Red Yeast Rice For Cardioprotection: A State-Of-The-Science Review

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Red Yeast Rice for Cardioprotection
A state-of-the-science review
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By Michael Traub, ND, DHANP, FABNO
Abstract
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About the Author
With the growing popularity of red yeast rice (RYR) as a

lipid-lowering agent, it is important to ensure that this
dietary supplement is safe and effective. The objective of
this review was to provide current evidence-based guidance
on the use of RYR. PubMed was searched for RYR studies
published 20092011. The review confirmed that RYR is
safe and efficacious for dyslipidemia and has other potential
cardioprotective applications.
Introduction
Michael Traub ND, DHANP,

FABNO, has been practicing in
Hawaii since 1985. He is
past-president of the American
Association of Naturopathic
Physicians (AANP) and
received the AANPs
Naturopathic Physician of the
Year award in 2006. He is the
author of Essentials of
Xuezhikang, extract of red yeast rice (RYR), is a traditional

Chinese medicine with multiple cardioprotective effects. RYR is a
fermented product of rice on which red yeast (Monascus
purpureus) has been grown. For centuries, Xuezhikang has been
used as a medicinal food in China to promote blood circulation.
It is used to make rice wine and to give Peking duck its red color.
RYR contains numerous statins, including lovastatin, and has
been shown in clinical trials to improve lipid profiles.1 In 1999,
articles began to be published about a RYR supplement tested in
Dermatological Diagnosis and
an American population at University of California, Los Angeles
Integrative Therapeutics. His
School of Medicine.2 A 2001 review appearing in Alternative
website is
Medicine Review brought more attention to RYR in the natural
www.michaeltraubnd.com.
medicine community,3 and this author reviewed the use of RYR in
a chapter of Integrative Cardiology, published in 2007.4 The focus
of the present review is on several studies published in the past 2 years on RYRs safety and
effectiveness for dyslipidemia and its potential cardioprotective applications for other cardiovascular
conditions as well.
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Background of RYR
Statin drugs are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that have been
demonstrated to reduce lipid levels and risk for stroke and coronary events and mortality.5 They have
also been shown to suppress the production of cholesterol and inflammatory cells in plaque,6 enhance
endothelial function, reduce serum fibrinogen, and possibly reduce thrombosis.7 These benefits are not
without the risk of some serious adverse effects: hepatoxicity, myositis, and rhabdomyolysis.
Hypothyroidism and hepatic and renal impairment increase the risk of myopathy.
Analysis of RYR has revealed 14 monacolins, which are HMG-CoA reductase inhibitors, in addition to
sterols, isoflavones, glycerides, and monounsaturated fatty acids.8 A common misconception is based
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several other end products, such as nonsterol isoprenoid end products, including coenzyme Q10
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(CoQ10) and dolichol. The CoQ10-lowering effect of statins and its compensation by administration of
CoQ10 were described 20 years ago and since then have been confirmed in numerous studies of
animals and humans.9 CoQ10 is involved in the stabilization of cell membranes and is a potent
scavenger of reactive oxygen species, preventing oxidative injury to DNA, lipids, proteins, and other
molecules.10 This action retards or prevents the development of many cardiovascular and possibly
neoplastic and neurodegenerative disease states. In some patients, statin-associated myopathy is due
to an inability of myocytes to efficiently use respiratory pathways to produce ATP. Therefore, reduced
levels of CoQ10 in these individuals who lack alternate pathways for ATP synthesis results in myopathy.
The high concentration of CoQ10 in cardiac muscle is also adversely affected in some patients taking
statins and may predispose an individual to congestive heart failure and cardiomyopathy.
Despite numerous clinical trials documenting a relatively good safety profile, side effects resulting from
treatment with statins occur not infrequently. Some of the adverse reactionsmyalgia; myopathies;
rhabdomyolysis; gastrointestinal symptoms, including hepatic injury; and the initiation or accelerated
progression of cataracts and neoplasiacould be a direct or indirect consequence of the CoQ10deficiency state associated with statin treatment. CoQ10 supplementation should be considered during
extended therapy with statins to support cellular bioenergetic demands.11
Dosage and practical considerations

