Commentary
European Journal of Preventive
The Red Yeast Rice story: How to
manufacture a tall tale from nature
Kellyanne Rose Gold1, Robert Gold2, Bharathi Avula3 and
Ikhlas A Khan3,4
Recently, we published a Letter to the Editor (‘‘Letter’’)
in Annals of Nutrition and Metabolism entitled ‘‘The
color of rice and the Chinese paradox’’.1 Red Yeast
Rice (RYR), the subject of the Letter, is touted as
‘‘nature’s source’’ of the statins. RYR has both been
consumed as a traditional food staple (‘‘traditional
RYR’’) by the eastern Chinese provinces over many
centuries2 and sold commercially as a health supple-
ment over the last two decades (‘‘RYR supplement’’).
Current popular belief is that traditional RYR and
RYR supplement are one in the same; however, as we
will describe, this is a misconception. In our Letter, we
presented the following hypothesis: could the lower
incidence of cardiovascular disease (CVD) observed in
Chinese provinces that consume traditional RYR com-
pared with those provinces that do not be related to the
lifetime of consumption of traditional RYR with its
presumed statin content? After the publication of our
Letter, we decided to reexamine the statin content of
traditional RYR. Our findings, in conjunction with the
following historical background, may impact our rec-
ommendation on the usage of RYR supplements to our
patients.
The discovery of the statins heralded a new era in the
management of both primary and secondary preven-
tion of CVD.3 A pioneering Japanese researcher,
Akira Endo, began searching for an inhibitor of
HMG-CoA reductase from the fermentation of literally
thousands of fungal broths.4 The HMG-CoA reductase
inhibitor he discovered was isolated from a fermenta-
tion catalyzed by Monascus purpureus, the same fun-
gus utilized in the preparation of traditional RYR.
The statin he isolated was Monacolin K (also known
as lovastatin).
The M. pupureus story begins in antiquity.
Traditional RYR has been a Chinese food staple con-
sumed for centuries in the Eastern Chinese Provinces;
it is a food product that results from the fermentation
of white rice and the fungus M. purpureus. The red
color is imparted by various pigments that result from
the fermentation process. RYR supplement capsules,
presumed to contain desiccated traditional RYR
Cardiology
2018, Vol. 25(1) 73–75
! The European Society of
Cardiology 2017
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/2047487317739080
journals.sagepub.com/home/ejpc
product, are ubiquitous in health food stores, pharma-
cies and supermarkets. The active ingredients in
RYR supplements are ascribed to the statin contents
(principle statin is lovastatin), which are also products
of the fermentation process. One of the initial articles
on RYR describes the efficacy of RYR supplement
in lowering serum lipids in a clinical setting in China.
The authors clearly state ‘‘the M. Purpureus prepar-
ation . . . is prepared by a traditional rice fermentation
method’’.5 However, the fermentation conditions were
modified to enhance statin production. Within several
years after the emergence of the first pharmaceutical
statin on the market, the RYR supplement industry
emerged. A ‘‘natural’’ supplement derived from a trad-
itional food with health benefits related to the natural
lovastatin content became the core of the marketing
strategy. This strategy was derailed in the late 1990s
by a United States Food and Drug Administration
(FDA) investigation which had ascertained that the
majority of the traditional RYR they tested contained
no statins.6 At the time, lovastatin was a pharmaceut-
ical on the market under FDA regulation. The FDA
reasoned that the absence of statins in traditional RYR
compared with statin content in RYR supplement
implied that the supplement industry was marketing a
regulated drug as an unregulated ‘‘natural’’ product.
This finding is not widely known and has not been
widely published in the medical literature. The FDA
subsequently mandated that no RYR supplement sold
1
University of Toledo College of Medicine and Life Sciences, Toledo, USA
2
Department of Internal Medicine, Olive View–UCLA Medical Center,
Los Angeles, USA
3
National Center for Natural Products Research, School of Pharmacy,
University of Mississippi, University, USA
4
Division of Pharmacognosy, Department of BioMolecular Sciences,
School of Pharmacy, University of Mississippi, University, USA
Corresponding author:
Kellyanne Rose Gold, University of Toledo College of Medicine and Life
Sciences, 2801 W. Bancroft Toledo, Ohio, 43606, USA.
Email: kellyannerosegold@gmail.com
74 European Journal of Preventive Cardiology 25(1)

