Complementary Therapies in Medicine (2012) 20, 466474

Available online at www.sciencedirect.com

journal homepage: www.elsevierhealth.com/journals/ctim

The effect of red yeast rice (Monascus purpureus) in

dyslipidemia and other disorders
Clinton W. Yang, Shaker A. Mousa
The Pharmaceutical Research Institute at the Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY
12144, USA
Available online 17 August 2012

KEYWORDS
Red yeast rice;
Dyslipidemia;
Coronary heart
disease;
Statins;
Diabetes;
Myocardial infarction;
Cancer;
Osteoporosis

Summary
Background: Red Yeast Rice (RYR) is a traditional Chinese food that is fermented and obtained
after red yeast (Monascus purpureus) is grown on rice. RYR contains Monacolin K (Lovastatin) and
other active ingredients that are thought to play a role in the management of cholesterol levels.
Recently, many clinical trials have focused on the uses of RYR, including for dyslipidemia, coronary heart disease, diabetes, osteoporosis, cancer, non-alcoholic fatty liver disease, fatigue,
and memory.
Objectives: The primary objective of this review is to evaluate the effectiveness of RYR on the
management of dyslipidemia. The secondary objective is to review studies that focus on the
other uses of RYR. The following search terms were used: red yeast rice, Xuezhikang, Hypocol,
Cholestin, Monascus purpureus combined with dyslipidemia, hypercholesterolemia, hyperlipidemia, lipid, cardiovascular, coronary, atherosclerosis, diabetes, sugar, bone, osteoporosis,
liver, fatigue, memory, Alzheimers, dementia.
Results: Studies reviewed show that RYR signicantly lowered LDL cholesterol and total
cholesterol. Effects on triglycerides and HDL cholesterol were also observed in some studies.
Compared with statins, RYR was shown to have an equal efcacy to statins when combined with
or without other dietary supplements. RYR also appeared to be superior to placebo in preventing
nonfatal myocardial infarction, total coronary heart disease events, and total deaths. On the
other hand, information on diabetes, osteoporosis, cancer, non-alcoholic fatty liver disease,
fatigue, and memory are currently limited although in vivo and in vitro studies have shown an
effect.
Conclusion: Results of RYR clinical trials presented here have limitations and RYRs clinical use
should be further investigated before using RYR as one of the alternative treatments for dyslipidemia management, despite the fact that the strongest evidence for RYR use is in dyslipidemia
versus other clinical conditions.
2012 Elsevier Ltd. All rights reserved.

Corresponding author. Tel.: +1 518 694 7397;

fax: +1 518 6947657.
E-mail address: shaker.mousa@acphs.edu (S.A. Mousa).

0965-2299/$ see front matter 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ctim.2012.07.004

The effect of red yeast rice (M. Purpureus) in dyslipidemia and other disorders

467

Contents
Background ..............................................................................................................
Methods..................................................................................................................
Results ...................................................................................................................
Effects on dyslipidemia..............................................................................................
Placebo-controlled studies....................................................................................
RYR versus statin .............................................................................................
China Coronary Secondary Prevention Study ..................................................................
Effect on coronary heart disease ....................................................................................
China Coronary Secondary Prevention Study ..................................................................
Effect on diabetes...................................................................................................
Other effects........................................................................................................
Discussion ..............................................................................................................
References .............................................................................................................

Background
Red Yeast Rice (RYR) is a traditional Chinese food that is fermented and obtained after red yeast (Monascus purpureus)
is grown on rice.1 The rst use of RYR was documented in
the Tang Dynasty (800 AD), when it was used primarily as a
preservative, coloring, and avoring agent on sh and meat.
In the Ming Dynasty (13681644), RYRs pharmacological use
was recorded in the ancient Chinese Pharmacopoeia, Ben
Cao Gang Mu-Dan Shi Bu Yi, to improve digestion, spleen,
blood circulation, and resolve blood stasis. 23 This mold is
still used mainly for coloring and avoring properties, especially in many food industries in Asia. In Japan, RYR, also
known as beni-koji, is used extensively in food coloring. RYR
has also been used in countries such as China, Taiwan, and
Philippines as a coloring and avoring agent in food, as well
as brewing wine and liquor.1,3 In the 1990s, many dietary
supplement companies started to manufacture and advertise the use of RYR as a cholesterol-lowering agent due to its
potential comparable effect to statins. However, it was not
ofcially marketed until 2001 in the US.4 Nowadays, many
commercially available RYR products are available around
the world such as Red Yeast Rice supplement, Xuezhikang,
M. purpureus rice, red mold rice, Cholestin, and HypoCol.5
The Adult Treatment Panel III (ATP III) Guideline has
identied the mainstay treatment options for dyslipidemia,
including 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (statins), bile acid sequestrants,
brates, niacin, and cholesterol absorption inhibitors.6
Among these pharmacological agents, statins possess the
greatest level of evidence regarding lipid lowering, incidence of coronary events, and prevention of death. Three
major clinical trials have shown that statins reduced coronary events by 2334% and decreased coronary heart disease
mortality by 2042%.79 However, despite the efcacy of
these agents in modulating lipid, cardiovascular events, and
death rate, the use of statins can be quite limiting due
to their safety and tolerability. For example, it is reported
that as many as 10% of patients developed statin-associated
myalgia, and the recurrence of myalgia can be as high as
57% when patients are challenged with a second statin.10,11
As a result, the adherence of statins could be as low as 40%
in less than 1 year of treatment. 12

