Red yeast rice



Red yeast rice, red rice koji  (べにこうじ, lit. 'red koji ') or akakoji (あかこぎ, also meaning 'red koji '), red fermented rice, red kojic rice, red koji rice, anka, or ang-kak, is a bright reddish purple fermented rice, which acquires its colour from being cultivated with the mold Monascus purpureus.

Red yeast rice is what is referred to, in Japanese, as a koji, meaning 'grain or bean overgrown with a mold culture', a food preparation tradition going back to ca. 300 BC. In both the scientific and popular literature in English that draws principally on Japanese, it is most often known as "red rice koji". English works favoring Chinese sources may prefer the translation "red yeast rice".

Due to the low cost of chemical dyes, some producers of red yeast rice have tried to modify their products with red dye #2 Sudan Red G.

Culinary
Red yeast rice is used to colour a wide variety of food products, including pickled tofu, red rice vinegar, char siu, Peking Duck, and Chinese pastries that require red food colouring. It is also traditionally used in the production of several types of Chinese wine, Japanese sake (akaisake), and Korean rice wine (hongju), imparting a reddish colour to these wines. Although used mainly for its colour in cuisine, red yeast rice imparts a subtle but pleasant taste to food and is commonly used in the cuisine of Fujian regions of China.

Traditional Chinese medicine
In addition to its culinary use, red yeast rice is also used in Chinese herbology and traditional Chinese medicine. Its use has been documented as far back as the Tang Dynasty in China in 800 AD. It is taken internally to invigorate the body, aid in digestion, and revitalize the blood. A more complete description is in the traditional Chinese pharmacopoeia, Ben Cao Gang Mu-Dan Shi Bu Yi, from the Ming Dynasty (1378–1644).

Red yeast rice and drugs
In the late 1970s, researchers in the United States and Japan were isolating lovastatin from Aspergillus and monacolins from Monascus, respectively, the latter being the same fungus used to make red yeast rice but cultured under carefully controlled conditions. Chemical analysis soon showed that lovastatin and monacolin K are identical. The article "The origin of statins" summarizes how the two isolations, documentations and patent applications were just months apart. Lovastatin became the patented, prescription drug Mevacor for Merck & Co. Red yeast rice went on to become a contentious non-prescription dietary supplement in the United States and other countries.

Lovastatin and other prescription "statin" drugs inhibit cholesterol synthesis by blocking action of the enzyme HMG-CoA reductase. As a consequence, circulating total cholesterol and LDL-cholesterol are lowered. In a meta-analysis of 91 randomized clinical trials of ≥12 weeks duration, totaling 68,485 participants, LDL-cholesterol was lowered by 24-49% depending on the statin. Different strains of Monascus fungus will produce different amounts of monacolins. The 'Went' strain of Monascus purpureus (purpureus = dark red in Latin), when properly fermented and processed, will yield a dried red yeast rice powder that is approximately 0.4% monacolins, of which roughly half will be monacolin K (identical to lovastatin). Monacolin content of a red yeast rice product is described in a 2008 clinical trial report.

Regulatory restrictions
The Food and Drug Administration (FDA) position is that red yeast rice products that contain monacolin K, i.e., lovastatin, are identical to a drug and, thus, subject to regulation as a drug. In 1998, the FDA initiated action to ban a product (Cholestin) containing red yeast rice extract. The U.S. District Court in Utah allowed the product to be sold without restriction. This decision was reversed on appeal to the U.S. Court of Appeals. (Moore, 2001) (see Further Reading: PDRhealth). Shortly thereafter, the FDA sent Warning Letters to companies selling red yeast rice. The product disappeared from the market for a few years.