Ankflavin

description translated from Chinese label product name in English ‘‘GUGUXIAN’’; Sample 6: Red Yeast Rice, Monascus purpureus powder extract 0.4% Monacolin K; Sample 7: Red Glutinous Rice (no
Sample 1: Red Yeast Rice authentic rice sample, product of China; Sample 2: Red Yeast Rice authentic, description translated from Chinese label, ‘‘Semen Oryzae Cum Monasco,’’ product of People’s Republic
of China; Sample 3: Red Yeast Rice authentic, description translated from Chinese label; Sample 4 Red Yeast Rice authentic, description translated from Chinese label; Sample 5: Red Yeast Rice authentic,
in the United States may legally contain more than
trace amounts of statins.

ND
ND
þ
þ
þ
þ
þ
In the course of our investigation we discovered that
the industrial production of supplemental RYR and

Monasfluore
some pharmaceutical statins (lovastatin) are similar,
if not identical. Adjustments of various parameters

ND
ND
such as pH, oxygen tension and temperature, as well

þ
þ
þ
þ
þ
rubramine Monascin B
as specific strain of Monascus may be manipulated to
increase the production of statins.7–9 In contrast, the
industrial production of supplemental RYR is dissimi-

ND
ND
þ
þ
þ
þ
þ
lar from the recipe for traditional RYR. In fact, RYR
supplement with higher statin content is often not red.

Monacolin monacolin Sudan Rubropunct Monasco

Additionally, lovastatin producing strains of Monascus
are poor producers of red pigments.9 The conditions

ND
ND
þ
þ
þ
þ
þ
which optimize statin production minimize red pigment
production. One of the key methodologies utilized to

Pigments
maximize statin content is maintenance of fermentation

Red G atamine
temperature at 25 C. The traditional RYR fermenta-

ND
ND
þ
þ
þ
þ
þ
tion generates heat that leads to higher fermentation
temperatures and a red color. Another byproduct of
this process is the production of the renal toxic meta-

ND
ND
ND
ND
ND
ND
ND
bolite, citrinin, which has been found in some RYR
supplements.10
Dehydro
Traditional RYR was purchased directly from

ND
ND
ND
ND
ND

ND
China, from Chinese grocers in Los Angeles, and

0.6
K
from the Internet. In conjunction with the University
of Mississippi Natural Products Lab, which utilizes
more sensitive assays than the initial FDA investiga-
ND
ND
ND
ND
ND

ND
tion, we analyzed numerous samples of traditional

1.4
Mevastatin K

RYR and two control samples. The quantitative ana-

lyses of several samples of traditional RYR are consist-
ent (see Table 1, samples 1–5). No statins were present
ND
ND
ND
ND
ND
ND
and the samples tested positive for typical Monascus ND
pigments. Sample 6 was a preparation of supplemental

DUL: detected under limits of quantification; ND: not detected; þ: detected

Monacolin

RYR with Monacolin K content advertised as 0.4%.

Citrinin diol lactone K acid

indication fermented rice product on Chinese label), product of Taiwan.

This powdered sample contained statin metabolites and
Level of detection: 0.1 mg/ml for monacolins and 0.2 mg/ml for citrinin.
0.49
Monacolins (mg/g)

ND
ND
ND
ND
ND

ND

was red, but contained none of the red pigment typic-

ally produced during traditional RYR fermentation.
Furthermore, according to the prior literature, in prop-
Lovastatin

erly prepared RYR, the ratio of Monacolin K to

0.04

Monacolin K acid varies between 2:1 and 1.5:1.11 The

ND
ND
ND
ND
ND

ND

ratio noted in analysis of sample 6 is 3:1, which suggests

spiking of the sample with purified lovastatin. Sample 7
DUL
DUL
DUL
DUL
DUL
ND
ND

was Red Glutinous Rice, which is not a fermented

Table 1. Analysis of seven samples.

product and did not contain statins or pigment. With

Amount

this result, we essentially confirmed an important and

499.8
499.4
500.8
499.6
500.5
500.4
500.3
(mg)

not well-known conclusion from the FDA investiga-

tion. Additionally, our argument in our Letter to the
Editor was proven false simply because of the absence
1
2
3
4
5
6
7
Sample

Sample
Sample
Sample
Sample
Sample
Sample
Sample

of statin content in the traditional RYR samples.

