. Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents in humans. Arzneimittelforschung. 2007;57:26–30.

    PubMed  CAS  Google Scholar 

  15. 15.

    Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nature Med. 2004;10;1344–1351.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999;69:231–236.

    PubMed  CAS  Google Scholar 

  17. 17.

    Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial. Ann Intern Med. 2009;150:830–839, W147–9.

    PubMed  Google Scholar 

  18. 18.

    Pons P, Rodriguez M, Robaina C, et al. Effects of successive dose increases of policosanol on the lipid profile of patients with type II hypercholesterolaemia and tolerability to treatment. Int J Clin Pharmacol Res. 1994;14:27–33.

    PubMed  CAS  Google Scholar 

  19. 19.

    Greyling A, De Witt C, Oosthuizen W, et al. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolaemic and heterozygous familial hypercholesterolaemic subjects. Br J Nutr. 2006;95:968–975.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Janikula M. Policosanol: a new treatment for cardiovascular disease? Altern Med Rev. 2002;7:203–217.

    PubMed  Google Scholar 

  21. 21.

    Singh DK, Li L, Porter TD. Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase. J Pharmacol Exp Ther. 2006;318:1020–1026.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Affuso F, Ruvolo A, Micillo F, et al. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010;20:656–661.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Ni YX. Therapeutic effect of berberine on 60 patients with type II diabetes mellitus and experimental research. Zhong Xi Yi Jie He Za Zhi. 1988;8707:711–713.

    Google Scholar 

  24. 24.

    Brusq JM, Ancellin N, Grondin P, et al. Inhibition of lipid synthesis through activation of AMPkinase: an additional mechanism for the hypolipidemic effects of Berberine. J Lipid Res. 2006;47:1281–1288.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocr Metab. 2008;93:2559–2565.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Pan GY, Huang ZJ, Wang GJ. The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med. 2003;69:632–636.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Kong WJ, Zhang H, Song DQ, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism. 2009;58:109–119.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Giuseppe Marazzi.

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Marazzi, G., Cacciotti, L., Pelliccia, F. et al. Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Adv Therapy 28, 1105–1113 (2011). https://doi.org/10.1007/s12325-011-0082-5

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Keywords

  • berberine
  • elderly patients
  • hypercholesterolemia, nutraceuticals
  • policosanol
  • red yeast rice
  • statin-intolerant
  • statins