467
467
468
468
468
468
470
470
470
471
471
471
472

Due to the limited applicability of statins, the use of

alternative therapies, such as RYR, is becoming popular.13
In 2008, American consumers spent $20 million on RYR, an
80% increase from 2005.14 The cholesterol-lowering effect
of RYR is thought to be due to Monacolin K, also known as
Lovastatin, as well as a family of 8 other Monacolin-related
substances.3,15 Thus, the primary mechanism of action of
RYR is thought to be mimicking the statins. In addition to the
HMG-CoA reductase inhibitor, RYR contains other substances
that also play a role in lowering cholesterol such as sterols,
isoavones, and monounsaturated fatty acids, as demonstrated in many reviews.3,1618 These substances, along with
Monacolin K, are also thought to have a protection effect
not only on cholesterol levels, but also on diabetes, cancer,
osteoporosis, stroke, Alzheimers, and other dementias.1 An
animal study pointed out that RYR prevented the increase
of serum total cholesterol in rabbits fed with atherogenic
diet.19 A previous review outlined 93 randomized human trials on the effectiveness and safety of different RYR products
on primary dyslipidemia and showed that RYR effectively
decreased total cholesterol, triglycerides, and LDL, and
increased HDL levels compared with placebo.5 However,
more recent studies have focused on more patient populations with longer follow-up, patients with pre-existing
medical conditions, how RYR compares to statins, and other
potential uses of RYR other than dyslipidemia. The primary
objective of this review is to focus on the more recent trials
on the use of RYR on dyslipidemia. The secondary objective
is to concentrate on the other proposed uses of RYR, including coronary heart diseases and diabetes. We will also briey
discuss the use of RYR on osteoporosis, cancer, non-alcoholic
fatty liver disease, fatigue, and memory.

Methods
We used PubMed, Medscape, and Google Scholar as our
primary literature search tools. The following inclusion criteria were used to screen out irrelevant studies: the years
20052010 regarding the use of RYR on dyslipidemia only;
in the form of a clinical trial; written in English because
no interpreter was available at our site; and clinical trials had to focus on adults 18+ years old. Because only
animal studies were done on a few of the diseases of

468
interest, we did not exclude animal studies. We searched
all the terms related to RYR and all diseases of interest.
The following objective search terms were used: red yeast
rice, Xuezhikang, Hypocol, Cholestin, Monascus purpureus
combined with dyslipidemia, hypercholesterolemia, hyperlipidemia, lipid, cardiovascular, coronary, atherosclerosis,
diabetes, sugar, bone, osteoporosis, liver, fatigue, memory,
Alzheimers, dementia. We included all patients regardless
of their cholesterol levels, co-existing diseases, preparation
of RYR, and study design. We excluded studies that focused
on animal studies on dyslipidemia, coronary heart disease,
and diabetes only. It should also be noted that this comprehensive review is not a systematic review.

Results
A total of 22 clinical trials were identied that were relevant
to our objective. Of these, 11 focused on the use of RYR on
dyslipidemia, 5 on coronary heart disease, 2 on diabetes, 2
on bone formation, 3 on memory, 1 on non-alcoholic fatty
liver disease, 1 on fatigue, and 2 on the prevention of cancer.
Some of the clinical trials analyzed more than 1 outcome.

Effects on dyslipidemia
Placebo-controlled studies
Three different studies investigated the effect of RYR on
hypercholesterolemic patients in Norway,20 Taiwan,21 and
the US.22 The US study also enrolled patients with therapeutic lifestyle change in addition to RYR. The population
number, study design, dosage, and follow-up period are
included in Table 1. Each study used the same brand of
RYR. Results from all 3 studies demonstrated a signicant
reduction in total cholesterol by 15.5% (p < 0.001)20 ; 23.7%
(p < 0.001),21 and 14.9% (p = 0.016).22 A signicant reduction
in LDL cholesterol by 23% (p < 0.001),20 27.7% (p < 0.001),21
and 21.3% (p = 0.011)22 was also observed. In addition, in the
Taiwan study, a slight but signicant reduction in triglycerides was demonstrated (p < 0.05).
However, these studies have limitations, including their
small population, short duration, and that they were singlesited. Bogsrud et al.20 and Becker et al.22 also measured
the active ingredients in their RYR preparations and found
the Monacolin K (Lovastatin) contents to be 7.2 mg and
1.02 mg, respectively. The AFCAPS/TexCAPS trial showed
that 2040 mg of Lovastatin decreased total cholesterol and
LDL cholesterol by 21.5% and 27.7%, respectively.23 It is
impossible to conclude that the Monacolin K (Lovastatin)
content in these RYR preparations has the same effect as a
standard dose of Lovastatin. It has been suggested that RYR
may have a lipid-lowering effect beyond Monacolin K alone.
Aside from the HMG-CoA reductase inhibitor, RYR contains
beta-sitosterol and capesterol, which are both thought to
have an inhibitory effect on the cholesterol absorption of
the intestine.1,3,24 In addition, RYR suppresses adipogenesis by regulating adipogenic transcription factor in 3T3-L1
cells, and decreasing glycerol-3-phosphate dehydrogenase
activity.25 RYR also contains unsaturated fatty acids, ber,
trace elements such as oleic, linoeic, and linolenic acids;
and Vitamin B complex such as niacin, which are all thought
to play a role in reducing serum cholesterol levels.1,18 As a

