Red Yeast Rice and Cholesterol

Red yeast rice is purported to lower cholesterol.

Red yeast rice is rice that has been fermented by the red yeast, Monascus purpureus. It has been used by the Chinese for many centuries as a food preservative, food colorant (it is responsible for the red color of Peking duck), spice, and an ingredient in rice wine. Red yeast rice continues to be a dietary staple in China, Japan, and Asian communities in the United States, with an estimated average consumption of 14-55 grams of red yeast rice per day per person.

Red yeast rice also has been used in China for over 1,000 years for medicinal purposes. Red yeast rice was described in an ancient Chinese list of drugs as useful for improving blood circulation and for alleviating indigestion and diarrhea.

Recently, red yeast rice has been developed by Chinese and American scientists as a product to lower blood lipids, including cholesterol and triglycerides.

Small scale studies using pharmaceutical-grade red rice yeast have continued to demonstrate efficacy and safety. However, in the United States it is no longer legal to sell supplements of red yeast rice that contain more than trace amounts of cholesterol lowering substances. For example, the active ingredients of red rice yeast have been removed from Cholestin marketed in the United States. (Hypocol, another product containing red yeast rice is no longer being sold in the United States.)

The reasons the Food and Drug Administration (FDA) has ruled that it is illegal to sell red yeast rice that contains more than trace amounts of the cholesterol-lowering substances and to promote red yeast rice for lowering cholesterol levels.

• First, statin drugs are associated with muscle and kidney injury when used alone or combined with other medications. There is concern that patients who already take statin drugs with or without these other medications may increase their risk of muscle or kidney injury.
• Second, the FDA considers the products containing red yeast rice with high levels of cholesterol lowering substances to be new, unapproved drugs for which marketing violates the Federal Food, Drug, and Cosmetic Act.

There are three major preparations of red yeast rice:

1. Zhitai,
2. Cholestin or Hypocol, and
3. Xuezhikang.

Zhitai

Zhitai is produced by the fermentation of a mixture of different strains of Monascus purpureus on whole grain rice. Zhitai contains mainly rice and yeast but is mostly rice by weight.

Cholestin or HypoCol

Cholestin or HypoCol is produced by the fermentation of selected strains of Monascus purpureus, using a proprietary process that produces a certain concentration of monacolin K (monacolin K is lovastatin, which is believed to be the major cholesterol-lowering ingredient).

Xuezhikang

Xuezhikang is produced by mixing the rice and red yeast with alcohol and then processing it to remove most of the rice gluten. Xuezhikang contains 40% more cholesterol-lowering ingredients than Cholestin or Hypocol.

In Singapore, red yeast rice is available as Hypocol (NatureWise, Wearnes Biotech & Medicals (1998) PTE LTD).

At one time, Cholestin contained red yeast rice, and at that time scientists at Pharmanex and the UCLA Center for Human Nutrition analyzed the properties Cholestin. The composition by weight is:

• starch (73%),
• protein (5.8%)
• moisture (3%-6%),
• unsaturated fatty acids (1.5%),
• monacolins (0.4%),
• ash (3%), and
• trace amounts of calcium, iron, magnesium, and copper.

There are no additives, preservatives, heavy metals, or toxic substances, such as citrinic acid.

In 1977, Professor Endo in Japan discovered a natural cholesterol-lowering substance that is produced by a strain of Monascus yeast. This substance inhibits HMG-CoA reductase, an enzyme that is important for the production of cholesterol in the body. Professor Endo named this substance moncacolin K. Since then, scientists have discovered a total of eight monacolin-like substances that have cholesterol-lowering properties.

Monacolin K is lovastatin, the active ingredient in the popular statin drug, lovastatin (Mevacor), which is used for lowering cholesterol. Lovastatin also is believed to be the main cholesterol-lowering ingredient in HypoCol. The lovastatin in Mevacor is highly purified and concentrated, the lovastatin in HypoCol is not. Thus, they contain much lower concentrations of lovastatin than Mevacor. For example, each 600-mg capsule of Cholestin contains less than 2.4 mg of lovastatin (when this ingredient was contained in the product), whereas tablets of Mevacor contain 10 mg or more of this ingredient.

Because none of the components are purified and concentrated, HypoCol and Cholestin (marketed outside of the US) contain a mixture of the eight yeast-produced monacolins, unsaturated fatty acids, and certain anti-oxidants. Some scientists believe that these other monacolins, unsaturated fatty acids, and anti-oxidants may work together favorably with lovastatin to enhance its cholesterol-lowering effects, as well as its ability in lowering triglycerides and increasing HDL cholesterol. (HDL is considered the "good" form of cholesterol since high levels of HDL cholesterol protect against heart attacks.) Further studies in animals and humans will be necessary to test these theories.

