Safety and Efficacy of Red Yeast Rice (Monascus purpureus) as an Alternative Therapy for Hyperlipidemia

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Abstract
Red yeast rice is a Chinese fermented rice product (Monascus purpureus) that some have claimed improves blood circulation by decreasing cholesterol and triglyceride levels in humans. The supplement contains naturally occurring monacolin K, the active ingredient found in Merck's prescription agent lovastatin (Mevacor). Lovastatin is associated with various adverse effects such as myopathy and abnormal liver function test results, which can lead to serious problems if patients are not monitored and treated. The inclusion of lovastatin in red yeast rice and the lack of dietary supplement regulation by the FDA raise safety concerns for health care professionals as well as for patients. Studies have shown that red yeast rice products can be beneficial in lowering serum cholesterol levels, but they are not without risk. Furthermore, product uniformity, purity, labeling, and safety cannot be guaranteed.
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is monacolin K, which has the same chemical structure as
lovastatin. Although levels of lovastatin vary in the product,
2.4 g of red yeast rice daily may contain about 4.8 mg of lov -
astatin, or 0.2% of the total dose. Red yeast rice supplements
may also contain isoflavonoids, monounsaturated fats, and
sterols that help to reduce cholesterol levels even further.
3
The natural inclusion of low-dose lovastatin raises concerns
for patient safety. In 2007, the FDA warned consumers to avoid
red yeast rice supplements promoted on the Internet (Red
Yeast Rice, Red Yeast Rice/Policosonal Complex, and
Cholestrix) to lower cholesterol because of the possibility of
myopathy, leading to kidney impairment.
6
The widespread
use of evidence-based medicine has caused health care pro-
fessionals to become skeptical about dietary supplement use.
The lack of studies and regulations to ensure the safety of these
products has the result of steering health care professionals
away from herbal products and toward prescription medica-
tions that have been demonstrated to be safe and efficacious.
Health care practitioners should become aware of herbal prod-
ucts that patients might be using in place of commonly pre-
scribed medications. This article reviews the safety and
effectiveness of red yeast rice as a “natural” alternative treat-
ment to statins for hypercholesterolemia.
LITERATURE FINDINGS
Before performing a MEDLINE search, we identified the most
appropriate search terms using the MeSH (medical subject
headings) database provided by the National Library of Med-
icine (www.pubmed.gov). Instead of using this database to
perform the search, we conducted a “text word” search (from
1966 to November 2008) using PubMed to include articles
indexed for M
EDLINE as well as those not yet indexed (those
that do not yet have MeSH terms assigned).
When a relevant article was located, we reviewed the MeSH
terms assigned to that article to identify other relevant search
terms. To be as complete as possible, we did not use any lim-
itations.
PubMed includes millions of citations from M
EDLINE and
other life science journals for biomedical articles. We reviewed
the bibliographies of all relevant articles to identify any other
pertinent articles that the previous searches might have
missed. Our article includes some of the more provocative data
about red yeast rice but might not include all available relevant
literature.
Matthew Klimek and Adeleye Ogunkanmi are postdoctoral fellows
at Rutgers University Ernest Mario School of Pharmacy in Piscat-
away, New Jersey. Shan Wang is a clinical pharmacist at Winthrop
University Hospital in Mineola, New York.
Accepted for publication March 9, 2009
Safety and Efficacy of Red Yeast Rice
(Monascus purpureus)
as an Alternative
Therapy for Hyperlipidemia
Matthew Klimek, PharmD, Shan Wang, PharmD, and Adeleye Ogunkanmi, PharmD
Key words: red yeast rice, Monascus purpureus, hyper -
lipidemia, myopathy, dietary supplement, lovastatin
ABSTRACT
Red yeast rice is a Chinese fermented rice product (Mon as -
cus purpureus) that some have claimed improves blood circu-
lation by decreasing cholesterol and triglyceride levels in hu-
mans. The supplement contains naturally occurring monacolin
K, the active ingredient found in Merck’s prescription agent
lovastatin (Mevacor). Lovastatin is associated with various
adverse effects such as myopathy and abnormal liver function
test results, which can lead to serious problems if patients are
not monitored and treated. The inclusion of lova statin in red
yeast rice and the lack of dietary supplement regulation by the
FDA raise safety concerns for health care professionals as
well as for patients. Studies have shown that red yeast rice prod-
ucts can be beneficial in lowering serum cholesterol levels, but
they are not without risk. Furthermore, product uniformity,
purity, labeling, and safety cannot be guaranteed.
