The Role of Adverse Event Reporting in the FDA Response to a Multistate Outbreak of Liver Disease Associated with a Dietary Supplement.

OBJECTIVE: Liver disease is a potential complication from using dietary supplements. This study investigated an outbreak of non-viral liver disease associated with the use of OxyELITE Pro(TM), a dietary supplement used for weight loss and/or muscle building. METHODS: Illness details were ascertained from MedWatch reports submitted to the U.S. Food and Drug Administration (FDA) describing consumers who ingested OxyELITE Pro alone or in combination with other dietary supplements. FDA's Forensic Chemistry Center analyzed samples of OxyELITE Pro. RESULTS: From February 2012 to February 2014, FDA received 114 reports of adverse events of all kinds involving consumers who ingested OxyELITE Pro. The onset of illness for the first report was December 2010 and for the last report was January 2014. Thirty-three states, two foreign nations, and Puerto Rico submitted reports. Fifty-five of the reports (48%) described liver disease in the absence of viral infection, gallbladder disease, autoimmune disease, or other known causes of liver damage. A total of 33 (60%) of these patients were hospitalized, and three underwent liver transplantation. In early 2013, OxyELITE Pro products entered the market with a formulation distinct from products sold previously. The new formulation replaced 1,3-dimethylamylamine with aegeline. However, the manufacturer failed to submit to FDA a required "new dietary ingredient" notice for the use of aegeline in OxyELITE Pro products. Laboratory analysis identified no drugs, poisons, pharmaceuticals, toxic metals, usnic acid, N-Nitroso-fenfluramine, pyrrolizidine alkaloids, aristocholic acid, or phenethylamines in the products. CONCLUSIONS: Vigilant surveillance is required for adverse events linked to the use of dietary supplements.

Hepatotoxicity due to hydroxycut: a case series.

OBJECTIVES: Muscletech Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada) was a popular weight-loss supplement that was recalled by the manufacturer in May 2009 on the basis of reports of hepatotoxicity associated with this supplement. We sought to characterize the clinical presentation of Hydroxycut-associated liver injury and to adjudicate these cases for causal association with Hydroxycut. METHODS: We assessed the causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study. RESULTS: Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized, and three of eight patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database, including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting, and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed eight cases as definite, five highly likely, two probable, and two were considered to be possible. CONCLUSIONS: Hydroxycut has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight-loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated.

Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS).

BACKGROUND: Following the marketing ban of ephedra-containing supplements in April 2004, many manufacturers substituted the herb Citrus aurantium for ephedra and marketed the products as "ephedra-free" supplements. Extracts of C. aurantium contain synephrine, a sympathomimetic alkaloid. OBJECTIVE: To determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. METHODS: We used the 2004 California Behavioral Risk Factor Surveillance Survey to determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. RESULTS: Two percent (n = 70) of the 4140 survey respondents reported taking a dietary supplement containing C. aurantium in the previous year. Reasons stated included energy enhancement, weight loss, and appetite suppression. Compared with nonusers, users were more likely to report being single, aged 18-34 years, and Hispanic; consuming 3 or more alcoholic drinks on days that they imbibed; and having a heavier body mass index. Among the 5 users who reported experiencing an adverse event that they attributed to the supplement, 3 indicated that the severity was mild. CONCLUSIONS: Given that supplements containing ephedra were banned in April 2004, the results from this study may serve as a baseline estimate against which future studies of the use of C. aurantium products may be compared.

Sulfites--a food and drug administration review of recalls and reported adverse events.

Sulfite-sensitive individuals can experience adverse reactions after consuming foods containing sulfiting agents (sulfites), and some of these reactions may be severe. In the 1980s and 1990s, the U.S. Food and Drug Administration (FDA) acted to reduce the likelihood that sulfite-sensitive individuals would unknowingly consume foods containing sulfites. The FDA prohibited the use of sulfites on fruits and vegetables (except potatoes) to be served or presented fresh to the public and required that the presence of detectable levels of sulfites be declared on food labels, even when these sulfites are used as a processing aid or are a component of another ingredient in the food. In the present study, data from FDA recall records and adverse event reports were used to examine the current status of problems of sensitivity to sulfites in foods. From 1996 through 1999, the FDA processed a total of 59 recalls of foods containing undeclared sulfites; these 59 recalls involved 93 different food products. Fifty (55%) of the recalled products were classified as class I, a designation indicating that a consumer reasonably could have ingested > or = 10 mg of undeclared sulfites on a single occasion, a level that could potentially cause a serious adverse reaction in a susceptible person. From 1996 through mid-1999, the FDA received a total of 34 reports of adverse reactions allegedly due to eating foods containing undeclared sulfites. The average of 10 reports per year, although derived from a passive surveillance system, was lower than the average of 111 reports per year that the FDA received from 1980 to 1987, a decrease that may have resulted in part from FDA regulatory action.