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Red Yeast Rice—Cholesterol-Busting SuperFood or Just Another Pharmaceutical?


04.11.2010 17:47
by Ed Sharpe

When is a natural food product not a natural food product? Whenever the FDA says so, judging by the results of a recent court case.

Red yeast rice is an all-natural whole food powder made from dried fermented rice, with a remarkable ability to lower LDL-cholesterol levels with minimal side effects. In a double-blind, placebo-controlled study at UCLA, a dose of 2.4 grams of red yeast rice powder per day decreased LDL-cholesterol by 18% after 8 weeks.1 Similar studies conducted in China with a more concentrated form of the same product resulted in decreases in LDL-cholesterol of up to 32% after 8 weeks.2,3 Pretty impressive results for a nutraceutical, you’d have to agree.

Problem is, back in 1998 the Food and Drug Administration (FDA) decided that the brand of red yeast rice used in the UCLA study was really an unapproved new drug and not a food. Pharmanex, the manufacturer of that brand, took the FDA to court but after a lengthy legal battle ultimately lost its case in the spring of 2001. The Federal District Court judge who had originally ruled against the FDA and in favor of the company was forced to reverse his earlier decision. In so doing, the court upheld a strict interpretation of DSHEA, the Dietary Supplement Health Education Act of 1994, which says that once a substance has been approved as a prescription drug, it cannot be marketed subsequently as a dietary supplement even if it is completely natural and derived from food.

The issue that had the FDA up in arms is that some forms of red yeast rice contain large amounts of monacolin K, a natural substance closely related to lovastatin.4 Lovastatin, of course, is the powerful anti-cholesterol drug marketed by Merck & Co. under the tradename Mevacor. But is red yeast rice really identical to lovastatin? The evidence shows that it is not—red yeast rice contains additional food-derived accessory factors and seems to be more effective than isolated, purified lovastatin.1

To get a handle on the issues involved, let’s first look into the history of the product. For centuries fermented rice products such as red yeast rice have been consumed in Asia 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.1

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 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.

The therapeutic effects attributed to red yeast rice appear to be due to the presence of Monascus pigment and other natural metabolites generated during fermentation. For example, an extract of M. anka was shown to be a potent free radical scavenger capable of protecting the liver from oxidative injury.5,6 The antioxidant and antibiotic properties of Monascus pigment would account for the traditional use of M. anka extract as a food preservative. Other components of M. anka pigment have anti-inflammatory activity and have been reported to suppress skin cancer caused by tumor promoters in experimental animals.7,8 What’s more, beni-koji (Japanese red yeast rice) has shown clinical benefit in treating high blood pressure in humans in a double-blind study versus placebo.9

But the most important feature of dietary red yeast rice, from the point of view of the present discussion, is the ability of some varieties to decrease elevated serum triglycerides, i.e., fats, as well as LDL (“bad”) cholesterol while leaving unaffected or even increasing HDL (“good”) cholesterol.1-3,10 The fungi responsible for the cholesterol-lowering effects are M. anka10 and M. purpureus Went.1-3 (Went was the Dutch scientist who first isolated the Monascus species named for him from fermented rice just over a century ago in Indonesia.) These fungi and related species can produce a series of compounds known as monacolins, of which the most famous is monacolin K, the acid form of lovastatin. Like lovastatin and other statin drugs, all monacolins inhibit the enzyme HMG-CoA reductase which catalyzes a key step in the biosynthesis of cholesterol.

The monacolin-rich red yeast rice that so upset the FDA was made with a strain of M. purpureus Went. Since much of the red yeast rice consumed as food throughout Asia is also made with M. purpureus Went, what distinguishes the food product from a drug? The answer, according to FDA, is that the traditional food product contains much smaller amounts of monacolins than are found in the lipid-lowering nutraceutical. In other words, the nutraceutical rice was cultured under special conditions in order to maximize the yield of drug-like substances equivalent to lovastatin. The manufacturer, on the other hand, argued that it was necessary to culture a specific strain of M. purpureus Went in a standardized fashion to guarantee that consumers received a product of known and consistent potency.

