Is Red Yeast Rice a Good Alternative to Statin Drugs?

In the pharmacy, I’m often asked for “non-drug” solutions to various illnesses. In some cases, a desire to avoid medication can push people to make overdue and important diet or lifestyle changes. But in many cases, consumers simply want to avoid prescription drugs, asking if there’s something they can buy, preferably “natural”, that can help them.

This belief, that “natural” is preferable to anything “synthetic” is actively promoted by the natural health products industry, and it’s referred to by science-based health practitioners as the naturalistic fallacy: Anything that comes from natural sources is believed to be good, helpful, and non-toxic, and anything that is synthesized is therefore artificial, unnatural, and dangerous. It’s an incorrect assumption. Many natural products are toxic (e.g., botulism, strychnine, lead, and arsenic). And many of the drugs we use today are derived from, or based on, products found in nature.  Nature represents a remarkable drug synthesis lab, and there are many commercially-manufactured drugs that are identical to, or based on, natural sources. But being “natural” has no relationship to whether a chemical is safe to humans or effective to treat a specific condition. Natural product advocates almost seem to think that the ideal treatment for any condition is just “out there” in its natural state, as if created specifically for our purposes, and just awaiting our discovery, ready to consume in its natural state. But that isn’t the case.

Consider paclitaxel, for example. It’s a cancer treatment (“chemo”) drug derived from the bark of the Pacific yew tree. Once the active chemical in the bark was identified, it was purified, isolated, and subsequently manufactured in a lab. It’s given by an intravenous injection. Science has found an effective drug, avoided having cancer patients consume huge quantities of tree bark, and saved a plant species from possible extinction. (For more information on the naturalistic fallacy and the story of Taxol, check out, “Why we don’t prescribe bark for cancer” over at the Science-Based Medicine Blog.

Among natural products for the treatment of high cholesterol, red yeast rice (RYR) is among the most requested alternatives to prescription statins. And there’s a reason why: it actually works – it lowers bad (LDL) cholesterol! But before we start treating high cholesterol with yeast, let’s dig a bit deeper.

Red yeast rice is created by fermenting rice with the Monascus purpureus yeast. What’s remarkable about this fermentation process is one of the by-products: A chemical called monacolin K is produced, which is chemically identical to the drug lovastatin (sold by Merck under the brand name Mevacor). [1] The fermentation process produces other chemicals, including sterols such as beta-sitosterol, isoflavones, and monounsaturaed fatty acids. [1] It’s believed that the cholesterol lowering-effects are mainly due to the lovastatin, but the other active ingredients may also contribute some effect. [1]

Lovastatin is a “statin”, part of a group of drugs that have dramatically changed how cardiovascular disease is treated. In the right patients, statins can dramatically reduce the risk of illness and death. [2] Lovastatin has been extensively studied and we can predict with reasonable accuracy how it will work in the body, and how much a specific dose will lower your cholesterol. There is a well-established correlation between the amount your cholesterol is lowered, and a decrease in risk of disease. For example, lowering your LDL-C by 1 mmol/L can reduce major coronary events by 25%, the risk of cardiac death by 19%, and offer a 12% overall decrease in death. [2]

Side Effects of Lovastatin and Red Yeast Rice

Lovastatin’s most common side effects include stomach upset and dizziness. Myopathy, or muscle pain, is an important reason for people to have trouble tolerating statins, and affects about one in ten people that take it. [3] The reason for this type of muscle reaction is unclear, although it is more common with higher doses. In some cases the pain may be mild and tolerable, and people can continue taking lovastatin. In rare but severe cases, rhabomyolysis is a severe reaction that can be life threatening. [3] Because of the side effect profile, liver function tests and other lab tests are done periodically in patients taking lovastatin. Because red yeast rice contains lovastatin, these tests should also be considered essential for anyone that takes it.

Citrinin is a byproduct of red yeast rice preparation, and has been found in some commercially-manufactured products. [1] It can cause permanent, potentially irreversible kidney damage. It is not present in prescription lovastatin tablets.

Clinical Effects of Red Yeast Rice

Several specific brands of RYR have been studied for their medicinal effects. As you might expect for a product that contains lovastatin, RYR lowers low-density lipoprotein and cholesterol levels after 8-12 weeks – behaving exactly like lovastatin. Doses range from 1.2 grams to over 3 grams per day. Given the different manufacturing standards and practices, one cannot assume one brand of RYR is equivalent to another. [1]

