This product, with its colorful, tongue-twisting name, is causing quite a sensation among herbal proponents as an alternative to prescription statins for lipid control. Chinese and other east Asian cultures have used red yeast rice since the Tang dynasty (circa 800 ad) as a food coloring and preservative.1 Medically, red yeast rice was discussed as a treatment for indigestion, diarrhea, and improved blood circulation in a Chinese pharmacopoeia during the Ming dynasty (1368-1644).2
Now classified as a traditional medicine in the Pharmacopoeia of the People’s Republic of China,2 red yeast rice actually combines two botanical species. White rice is washed, cooked, and then fermented with the yeast fungus Monascus purpureus to create a paste that is then dried, powdered, and sold in capsules.1 The powder contains an anticholesterol agent that exerts an HMG-CoA reductase inhibition and is molecularly similar to lova-statin. This 3-hydroxy-3-methylglutaryl-coenzyme A competitively blocks cholesterol biosynthesis in the liver.3 Like prescription statins, red yeast rice also lowers inflammatory C-reactive protein (CRP), which works with other inflammatory chemicals to produce endothelial injury and subsequent atherosclerotic damage.3
Evidence of effectiveness
Chinese researchers have done a number of meta-analyses on red yeast rice. One of them, which looked at trials that involved at least 2,000 participants, showed mean lipid reductions of 13 mg/dL for LDL and 7.3 mg/dL for triglycerides along with an increase in HDL of 2.7 mg/dL.4
Another meta-analysis of randomized, controlled trials featured the larger China Coronary Secondary Prevention Study (CCSPS). More than 4,800 participants were given 0.6 mg of red yeast rice twice daily or placebo. The patients were followed for an average of four years, and data were compiled for fatal cardiac events or nonfatal MIs. In the treatment arm, these primary end points were reduced by more than 45% compared with placebo.5 Overall cholesterol reductions were more modest, with LDL reductions averaging 14.7%.5
This apparent mismatch between LDL numbers and cardiac events excites both statin manufacturers and red yeast rice proponents. The key is felt to lie in the anti-inflammatory action of these compounds and may even indicate that this action is at least as significant as the lipid-modulating effects.
In the CCSPS trial, the daily dose of the red yeast rice formulation was chemically equal to about 10 mg per day of prescription lovastatin, but the end-point data mirrored doses of lovastatin in the 20- to 40-mg range.5 This and similar studies now have herbal researchers looking for a possible additional anti-inflammatory benefit that the red yeast rice possesses over and above that of a prescription statin.
Another Chinese trial, published in 2004, may shed light on this added anti-inflammatory property. In this study, 50 patients with known heart disease were randomized to red yeast rice or placebo for six weeks. As in other trials, lipid levels were monitored, but key endothelial irritant factors of high-sensitivity CRP (hs-CRP) and flow-mediated vasodilatation changes were also analyzed. At the end of the study period, the treatment group showed a 50% reduction in hs-CRP levels and 12% improvement over placebo in postprandial vessel dilation.6
Safety and regulatory issues
Now for the other side of the story: Because of the molecular similarity between the active ingredients in red yeast rice and lovastatin, the FDA granted a patent-infringement challenge from the pharmaceutical industry and ruled that traditional red yeast rice could no longer be marketed in the United States unless the lovastatin entity was removed.7
These altered red rice yeast products are still available, and people do buy them. However, the manufacturing processes are unregulated, raising significant concerns about safety. Reports have surfaced of contamination with citrinin, a neurotoxin that can develop during fermentation.8
Because dietary supplements are not subject to the same quality tests as prescription pharmaceuticals, consumers must to be very careful about the source and purity of any red yeast rice products sold in this country. Manufacturers’ quality standards can be researched on their Web sites and on subscription databases such as Consumerlab.
Dose and interactions
Red yeast rice is typically supplied in a powder-filled capsule. Daily dose is 1.2-2.4 g.2
Adverse effects from interactions with other drugs closely mimic those of the prescription statins, including myalgias and elevated liver enzymes. In all the trials researched, only one death from anaphylaxis was determined to be caused by the yeast used in fermentation.2
Red yeast rice is certainly intriguing. However, in light of the high degree of uncertainty as to its purity and safety and the easy availability of low-cost, proven statin pharmaceuticals, choosing red yeast rice over a prescription drug could be a dangerous gamble. Future studies will bear watching. Approved products may eventually appear in the marketplace, but until then, patients should resist the urge to “go natural” and stick to a conventional, regulated prescription drug.
1. Thompson Coon JS, Ernst E. Herbs for serum cholesterol reduction: a systematic view. J Fam Pract. 2003;52:468-478.
2. Zhang ML, Peng C-X, ZhouY-F, inventors. Peking University, Beijing, assignee. Methods and compositions employing red rice fermentation products. U.S. Patent: 6632428. October 14, 2003.
3. Patrick L, Uzick M. Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev. 2001;6:248-271.
4. Liu J, Zhang J, Shi Y, et al. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin Med. 2006;1:1-13.
5. Ong HT, Cheah JS. Statin alternatives or just placebo: an objective review of omega-3, red yeast rice, and garlic in cardiovascular therapeutics. Chin Med J (Engl). 2008;121:1588-1594.
6. Zhao SP, Liu L, Cheng YC, Shishehbor MH, et al. Xuezhikang, an extract of cholestin, protects endothelial function through anti-inflammatory and lipid-lowering mechanisms in patients with coronary heart disease. Circulation. 2004;110:915-920.
7. FDA warns consumers to avoid red yeast rice products promoted on Internet as treatments for high cholesterol; products found to contain unauthorized drug [press release]. Washington, D.C.: FDA; August 9, 2007.
8. Lin CC, Li TC, Lai MM. Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia. Eur J Endocrinol. 2005;153:679-686.
All electronic documents accessed April 3, 2008