Chinese scientists conducted most of the animal and human studies on this issue, using either Zhitai or Xuezhikang. The results of some 17 studies involving approximately 900 Chinese subjects with modestly elevated cholesterol levels have been published. In eight of these studies, there was a control group that received a placebo (a pill with no active ingredients) for comparison purposes. In nine of the studies, there was no placebo control group.

These studies consistently showed that Zhitai and Xuezhikang:

• lower total cholesterol (by an average of 10%-30%),
• lower LDL cholesterol (by an average of 10%-20%),
• lower triglycerides (by an average of 15%-25%), and
• increase HDL (by an average of 7%-15%).

Scientists at the UCLA Center for Human Nutrition studied Cholestin in a 12-week, double-blind, placebo-controlled trial involving 83 American adults with borderline-high to moderately elevated cholesterol. They found that Cholestin (when red yeast rice was an ingredient in this product) reduced total cholesterol, LDL cholesterol, and triglyceride levels but had no effect on HDL cholesterol. This study was published in the American Journal of Clinical Nutrition (1999;69:231-7).

Lowering LDL and increasing HDL cholesterol prevents atherosclerosis (a build-up of plaque) of the heart's arteries. Since atherosclerosis causes heart attacks, lowering the LDL and increasing HDL cholesterol should lower the risk of heart attacks. In fact, several large, long-term, placebo-controlled clinical trials have shown clearly that lowering LDL cholesterol with diet and statin drugs [pravastatin (Pravachol), lovastatin (Mevacor), and simvastatin (Zocor) reduces the risk of heart attacks. No large, long-term studies of red yeast rice products for the prevention of heart attacks have yet been conducted. However, animal studies are underway at UCLA comparing red yeast rice to a statin drug (such as Mevacor) for the prevention and treatment of atherosclerosis.

Animal studies have been conducted in China using high doses of red yeast rice products. No damage to the kidneys, liver, or other organs was demonstrated in these studies.

Human trials in China and in the United States reported only rare and minor side effects of heartburn or indigestion with the use of red yeast rice products. No liver, kidney, or muscle toxicity has been reported.

However, human trials in the United States and China have generally lasted only a few weeks to a few months. Thus, conclusive proof of long-term safety (over a period of many years) will have to await further data (such as from data received after the products have been marketed or long-term clinical trials).

Scientists conducting the studies generally believe that red yeast rice is safe in the long term since it has been a food staple for thousands of years in Asian countries without reports of toxicity. They attribute the safety of red yeast rice products to the process of preparation that does not involve the isolation and concentration of a single ingredient. Although it is true that isolation and concentration enhance the potency of a single ingredient, these factors also increase the risk of side effects.

Not all red yeast rice products contain the same concentrations of the cholesterol-lowering ingredients. Moreover, it is illegal in the United States to sell red yeast rice products that contain more than trace amounts of cholesterol lowering substances. Therefore, the red yeast rice products that are available in the United States do not contain levels of cholesterol lowering substances that are likely to cause side effects. Nevertheless, certain products also may contain unacceptably high levels of an undesirable and toxic substance called citrinic acid.

There is not yet consensus among scientists and doctors as to the role, if any, of red yeast rice in treating elevated cholesterol. Therefore, a doctor familiar with a patient's personal medical condition and his/her family history of heart diseases should be prescribing cholesterol-lowering measures.

Generally in the United States, when diet, weight loss, and exercise are insufficient in lowering cholesterol to optimal levels, many doctors recommend using a statin drug since large long-term trials have consistently shown that statins [such as pravastatin (Pravachol), simvastatin (Zocor), lovastatin (Mevacor), and atorvastatin (Lipitor)] are safe and effective in lowering LDL cholesterol and decreasing the risk of heart attacks and strokes.

Although similar studies are not available for red yeast rice products, given the minimal amounts of cholesterol lowering substances that they are allowed to contain in the U.S., it would be expected that legal red yeast rice products would not be very effective at lowering cholesterol levels.

Patients with moderate to severe cholesterol abnormalities, and patients who are at high risk of developing heart attacks or strokes are not candidates for red yeast rice. Examples of patients that are at high risk of heart attacks include

• patients who had prior heart attacks and strokes,
• patients with diabetes mellitus, and
• patients with atherosclerosis in the arteries that supply blood to the brain and to the extremities (peripheral artery disease).

In these patients, red yeast rice containing legal amounts of cholesterol lowering substances (along with weight loss, diet, and exercise) is not potent enough to achieve the degree of cholesterol lowering desired.