BACKGROUND
Despite the increase in FDA-approved prescription med-
ications, alternative therapies have become more prevalent in
the U.S. About 42% of Americans use alternative medicine, and
the demand for these therapies continues to grow.
1,2
In 1997,
patients paid approximately 629 million visits to alternative
medicine practitioners, a rate that was 47% higher than in 1990.
At approximately $27 billion, total out-of-pocket expenditures
for alternative therapies exceeded total out-of-pocket expen-
ditures for all hospitalizations in the U.S.
1
Red yeast rice, a Chinese dietary supplement, has gained
popularity because of its properties as a natural statin. This fer-
mented rice product is used as a medicinal food to improve
blood circulation by decreasing cholesterol and triglyceride
levels.
3,4
The supplement contains varying amounts of natural
monacolins as a result of the different strains of Monascus
purpureus used in fermentation.
5
Monacolins lower choles-
terol by inhibiting HMG–CoA (5-hydroxy-3-methylglutaryl-
coenzyme A) reductase, the rate-limiting step for cholesterol
synthesis in the liver. The primary monacolin in red yeast rice
Disclosure. The authors have no financial or commercial relation-
ships to report in regard to this article.
314
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• June 2009 • Vol. 34 No. 6
EFFICACY
Lu et al.
7
Lu et al. conducted a randomized, double-blind, placebo-
controlled clinical trial of 4,870 Chinese subjects over 4.5 years
to evaluate the efficacy of Xuezhikang (XZK), an extract of
cholestin and derived from fermented red yeast rice. The
study medication consisted of 300-mg capsules of XZK. Each
capsule contained 2.5 to 3.2 mg of lovastatin and a small amount
of hydroxyl acid, ergosterol, and other components. To be in-
cluded in the study, patients must have had a myocardial in-
farction (MI) within 60 months of enrollment.
Patients underwent a four-week initial period of a controlled
diet beginning with the cessation of all lipid-lowering agents.
At the end of four weeks, baseline lipid levels were measured.
Baseline characteristics were similar for all treatment groups
except for sex (3,986 men and 884 women).
Mean low-density lipoprotein-cholesterol (LDL-C) levels
were 129 mg/dL in both groups at baseline. Patients treated
with XZK showed a significant decrease in frequency of major
coronary events such as nonfatal MI and death from coronary
or cardiac causes when compared with those receiving placebo
(–10.4% and –5.7%, respectively; P < 0.001). They also experi-
enced a 33% decrease in the need for coronary revasculariza-
tion compared with the placebo recipients (P = 0.004).
Within eight weeks after randomization, total cholesterol
(–10.9%) and LDL-C (–17.6%) levels decreased significantly
and were maintained over the duration of the study in the
XZK-treated group (P < 0.001). The authors concluded that
XZK demonstrated efficacy in decreasing cholesterol, recur-
rent coronary events, and mortality rates.
Lin et al.
8
Lin and coworkers assessed the lipid-lowering effect and
safety of M. purpureus in a randomized, double-blind, placebo-
controlledstudy of 79 patients 23 to 65 years of age with hyper -
lipidemia. Subjects received M. purpureus 600 mg twice daily
or placebo for eight weeks. The meanbaseline LDL-C level was
203.9 mg/dL. At week eight, M. purpureus therapy signifi-
cantly reduced concentrations of LDL-C by 27.7%, total cho-
lesterol by 21.5%, triglycerides by15.8%, and apolipoprotein B
(apo-B) by 26%. High-density lipoprotein-C (HDL-C) and
apolipoprotein A-I (apo A-I) levels were increased nonsignifi-
cantly by0.9% and 3.4%, respectively.
Gheith et al.
