It was a case that might have puzzled TV's acerbic Dr. House.
A 33-year-old woman with dark urine and yellowish skin complained of profound fatigue when she showed up at the emergency room at Yale-New Haven Hospital. Lab tests showed she had acute liver inflammation.
Joseph Lim, a liver specialist at Yale, was on the case. He noted that the woman had been taking Hydroxycut supplements for weight loss for two weeks. Several reports in the medical literature had linked Hydroxycut (which is used for both bodybuilding and weight loss) to liver damage.
When his patient stopped taking the popular supplement, she improved, leading Lim to finger the product.
He has been far from the only critic. On May 1, the Food and Drug Administration warned consumers to stop taking Hydroxycut, which had been linked to liver damage and jaundice in 23 case reports received by the agency.
These complaints include one liver transplant and one fatality, a 19-year-old male from the southwestern United States, the FDA said.
Iovate Health Sciences, the Ontario-based manufacturer, voluntarily recalled 14 Hydroxycut products (two, Hoodia and Hydroxycut Cleanse, were not recalled because they contain different ingredients).
An Iovate spokeswoman referred a reporter to a statement on the company's Web site, which said that few adverse reports had surfaced compared to the numbers of Hydroxycut users, and that the company issued the recall from "an abundance of caution."
Lim said he supported the FDA's warning because the supplements are widely used and have undergone far less scrutiny than many people realize.
Dietary supplements are not tested by the FDA for safety or efficacy. The FDA relies on consumers, doctors, or manufacturers to alert them to health issues, but this can take time.
An estimated 15 percent of the U.S. population use over-the-counter weight-loss supplements, and Hydroxycut marketing declares it to be "America's No. 1 selling weight-loss supplement" in the United States.
The company sold more than nine million bottles of Hydroxycut in 2008, executives told the FDA.
Yet it remains unclear how many people Hydroxycut may have injured or even which of its ingredients are dangerous.
A visit to a local drug store showed that while Hydroxycut had been pulled from the shelves, many of its ingredients were widely available in other products still for sale. The FDA's Vasilios Frankos, director of the Division of Dietary Supplements Program, said last month that the agency was investigating those ingredients and other products that contain them.
The Hydroxycut ingredient that shares the product's name, hydroxycitric acid or HCA, has a long history. Drugmaker Hoffmann-La Roche tried to turn HCA into a weight-loss drug in the mid-1970s, but abandoned the research even before human testing because of toxicities in animals, said company spokesperson Darien Wilson. HCA is derived from the rind of a pumpkinlike tropical fruit that grows on the Garcinia cambogia tree.
Besides HCA, Lim said, two other ingredients could be toxic: the mineral chromium and Camellia sinensis, the tea plant. When ingested, both have been implicated in the medical literature as potential liver toxins.
So just recalling Hydroxycut hasn't fully protected the public, said Ano Lobb, an independent public health researcher for academic, nonprofit, and government entities.
"Hydroxycut is dangerous, so [consumers] look down the shelf and grab another weight-loss supplement," said Lobb, who a few weeks before the FDA's announcement published an article about the links between Hydroxycut and liver damage. "The message should be that [weight-loss and bodybuilding] supplements are some of the most dangerous."
Lobb became interested in Hydroxycut after seeing some of its ubiquitous advertisements featuring a formerly chubby, currently ripped medical doctor. "They kept citing clinical evidence that the product works. I wanted to know what that evidence was," Lobb said.
Hydroxycut packaging claims it increases energy and burns calories with "clinically proven" ingredients. Lobb found that the weight-loss studies yielded inconsistent results at best. "Besides the industry-funded studies, which should be viewed with some skepticism, they tended to be on animals," he said.
"There should be more evidence out there before it goes to market," Lobb added. Now, the burden "falls to the consumer."
Considering the supplement's popularity and the number of events reported, the FDA called the liver complications "relatively rare."
However, most experts agree that adverse events are dramatically underreported. A doctor or consumer won't always connect a supplement to a medical condition. And patients often fail to tell their doctors about supplement use.
Even then, the chances that a case will reach the FDA are slim. An FDA-commissioned study from 2001 found the FDA received only about 1 percent of supplement-related adverse-event reports.
The one Hydroxycut-related death cited by the FDA took two years to reach the agency. Such a delay isn't unusual, said Linda Katz, the FDA's interim chief medical officer for its Center for Food Safety and Applied Nutrition.
The FDA's decision to warn against Hydroxycut was also prompted by four cases in the medical literature reporting that Hydroxycut had caused liver toxicity.
The case reports - Lim wrote the most recent - follow a similar course: a sudden illness, sometimes requiring hospitalization, in the weeks or months after starting Hydroxycut, followed by improvement after stopping the supplement.
But not all liver disease follows this pattern.
Philadelphia lawyer Jamie Sheller of Sheller P.C. represents several clients who believe Hydroxycut harmed them. A Toronto firm, Juroviesky & Ricci L.L.P., has also filed a class-action lawsuit against the makers of Hydroxycut.
One of Sheller's clients, Stephen Snuffer, 59, a Mormon, was shocked to learn he had liver disease after a health insurance screening in December.
Hydroxycut had been part of Snuffer's daily routine for five years.
An independent insurance agent and author who lives on his own mountain in Cool Ridge, W. Va., Snuffer had assumed anything sold at GNC was healthy. "I used it as a supplement to prevent me from being hungry," he said. "I don't have time to stop and eat on the road."
Snuffer's liver enzyme levels indicate liver damage, but are far from those generally associated with acute liver toxicity. Even so, they are high enough to make individual insurance too expensive.
If cases such as Snuffer's can be attributed to Hydroxycut, the number of victims could rise substantially.