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The Mechanism of Red Yeast Rice's (Monascus purpureus rice) Lipid Lowering Effect

Summary:

  • Red yeast rice is made from fermented rice containing the mold, Monascus purpureus and historically has been marketed in China for its medicinal properties.  Other marketed names or brands include Cholestin and Xuezhikang.
  • Batches of red yeast rice produced can contain varying amounts of an active ingredient called, monacolin K, which is structurally similar to the statin medication, lovastatin (Mevacor).
  • The lipid lowering properties of red yeast rice does appear to be multifactorial and includes the ability to inhibit the activity of the rate limiting step of hepatic cholesterol biosynthesis in a dose-dependent manner, indirectly cause an upregulation or availability of LDL-receptors in the liver, and possibly by increasing the hepatic excretion of bile acids, thereby increasing the need for the availability of intrahepatic cholesterol to be used for the synthesis of additional bile.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Reviewer:
Donald S. Nuzum, PharmD, BCACP, CDE
Last Reviewed: August 2015

Explanation

  • Red yeast rice is made from fermented rice containing the mold, Monascus purpureus and historically has been marketed in China for its medicinal properties and as a food preservative to maintain taste and color of meat and fish.  Other marketed names or brands include Cholestin and Xuezhikang.  As it relates to its medicinal properties, the most cited effect includes its ability to improve the lipid profile and possibly reduce the risk for cardiovascular events.1-13  This appears to be due to red yeast rice's ability to reduce the total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), triglycerides (TG) and possibly increase the high density lipoprotein cholesterol (HDL-C).1-10 

    Are there any active ingredients in red yeast contributing to this lipid lower effect?
    Yes. Depending on the conditions of fermentation, the batches of red yeast rice produced can contain varying amounts of an active ingredient called, monacolin K.14-17  This is relevant to understanding its apparent mechanism of action since monacolin K is also known as mevinolin and is structurally similar to the HMG CoA reductase inhibitor  lovastatin (Mevacor) .17-19  It has been reported that Cholestin in particular is known to contain 0.4% HMG-CoA reductase inhibitors by weight, as well as other isoflavones, monosaturated fatty acids, and sterols.17 

    Do the ingredients found in red yeast rice work in the same manner as the statin medications currently on the market?
    Yes, but the lipid lowering properties of red yeast rice does appear to be multifactorial.   One of the first and more obvious mechanisms to be supported is red yeast rice's ability to inhibit the activity of the rate limiting step of hepatic cholesterol biosynthesis in a dose-dependent manner.19  This is due to its ability to inhibit the activity of the enzyme, HMG CoA reductase.  As a quick summary, cholesterol is made within the liver or hepatocyte.  This process is started when an acetyl CoA and acetoacetyl CoA come together to form 3-hydroxy-3-methylglutaryl CoA (HMG CoA).  The newly formed HMG CoA is then reduced to mevalonate through the enzyme, HMG CoA reductase.20,21  The newly formed mevalonate eventually gets converted into isopentenyl pyrophosphate, which then continues on through a number of reactions, one of which leads to the formation of cholesterol.  Therefore, an interruption in the conversion of HMG CoA to mevalonate can disrupt the hepatic synthesis of cholesterol. 

    The reduced intrahepatic cholesterol concentrations result in the upregulation or availability of LDL-receptors in the liver.20,21  The purpose of the upregulated or additional LDL-receptors is to pull cholesterol out of circulation and bring it into the liver to replace what was not made.  As such, the plasma cholesterol levels will decrease through two mechanisms: 1) through a reduction in the hepatic synthesis of cholesterol and 2) through an increase in the removal of circulating cholesterol from the plasma for the liver to use.  Additionally, recent animal data in hamsters suggested that red yeast rice also increases the hepatic excretion of bile acids, thereby increasing need for the availability of intrahepatic cholesterol to be used for the synthesis of additional bile.15  Therefore, this reduction in TC, LDL-C, TG and possibly an increase in HDL-C can reduce the risk associated with the formation of atherosclerotic lesions.