C.W. Yang, S.A. Mousa

result, a comparative study between RYR and statins would
have to be performed to compare their efcacy.

RYR versus statin

There were 3 studies that compared the use of RYR to a
statin (Table 1). Halbert et al. compared the lipids levels
between RYR and Pravastatin as a secondary endpoint.14
Result showed that there were no differences between the
RYR and Pravastatin group with regard to total cholesterol
(23% decrease, p = 0.23), LDL cholesterol (30.2% decrease,
p = 0.194), triglycerides (7.8% decrease, p = 0.96), or HDL
cholesterol (3.8% increase, p = 0.114).14 However, the study
evaluated lipid proles as a secondary variable, and therefore the population may not be enough for one to observe a
difference.
Becker et al. compared lipid levels between the uses of
RYR combined with sh oil to Simvastatin alone (Table 1).26
Results illustrated a signicant decrease in triglyceride
level in the RYR + sh oil group (50.8%) compared to the
Simvastatin group (p = 0.003). There was no signicant difference with regard to total cholesterol, LDL cholesterol,
and HDL cholesterol.26 However, the study failed to determine whether the lowering effects of triglyceride and other
lipids are due to sh oil alone. It has been shown that 24 g
of sh oil alone typically can lower triglyceride 2040%.27
Thus, further study would be necessary in determining RYRs
effect alone on triglyceride levels. Cicero et al. conducted
a pilot study comparing the efcacy of DIF1STAT to Pravastatin alone on patients with low risk of cardiovascular
disease.28 DIF1STAT is a patented dietary supplement containing 340 mg M. purpureus extract, 10 mg octacosanol,
and 27 mg niacin. Results showed a slight, but signicant
decrease in HDL cholesterol in the dietary supplement group
(p < 0.05), while there was no difference in LDL, total cholesterol, or triglycerides compared to the Pravastatin group.28
However, the effects of niacin and octacosanols on lipid proles have been established in a few reviews, and therefore
it is hard to determine whether the effect on lipid proles
is due to octacosanols and/or niacin alone.29,30
The above 3 trials all compared the effect of an alternative regimen (a combination of RYR, and/or other dietary
supplements) to a statin. All the result showed that RYR,
whether combined with therapeutic lifestyle change or
other dietary supplement, has the same efcacy as statins
alone. This implies that RYR may be a substitute treatment
for patients who are unwilling to tolerate statins adverse
effects, prescription costs, and physician visit cost or time.
The main side effects of statins are the incidence of intolerable myalgia and increased liver function test,31,32 which
contributes the low adherence rate for statins.12 Using RYR
as a substitute for statins may help patients to achieve their
lipid goals while reducing the cost and side effects from
statin. A meta-analysis involving 93 clinical trials evaluating
patients taking RYR did not report myalgia as one of the side
effects, but has reported a small proportion of participants
suffered from slightly increased ALT levels.5 One case report
documented a patient taking 600 mg of RYR twice daily experienced fever and severely elevated ALT (1034 U/L; normal
range 972 U/L). A liver biopsy showed lobular inammation
that is compatible with ndings of drug-induced hepatitis. Symptoms improved signicantly upon cessation of the

Summary of results regarding the use of RYR in dyslipidemic patients.

Study Design

Patients

Dosage

Follow-up Total cholesterol

vs. placebo

LDL vs. placebo

Triglycerides vs.
placebo

HDL vs. placebo

Reference

R, D, P

42, from Norway, with

hyperlipidemia
79, Chinese
62, American

N/A

16 weeks Reduced

Reduced

No difference

No difference

20

600 mg twice daily

1800 mg twice daily +
TLC
600 mg twice daily

8 weeks Reduced
24 weeks Reduced

Reduced
Reduced

Reduced
No difference

No difference
No difference

21
22

4.5 years Reduced

Reduced

Reduced

Increased

34 (CCSPS)

600 mg twice daily

4.5 years Reduced

Reduced

Reduced

Increased

36 (CCSPS)

600 mg twice daily

4.5 years Reduced

Reduced

Reduced

Reduced

35 (CCSPS)

600 mg twice daily

600 mg twice daily

4.5 years Reduced

4.5 years Reduced

Reduced
Reduced

Reduced
Reduced

No difference
Reduced

38 (CCSPS)
37 (CCSPS)

RYR 3.6 g or 2.4 g twice

daily; Fish oil
2400 mg twice daily

12 weeks No difference (vs.