The largest clinical trial, by Lu et al, was published in 2008 and studied almost 5000 Chinese subjects over 4.5 years. A RYR supplement (Xuezhikang) was taken daily which contained 2.5 – 3.2 mg of lovastatin. Patients treated with the supplement were found to have reduced cholesterol and triglyceride levels, and a decreased risk of heart attacks and deaths from heart-related causes. [4]This finding is what we would expect; given the active ingredient was lovastatin. While the dose of lovastatin was low, related compounds may have contributed to the cholesterol-lowering effects. Smaller trials by (Lun) and (Gheith) largely show the same effects as the Lu study. Red yeast rice lowered LDL cholesterol significantly in all trials. [4]

What was most interesting and promising about these trials is that red yeast rice was well tolerated. [4] In the trial by Lin, there were no elevations in blood enzymes associated with muscle pain. While it’s important to note that muscle pain can occur without enzyme elevations, it’s still an interesting finding, and worthy of more investigation. [5] This led to the most recent study:

Becker and associates studied the use of red yeast rice in patients who had experienced muscle pain from at least one prescription statin. [6] A small placebo-controlled, double-blind trial, patients took red yeast rice (1800 mg, twice per day) or a matching placebo. All patients received lifestyle counselling. After 12 and then 24 weeks, patients taking red yeast rice had significant improvements in their cholesterol, compared to the placebo group. The most interesting finding was that patients taking red yeast rice didn’t have more muscle pain than the placebo group.

But let’s look a bit closer. Only 30% of the patients taking red yeast rice were able to achieve their cholesterol targets. This isn’t unexpected, as the dose of lovastatin was just over 6 mg per day, and the total amount of statin-like drugs was about 13 mg. Since we know that muscle pain risk increases with dose, it’s not surprising that only two patients out of 29 had muscle pain: The dose was small. Lovastatin doses typically start at 20mg per day, and go as high as 80 mg per day. So the lack of difference between the groups could be the low dose of the red yeast rice, or it could be that the study was just too small to detect a difference.

Overall it’s an interesting study, but it was too small to draw firm conclusions about the usefulness of red yeast rice compared to statin drugs in patients with muscle pain. It does not provide evidence that red yeast rice is better tolerated than a comparable dose of prescription lovastatin.

Regulatory action

The FDA considers red yeast rice to be a drug and prohibits commercially-manufactured products from containing any lovastatin. [1] Despite this prohibition, testing of products that are currently marketed in the U.S. reveals that some products do appear to contain lovastatin. [1] These tests have also demonstrated that stated content and actual content can differ widely. One published set of tests also revealed that RYR products can contain measurable amounts of a citrinin, a dangerous contaminant that can cause kidney damage. In light of the status of red yeast rice with the FDA, there’s no reason to expect that any commercially available products will offer any meaningful cholesterol-lowering benefits.

In Canada, no red yeast rice products appear to have been approved by Health Canada’s Natural Health Products Directorate. Consequently, there’s no assurance that even Health Canada’s lowered standards for natural health product efficacy and safety (compared with standards for prescription drugs) have been applied to products that are currently openly sold in Canada. In light of this, there is no evidence to suggest that red yeast products that may be found in Canadian pharmacies are safe or effective.

Safety Issues

Assuming one can find a red yeast rice product of acceptable quality, (and free of kidney-toxic contaminants) then based on the published clinical trials, red yeast rice seems to be as safe as prescription lovastatin when taken for several weeks. [1] Prescription lovastatin products have been studied in clinical trials in thousands of people and is generally well-tolerated, even with long-term use.

Lovastatin causes birth defects in animal studies, so it is considered unsafe to use pregnant women. Consequently, red yeast rice should also be avoided by pregnant women. [1]

Drug Interactions

Lovastatin can affect how other drugs behave in the body, and how it works can also be affected by other drugs. These drug interactions are extensive, well known and documented, and should be considered just as relevant with red yeast rice. An incomplete list can be found here. Lovastatin, and therefore RYR, can also be affected by “natural” products like coenzyme Q-10, grapefruit juice, and herbs like St. John’s wort. [1] Users of prescription lovastatin will typically have their prescription checked against any other prescription drugs the pharmacist knows you are taking. Some pharmacies may offer this service to consumers that buy natural products, like red yeast rice. (Tip: Ask the pharmacist to check your prescription drugs against both RYR and lovastatin).

Cost

Merck’s Mevacor lost its patent protection several years ago, and it’s now a very inexpensive prescription drug. Lovastatin continues to be a widely-used drug and is an effective (and much less expensive) alternative to still-patented prescription statins like Crestor and Lipitor.

Lovastatin is among the $4/mth prescriptions available in U.S. pharmacies like Walgreens and Wal-Mart. Consequently, a year’s supply may cost as little as $48. In Canada, 20 mg of lovastatin costs $0.8657, so a year’s supply from your pharmacy will cost you about $400, assuming typical pharmacy fees. Higher doses cost $600 and up per year.

