Red Yeast Rice Extract: Will Positive Results Lead to Round 2 of Regulatory Controversy?
Red Yeast Rice Extract: Will Positive Results Lead to Round 2 of Regulatory Controversy?
Abstract & Commentary
By Dónal P. O'Mathúna, PhD. Dr. O'Mathúna is Senior Lecturer in Ethics, Decision-Making & Evidence, School of Nursing, Dublin City University, Ireland; he reports no financial relationship to this field of study.
Synopsis: A subgroup analysis on elderly Chinese patients with a history of myocardial infarction (MI) revealed beneficial effects of Xuezhikang, a red yeast rice extract. Risk of coronary and all-cause deaths were significantly lowered, total cholesterol and LDL- cholesterol levels were reduced, and HDL-cholesterol levels were increased significantly compared to placebo.
Source: Li JJ, 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.
Xuezhikang, a partial extract of red yeast rice (RYR) containing statins, has a marked impact on lipids. The purpose of this study was to evaluate the effect of Xuezhikang on cardiovascular events and mortality in elderly Chinese hypertensive (average 139/83 mm Hg) patients with a history of myocardial infarction (MI). Almost 5,000 people were enrolled between 1996 and 2000 in the Chinese Coronary Secondary Prevention Study. Among all the participants, 1,530 were identified as elderly hypertensive patients (age ≥ 65 years) with a previous MI. This article reports the subgroup analysis of this group. The participants were randomly assigned either to placebo or Xuezhikang (0.6 g twice daily) for an average of 4.5 years. The primary endpoint was recurrent fatal or nonfatal MI, sudden death, or other fatal coronary events. The secondary endpoint was all-cause mortality and other clinical events, including adverse effects.
There were 68 cases of coronary events (8.8%) detected in the Xuezhikang group and 108 cases (14.3%) in the placebo group (38.2% risk reduction by Xuezhikang therapy). Death from coronary heart disease (CHD) totaled 49 cases in the Xuezhikang group (6.4%) and 68 cases in the placebo group (9.0%), indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2%. The risk for all-cause death was 36.3% lower in the Xuezhikang group. Total cholesterol was reduced 11.3% and LDL-cholesterol 21.2% in the Xuezhikang group, which was significantly lower than in the placebo group (P < 0.0001). Triglyceride levels fell 12.1% more than in placebo (P = 0.0031). HDL-cholesterol levels increased by 4.0% while the placebo group showed no change. The two groups did not differ significantly in blood pressure levels after 4.5 years. The incidence of adverse events did not differ between the two groups (2.1% in the Xuezhikang group and 1.2% in placebo; P > 0.05).
The study authors concluded that Xuezhikang effectively and safely reduces cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI. This well-conducted study suggests that high-quality, standardized RYR products may be useful in treating elderly hypertensive patients with coronary heart disease.
Commentary
Red yeast rice has had a promising, yet controversial, history.1 It is made by fermenting rice with a specific yeast called Monascus purpureus. The resulting material is a deep red color and used as a food preservative in some Chinese dishes. In traditional Chinese medicine it has a reputation for improving circulation and preventing blood clotting.
Animal studies in China in the 1990s demonstrated beneficial effects on cholesterol levels. A U.S. dietary supplement manufacturer, Pharmanex, developed a formulation called Cholestin®. They also sponsored the first Western clinical trial with Cholestin, which showed beneficial effects on cholesterol.2 Analyses of Cholestin showed that it contained a group of statins called monaclonins. The most abundant of these is monaclonin K, also known as lovastatin. A regulatory battle ensued between Pharmanex and the FDA. After a number of appeals, Cholestin was ruled to be an unapproved drug and taken off the market.1 It reappeared soon afterwards, claiming to have similar health-related benefits, but without containing RYR. Meanwhile, other RYR products remain on the market, and researchers, primarily in China, have continued to study its benefits in Chinese patients. However, as was reported in the September issue of this publication, RYR is also being studied in Western patients and showing encouraging results.
This study by Li and colleagues was performed to the highest standards. The complete study was conducted at 66 different centers across 19 provinces in China. Randomization was conducted using numbers allocated by the study data center. Baseline characteristics did not differ significantly between the two groups. However, almost three times as many men enrolled in the study compared to women, which may limit the generalizability of its results. The capsules were standardized to contain 2.5-3.2 mg of monaclonin K. This dose was relatively low compared to other trials, which have given 2,400 mg or more of red yeast rice daily. An independent data and safety monitoring committee reviewed safety and efficacy data. Reports of various outcomes and adverse events were supported by objective data wherever possible. Seventeen participants were lost to follow-up (1.1%), with 7 in the Xuezhikang group and 10 in the placebo group.
The study was discontinued at the second interim analysis point because statistically significant benefit was obtained with the primary endpoint (P < 0.05). A relatively small number of adverse events occurred in the Xuezhikang group (16 vs. 9 in the placebo group). The adverse events reported included gastrointestinal discomfort, allergic reaction, myalgia, psychoneurological symptoms, erectile dysfunction, and edema.
This study adds to the growing number of trials reporting beneficial cholesterol-lowering effects of RYR.3 These researchers appear to have used a high-quality, standardized formulation of Xuezhikang. However, questions have regularly been raised about the quality and consistency of RYR available to the general public.4 In 2007, the FDA warned consumers to avoid RYR products available on the Internet because they contained unknown amounts of lovastatin.5 Case reports have been published of RYR causing the same types of adverse effects as statins, in particular muscle weakness and soreness, aching joints, and kidney problems.3
While RYR itself is demonstrating efficacy, the active ingredients appear to be statins. Therefore, people taking RYR should be attentive to the side effects and drug interactions known with statins. However, since RYR products are readily available as dietary supplements, many may not be monitoring themselves for such adverse effects. The regulatory situation with dietary supplements also makes it very difficult for clinicians to know which brands are reliable. Until reliable, high-quality brands can be clearly identified, consumers and clinicians will be left deciding in the dark.
References
1. O'Mathúna DP. Cholestin® for the treatment of hypercholesterolemia. Altern Med Alert 1999;2:37-41.
2. Heber D, et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231-236.
3. Klimek M, et al. Safety and efficacy of red yeast rice (Monascus purpureus) as an alternative therapy for hyperlipidemia. Pharm Therap 2009;34:313-327.
4. Phillips PS. Balancing randomized trials with anecdote. Ann Intern Med 2009;150:885-886.
5. FDA Warns Consumers to Avoid Red Yeast Rice Products Promoted on Internet as Treatments for High Cholesterol; Products found to contain unauthorized drug. Released Aug. 9, 2007. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108962.htm. Accessed Oct. 7, 2009.
A subgroup analysis on elderly Chinese patients with a history of myocardial infarction (MI) revealed beneficial effects of Xuezhikang, a red yeast rice extract. Risk of coronary and all-cause deaths were significantly lowered, total cholesterol and LDL- cholesterol levels were reduced, and HDL-cholesterol levels were increased significantly compared to placebo.Subscribe Now for Access
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