9
Gheith and colleagues compared the efficacy and safety of
M. purpureus Went rice (red yeast rice) with fluvastatin (Lescol,
Novartis) in the management of nephrotic dyslipidemia. The
investigators conducted an open-label study of 72 patients with
dyslipidemia secondary to idiopathic persistent nephrotic
syndrome. Patients were randomly divided into three groups:
20 patients received M. purpureus Went rice 600 mg twice a day
for one month, then 600 mg once daily; 30 patients were treated
with fluvastatin 20 mg daily; and 22 controls group received no
therapy.
The fluvastatin group had average total cholesterol readings
of 436, 333, 313, and 302 mg/dL at baseline, three months, six
months, and one year, respectively. Similar reductions were ob-
served in the Went rice group, with cholesterol averages of 457
mg/dL at baseline, 408 mg/dL at three months, 283 mg/dL at
six months, and 303 mg/dL at one year. A significant reduction
in proteinuria was noted in the fluvastatin group (8.3 g/day at
baseline vs. 2.4 g/day at one year) and in the Went rice group
(8.6 g/day at baseline vs. 3.2 g/day at one year) but not in the
control arm.
Compared with baseline evaluations, there was no clinical
evidence of myopathy or neuropathy in patients who received
statins or Went rice. The authors concluded that M. purpureus
Went rice was a safe and effective strategy for treating
nephrotic dyslipidemia.
Summary
In each of these studies, M. purpureus provided beneficial
effects in hyperlipidemic patients
7–9
and might have also pos-
itively affected cardiac outcomes.
7
Studies like these give con-
fidence to patients seeking alternative cholesterol-lowering
therapies in place of more conventional statin therapies.
SAFETY
All three controlled trials (Lu, Lin, Gheith) showed that
M. purpureus was well tolerated with few safety concerns.
7–9
In
the trial conducted by Lin et al.,
8
none of the subjects receiving
M. purpureus experienced alanine aminotransferase (ALT),
aspar tate aminotransferase (AST), or creatine phosphokinase
(CPK) measurements that were more than three times the
upper limit of normal (ULN) at the fourth or eighth week.
Gheithet al.
9
also found no evidence of significant adverse
effects in neuromuscular function associated with M. purpureus.
Despite these findings, published case reports show
potential safety problems with the use of red yeast rice. The
following case reports of myopathy and rhabdomyolysis illus-
trate these potential dangers.
Myopathy
Vercelli et al.
10
A 76-year-old man with type-2 diabetes received statins for
four years; 20 mg of simvastatin (Zocor, Merck) daily for two
years, followed by 20 mg of atorvastatin (Lipitor, Pfizer) daily
for two years. After four years of therapy, atorvastatin was
discontinued upon patient complaints of generalized muscle
weakness and serum creatinine kinase (CK) levels of 3,000
U/L. Six months later, generalized muscle weakness improved
slightly, but CK levels climbed to 3,700 U/L.
An open quadriceps muscle biopsy revealed muscular
atrophy. The patient then admitted that three months after
discontinuing atorvastatin, he had begun using a product
derived from red yeast rice as an alternative therapy to lower
cholesterol. Red yeast rice was discontinued at this point. Mus-
cle weakness improved and CK levels fell to 1,000 U/L three
months after he stopped taking red yeast rice. The authors
concluded that patients with statin-induced muscle damage
should not use red yeast rice as a way to lower cholesterol.
Smith et al.
4
Smith and colleagues described a case of symptomatic
myopathy associated with the use of Chinese red yeast rice.
4
A 50-year-old man visited his primary care physician, report-
ing joint pain and muscle weakness for two months. At pres-
Red Yeast Rice for Hyperlipidemia
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entation, he had diffuse body aching, upper-extremity weak-
ness, and lower-back stiffness along with a CK level of 358 U/L.
He had no history of muscle diseases or problems. According
to the patient, the only new medications in his regimen were
ginseng, Chinese red yeast rice, and rofecoxib (Vioxx, Merck).
The patient had started taking ginseng and Chinese red yeast
rice four weeks before his symptoms developed and then
started to take rofecoxib after the onset of symptoms. He was
instructed to discontinue both of these products. At the three-
week follow-up visit, his muscle weakness and joint pain
resolved completely and the CK level fell to 179 U/L. Eight
months later, the patient resumed taking Chinese red yeast
rice, and his CK level increased again to 212 U/L.
