Clinically proven diet pills... oh, really?

WHEN a California judge handed down a US$12.5 million (S$21 million) false-advertising judgment against the maker of a herbal-stimulant-based weight-loss pill late last month, he also issued what amounted to a Bill of reproach against the science of dietary supplements.

The company, Cytodyne Technologies, maker of Xenadrine RFA-1, the supplement implicated in the death of a Baltimore Orioles baseball pitcher, had not just exaggerated the findings of clinical trials it commissioned, said Superior Court Judge Ronald L. Styn. It had also cajoled some researchers into fudging results in published scientific articles.

He concluded that the researchers had set out to create a study which 'justified the money being spent' by Cytodyne and which would ensure that they received further work from the company.

The case is part of a swelling tide of litigation which is raising questions about the way makers of ephedra, a herbal stimulant, and other dietary supplements use - and often misuse - 'scientific proof' to market products.

Under pressure in the courts and from regulators, a number of manufacturers, including Cytodyne, have refashioned some of their weight-loss products without the herbal stimulant.

The federal government is considering a ban.

But experts say an ingredient switch does nothing to alter the industry's reliance on questionable science.

In fact, they are concerned, as there is little rigorous research on ephedra substitutes.

The truth is, supplement makers are not obliged to do any research.

A 1994 law exempts them from having to prove, as drug manufacturers do, that their products are harmless and effective. But at a time of concern about the safety and effectiveness of its products, the US$18 billion-a-year supplement industry has embraced research because, when carefully aimed, it can be worth the money.

But because it is not regulated, its research can prove less than scientific, experts say.

'There will be 250 to 300 clinical trials on supplements this year,' said Mr Anthony Almada, a consultant and founder of sports nutrition company EAS, who advocates scientific research on products but is a critic of the way supplement makers conduct it.

'The rigour applied in these studies, on average, is somewhat notably less than that of a drug study,' he said.

Often relying on as few as 12 subjects, these studies are scaled-down versions of the double-blind, placebo-controlled clinical trials required before drugs can be approved.

Some are published in abbreviated form at meetings of scientific organisations, or in obscure journals, providing a basis for claims like 'clinically proven'.

An industry spokesman, Dr Steven Dentali, vice-president of science and technical affairs at the American Herbal Products Association, acknowledged that 'whenever there's a desired outcome, you've got the potential for bias'. But he argues that supplement science is no worse than that done for pharmaceuticals.

'There's an interest in making sure you do good science and represent it properly because there's a spotlight on the industry,' he said.

Even the best available science on ephedra is ambiguous. The United States Food and Drug Administration has collected reports linking it to more than 100 deaths. But often, studies have been too small and too limited - using only healthy subjects - to assess dangers.

In March, the Rand Corp issued an analysis combining the results of the many small studies. It found legitimate evidence that ephedra works for short-term weight loss, but can produce numerous cardiac side effects.

Lawsuit documents, including e-mail messages and detailed experiment records, show how the demands of marketing have sometimes compromised those of science. They show how companies and researchers suppressed negative data; removed product names from abstracts when the conclusions showed no positive effects; changed statistical methods to see if results improved; and left out subjects who complained of side effects like heart palpitations and high blood pressure.

One company, a Canadian concern called Muscletech Research and Development, commissioned a number of studies in 2001, when the ephedra industry was beginning to come under pressure from regulators.

Muscletech, maker of an ephedra-and-caffeine weight-loss product called Hydroxycut, was then in the midst of a major advertising campaign.

Splashy advertisements featured personal testimonials and before-and-after photographs, and, often in big type, the results of trials.

Documents from a federal lawsuit in Oklahoma show how studies were massaged for advertising copy.

One study, for instance, found that Hydroxycut users lost 6.8kg of fat mass in 12 weeks, while those taking a placebo lost 4.5kg.

In an internal memorandum accompanying the study, a Muscletech official warned: 'None of these results can be deemed significant.' He added that, 'Hydroxycut can't be claimed as superior' to the placebo.

To get around it, he proposed that copywriters simply say, 'Lose 15 pounds of fat in 12 weeks with Hydroxycut and exercise!'

Another study found Hydroxycut had no apparent effect. It went unpublished.

Suppression of study results is a common practice, said Mr Almada.

Lawyer Jeff Bauer, who sued Muscletech in the Oklahoma case, agreed. 'They don't have to turn the data over to anyone,' he said.

'If they had people dying, I don't think they'd have to tell anyone.' -- New York Times News Service.