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REVIEW of THE STUDIES on THE RED YEAST RICE (Monascus purpureus)
Özlem ERDOĞRUL1, Sebile AZIRAK2
1Department of Food Science, Faculty of Agriculture, University of Kahramanmaraş
Sütçü İmam, 2Department of Biology, Faculty of Science and Arts, University of
Kahramanmaraş Sütçü İmam, Turkey
e-mail : oerdogrul@ksu.edu.tr
Abstract
Monascus purpureus is a red mold species which may be cultivated on starch containing
substrates. The solid state fermentation of rice by Monascus has a long tradition in East
Asian countries which dates back at least to the first century A.D. For centuries
fermented rice products such as red yeast rice have been consumed in Asia and
Indonesia as dietary staples and food additives. It is formed during the fermentation of
rice and it is called as in China ‘Ang Khak’ or ‘Hong Qu’ (pronounced approximately
‘Hong Zhu’ (rhymes with French ‘rue’). The Japanese know the product under the name
Koji, Ang-Khak, Beni-Koji, Red-Koji, Rotschimmelreis (in Europe) or Red Mould (in
the USA).
Red yeast rice is used as food or food additives. Red yeast rice, an Asian dietary staple
made by fermenting yeast (Monascus purpureus) on rice, is rapidly gaining recognition
as a cholesterol-lowering agent in United States. Indonesia, Japan, Taiwan, and
Philippine people are been used as Monascus-nata complex. It is used as coloring and
flavoring agents and also reduces total cholesterol, hyperlipidemia. Other exciting
applications for red yeast rice are suggested by recent discoveries that lovastatin and
other statin drugs may be useful for treating or preventing cancer, osteoporosis, stroke,
Alzheimer’s disease and other dementias, and macular degeneration.
Key Words: Monascus purpureus, red mold species, Ang Kak, Koji, starch
Introduction
Historical and traditional use of Monascus purpureus
Monascus purpureus is a red mold species which may be cultivated on starch containing
substrates. The solid state fermentation of rice by Monascus has a long tradition in East
Asian countries which dates back at least to the first century A.D. (Meyer, 1990). For
centuries fermented rice products such as red yeast rice have been consumed in Asia
Turkish Electronic Journal of Biotechnology
Vol 2, p:37-49, 2004
© Biotechnology Association
38
and Indonesia as dietary staples and food additives. In Japan red yeast rice is known as
beni-koji and its pigment is widely used as food coloring. Red yeast rice has also been
used in China, Taiwan, Okinawa, and the Philippines as a preservative for meat and
fish, for adding color and flavor to food, and even for brewing wine and liquor.
Interestingly, red yeast rice is also mentioned in an ancient Chinese pharmacopoeia of
medicinal foods and herbs, the Ben Cao Gang Mu of Li Shi-zhen, where it is described
as a medication useful for improving digestion and revitalizing the blood (Heber et al.
1999). A health promoting effect is ascribed traditionally to the product, thus in a book
on Chinese medicine published in Beijing in 1590 by Li, Shin-Chun (1590). The first
accounts of this mould appeared more than 2000 years ago in the monograph by Li-
Shin-Chun (1590). This book describes the utilization of a pigment as a coloring agent
and as a medicine in the treatment of various diseases.
The fermentate is obtained as scarlet to purple red grains which have the original rice
grain structure well preserved. It is formed during the fermentation of rice and it is
called as in China ‘Ang Khak’ or ‘Hong Qu’ (pronounced approximately ‘Hong Zhu’
(rhymes with French ‘rue’). The Japanese know the product under the name Koji, Ang-
Khak, Beni-Koji, Red-Koji, Rotschimmelreis (in Europe) or Red Mould (in the USA)
(Bakosova et al. 2001).
Up to now, this mould is still used because of its coloring and flavoring properties, in
the food industry of many Asian countries for processing of poultry, fish, and meat
products. The main application is however, as a food additive, in particular to meat as a
preservative and condiment. Its use in the rice wine manufacture is due to its high
content of alpha-amylase which promotes the conversion of starch into glucose. The
attractive red color of rice wine is caused by Monascus pigments. Monascus became
known in Europe through the investigations of Dutch scientist who observed the use of
red mold rice by the population in Java. They isolated and classified various Monascus
species botanically (Tieghem, 1884; Went, 1895).
The Botanical Data, Active Constituents and The Pigments of Monascus purpureus
A special group of natural pigments includes coloring agents produced by micro-
organisms. The typical representatives of this group are the pigments of the mould
Monascus spp. belonging to family Aspergillaceae, the genus Monascus (Slugen et al.