Mueller
11
A case of symptomatic myopathy was attributed to red yeast
rice in a 61-year-old woman with hyperlipidemia.
11
She was
started on simvastatin 20 mg daily along with estradiol from a
transdermal patch at a dose of 0.05 mg/week, aspirin 81 mg
daily, and a multivitamin. The patient was otherwise in good
health; vital signs and laboratory parameters were within nor-
mal limits. After four months of therapy, simvastatin was in-
creased to 40 mg daily. At this point, the CK level was 189 U/L.
Within one month, diffuse myalgia and an elevated CK level
of 451 U/L were reported.
After simvastatin was discontinued, symptoms resolved and
CK levels returned to 170 U/L. Soon afterward, the patient
began using red yeast rice 600 mg twice daily as an alternative
treatment. Three months later, diffuse myalgia returned and
CK levels increased to 475 U/L. Red yeast rice was then dis-
continued; symptoms resolved, and CK levels decreased to 122
U/L. Like simvastatin, red yeast rice caused diffuse myalgia
and elevated CK levels. After these products were discontin-
ued, symptoms resolved soon thereafter.
Summary
Although the effects of red yeast rice are mild, the product
can cause muscle pain and weakness similar to that associated
with conventional statins. These events can become serious if
the patient’s intake is not monitored appropriately. Awareness
of the previous two cases can help health care professionals
understand the potential for myopathy when red yeast rice is
used as a natural alternative to statins.
Rhabdomyolysis
Prasad et al.
12
Prasad and coworkers reported on a 28-year-old stable renal
transplant recipient who developed rhabdomyolysis after ther-
apy with red yeast rice.
12
The patient experienced an asymp-
tomatic elevation of CK to 1,050 IU/L; a second assessment
showed a CK level of 2,600 IU/L. After questioning, the patient
stated she had taken red yeast rice for the previous two months
to lower cholesterol naturally. After she stopped taking the sup-
plement, her CK levels fell to 600 IU/L within two weeks and
she remained clinically asymptomatic.
The patient was also taking cyclosporine to prevent trans-
plant rejection. Cyclosporine, a known cytochrome P450 3A4
inhibitor, most likely elevated red yeast rice serum concen-
trations by inhibiting its metabolism. It is important to note the
probable drug–herbal interaction between cyclosporine and
red yeast rice. Cyclosporine is a commonly prescribed pre-
scription medication, and taking concomitant red yeast rice can
result in serious rhabdomyolysis.
Consistency and Content of Red Yeast Rice
Besides the adverse effects caused by M. purpureus, the
composition of red yeast rice can cause patient harm if quality
control is inadequate. Heber et al. conducted an analysis of nine
proprietary Chinese red yeast rice dietary supplements: Cho-
lesterex, Cholestene, Cholactive, Cholester-Reg, Beyond Cho-
lesterol, Hongqu, Cholesterol Power, red yeast rice, and
Cholestin.
13
The authors of this study aimed (1) to determine
whether the cholesterol-lowering effect of red yeast rice was
consistent among all red yeast rice products and (2) to detect
impurities in the product. They measured monacolin concen-
trations in each supplement along with citrinin, a nephrotoxic
by-product of fermentation (Table 1). Citrinin, a dangerous
nephrotoxin, was measured by radioimmunoassay and served
as an indicator of potential danger as a result of its contents
other than the active ingredients.
Results showed a wide rage of monacolin K (0.15–3.37 mg)
and monacolin L (less than 0.006–0.02 mg) content per capsule.
Only one of the tested products included all 10 monacolin
compounds that a quality red yeast rice product should con-
tain. Citrinin was found at measurable concentrations in seven
of nine preparations (0.47–64.7 mcg/capsule). The quality and
contents varied between each product, indicating that not all
red yeast rice products are equal. The authors concluded that
standardized manufacturing practices and adequate labeling
are needed to ensure the equivalence of active ingredients for
efficacy and a low concentration of unwanted fermentation
by-products to ensure safety.
