Pamela A. Popper, Ph.D., N.D.
Wellness Forum Health
Red yeast rice (RYR) has been used in traditional Chinese medicine for hundreds of years. It is also used in food products such as rice vinegar, pickled tofu, and Peking duck. Historically it has been used medicinally to “revitalize blood” and improve digestion. Today it is most commonly used to lower plasma cholesterol levels, but is also recommended for other conditions including diabetes, Alzheimer’s disease, and dementia.
RYR is made by fermenting rice with a fungus. Its lipid-lowering effects are attributed to constituents called monacolins; 14 monacolins have been identified so far. Monacolin K is one of them and is chemically identical to Mevacor (lovastatin), a cholesterol-lowering drug.
One of the problems with red yeast rice is inconsistency in manufacturing. One analysis of 12 commercial products showed that total monacolin content ranged from 0.31 to 11.15 mg per 600 mg capsule, and that content of monacolin K ranged from 0.10 to 10.09 mg per 600 mg capsule.[i]
How does prescription lovastatin compare with RYR? One study showed that RYR was more bioavailable than lovastatin.[ii] Another study showed that RYR was more effective than lovastatin, and the researchers suggested that the effect might be due to the synergistic action of monacolin K with other monacolins and with other naturally occurring constituents in RYR.[iii]
There are many studies showing that RYR is effective for lowering plasma cholesterol. In one study, 52 physicians and their spouses with plasma cholesterol levels higher than 200 mg/dl were randomized to take RYR or placebo for 8 weeks. Subjects taking RYR showed an average 15% reduction in total cholesterol and 22% reduction in LDL cholesterol. There was no reduction in total or LDL cholesterol in the placebo group.[iv]
A meta-analysis of 93 randomized trials that compared RYR with placebo, no treatment, statins, and other cholesterol-lowering substances showed significant benefit, although the researchers noted methodological weaknesses in many of the trials. Nonetheless, the analysis showed that RYR reduced total cholesterol by an average of 35 mg/dl, LDL cholesterol by an average of 28.1 mg/dl, and triglycerides by an average of 36.3 mg/dl. They noted that the effect was similar to statin drugs, and better than both fish oil and niacin. Side effects were reported in 77 trials and the incidence rate ranged from 1.3% to 36%. The most common were dizziness, reduced appetite, nausea, abdominal distension, diarrhea, and gastrointestinal discomfort. No serious events were reported.[v]
However, side effects similar to those associated with statin drugs have been reported. The Italian Surveillance System of Natural Products reported muscle disorders including myopathy in 7 patients between 2002 and 2007.[vi]
Case reports have included a middle-aged man who developed joint pain and muscle weakness after taking RYR for 3 months. His lab results showed a moderately elevated creatine phosphokinase level. When he stopped taking RYR, symptoms resolved and his markers returned to normal. When he started taking RYR again, creatine phosphokinase levels increased again.[vii]
Another case report involved a 63-year old woman who presented with severely elevated liver enzymes and hepatotoxicity as a result of taking RYR, both of which resolved after discontinuation of the product. The researchers concluded, “The choice of an alternative medicine approach in this case subjected the patient to “re-challenge” with the official medicine agent that had previously caused mild hepatotoxicity. Physicians should keep in mind that “alternative” medicine is not always the safest alternative and sometimes it is not even “alternative.”[viii]
According to the National Institutes of Health, the same side effects associated with lovastatin can also occur as a result of taking RYR, and these include muscle myopathy, rhabdomyolysis, and liver toxicity. The NIH states that all of these side effects have been reported by people taking RYR. The NIH also says that RYR is not safe for pregnant or breastfeeding women.
RYR can also interact with several drugs to increase the risk of rhabdomolysis, and those drugs include cholesterol-lowering drugs, antibiotics, antidepressants, and antifungal medications.[ix]
The NIH site also referenced product inconsistencies, with an additional caution. When the culturing of RYR is not properly controlled, a mycotoxin called citrinin can form, which has been shown to cause kidney failure in animal studies. A 2011 analysis showed that 4 out of 11 products contained citrinin.
Sales of RYR were about $20 million in both 2008 and 2009. In 1998, the FDA ruled that RYR products that contained a significant amount of monacolins were considered drugs, not dietary supplements. The FDA has issued warning letters to several companies informing them that their products should not be marketed as dietary supplements, but many RYR products with high monacolin content remain on the market. The problem for the consumer is that it is impossible to know how much monacolin is in most products, and whether or not the products contain the contaminant citrinin. Most product labels only list the amount of RYR, not the monacolin K or total monacolin content.
Are there circumstances in which RYR should be used? While it is true that RYR can be safer than pharmaceutical drugs for lowering cholesterol (the incidence and severity of side effects is significantly higher for statin drugs), the unpredictability of RYR products is very concerning. Some of this is a labeling issue; in order to avoid FDA enforcement action, makers of RYR products have to conceal monacolin content. But some is a quality control problem, and with over one third of products tested containing citrinin, I do not think it is safe to take RYR.
The issue becomes somewhat moot, however, if patients with high plasma cholesterol are shown how to lower their cholesterol levels with diet. It works for almost all patients, and this approach prevents them from having to make a choice between two rather bad options – statin drugs or RYR.
[i] Gordon R, Cooperman T, Obermeyer W, Becker D. “Marked variability of monacolin levels in commercial red yeast rice products: buyer beware!” Arch Intern Med 2010 Oct 25;170(19):1722-1727
[ii] Chen C, Yang J, Uang Y, Lin C. “Improved dissolution rate and oral bioavailability of lovastatin in red yeast rice products.” Int J Pharm 2013 Feb 28;444(1-2):18-24
[iii] Li Z, Seeram N, Lee R et al. “Plasma clearance of lovastatin versus chinese red yeast rice in healthy volunteers.” Altern Complement Med 2005 Dec 11(6):1031-1038
[iv] Verhoeven V, Lopez Hartmann M, Remmen R, Wens J, Apers S, Van Royen P. “Red yeast rice lowers cholesterol in physicians – a double blind, placebo controlled randomized trial.” BMC Complement Altern Med 2013 Jul 18;13:178
[v] Liu J, Zhang J, Shi Y, Grimsgaard S, Alraek T, Fonnebo V. “Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials.” Chin Med. 2006 Nov 23; 1: 4. doi: 10.1186/1749-8546-1-4
[vi] 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 Oct;66(4):572-574
[vii] Smith D, Olive K. “Chinese red rice-induced myopathy.” South Med J 2003 Dec;96(12):1265-1267
[viii] Grieco A, Miele L, Pompili M et al. “Acute hepatitis caused by a natural lipid-lowering product: when “alternative” medicine is no “alternative” at all.” J Hepatol 2009 Jun;50(6):1273-1277