Simvastatin)
12 weeks No difference (vs.
Pravastatin)
8 weeks No difference (vs.
Pravastatin)

No difference (vs.
Simvastatin)
No difference (vs.
Pravastatin)
No difference (vs.
Pravastatin)

Reduced (vs.
Simvastatin)
No difference (vs.
Pravastatin)
No difference (vs.
Pravastatin)

No difference (vs.
Simvastatin)
No difference (vs.
Pravastatin)
Reduced (vs.
Pravastatin)

26

R, D, P
R, D, P
R, D, P, M

R, open-labeled

4870, Chinese, with

history of MI
2704, Chinese,
hypertensive with
history of MI
1530, Chinese
hypertensive, 65+ years
59, Chinese, diabetic
1445, Chinese, elderly
with history of MI
74, American

R, blinded

43, American

R, D, P, M, PH

R, D, P, M, PH
R, D, P, M, PH
R, D, P, M, PH

D, not randomized 111, Italian, with low

cardiovascular risk

RYR 340 mg;

octacosanol; niacin

The effect of red yeast rice (M. Purpureus) in dyslipidemia and other disorders

Table 1

14
28

R = randomized; D = double-blinded; P = placebo-controoled; M = multi-center; PH = post hoc analysis; MI = myocardial infarction; TLC = therapeutic lifestyle change; CCSPS = China coronary
secondary prevention study.

469

470
RYR.33 Thus, RYR should be used with caution in patients
with a history of statin-induced elevated liver function test.
These studies are limited by their short duration, small
sample size, and that they are single-sited. The studies from
Becker et al. and Cicero et al. are also open-labeled and
un-blinded. These studies are at best preliminary for demonstrating RYR as a potential substitute for statin.
China Coronary Secondary Prevention Study
The China Coronary Secondary Prevention Study (CCSPS)
is the largest randomized, double-blinded, placebocontrolled, and multi-centered study focusing on RYR thus
far to our knowledge.34 The study recruited 4870 Chinese
patients with a history of acute myocardial infarction and
hypercholesterolemia across 19 provinces in China in 66
medical centers. Although the primary objective of the
study was to evaluate the use of Xuezhikang (a RYR preparation) on secondary prevention of coronary heart disease,
the study included fasting lipid levels as a secondary endpoint. Patients were followed up for an average of 4.5
years, and the longest period was 7 years. All patients were
maintained on a stable diet and lifestyle during followup. Results from this study showed that RYR decreased
total cholesterol and LDL cholesterol by 13.2% and 20.2%,
respectively, compared to placebo. RYR also showed a signicant reduction in triglyceride and a signicant elevation
in HDL cholesterol.34 There were also 4 post hoc subgroup analyses evaluating patients in specic subgroups
in the CCSPS study. All patients with hypertension, type
II diabetes, elderly patients, and elderly patients with
hypertension were investigated. Overall, there was a signicant reduction in total cholesterol (10.912.1%) and
LDL cholesterol (16.921.2%). There was also a signicant
reduction in triglycerides and elevation in HDL cholesterol
in all post hoc subgroup analyses, except patients with
Type II diabetes.3538
The major limitation of this trial is its applicability to the
non-Chinese population. It is unknown whether the study
result could be applied to patients of different races or
patients living in different geographical areas. Although
these studies have not been done, a study comparing the
differences in rosuvastatin pharmacokinetics in different
patient populations has been done. The study emphasized
that the plasma concentrationtime curve of rosuvastatin
was signicantly higher in Chinese, Maley, and Asian-Indian
subjects compared with white subjects living in the same
area.39 This suggests that Chinese patients may benet
more from statins compared to the Western population. The
main lipid-lowering active ingredient of RYR is Monacolin K
(Lovastatin),3 and therefore it is possible that the Chinese
population in CCSPS would have an exaggerated effect compared to the other races. A study comparing the efcacy
of RYR across different populations would have to be conducted before applying the results of CCSPS to the Western
or other populations.

