Red yeast rice is a traditional Chinese culinary and medicinal herbal ingredient. The use of red yeast rice dates as far back as the reign of the Tang Dynasty (approximately 800 AD). Over the past several centuries, red yeast rice has been used to improve the digestive process, lower cholesterol, and enhance blood circulation.1 In recent years, red yeast rice has been proffered as an alternative to statin therapy for patients with dyslipidemia.1 However, the safety and side effect profile of red yeast rice use is not well established.

What is Red Yeast Rice?

Red yeast rice is produced by fermenting cooked rice kernels with Monascus purpureus, which is responsible for this supplement’s red hue. Several chemical constituents have been isolated from red yeast rice such as organic acids, sterols, flavonoids, monacolins, and polysaccharides.1 Moreover, the pharmacologic extracts of red yeast rice may be effective in the treatment of cancer, osteoporosis, diabetes, hyperlipidemia, atherosclerotic disease, hypertension, and fatigue.1 

Depending on the fermentation conditions and strains of Monascus purpureus used to make red yeast rice, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibiting monacolins may be produced as metabolites.2 Similar to traditional statins, monacolins inhibit HMG-CoA, which is the limiting factor for hepatic-mediated cholesterol synthesis.3,4 Of particular interest is the production of monacolin K, which is structurally identical to lovastatin and is the most abundant monacolin compound found in red yeast rice.4-6 Monacolin K inhibits HMG-CoA activity, resulting in reduced endogenous cholesterol synthesis and reduced blood cholesterol levels.7


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Statins have long been the mainstay of lipid-lowering therapy. Although these agents are generally well-tolerated, some patients seek out alternative therapies because they experience or are concerned about side effects including muscle pain, fatigue, gastrointestinal problems, and, in rare cases, liver damage.2 The structure of red yeast rice mirrors that of traditional statins.3 Several studies and meta-analyses have documented the efficacy of red rice yeast in lowering lipid levels, including low-density lipoprotein cholesterol (LDL-C) and triglycerides.1-3,5-10 

In a meta-analysis of 20 randomized studies, Gerards et al compared red yeast rice with a known content of monacolin K against placebo or an active control group for at least 4 weeks.2  Red yeast rice was associated with a 1.02 mmol/L (95% CI, -1.20 to -0.83) decrease in LDL-C cholesterol compared with placebo and a similar reduction in LDL-C as that of statin therapy (0.03 mmol/L; 95% CI, -0.36 to 0.41).2 A subanalysis of 3 studies comparing red yeast rice with monacolin K 10 mg daily to statin therapy (pravastatin 40 mg/d, simvastatin 10 mg/d, lovastatin 20 mg/d) showed no significant difference between the interventions: mean difference of change scores were 0.03 mmol/L (95% CI, −0.36 to 0.41) for LDL and -0.05 mmol/L (95% CI, -0.28 to 0.18) for total cholesterol.2

Although the lipid-lowering properties of red yeast rice have demonstrated great promise, safety issues must be considered, including the variability of monacolin K content from product to product, presence of citrinin (a mycotoxin often found in food), drug-drug interactions, and potential side effects.

Safety Concerns With Red Yeast Rice

The US Food and Drug Administration (FDA) has labeled red yeast rice as an unapproved drug because the compound may contain a significant amount of monacolin K.3,5 The concentration of monacolin K in commercial red yeast products often varies greatly from manufacturer to manufacturer.1,2,5,7,9-11 The FDA has warned companies that red yeast rice products containing more than a trace amount of monacolin K cannot be sold legally as dietary supplements.5 Of note, the amount of monacolin-K found in products is rarely disclosed on product labels.5 Therefore, the impact on blood cholesterol levels across individuals and studies can be difficult to discern.7

Of all the chemical constituents isolated from red yeast rice, citrinin is of particular concern.1 Citrinin is a polyketide secondary metabolite produced by fungi, including Monascus purpureus. If the culturing process of monacolin K is flawed, citrinin can form. Citrinin has been linked to kidney damage.1,5,8 Further, citrinin has been linked to genetic abnormalities.5 An analysis found that 4 of 11 red yeast preparations sold as dietary supplements contained citrinin.5