Based on a quick scan of internet retailers, red yeast rice products can cost $20-$60 per month, depending on the brand sold and the dose taken. Based on an equivalent amount of cholesterol-lowering, red yeast rice may be significantly more expensive than the prescription alternative.

Lovastatin vs. Red Yeast Rice: The Bottom Line

Characteristic	Lovastatin 20mg tablets	Red Yeast Rice 3g
Actual amount of drug	20mg	Unknown, may vary
Dose variation between different batches/lots	Effectively none	Unknown, may be significant
Variation between brands	Effectively none	Unknown, may be significant
Manufactured	FDA/Health Canada/ etc. approved and inspected facility	Unknown, varies by company
Manufacturing standards	Facilities in most countries (esp USA/CAN) would have to adhere to Good Manufacturing Practices (GMP) standards for prescription drugs.	Unknown. GMP standards are slowly being implemented in Canada and the USA. [4] Standards may vary from prescription drugs manufacturing requirements.
Contaminants	None	Unknown
Other ingredients	Only excipients (inert ingredients)	May contain other biologically active products that contribute to the cholesterol-lowering effects
Tracking and monitoring of adverse effects	Adverse events reported by consumers and health professionals must be collected by the manufacturer and reported to regulators like the FDA and Health Canada	None, unless self-reported to regulatory agencies like the FDA and Health Canada
Presence of kidney toxin citrinin	None	Has been identified in some products. Difficult to identify safe products.
Association with known benefits	Well established clinical benefits from lovastatin use when dose is adjusted to achieve certain cholesterol targets.	Clinical benefit probably exists (if a known, consistent dose is taken). Overall effects not as well documented as lovastatin. May be difficult to reach cholesterol targets with use.
Absorption in body	Well understood and clinically tested to deliver listed dose into bloodstream	Unknown but appears to be well absorbed. Unclear if this varies between products.
Monitoring for drug interactions with other prescription drugs	Automatically done by pharmacist as a duty of care	None, unless done by self or requested of pharmacist.
Monitoring for side effects	Automatically done by physician and pharmacist as a duty of care	Not routinely done by health professional
Monitoring for effectiveness	Automatically done by physician as a duty of care	None, unless requested
Insurance coverage	Most will cover	Unlikely
Cost if uninsured	$48/yr (USA)$400/yr+ (Canada)	$240-$720/yr (based on $20-$60/mth)

(References for table comments in text of article)

Evaluation

Most natural health products lack any convincing evidence that they are safe and effective for the claimed effects. As red yeast rice does contain lovastatin, this unique product actually has medicinal effects. Unfortunately, unlike the prescription drug, the consumption of  red yeast rice in its “natural” form is significantly more risky and potentially less effective. With a similar risk of rare but very serious side effects, the additional risk of contamination and kidney damage, and the dangers of therapy without monitoring by health professionals, makes red yeast rice a poor choice as a self-treatment for cholesterol lowering.

Conclusion

There is no patient-related or health-related reason for red yeast rice to be sold in pharmacies. Red yeast rice is a natural source of lovastatin that offers the consumer less efficacy,  potential serious side effects, and likely a higher cost. Lovastatin is a potent drug that requires monitoring by health professionals to maximize benefit and minimize risk.

Any pharmacy that sells red yeast rice put profit ahead of patient care and patient safety. Until manufacturing standards improve, and a valid reason to take red yeast rice appears, there’s no reason to consider taking red yeast rice for any medical condition.

For Further Information

Dr. Mark Crislip discussed red yeast rice in a recent episode of his excellent podcast, Quackcast.

The Healthy Skeptic of the LA times discussed red yeast rice in the article Statin Free Supplement? Not Quite.

References

[1] Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2009 [cited 23 July 2009] Available from: http://www.naturaldatabase.com. Subscription required to view.

[2] McPherson R, Frohlich J, Fodor G, Genest J. Canadian Cardiovascular Society position statement – Recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol. 2006 Sep ;22(11):913–927.

[3] Joy TR, Hegele RA. Narrative Review: Statin-Related Myopathy. Ann Intern Med. 2009 Jun 16;150(12):858-868.

[4] Klimek M, Wang S, Ogunkanmi A. Safety and Efficacy of Red Yeast Rice (Monascus purpureus) as an Alternative Therapy for Hyperlipidemia. P&T. 2009 Jun ;34(6):313–327.

[5] Mohaupt MG, Karas RH, Babiychuk EB, Sanchez-Freire V, Monastyrskaya K, Iyer L, et al. Association between statin-associated myopathy and skeletal muscle damage. CMAJ. 2009 Jul 7;181(1-2):E11-18.

[6] Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, & Rader DJ (2009). Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial Annals of internal medicine, 150 (12), 830-839 DOI: 19528562