13
DISCUSSION
The efficacy of dietary supplements is usually questionable
because of the lack of controlled clinical trials supporting their
use. Two randomized, double-blind, placebo-controlled trials
7,8
and an open-label trial
9
demonstrated that red yeast rice might
be effective in lowering LDL-C levels.
Lu et al. further demonstrated that red yeast rice might be
able to reduce cardiac events and provide positive effects on
cardiovascular outcomes in a fashion similar to that of pre-
scription statin therapy.
7
Although larger-scale trials are nec-
essary to confirm these findings, red yeast rice seems prom-
ising in the treatment of hyperlipidemia. Such efficacy data
influence patients to try natural remedies before using more
common prescription drug therapies. The vast amount of data
demonstrating the benefits of statin therapy in cardiovascular
disease supports its continued use, but practitioners should be
aware of alternative therapies being used by their patients.
Unlike prescription drugs, dietary supplements have not
traditionally undergone extensive testing by the FDA. Without
adequate testing, dietary supplements are not guaranteed to
contain the quantity or quality of ingredients stated on the prod-
uct label. As shown by Heber et al.,red yeast rice is no excep-
tion.
13
Each of the nine products tested had different monacolin
levels. Supplements with a lower monacolin content would be
less effective in lowering cholesterol.
Red Yeast Rice for Hyperlipidemia
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• June 2009 • Vol. 34 No. 6
Seven of the tested samples contained citrinin, a mycotoxin
produced by a variety of fungi in the production of foods in-
tended for human consumption such as grain, cheese, and red
pigments. Citrinin is a nephrotoxin in all animal species tested,
but its acute toxicity varies.
14
Citrinin is genotoxic at high con-
centrations in cultured human lymphocytes; therefore, its con-
centration in supplements should be minimal.
15
Inconsistencies such as these led the FDA to require current
good manufacturing practices (CGMPs) for dietary supple-
ments.
16
Final CGMPs were expected to become effective in
June 2008 for large companies and are to be implemented in
June 2009 for companies with fewer than 500 employees and
in June 2010 for companies with fewer than 20 employees.
Under this ruling, all domestic and foreign supplements must
be processed in a consistent manner and to meet quality stan-
dards. To demonstrate quality and consistency, tests will be
performed on all supplements to ensure their identity, purity,
strength, and composition.
Statin drugs such as Merck’s Mevacor (lovastatin) are
associated with various side effects such as headache, dizzi-
ness, rash, upset stomach, and hepatic dysfunction. The most
common adverse effect is muscle weakness, which can be a
sign of more serious myopathy or, in rare cases, rhabdo -
myolysis.
17
Double-blind, controlled clinical trials have dem -
onstrated that red yeast rice is effective and well tolerated in
a wide range of patients;
7,8
however, case reports have linked
it to muscular myopathy and rhabdomyolysis. In three cases
described here,
4,10,11
red yeast rice caused or exacerbated my-
opathy marked by elevated serum CK levels. Rhabdomyolysis,
the most severe adverse effect associated with statins,
occurred in a renal transplant patient who used red yeast rice
while concomitantly taking cyclosporine.
12
Although the more
reliable controlled trials showed no need for safety concerns,
case reports warn of the possibility of adverse effects with
wider use. These reports should not be ignored for patients
who are taking red yeast rice as an alternative to common pre-
scription statins.
Lovastatin as a prescription drug is contraindicated in preg-
nancy and is a Category X agent. This labeling is a main rea-
son for the FDA’s rejection of the application submitted by
Merck to sell lovastatin over the counter.
18
Red yeast rice,
when used by pregnant women, places the fetus at unneces-
sary risk of central nervous system defects during the first
trimester. Although red yeast rice contains a lower dose of
lovastatin compared with the FDA-approved product, the risk
posed may be similar.
CONCLUSION
Despite the growing interest in dietary supplements, red
yeast rice (M. purpureus) is not recommended for patients with
hypercholesterolemia. A lack of uniformity among products,
the possibility of contamination, and the risk of severe ad-
verse reactions pose a threat to individuals using this product.