Effect on coronary heart disease

Cardiovascular disease, including coronary heart disease
(CHD), is the number one cause of death globally. A statistic
from the NHANEs trial for the year 2006 pointed out that 80

C.W. Yang, S.A. Mousa

million Americans have one or more types of cardiovascular
disease, of whom 16.8 million have CHD alone. Of those, cardiovascular disease accounted for approximately 2.4 million
deaths, and CHD for 425,000 deaths.40 Controlling risk factors such as serum cholesterol is one of the most important
methods in the primary and secondary prevention of CHD,
especially in the older population.41 A meta-analysis examining the effect of an HMG-CoA reductase inhibitor (statin)
on all-cause mortality in patients with a history of CHD provided a strong justication for the use of statin therapy in
patients with pre-existing CHD, especially in the older population who are at an increased risk for CHD.42 Therefore,
patients using statins may have effects beyond lipid lowering, such as preventing the incidence of death caused by
CHD.
As a result of RYR containing Monacolin K (Lovastatin), thought to mimic the statin activity, using RYR
as a lipid-lowering agent may also prevent morbidity
and mortality caused by CHD. Although previous metaanalysis and this review have shown an efcacy of RYR
in controlling CHD risk factors such as dyslipidemia, there
is no evidence regarding the relationship between RYR
and CHD events, which is obviously the most important
outcome.5
Preliminary studies have shown that RYR is effective in improving abnormal physiological values associated
with CHD. Lin et al. illustrated that RYR inhibits
homocysteine-induced reactive oxygen species generation,
nuclear factor-kappa B activation, and vascular cell adhesion molecule-1 expression in human aortic endothelial
cells.43 Wang et al. conducted a double-blinded, randomized trial on patients with acute coronary syndrome
and found that RYR effectively reduced endothelin-1 and
C-reactive protein, while increasing ow-mediated vasodilation and nitric oxide.44 Finally, Zhao et al. demonstrated
the effectiveness of RYR in decreasing C-reactive protein and improving ow-mediated vasodilation in patients
with CHD.45 All these results provided a modest justication for the potential efcacy of RYR in the management
of CHD.

China Coronary Secondary Prevention Study

The CCSPS is the only study to our knowledge that analyzed the relationship between RYR and CHD events. The
primary objective of the study was to evaluate whether
the lipid-lowering therapy of RYR reduces the risk of coronary event and all-cause death in Chinese patients with CHD
and hyperlipidemia. Primary endpoints included non-fatal
myocardial infarction (MI), fatal MI, sudden death, other
CHD death, and total CHD events. Results show that RYR
signicantly decreased the risk of non-fatal MI events and
overall CHD events, but failed to demonstrate an effect
in other CHD endpoints.34 Post hoc subgroup analyses were
conducted in addition to the primary analysis (Table 2).3538
In summary, all post hoc subgroup analyses demonstrated
a consensus with regard to nonfatal MI, total CHD events,
and total death. However, as mentioned above, the major
limitation of this large, multi-centered trial is its external
validity to the other patient populations outside of China.
Future studies are recommended to include the Western
populations.

38
to

Other effects
RYR has been shown to have other effects beyond dyslipidemia and CHD. In vivo and in vitro studies have successfully
justied the possible efcacy of RYR in cancer, osteoporosis,
non-alcoholic fatty liver disease, fatigue, and memory.5058
However, more extensive human studies are necessary to
conrm these results before they can be applied clinically
in humans.

N/A

to

MI = myocardial infarction; CHD = coronary heart disease.

Reduced compared to
placebo
Type II Diabetes

No difference

Discussion

No difference

No difference
Reduced compared to
placebo
Hypertension + Elderly

No difference

No difference

to
N/A
No difference
Reduced compared to
placebo
Elderly

No difference

Diabetes is a common disease affecting 35% among the

Western population. Patients with diabetes are thought to
have a signicantly higher risk of death from CHD than
non-diabetic individuals.4647 An animal study conducted
by Chang et al. shows a decrease in glucose level in
streptozotocin-induced diabetic rats lacking insulin.48 However, current human studies regarding the use of RYR in
diabetes is limited. Fang and Li conducted an observational study evaluating 45 patients for 8 weeks and showed
that RYR signicantly decreased fasting blood glucose in
patients with or without hyperlipidemia compared to baseline (p < 0.05).49 On the other hand, Bogsrud et al. found
no differences between the groups with regard to glucose
tolerance.20 Thus, the role of RYR in the management of
diabetes is currently unclear.

to

35
to

37
to

36
to

Reduced
compared
placebo
Reduced
compared
placebo
Reduced
compared
placebo
Reduced
compared
placebo
Reduced
compared
placebo
Reduced
compared
placebo
Reduced
compared
placebo
Reduced
compared
placebo
No difference
No difference
Reduced compared to
placebo
Hypertension

No difference

to

Total death
Total CHD events
Blood pressure
Sudden death
Nonfatal MI

Fatal MI

471

Effect on diabetes

Patient characteristics

Table 2

Post hoc subgroup analysis in the China Coronary Secondary Prevention Study.

