Liver injury from herbals and dietary supplements may be rising in some parts of US

Last Updated: 2014-09-22

By Will Boggs MD

NEW YORK (Reuters Health) - Liver injury from herbal medicines and dietary supplements appears to be on the rise in some parts of the country, according to data from the U.S. Drug-Induced Liver Injury Network (DILIN).

"More research is needed to identify more accurately what supplements, or ingredients thereof, cause liver injury and why," Dr. Victor J. Navarro from Einstein Medical Center in Philadelphia told Reuters Health by email. "Also, regulators must take note that current regulation of dietary supplements leans more toward protection of the manufacturer than the consumer."

About half of the U.S. adult population say they use herbals and dietary supplements, and there have been recent cases of life-threatening hepatotoxicity associated with the use of at least one of them (OxyElite Pro).

Dr. Navarro and colleagues examined the burden and characteristics of liver damage attributed to these products in the DILIN and compared the injuries with those caused by conventional medications. They excluded all cases related to acetaminophen, which account for the vast majority of medication-induced liver injuries.

The researchers defined liver injury as jaundice or coagulopathy in the presence of liver enzyme abnormalities or elevations of ALT or AST above five times the upper limit of normal or elevations of alkaline phosphatase above two times the upper limit of normal on two consecutive measurements at least 24 hours apart.

As for causality, medications were considered individually, whereas all herbals and dietary supplements taken by any patient were grouped together and adjudicated as a single agent, even if several were taken concurrently.

Ultimately, the analysis included 839 patients whose "definite," "very likely," or "probable" liver injuries were reported in the 10 years between 2004 and 2013. Most of these injuries (85%) were attributed to medications, and the rest were chalked up to herbals or dietary supplements.

The researchers divided those taking herbals and supplements into two groups based on whether they took the substances for bodybuilding purposes (45/130) or not (85/130).

During the first two years, cases attributed to herbals and dietary supplements accounted for 7% (eight cases) of the non-acetaminophen liver injuries. By the end of the study period, they accounted for 20% (63 cases in three years).

Liver transplantation was required more commonly in the nonbodybuilding supplements group (13%, 12 cases) than in the medications group (3%, 21 cases).

Based on the DILIN severity score, people taking herbals and dietary supplements had more severe cases than did those on conventional medications, the researchers report in Hepatology, online August 25.

The 130 patients in the herbals and dietary supplements group reported taking a total of 217 products, with only a minority of those products having a single ingredient and with 10% (bodybuilding) to 13% (nonbodybuilding) of the products containing more than 20 ingredients.

"Contrary to widespread belief, this study demonstrates that herbals and dietary supplement products are not always safe," the researchers conclude. "Indeed, our data suggest that, relative to conventional medication-induced hepatotoxicity, liver injury from herbal and dietary supplements not only occurs, but also may be increasing in frequency over time in the populations surrounding the DILIN centers and, probably, in the United States as a whole."

"The DILIN is not a population-based study, and although there was an increasing proportion of disease attributable to herbals and dietary supplements during the study, it cannot be concluded that the problem is actually on the rise in the United States," they add.

"Ask patients if they use supplements and always suspect them to be a cause for any unusual presentation, liver disease or otherwise," Dr. Navarro concluded.

How can patients protect themselves from supplement-related liver injury? "First, discuss their use with a qualified physician who understands their specific medical history and has knowledge of their other medications," Dr. Navarro suggested. "Second, if they choose to use supplements, they should stay within the labeled recommendations. Last, they should report any new symptoms to their doctor."

Dr. Rolf Teschke from Goethe University Frankfurt/Main in Germany, who studies medication-related liver toxicity, said most herbals and dietary supplements carry some risk of liver toxicity.

The risk is small but unpredictable, he told Reuters Health by email, and may be related to genetic susceptibility.

"Physicians often are confronted with patients who have increased liver values of primarily unknown etiology," Dr. Teschke said. "Apart from questioning regarding synthetic drugs as possible cause, the use of herbals and dietary supplements should be excluded by thorough investigation and repetitive questionings, since they are considered as natural and thereby perceived erroneously as safe."

He also criticized DILIN's causality assessments for not being quantitative.

"Other experts in the field worldwide prefer the use of the scale of CIOMS (Council for International Organizations of Medical Sciences), which is liver specific, structured, and quantitative based on specific items which are individually scored by -3 to +3 points, while the sum of the individual scores provides the respective causality grading," Dr. Teschke said. "The CIOMS scale can easily be applied already at the bedside of the patient, with results quickly available without the time-consuming expert-based procedure."

"Herbal and dietary supplements commonly are mixtures of multiple ingredients which prevent a clear causality assessment to one single ingredient," Dr. Teschke said. "The DILIN method is not prepared assessing various comedicated compounds, as opposed to the CIOMS scale, which facilitates such assessment."

SOURCE: http://bit.ly/XNJwxK

Hepatology 2014.