Hyperlipidemia is a common disease associated with coronary artery disease (CAD).1 CAD can lead to many medical complications including stroke, myocardial infarction and even death. An estimated 52 million individuals are diagnosed with hyperlipidemia with 13 million individuals being treated with statin therapy, which can be difficult in terms of adherence.2 It's estimated that 50% of individuals on statin therapy stop taking their medication within the first year and 75% stop taking their medication within the first 2 years.2 One reason for stopping statins is their adverse reactions-statins can cause myalgias, muscle weakness, fatigue, elevated liver enzymes and increased blood sugar levels.3 The undesirable adverse reactions and poor adherence to statin therapy should be two drivers behind finding alternative treatment options for hyperlipidemia. One potential alternative to statin use is a hyperlipidemia diet which includes red yeast rice (Monascus purpureus). Red yeast rice is a Chinese dietary supplement used for lowering lipid levels. One of the chemical components of red yeast rice, monacolin K, is chemically identical to the active ingredient in lovastatin, which may help explain its lipid lowering properties.4 A literature review was conducted to determine the potential safety and efficacy of red yeast rice for treating hyperlipidemia.
Examining the Evidence
A randomized controlled trial (RCT) included 43 adults with a diagnosis of hyperlipidemia who discontinued their statin use due to complaints of statin-associated myalgia (SAMs). The patients were placed in study groups comparing the use of red yeast rice to pravastatin.5 The subjects were randomly assigned to red yeast rice 2,400 mg twice daily or pravastatin 20 mg twice daily for 12 weeks.5 All subjects were also enrolled in a 12-week therapeutic lifestyle change program. Of the 43 participants enrolled in the study, one participant from the red yeast rice group withdrew with complaints of myalgia and two participants from the pravastatin group withdrew. There was minimal difference noted in muscle strength and mean pain scores between the groups. The low-density lipoprotein (LDL) levels showed similar reductions of 30% in participants using red yeast rice and 27% in the group taking pravastatin. The overall results demonstrated that participants in the red yeast rice group tolerated the use of red yeast rice as well as the pravastatin group with comparable benefits in LDL reduction, thus supporting the use of red yeast rice as a stain alternative.5
Another RCT examined adiponectin, leptin, total cholesterol, high-density lipoprotein (HDL), LDL, and triglycerides in patients with hyperlipidemia who were treated for 8 weeks with red yeast rice.6 Thirty patients identified with primary hyperlipidemia received 600 mg of red yeast rice twice daily with additional follow-up at 4 and 8 weeks. Results measured at week eight demonstrated a significant reduction in LDL by more than38 mg/dL + 30.9 and a total cholesterol reduction of over 44 mg/dl + 27.5 with a P-value set at < 0.0001.6 Results from this study suggest that red yeast rice appears to protect patients from cardiac disorders.6
The third study examined the use of a Mediterranean diet (MD) in conjunction with red yeast rice to lower serum cholesterol levels.7 The 24-week study assessed 171 statin-intolerant patients with or without type 2 diabetes mellitus and hyperlipidemia by placing them into four groups that used MD alone or in combination with red yeast rice. Serum levels of LDL, HDL, total cholesterol, triglycerides, liver enzymes, and creatinine phosphokinase (CPK) were evaluated. The four patient groups were as follows: Group one included 46 patients with type 2 diabetes treated with MD alone; group two included 44 patients with type 2 diabetes treated with MD and red yeast rice; group three included 38 patients with hyperlipidemia treated with MD alone; and group four included 43 patients with hyperlipidemia treated with MD and red yeast rice.7 LDL was significantly reduced in patients unable to tolerate statin therapy with a presumably low cardiovascular risk in the MD alone group. When MD and red yeast rice were combined, however, an even greater reduction in LDL was seen.7
A double-blind RCT conducted at nine sites in India examined 210 participants newly diagnosed with hyperlipidemia (LDL > 120) without a history of cardiovascular disease.8 They were randomized to receive one capsule of a nutritional supplement containing standardized extracts of red yeast rice, grape seed, and coenzyme Q10 (Co-Q10) or a placebo twice daily. Additionally, patients were encouraged to demonstrate lifestyle modifications, such as consuming a low-fat diet and exercising, as well as taking medications as prescribed for 12 weeks. The mean LDL level for both treatment groups was ~ 148 mg/dL before interventions. The intervention group had a significant time-dependent reduction in LDL and total cholesterol with no difference in safety parameters when compared to the placebo group after 12 weeks of treatment. This study supported the use of red yeast rice in combination with grapeseed and Co-Q10 in lowering LDL and total cholesterol in subjects with hyperlipidemia. The reductions were comparable to patients following moderately intense statin therapy.8