Reference

The effect of red yeast rice (M. Purpureus) in dyslipidemia and other disorders

RYR containing Monacolin K (Lovastatin) has important

function in the management of dyslipidemia and CHD, as
demonstrated in this review. RYR also exhibits equal efcacy to Pravastatin and Simvastatin when combined with or
without other dietary supplement in lowering cholesterol
levels. In addition, in vivo and in vitro studies have shown
efcacy in osteoporosis, cancer, non-alcoholic fatty liver disease, fatigue, and memory, although a need to explore its
use clinically in humans is necessary. With all these considerations, RYR demonstrates an effect beyond lipid lowering. A
summary of the current level of evidence of its uses is given
in Table 3.
However, despite the current evidences available, future
work must be done before this product can be recommended. Not all commercially available RYR products are
created equally. Some RYR products may contain more or
less active and toxic ingredients that may exhibit marked
efcacy or toxicities.59 Physicians recommending this product to patients for dyslipidemia or CHD prevention should
be cautious in selecting consistent brands of products for
patients. Physicians should also be aware that RYR should
not be used in place of statins, or for those patients who
cannot tolerate statin-associated myalgia. Future studies
involving larger populations, longer follow-up, and focusing
on Western populations in different geographic areas taking more than one commercially available product would
have to be analyzed and compared before RYR can be safely
recommended as a substitute for statins.
Principle ndings: Despite the fact that the strongest evidence for RYR use is in dyslipidemia versus other clinical
conditions, clinical use of RYR should be further investigated

472
Table 3

C.W. Yang, S.A. Mousa

Level of evidence of RYR use.

RYR use

Level of evidence

Dyslipidemiaa
Coronary heart disease
Diabetes
Cancer
Osteoporosis
Non-alcoholic fatty liver disease
Fatigue
Memory

A/B
B/C
C/D
C
C
C
C
C

A = strong positive scientic evidence; B = positive scientic evidence; C = unclear scientic evidence; D = negative scientic
evidence; E = strong negative scientic evidence. Grading system
adopted from Natural Standard: The Authority on Integrative
Medicine.60.
a Despite the overall positive scientic evidence and in some
trials the strong scientic evidence, more rigorous, double-blind
multicenter trials are required prior to making any recommendations.

before using RYR as one of the alternative treatments for the

management of dyslipidemia.
Strengths and weaknesses of this review: This review provides a comprehensive assessment of clinical experiences
with RYR and the relative level of evidence as summarized
in Table 3. However, this review is not a systematic review
and provides all available clinical experiences with RYR in
various clinical settings regardless of the strength of the
evidence. We have to consider the following limitations:
(a) lack of clear denition and criteria for randomization;
(b) most available trials did not use double-blind randomization; and (c) all trials did not account for the different
types of biases such as attrition, reporting, and publication.
Unanswered questions: It is clear that further randomized, double-blind clinical trials in dyslipidemia and other
indications are required before making recommendations.
In conclusion, data suggest potential benets of RYR in
dyslipidemia versus other investigated clinical conditions.
However, before making any recommendation even for the
use of RYR as an alternative to statins, more rigorous,
double-blind randomized clinical trials in comparing the efcacy and safety to statins are warranted.

References
1. Erdogrul O, Azirak S. A review on the red yeast rice
(Monascus purpureus). KSU Journal of Science and Engineering
2005;8:105.
2. Monograph. Monascus purpureus (red yeast rice). Alternative
Medicine Review 2004;9:20810.
3. Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL.
Cholesterol-lowering effects of a proprietary Chinese red-yeastrice dietary supplement. American Journal of Clinical Nutrition
1999;69:2316.
4. Journoud M, Jones PJ. Red yeast rice: a new hypolipidemic drug.
Life Sciences 2004;74:267583.
5. Liu J, Zhang J, Shi Y, Grimsgaard S, Alraek T, Fonnebo V. Chinese
red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chinese
Medicine 2006;1:4.

6. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection,
evaluation, and treatment of high blood cholesterol in adults
(Adult Treatment Panel III). JAMA: The Journal of the American
Medical Association 2001;285:248697.
7. Randomised trial of cholesterol lowering in 4444 patients with
coronary heart disease: the Scandinavian Simvastatin Survival
Study (4S). Lancet 1994;344:13839.
8. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range
of initial cholesterol levels. The Long-Term Intervention with
Pravastatin in Ischaemic Disease (LIPID) Study Group. New England Journal of Medicine 1998;339:134957.
9. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole
TG, et al. The effect of pravastatin on coronary events after
myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. New
England Journal of Medicine 1996;335:10019.
10. Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to
moderate muscular symptoms with high-dosage statin therapy
in hyperlipidemic patientsthe PRIMO study. Cardiovascular
Drugs and Therapy 2005;19:40314.
11. Kashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S,
Ko DT, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation
2006;114:278897.
12. Hansen KE, Hildebrand JP, Ferguson EE, Stein JH. Outcomes in
45 patients with statin-associated myopathy. Archives of Internal Medicine 2005;165:26716.
13. Kelly JP, Kaufman DW, Kelley K, Rosenberg L, Anderson TE,
Mitchell AA. Recent trends in use of herbal and other natural
products. Archives of Internal Medicine 2005;165:2816.
14. Halbert SC, French B, Gordon RY, Farrar JT, Schmitz K, Morris PB, et al. Tolerability of red yeast rice (2,400 mg twice
daily) versus pravastatin (20 mg twice daily) in patients with
previous statin intolerance. American Journal of Cardiology
2010;105:198204.
15. Endo A. Monacolin K, a new hypocholesterolemic agent
produced by a Monascus species. Journal of Antibiotics
1979;32:8524.
16. Malinowski JM, Gehret MM. Phytosterols for dyslipidemia. American Journal of Health-System Pharmacy 2010;67:116573.
17. Zdrenghea D, Pop D, Colcear D. Effect of dietary isoavones
on plasma cholesterol. Romanian Journal of Internal Medicine
2006;44:35363.
18. Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, et al. Constituents of red
yeast rice, a traditional Chinese food and medicine. Journal of
Agricultural and Food Chemistry 2000;48:52205.
19. Zhu Y, Li C, Wang Y. Effects of Xuezhikang on blood lipids
and lipoprotein concentrations of rabbits and quails with
hyperlipidemia. Chinese Journal of Pharmacology 1995;30:
48.
20. Bogsrud MP, Ose L, Langslet G, Ottestad I, Strom EC, Hagve TA,
et al. HypoCol (red yeast rice) lowers plasma cholesterol a
randomized placebo controlled study. Scandinavian Cardiovascular Journal 2010;44:197200.
21. Lin CC, Li TC, Lai MM. Efcacy and safety of Monascus purpureus
Went rice in subjects with hyperlipidemia. European Journal
of Endocrinology/European Federation of Endocrine Societies
2005;153:67986.
22. Becker DJ, Gordon RY, Halbert SC, French B, Morris PB,
Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant
patients: a randomized trial. Annals of Internal Medicine
2009;150(830839):W147839.
23. Downs JR, Cleareld M, Weis S, Whitney E, Shapiro DR, Beere PA,
et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results
of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis

