Nutraceuticals and nootropics for anti-aging

I am a long-time user of Red Yeast Rice which I use to control my cholesterol. I’ve never used statin drugs. Recently I learned from a Wikipedia article¹ that Red Yeast Rice is under attack by the U.S. Food and Drug Administration because of its cholesterol-lowering properties. The article implied that RYR may be removed from the market at any time. How does RYR compare with statin drugs in effectiveness, safety, and cost? Should I be worried about my supply of RYR being cut off?

A quick answer is that Red Yeast Rice (RYR, aka ‘Red Rice Yeast’) contains more than half a dozen substances that act like statin drugs. These, together with several other yeast-generated substances, regulate cholesterol levels more effectively and safely than do the single-substance statin drugs sold by pharmaceutical companies. The cost of using statin drugs varies tremendously, depending on dosage and brand, but they are always more expensive than RYR — sometimes incredibly so.

And yes, you should be worried that the U.S. Food and Drug Administration will cut off your supply of RYR. (More about that below.)

Overview

The red-colored yeast Monascus purpureus is a traditional Chinese food coloring and herbal remedy. The yeast is grown on wet white rice, which becomes permeated with the colored yeast. The resulting red rice is dried and pulverized and the powder sold as a traditional remedy for promoting blood circulation, soothing upset stomach, and for other medical purposes.^1,2 In Asia the red rice is also sold for dietary consumption as whole red grains or as a wet paste.¹

Red yeast rice has been used medicinally in China for at least several hundred years³ and has been a food ingredient for about 2000 years. RYR is “a dietary staple in many Asian countries, including China and Japan, with typical consumption ranging from 14 to 55 g/person/d (0.5 to 2 oz).”⁴ This substance could plausibly account for the low level of cardiovascular disease found in Asian populations.⁵

Modern RYR supplements are usually extracts of Red Yeast Rice — unneeded starches and gums have been removed by alcohol extraction to make the powdered product more potent, less perishable, and easily dosed. The Chinese name for such extracted RYR products is Xue Zhi Kang (aka ‘Xuezhikang’).⁶

How RYR affects cardiovascular disease

• RYR inhibits the body’s synthesis of cholesterol⁷
• RYR inhibits the body’s production of C-Reactive Protein⁸

The dried yeast contains a family of compounds (‘monacolins’) that inhibit HMG-CoA reductase (an enzyme responsible for making cholesterol in the body⁹). These inhibitors are similar in chemical structure to the expensive ‘statin’ drugs that are sold as prescription remedies for high cholesterol. In addition, the red yeast contains a variety of other medically active compounds, including flavonoids and sterols, that may contribute to the yeast’s cholesterol-regulating activity.^9,10

The monacolins in RYR also suppress the body’s production of C-Reactive Protein (‘CRP’). CRP is a protein involved in inflammation, and inflammation is considered to be the primary process that causes plaques to develop in arteries. By suppressing CRP, red yeast rice appears to be helping to suppress the inflammation responsible for atherosclerosis.^5,9

The efficacy of RYR

Ten or more clinical studies of RYR have been performed; all have shown that RYR supplementation brings about significant reductions in LDL cholesterol and triglycerides — reductions of at least 30% are achievable in patients with high lipid levels.¹¹ HDL (‘good cholesterol’) increased slightly in at least one study.¹² In a 2003 animal study an extract of RYR actually reduced the size of atherosclerotic plaques in arteries.¹³

No clinical studies have been performed to directly compare RYR and statin drugs with regard to their maximum potential for improving cholesterol profiles. The results found in separate studies, however, have given rise to the belief that RYR is at least as effective as statin drugs, while causing far fewer side effects. Why should this be? The dose of lovastatin provided by RYR supplements is far less than the dose used in prescription lovastatin drugs — consequently RYR users typically experience no lovastatin side effects. As for efficacy: the small size of the lovastatin dose provided by RYR is more than made up for by the presence of small amounts of various other substances which dramatically enhance this supplement’s effectiveness.¹⁰

Miscellaneous facts about RYR

• In a recent experiment with rabbits, a profound suppression of atherosclerosis development was achieved by a supplement combination consisting of RYR, policosanol, and the carotenoid ‘astaxanthin’ (the red substance in salmon and shellfish).¹⁴

• Vitamin E has many of the same effects on cardiovascular disease as RYR, as has been shown in a number of clinical trials.⁹ But vitamin E acts through a different mechanism than RYR. It therefore makes sense to use these two supplements together to take advantage of synergistic effects.

