Over the years I’ve had a number of patients tell me that they prefer to take over-the-counter (OTC) dietary supplements containing “natural” cholesterol-lowering ingredients rather than the statin drug I have prescribed.
Red yeast rice (RYR) is a common ingredient in these supplements and is promoted widely and enthusiastically across the internet and in supplement or natural food stores for the purpose of lowering cholesterol and heart disease risk.
RYR has been used for centuries in China for coloring, food, and medicine. It is made by fermenting red rice with a specific type of yeast (Monascus purpureus).
Red yeast rice contains chemicals that are similar to prescription statin medications. One of these, called monacolin K, is chemically identical to the statin drug lovastatin (brand name Mevacor).
The History Of Statin Drug Development
The history of the discovery and isolation of lovastatin, the first FDA-approved statin, is worthy of a digression here as I think it illustrates the process of discovery, isolation and characterization of a chemical from a natural source that becomes a safe and effective treatment that doctors can prescribe.
Akin Endo, whose research over decades was crucial to discovering statins, writes that he was inspired by Alexander Fleming, who discovered penicillin in the blue-green mold belonging to the genus Penicillium in 1928.
“Although no metabolites that inhibited any enzymes involved in cholesterol synthesis had been isolated previously, I speculated that fungi like molds and mushrooms would produce antibiotics that inhibited HMG-CoA reductase. Inhibition of HMG-CoA reductase would thus be lethal to these microbes.”
Endo began analyzing thousands of molds and fungi for biologically active chemicals that would inhibit HMG-CoA reductase. In 1971, after studying 3800 different strains of fungi he found a promising candidate: citrinin.
Unfortunately, Endo found that
“Citrinin strongly inhibited HMGCoA reductase and, furthermore, lowered serum cholesterol levels in rats. However, the research was suspended because of its toxicity to the kidneys. “
Endo spent another 10 years isolating another promising HMG-CoA reductase inhibitor, “compactin, ” from mold and studying it in rats and other animals. Compactin demonstrated marked cholesterol-lowering properties in dogs and monkeys and in the few humans who received it but the pharmaceutical company he worked for shut down the project after it appeared that in doses 200 times what were considered appropriate, it increased lymphoma risk in dogs.
The large pharmaceutical company, Merck, got wind of Endo’s studies with compactin, studied his data, and realized the potential of similar but safer HMG-CoA reductase inhibitors. Drugs that inhibited HMG-CoA reductase were now being termed statins.
Merck set out to find its own statins and in February 1979 isolated a statin very similar to compactin in chemical structure, called mevinolin, from the fungus Aspergillus terreus.
Endo, working separately and also in February 1979, isolated another statin (named monacolin K) from cultures of Monascus ruber (RYR). In the fall of the same year, it was confirmed that monacolin K and mevinolin were the same compound (later both changed to lovastatin).
The drug showed dramatic activity in lowering LDL cholesterol, with very few side effects. This led Merck to begin large-scale clinical trials of lovastatin in patients at high risk and long-term toxicity studies in dogs in 1984. The drug dramatically reduced cholesterol levels and was well tolerated. No tumors were detected. In 1987, Merck gained FDA approval RYRand lovastatin became the first commercial statin.
Since then, six other statin drugs, some of which are synthesized in the laboratory rather than isolated from mold, have been approved for human therapy. These drugs have prevented thousands of heart attacks and contributed to the dramatic drop in cardiovascular deaths seen in developed countries over the last 30 years.
RYR And Cholesterol Lowering
This brings us back to RYR and its ability to lower cholesterol. Small studies using a version of RYR that contained lovastatin have demonstrated a reduction in cholesterol compared to placebo.
However, because many red yeast rice supplements contained lovastatin (also called monacolin), in May 1998, the FDA ruled that Cholestin (the RYR product used in the studies showing cholesterol-lowering benefit) was not a dietary supplement but an unapproved drug.
As a result, Pharmanex removed RYR from Cholestin. Since that ruling, the FDA has written warning letters to several other dietary supplement manufacturers to remove drug claims or eliminate red yeast rice with high lovastatin levels from their products, including Heart and Cholesterol (Mason Vitamins, Miami Lakes, Florida) Cholestrix (Sunburst Biorganics, Baldwin, New York), Red Yeast Rice and Red Yeast Rice/Policosanol Complex , and Red Yeast Rice (Nature’s Way Products Inc, )
A study in 2010, found levels of monacolins varying one-hundred fold in 12 RYR preparations available commercially (total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule).
Even more worrisome was that four products had elevated levels of citrinin. You remember citrinin, don’t you? That is the chemical that Endo initially identified as a candidate for cholesterol-lowering drug but rejected because it was causing kidney failure in his rats.
Because of limited government oversight and variable manufacturing processes, one can also expect that the same manufacturer will have marked variations in monacolin content and citrinin from batch to batch or bottle to bottle.
Problems With Alternative Medicine In General
These problems with RYR supplements are typical of all supplements. As the authors wrote
“Our results highlight an important issue with red yeast rice and many other alternative medicines: the lack of standardization of active constituents. Standardization of ingredients is difficult for several reasons: (1) There are variable growth and/or culture conditions and differences in harvesting and processing among manufacturers; (2) medicinal agents from natural sources are complex substances with many chemical constituents, many of which have unclear roles in their pharmacologic activity; and (3) different manufacturers may standardize products to amounts of 1 or 2 chemicals thought to be active ingredients, while other constituents are not standardized and may also have biologic and pharmacologic activity.”
