Red Yeast Rice
By Densie Webb, PhD, RD
Today’s Dietitian
Vol. 26 No. 3 P. 16
Today’s Dietitian combs the recent research on its safety, efficacy, and dosing recommendations for lowering cholesterol.
If your clients and patients ask you about red yeast rice, also known as Hong Qu, Hon-Chi, Anka, or red Koji, and whether they should take it to lower their cholesterol levels, you may want to read on.1
As with most unregulated dietary supplements, the research and facts on red yeast rice are complicated, and there are questions about its efficacy and safety that remain unanswered. First, the basics: Red yeast rice is the product of rice fermentation with the yeast, Monacolin purpureus or other members of the same fungal family, which turns the rice red.2 Red yeast rice has been found to contain 25% to 73% sugars (mainly starch), 14% to 31% protein, 1% to 5% fatty acids, pigments, sterols, and isoflavones.3 Red yeast rice has been used as a food and traditional medicine in China for more than 1,000 years. Depending on the specific strain of yeast used and the conditions of fermentation, red yeast rice can be rich in substances known as monacolins, especially monacolin K, which is structurally identical to lovastatin (Mevacor). Statins, such as lovastatin, are a mainstay of treatment for elevated cholesterol when pharmacologic intervention is the recommended course of action.4 Monacolin K targets the same key enzyme of cholesterol biosynthesis that lovastatin does, thus reducing the amount of cholesterol produced by the liver.5
Supplement Analyses
ConsumerLab.com conducted a review and analyzed red yeast rice supplements in 2022 and found that not only do red yeast rice supplements typically not list the amount of lovastatin or monacolin K they contain on the label but also the amounts vary greatly, and not all contain the amount of lovastatin needed to lower cholesterol. Sometimes they contain none at all.7
ConsumerLab.com found that the amount in the tested supplements ranged from none to 7.5 mg per two-pill serving. The amount of monacolin K or lovastatin found in products, even within the same brand, can vary from one batch to another. For example, ConsumerLab’s testing revealed that compared with tests run in 2018, the amount of lovastatin found in one product had dropped by 91%. Oddly, one brand that claimed to “support cardiovascular and heart health also boasted to be free of ‘monacolin K,’” the very ingredient that has been shown to reduce blood cholesterol levels.7
Dosage
Red yeast rice contains two main forms of monacolin K, a lactone (inactive) and a hydroxyl acid (active) form. The proportion of the active acid form in red yeast rice can vary from 5% to 100% of the monacolin content.6 There are currently no established and universally accepted guidelines for the dosing of red yeast rice or whether red yeast rice is recommended for the reduction of blood cholesterol levels. Typically, 1,200 to 2,400 mg of red yeast rice is taken daily to lower cholesterol.7
However, clinical studies have administered doses of red yeast rice ranging from 1,200 to 4,800 mg per day, usually divided into two doses during the day.7 There’s little agreement among professional organizations on what a safe and effective dose should be for red yeast rice. According to Whitney Linsenmeyer, PhD, RD, LD, an assistant professor at Saint Louis University in the department of nutrition and dietetics, and a spokesperson for the Academy of Nutrition and Dietetics, “Formulations of products from various companies will always continue to evolve, so ongoing monitoring for safety and efficacy is needed.”
The price per dose of a red yeast rice supplement also varies. ConsumerLab’s comparison found that the price of a 10 mg dose of lovastatin from red yeast rice ranged from a low of $0.23 to a high of $16.81.
In addition to the lack of standardization regarding the contents and dosages of red yeast rice supplements, health care organizations also have developed their own guidelines.