The final RCT was conducted in a cardiology practice in Philadelphia. There were 62 study participants with an age range of 21 to 80 years. Inclusion criteria were documented hyperlipidemia, history of myalgia related to mono-statin therapy use, and discontinuation of medication resulting in muscle pain resolution. Participants were randomly divided into two groups. The first group received three 600 mg tablets of red yeast rice twice daily and the other group received three placebo capsules twice daily.9 Additionally, all participants were enrolled in a lifestyle modification program that included 12 weekly meetings that lasted 3.5 hours each. During the meetings, patients were instructed on nutrition, exercise, relaxation techniques, and cardiovascular disease. They were also encouraged to follow a the MD diet, which included reducing saturated total fat intake.9 Blood specimens were collected from the subjects and analyzed at baseline, week 12, and week 24 to determine if the LDL decreased. Secondary outcome measures included HDL, triglycerides, total cholesterol, liver enzymes, CPK, pain inventory scale, and weight. The treatment group had an overall decrease in LDL levels by 43 mg/dL from baseline at week 12 and a decrease of 35 mg/dL at week 24. The placebo group had a decrease in LDL levels by 11 mg/dL and 15 mg/dL, respectively. Additionally, at weeks 12 and 24, patients in the treatment group had a significant improvement in the average level of total serum cholesterol.9
When reviewing studies regarding the use of red yeast rice in lowering of cholesterol levels, data were limited. The sample sizes in the trials evaluated were small and may not properly represent the population of patients with hyperlipidemia or individuals on statin therapy. Additionally, fewer than 10 studies examined the use of red yeast rice in the treatment of hyperlipidemia within the past 5 years. Further studies would be beneficial with diverse participants using red yeast rice with and without lifestyle changes. Of the studies reviewed, the examination of total cholesterol, liver enzymes and CPK levels offered additional support for the use of red yeast rice.5 Perception of myalgia in study subjects after discontinuation of statin therapy and initiation of red yeast rice would be beneficial. Studies completed to-date has shown impressive results in the use of red yeast rice in the treatment of hyperlipidemia. However, more information is needed to support the use of red yeast rice as an alternative treatment to statin use.
Best practice guidelines for the use of red yeast rice in the treatment of hyperlipidemia are not available. Searching the National Guidelines Clearinghouse resulted in one article using the keyword phrase "red yeast rice". In the treatment of hyperlipidemia, a mention within the recommendation was the use of red yeast rice as a complementary and herbal remedy.10 However, this recommendation was not discussed in detail. There was no recommended dosing or conclusive statement that this would be a safe and effective alternative to statin therapy.
Current guidelines do not support the use of red yeast rice for the treatment of hyperlipidemia, despite numerous studies that report effectiveness in treatment.4 According to the U.S. Food and Drug Administration (FDA), red yeast rice contains a large amount of monacolin K, which is considered a new drug rather than a dietary supplement. Studies that have reported a significant decrease in lipid levels with the use of red yeast rice only assessed products with large amounts of monacolin K, but red yeast rice supplements often report how much red yeast rice is present in each capsule, not the amount of monacolin K.11 Adverse effects such as myopathy, liver toxicity, and rhabdomyolysis have been reported with the use of monacolin K. Additionally, if red yeast rice is not properly cultured, citrinin can form, which may cause kidney and human cell damage.4 Citrinin was found in one-third of the red yeast rice products tested.12
Studies that have reported success in the treatment of hyperlipidemia have used large amounts of monacolin K, which is considered a new and unstudied drug. As with statin therapy, there are potential side effects and risks with the use of red yeast rice. Lack of FDA approval and high variability of over-the-counter red yeast rice supplements, best practice guidelines suggest avoiding red yeast rice. Until there is continuity among red yeast rice products and further evaluation of monacolin K, it cannot be suggested for individuals to use red yeast rice for the treatment of hyperlipidemia.