Because monacolin K is extensively metabolized by cytochrome P450 3A4 (CYP34A), as are many statins, serious side effects may occur secondary to CYP3A4 potentiation with concomitant ingestion of CYP3A4 inhibitors (clarithromycin, erythromycin, HIV protease inhibitors, ketoconazole, itraconazole, nefazodone, and telithromycin).8,10,12  Musculoskeletal deleterious effects are particularly prevalent.8,10,12 Ingestion of red yeast rice may be associated with a similar risk for liver damage as statins when taken with azathioprine, cyclosporine, cimetidine, diclofenac, gemfibrozil, itraconazole, rosiglitazone, valproic acid, statins, and methotrexate.8,13,14 Concomitant ingestion of red yeast rice and anticoagulants may increase bleeding risks.15

Similar to statins, reported side effects of red yeast rice include myopathies, rhabdomyolysis, liver dysfunction, gastrointestinal distress, peripheral neuropathy, erectile dysfunction, and cutaneous reactions.1-3,7,10,16 In the meta-analysis by Gerards et al, the risk for myopathies, liver abnormalities, and kidney injury was not different between the red yeast rice and control groups, which included active controls such as statin therapy.2

Conclusion

Red yeast rice has gained notable popularity over the past few years, especially for the treatment of dyslipidemia. However, before recommending use of red yeast rice for individuals with dyslipidemia, careful consideration of risks and benefits should be carried out by both nontraditional and traditional health care providers.

Patricia Dempsey, DNP, APN-BC, PPCNP-BC, is a specialist professor and interim MSN program director at Marjorie K. Unterberg School of Nursing and Health Studies, Monmouth University, West Long Branch, New Jersey.

References

1. Zhu B, Qi F, Wu J, Yin G, Hua J, Zhang Q, Qin L. Red yeast rice: a systematic review of the traditional uses, chemistry, pharmacology, and quality control of an important Chinese folk medicine. Front Pharmacol. 2019;10:1449. doi:10.3389/fphar.2019.01449

2. Gerards MC, Terlou RJ, Yu H, Koks CH, Gerdes VE. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain – a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415-23. doi:10.1016/j.atherosclerosis.2015.04.004

3. Peng D, Fong A, Pelt AV. Original research: The Effects of red yeast rice supplementation on cholesterol levels in adults. Am J Nurs. 2017;117(8):46-54. doi:10.1097/01.NAJ.0000521973.38717.2e

4. Lachenmeier DW, Monakhova YB, Kuballa T, et al. NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements. Chin Med. 2012;7:8. doi:10.1186/1749-8546-7-8

5. National Institutes of Health. Red yeast rice. Updated July 2013. Accessed December 6, 2021. https://www.nccih.nih.gov/health/red-yeast-rice

6. Ong YC, Aziz Z. Systematic review of red yeast rice compared with simvastatin in dyslipidaemia. J Clin Pharm Ther. 2016;41(2):170-9. doi:10.1111/jcpt.12374

7. Heinz T, Schuchardt JP, Möller K, Hadji P, Hahn A. Low daily dose of 3 mg monacolin K from RYR reduces the concentration of LDL-C in a randomized, placebo-controlled intervention. Nutr Res. 2016;36(10):1162-1170. doi:10.1016/j.nutres.2016.07.005

8. Cicero AFG, Fogacci F, Zambon A. Red yeast rice for hypercholesterolemia: JACC Focus Seminar. J Am Coll Cardiol. 2021;77(5):620-628. doi:10.1016/j.jacc.2020.11.056

9. Ross SM. Red yeast rice: The efficacy of Monascus purpureus yeast for treatment of hyperlipidemia a modifiable risk factor of cardiovascular disease. Holist Nurs Pract. 2017;31(1):52-58. doi:10.1097/HNP.0000000000000192

10. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes M, Aggett P, Aguilar F, et al. Scientific opinion on the safety of monacolins in red yeast rice. EFSA J. 2018;16(8):e05368. doi:10.2903/j.efsa.2018.5368

11. 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):1722-7. doi:10.1001/archinternmed.2010.382

12. Rowan CG, Brunelli SM, Munson J, et al. Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network. Pharmacoepidemiol Drug Saf. 2012;21(5):494-506. doi:10.1002/pds.3199

13. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Red Yeast Rice. Updated June 4, 2018. https://www.ncbi.nlm.nih.gov/books/NBK548168/

14. Mount Sinai. Health library: red yeast rice. https://www.mountsinai.org/health-library/supplement/red-yeast-rice

15. Mazzanti G, Moro PA, Raschi E, Da Cas R, Menniti-Ippolito F. Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol. 2017;83(4):894-908. doi:10.1111/bcp.13171

16. Mazzanti G, Moro PA, Raschi E, DaCas R, Menniti-Ippolito F. Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol. 2017;83(4):894-908. Doi:10.1111/bcp.13171