Reply to EG Bliznakov

UCLA Center for Human Nutrition, Warren Hall Laboratory, 900 Veterans Avenue, Room 12-217, Los Angeles, CA 90095 E-mail: dheber{at}mednet.ucla.edu

Dear Sir:

Bliznakov, in his letter, "More on the Chinese red-yeast-rice supplement and its cholesterol-lowering effect," brings up some issues that are outside the scope of our paper regarding the use of Chinese red yeast rice to lower cholesterol (1) and other issues that are irrelevant to the scientific and public health significance of our work.

First, he states that the study was "very short-term." We believe that the duration of our study, 12 wk, was more than adequate to determine the effects of an inhibitor of cholesterol biosynthesis on serum lipids; our patients had already achieved a maximal effect by week 8. In our view, the only reason to conduct longer and larger studies would be to directly test the efficacy of Chinese red yeast rice in preventing heart attacks, as was done in studies with several statins, as cited in our paper (2–5). Furthermore, the utility of cholesterol as an intermediate biomarker for myocardial infarction has been well established in men and women with cholesterol concentrations >6.2 mmol/L (240 mg/dL) as well as in those with cholesterol concentrations between 5.2 and 6.2 mmol/L (200 and 240 mg/dL). For every 1% reduction in total cholesterol, there is a 2% reduction in the risk of fatal and nonfatal myocardial infarction (6, 7). After we showed a marked 16–18% reduction in cholesterol concentrations, we completed the scope of work for our phase 2 study. Only large-scale phase 3 studies can answer ultimate questions of the public health effect of the widespread use of Chinese red yeast rice as a food ingredient (8) or dietary supplement (1).

Second, it is not clear to me why Bliznakov objected to the number of patients in the trial (n = 83, with 42 in the treatment group) because our findings were both clinically and statistically significant. In fact, although the difference in total cholesterol from baseline was significant (P < 0.05), the difference from baseline in LDL cholesterol was highly significant (P < 0.001). Although we do not wish to promote the common myth in the literature that greater levels of statistical significance indicate more clinically significant differences, the data we collected were both physiologically and statistically significant.

Third, I agree with Bliznakov that more research is needed on both the mechanisms of action and the effects of the other 9 monacolins in Chinese red yeast rice, and we recently applied for federal funds to conduct research on the cellular and molecular aspects of the actions of this monacolin mixture compared with those of lovastatin, including its effects on coenzyme Q₁₀, which is a potent antioxidant carried on LDLs.

Fourth, we reported that the red-yeast-rice product we used was produced by the traditional solid-phase fermentation method. The preparation used in our study was identical to the proprietary product Cholestin, now available as a dietary supplement (Pharmanex, Inc, San Francisco).

Finally, I do not share Bliznakov's view that "we now need a second generation of cholesterol-lowering agents with much more specific effects." Many physicians have patients who have lost weight and follow a healthy diet and lifestyle, but still have elevated cholesterol concentrations. Are we to prescribe statins for these millions of patients? As a society, we are faced with rapidly increasing health care costs, including significant amounts of money spent for prescription drugs. Dietary supplements such as Chinese red yeast rice provide an alternative to prescription drugs. Because they may cost less and do not require a prescription, they are more accessible and may be used more widely. Research sponsored by the Office of Dietary Supplements Research of the National Institutes of Health in conjunction with other divisions of the National Institutes of Health and funding from private foundations will, I hope, provide the scientific base to address many of the public's concerns regarding dietary supplements.

REFERENCES

1. Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VLW. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231–6.
2. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–7.
3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–9.
4. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–9.
5. Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol 1994;74:667–73.
6. 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;279:1615–22.
7. Pearson TA. Commentary: lipid-lowering therapy in low-risk patients. JAMA 1998;279:1659–61.
8. Mei F. Red yeast flavored duck. In: Fang Mei's illustrated cookbook of regional Chinese cuisine. Guangxi, China: Guangxi National Press, 1990:177–88.