Red Yeast Rice Safety Advantage Over Rx Statins Cited By UCLA Researcher

Differentiating the metabolic activity of red yeast rice from that of Rx statins could create a "widescale public health prevention" need for botanical supplements unencumbered by the toxicity and safety concerns associated with cholesterol-lowering drugs, according to a University of California at Los Angeles researcher.

Making statin drugs available OTC would create a temptation by consumers to disregard lifestyle factors in lowering their cholesterol and, instead, rely only on statin therapy, David Heber, MD/PhD, opined at the Council for Responsible Nutrition's annual conference in Miami Sept. 19.

"The temptation would be to take in not 10 mg of statin, but 20, 40 or 80 [mg]. They'll take more pills in an unregulated way because we know the toxicity of statins is related to dose," said Heber. "Above 40 mg there's a 4% incidence of muscle dysfunction and liver dysfunction."

"However, [with] Chinese red yeast, at least in animal studies at 500 to 1,000 times the human dose, there is no toxicity," noted Heber, who has conducted research on Pharmanex' Chinese red yeast rice supplement Cholestin and cholesterol reduction.

Heber, director of UCLA's botanical dietary supplements research center, noted red yeast rice contains nine monacolin compounds structurally identical or similar to lovastatin (Merck's Rx statin Mevacor).

"We believe the combination of the nine different monacolins will be metabolized differently than Mevacor," Heber said. "It's critical that we show that because I believe that the FDA correctly turned down the application for over-the-counter statins."

In joint meetings July 13-14, FDA's Nonprescription Drugs and Endocrinologic & Metabolic Drugs Advisory Committees voted against OTC switch of Mevacor and Bristol-Myers Squibb's Pravachol (¹ (Also see "Mevacor Study Comparing Rx, OTC Use Is Among FDA Panel Suggestions" - Pink Sheet, 17 Jul, 2000.)).

The committees appeared more receptive to potentially switching Pravachol. A perceived safety difference between the two products, particularly with regard to interactions, was one factor in the deliberations. While a majority of committee members found both statins had adequate safety profiles for switch, the vote on Mevacor (7-6) was closer than Pravachol (11-3) (² (Also see "Pravachol Low Drug Interaction Profile Deemed Favorable During OTC Review" - Pink Sheet, 24 Jul, 2000.)).

FDA's Office of Post-Marketing Drug Risk Assessment has urged that "liver failure" be added to the list of statin-related adverse events. Both Merck and Bristol asserted ongoing liver function tests are unnecessary for the drugs.

In recent comments to FDA, the American Heart Association suggested OTC statins would be "better tested for safety and efficacy" than dietary supplements "that have not been rigorously tested" (³ (Also see "OTC Switch Expert Panels Supported By AHA" - Pink Sheet, 18 Sep, 2000.)).

In addition to conducting basic and clinical research on red yeast rice and other botanicals, one of the UCLA center's goals is to establish that multiple ingredients act differently than a single purified substance.

Such an approach "really flies in the face of what has been a tenet of the pharmaceutical industry, which is that you take a crude substance, purify it, define a single substance as the active compound and then you purify that compound, crystallize it, make it into a salt and then test that purified compound in humans," Heber maintained.

For instance, the center is examining whether the multiple catechins found in green tea are more active than one particular catechin, EGCG, in blocking oxidation and angiogenesis.

Noting there exists a "large population now in America that has been treated for primary tumor," Heber said the baby boomer generation's attention is turning to prevention. "Green tea inhibits new tumor blood vessel growth. We've already shown in our center...that multiple elements of green tea have this anti-angiogenic effect, not just EGCG."

UCLA and the University of Illinois at Chicago were the first two botanical research centers designated by NIH's Office of Dietary Supplements and National Center for Complementary & Alternative Medicine. On Sept. 20, NIH announced the funding of two more centers to study polyphenols and Ayurvedic medicine (⁴ (Also see "New Botanical Centers To Focus On Polyphenols, Ayurvedic Medicine" - Pink Sheet, 25 Sep, 2000.)).

The UIC center is focusing research on 10 herbals that may benefit women's health issues, including menopause. The center plans to start Phase I studies on red clover and black cohosh either late this year or in January, followed by a Phase II study which will examine the herbals' effectiveness in reducing the severity and frequency of hot flashes, Center Director Norman Farnsworth, PhD, announced at the CRN conference.