Qi Spot

Three days ago, I wrote an article about red yeast rice and it’s popular derivative drug Xue Zhi Kang. <http://qi-spot.com/2009/10/27/red-yeast-rice-for-cholesterol-fermented-fun/>.  Now, Medscape has put online a study about it.  Here it is with the usual highlights and commentary:

Red Yeast Rice and Hyperlipidemia: How Strong Is the Evidence?

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, have proven to be effective in reducing lipid levels and improving the risk for cardiovascular disease. However, many patients may not tolerate statins over time, partly due to statin-associated myopathy. Does red yeast rice present a valid alternative treatment for patients with this adverse event? The randomized trial discussed in this review examined the efficacy, safety, and tolerability of red yeast rice among a cohort of patients with a history of statin-associated myopathy.

The significant benefits of statins are hard to refute. These are being reported even among patients at a low risk for cardiovascular disease. For example, in a 2009 study, within 12 months of the initiation of treatment, rosuvastatin was associated with significant regression of carotid intima-media thickness — a strong surrogate marker for cardiovascular events.[1] Moreover, statin treatment among low-risk patients is associated with a reduction in the risk for cardiovascular events. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) examined treatment with lovastatin vs placebo among patients without a history of cardiovascular events.[2] Researchers found that lovastatin reduced the risk for first coronary heart disease events by nearly half over an average follow-up time of 5.2 years. This included a 40% reduction in the risk for myocardial infarction. There was also no significant difference in the rate of severe adverse events when comparing the lovastatin and placebo groups.

In English:  Statins work.  Statins also harm muscles sometimes.  Can Red Yest Rice work for those who can’t take statins?

Sigh, gotta love it.  The question is not “can we use herbal medicine/diet instead of statins” but “can we use them when patient’s can’t tolerate statins”.

The next few paragraphs deal with explaining the very rare side effects of statins.  We’ll leave it to the curious reader to follow the link later on.  Now we focus on red yeast rice!

One strategy in the management of patients with statin-associated myopathy could involve the use of red yeast rice, the fermented product of the yeast species Monascus purpureus grown on rice. It has been used for medicinal and nonmedicinal purposes in China since 900 A.D., and it is promoted there as a means to improve circulation. Red yeast rice contains several compounds collectively known as monacolins, one of which is monacolin K, a powerful HMG-CoA reductase inhibitor and the same chemical as lovastatin. Because of this, red yeast rice has received increased attention in Western countries as a means to treat hyperlipidemia, and there is good research to support its efficacy. In one placebo-controlled trial of 83 individuals with hyperlipidemia, red yeast rice was associated with mean reductions in the concentrations of total and LDL cholesterol of 18% and 22%, respectively, over 12 weeks of treatment.[7] Red yeast rice also reduced serum triglyceride levels by 7% but did not significantly alter high-density lipoprotein (HDL) cholesterol levels. In another placebo-controlled trial, red yeast rice reduced total and LDL cholesterol levels by 27.7% and 21.5%, respectively, and red yeast rice decreased apolipoprotein B levels by 26%.[8]

In English, again – Red Yeast rice was proven to reduce bad cholesterol but not good cholesterol!

To help determine whether red yeast rice may be useful among patients with hyperlipidemia who do not tolerate a statin, the study under discussion in this review compared red yeast rice and placebo among patients with statin-associated myopathy. Patients from one cardiology practice in the United States were eligible for study participation if they were between 21 and 80 years old and had discontinued a statin because of myalgia. Participants’ LDL cholesterol levels were between 100 and 210 mg/dL at baseline, and patients with a serum triglyceride level of 400 mg/dL or more were excluded from study participation, as were those with a history of coronary heart disease.

Sixty-two patients underwent randomization to treatment with 3 red yeast rice 600-mg capsules twice daily, or matching placebo capsules with the same dosing schedule. The treatment period was 24 weeks. All study participants had previously been enrolled in a 12-week trial of lifestyle counseling to prevent cardiovascular disease. The mean age of the participants was 61 years, and 65% of the participants were women. The mean patient weight at baseline was 81 kg. The 2 groups were similar at baseline, except for a slightly higher mean pain score in the placebo cohort.

The main study outcome was LDL cholesterol level, as measured at baseline, week 12, and week 24. The mean values in the placebo group were 165 mg/dL, 154 mg/dL, and 149.8 mg/dL at baseline, week 12, and week 24. The respective levels of LDL cholesterol in the red yeast rice group were significantly better during the active trial period (163 mg/dL, 120 mg/dL, and 128 mg/dL, respectively). This represented a decrease in the baseline LDL cholesterol level of -27.3% at 12 weeks and -21.3% at 24 weeks in the red yeast rice group. Total cholesterol levels were also improved in the red yeast rice vs placebo groups, but there was no treatment difference in HDL cholesterol or triglyceride levels.

Researchers also examined other lipid values and patient weight, as well as specific surveys for bodily pain and laboratory assessments of creatine phosphokinase levels and liver-associated enzymes. There was no significant difference between the red yeast rice and placebo groups in the rate of adverse events and bodily pain, even when the researchers performed a subgroup analysis that was based on the number of statins that patients had previously tried. Four patients discontinued treatment in the red yeast rice group, compared with 1 patient in the placebo group. Creatine phosphokinase and liver-associated enzyme levels remained similar between the groups. Both treatment groups experienced a weight loss of approximately 3.5 kg from baseline.

