Red yeast rice product analysis misstates GMP issue, consultant asserts

The research article, titled “Variability in strength of red yeast rice supplements purchased from mainstream retailers,” was published recently in the journal European Journal of Preventive Cardiology. The authors—prominent dietary supplement industry critic Dr. Pieter Cohen, MD the Harvard University Medical School as well as Bharathi Avula PhD and Ikhlas Khan PhD of the National Center for Natural Products Research at the University of Mississippi—analyzed 28 samples of products purchased on the market for their levels of monacolin K, the constituent of red yeast rice that is also the molecule in the prescription medication lovastatin.

Levels varied by as much as 60-fold

The authors found that the levels of monacolin K in the red yeast rice supplements tested varies by as much as 60-fold. In addition, two of the supplements tested contained no monacolin K. When following the recommended dosages on the products, a consumer’s intake of monacolin K via these supplements could vary by as much as 120-fold, the authors said.

“Our findings highlight the wide variability of a pharmacologically active statin in red yeast rice supplements purchased from mainstream retailers after the introduction of the FDA’s current good manufacturing practices intended to assure the composition and strength of dietary supplements,” the authors concluded.

Faulty conclusion

While the variability of the products is troubling, natural products industry consultant Steven Dentali, PhD, believes the inference that this is a problem with GMPs is a faulty conclusion. Dr Dentali has long experience in the botanical sector, having served as the chief science officer for the American Herbal Products Association as well as an expert on botanical ingredients for Herbalife.

“This is a stunning example of good work with a faulty conclusion. They are assuming that following GMPs would control for the amount of lovastatin in the products,” Dr Dentali told NutraIngredients-USA.

The issue with red yeast rice is a complicated and counterintuitive one, Dr Dentali said. ‘Traditional’ red yeast rice is a fermented product that comes out of Traditional Chinese Medicine. In its natural state, the product contains a range of fermenting microorganisms, and thus varies to some degree in its makeup, though by all accounts the monacolin K levels in this form of the product are low.

Pharmanex precedent

But a court case from almost two decades ago supports FDA’s authority to drill down to constituents of botanicals to determine whether those substances meet the definition of a dietary supplement. In the Pharmanex vs Shalala case in 1998, FDA prevailed in its determination that a Pharmanex red yeast rice product on the market at that time had overly high levels of monacolin K and that red yeast rice products that had more than trace amounts of this molecule were in fact unapproved drugs. This determination hinged on a decision that monacolin K as a constituent had not been on the market before the filing of an IND application on lovastatin in 1987, a filing that eventually led to the marketing of the prescription drug Mevacor.

The law firm Kleinfeld, Kaplan and Becker (KKB) recently published a paper that lays out how the issue with monacolin K in red yeast rice has implications for the more recent questions swirling around the legal status of CBDs, a non-narcotic fraction of cannabis. According to the paper, in the Pharmanex case the court affirmed FDA’s ability to assert that, “lovastatin [monacolin K] was an ‘article’ that had already been approved as a drug and was therefore excluded from the definition of ‘dietary supplement.’”

GMP compliance, monacolin K levels are two different things

Dr Dentali said that a dietary supplement company operating in today’s market that is playing by the rules, in other words, following GMPs to the letter, can market a red yeast rice supplement, but it cannot legally manipulate the monacolin K levels in the product.

“FDA’s position is that if the monacolin K level in the product is elevated, you’ve done something to elevate it, such as by selecting certain strains of yeast that produce more monacolin K,” he said.

So, in Dr Dentali’s view, the issue is not that GMPs don't work, but that enforcement is lacking. In its CBD paper, KKB said that, “Dietary supplements that contain red yeast rice are widely marketed, and FDA tests such products from time to time to determine if they contain lovastatin at or below the levels of traditional red yeast rice products.” So, if there are in fact red yeast rice supplements on the market that are rich in monacolin K, the process that KKB is alluding to is not happening often enough.

“The conclusion of Cohen et al. that GMPs don’t work. It’s good work and it raises significant issues but it does not impugn GMPs, in my opinion. If we are going to have criticisms of GMPs, let’s at least have legitimate ones,” Dr Dentali said.

Online botanicals conference

Dentali will be among the speakers for NutraIngredients-USA’s upcoming Online Conference on Botanicals, which is scheduled for Thursday, July 13. In addition to Dentali, speakers include Roy Upton, founder of the American Herbal Pharmacopeia, Michael McGuffin, President of the American Herbal Products Association, Rick Kingston, PharmD, of SafetyCall International, Mark Blumenthal, founder of the American Botanical Council, Marc Brush, a principal in the consulting firm Natch, as well as experts from Sabinsa Corporation and Valensa International. For more information and to register for this FREE event, click here.