Written by Trang Tran, Pharm.D. Candidate | Reviewed by Dr. Amy Knaperek, Pharm.D.
Remarkably, the 2007 National Health Interview Survey revealed that an estimated 1.8 million Americans had used complementary health approaches for cholesterol. Even more, sales of red yeast rice (RYR) skyrocketed to $20 million in 2008. Although statins are the cornerstone of cholesterol management in conventional medicine, many have turned to RYR as an alternative to statins for reasons such as the unwillingness to try a pharmaceutical drug or the inability to tolerate the side effects of statins.
Let’s dive in to learn more about nature’s statin.
What is red yeast rice?
Red yeast rice or RYR is an ancient natural product that is produced by the fermentation of rice by red yeast (Monascus purpureus). The red coloration is due to the pigments produced during the process of fermentation. Red yeast rice is composed of unsaturated fatty acids, phytosterols, and various subtypes of monacolins.
Traditionally, RYR has been used for the making of rice wine, flavoring, coloring, and preservation of food, and in traditional Chinese medicine.
What is the role of red yeast rice in dyslipidemia?
Dyslipidemia refers to the imbalance of cholesterol levels, typically high low-density lipoprotein cholesterol (LDL-C) and triglycerides and low high-density lipoprotein cholesterol (HDL-C). While conventional medicine focuses on lowering the LDL-C and raising the HDL-C, functional medicine takes into account the size of these lipoprotein particles more so than the quantity. Check out this blog post here to explore more about cholesterol from a functional medicine standpoint.
So back to RYR. One of the several bioactive components that RYR contains is monacolin K, which is structurally identical to lovastatin (Mevacor). Therefore, the mechanism by which RYR lowers cholesterol is just like statins (cholesterol-lowering drugs). That is, RYR inhibits the rate-limiting enzyme called HMG-CoA reductase, thereby inhibiting cholesterol production in the liver. The effectiveness of RYR is directly related to the amount of monacolin K (up to 10 mg per day). Although monacolin K is structurally related to lovastatin, it is important to note that whereas lovastatin is given as a single active ingredient, monacolin K is only one of many RYR components.
A meta-analysis of 20 randomized controlled trials with varying doses of RYR (1,200 mg and 4,800 mg per day) containing from 4.8 mg to 24 mg of monacolin K demonstrated that RYR reduced LDL-C by 39.4 mg/dL after 2 to 24 months of treatment compared to placebo. Additionally, the results yielded a small increase in HDL-C and a decrease in triglycerides compared to placebo. The cholesterol-lowering effect of monacolin K was not different from pravastatin 40 mg and lovastatin 20 mg.
Red yeast rice contains additional compounds with potential cholesterol-lowering properties, thereby suggesting that other compounds contained within RYR may synergistically contribute to the cholesterol-lowering effect.
Furthermore, a trial from China involving 1,445 patients aged 65 to 75 years with a history of heart attack demonstrated that RYR supplementation over the course of four years reduced the risk of heart disease, stroke, and the need for surgical or non-surgical interventions compared to placebo.
Red yeast rice may increase lipid excretion in the bowel when combined with plant sterols, soluble fibers, probiotic, or glucomannan (a type of water-soluble dietary fiber), enhance the liver uptake of cholesterol when combined with berberine, or induce LDL-C excretion when combined with chlorogenic acid (a polyphenol) or berberine.
A meta-analysis of fourteen randomized controlled trials demonstrated that combination products containing RYR improve not only cholesterol but also blood sugar levels.
Aside from improving the lipid profile, RYR may also possess blood-pressure lowering, anti-inflammatory, antidiabetic, and anticancer properties.
What are the similarities and differences between red yeast rice and statins?
Whereas lovastatin and other statins are marketed as drugs, RYR is marketed as a food supplement.
Compared with low to moderate-intensity statins, RYR was shown to have an equal efficacy to statins. The muscle-related side effect profile of monacolin K is comparable to that of statin therapy (i.e., pravastatin 40 mg, simvastatin 10 mg, or lovastatin 20 mg).