Again in English: Red Yeast rice caused “bad cholesterol” to go down.  It did not cause any significant difference in both body pain (known statin side effect) and liver and kidney problems between the two groups.

And for their conclusion!

The collective research suggests that red yeast rice is effective and safe in improving the lipid profile among patients with hyperlipidemia. Some research even has suggested that red yeast rice, along with other nonprescription treatment, may be as or more effective than a statin. Becker and colleagues compared treatment with simvastatin 40 mg daily vs combination therapy consisting of enrollment in an intensive lifestyle intervention, fish oil supplementation, and red yeast rice supplementation.[9] The reduction in LDL cholesterol was approximately 40% in both treatment groups, and patients receiving the combination treatment experienced a greater reduction in body weight and serum triglycerides. Although these results are impressive, it is unclear which of the nonstatin interventions was most effective in improving study outcomes.

Red yeast rice does not have the impressive track record of statins in terms of the prevention of cardiovascular events. However, a trial of 5000 individuals with a history of previous myocardial infarction demonstrated that red yeast rice reduced the risk for nonfatal myocardial infarction by 62% and coronary disease mortality by 31% compared with placebo.[10] Red yeast rice also reduced overall mortality by one third compared with placebo.

More research is required with regard to the clinical outcomes of red yeast rice before this treatment can be recommended as an alternative to statins to treatment-naive patients with hyperlipidemia. Concerns about red yeast rice toxicity have been based on monacolin K, the natural lovastatin. Myopathy and rhabdomyolysis,[11,12] similar to that seen with lovastatin, have been reported in case reports. Hepatotoxicity is the main concern, with reports on red yeast rice’s effects on the liver being variable. Some studies have shown theoretical potential for hepatic damage,[13,14] and others have reported no harm in humans.[15] In some animal studies (rats and mice), high doses were tolerated without liver toxicity.[16-18] Because of this finding, statins themselves and any agents that interact with statins should be avoided by those taking red yeast rice.

There are also common questions associated with any complementary and alternative therapy about standardization of the preparation and reimbursement for long-term treatment. However, among special cohorts of patients, particularly those with statin-associated myopathy, red yeast rice appears to be a viable alternative treatment. Physicians should weigh the potential risks and benefits of statins vs alternative treatments for individual patients on the basis of their history of treatment and cardiovascular risk.

Charles P. Vega, MD “Red Yeast Rice and Hyperlipidemia: How Strong Is the Evidence?”  http://www.medscape.com Published: 10/28/2009, Retrieved 10/29/09<http://www.medscape.com/viewarticle/711114>

Vega cites the following as references:

1.  Bots ML, Palmer MK, Dogan S, et al; METEOR Study Group. Intensive lipid lowering may reduce progression of carotid atherosclerosis within 12 months of the treatment: the METEOR study. J Intern Med. 2009;265:698-707.
2. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615-1622.
3. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97:52C-60C.
4. Hansen KE, Hildebrand JP, Ferguson EE, Stein JH. Outcomes in 45 patients with statin-associated myopathy. Arch Intern Med. 2005;165:2671-2676.
5. Avorn J, Monette J, Lacour A, et al. Persistence of use of lipid-lowering medications: a cross-national study. JAMA. 1998;279:1458-1462.
6. Young JM, Florkowski CM, Molyneux SL, et al. Effect of coenzyme Q10 supplementation on simvastatin-induced myalgia. Am J Cardiol. 2007;100:1400-1403.
7. 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;69:231-236.
8. Lin CC, Li TC, Lai MM. Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia. Eur J Endocrinol. 2005;153:679-686.
9. Becker DJ, Gordon RY, Morris PB, et al. Simvastatin vs. therapeutic lifestyle changes and supplements: randomized primary prevention trial. Mayo Clin Proc. 2008;83:758-764.
10. Lu Z, Kou W, Du B, et al; Chinese Coronary Secondary Prevention Study Group. Effect of Xuezhikang, an extract from red yeast rice, on coronary events in a Chinese population with previous myocardial infarction. Am J Cardiol. 2008;101:1689-1693.
11. Smith DJ, Olive KE. Chinese red rice-induced myopathy. South Med J. 2003;96:1265-1267.
12. Rhabdomyolysis linked to Chinese red yeast rice. Prescrire Int. 2008;17:64.
13. Lu ZL, Xu S, Kou WR. The clinical observation of treatment of hyperlipidemia with different dose of Xuezhikang. National Symposium of Clinical Therapies for Cardiovascular Diseases. 1995;1997:53-57.
14. Wang J, Lu Z, Chi J, 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;58:964-978.
15. Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998;63:397-402.
16. Changling L, Yafang L, Zhonglin H. Toxicity study for Monascus purpureus (red yeast) extract [abstract]. Chin Pharmacol Soc. 1995;12:12.
17. Li C, Li Y, Hou Z, et al. Experimental studies on toxicology of Xuezhikang. Commun Chin Pharmacol Soc. 1995;12:12.
18. Blanc PJ, Laussac JP, Le Bars J, et al. Characterization of monascidin A from Monascus as citrinin. Int J Food Microbiol. 1995;27:201-213.