FDA Claims Of Citrus Aurantium Prove To Be Greatly Exaggerated

FDA Claims Of Citrus Aurantium Prove To Be Greatly Exaggerated
by Marc Ullman

On April 11, 2004, The New York Times ran a story discussing actions taken by the Food and Drug Administration (FDA) against ephedra and the approaching ban that took effect the next day. The article also discussed the ongoing search for a suitable ephedra replacement, and quoted long-time supplement industry foe Sen. Richard Durbin (D-Ill.) as warning that many ephedra-free products are just as dangerous as ephedra was. In support of this proposition, the report also noted, A spokeswoman for the FDA said that [Citrus aurantium/bitter orange] had been associated with seven deaths and 85 adverse reactions. Almost immediately thereafter, surprised at the apparently large number of adverse event reports (AERs) in FDAs possession, various industry leaders called upon FDA to substantiate this statement, and to issue a clarification of any misleading impression it may have created. Indeed, almost immediately, suspicions arose that these numbers were somehow inflated.

On April 14, my firm filed a Freedom of Information Act (FOIA) request with FDA seeking the data to back up this assertion. By its own rules, FDA should have responded to this request by April 24; when no response was forthcoming, a second letter was sent to FDA, noting it was in violation of the law, and raising the possibility of litigation. By this time, the question was where was the evidence backing up the numbers disclosed to the Times, and why was FDA derelict in responding to the request that it fulfill its legal obligations to provide the material requested?

On May 21, when FDA finally provided its response to the FOIA request, the reason for the delay was immediately obvious. (FDA was presented with at least two other similar FOIA requests in mid-April. Neither was responded to for over a month). The supposed threat to consumer health posed by Citrus aurantium was greatly exaggerated by the agency spokeswoman, if such a threat even exists at all.

In its response to the April 14 FOIA, FDA disclosed it had conducted no research whatsoever concerning either the safety or efficacy of Citrus aurantium. The agency also acknowledged it had no explanation for its failure to alert the public about the alleged adverse events until the eve of ephedras removal from the market. FDA did, however, produce the files it claimed contained the adverse events mentioned by the Times. A review of those indicates that the numbers released by FDA are grossly inflated, and a review of the specific AERs strongly suggests FDA is once again trying to generate alarm over a so-called public health threat based upon a gross exaggeration of the nature of the adverse events in its possession. FDAs present actions are reminiscent of its fatally flawed 1997 attempt to promulgate regulations governing the sale of ephedra based upon AERs. The proposed regulation was withdrawn following a General Accounting Office (GAO) review, which noted FDAs failure to even attempt to validate the substance of any of the AERs upon which it relied. Some of these included so-called ephedra-related deaths where the coroners report actually listed shotgun blast to the chest as the cause of death, or so-called adverse events as the 80-year-old woman who claimed ephedra caused her menstrual cycle to resume.

In order to fully appreciate the deceit involved in the data disclosed by the FDA spokeswoman to the Times, it is important to note that of the thousands of pages produced in response to the FOIA, there was a total of 20 AERs involving products where Citrus aurantium was not combined with ephedra and/or other dietary ingredients with a stimulant effect. (One additional AER provides an ingredient list that does not include ephedra, but refers to the consumers use of a product known to contain ephedra as an ingredient). Indeed, the vast majority of the AER files produced by FDA involved products that included ephedra in their formulas. In other words, they were already included in FDAs roster of ephedra-related AERs. The best-case scenario, then, is one of accidental double-counting. History, however, suggests this may have been something more nefarious. Consider, while a number of these products contained vitamin C, there have been no alarming reports concerning vitamin C.

Additional questions concerning credibility of FDAs data arose when some of the particular AERs were reviewed. A few examples include:

• ARMS (Adverse Event Report Monitoring System) 13037 B: The consumer was using an ephedra-based diet pill. Sometime later, she developed blood clots in her leg and complained to FDA that the dietary supplement she was using was the cause. However, this file contains a physicians report concluding the blood clots were likely caused by deep tissue trauma to the patients left leg.
• ARMS 10328 B: The AER involves a traditional Asian remedy for arthritis that the consumer alleged caused severe abdominal pain and nausea. FDA was sent some brown capsules, but no product label. The consumer did send in hand-written notes indicating that over 20 herbs were included in the product, including both ephedra and bitter orange. FDA had the pills tested, and found that no ephedrine could be detected. No testing was done for any constituent of Citrus aurantium.
• ARMS 12483 B: The consumer collapsed after taking an ephedra weight-loss supplement that included bitter orange in a proprietary blend. The blood analysis conducted at the hospital following this collapse indicated the presence of both amphetamines and barbiturates.
• ARMS 13510 B: This involves a consumer who was using an ephedra diet pill and reported to FDA that it had caused a stroke. Medical records included in this file, however, indicate this consumer, sadly, was actually suffering from a brain tumor. How this is considered a Citrus aurantium AER is inexplicable.
• ARMS 13682 B: This AER relates to a consumer complaint regarding a product combining Citrus aurantium and kola nut (a caffeine source) that reportedly caused a seizure and cardiac arrest. The medical history included in the file indicates this consumer also has a history of three previous myocardial infarctions as well as cocaine and amphetamine abuse.

The material produced by the agency is rife with ARMS such as these. It is hard to believe the individual who reported to the Times could have been unaware of this, especially given FDAs rebuff by the GAO in 1997. If, however, that is the case, discussing these files in a manner that would inevitably result in a newspaper report that linked Citrus aurantium to seven deaths and 85 adverse events was simply irresponsible. FDAs failure to heed industry leaders calls for a statement clarifying the true nature of these AERs, coupled with its unreasonable, illegal delay in responding to valid FOIA requests (long enough to allow any injury to the industry caused by the misleading report to fester), unfortunately points to the possibility that this was an intentional act of malice. Why would FDA do this, and where is it going? Just take a look at ephedra.