The therapeutic dosage of RYR is 1,2004,800 mg daily. As with statin therapy, the lower dosage is
sufficient for many patients, and higher dosages can be reserved for those whose lipid profiles do not
adequately respond at the lower dose. Monacolins in RYR are light-sensitive and thermal-sensitive;
therefore RYR should be stored in a cool place and protected from light.12 Administration of CoQ10, 50
mg daily, is reasonable to use with RYR to prevent the theoretical CoQ10 deficiency that could occur.
Niacin has been reported to increase the efficacy of statins,13and there is no reason to suspect that the
same would not be true in combination with RYR. A dosage of 100 mg niacin daily has been used in the
authors practice for this purpose. A small study found that in 10 of 12 patients with statin-induced
myopathy unresponsive to CoQ10 supplementation, creatine monohydrate, 5 grams twice daily, was
effective in providing tolerance to statins.14 Creatine supplementation should be limited to those with
normal renal function.
It remains unlikely, though unclear whether the lipid-lowering effect of RYR is due solely to the monacolin
K content, or if other monacolins, sterols, and isoflavones contribute. The monacolin K content in RYR,
although variable, does not come close to approaching the therapeutic dosages of lovastatin (2040 mg
daily). The lovastatin content of RYR, depending on the strain and manufacturer, is generally around 0.2
percent of total product.1 At a daily dosage of 1,200 mg of RYR, the lovastatin dosage would be 2.4
mg.
Adverse reactions to RYR

With the wide use of RYR over the past 20 years, safety concerns appear much less prevalent than for
statin drugs. One case report exists of acute hepatitis associated with a RYR-containing product.15A
63-year-old woman presented with severe hypertransaminasemia that had developed progressively over
a few weeks. For 6 months she had been taking Equisterol, an over-the-counter lipid-lowering product
containing guggulsterol and RYR extract. The product had been prescribed for hypercholesterolemia
because the patient had developed hepatotoxicity while on lovastatin. Liver biopsy revealed severe
lobular necroinflammatory changes with an eosinophilic infiltrate. The episode was regarded as an
adverse drug reaction after exclusion of other possible causes of acute liver disease and the prompt
normalization of liver function tests after Equisterol had been discontinued.
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philosophically opposed to statins, may benefit

from RYR.
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Another case report mentions an adverse drug-nutrient interaction between cyclosporine and a
RYR-containing preparation.16
Citrinin is a nephrotoxin found in some sources of RYR. Gordon et al sent 12 commercial RYR products
out for analysis and found that citrinin was present in one-third of the products tested.8 It is important to
use only RYR that is certified citrinin-free.
Review of recent studies of RYR (20092011)