For an analogous situation, let’s imagine what would have happened if hypericin, the active compound in St. John’s wort, had been patented and approved as an anti-depressant drug a decade or two ago. Had that in fact happened, it would not be possible today to buy St. John’s wort capsules standardized to a given hypericin dosage per cap, although it might still be possible to purchase unstandardized St. John’s wort as an herbal supplement. The only difference between this hypothetical case and the present one involving red yeast rice is that hypericin was never approved as a prescription drug, whereas monacolin K (or rather lovastatin) was.

But is monacolin-rich red yeast rice really a food? It is in my book, since it’s just ground-up fermented rice with no other additives, but it’s clearly a superfood with some potent medicinal properties. To give another example, anyone can freely purchase a familiar lovastatin-containing fungus in most supermarkets. The fungus is called Pleurotus ostreatus and is otherwise known as the oyster mushroom.11 It’s unquestionably a food but it doesn’t provide a standardized dose of lovastatin, so I can’t tell you how many mushrooms you’d have to eat each day to lower your cholesterol. The irony is that if I were the owner of that supermarket and could somehow come up with a process for standardizing the lovastatin content of oyster mushrooms, I would suddenly find myself unable to sell any without running afoul of FDA regulations. Such are the absurdities of the current regulatory scene.

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 b-sitosterol and campesterol (1) which are known to interfere with cholesterol absorption in the intestines.12 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,13 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,14 and B-complex vitamins such as niacin,15 all of which have known benefits in decreasing serum lipids such as triglycerides and cholesterol.

The key point here is that rice fermented with M. purpureus Went is a whole food with many components acting in concert to decrease serum lipid levels. An analogy could be made to the difference in effectiveness between citrus-derived vitamin C with its full complement of natural flavonoids, and pure, crystalline vitamin C synthesized from corn sugar. There’s no difference chemically between each kind of vitamin C, but only one kind comes with a range of natural food-derived accessory factors that magnify the antioxidant capability of vitamin C.

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.16 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,17 osteoporosis18,19 stroke,20 Alzheimer’s disease and other dementias,21-23 and macular degeneration.24

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), dizziness and liver toxicity. Side effects including muscle pain, dizziness 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. Try increasing the dose of red yeast rice gradually from 1 to 4 capsules per day, and halt and reduce the dosage in the event any adverse symptoms arise. Since all HMG-CoA reductase inhibitors also interfere with coenzyme Q10 production, it is advisable to supplement with CoQ10 on a daily basis. According to a report from the National Cancer Institute, supplementing with CoQ10 can prevent the occurrence of myopathy induced by lovastatin.25 Even for those taking CoQ10 with red yeast rice, however, any symptoms of muscle pain or weakness should be brought to the immediate attention of one’s health care professional.

Of course, the above cautions apply only to those lucky enough to own some red yeast rice capsules in the first place. After Pharmanex lost its most recent court decision it suspended its US sales. And although the court decision was limited only to the Pharmanex brand and not to other brands of red yeast rice, at least one wholesale supplier of nutritional products recently reported having his entire stock of red yeast rice confiscated by the FDA.

LifeLink has a limited supply of red yeast rice still available. Get some while you can before this nutrient-dense superfood disappears forever from our shelves.

References.

[1] Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999;69:231–6.
 
[2] Wang J, Lu ZL, Chi JM, Wang WH, Su MZ, et al. Multicenter clinical trial of the serum lipid lowering effects of a Monascus purpureus (red yeast) rice preparation from traditional Chinese medicine. Curr Ther Res. 1997;58(12):964–78.

