June 21, 2004
FDA Claims Of Citrus Aurantium Prove To Be Greatly Exaggerated
OnApril 11, 2004, The New York Times rana story discussing actions taken by the Food and Drug Administration (FDA)against ephedra and the approaching ban that took effect the next day. Thearticle also discussed the ongoing search for a suitable ephedra replacement,and quoted long-time supplement industry foe Sen. Richard Durbin (D-Ill.) aswarning that many ephedra-free products are just as dangerous as ephedra was.In support of this proposition, the report also noted, A spokeswoman for theFDA said that [Citrus aurantium/bitterorange] had been associated with seven deaths and 85 adverse reactions.Almost immediately thereafter, surprised at the apparently large number ofadverse event reports (AERs) in FDAs possession, various industry leaderscalled upon FDA to substantiate this statement, and to issue a clarification ofany 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 wasforthcoming, a second letter was sent to FDA, noting it was in violation of thelaw, and raising the possibility of litigation. By this time, the question waswhere 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 legalobligations to provide the material requested?
On May 21, when FDA finally provided its response to the FOIArequest, the reason for the delay was immediately obvious. (FDA was presentedwith at least two other similar FOIA requests in mid-April. Neither wasresponded to for over a month). The supposed threat to consumer health posed by Citrusaurantium was greatly exaggerated by the agencyspokeswoman, if such a threat even exists at all.
In its response to the April 14 FOIA, FDA disclosed it hadconducted no research whatsoever concerning either the safety or efficacy of Citrusaurantium. The agency also acknowledged it had noexplanation for its failure to alert the public about the alleged adverse eventsuntil the eve of ephedras removal from the market. FDA did, however, producethe files it claimed contained the adverse events mentioned by the Times.A review of those indicates that the numbers released by FDA are grosslyinflated, and a review of the specific AERs strongly suggests FDA is once againtrying to generate alarm over a so-called public health threat based upon agross exaggeration of the nature of the adverse events in its possession. FDAspresent actions are reminiscent of its fatally flawed 1997 attempt to promulgateregulations governing the sale of ephedra based upon AERs. The proposedregulation was withdrawn following a General Accounting Office (GAO) review,which noted FDAs failure to even attempt to validate the substance of any ofthe AERs upon which it relied. Some of these included so-called ephedra-relateddeaths where the coroners report actually listed shotgun blast to thechest as the cause of death, or so-called adverse events as the 80-year-oldwoman who claimed ephedra caused her menstrual cycle to resume.
In order to fully appreciate the deceit involved in the datadisclosed by the FDA spokeswoman to the Times,it is important to note that of the thousands of pages produced in response tothe FOIA, there was a total of 20 AERs involving products where Citrusaurantium was not combined with ephedra and/or otherdietary ingredients with a stimulant effect. (One additional AER provides aningredient list that does not include ephedra, but refers to the consumersuse of a product known to contain ephedra as an ingredient). Indeed, the vastmajority of the AER files produced by FDA involved products that includedephedra in their formulas. In other words, they were already included in FDAsroster of ephedra-related AERs. The best-case scenario, then, is one ofaccidental double-counting. History, however, suggests this may have beensomething more nefarious. Consider, while a number of these products containedvitamin C, there have been no alarming reports concerning vitamin C.
Additional questions concerning credibility of FDAs dataarose when some of the particular AERs were reviewed. A few examples include:
ARMS (Adverse Event Report Monitoring System) 13037 B: Theconsumer was using an ephedra-based diet pill. Sometime later, she developedblood clots in her leg and complained to FDA that the dietary supplement she wasusing was the cause. However, this file contains a physicians reportconcluding the blood clots were likely caused by deep tissue trauma to thepatients left leg.
ARMS 10328 B: The AER involves a traditional Asian remedyfor 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 inhand-written notes indicating that over 20 herbs were included in the product,including both ephedra and bitter orange. FDA had the pills tested, and foundthat no ephedrine could be detected. No testing was done for any constituent ofCitrusaurantium.
ARMS 12483 B: The consumer collapsed after taking an ephedra weight-loss supplement that included bitter orange in a proprietaryblend. The blood analysis conducted at the hospital following this collapseindicated 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 thisconsumer, sadly, was actually suffering from a brain tumor. How this isconsidered a Citrus aurantium AERis inexplicable.
ARMS 13682 B: This AER relates to a consumer complaintregarding a product combining Citrus aurantium andkola nut (a caffeine source) that reportedly caused a seizure and cardiacarrest. The medical history included in the file indicates this consumer alsohas a history of three previous myocardial infarctions as well as cocaine andamphetamine abuse.
The material produced by the agency is rife with ARMS such asthese. It is hard to believe the individual who reported to the Timescould have been unaware of this, especially given FDAsrebuff by the GAO in 1997. If, however, that is the case, discussing these filesin a manner that would inevitably result in a newspaper report that linked Citrusaurantium to seven deaths and 85 adverse eventswas simply irresponsible. FDAs failure to heed industry leaders calls fora statement clarifying the true nature of these AERs, coupled with itsunreasonable, illegal delay in responding to valid FOIA requests (long enough toallow any injury to the industry caused by the misleading report to fester),unfortunately points to the possibility that this was an intentional act ofmalice. Why would FDA do this, and where is it going? Just take a look atephedra.
Marc Ullman is a partner in New York Citys Ullman, Shapiro & Ullman LLP. His practice includes the counseling of clients in all areas relating to the marketing of natural products. He can be reached at [email protected] or (212) 571-0068. Lauren Lamensdorf, a summer intern at Ullman, Shapiro & Ullman LLP, assisted in the preparation of this article.
Editors Note: INSIDER welcomes industry commentary andletters to the editor. Direct your comments to Heather Granato, FAX (480)990-0819, [email protected]. Letters may be edited for content or clarity anddo not necessarily represent the views of Virgo Publishing or INSIDER.
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