Statins are known to deplete coenzyme Q10 (CoQ10), but does RYR exert the same effect? Due to the same mechanism of action, it follows that RYR would likewise deplete CoQ10. Studies performed in rodents indicated that high doses of RYR have been found to suppress CoQ10 levels in the liver and heart.
Due to its similarity with lovastatin, the US Food and Drug Administration considers monacolin K an unapproved drug and thus marketing of products that label the monacolin content is prohibited. As a result, the labels on such products usually state the amount of red yeast rice, not the amount of monacolin K. Without knowing how much monacolin K is contained within the RYR supplement, the efficacy and safety of such a product are questionable.
On the other hand, the European Food Safety Authority (EFSA) has established that a daily dietary intake level of at least 10 mg of monacolin K from RYR helps maintain normal blood LDL-C concentrations. Notably, the EFSA approved a health claim that RYR products may have a pharmacotherapeutic effect.
Who is a candidate for red yeast rice?
Those with mild to moderate high cholesterol with no additional cardiovascular risk factors and thus deemed ineligible for statin therapy may be a candidate for red yeast rice as an adjunct to diet therapy. Additionally, those who are previously intolerant to statin therapy despite modifying the dose and type of statin or applying alternate-day statin therapy may consider RYR, which may be tolerable especially if the RYR contains low monacolin K content (3 mg/day). And for those unwilling to take statins despite their physician recommendation due to personal preference for a natural product, RYR might be a reasonable alternative, especially as an add-on to ezetimibe (a drug that inhibits cholesterol absorption in the small intestine).
What are the safety concerns of red yeast rice?
Not only does being chemically identical to lovastatin makes RYR possess similar therapeutic effects as statins, but it also makes it possess similar side effects as statins. Red yeast rice may have the same serious side effects of statins such as muscle pain and weakness, muscle fiber breakdown, and liver toxicity. However, most of the adverse events described were reversible. Despite the similar mechanism of action with statins, a daily dose of 3 to 10 mg monacolin K has only minimal associated risks, and mild muscle symptoms are seen only in those who are unable to tolerate a minimal dose of statin. Of note, those with confirmed complete statin intolerance (about 3-5% are affected) should avoid RYR because it contains a statin.
A meta-analysis of 53 randomized controlled trials demonstrated that monacolin K was not associated with an increased risk of muscle adverse events or serious adverse events and was associated with a reduced risk of non-musculoskeletal adverse events.
It is also important to take note of potential interactions of monacolin K with certain foods and drugs such as the following: grapefruit juice, prescription statin drugs, cyclosporine, HIV protease inhibitors, fibrates, niacin, coumarin, nefazodone, macrolides, and antifungals. All of these may increase the risk of muscle symptoms.
Citrinin, a metabolite that is derived from fermentation, has been demonstrated to be toxic to the kidneys in animal studies. Thus, the quality of the RYR product is crucial and it is recommended to opt for citrinin-free RYR preparations.
Because the monacolin content of RYR varies widely and could be extensively different and there is a lack of assurance about the efficacy, safety, and lack of standardized preparation methods of RYR products, such products may yield unpredictable therapeutic efficacy or side effects. To monitor for efficacy, a lipid panel may be obtained at baseline and thereafter and to monitor for safety, liver function tests may be obtained at baseline along with monitoring for signs and symptoms of muscle pain or weakness which should be reported to one’s healthcare provider.
The Bottom Line
Monacolin K, one of the components of red yeast rice, is structurally similar to lovastatin and works just like statins to lower cholesterol. However, the difference is that statin drugs are single active ingredients and are marketed as drugs, whereas monacolin K is only one of many other components contained within RYR and is marketed as a food supplement.
The efficacy of RYR was shown to be comparable to low to moderate-intensity statins and thus statins may be considered in those with mildly to moderately elevated cholesterol levels with no additional cardiovascular risk factors who are ineligible for statin therapy or in those who are intolerant to statin therapy or in those who prefer using a natural product.