1997). The mould belongs to the polycetides and has a slight bactericidal effect. The
39
production of pigments by this mould was studied by Evans and Wang (Evans and
Wang, 1987) and Juzlova (Juzlova et al., 1994). The mixtures of pigments are stable
from the chemical point of view. As reported, the group includes the orange pigments
called Monascorubin and Rubropunctatin, the yellow pigments called Monascin and
Ankaflavin, and the red pigments called Monascorubramin and Rubropunctamin
(Meyer, 1990; Margalith, 1992). Furthermore, the mould also contains another
substance belonging to the polycetides- Mevinolin (Lovastatin, Monacolin and
Mevacor). This is commonly used as a medicine in the therapy of hypercholesterolemia
(Chen and Johns, 1993). Monascus spp. has been well known for red pigment
production but less study was investigated for yellow pigment production. A Monascus
purpureus mutant strain-YLC1 was obtained for yellow pigment production (Chen and
Johns, 1993; Evans and Wang, 1987).
Various uses of Monascus purpureus
Red yeast rice is one traditional Chinese material that has been shown in animal and
pilot human studies to effectively lower serum lipid levels. Red yeast rice, also known
as Monascus purpureus rice, is derived from the strain of M. purpureus Went yeast and
is prepared by a traditional rice fermentation method. It has been shown that red yeast
rice contains compounds with HMG-CoA reductase inhibitor activity, which is
responsible for the inhibition of cholesterol synthesis in the liver. In addition to rice
starch, protein, fibre, sterols, and fatty acids, red yeast rice contains numerous active
constituents, including Monacolin K, dihydromoncolin, and Monacolin I to VI.
Researchers have determined that one of the ingredients in red yeast rice, called
monacolin K, inhibits the production of cholesterol by stopping the action of a key
enzyme in the liver (e.g., HMG-CoA reductase) that is responsible for manufacturing
cholesterol. Among many other things, red yeast rice contains at least nine substances
that are similar in structure to the active ingredients in statin drugs. These substances
inhibit the activity of the enzyme necessary for the body’s production of cholesterol
(Heber et al. 1999).
Red yeast rice also contains unsaturated fatty acids that may also help reduce serum
lipids (Wang, 1997). Red yeast rice extract may help to reduce total cholesterol levels,
lower levels of LDH (bad) cholesterol, increase levels of HDL (good) cholesterol, and
lower the level unhealthy fats called triglycerides. It appears to accomplish this by
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restricting the liver’s production of cholesterol itself. Interestingly, the compound
responsible for the effect-mevinolin is chemically identical to the cholesterol-lowering
compound lovastatin, sold as the prescription drug Mevacor. Mevinolin is also similar
to the active ingredients in such cholesterol medications as Zocor (simvastatin) and
Lipiton (atorvastatin). Unsaturated fatty acids in red yeast rice extract are also believed
to help, possibly in lowering triglycerides (Heber, 1999; Wang et al. 1997; Qin et al.
1998).
There’s still another reason for regarding red yeast rice as a food, and that is the fact that
the product contains many other synergistic nutrients with lipid-lowering properties in
addition to monacolins. For example, red yeast rice has been reported to contain sterols
such as beta-sitosterol and campesterol (Heber et al. 1999), which are known to
interfere with cholesterol absorption in the intestines (Moghadasian and Frohlich, 1999).
Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical
and experimental evidence. The combination of such dietary sterols with statin drugs
has in fact been suggested as a more effective means of lowering cholesterol than statins
alone (Plat and Mensink, 2001) so it makes sense to consume a single food which
naturally combines both kinds of anti-cholesterol activity. Red yeast rice also contains
fiber, trace elements such as magnesium, unsaturated fatty acids such as oleic, linoleic,
and linolenic acids (Ma et al. 2000) and B-complex vitamins such as niacin (Palo et al.
1960) all of which have known benefits in decreasing serum lipids such as triglycerides
and cholesterol.
Red yeast rice, an Asian dietary staple made by fermenting yeast (Monascus purpureus)
on rice, is rapidly gaining recognition as a cholesterol-lowering agent in United States.
Indonesia, Japan, Taiwan, and Philippine people are been used as Monascus-nata
complex (Sheu et al. 2000).
Fermentation conditions for coloration
Carbon source, nitrogen source, and pH have been shown to influence pigment
production by Monascus purpureus (Su, 1978; Wong et al. 1981; Lin and Demain,
1991; Chen and Johns, 1993).
The microorganisms used for fermenting red yeast rice are various species of a
filamentous fungus known as Monascus. The Monascus group includes M. anka, M.
ruber, and a strain of M. ruber known as M. purpureus, among others. (Ruber and
41
purpureus are the Latin words for red and purple, respectively.) These fungi can
produce an intense red pigment as well as other metabolic byproducts when cultivated
on cooked nonglutinous rice (Ma et al. 2000; Su, 1978; Wong et al. 1981).
