Tuesday, May 22, 2012

DDW: Body-Building Supplements Top List of Hepatotoxic Agents

Herbal, Dietary Supplements Take Toll on Liver

By Cole Petrochko, Associate Staff Writer, MedPage Today
#This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

#Patients taking herbal and dietary supplements may be at risk for liver injury severe enough to warrant an organ transplant.

#Note that those who had liver injury resulting from either body building or weight-loss supplements also tended to have a longer latency time between exposure and injury compared with liver injury from other medications or the miscellaneous category of dietary supplements.

In a review of national data, supplements accounted for 18% of liver injuries in the U.S., Jose Serrano, MD, of the National Institutes of Health, reported during a press briefing at Digestive Disease Week.

"The number of cases in our network has increased over the years," Serrano said during the briefing. "There were no deaths, but 7% of patients needed a liver transplant. These are not trivial consequences."

It's estimated that as much as 40% of the U.S. population uses herbal or dietary supplements, but their potential side effects, including hepatotoxicity, are not well defined.

The researchers looked at data from the Drug Induced Liver Injury Network, which evaluated patient information from eight sites across the U.S. from 2003 to 2011.

Of 679 cases of liver injury, 93 were attributed to herbal or dietary supplements, Serrano said, adding that these patients tended to be younger than those who have similar liver injuries due to other medications. The majority of these patients were white.

Among patients that had used supplements, 33% used them for body building, 26% for weight loss, and the remaining 31% used a variety of other types of supplements.

Serrano said the symptoms of liver injury caused by supplements weren't different from those caused by other medications. But one factor that distinguished liver injury from body building supplements over the others was itching, which occurred in 86% of patients.

Those who had liver injury resulting from either body building or weight-loss supplements also tended to have a longer latency time between exposure and injury compared with liver injury from other medications or the miscellaneous category of dietary supplements.

Weight-loss products also appeared to be associated with a more hepatocellular pattern of injury, while body building supplements (usually anabolic steroids) had a more mixed pattern with increments on total bilirubin, Serrano said.

Most of the patients (66%) had to be hospitalized, and 11% developed alterations in liver function that persisted for at least 6 months, he added. The median serum alanine-aminotransferase (ALT) at presentation was 533 U/L, the alkaline phophatase was 166 U/L, and the total bilirubin was 7 mg/dL.

The R-value, which represents liver injury pattern, was in the hepatocellular range (>5%) in 65% of the patients with a median ALT of 1,275 U/L. The range for normal ALT is generally between 7 and 56 units U/L.

Symptoms included:
  • Jaundice (78% of patients)
  • Nausea (60%)
  • Itching (58%)
  • Abdominal pain (47%)
The majority of patients (60%) used only one type of supplement, while 23% used two or more supplements, and 16% used at least one supplement concurrently with prescription drugs.

While the most common injury pattern seen was hepatocellular, the distribution of overall causality scores was not significantly different across injury patterns (P=0.30), the authors stated.

The biggest risk to patients that use supplements is not reporting supplement use to a healthcare professional, noted Donald Jensen, MD, of the University of Chicago and DDW press conference moderator.

"Patients need to be label readers," Jensen told MedPage Today. "They can't just assume that everything out there is safe. There are things out there that can be potentially damaging."

He added that patients think supplements "are food or that they're very safe. And there are some herbal medicines that probably are safe and may even do some benefit for people. I don't want to throw everything in the trash can. But, on the other hand, there are enough [supplements] that are damaging."

He said that future research on supplements should focus on potential patient interactions with herbal supplements, noting that not all patients have negative interactions with them.

"I don't think we're going to stop people from taking herbal medicines," he said. "I'd like to see the FDA regulate the toxic ones better, but otherwise I think the important next step is some scientific understanding of why some people get damaged and others don't."

Navarro disclosed consultancy work for Merck.

Co-authors disclosed relationships with Boehringer-Ingelheim, Clinuvel, Novartis, American Porphyria Foundation, Iron Disorder Institute, Vertex, Lundbeck, Bristol-Meyers Squibb, GlaxoSmithKline, Siemens Medical Solutions, Roche, Gilead Sciences, Tibotec, and Catalent.

Primary source: Digestive Disease Week
Source reference:
Navarro VJ, et al "Herbal and dietary supplement induced hepatotoxicity in the U.S." DDW 2012; Abstract 167.


From Medscape Medical News > Conference News

Body-Building Supplements Top List of Hepatotoxic Agents
Caroline Helwick

May 22, 2012 (San Diego, California) — Supplements used for body-building and weight loss were the most frequent cause of liver injury related to herbal or dietary supplements in a review of the 8-center US Drug-Induced Liver Injury Network (DILIN).