Although RYR possesses a similar muscle-related side effect profile as statins, monacolin K was shown to be as well tolerated as some low-intensity and moderate-intensity statins.
Since RYR interacts with certain medications and foods, please consult with your healthcare provider or pharmacist to determine if RYR is for you.
Due to the varying amount of monacolin K content, the lack of standardization in the preparation methods, and the possibility of the presence of the toxic metabolite (citrinin) or other contaminants, the therapeutic efficacy and safety of RYR supplement may be unpredictable. For these reasons, it is essential to have regular follow-up with a medical professional to monitor for potential side effects and drug/food interactions as well as be cognizant of the quality of the RYR products.
Banach M, Bruckert E, Descamps OS, et al. The role of red yeast rice (RYR) supplementation in plasma cholesterol control: A review and expert opinion. Atheroscler Suppl. 2019;39:e1-e8. doi:10.1016/j.atherosclerosissup.2019.08.023
Cicero AFG, Fogacci F, Banach M. Red Yeast Rice for Hypercholesterolemia. Methodist Debakey Cardiovasc J. 2019;15(3):192-199. doi:10.14797/mdcj-15-3-192
Dujovne CA. Red Yeast Rice Preparations: Are They Suitable Substitutions for Statins?. Am J Med. 2017;130(10):1148-1150. doi:10.1016/j.amjmed.2017.05.013
Fukami H, Higa Y, Hisano T, Asano K, Hirata T, Nishibe S. A Review of Red Yeast Rice, a Traditional Fermented Food in Japan and East Asia: Its Characteristic Ingredients and Application in the Maintenance and Improvement of Health in Lipid Metabolism and the Circulatory System. Molecules. 2021;26(6):1619. Published 2021 Mar 15. doi:10.3390/molecules26061619
Halbert SC, French B, Gordon RY, et al. Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance. Am J Cardiol. 2010;105(2):198-204. doi:10.1016/j.amjcard.2009.08.672
Kłosiewicz-Latoszek L, Cybulska B, Stoś K, Tyszko P. Hypolipaemic nutraceutics: red yeast rice and Armolipid, berberine and bergamot. Ann Agric Environ Med. 2021;28(1):81-88. doi:10.26444/aaem/130629
Nguyen T, Karl M, Santini A. Red Yeast Rice. Foods. 2017;6(3):19. Published 2017 Mar 1. doi:10.3390/foods6030019
Red Yeast Rice. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/red-yeast-rice. Accessed April 7, 2022.
Shamim S, Al Badarin FJ, DiNicolantonio JJ, Lavie CJ, O'Keefe JH. Red yeast rice for dysipidemia. Mo Med. 2013;110(4):349-354.
Steffen C. Rotschimmelreis: Ein bedenkliches Nahrungsergänzungsmittel? [Red yeast rice: An unsafe food supplement?]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2017;60(3):292-296. doi:10.1007/s00103-016-2503-8
Twarużek M, Ałtyn I, Kosicki R. Dietary Supplements Based on Red Yeast Rice-A Source of Citrinin?. Toxins (Basel). 2021;13(7):497. Published 2021 Jul 17. doi:10.3390/toxins13070497
Vercelli L, Mongini T, Olivero N, Rodolico C, Musumeci O, Palmucci L. Chinese red rice depletes muscle coenzyme Q10 and maintains muscle damage after discontinuation of statin treatment. J Am Geriatr Soc. 2006;54(4):718-720. doi:10.1111/j.1532-5415.2006.00668_7.x
Yang CW, Mousa SA. The effect of red yeast rice (Monascus purpureus) in dyslipidemia and other disorders. Complement Ther Med. 2012;20(6):466-474. doi:10.1016/j.ctim.2012.07.004
Image link: https://files.nccih.nih.gov/files/red-yeast-rice-GettyImages-1016943388-square.jpg