    References:

    1. Li JJ, Wang Y, Nie SP et al.  Xuezhikang, an extract of cholestin, decreases plasma inflammatory markers and endothelin-1, improve exercise-induced ischemia and subjective feelings in patients with cardiac syndrome X.  Int J Card 2007;122:82-4.
    2. Hu Cl, Li YB, Tang YH et al.  Effects of withdrawal of Xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with coronary artery disease.  Cariovasc Drugs Ther 2006;20:185-191.
    3. Li JJ, Hu SS, Fang CH et al.  Effects of xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term course study in patients with stable angina.  Clinica Chimica Acta  2005;352:217-24.
    4. Cicero AFG, 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.  Complement Ther Med  2005;13:273-8.
    5. Zhao SP, Liu L, Cheng YC et al.  Effects of xuezhikang, a cholestin extract, on reflecting postprandial triglyceridemia after a high-fat meal in patients with coronary heart disease.  Atherosclerosis  2003;168:375-80.
    6. Keithley JK, Swanson B, Sha BE et al.  A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia.  Nutrition  2002;18:201-4. 
    7. Gheith O, Sheashaa H, Abdelsalam M et al.  Efficacy and safety of Monascus purpureus Went rice in subjects with secondary hyperlipidemia.  Clin Exp Nephrol 2008;12:189-194.
    8. Liu L, Zhao SP, Cheng YC et al. Xuezhikang decreases serum lipoprotein(a) and C-reactive protein concentrations in patients with coronary heart disease.  Clinical Chemistry  2003;49:1347-1352.
    9. Lin CC, Li TC, Lai MM.  Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia.  Eur J Endocrinol 2005;153:679-86. 
    10. Zhao SP, Lu ZL, Du BM et al.  Xuezhikang, an extract of cholestin, reduces cardiovascular events in type 2 diabetes patients with coronary heart disease: subgroup analysis of patients with type 2 diabetes from China coronary secondary prevention study (CCSPS).  J Card Pharmacol  2007;49:81-4.
    11. Li JJ, Lu ZL, Kou WR et al.  Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS).  J Clin Pharmacol  2009;49:947-956.
    12. 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;101:1689-93.
    13. Lu ZL, Collaborative Group for China Coronary Secondary Prevention Using Xuezhikang.  China coronary secondary prevention study (CCSPS).  Zhonghua Xin Xue Guan Bing Za Zhi  2005;33:109-15.
    14. Li YG, Zhang F, Wang ZT et al.  Identification and chemical profiling of monacolins in red yeast rice using high-performance liquid chromatography with photodiode array detector and mass spectrometry.  J Pharm Biomed Anal 2004;35:1101-1012.
    15.  Ma KY, Zhang ZS, Zhao SX et al.  Red yeast rice increases excretion of bile acids in hamsters.  Biomed Environ Sci  2009;22:269-77.
    16. Ma J, Li Y, Ye Q et al.  Constituents of red yeast rice, a traditional Chinese food and medicine.  J Agric Food Chem 2000;48:5220-5. 
    17. Heber D, Yip I, Ashley JM et al.  Cholesterol-lowering effects of a proprietary Chinese red-yeast rice dietary supplement.  Am J Clin Nutr  1999;69:231-6.
    18. Havel RJ, Hunninghake DB, Illingworth DR et al.  Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia.  A multicenter study.  Ann Intern Med 1987;107:609-15.
    19. Man RY, Lynn EG, Cheung F et al.  Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2).  Mol Cell Biochem  2002;233:153-158. 
    20. Honda A, Salen G, Nguyen LB et al.  Down-regulation of cholesterol biosynthesis in sitosterolemia: diminished activities of acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase, reductase, squalene synthase, and 7-dehydrocholesterol delta7-reductase in liver and mononuclear leukocytes.  J Lipid Res 1998;39:44-50.
    21. Kwiterovich PO Jr.  The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review.  Am J Cardiol 2000 86(12A):5L-10L.
    22. Food and Drug Administration.  FDA warns consumers to avoid red yeast rice products promoted on internet as treatments for high cholesterol products found to contain unauthorized drug.  FDA News Release.  August 9, 2007.

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MESH Terms & Keywords

  • Red Yeast Rice, Monascus purpureus, Cholestin, Xuezhikang, Red Yeast Rice Lipid Lowering