The effect of red yeast rice (M. Purpureus) in dyslipidemia and other disorders

24.

25.

26.

27.

28.

29.

30.
31.
32.
33.

34.
35.

36.

37.

38.

39.

40.

Prevention Study. JAMA: The Journal of the American Medical

Association 1998;279:161522.
Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical
and experimental evidence. American Journal of Medicine
1999;107:58894.
Jeon T, Hwang SG, Hirai S, Matsui T, Yano H, Kawada T, et al. Red
yeast rice extracts suppress adipogenesis by down-regulating
adipogenic transcription factors and gene expression in 3T3-L1
cells. Life Sciences 2004;75:3195203.
Becker DJ, Gordon RY, Morris PB, Yorko J, Gordon YJ, Li M, et al.
Simvastatin vs therapeutic lifestyle changes and supplements:
randomized primary prevention trial. Mayo Clinic Proceedings
2008;83:75864.
Kris-Etherton PM, Harris WS, Appel LJ. Omega-3 fatty acids
and cardiovascular disease: new recommendations from the
American Heart Association. Arteriosclerosis, Thrombosis, and
Vascular Biology 2003;23:1512.
Cicero AF, Brancaleoni M, Laghi L, Donati F, Mino M. Antihyperlipidaemic effect of a Monascus purpureus brand dietary
supplement on a large sample of subjects at low risk for cardiovascular disease: a pilot study. Complementary Therapies in
Medicine 2005;13:2738.
Marinangeli CP, Jones PJ, Kassis AN, Eskin MN. Policosanols as
nutraceuticals: fact or ction. Critical Reviews in Food Science
and Nutrition 2010;50:25967.
Perry CM. Extended-release niacin (nicotinic acid)/laropiprant.
Drugs 2009;69:166579.
Meador BM, Huey KA. Statin-associated myopathy and its exacerbation with exercise. Muscle and Nerve 2010;42:46979.
Andrus MR, East J. Use of statins in patients with chronic hepatitis C. Southern Medical Journal 2010;103:101822 [quiz 1023].
Roselle H, Ekatan A, Tzeng J, Sapienza M, Kocher J. Symptomatic hepatitis associated with the use of herbal red yeast
rice. Annals of Internal Medicine 2008;149:5167.
Lu ZL. China coronary secondary prevention study (CCSPS).
Zhonghua Xin Xue Guan Bing Za Zhi 2005;33:10915.
Li JJ, Lu ZL, Kou WR, Chen Z, Wu YF, Yu XH, et al. Benecial impact of Xuezhikang on cardiovascular events and
mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention
Study (CCSPS). Journal of Clinical Pharmacology 2009;49:
94756.
Li JJ, Lu ZL, Kou WR, Chen Z, Wu YF, Yu XH, et al. Impact
of Xuezhikang on coronary events in hypertensive patients
with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). Annals of Medicine
2010;42:23140.
Ye P, Lu ZL, Du BM, Chen Z, Wu YF, Yu XH, et al. Effect of
xuezhikang on cardiovascular events and mortality in elderly
patients with a history of myocardial infarction: a subgroup
analysis of elderly subjects from the China Coronary Secondary
Prevention Study. Journal of the American Geriatrics Society
2007;55:101522.
Zhao SP, Lu ZL, Du BM, Chen Z, Wu YF, Yu XH, et al. Xuezhikang,
an extract of cholestin, reduces cardiovascular events in type 2
diabetes patients with coronary heart disease: subgroup analysis of patients with type 2 diabetes from China coronary
secondary prevention study (CCSPS). Journal of Cardiovascular
Pharmacology 2007;49:814.
Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose
H, et al. Rosuvastatin pharmacokinetics and pharmacogenetics
in white and Asian subjects residing in the same environment.
Clinical Pharmacology and Therapeutics 2005;78:33041.
Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De
Simone G, et al. Heart disease and stroke statistics2010
update: a report from the American Heart Association. Circulation 2010;121:e46215.