Professional Organizations’ Recommendations
• The European Society of Cardiology/European Atherosclerosis Society has recommended the use of red yeast rice in patients with statin intolerance.8
• A product called Xeuzhikang, a Chinese patented medicine with red yeast rice as its primary component, is listed in the primary prevention guidelines for CVD in China.9
• The 2016 Joint Position Statement of the Italian Society of Diabetology and the Italian Society for the Study of Arteriosclerosis on nutraceuticals for the treatment of hypercholesterolemia advised the use of red yeast rice preparations containing up to 10 mg/day of monacolin K for patients with mild to moderate hypercholesterolemia.10
• The 2021 European Society of Cardiology guidelines on atherosclerotic CVD prevention states that red yeast rice supplements aren’t recommended.4
• The American College of Cardiology/American Heart Association’s 2018 guidelines on the management of blood cholesterol and 2019 guidelines on the primary prevention of atherosclerotic CVD don’t mention red yeast rice.11,12
Research
“Red yeast rice has been fairly widely researched with randomized controlled trials and subsequent systematic reviews and meta-analyses since the late 1990s and early 2000s,” Linsenmeyer says. “Current evidence supports that red yeast rice products that contain monacolin K may effectively lower blood cholesterol levels, blood glucose levels, and blood pressure, all of which may reduce cardiovascular disease,” she says. There’s also some evidence that red yeast rice has anti-inflammatory potential.2
A multicenter, prospective, randomized, open-label, eight-week study conducted in China found that red yeast rice is an effective therapy for reducing blood cholesterol, whether prescribed at 600 mg twice per day or 1,200 mg once per day.9 A systematic review and meta-analysis found that red yeast rice preparations reduced mortality, major adverse cardiovascular events, and several risk factors for metabolic syndrome, including hypertension, elevated blood glucose, and lipid levels, without compromising safety.1 However, all of the studies included in the analysis had administered Xeuzhikang, the Chinese patented medicine that contains red yeast rice, not red yeast rice supplements typically for sale in the United States.
Among those studies, researchers found that red yeast rice as Xeuzhikang, taken for at least four weeks, showed 15 to 34% reductions in LDL-C, and one study found an 18% decrease in total cholesterol. The reductions were relative to both baseline and placebo.6,13
A recent review concluded that red yeast rice shouldn’t replace conventional therapies to manage cholesterol levels but that it may be used for patients with statin intolerance or if patients have a strong preference for a nonpharmaceutical option. To date, however, it’s unknown whether the red yeast rice supplements on store shelves are similar to the red yeast rice products used in most of the cited studies.2
Safety
The message regarding the safety of red yeast rice has been confusing in the medical community. While a meta-analysis and systematic review of randomized controlled studies have shown red yeast rice to be well tolerated by patients at doses providing 10 mg of monacolin K per day, the FDA has deemed some red yeast rice products as drugs without approval and has ruled that manufacturers can’t legally sell products with even trace amounts of monacolin K as dietary supplements.
The FDA’s decision was based on its approval of lovastatin as a drug before red yeast rice was widely marketed as a dietary supplement in the United States.5 The agency has sent warning letters to companies selling red yeast rice supplements that contain enhanced or added lovastatin. However, a variety of red yeast rice supplements of unknown quality and efficacy are readily available in the United States.
The Mayo Clinic lists abdominal discomfort, heartburn, gas, headache, and dizziness as possible side effects from taking red yeast rice supplements. Possible interactions with other drugs include alcohol; immunosuppressive drugs; grapefruit; drugs, herbs, and other supplements that may be toxic to the liver; high-dose niacin; St John’s wort; and other statins.1
“The FDA position on red yeast rice gives much greater pause compared to recommending an essential nutrient, such as vitamin C or a multivitamin. Because of the risk for interactions with other nutraceuticals, medications, and foods, I would always recommend my patients consult with their physician before using red yeast rice,” Linsenmeyer says.
Still, a 2023 study on the safety of red yeast rice that analyzed the FDA reporting systems found that the risk of rhabdomyolysis, in which muscle breaks down and protein and electrolytes are released into the blood, or severe acute hepatitis, is extremely rare when compared with statins.15 No guidance is available for using red yeast rice supplements in addition to a statin. Because levels of monacolin K usually aren’t included on product labels, it’s impossible to know the amount being ingested. “The concern,” Linsenmeyer says, “is that taking red yeast rice and statins at the same time could easily lead to overdosing and side effects, especially when the amount of active compounds in the red yeast rice supplements is unknown.”
The European Food Safety Authority (EFSA) also issued a warning against red yeast rice supplements in 2018, stating that exposure to monacolin K from red yeast rice could lead to severe side effects, and the EFSA couldn’t identify a guaranteed safe level of monacolins from red yeast rice products.