Overall, red yeast rice has not been shown to be a safe alter-
native to statins for patients with hyperlipidemia despite its
demonstrated efficacy in controlled clinical trials. Physicians
should be aware of its popularity as a “natural” way to lower
serum cholesterol, and they should discuss the risks and ben-
efits of this supplement with their patients.
REFERENCES
1. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative
medicine use in the United States, 1990–1997: Results of a follow-
up national survey. JAMA 1998;280(18):156–175.
2. Kessler RC, Davis RB, Foster DF, et al. Long-term trends in the
use of complementary and alternative medical therapies in the
United States. Ann Intern Med 2001;135:262–268.
3. Patrick L, Uzick M. Cardiovascular disease: C-reactive protein and
the inflammatory disease paradigm: HMG–CoA reductase inhib -
itors, alpha-tocopherol, red yeast rice, and olive oil polyphenols:
A review of literature. Altern Med Rev 2001;6(3):248–270.
4. Smith DJ, Olive KE. Chinese red rice–induced myopathy. South
Med J 2003;96(12):1265–1267.
5. Liu J, Zhang J, Shi Y, et al. Chinese red yeast rice (Monascus pur-
pureus) for primary hyperlipidemia: A meta-analysis of random-
ized controlled trials. Chinese Med 2006;1(4):1–13.
Red Yeast Rice for Hyperlipidemia
Monacolin K Monacolin L Citrinin
Red Yeast Rice Supplements (mg per Capsule) (mg per Capsule) (mcg per Capsule)
Cholesterex
a
1.35 <0.006 4.87
Cholestene
b
2.87 <0.006 2.22
Cholactive
c
1.80 <0.006 6.06
Cholester-Reg
d
3.37 <0.006 3.23
Beyond Cholesterol
e
0.15 0.02 No data available*
Hongqu
f
2.86 <0.005 11.82
Cholesterol Power
g
2.51 <0.007 0.47
Red Yeast Rice
h
1.56 <0.006 64.7
Cholestin
i
2.46 0.015 No data available*
* Limits of detectability = 0.04 mcg per capsule.
(a) Oralabs, Englewood, Colo.; (b) HPF, LLC, Hatboro, Pa.; (c) Herbscience, Windmill Health Products, West Caldwell, N.J.; (d) Nature’s Sun-
shine, Provo, Utah; (e) TwinLab, Hauppauge, N.Y.; (f) Nature’s Sunshine, Provo, Utah; (g) Nature’s Herbs, Hauppauge, N.Y.; (h) Solaray, Park City,
Utah; (i) Pharmanex, Brisbane, Calif.
Adapted with permission from Heber S, Audra L, Qing-Yi L, et al. J Altern Complement Med 2001;7(2):133–139. Copyright, Mary Ann Liebert
Publishers, Inc.
13
Table 1 Contents of Monacolin and Citrinin in Chinese Red Yeast Rice Products
continued on page 327
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6. FDA warns consumers to avoid red yeast rice products promoted
on Internet as treatments for high cholesterol. August 9, 2007.
Available at: www.fda.gov/bbs/topics/NEWS/2007/NEW01678.
html. Accessed March 3, 2008.
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red yeast Chinese rice, on coronary events in a Chinese popula-
tion with previous myocardial infarction. Am J Cardiol 2008;
101(12):1689–1693.
8. Lin CC, Li TC, Lai MM. Efficacy and safety of Monascus purpureus
Went rice in subjects with hyperlipidemia. Eur J Endocrinol
2005;153(5):679–686.
9. Gheith O, Sheashaa H, Abdelsalam M, et al. Efficacy and safety
of Monascus purpureus Went rice in subjects with secondary
hyperlipidemia. Clin Exp Nephrol 2008;12(3):189–194.
10. Vercelli L, Mongini T, Olivero N, et al. Chinese red rice depletes
muscle coenzyme Q
10
and maintains muscle damage after discon-
tinuation of statin treatment. J Am Geriatr Soc 2006;54(4):718–720.
11. Mueller PS. Symptomatic myopathy due to red yeast rice. Ann
Intern Med 2006;145(6):474–475.
