Red Yeast Rice — Still Alive and Kicking
Red Yeast Rice Still Alive and Kicking
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.
Synopsis: Red yeast rice and therapeutic lifestyle changes decrease LDL-cholesterol levels without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.
Source: Becker DJ, et al. Red yeast rice for dyslipidemia in statin-intolerant patients: A randomized trial. Ann Intern Med 2009;150:830-839.
Statins (HMG-COA reductase inhibitors) have proven to be the most effective lipid-lowering medications in our armamentarium and have also been demonstrated to be effective for both primary and secondary prevention of coronary artery disease.1-3 Although statins are generally well tolerated, small numbers of patients do develop gastrointestinal symptoms, liver function abnormalities (usually transient), or most frequently, clinically benign statin-associated myalgias (SAMs), which on rare occasions may deteriorate into an active myositis and/or into potentially life-threatening rhabdomyolysis, both of which are more serious complications of statin therapy.4 Because of SAMs, physicians and patients have sought alternative drug therapies such as ezetimibe, bile acid-binding resins, and niacin to manage hyperlipidemia. One of the most commonly utilized alternative lipid-lowering therapeutic agents has been red yeast rice, which is a widely available dietary supplement that has been used as an herbal medication in China for centuries.
Becker and associates performed a small study to evaluate the effectiveness and tolerability of red yeast rice combined with therapeutic lifestyle changes to treat dyslipidemic patients who could not tolerate statin therapy without developing SAMs.5 This relatively small, single-site study compared a group of patients with hyper-cholesterolemia who had discontinued at least one statin because of SAMs with resolution of the muscle pain when the medication was discontinued, with a control group of patients. Actively treated patients received three 600 mg capsules of red yeast rice twice-daily for 24 weeks and the control group of patients received placebo in similar doses. All patients were also enrolled in a multidisciplinary, 12-week therapeutic lifestyle change program,6 which patients attended weekly for 31 half-hour meetings, and received education and instruction in cardiovascular disease, nutrition, exercise, and relaxation techniques. LDL-cholesterol decreased by 35 mg/dL in the treatment group and by 15 mg/dL in the control group by week 24. The authors concluded that red yeast rice and therapeutic lifestyle changes decreased LDL-cholesterol levels without increasing CPK or pain levels and that the therapeutic combination may be a treatment option for dyslipidemia patients who could not tolerate statin therapy.
Commentary
The study performed by Becker and his group did demonstrate that red yeast rice reduced LDL-cholesterol, but they noted that the study had possible shortcomings in that it was an extremely small (31 active patients and 31 control patients) study, was performed at a single site, was of short duration (24 weeks), and focused only on laboratory measures. Although the chemical composition of the red yeast rice used in the study was known and carefully controlled, it must be recognized that the lack of consistency and control of the red yeast rice obtained from different manufacturers is a major problem, which probably will require FDA supervision.7,8 Clinical outcomes were not determined in either group of patients. Two of the 29 (7%) patients in the red yeast rice group developed persistent, intolerable myalgias and discontinued treatment. The frequency of occurrence of SAMs in the general population of patients treated with statin drugs is generally accepted as being quite low; however, the data are poorly defined and in some studies have been demonstrated to be as high as 10%,9,10 a complication rate not terribly different from the 7% of patients who received red yeast rice and who developed SAMs in the Becker study.5 Finally, it is important to note that the red yeast rice used in this study contained lovastatin in a daily dose of 6 mg/day (or 42 mg per week) which, although is far less than the usual therapeutic dose of 10-80 mg/d, may be an adequate LDL-cholesterol-lowering dose for selected individuals. It should also be noted that other statins such as atorvastatin and rosuvastatin have relatively long plasma half-lives of 15 and 20 hours, respectively,11 which renders them both potentially suitable for non-daily dosing regimens and may effectively lower LDL-cholesterol levels with a minimum of adverse effects because of the low total statin dosage. Alternate day dosing of atorvastatin12 has reduced LDL-cholesterol by 38% with no development of myopathy and similar results were obtained with alternate day and even weekly doses of rosuvastatin13 without development of significant SAMs. Of course, none of these studies have been structured to determine whether cardiovascular risk reduction occurs with these small doses of statin drugs.
One of the most important facts that must be recognized is that statin drugs have clearly been demonstrated to have positive effects on the primary and secondary prevention of coronary artery disease and are not just effective in lowering LDL-cholesterol. None of the alternative medications, including red yeast rice, have been demonstrated to have positive outcome studies and one cannot simply presume that lowering the LDL-cholesterol will result in reductions in primary and/or secondary coronary artery disease events. Also, future studies with red yeast rice should address a number of questions such as: 1) Does this product reduce the incidence of SAMs when compared with statin therapy rather than simply comparing the results to only a placebo; 2) Is red yeast rice effective in patients with previous SAMs who are not enrolled in a lifestyle change program; and 3) Did the lifestyle change program itself decrease the incidence of SAMs in the red yeast rice group.
In summary, statin therapy even in non-daily doses would appear to be preferable to non-statin therapy including red yeast rice until it has been clearly demonstrated that non-statin therapy has beneficial clinical outcome effects rather than simply acting as an agent that modestly lowers LDL-cholesterol values. The occurrence of SAMs, although infrequent, will forcibly guide our clinical choices in any individual patient but, if at all possible, statin therapy if tolerated even in only non-daily doses is probably preferable to alternative medications including red yeast rice for the treatment of hyperlipidemia until qualified clinical studies demonstrating statistically significant beneficial outcomes have been performed with the alternative medications.
References
1. Downs JR, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of the AFCAPS/TexCAP. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615-1622.
2. Collins R, et al; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with the simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial. Lancet 2003;361:205-216.
3. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-lowering treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002;288:2998-3007.
4. Bays H. Statin safety: An overview and assessment of the data 2005. Am J Cardiol 2006;97(8A):6C-26C.
5. Becker DJ, et al. Red yeast rice for dyslipidemia in statin-intolerant patients: A randomized trial. Ann Intern Med 2009;150:830-839.
6. Becker DJ, et al. Simvastatin vs therapeutic lifestyle changes and supplements: Randomized primary prevention trial. Mayo Clin Proc 2008;83:758-764.
7. Harding A. Contamination common in red yeast rice products. New York: Thomson Reuters; 2008. Available at: www.reuters.com/article/healthNews/idUSCOL.97022820080709. Accessed April 22, 2009.
8. Heber D, et al. An analysis of nine proprietary Chinese red yeast rice dietary supplements: Implications of variability in chemical profile and contents. J Altern Complement Med 2001;7:133-139.
9. Bruckert E, et al. Mild to moderate muscular symptoms with high-dose statin therapy and hyperlipidemic patientsthe PRIMO study. Cardiovasc Drugs Ther 2005;19:403-414.
10. Kashani A, et al. Risks associated with statin therapy: A systematic overview of randomized clinical trials. Circulation 2006;114:2788-2797.
11. Baker SK, Samjoo IA. A neuromuscular approach to statin-related myotoxicity. Can J Neurol Sci 2008;35:8-21.
12. Matalka MS, et al. Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing Atorvastatin Study (ADDAS). Am Heart J 2002;144:674-677.
13. Backes JM, et al. Effects of once weekly rosuvastatin among patients with a prior statin intolerance. Am J Cardiol 2007;100:554-555.
Red yeast rice and therapeutic lifestyle changes decrease LDL-cholesterol levels without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.Subscribe Now for Access
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