In 2003, red yeast rice products began to reappear in the U.S. market. As of 2010, there are at least 30 brands available. Many of these avoid the FDA restriction by not having any appreciable monacolin content. Their labels and websites say no more than "fermented according to traditional Asian methods" or "similar to that used in culinary applications." The labeling on these products often says nothing about cholesterol. If they do not contain lovastatin, do not claim to contain lovastatin, and do not make a claim to lower cholesterol, they are not subject to FDA action. Two reviews confirm that the monacolin content of red yeast rice dietary supplements can vary over a wide range, with some containing negligible monacolins. In 2007, the FDA sent Warning Letters to two dietary supplement companies. One was making a monacolin content claim about its RYR product and the other was not, but the FDA noted that both products contained monacolins. Both products were withdrawn. The FDA also issued a warning press release (see Further Reading; FDA 2007). The crux of the release was that consumers should "…not buy or eat red yeast rice products…may contain an unauthorized drug that could be harmful to health." The rationale for "…harmful to health…" was that consumers might not understand that the dangers of monacolin-containing red yeast rice might be the same as those of prescription statin drugs.

Clinical evidence
The amount typically used in clinical trials is 1200–2400 mg/day of red yeast rice containing approximately 10 mg total monacolins, of which half are monacolin K. This does raise a question about the function of the other monacolins and non-monacolin compounds in the products, as the monacolin K content is lower than what is usually considered effective for lovastatin (20–80 mg/dy). In 2006, Liu et al. published a meta-analysis of clinical trials. The article cited 93 published, controlled clinical trials (91 published in Chinese). Total cholesterol decreased by 35 mg/dl, LDL-cholesterol by 28 mg/dl, triglycerides by 35 mg/dl, and HDL-cholesterol increased by 6 mg/dl. The incidence of reported adverse effects ranged from 1.3% to 36%. Of the clinical trials reviewed in the meta-analysis, the only study conducted in the United States reported a 22% reduction of LDL-cholesterol after 12 weeks.

Subsequent to the 2006 meta-analysis, there developed a number of articles reporting on a massive trial conducted in China: the China Coronary Secondary Prevention Study (CCSPS). Close to 5,000 post-heart attack patients were enrolled for an average of 4.5 years to receive either a placebo or a RYR product named Xuezhikang (血脂康). This is a patented-process (U.S. patent #6,046,022), ethanol extract of red yeast rice, with a total monacolins content of approx. 0.8%. It is also sold as Lipascor. Key CCSPS results: In the treated group, risk of subsequent heart attacks was reduced by 45%, cardio deaths by 31%, and all-cause deaths by 33%. Some of the articles report on subsets of the population, i.e., just diabetics or just hypertensives.

These heart attack and cardiovascular death outcomes appear to be better than what has been reported for prescription drugs. A 2008 review pointed out that the cardioprotective effects of statins in Japanese populations occur at lower doses than are needed in Western populations, and theorized that the low amount of monacolins found in Xuezhikang may be more effectively athero-protective than expected in the Chinese population in the CCSPS study for the same reason. Others have speculated that phytosterols or unknown substances in Xuezhikang also contribute to the benefits.

Safety
The safety of red yeast rice products has not been established, and some commercial supplements have been found to contain high levels of the toxin citrinin. As commercial products will have highly variable amounts of monacolins, and rarely declare this content on the label, defining risk is difficult. Ingredient suppliers have also been suspected of "spiking" red yeast rice preparations with purified lovastatin. As evidence, one published analysis reported several commercial products as being almost entirely monacolin K - which would occur if the drug lovastatin was added - rather than the expected composition of many monacolin compounds. Statin drugs are known to cause muscle and liver damage. Statin-associated rhabdomyolysis can lead to kidney damage and possibly kidney failure (renal failure). This is why they are prescription drugs rather than over-the-counter, and with recommendations that the patients' physicians schedule liver function tests on a regular basis. There are many case reports in the literature of muscle myopathy and liver damage resulting from red yeast rice usage. In 2009 Becker et al. reported on a U.S. trial that enrolled 62 patients with known statin-associated myalgias. Half got a RYR product (3600 mg/day, 13 mg monacolins, 6 mg monacolin k) for 24 weeks; and half were administered a placebo. In the treated group, LDL-cholesterol declined 21%. Two patients dropped out because of myalgia, 1 for diarrhea, and 1 for dizziness. In the placebo group, one dropped out for myalgia. Creatine phosphokinase increased slightly in the treated group (from 122 to 128 IU/L) versus decreasing with placebo (117 to 101 IU/L), but the shifts were not statistically significant. For those having completed the trial, subjective muscle pain scores were similar for the two groups.