Implications for Practice
Lowering of cholesterol levels is essential in the treatment and avoidance of cardiac morbidity. Although the gold standard is the use of statin therapy to lower serum cholesterol levels, many patients are unable to take these medications due to the uncomfortable adverse reactions and myalgias. Given the overall decrease in LDL cholesterol levels by 30% for patients taking red yeast rice vs a 27% decrease among patients taking pravastatin, the former may be an attractive alternative for patients who are unable to use statin therapy.4 Patients seeking alternatives may use red yeast rice, but providers must be aware of its potential adverse reactions.
Education is key in the treatment of hyperlipidemia. Open discussions between the patient and the provider about hyperlipidemia and treatment options are imperative. Lifestyle modifications, including consuming a low-fat diet and exercise, are also important and essential for lowering cholesterol levels in patients at risk for future cardiac events.
Conclusions and Recommendations
Although data are limited, there appears to be a positive influence while on a hyperlipidemia diet which includes the use of red yeast rice. Red yeast rice carries similar potential adverse reactions as stain therapy, but in the reviewed studies, there were minimal reported adverse events. Red yeast rice may be an effective alternative to the use of a statin in the treatment of hyperlipidemia. However, there are no FDA regulated red yeast rice products available over the counter and many of the red yeast rice supplements do not mention the amount of monacolin K contained in the product. This means that until an FDA-regulated red yeast rice product is available, and further research on monacolin K performed, red yeast rice cannot be recommended for individuals for the treatment of hyperlipidemia.
1. American Heart Association. About cholesterol. 2016. http://www.heart.org/HEARTORG/Conditions/Cholesterol/AboutCholesterol/About-Cholesterol_UCM_001220_Article.jsp#.WJEDA9QrJko.
2. Lin JS. An alternative treatment of hyperlipidemia with red yeast rice: A case report. J Med Case Rep. 2010;4:4.
3. Li J, Jiang L, Jia Z, et al. A meta-analysis of red yeast rice: An effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014;9(6): e98611.
4. National Center for Complementary and Integrative Health. Red yeast rice. 2013. https://nccih.nih.gov/health/redyeastrice.
5. 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 stain intolerance. Am J Cardiol. 2010;105(2): 198-204.
6. Lee CY, Jan MS, Yu MC, et al. Relationship between adiponectin and leptin, and blood lipids in hyperlipidemia patients treated with red yeast rice. Forsch Komplementmed. 2013;20(3):197-203.
7. Sartore G, Burlina S, Ragazzi E, et al. Mediterranean diet and red yeast rice supplementation for the management of hyperlipidemia in statin- intolerant patients with or without type 2 diabetes. Evid Based Complement Alternat Med. 2013;2013:743473.
8. Kasliwal RR, Bansal M, Gupta R, et al. Evaluation series on safety and efficacy of nutritional supplements in patients with newly diagnosed hyperlipidemia. Am J Cardiol. 2015;65(10).
9. Ross SM. Red yeast rice: Efficacy and tolerability of monascus purpureus yeast, for treatment of hyperlipidemia in patients with statin-induced myalgias. Holist Nurs Pract. 2012;26(3):173-175.
10. Fujimoto M, Tsuneyama K, Chen SY, et al. Study of the effects of monacolin k and other constituents of red yeast rice on obesity, insulin-resistance, hyperlipidemia, and nonalcoholic steatohepatitis using a mouse model of metabolic syndrome. Evid Based Complement Alternat Med. 2012;2012:892697.
11. National Guidelines Clearinghouse. Disorders of lipid metabolism. Evidence-based nutrition practice guideline. 2001. https://www.guidelines.gov/summaries/summary/32479/disorders-of-lipid-metabolism-evidencebased-nutrition-practice-guideline?q=red+yeast+rice
12. FDA. New dietary ingredients in dietary supplements- background for industry. 2016. http://www.fda.gov/Food/DietarySupplements/NewDietaryIngredientsNotificationProcess/ucm109764.htm.
Millie Kooistra is an FNP at Wellness for Life in Terre Haute, IN, Alaina Roman is an FNP, and Susan Eley is an associate professor at Indiana State Univeristy and FNP in private practice.