The findings were reported here at Digestive Disease Week (DDW) 2012 by Victor J. Navarro, MD, professor of medicine, pharmacology and experimental therapeutics at Thomas Jefferson University in Philadelphia, Pennsylvania.

"Body-building and weight-loss supplements were implicated in 31% and 18% of cases, respectively," Dr. Navarro said. "Hepatotoxicity due to herbal/dietary supplements can be severe, resulting in transplantation in 7% of cases."

Dietary supplements include herbal remedies, body-building supplements, health food supplements, and any such substance bought over the counter or online that is not prescribed by a physician.
Hepatotoxicity from medication is the primary reason for drug withdrawal. Although up to 40% of Americans are believed to take at least 1 herbal or dietary supplement, the potential toxicity of these products is not well defined, Dr. Navarro said.

Dr. Navarro and colleagues, therefore, examined DILIN's experience with consecutive cases of hepatotoxicity attributable to herbal/dietary supplements between 2003 and 2011. They detailed the different types of products that were implicated and described the clinical characteristics, severity, and causality associated with cases of non–acetaminophen-related liver injury, as defined by strict criteria for liver enzyme elevation.

Clinical and laboratory data were collected for all patients, who were assigned DILIN severity scores by expert opinion. Patients were followed until their injury resolved.

The investigators identified 1048 total cases over the 8 years, of which 18.4% were deemed potentially attributable to herbal/dietary supplement use, Dr. Navarro reported.

He presented an analysis of 93 cases that had been fully "vetted" for cause of liver injury related to body-building supplements to provide more details of problem.

The analysis showed that 31% of cases appeared to be solely due to body-building supplements and 18% were solely due to weight-loss products. Less commonly (<10% each), immune support products, cough and cold formulations, and products marketed for mental health were implicated. Rarely, there were associations between liver injury and multiple vitamins; Chinese herbs; anti-inflammatory/analgesic compounds; energy boosters; sleep aids; and supplements for sexual performance, joint support, and gastrointestinal health.

Clinical Features of Injury Differed
"Among the implicated categories of products, body-building supplements (usually anabolic steroids) were more likely to be judged responsible for injury compared to other types of herbal and dietary supplements," he said.

Users of these products were all male, had a mean age of 35 years, were largely white (83%), and were often overweight (mean body mass index [BMI], 28.6 kg/m2). They experienced a longer latency between taking the product and falling ill, and they had a "striking" degree of hyperbilirubinemia. Their cases were also much more likely to be scored as "definitely" attributable to the supplement.
"The duration of their injury was much longer, as compared with the other populations," Dr. Navarro noted. "They had itching, anorexia, and weight loss. In other words, their lives were derailed for a longer period."

For liver injury due to weight-loss products, the typical user was female (65%), had a mean age of 37 years, was white (65%), and was overweight (BMI, 28.4 kg/m2). These patients were particularly notable for their hepatocellular injury (vs cholestatic or mixed injury), meaning their livers were "more inflamed," he explained.

Ingestion of a body-building supplement resulted in hospitalization in 52% of these cases and in liver or other organ failure for 7%, but none required transplants. Patients who fell ill because of weight-loss products were hospitalized 47% of the time, 12% experienced organ failure, and 12% required transplantation.

In the group of patients whose injury was related to an herbal or dietary product other than body-building or weight-loss supplements, the rate of hospitalization was 32%, organ failure occurred in 15%, and 11% underwent transplantation.

Dr. Navarro said he does not know "the denominator," ie, how many Americans currently use supplements; therefore, the ratio of use to injury cannot be determined. "I wish we did know," he said, "but we do know that in dollars, it's about $19 billion a year."

Making these products safer will be a challenge, he added. "The regulatory environment is a confounding factor in our research," he noted, explaining that ingredients can change from batch to batch. "The environment is permissive enough that we will be challenged to determine what within a certain product is actually causing the injury."

William Lee, MD, from the University of Texas Southwestern in Dallas, has treated patients who were part of the DILIN database. He commented, "It is very clear that the body-building drugs — typically anabolic steroids they get from the gym — have this effect on young men. They turn bright yellow and stay yellow for about 3 months at a time, though they virtually all recover. It just takes a long time. Weight-loss drugs cause more liver damage and not as much jaundice," he said.

Dr. Lee said that he would discourage anyone from using an herbal/dietary supplement. "The public wants to use these products all the time, but there is toxicity, and the body-building and weight-loss supplements are the main concerns."

Dr. Navarro disclosed he is a consultant for Merck & Co. Dr. Lee has disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2012. Abstract #167. Presented May 19, 2012.

Medscape Conference News

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