Identifying possible risks linked to dietary supplements - such as the recalled line of Hydroxycut weight-loss products - is challenging because FDA generally works with post-market information, an agency executive said.

Iovate Health Sciences voluntarily recalled 14 Hydroxycut products after FDA received adverse event reports concerning one death and 22 cases of serious liver problems possibly associated with use of the products, the Center for Food Safety and Applied Nutrition said May 1.

The adverse events were "reported by patients at the doses of Hydroxycut recommended on the bottle," according to FDA. The agency began receiving reports of liver-related illness possibly linked to the products in 2002.

Iovate could not be reached for comment.

CFSAN said consumers should discontinue use of Oakville, Ontario-based Iovate's line to avoid any undue risk. The products, also available from MuscleTech, are marketed for weight-loss, as fat-burners, energy enhancers, low-carbohydrate diet aids and for water loss.

Linda Katz, CFSAN's interim medical officer, said while Hydroxycut-related adverse events have been reported to the agency previously, the AER system makes it difficult to identify risks linked to particular products.

"Part of the problem is that FDA looks at dietary supplements from a post-marketing perspective," Katz said, adding that an "isolated" AER "is often difficult to follow" and establish a possible link.

However, once CFSAN collected and analyzed the Hydroxycut AER data, the next step was clear.

"Now is the time we felt we had enough information to go forward to talk to the company and to request a recall of the products," Katz said.

Further, Hydroxycut's multiple reformulations, including after ephedra was banned as a supplement ingredient in 2004, have complicated the process of linking adverse events to the products (¹ Also see "Supreme Court Refuses Ephedra Case, Battle Against Risk-Benefit Continues" - Pink Sheet, 21 May, 2007., p. 3).

FDA says it is difficult to determine what ingredient or ingredients are responsible for the adverse events because the products contain multiple substances, including herbal extracts. While ingredients in the 14 products overlap, no single substance is in each.

"What we have are proprietary blends of ingredients and the amount of that blend varies from product to product," Bill Frankos, director of CFSAN's Division of Dietary Supplement Programs, explained.

"It makes it difficult" to compare the products, he added. "It's very hard to draw a specific ingredient determination when you have products like that."

Supplement AERs Are "Vital"

Even though AERs provide post-market information, Frankos said the system is "vital in identifying unsafe dietary supplements."

Under provisions of the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006 - which made AERs for supplements and non-monograph OTC drugs mandatory - CFSAN could demand to inspect Iovate's records (² Also see "AER Label Guidance Holds To Requiring Full Addresses For OTCs, Supplements" - Pink Sheet, 15 December, 2008., p. 9).

Prior to the law's enactment, FDA did not have authority to inspect a firm's AER records. The law requires firms to keep AERs for six years.

The Natural Products Association and the Council for Responsible Nutrition say the Hydroxycut recall shows the AER system works.

Daniel Fabricant, NPA's VP of scientific and regulatory affairs at the Natural Products Association, noted information compiled by Iovate prompted FDA's request for a recall. The firm likely had plenty of AER data that FDA could "comb through," he said.

CRN President and CEO Steve Mister pointed out AERs "do not establish causality, nor is enough known at this point to determine whether the adverse events associated with these products were idiosyncratic, dose-related, ingredient-related or simply random."

Two Hydroxycut-branded products - Hydroxycut Cleanse and Hoodia products - are not on recall.

- Katie Stevenson (k.stevenson@elsevier.com)

Hydroxycut Recall Sheds Light On Pros And Cons Of AER System

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