473

41. Benfante R, Reed D, Frank J. Do coronary heart disease risk

factors measured in the elderly have the same predictive roles
as in the middle aged Comparisons of relative and attributable
risks. Annals of Epidemiology 1992;2:27382.
42. Thomas JE, Tershakovec AM, Jones-Burton C, Sayeed RA,
Foody JM. Lipid lowering for secondary prevention of cardiovascular disease in older adults. Drugs and Aging 2010;27:
95972.
43. Lin CP, Chen YH, Chen JW, Leu HB, Liu TZ, Liu PL, et al. Cholestin
(Monascus purpureus rice) inhibits homocysteine-induced
reactive oxygen species generation, nuclear factor-kappaB activation, and vascular cell adhesion molecule-1 expression in
human aortic endothelial cells. Journal of Biomedical Science
2008;15:18396.
44. Wang WH, Zhang H, Yu YL, Ge Z, Xue C, Zhang P. Intervention
of xuezhikang on patients of acute coronary syndrome with different levels of blood lipids. Zhongguo Zhong Xi Yi Jie He Za Zhi
2004;24:10736.
45. Zhao SP, Liu L, Cheng YC, Shishehbor MH, Liu MH, Peng DQ,
et al. Xuezhikang, an extract of cholestin, protects endothelial
function through antiinammatory and lipid-lowering mechanisms in patients with coronary heart disease. Circulation
2004;110:91520.
46. Pyorala K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes/Metabolism Reviews
1987;3:463524.
47. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes
and in nondiabetic subjects with and without prior myocardial infarction. New England Journal of Medicine 1998;339:
22934.
48. Chang JC, Wu MC, Liu IM, Cheng JT. Plasma glucose-lowering
action of Hon-Chi in streptozotocin-induced diabetic rats. Hormone and Metabolic Research 2006;38:7681.
49. Fang Y, Li W. Effect of Xuezhikang on lipid metabolism and islet
b cell function in type II diabetes mellitus patients. Journal of
Capital Medicine 2000;7:445.
50. Gutierrez GE. Red yeast rice stimulates bone formation in rats.
Nutrition Research 2006;26:1249.
51. Wong RW, Rabie B. Chinese red yeast rice (Monascus purpureusfermented rice) promotes bone formation. Chinese Medicine
2008;3:4.
52. Hong XZ, Li LD, Wu LM. Effects of fenobrate and xuezhikang
on high-fat diet-induced non-alcoholic fatty liver disease.
Clinical and Experimental Pharmacology and Physiology
2007;34:2735.
53. Wang JJ, Shieh MJ, Kuo SL, Lee CL, Pan TM. Effect of red
mold rice on antifatigue and exercise-related changes in lipid
peroxidation in endurance exercise. Applied Microbiology and
Biotechnology 2006;70:24753.
54. Lee CL, Kuo TF, Wang JJ, Pan TM. Red mold rice ameliorates impairment of memory and learning ability in
intracerebroventricular amyloid beta-infused rat by repressing
amyloid beta accumulation. Journal of Neuroscience Research
2007;85:317182.
55. Lee BH, Ho BY, Wang CT, Pan TM. Red mold rice promoted antioxidase activity against oxidative injury and improved the memory
ability of zinc-decient rats. Journal of Agricultural and Food
Chemistry 2009;57:106007.
56. Lee CL, Wang JJ, Pan TM. Red mold rice extract
represses amyloid beta peptide-induced neurotoxicity via
potent synergism of anti-inammatory and antioxidative
effect. Applied Microbiology and Biotechnology 2008;79:
82941.
57. Tsai RL, Ho BY, Pan TM. Red mold rice mitigates oral carcinogenesis in 7,12-dimethyl-1,2-benz[a]anthracene-induced oral
carcinogenesis in hamster. Evidence-based Complementary and
Alternative Medicine 2011;2011, 245209.

474
58. Hong MY, Seeram NP, Zhang Y, Heber D. Anticancer effects of
Chinese red yeast rice versus monacolin K alone on colon cancer
cells. The Journal of Nutritional Biochemistry 2008;19:44858.
59. Gordon RY, Cooperman T, Obermeyer W, Becker DJ. Marked
variability of monacolin levels in commercial red yeast

C.W. Yang, S.A. Mousa

rice products: buyer beware! Archives of Internal Medicine
2010;170:17227.
60. Natural Standard: The Authority on Integrative Medicine; 2012.
Available from: http://www.naturalstandard.com/ [accessed
26.06.12].