The absence of statin content in the traditional RYR
#

food products provides an additional solid argument

19248
19249
19250
19251
19252
19253
19254
Code

against the usage of RYR supplements by our patients

# #

who insist on using a ‘‘natural product.’’ RYR supple-

ment is a product produced by industrial methods
1
2
3
4
5
6
7
Gold et al.
under carefully controlled conditions. There exists a
marked variability in the statin content in commercial
RYR supplements.12 The literature has additionally
documented that some producers may spike their prod-
uct with pharmaceutical lovastatin.13 Therefore, at a
minimum, our patients who insist on taking RYR sup-
plements should be advised to consult the consumer-
labs.com website. This website provides valuable
information on various RYR products and statin con-
tent confirmed by independent laboratories.
Author contribution
RG and KG contributed to the conception or design of the
work. RG, KG, BA, and IK contributed to the acquisition,
analysis, or interpretation of data for the work. RG and KG
drafted the manuscript. BA and IK critically revised the
manuscript. All gave final approval and agree to be account-
able for all aspects of work ensuring integrity and accuracy.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
References
1. Gold RA, Modilevsky T and Gold KR. The color of rice
and the Chinese paradox. Ann Nutr Metab 2016; 68:
128–129.
2. Heber D, Yip I, Ashley JM, et al. Cholesterol-lowering
effects of a proprietary Chinese red-yeast-rice dietary sup-
plement. Am J Clin Nutr 1999; 69: 231–236.
3. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European
Guidelines on cardiovascular disease prevention in clinical
practice: The Sixth Joint Task Force of the European
Society of Cardiology and Other Societies on
Cardiovascular Disease Prevention in Clinical Practice
75
(constituted by representatives of 10 societies and by
invited experts): Developed with the special contribution
of the European Association for Cardiovascular
Prevention & Rehabilitation (EACPR). Eur J Prev
Cardiol 2016; 23: Np1-np96.
4. Endo A. A historical perspective on the discovery of sta-
tins. Proc Jpn Acad Ser B Phys Biol Sci 2010; 86:
484–493.
5. Wang JX, Lu ZL, Chi JM, et al. Multicenter clinical trial
of the serum lipid-lowering effects of a Monascus purpur-
eus (red yeast) rice preparation from traditional Chinese
medicine. Curr Ther Res 1997; 58: 964–978.
6. US Department of Health and Human Services FaDA.
Pharmanex, Inc., administrative proceeding, Docket no.
97P-0441; final decision. 1998/05/20. Available at:
https://www.fda.gov/ohrms/dockets/dockets/97p0441/
ans0002.pdf.
7. Steffen C. Bundesgesundheitsblatt,
Gesundheitsforschung. [Red yeast rice: An unsafe food
supplement?]. Gesundheitsschutz 2017; 60: 292–296.
8. Pattanagul P, Pinthong R, Phianmongkhol A, et al.
Mevinolin, citrinin and pigments of adlay angkak fer-
mented by Monascus sp. Int J Food Microbiol 2008;
126: 20–23.
9. Seenivasan A, Subhagar S, Aravindan R, et al. Microbial
production and biomedical applications of lovastatin.
Indian J Pharm Sci 2008; 70: 701–709.
10. Childress L, Gay A, Zargar A, et al. Review of red yeast
rice content and current Food and Drug Administration
oversight. J Clin Lipidol 2013; 7: 117–122.
11. Ma J, Li Y, Ye Q, et al. Constituents of red yeast rice, a
traditional Chinese food and medicine. J Agric Food
Chem 2000; 48: 5220–5225.
12. Cohen PA, Avula B and Khan IA. Variability in strength
of red yeast rice supplements purchased from mainstream
retailers. Eur J Prev Cardiol 2017; 24: 1431–1434.
13. Li YG, Zhang F, Wang ZT, et al. Identification and
chemical profiling of monacolins in red yeast rice using
high-performance liquid chromatography with photo-
diode array detector and mass spectrometry. J Pharm
Biomed Anal 2004; 35: 1101–1112.