Moreover, there’s concern about unsafe levels of citrinin, a byproduct of the fermentation process. Animal studies have shown citrinin to be nephrotoxic and possibly hepatotoxic and has been associated with cancer as well as inducing reproductive toxicity and birth defects in animals.6 While no reproductive effects have been reported in humans, EFSA has set a safe limit of citrinin to 0.2μg/kg of body weight per day. However, in 2010 ConsumerLab found citrinin levels in red yeast rice supplements to be as high as 114μg per capsule.16 An updated ConsumerLab analysis found 4.6μg to 17μg per daily dose of some products, which is still significantly above the EFSA recommended limit, and a greater number of products were found to be contaminated with citrinin than in previous reviews.7 Citrinin contamination also was found to be associated with low monacolin levels. Two red yeast rice products ConsumerLab analyzed were found to contain either citrinin only or insignificant amounts of lovastatin.
Bottom Line
A recent review of research using red yeast rice concluded that the current evidence shows that red yeast rice delivers a modestly effective dose of monacolin K and contains other components that may provide additional benefits. However, because the FDA doesn’t tightly regulate dietary supplements, including red yeast rice, Linsenmeyer recommends consumers look for brands that have been reviewed by independent quality assurance organizations, such as ConsumerLab.com, the US Pharmacopeia, and the National Safety Foundation. But, she says, “Dietary changes, such as those in the DASH diet, the Mediterranean diet, the Therapeutic Lifestyle Changes diet, and the AHA [American Heart Association] diet, should remain a focus for reducing the risk of cardiovascular disease, regardless of the dietary supplements or prescription medications a patient may be taking.”
— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.
References
1. Yuan R, Yuan Y, Wang L, et al. Red yeast rice preparations reduce mortality, major cardiovascular adverse events, and risk factors for metabolic syndrome: a systematic review and meta-analysis. Front Pharmacol. 2022;13:744928.
2. Buzzelli L, Segreti A, Di Gioia D, et al. Alternative lipid lowering strategies: state-of-the-art review of red yeast rice. Fitoterapia. 2024;172:105719.
3. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;290:140-205.
4. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227-3337.
5. Red yeast rice: what you need to know. National Institutes of Health; National Center for Complementary and Integrative Health website. https://www.nccih.nih.gov/health/red-yeast-rice. Updated November 2022.
6. Cicero AFG, Fogacci F, Stoian AP, Toth PP. Red yeast rice for the improvement of lipid profiles in mild-to-moderate hypercholesterolemia: a narrative review. Nutrients. 2023;15(10):2288.
7. Red yeast rice supplements review. ConsumerLab website. https://www.consumerlab.com/reviews/red-yeast-rice-supplements-review/red-yeast-rice/. Published May 19, 2022. Updated September 27, 2022.
8. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188.
9. Hu D. Han Y, Ning G, Ma C. Chinese guideline on the primary prevention of cardiovascular diseases. Cardiology Discovery. 2021;1:70-104.
10. Pirro M, Vetrani C, Bianchi C, Mannarino MR, Bernini F, Rivellese AA. Joint position statement on "nutraceuticals for the treatment of hypercholesterolemia" of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA). Nutr Metab Cardiovasc Dis. 2017;27(1):2-17.
11. Cicero AFG, Colletti A, Bajraktari G, et al. Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Arch Med Sci. 2017;13(5):965-1005.
12. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;140(11):e596-e646.
13. Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999;69(2):231-236.
14. Red yeast rice. Mayo Clinic website. https://www.mayoclinic.org/drugs-supplements-red-yeast-rice/art-20363074. Published August 10, 2023.
15. Banach M. Norata GD. Rhabdomyolysis or severe acute hepatitis associated with the use of red yeast rice extracts: an update from the adverse event reporting systems. Curr Atheroscler Rep. 2023;25(11):879-888.
16. Gordon RY, Cooperman T, Obermeyer W, Becker DJ. Marked variability of monacolin levels in commercial red yeast rice products: buyer beware! Arch Intern Med. 2010;170(19):1722-1727.