12. Prasad GV, Wong T, Meliton G, et al. Rhabdomyolysis due to red
yeast rice (Monascus purpureus) in a renal transplant recipient.
Transplantation 2002;74(8):1200–1201.
13. Heber S, Audra L, Qing-Yi L, et al. An analysis of nine propriety
Chinese red yeast rice dietary supplements: Implications of vari-
ability in chemical profile and contents. J Altern Complement Med
2001;7(2):133–139.
14. Bennett JW, Klich M. Mycotoxins. Clin Microbiol Rev 2003;16(3):
497–516.
15. Donmez-Altuntas H, Dumlupinar G, Imamoglu Z, et al. Effects of
the mycotoxin citrinin on micronucleus formation in a cyto -
kinesis-block genotoxicity assay in cultured human lymphocytes.
J Applied Toxicol 2007;27(4):337–341.
16. FDA. Dietary supplement current good manufacturing practices
(CGMPs) and interim final rule (IFR) facts, 2007. Available at:
www.cfsan.fda.gov/~dms/dscgmps6.html. Accessed August 27,
2007.
17. Mevacor (lovastatin), package insert. Updated September 2008.
Merck & Co. Available at: www. merck.com/product/usa/
pi_circulars/m/mevacor/mevacor_pi.pdf. Accessed September
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18. Dyer O. FDA rejects sale of over the counter statins. BMJ 2005;
330(7484):164. I
continued from page 316
Red Yeast Rice for Hyperlipidemia
    • "Citrinin is a nephrotoxin elaborated by many fungal genera as Penicillium, Aspergillus, and Monascus (Flajs and Peraica 2009). Apart from lethal effect on kidney, this mycotoxin has been shown to be a teratogen (deleterious to embryo or fetus) (Flajs and Peraica 2009) and genotoxin at high concentrations in cultured human lymphocytes (Klimek et al. 2009). A meta-analysis of twenty studies on RYR showed safety consideration is low, as the instances of hepatic and renal impairment ranged from 0 to 5 % (Gerards et al. 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Red yeast rice (RYR), the fermentation product of mold Monascus purpureus has been an integral part of Oriental food and traditional Chinese medicine, long before the discovery of their medicinal roles. With the identification of bioactive components as polyketide pigments (statins), and unsaturated fatty acids, RYR has gained a nutraceutical status. Hypercholesterolemic effect of this fermented compound has been validated and monacolin K has been recognized as the pivotal component in cholesterol alleviation. Functional similarity with commercial drug lovastatin sans the side effects has catapulted its popularity in other parts of the world as well. Apart from the hypotensive role, ameliorative benefits of RYR as anti-inflammatory, antidiabetic, anticancer and osteogenic agent have emerged, fueling intense research on it. Mechanistic studies have revealed their interaction with functional agents like coenzyme Q10, astaxanthin, vitamin D, folic acid, policosanol, and berberine. On the other hand, concurrence of mycotoxin citrinin and variable content of statin has marred its integration in mainstream medication. In this disputable scenario, evaluation of the scopes and lacunae to overcome seems to contribute to an eminent area of healthcare. Graphical Abstract Red yeast rice (RYR), the rice-based fermentation product of mold Monascus purpureus is a functional food. Its bioactive component monacolin K acts like synthetic drug lovastatin, without the severe side effects of the latter. RYR has been validated to lower cholesterol, control high blood pressure; confer anti-flammation, hypoglycaemic, anticancer and osteogenic properties. However, dose inconsistency and co-occurrence of toxin citrinin hampers its dietary supplementation prospect. Further research might facilitate development of RYR as a nutraceutical.
