The Role of Red Yeast Rice Based Preparations for Non-Pharmacological Correction of Dyslipidemia in Patients with Low and Moderate Cardiovascular Risk (Expert Opinion)

The Russian Federation is among countries with high cardiovascular risk. Hypercholesterolemia is a leading risk factor for the development of atherosclerotic cardiovascular diseases. To achieve low-density lipoprotein cholesterol (LDL-C) targets, such approaches as lifestyle changes and pharmacological correction, based on the use of statins, are applied. At the same time, a significant proportion of the population has moderate hypercholesterolemia and is characterized by low or moderate cardiovascular risk. Although first-line recommendations should be followed, a healthy lifestyle alone is not enough to achieve target levels of LDL-C, which means that even people with low to moderate risk may end up with the prospect of lifelong therapy with lipid-lowering drugs. These individuals do not have an indication for lipid-lowering therapy, and they are usually recommended a change in diet and supplementation. Innovative nutritional strategies have been developed to manage dyslipidemia. They were based either on changing some “risky” food components or on encouraging the consumption of “healthy” functional foods and/or nutraceuticals. Nutraceuticals (registered as food supplements in Russia) is an innovative way to help control LDL-C at low and moderate risk individuals without lipid-lowering drugs and as nutritive support for the cholesterol-lowering diet. Red yeast rice (RYR) based preparations have been already developed and available at the moment. RYR based preparations can be considered in patients with low and moderate cardiovascular risk, who have not reached the target level of LDL-C and have no indications for statin therapy or have statin intolerance. RYR based preparations contains a statin-like substance monacolin K in a dose of 3 mg. In randomized clinical trials, it was proved that the use of high-quality RYR nutraceutical leads to a decrease in LDL-C by an average of 20% without increasing the risk of side effects like for statins. Evaluation of dietary supplements and functional foods should necessarily include not only evidence of beneficial effects with respect to effects on the lipid profile and atherosclerosis, but also proven good tolerability. The manufacturing standard for these products is also important, guaranteeing component standardization and quality. RYR analogues should guarantee the absence of mycotoxin in their composition. In Russia, programs are needed for the primary prevention of atherosclerotic cardiovascular diseases with effects on hypercholesterolemia at the population level.

1. Ference B.A., Ginsberg H.N., Graham I., et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459-72. DOI:10.1093/eurheartj/ehx144.

2. Baigent C., Blackwell L., Emberson J., et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81. DOI:10.1016/S0140-6736(10)61350-5.

3. Baigent C., Keech A., Kearney P.M., et al. Cholesterol Treatment Trialists C. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-78. DOI:10.1016/S01406736(05)67394-1.

4. Sabatine M.S., Giugliano R.P., Keech A.C., et al. Committee FS Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-22. DOI:10.1056/nejmoa1615664.

5. Schwartz G.G., Steg P.G., Szarek M et al. Committees OO Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-107. DOI:10.1056/NEJMoa1801174.

6. Mach F., Baigent C., Catapano A.L., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-88. DOI:10.1093/eurheartj/ehz455.

7. Banach M., Penson P.E. What have we learned about lipids and cardiovascular risk from PCSK9 inhibitor outcome trials: ODYSSEY and FOURIER? Cardiovasc Res. 2019;115(3):e26-31. DOI:10.1093/cvr/cvy301.

8. Metelskaya V.A., Shalnova S.A., Deev A.D., et al. An analysis of the prevalence of indicators characterizing the atherogenicity of the lipoprotein spectrum in residents of the Russian Federation (according to the ESSE-RF study). Prophylactic Medicine. 2016;19(1):15-23 (In Russ.) DOI:10.17116/profmed201619115-23.

9. Endo A., Hasumi K., Negishi S. Monacolins J and L, new inhibitors of cholesterol biosynthesis produced by Monascus ruber. J Antibiot (Tokyo). 1985;38(3):420-2. DOI:10.7164/antibiotics.38.420.

10. Beltran D., Frutos-Lison M.D., Espin J.C., Garcia-Villalba R. Re-examining the role of the gut microbiota in the conversion of the lipid-lowering statin monacolin K (lovastatin) into its active beta-hydroxy acid metabolite. Food Funct. 2019;10(4):1787-91. DOI:10.1039/c8fo02594k.