[3] Qin SC, Zhang WQ, Qi P, Zhao ML, Dong ZN, et al. Effect of Xuezhikang on older hyperlipoidemia patients through random double-blind comparison trial. Chin J Internal Med. 1998;37(6):401-2.

[4] Endo A. Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Antibiot (Tokyo). 1980;33(3):334-6.

[5] Aniya Y, Yokomakura T, Yonamine M, Nagamine T, Nakanishi H. Protective effect of the mold Monascus anka against acetaminophen-induced liver toxicity in rats. Jpn J Pharmacol. 1998;78(1):79-82.

[6] Aniya Y, Yokomakura T, Yonamine M, Shimada K, Nagamine T, et al. Screening of antioxidant action of various molds and protection of Monascus anka against experimentally induced liver injuries of rats. Gen Pharmacol. 1999;32(2):225-31.

[7] Yasukawa K, Takahashi M, Natori S, Kawai K, Yamazaki M, et al. Azaphilones inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mice. Oncology. 1994;51(1):108-12.

[8] Yasukawa K, Takahashi M, Yamanouchi S, Takido M. Inhibitory effect of oral administration of Monascus pigment on tumor promotion in two-stage carcinogenesis in mouse skin. Oncology. 1996;53(3):247-9.

[9] Kushiro T, Hashida J, Kawamura H, Mitsubayashi H, Saito T, et al. Clinical effects of beni-koji in mild essential hypertension. A multi-center double-blind comparison with placebo [in Japanese]. Jpn J Nephrol. 1996;38(12):625-33.

[10] Wang IK, Lin-Shiau SY, Chen PC, Lin JK. Hypotriglyceridemic effect of Anka (a fermented rice product of monascus sp.) in rats. J Agric Food Chem. 2000;48(8):3183-9.

[11] Gunde-Cimerman N, Cimerman A. Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase-lovastatin. Exp Mycol. 1995;19(1):1-6.

[12] Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am J Med. 1999;107(6):588-94.

[13] Plat J, Mensink RP. Effects of plant sterols and stanols on lipid metabolism and cardiovascular risk. Nutr Metab Cardiovasc Dis. 2001;11(1):31-40.

[14] Ma J, Li Y, Ye Q, Li J, Hua Y, et al. Constituents of red yeast rice, a traditional Chinese food and medicine. J Agric Food Chem. 2000;48(11):5220-5.

[15] Palo MA, Vidal-Adeva L, Maceda LM. A study on ang-kak and its production. Philipp J Sci. 1960;89(1):1-19.

[16] Fang YH,  Li W. Effect of Xuezhikang on lipid metabolism and islet b cell function in Type II diabetic patients. J Capital Med. 2000;7(2): 44-45.

[17] Dimitroulakos J, Ye LY, Benzaquen M, Moore MJ, Kamel-Reid S, et al.Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. Clin Cancer Res. 2001;7(1):158-67.

[18] Edwards CJ, Hart DJ, Spector TD. Oral statins and increased bone-mineral density in postmenopausal women. Lancet. 2000;355(9222):2218-9.

[19] Garrett IR, Gutierrez G, Mundy GR. Statins and bone formation. Curr Pharm Des. 2001;7(8):715-36.

[20] Vaughan CJ, Delanty N, Basson CT. Do statins afford neuroprotection in patients with cerebral ischaemia and stroke? CNS Drugs. 2001;15(8):589-96.

[21] Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol. 2000;57(10):1439-43.

[22] Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000;356(9242):1627-31.

[23] Friedhoff LT, Cullen EI, Geoghagen NS, Buxbaum JD. Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide. Int J Neuropsychopharmacol. 2001;4(2):127-30.

[24] Hall NF, Gale CR, Syddall H, Phillips DI, Martyn CN. Risk of macular degeneration in users of statins: cross sectional study. BMJ. 2001;323(7309):375-6.
 
[25] Thibault A, Samid D, Tompkins AC, Figg WD, Cooper MR, et al. Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res. 1996;2(3):483-91.