Cost comparison

The expensive way to lower the body’s LDL cholesterol levels is to use brand-name ‘statin’ drugs. There are six prescription statins currently on the market in the U.S. Although prices vary dramatically depending on who is selling them, the following prices represent the low end of the price range for non-generic statins:

• Lipitor® (atorvastatin) $78/month
• Lescol® (fluvastatin) $64/month
• Mevacor® (lovastatin) $60/month
• Pravachol® (pravastatin) $95/month
• Zocor® (simvastatin) $83/month
• Crestor® (rosuvastatin) $91/month
• Several of these are now available as generic drugs, at prices around $20/month.

Red Yeast Rice extracts cost even less than generic statin drugs. For example, LifeLink’s Red Rice Yeast Extract costs about $17/month.

These cost comparisons do not take into account the cost of dealing with side effects. It should be kept in mind that the statin drugs, whether brand-name or generic, contain fairly high dosages of single substances and therefore have more serious side effects than RYR which contains low doses of many active substances.

The FDA does intend to cut you off

The U.S. Food and Drug Administration is indeed committed to eliminating the public’s access to Red Yeast Rice, particularly the RYR extracts since these are effective alternatives to the statin drugs. The FDA has a track record of trying to eliminate products that compete for sales with products of the medical and pharmaceutical industries.

Accordingly, in 1998 the FDA made a major move against RYR: it announced that an RYR extract called ‘Cholestin’ (sold by Pharmanex, Inc.) was an unapproved drug rather than a supplement, and ordered Pharmanex to stop selling it. Pharmanex took the FDA to court and won¹⁵ — but only temporarily. A later court decision sided with the FDA, and so Cholestin was removed from the U.S. market. (Pharmanex later reformulated Cholestin using no RYR. But with the key ingredient gone, the product’s credibility has been impacted. It’s a pity that FDA officials cannot be personally sued for damages.)

In the years following the Cholestin action the FDA has been conducting a low-level harrassment campaign against the supplement industry to discourage the sale of RYR products. The agency occasionally sends out threatening letters to selected supplement marketers and forces them to destroy their inventories,^16,17 but it hasn’t made any concerted effort to shut down RYR sales. Why is the FDA using a low-level approach here instead of the SWAT-team approach that it has used in other situations? My speculation is that the agency is reluctant to anger too many RYR users at the same time since that could lead to media attention, with users telling reporters that the FDA is killing people by denying them access to effective, affordable treatments for dangerous cholesterol problems.

Meanwhile, the pharmaceutical company Merck & Co. has made more than one attempt to get FDA approval for an over-the-counter, low-dose lovastatin product (‘Mevacor®’), and has been turned down. Why? Two reasons: first, the agency considers the American people incompetent to make self-treatment decisions. As one FDA consultant put it, “Diet and exercise … may be thought to be less important if the primary strategy seems to be a statin drug.”¹⁸ Second, the agency does not want to set a precedent for allowing people to obtain highly effective drugs without having to hire a physician to prescribe them. “The panel felt that over-the-counter approval of Mevacor would lead to scores of other products to reduce bad cholesterol, tame high blood pressure, and keep diabetes in check.”¹⁹ Heaven forbid that we should have such choices!

Cautions

RYR, like the statin drugs, suppresses the body’s levels of CoQ10 (coenzyme Q10, a substance required for metabolism).^20,21 Users of RYR should therefore also use a CoQ10 supplement.

Pregnant women should avoid using RYR or any statin drug.^22,23

Sudden termination of RYR usage can have a significant rebound effect on C-Reactive Protein, LDL and HDL. (The same is true for statin drugs.) RYR users who want to stop using RYR — especially those with severe cardiovascular disease — should therefore reduce the dosage of RYR gradually over a period of about a week.⁸

Contraindications for lovastatin: pregnancy, nursing, liver or kidney impairment, co-administration with niacin, gemfibrozil, cyclosporin, azole antifungals, erythromycin, clarithromycin, nefazodone, protease inhibitors.^9,22

Recommended reviews about RYR

For a good overview of the subject of Red Yeast Rice I recommend the following review articles: Patrick,⁹ Heber²⁴, Raloff²⁵, Wikipedia¹, Lee²⁶

— Dr. Alexis Zarkov, Ph.D.

You can contact Dr. Zarkov at AskDrZarkov@yahoo.com.