11. Chen C.H., Uang Y.S., Wang S.T., et al. Interaction between red yeast rice and CYP450 enzymes/Pglycoprotein and its implication for the clinical pharmacokinetics of lovastatin. Evid Based Complement Alternat Med. 2012;2012:127043. DOI:10.1155/2012/127043.

12. Doughari J.H. The occurrence, properties and significance of citrinin mycotoxin. J Plant Pathol Micriobiol. 2015;6(11):321 W147-839. DOI:10.4172/2157-7471.1000321.

13. Song J., Luo J., Ma Z., et al. Quality and authenticity control of functional red yeast rice-A review. Molecules. 2019;24(10): pii E1944. DOI:10.3390/molecules24101944.

14. Heinz T., Schuchardt J.P., Moller K., et al. Low daily dose of 3 mg monacolin K from RYR reduces the concentration of LDL-C in a randomized, placebo-controlled intervention. Nutr Res. 2016;36(10):1162-70. DOI:10.1016/j.nutres.2016.07.005.

15. Becker D.J., Gordon R.Y., Halbert S.C., et al. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial. Ann Intern Med. 2009;150(12):830-9. DOI:10.7326/0003-4819-150-12200906160-00006.

16. Bogsrud M.P., Ose L., Langslet G., et al. HypoCol (red yeast rice) lowers plasma cholesterol a randomized placebo controlled study. Scand Cardiovasc J. 2010;44(4):197-200. DOI:10.3109/14017431003624123.

17. Mazzanti G., Moro P.A., Raschi E., et al. Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol. 2017;83(4):894-908. DOI:10.1111/bcp.13171.

18. Gerards M.C., Terlou R.J., Yu H., et al. Traditional Chinese lipidlowering agent red yeast rice results in significant LDL reduction but safety is uncertain a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415-23. DOI:10.1016/j.atherosclerosis.2015.04.004.

19. Fogacci F., Banach M., Mikhailidis D.P., et al. Lipid, Blood Pressure Meta-analysis Collaboration G, International Lipid Expert P. Safety of red yeast rice supplementation: a systematic review and metaanalysis of randomized controlled trials. Pharmacol Res. 2019;143:1-16. DOI:10.1016/j.phrs.2019.02.028.

20. 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. 2008;101(12):1689-93. DOI:10.1016/j.amjcard.2008.02.056.

21. Banach M., Rizzo M., Toth P.P, et al. Statin intolerance an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci. 2015;11(1):1-23. DOI:10.5114/aoms.2015.49807.

22. Banach M., Stulc T., Dent R., Toth P.P. Statin non-adherence and residual cardiovascular risk: there is need for substantial improvement. Int J Cardiol. 2016;225:184-96. DOI:10.1016/j.ijcard.2016.09.075.

23. Banach M., Patti A.M.., Giglio RV., et al. International lipid expert Panel. The role of nutraceuticals in statin intolerant patients. J Am Coll Cardiol. 2018;72(1):96-118. DOI:10.1016/j.jacc. 2018.04.040.

24. Rosenson R.S., Baker S., Banach M., et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70(10):1290-301. DOI:10.1016/j.jacc.2017.07.752.

25. Ference B.A., Majeed F., Penumetcha R., et al. Effect of naturally random allocation to lower lowdensity lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 x 2 factorial Mendelian randomization study. J Am Coll Cardiol. 2015;65(15):1552-61. DOI:10.1016/j.jacc.2015.02.020.

26. Serban M.C., Colantonio L.D, Manthripragada A.D., et al. Statin intolerance and risk of coronary heart events and all-cause mortality following myocardial infarction. J Am Coll Cardiol. 2017;69(11):1386-95. DOI:10.1016/j.jacc.2016.12.036.

27. Banach M., Bruckert E., Descamps O.S., et al. The role of red yeast rice (RYR) supplementation in plasma cholesterol control: A review and expert opinion. Atheroscler Suppl. 2019;39:e1-e8. DOI:10.1016/j.atherosclerosissup.2019.08.023.