How supplements can bite their buyers

When Phillies reliever J.C. Romero ventured into a Cherry Hill Vitamin Shoppe last July, he got more than he bargained for: The 6-OXO Extreme supplement he bought apparently led him to test positive for a testosterone-boosting substance banned by Major League Baseball.

Romero says he believed, based on assurances from the MLB Players Association that were later retracted, that anything bought at a U.S. retail store should be safe. Baseball officials say players have been repeatedly warned that some legally purchased supplements may produce positive drug tests.

Romero's 50-game suspension has drawn new attention to a business that has often stirred controversy. Fifteen years after Congress and the Clinton administration put the dietary-supplement industry on a loose leash, the $25-billion-a-year business still sometimes bites its customers.

Supplement-makers and industry groups praise the 1994 law, which relies heavily on self-regulation rather than close control by the Food and Drug Administration.

"We think it's a good law," said Michael McGuffin, president of American Herbal Products Association, who said his group supported 2006 amendments requiring supplement-makers to report "serious adverse events" linked to supplement use to the FDA. "It's a law that serves the purposes of consumers, and it serves the purposes of the industry."

Critics, including consumer groups, doctors, and members of Congress, counter that the system remains seriously flawed. They say the fact that 6-OXO Extreme could be marketed without the FDA's knowledge or approval highlights some of the 1994 law's limitations.

"The dietary-supplement industry is essentially unregulated," said Bruce Silverglade, legal director of the Center for Science in the Public Interest, a research and advocacy group. "The FDA lacks the authority it needs to ensure products are safe before they're marketed."

Silverglade said that although some supplements can be beneficial and others are largely benign, the system can leave buyers unaware that some products are as potent - and potentially dangerous - as tightly regulated prescription drugs.

Major League Baseball is among the supplement industry's harshest critics.

"There is inadequate testing of these products before they come to market," said Rob Manfred, Major League Baseball's executive vice president of labor relations. "We have consistently advocated for stricter federal regulation of supplements."

Baseball has reasons for its concerns.

After nearly a decade of complaints and mounting evidence linking the herbal stimulant ephedra to heart attacks and strokes, the FDA succeeded in banning ephedra-based supplements only after the high-profile 2003 death of Orioles pitcher Steve Bechler.

And after years of off-the-charts power hitting, it took the Barry Bonds steroid scandal to prompt Major League Baseball, and then Congress, to crack down on the use of muscle-building anabolic steroids and also on supplements containing precursor chemicals. One of those was Androstenedione, used by slugger Mark McGwire en route to hitting a record-shattering 70 home runs in 1998.

Androstenedione played a role in the Romero case - sources say that is what he tested positive for - though it remains unclear why.

The product Romero bought, 6-OXO Extreme, was developed by Patrick Arnold - the chemist who introduced Androstenedione to the U.S. market and who also developed the undetectable designer steroid known as "the Clear" that was provided to Bonds.

Arnold says his new supplement boosts testosterone through a different mechanism, and initially insisted that it should not cause a positive test for Androstenedione. Last week, he suggested that 6-OXO could produce a "false positive" because of testing methods - an argument disputed by the head of baseball's drug-testing lab.

The '94 law's critics say 6-OXO Extreme's path to market illustrates some of the system's shortcomings.

The law treats supplement ingredients differently depending on when they were introduced. If an ingredient was not on the market in 1994, it requires a supplement-maker to submit notice of a "new dietary ingredient" to the FDA before marketing the ingredient, including an explanation of why the ingredient can "reasonably be expected to be safe."

There is one exception: The law exempts ingredients that "have been present in the food supply as an article used for food in a form in which the food has not been chemically altered."

Arnold did not submit a new-ingredient notice for 6-OXO Extreme or its predecessor, 6-OXO. Asked why, he cited the "present in the food supply" exemption.

In an e-mail exchange, Arnold quoted an analysis that examined tissues from slaughtered cattle and sheep and concluded that "the compound 6-OXO was unequivocally identified in both bovine kidney and subcutaneous fat."

Steve Mister, president of the Council for Responsible Nutrition, a supplement-industry trade association, questioned Arnold's reasoning.

"We interpret the law to mean that the mere presence of a chemical in some minute quantity in another item, such as animal meat or organs, in and of itself, is not sufficient to exempt a company from going through this premarket approval process," Mister said in an e-mail.

It is not clear whether the FDA would have objected to the ingredient's use - or whether its objections would have made any difference, anyway.

Under the 1994 law, a supplement-maker must have evidence that a new dietary ingredient is safe. Arnold has said two studies have demonstrated 6-OXO's safety, including a Baylor University study published in the Journal of the International Society of Sports Nutrition.

And under the law's loose regulatory framework, the FDA's objections do not necessarily stop a product from hitting store shelves.

According to the American Herbal Products Association, which tracks new-ingredient notices to the FDA, the agency has voiced objections to more than 300 of 474 notices since 1994. The rest were "filed" - a sort of tacit approval.

McGuffin, the association's president, said FDA objections do not block a new ingredient's sale.

"It's not hard and fast. The law doesn't say that if the FDA refuses to file, then your product is illegal," McGuffin said.

An FDA spokesman agreed and said some companies essentially ignore the objections.

"Firms can and sometimes do choose to market a product contrary to FDA's stated judgment, at the risk that FDA will initiate enforcement action against it," spokesman Michael Herndon said in an e-mail.

Has the FDA tried to block supplement-makers from marketing new ingredients despite its objections?

"To date, FDA has not taken an enforcement action against any such product," Herndon said.

At least one of the studies on 6-OXO that Arnold said demonstrated its safety also appeared to show it was ineffective for the training effect that Romero and other buyers presumably want, according to one of the Baylor study's co-authors.

"To me, the take-home was that when you used this during training, it didn't cause an increase in muscle mass or weight gain," said exercise physiologist Richard Kreider, who now heads the Department of Health and Kinesiology at Texas A&M University. "The bottom line is that it had no effect on body composition."