Chinese Red Yeast Rice: A Natural Statin?
July 2001; Volume 3; 53-55
By John McPartland, DO, MS
Red yeast rice is a confusing but accurate name for a dietary supplement that lowers cholesterol and triglyceride levels. The product consists of cooked, non-glutinous white rice fermented by the yeast Monascus purpureus, which is subsequently sterilized, dried, pulverized, and packed into capsules. Red yeast rice is a dietary staple in many Asian countries, with typical dietary consumption ranging from 14 to 55 g/d.1 The product has been used for at least 13 centuries in China, where it is known as hong qu. In China, red yeast rice is used as a table condiment, a culinary spice, and for food coloring (e.g., the color of Peking Duck). Red yeast rice also is prescribed in traditional Chinese medicine to promote blood circulation.
A double-blind, placebo-controlled study of 83 California men and women found that subjects taking 2.4 g/d red yeast rice significantly lowered their cholesterol from 250 mg/dL to 208 mg/dL (17%) after eight weeks.1 LDL levels dropped from 173 to 134 (22%), triglycerides dropped from 133 to 118 (12%), and HDL levels did not change. There were no significant changes in the control group. Dietary intake also was monitored, and there were no differences between the two groups in total calories, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, and fiber. There were no serious adverse effects and no changes in liver function tests. This study was funded by Pharmanex, the manufacturer of Cholestin, a standardized extract of red yeast rice. At least six animal studies and less rigorous clinical trials previously have been conducted in China; most of them report more impressive results (30-60% reduction in cholesterol).
In 1979, the primary active ingredient in red yeast rice was identified as monacolin K.2 Monacolin K inhibits HMG-CoA reductase, a liver enzyme that initiates sterol biosynthesis. This mechanism is shared by synthetic "statin" pharmaceuticals, such as atorvastatin (Lipitor), pravastatin (Pravachol), simvastatin (Zocor), and lovastatin (Mevacor). Indeed, monacolin K proved to be identical to lovastatin, and in 1997 the FDA banned imports of red yeast rice, specifically Cholestin.3 The FDA claimed Cholestin constituted an unapproved use of a patented drug; Pharmanex countered by saying Mevacor should have its patent revoked because Merck did not "invent" lovastatin, a naturally occurring compound. The FDA claimed that Pharmanex altered the traditional fermentation process to produce a lovastatin-rich product. There were rumors of genetically altered organisms; none of these allegations appear to be true. A year later, the ban was reversed in Federal District Court; Judge Dale Kimball cited "substantial and serious questions regarding the lawfulness of the FDA’s actions."4 The FDA has appealed the decision.
Red yeast rice reduces cholesterol by a greater proportion than can be attributed to its lovastatin content alone.1 If lovastatin can be likened to a "silver bullet" against hyperlipidemia, then red yeast rice is best characterized as a "synergistic shotgun." It contains a complex array of potential lipid-lowering agents, including monacolin K and 10 other monacolin analogs, omega-3 fatty acids, isoflavones, and plant sterols.3 In addition to therapeutic synergism, a second benefit of herbal medicines may be that of a reduced side effect profile; herbs often are weaker than drugs. Herbalists claim that polypharmaceutical herbs contain compounds that mitigate the side effects of their primary active ingredients,5 but this concept has not been proven. Extensive animal studies of red yeast rice have shown no acute or chronic toxic effects.1 Lovastatin, on the other hand, can cause rare cases of liver damage and rhabdomyolysis. The difference may be simply a matter of dose; 2.4 g red yeast rice contains about 5 mg of lovastatin, whereas a daily Mevacor dose ranges from 20-80 mg.3 A one-month supply of Cholestin costs about $20-30; cholesterol- lowering drugs average $187/month.6
Red yeast rice occasionally causes heartburn or flatulence, which can be avoided by taking the supplement with meals. Pregnant or nursing women should consult with their physician before taking any lipid-reducing agent. Individuals are cautioned from taking any lovastatin product if they have liver disease or if they are taking gemfibrozil (Lopid) or other lipid-lowering agents. Side effects from Mevacor may arise when it is taken with compounds that inhibit the drug-metabolizing enzyme cytochrome P-450 3A4, such as antifungal medicines (fluconazole, ketoconazole, etc.) macrolides (erythromycin, azithromycin), quinolones (cipro- floxacin, norfloxacin), protease inhibitors (indinavir, nelfinavir), cimetidine, and even grapefruit juice.7 Lastly, statins can deplete Coenzyme Q10 levels,8 so individuals concerned about heart disease may want to add 50 mg CoQ10 bid when taking red yeast rice supplements.
After Pharmanex won its case against the FDA and Merck, several other manufacturers have released red yeast rice products. These products, however, may contain other strains of Monascus and undergo different fermentation and manufacturing processes. The beneficial effects of red yeast rice have been shown only with the manufacturer-funded trials of Cholestin. The me-too products have not been evaluated in clinical trials.
Commercial products vary substantially. A recent chemical analysis of nine commercially available red yeast rice dietary supplements found that total monacolin content ranged from 0% to 0.58%; levels of monacolin K (lovastatin) ranged from 0.15 mg to 3.37 mg/capsule.6 Citrinin, a nephrotoxic mycotoxin that can form if fermentation conditions are not carefully controlled, was detectable in seven of nine preparations in amounts ranging from 0.47 to 64.7 mg/capsule.
|Table 1: Monacolin K and citrinin content of red yeast rice supplements|
|Supplement/Manufacturer|| Monacolin K
|Beyond Cholesterol/TwinLab||0.15||< 0.04|
|Cholesterol Power/Nature’s Herbs||2.51||< 0.47|
|Adapted from: 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.|
Some products compensate for suboptimal doses of red yeast rice by adding other lipid-lowering agents, such as gugulipid (from the Ayurvedic herb Commiphora mukul). This looks good on the label, but discerning consumers will note that these accessories are provided at sub-therapeutic levels.
1. Heber D, et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231-236.
2. Endo A. Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. J Antibiot (Tokyo) 1979;32:852-854.
3. McCarthy M. FDA bans red yeast rice product. Lancet 1998;351:1637.
4. Israelsen LD. Federal court upholds dietary supplement status of Cholestin. HerbalGram 1999;46:26,28.
5. McPartland JM, Pruitt PL. Side effects of pharmaceuticals not elicited by comparable herbal medicines: The case of tetrahydrocannabinol and marijuana. Altern Ther Health Med 1999;5:57-62.
6. 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.
7. Cytochrome P450 drug interaction table. Department of Pharmacology, Georgetown University. Available at: www.dml.georgetown.edu/depts/pharmacology/p450ref6.html#3A457inh. Accessed February 28, 2001.
8. Bliznakov EG. More on the Chinese red-yeast-rice supplement and its cholesterol-lowering effect. Am J Clin Nutr 2000;71:152-154.