Monascus sp. 94-25 strain was isolated from red rice with the purpose of red pigments
sub-merged production. Morphological characterization on the taxonomically important
for the genus media showed that the strain produced cleistothecia with oval ascospores
and aleiroconidia. Comparison with a referent strain Monascus purpureus Went 109.07
was made and it was proved that there were no considerable differences between both
strains. Monascus sp. 94-25 was a prototroph and had optimal growth temperature 34oC.
Investigation of the fermentation and assimilation capacity of both strains was
performed. It was found that both of them assimilated well glucose, while highest
fermentation ability was observed when grown on galactose. Similarly to the referent
strain Monascus sp. 94-25 could grow on starch and protein containing natural
substrates. Regarding the morphological and biochemical investigations the newly
isolated strain 94-25 could be considered as Monascus purpureus (Rasheva et al. 1998,
Qin et al. 1998).
Pharmacological effects of Monascus fermentate
Scientific investigations have confirmed pharmacological effects of Monascus
fermentate (Endo and Monacolin, 1980) isolated from Monascus ruber a metabolite,
Monacolin K which normalized an artificially induced hyperlipoproteinemia in rats. The
reduced from of Monacolin K, Mevinolin has meanwhile been introduced as a
cholesterol reducing pharmaceutical (by Merck, Sharp and Dohme). Also simple
extracts of Monascus purpureus fermentate lower the cholesterol, the HDL cholesterol
and the triglyceride value in the blood of rats with and induced hyperlipoproteinemia
(Fink-Gremmels and Leistner, 1989). The observed effect is weaker than in
pharmaceutical preparations and is rather comparable to the effect of certain spices e.g.
of garlic (Hansel and Haas, 1984). A Japanese patient (Japan Kokai, 1985) describes the
blood pressure lowering by Monascus fermentate itself and by an alcoholic extract
thereof.
Monascus extract is marketed in Japan as a dietetic product (under the name Monacolin
by Maruzen). The preservative effect of Monascus fermentate has also been confirmed
by scientific investigation. Monascidin A, a component isolated from Monascus
42
purpureus cultures inhibits bacteria of the genera Bacillus, Streptococcus and
Pseudomonas (Wong and Bau, 1977; Wong and Koehler, 1981; Bau, 1977). Two
yellow pigments from Monascus purpureus had in low concentration a bacteriostatic
function against Bacillus subtilis (Wong and Koehler; 1981). Chen (1993) was observed
an inhibitory effect in particular against Staphylococcus aureus. Further research on the
bacteriostatic effect of Monascus fermentate was carried out by Fink-Gremmels et al.
1991 and Leistner and Dresel, 1991. Gram positive bacteria are generally stronger
inhibited than gram negative ones. Lactobacillus is not affected. The observation of
bacteriostatic effects has lead to the consideration to use Monascus fermentate at least
partially as a substitute for nitrite in meat preservation (Fink-Gremmels et al., 1991).
A scientific proof of the flavor enhancing properties of Monascus fermentate is difficult
to obtain. However, in a tasting panel tasters called Monascus containing noodles “more
salty” then normal noodles although there was actually no difference in the salt content.
Monascus extract containing meat products were generally classified as better tasting
than comparable products without Monascus (Fink-Gremmels et al., 1991). One may
speculate that the relishing effect of Monascus could be caused by flavor enhancing
oligopeptides produced by a partial hydrolysis of rice proteins by Monascus enzymes.
For the strong color of Monascus fermentate a number of yellow, red, and orange
colored pigments are responsible. The pigments are secondary metabolites of the
Monascus fermentation; they belong chemically to the group of Azaphilones which are
typical fungus metabolites. The chemical structure of most of them is known.
Depending on whether the yellow or red pigments predominate or are absent, the colors
of Monascus purpureus varies from orange yellow to scarlet to purple red. The color
can be influenced by the culture conditions, in particular by the pH value and by the
phosphorus and nitrogen source in the substrate (Meyer, 1990).
The other medicinal studies about red yeast rice
Along with its evaluation in animal trials (Li et al, 1998), red yeast rice has been
clinically investigated as a therapy for reducing cholesterol in two human trials. In one
study, both men and women taking 1.2 g (approximately 5 mg total monacolins) of red
yeast rice per day for two months had significant decreases in serum cholesterol levels
(WANG et al., 1997). In addition, persons taking red yeast rice had a significant
43
increase in HDL (good) cholesterol and a decrease in LDL (bad) cholesterol. Elevated
triglycerides were also found to be lowered (Qin et al. 1997-1998).
Heber et al., (1999), evaluated the lipid-lowering effects of red yeast rice dietary
supplement in US adults separate from effects of diet alone. Eighty-three healthy
subjects with hyperlipidemia and HDL cholesterol who were not being treated with
lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or
placebo and instructed to consume a diet providing 30 % of energy from fat, <10% from
saturated fat, and <300 mg cholesterol daily. Main outcome measures were total
cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9,
11, and 12. Total cholesterol concentrations decreased significantly between baseline
and 8 wk in the red yeast rice treated group compared with the placebo-treated group.
LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL
cholesterol did not change significantly. Red yeast rice significantly reduces total
cholesterol, LDL cholesterol, and a total triacylglycerol concentrations compared with
placebo and provides a new, novel, food-based approach to lowering cholesterol in the
general population.
In order to better understand the effectiveness of red yeast rice, Wang et al. (1997),
performed a randomized, single-blind trial in 502 patients who were diagnosed with
hyperlipidemia. In the red yeast rice using group reduction of hyperlipidemia was
significantly greater (Wang et al. 1997).
By the way, protection from cardiovascular disease is only one of many benefits of red
yeast rice consumption. A Chinese study demonstrated that red yeast rice extract
decreased insulin and blood glucose levels in a group of Type II diabetics (Fang and Li,
2000). Since Type II diabetes is characterized by insulin resistance and impaired
glucose tolerance, it appears that red yeast rice can increase insulin sensitivity in
diabetics, even in subjects without high lipid levels. Other exciting applications for red
yeast rice are suggested by recent discoveries that lovastatin and other statin drugs may
be useful for treating or preventing cancer (Dimitroulakos et al. 2001), osteoporosis
(Edwards et al. 2000; Garrett et al. 2001) , stroke (Vaughan et al. 2001), Alzheimer’s
disease and other dementias (Wolozin et al. 2000; Jick et al. 2000; Friedhoff et al.
2001), and macular degeneration (Hall et al. 2001)
44
Use of Monascus purpureus as food or food additives
Nata is a bacterial cellulose produced by Acetobacter aceti ssp. xylinum, was colored by
means of fermentation with Monascus purpureus. Scanning electron microscopy (SEM)
observations showed that the Monascus mycelium coulo grow through the cellulose
network of nata. The Monascus-nata complex has the potential to be new vegetarian
foodstuff (Sheu et al. 2000).
The use of Monascus microorganisms is also a rich source of natural color and produces
chemical species that give a red color. These include monascin, ankaflavin,
rubropunctatin and monascorubrin which have the following molecular skeleton in
Figure 1. Colorants are often added to fruit flavored yoghurt to enhance or replace the
natural color of the fruit. Pigments produced by the mold, Monascus purpureus, offer a
possible alternative to certified food dyes or natural pigments now used (Koehler, 2001,
Dweck, 2002).
Red yeast rice is commercially available in capsules and should be taken in the amount
of 1.2-2.4 grams (5-10 mg monacolins) per day in divided doses for a trial period of up
to 12 weeks (Heber et al. 1999; Wang et al. 1997).
Figure1. The molecular skeleton of monascin, ankaflavin, rubropunctatin and
monascorubrin
Side effects or interactions
Red yeast rice generally well tolerated with possible temporary mild side effects such as
hearth burn, wind, and dizziness (Wang et al. 1997). This product should not to be used
by individuals with liver disorders (Burnham et al. 1997).
Side effects with red yeast rice extract have been reported but tend to be mild and
resolve quickly upon discontinuation. These include headache, dizziness, hearth burn,
gas, and digestive tract discomfort.
45
The statins in red yeast rice extract pose the risk of rare but serious reactions, including
skeletal muscle damage, liver damage, and kidney toxicity. Approximately 1% to 2% of
people taking the drug lovastatin have such reactions. Symptoms may include
unexplained weakness, muscle pains and tenderness, and other flu like symptoms. It’s
still unclear whether these types of reactions occur with people taking the standardized
red yeast rice extract, however a recent, 12-week clinical trial, for example, liver and
kidney function in the participants remained normal (Edwards, 2000; Jick et al. 2000).
Red yeast rice should be used cautiously. It is not recommended for use by pregnant
women, by anyone with a liver disorder, or by those taking other cholesterol-lowering
medications simultaneously. The use of statin drugs such as lovastatin can sometimes
lead to side effects including myopathy (muscle dysfunction) and liver toxicity. Side
effects including muscle pain and fatigue may also occur with red yeast rice if
consumed at sufficiently high doses. For this reason an incremental dose schedule is
suggested, at least at first. Also It is not recommended for use the person who have
breast-feeding, liver disease, a serious infection, or a transplanted organ or have recent
had major surgery must be use careful. Under age 20, it has to avoid possible
complications because of the statin content in red yeast rice extracts. Also persons have
to avoid drinking more than two alcoholic drinks a day or large amounts of grapefruit
juice while taking red yeast rice extract. According to a report from the National Cancer
Institute, supplementing with CoQ10 can prevent the occurrence of myopathy induced
by lovastatin (Thibault et al. 1996).
More information on possible side effects should become available as results of studies
on red yeast rice extract are completed in the coming years.
46
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