A review published in the July-August 2011 Canadian Journal of Cardiology included 136 meta-analyses
and randomized controlled trials of lipid-lowering diets and dietary supplements and concluded that RYR,
along with green tea and red wine, could be considered for improvement of the lipid profile.17 The
authors state that omega-3 fatty acid supplementation can be recommended fully. These findings seem
to reflect the level of evidence more than the level of efficacy, as RYR is much more potent in
correcting dyslipidemia than green tea, red wine, and omega-3 fatty acids. Becker and Gordon et al
published results in the Annals of Internal Medicine, June 2009, of a randomized trial of RYR 1,800 mg
twice daily in people who were also enrolled in a therapeutic lifestyle change program. The trial showed
that showing that LDL cholesterol decreased by 43 mg/dL from baseline at week 12.1
Becker and Gordon, in collaboration with another group, published a study in the American Journal of
Cardiology in January 2010 on the tolerability of RYR 2,400 mg twice daily versus pravastatin 20 mg
twice daily for 12 weeks in statin-intolerant patients who were simultaneously enrolled in a therapeutic
lifestyle change program.18 The LDL cholesterol decreased 30% in the RYR group and 27% in the
pravastatin group.
Gordon et al published another article in the Archives of Internal Medicine in October 2010 on the
variability of monacolin levels in commercial RYR products.8 They note that RYR contains 14 active
monacolins that inhibit cholesterol synthesis. They had ConsumerLab send 12 commercial RYR
products out for analysis and found that total monacolins varied from 0.31 to 11.15 mg/capsule and
monacolin K (lovastatin) varied from 0.10 to 10.09 mg/capsule. Citrinin was present in one-third of the
products tested.
Another review article published in February 2011 by Becker and Gordon concluded that RYR was a
promising therapy for patients who object to statins on a philosophical basis or who have had statininduced myopathy.19 They warn, however, that RYR products carry the risk of toxic levels of citrinin, and
that until they are standardized, they should be used with caution.
A group of researchers reported in the American Journal of Cardiology in March 2010 that a review of
25 patients with myalgias, gastrointestinal intolerance, and/or elevated alanine aminotransferase levels
with previous use of other lipid-lowering agents who then took RYR had a decrease in LDL cholesterol of
21% and tolerated the treatment well.20 Abd and Jacobson from Emory University School of Medicine
reviewed statin-induced myopathy, and their findings were published in May 2011.21 Noting that
observational studies estimate 1015% of statin users develop myopathy, they reviewed the clinical
features, risk factors, and mechanisms and proposed an evidence-based algorithm for statin-intolerant
patients that was both patient-related and drug-related, including the option of RYR.
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No medical interventions for abdominal aortic aneurysm (AAA) have been discovered, and regular
monitoring has been the only option prior to surgical correction. In July 2011, a study was published in
the Journal of Nutritional Biochemistry showing that RYR suppressed angiotensin IIinduced AAA in
mice and may have preventive potential for patients with AAA.24
Li et al showed that RYR in rats inhibited tissue factor and hypercoagulable state through suppressing
nicotinamide adenine dinucleotide phosphate (NADP) oxidase and extracellular signal-regulated kinase
activation.25 They also showed that RYR was more potent than lovastatin in inhibiting NADP oxidase
activation, and that RYR significantly reduced blood coagulation activation in high cholesterol
dietinduced atherosclerotic rats.
Conclusion
In conclusion, the evidence for the safety and efficacy of RYR in dyslipidemia continues to be
confirmed. Patients for whom dietary modification, exercise, and stress management have been
unsuccessful, or who are statin-intolerant or philosophically opposed to statins, may benefit from RYR.
Although there is no evidence that RYR lowers blood pressure, animal studies suggest it may be
beneficial for patients with abdominal aortic aneurysm and hypercoagulable states.
References
1. Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized
trial. Ann Intern Med. 2009;150(12):830-9, W147-149.
2. 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 Feb;69(2):231-236.
3. Patrick, L, Uzick, M. Cardiovascular Disease: C-Reactive Protein and the Inflammatory Disease Paradigm: HMG-CoA Reductase Inhibitors,
alpha-Tocopherol, Red Yeast Rice, and Olive Oil Polyphenols. A Review of the Literature. Alt Med Rev 2001. 6(3).
4. Traub, M. Naturopathic Medicine, in Integrative Cardiology, ed. Vogel and Krucoff, 2007.
5. Heneghan C. Considerable uncertainty remains in the evidence for primary prevention of cardiovascular disease. Cochrane Database Syst
Rev. 2011 Jan 14;(8):ED000017.
6. Shiomi M, Ito T, Tsukada T, Et al. Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of
pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscler Thromb Vasc Biol 1995;15:1938-1944
7. Vaughan C, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996;348:1079-1082
8. 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 Oct 25;170(19):1722-1727.
9. Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner J. 2010 Spring;10(1):16-21.
10. Ibid.
11. Bliznakov EG, Wilkins DJ. Biochemical and clinical consequences of inhibiting coenzyme Q10 biosynthesis by lipid-lowering HMG-CoA
reductase inhibitors (statins): a critical overview. Adv Ther. 1998;15:218228.
12. Li YG, Liu H, Wang ZT. A validated stability-indicating HPLC with photodiode array detector (PDA) method for the stress tests of Monascus
purpureus-fermented rice, red yeast rice. J Pharm Biomed Anal. 2005 Sep 1;39(1-2):82-90.
13. Hochholzer W, Berg DD, Giugliano RP.The facts behind niacin. Ther Adv Cardiovasc Dis. 2011 Oct;5(5):227-240.
14. Shewmon DA, Craig JM. Creatine supplementation prevents statin-induced muscle toxicity. Ann Intern Med. 2010, 153:690-692 (letter).
15. Grieco A, Miele L, Pompili M, Biolato M, Vecchio FM, Grattagliano I, Gasbarrini G. Acute hepatitis caused by a natural lipid-lowering product:
when "alternative" medicine is no "alternative" at all. J Hepatol. 2009 Jun;50(6):1273-7.
16. Prasad GV, Wong T, Meliton G, Bhaloo S. Ryabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient.
Transplantation 2002;74:1200-1201.
17. Huang J, Frohlich J, Ignaszewski AP. The impact of dietary changes and dietary supplements on lipid profile. Can J Cardiol. 2011
Jul-Aug;27(4):488-505.
18. Halbert SC, French B, Gordon RY, Farrar JT, Schmitz K, Morris PB, Thompson PD, Rader DJ, Becker DJ. 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 Jan 15;105(2):198-204.
19. Gordon RY, Becker DJ. The role of red yeast rice for the physician. Curr Atheroscler Rep. 2011 Feb;13(1):73-80.
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previous myocardial infarction: data from the Chinese Coronary Secondary Prevention Study (CCSPS). Clin Exp
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Hypertens. 2010;32(8):491-498.
24. Xie X, Wang Y, Zhang S, Zhang G, Xu Y, Bi H, Daugherty A, Wang JA.Chinese red yeast rice attenuates the development of angiotensin
II-induced abdominal aortic aneurysm and atherosclerosis. J Nutr Biochem. 2011 Jul 15. [Epub ahead of print]
25. Li P, Yang Y, Liu M. Xuezhikang, Extract of Red Yeast Rice, Inhibited Tissue Factor and Hypercoagulable State Through Suppressing
Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Extracellular Signal-regulated Kinase Activation. J Cardiovasc Pharmacol. 2011
Sep;58(3):307-318.
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