    Article · May 2016
    • "The active hypocholesterolemic agent in RYR (mainly monacolin K) is produced during fermentation of rice with the yeast M. purpureus, which may concurringly form CIT. The actual cholesterol lowering activity of monacolins lies in their ability to inhibit the hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in the hepatic cholesterol synthesis (). Besides RYR-FS might be a cost-effective asset for health care systems (Heber et al., 1999) as they are less costly and in some cases statin-intolerant patients with statin-associated myalgia have shown a better tolerance to them (Becker et al., 2009; Halbert et al., 2010; Klimek et al., 2009). Because of this sudden gain in popularity combined with growing scientific concerns, the European Union has recently issued a regulation concerning RYR-FS, restricting their CIT content to 2,000 µg/kg (EC, 2014a). "
    [Show abstract] [Hide abstract] ABSTRACT: Mycotoxins may cause deleterious effects (among others nephrogenic, hepatogenic, carcinogenic, teratogenic, neurogenic) in animals and humans, therefore they have been intensely studied and monitored over the years. For citrinin (CIT), a nephrotoxic mycotoxin, however, this has not yet been the case. According to the latest European Food Safety Authority report, a correct risk assessment of CIT was not possible due to the lack of occurrence data. Besides, traces of CIT or its metabolite, dehydrocitrinone are widely (in up to 90% of samples) present in human urine according to recent Belgian and German scientific reports, which might imply chronic exposure. Only recently, a European maximum limit has been set for CIT in cholesterol reducing food supplements including red yeast fermented rice (RYR). During production of RYR through fungal (among others Monascus purpureus) fermentation of rice other components, like CIT, as well as nephrotoxic ochratoxin A (OTA) may form. Consequently, the present work attempted develop to a robust and routinely applicable ultra-high performance liquid chromatographytandem mass spectrometry (UHPLC-MS/MS) method for the analysis of CIT and OTA in food, feed and in RYR food supplements. The method was successfully validated based on EU/657/2002 and EU/519/2014 in RYR food supplements and wheat flour, achieving respective limits of quantification (LOQ) for CIT of 0.4 μg/kg and 0.1 μg/kg and for OTA of 15 μg/kg and 0.4 μg/kg. The average between-day recoveries varied from 72 to 110% with relative standard deviations ≤16%. Single-day validation in rice, curry and apple matrices showed LOQs ranging from 0.3-1.0 μg/kg. Next, the occurrence of CIT/OTA was surveyed in 138 RYR, food and feed samples, proving the potential of this method for future data acquisition within a risk assessment framework specifically for CIT, while also gaining information about the (co-)occurrence of OTA in edible matrices.
    Article · Mar 2016
    • "Moreover, RYR exerts beneficial effects in hyperlipidemia and might have also positively influenced cardiac outcomes (Lu et al., 2008). Based on these results, it has been suggested that hyperlipidemic patients may have option to choose alternative cholesterol-lowering therapies instead of more conventional statin therapies (Klimek, Wang, & Ogunkanmi, 2009). Besides, earlier clinical studies demonstrated that Xuezhikang, a partially purified extract of RYR could exert antiinflammatory actions (Li et al., 2005) and improve endothelial function (Lu et al., 2008 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Herbal drugs, which possess immunomodulatory, anti-inflammatory, anti-diabetic, anti-infective, and anti-allergic activities, encompass various therapeutic areas, and have been used as traditional medicines for thousands of years. Fermentation is an indispensable traditional technology for the improving the efficacy or reducing adverse effects of herbal medicines. The fermentation process has been shown to improve biological properties of plants, vegetables, and herbs. More specifically, fermentation causes decomposition and/or biotransformation of complex substrates into compatible components, thereby modulating product properties or changing the quantity of certain bioactive compounds. Accumulating evidence indicates the valuable contribution of probiotics and their fermented food products to health. In recent years, considerable attention has been paid to fermentation technology across the globe for improving herbal drugs through production and enrichment of additional bioactive metabolites of medicinal importance including isoflavones, saponins, phytosterols, and phenols. For example, the phenolic contents of the herbal preparation can be increased as a consequence of fermentation and a positive correlation between polyphenols and the anti-oxidant activities of herbs has been well demonstrated. This is in agreement with evidence showing fermentation-mediated enhancement of the pharmacological properties and therapeutic efficacies of herbal formulations against a number of diseases including obesity and inflammation. The subject of fermentation of herbal preparations has been maturing and gaining considerable attention of scientific and technical communities worldwide. In the current review we have addressed these issues in detail with emphasis on understanding the contribution of fermentation-derived bioactive substances to therapies against a number of diseases.
    Article · Dec 2015
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