Safety of Red Yeast Rice

Background

Red yeast is produced by fermenting rice with Monascus purpureus yeast.1 It is sold as a dietary supplement in the U.S. People use it to lower cholesterol. But not all red yeast rice products are legal, and some may be dangerous. This article reviews the regulatory and safety issues surrounding red yeast rice.

Regulatory Issues

Red yeast rice contains mevinic acids, also known as monacolins. These compounds competitively inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, blocking cholesterol biosynthesis. Monacolin K, or mevnolin, is better known as lovastatin.1

Red yeast rice that is fermented in the traditional way contains only trace amounts of lovastatin, if any.2 But the process can be manipulated to increase the amount of lovastatin and similar compounds by carefully controlling temperature and other growing conditions.1 Red yeast rice supplements produced this way cannot be legally sold as dietary supplements in the U.S. They're considered unapproved drugs.2 Even so, some products available to consumers provide therapeutic doses of lovastatin when taken as directed (e.g., 10 mg or more).2,3

Efficacy

Several studies have found that red yeast rice supplements lower LDL cholesterol. This is not surprising, considering the study participants were receiving 5 mg to 15 mg of lovastatin daily.3-5 Red yeast also contains sterols, including beta-sitosterol, campesterol, stigmasterol, and sapogenin; isoflavones and isoflavone glycosides; and monounsaturated fatty acids. It is unclear to what extent these other compounds contribute to efficacy. The overall cholesterol-lowering effect of red yeast is likely also the result of the combination of lovastatin, other mevinic acids, and other constituents.1

Safety

Red yeast that is not fermented correctly may contain citrinin. Citrinin is a toxin that may cause kidney failure.1 Several case reports of myopathy have been reported in patients taking red yeast rice products.6-8

Recently, a case of symptomatic hepatitis was reported in association with a red yeast rice product. The patient had taken red yeast rice 600 mg twice daily for about four months before presentation. She presented with a 10-week history of flu-like symptoms, but nausea, vomiting, diarrhea, chills, and fever prompted her to seek medical attention. Aspartate aminotransferase and alanine aminotransferase were over five and 14 times the upper limits of normal, respectively. Liver biopsy findings were consistent with drug-induced hepatitis. The product label did not list the specific ingredients. Symptoms and liver function tests resolved with product discontinuation.8

Drug Interactions

Red yeast rice with lovastatin has the potential for the same drug and food interactions as prescription lovastatin (e.g., gemfibrozil, CYP3A4 inhibitors, grapefruit juice).1 In one case report of asymptomatic creatine kinase elevation, the patient was also taking cyclosporine, which is known to inhibit lovastatin metabolism.6 In one case of myopathy, the patient was taking concomitant simvastatin.7

Commentary

Red yeast rice has recently been recommended in the lay press to lower cholesterol.9 Patients may believe it is safer than prescription statins. But because the actual statin content is unknown, and there is the potential for citrinin contamination, red yeast rice may actually be less safe than prescription statins. Even though red yeast rice sold as a dietary supplement in the U.S. should not contain significant amounts of lovastatin, some products do. Don't recommend red yeast rice. Learn about other natural products for hyperlipemia in our continuing education offering Natural Medicines in the Clinical Management of Hyperlipidemia.

Project Leader in preparation of this Detail-Document: Melanie Cupp, Pharm.D., BCPS

References

  1. Jellin JM, Gregory PJ, et al. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. (Accessed November 5, 2008).
  2. FDA warning letter. http://www.fda.gov/foi/warning_letters/s6692c.htm. (Accessed November 5, 2008).
  3. Becker DJ, Gordon RY, Morris PB, et al. Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial. Mayo Clin Proc 2008;83:758-64.
  4. Yovchevski PH, Doncheva NI. Low-dose statin concentration in red yeast rice: a confounding effect on outcome? Mayo Clin Proc 2008;83:1187.
  5. Liu J, Zhang J, Shi Y, et al. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chinese Med 2006;1:4.
  6. Mueller PS. Symptomatic myopathy due to red yeast rice. Ann Intern Med 2006;145:474-5.
  7. Lapi F, Gallo E, Bernasconi S, et al. Myopathies associated with red yeast rice and liquorice: spontaneous reports from the Italian Surveillance System of Natural Health Products. Br J Clin Pharmacol 2008;66:572-4.
  8. Cartin-Ceba R, Lu LB, Kolpakchi A. A "natural" threat. Am J Med 2007;120:e3-4.
  9. Roselle H, Ekatan A, Tzeng J, et al. Symptomatic hepatitis associated with the use of herbal red yeast rice. Ann Intern Med 2008;149:516-7.

Cite this Detail-Document as follows: Safety of red yeast rice. Pharmacist's Letter/Prescriber's Letter 2008;24(12):241203.

December 2008

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