Last modified 2007.Feb.6

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References

[1]  Red yeast rice Wikipedia article

[2]  Red Yeast Rice University of Maryland Medical Center website

[3]  Methods and compositions employing red rice fermentation products U.S. Patent #6,632,428 Mao Liang Zhang, et al.

[4]  Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999 Feb;69(2):231-6 Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL

[5]  Serum C-reactive protein as a marker for wellness assessment. Ann Clin Lab Sci. 2006; 36(2):163-9 Kao PC, Shiesh SC, Wu TJ

[6]  Red yeast rice (Monascus purpureus) Mayo Clinic website

[7]  Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2). Mol Cell Biochem. 2002 Apr;233(1-2):153-8 Man RY, Lynn EG, Cheung F, Tsang PS, O K.

[8]  Effects of withdrawal of Xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with coronary artery disease. Cardiovasc Drugs Ther. 2006 Jun; 20(3):185-91 Hu CL, Li YB, Tang YH, Chen JB, Liu J, Tang QZ, Zhang QH, Huang CX

[9]  Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev. 2001 Jun; 6(3):248-71 Patrick L, Uzick M

[10]  Plasma clearance of lovastatin versus chinese red yeast rice in healthy volunteers. J Altern Complement Med. 2005 Dec; 11(6):1031-8 Li Z, Seeram NP, Lee R, Thames G, Minutti C, Wang HJ, Heber D

[11]  Effects of xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with stable angina. Clin Chim Acta. 2005 Feb; 352(1-2):217-24 Li JJ, Hu SS, Fang CH, Hui RT, Miao LF, Yang YJ, Gao RL

[12]  [Intervention of xuezhikang on patients of acute coronary syndrome with different levels of blood lipids] Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Dec; 24(12):1073-6 Wang WH, Zhang H, Yu YL, Ge Z, Xue C, Zhang P

[13]  Hypolipidemic and anti-atherogenic effects of long-term Cholestin (Monascus purpureus-fermented rice, red yeast rice) in cholesterol fed rabbits. J Nutr Biochem. 2003 Jun; 14(6):314-8 Wei W, Li C, Wang Y, Su H, Zhu J, Kritchevsky D

[14]  Antiatherosclerotic efficacy of policosanol, red yeast rice extract and astaxanthin in the rabbit. Arzneimittelforschung. 2005; 55(6):312-7 Setnikar I, Senin P, Rovati LC

[15]  Dietary supplement or drug? The case of Cholestin [Editorial] American Journal of Clinical Nutrition, Vol. 69, No. 2, 175-176, February 1999 Richard J Havel

[16]  Warning Letters for Products Containing Red Yeast Rice FDA archives

[17]  [FDA forces Global Source and Consulting, Inc. to destroy RYR products] FDA archives, 2003

[18]  [Transcript of Advisory Committee meeting to discuss OTC approval for low-dose lovastatin] FDA website. July 13, 2000

[19]  FDA panel rejects sales of Mevacor over counter Boston Globe website. January 15, 2005 Diedtra Henderson

[20]  Muscle coenzyme Q10 level in statin-related myopathy. Arch Neurol. 2005 Nov; 62(11):1709-12 Lamperti C, Naini AB, Lucchini V, Prelle A, Bresolin N, Moggio M, Sciacco M, Kaufmann P, DiMauro S

[21]  Acute administration of red yeast rice (Monascus purpureus) depletes tissue coenzyme Q(10) levels in ICR mice. Br J Nutr. 2005 Jan; 93(1):131-5 Yang HT, Lin SH, Huang SY, Chou HJ

[22]  Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins. Am J Med Genet A. 2004 Dec 15;131(3):287-98 Edison RJ, Muenke M

[23]  The role of maternal toxicity in lovastatin-induced developmental toxicity. Birth Defects Res B Dev Reprod Toxicol. 2004 Jun;71(3):111-23. Lankas GR, Cukierski MA, Wise LD.

[24]  Herbs and atherosclerosis. Curr Atheroscler Rep. 2001 Jan; 3(1):93-6 Heber D

[25]  Cholesterol medicine for eggs? Science News 2003 July 12 Janet Raloff

[26]  Red Yeast Rice and Cholesterol - A Critical Review MedicineNet.com website Dennis Lee, M.D.

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Disclaimer: The information provided in this “Ask Dr. Zarkov” article contains no medical advice whatsoever — it contains biological information. Nothing in the article constitutes an effort to persuade readers to use, or not to use, this biological information as a basis for action.