One has to ask, given this background, why would a patient choose to take a “natural” OTC supplement containing an unknown amount of both a) effective cholesterol lowering chemicals and b) potentially toxic extraneous chemicals over the precisely formulated, carefully regulated, fully studied, pure statin drug available by prescription.
It’s especially baffling to me when one considers that lovastatin comes from RYR. Thus it would have to be considered “natural.”
Akira Endo spent decades carefully identifying the effective and safe chemical portion of RYR. It is now available as a generic costing pennies per pill.
We know exactly how many milligrams you are consuming. We know what benefits to expect and what side effects can occur based on studies on hundreds of thousands of patients who have taken a similar dosage.
You are much better off taking a prescribed statin drug than RYR.
10 thoughts on “Red Yeast Rice: Let's Lower Our Cholesterol With Unknown Amounts of a Statin Drug”
Thanks for the history lesson on RYR! I was curious why I hear so much about it for cholesterol. I personally prefer it as part of my soy sauce, where it does a nice job at fermentation. As someone who’s trained in evidence-based medicine, while also coming from a long line of East Asian physicians who have trained in “traditional” medicine who caught the very beginnings of westernized medical training and have MDs, I am SO fascinated by this cultural divide between the science-minded and the “alt-med”-minded. Somehow, my family manages to be of both minds! They cherry-pick between science and folk medicine and it drives me up the wall!!
It’s good not to feel guilty over having caused my own high cholesterol. That’s what I conclude from reading all your recent blogs on diet and cholesterol.
But, at the same time, it’s frustrating to know that there’s nothing I can do personally to change my predicament.
Is it true that there are no lifestyle choices that would make a difference?
Our livers must respond in some way to what we do every day, no?
There are lifestyle choices that make a difference: smoking cessation, regular exercise, staying near ideal body weight, a diet similar to the Mediterranean.
If you are already engaging in those choices and have premature or advanced atherosclerosis then its time to consider some medication help (see my post on dealing with the cardiovascular cards you’ve been dealt)
Hmm. In the late ’80s I tested 277 total cholesterol, so I quit meat. In six months I tested 207. In the early ’90s I again tested high, in the 250s. I quit Fritos and suchlike. In six months I was under 200.
Would I be the exception that “proves” the new understanding?
There seem to be plenty of exceptions. e.g. My mother-in-law has always had cholesterol in the 350s. Three hundred fifties. She’s 94 and operates just fine on her own steam.
I liked the argument for taking prescription medications instead of the herbal supplements.
Would you ever advise eating RYR as prophylaxis? Say I have a family history of CAD, am 21 years-old, and want to take good care of myself now so I’m healthier when I’m older, could RYR every now and then be beneficial? Now, the same question, but assuming no history of CAD.
My intuition is that since RYR has lovastatin, an HMG-Coa inhibitor, less of my metabolites overall will become cholesterol over the course of my life, and that this would greatly reduce cholesterol synthesis, and over time, greatly reduce the amount of cholesterol I would have had. What are your thoughts?
Ultimately, the arguments against RYR apply for your putative 21 year old with family history. You would be exposing yourself to the risks/benefits of a statin drug but without any knowledge of the amount you are taking and no guarantee of the consistency of the amount. In addition, there would be no monitoring for effectiveness or potential toxicity.
If you have no family history of CAD then absolutely don’t take statins or potential statins at the age of 21.
First of all, how does a pharmaceutical company get a patent on a naturally occurring compound?
Second, statin drugs are far from being side effect free, with 17% of patients reporting problems. See: http://www.npr.org/blogs/health/2013/04/03/176145911/side-effects-prompt-patients-to-stop-statins-cholesterol . Also noted are: cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. See: https://www.ncbi.nlm.nih.gov/pubmed/19159124 which referenced almost 900 studies. It suggests that statin side effects may signal the presence of a pro-oxidant effect. This article points out that adverse effects are often unrecognized by physicians and warns that adverse effects are “neither vanishingly rare nor or trivial impact.”
While it’s true that quality control is not uniformly stringent across all supplement manufacturers (although some are quite conscientious), it’s equally true that pharmaceutical companies do not accurately report data contrary to their own interests. The critical problem here is actually getting scientifically sound data upon which to base a decision.
If you read the article by Dr. Endo, you get an idea of the long, winding and expensive road that researchers and pharmaceutical companies usually have to take to get a chemical from the basic lab to the point where it is considered safe and effective by the FDA. If they could not have some years of protection from competition while selling it, they would have little chance of making a profit. Since profit is what companies seek, they would no longer spend any time or money (or they would drastically cut back expenditures) on research and development of medications.
At no point did I imply that statins are side effect free. The difference between prescription statins and natural remedies is that the former have been extensively evaluated, first in animals looking carefully for side effects and proper dosing for effect and then in randomized controlled large trials in humans demonstrating very clearly what side effects and benefits can be expected. In addition, the prescription statins are produced and delivered in a manner that guarantees purity and amount.
Agree entirely… about using prescription FDA approved medication over any “alternative” “natural” product.
But, concerning prescription statins, I wonder what you think of this:
Increasing the risk of acquiring diabetes by 46% cannot be good. Diabetes is the one condition to avoid if you don’t want cardiovascular disease. Is this wrong?
For the last two years or so it has been known that higher intensity statin therapy is associated with about a 9% higher risk of diabetes and I inform my patients of that risk in the discussion when starting statin therapy. Despite that higher risk of developing diabetes, the patients getting statins had lower risks of cardiovascular disease so the overall benefits of statins in the right population outweighs this small increased risk of diabetes.
There has been a lot of concern about this newer study that you reference. It has to be put into the context of all the other data we have and needs to be vetted further. There is nothing else that suggests such a high risk of diabetes with statin therapy