Tweet
Ephedrine Limits" Review
By Will Brink
For those of you who have not seen it, to follow what is called the Cantox Review.
The Cantox Review is probably the best review of the safety of ephedrine we have to date and sets an upper limit dose for safety which, oh so surprisingly (he says dripping with sarcasm!), the media and FDA appear to have all but ignored.
Makes great ammo when some one informs you that according to Fox News, that ephedrine has been shown to be worse for you than crack cocaine!
..........
- Cantox Report Establishes Ephedra Upper Limit, Finds FDA AERs Unhelpful
December 21, 2000 12:00am Source: F-D-C Reports, Inc.
Up to 90 mg per day of ephedrine alkaloids, based on three daily doses of 30 mg, is the safe upper limit for intake at which no adverse events were observed, according to a Cantox Health Sciences International report released Dec. 20.
'Based on the available scientific data, a [No Observed Adverse Event Level] of 90 mg/day of ephedrine alkaloids in ephedra' can be established, the report notes. The intake level was determined taking into account several studies, including eight conducted on ephedra efficacy in the obese from 1985 to 2000.
The long-awaited Cantox report - 'Safety Assessment and Determination of a Tolerable Upper Limit for Ephedra' - comes after FDA had withdrawn its 24 mg/d and 8 mg per serving ephedrine alkaloid recommendation that was to be part of the ephedra proposed reg.
The General Accounting Office raised concerns that the limits initially proposed by FDA were based on a small amount of questionable adverse event data.
The Canadian firm's report - an analysis of clinical and non-clinical studies as well as animal and toxicological data - had been delayed for several months while researchers analyzed data from an obesity study led by Columbia University's Carol Boozer and Patricia Daly, MD, formerly of Harvard University.
The Cantox report also sets a Lowest Observed Adverse Event Level of 150 mg/day, based on an evaluation of the same eight clinical studies of obese individuals. The LOAEL is the threshold at which any AE was observed.
The report adds that most of the events experienced at those dosage levels in the referenced trials 'were expected, anticipated physiological responses to ephedrine.'
With safety identified as the primary endpoint of the Cantox analysis, FDA's adverse event monitoring system also was factored into the writing of the report. However, the agency's AERs 'are not conclusive and therefore are not an adequate basis for identifying appropriate limits,' according to a Dec. 20 letter to FDA from the Council for Responsible Nutrition.
CRN, which sponsored the Cantox study, reiterates doubt as to the utility of the agency's AERs. 'Many contain little information of reliable quality. Others lack critical information needed for any possible assignment of causality,' the association noted. 'Reliable dosage information is missing from most.'
Additionally, CRN found many AERs may be misleading based on existing conditions of patients and intake of other substances. 'The overall rate of adverse effects is low, considering the amount of ephedra sold and consumed' in the U.S., the council concluded.
CRN's interpretation of FDA's AERs run counter to an analysis published by University of California at San Francisco researchers in the Dec. 21 New England Journal of Medicine.
Christine Haller, MD, and Neal Benowitz, MD, found that although the reliability of self-reported AEs raise questions, 87 of 140 adverse events included in the agency's database 'definitely,' 'probably' or 'possibly' were related to use of ephedrine alkaloid supplements. The USCF researchers urged prompt regulatory action due to the 'severity' of the AEs.
The Cantox report places particular emphasis on the recently completed Harvard/Columbia clinical trial conducted by Boozer et al., largely basing the 90 mg/d ephedrine alkaloids intake on their study protocol and findings.
The study found supplements containing ephedra and caffeine were efficacious in promoting loss of body weight and body fat in healthy obese subjects, with only 'transient increases in blood pressure and heart rate,' Boozer commented at a Dec. 20 press conference releasing the Cantox data. FDA remains opposed to combination supplements containing ephedrine and caffeine.
CRN asks that the Cantox report be added to the public comments accepted by FDA in concluding a final rule on ephedra supplements. The Dec. 20 submission of the data comes after the agency first moved the comment deadline from May 18 to July 3, then to Sept. 30.
By Will Brink
For those of you who have not seen it, to follow what is called the Cantox Review.
The Cantox Review is probably the best review of the safety of ephedrine we have to date and sets an upper limit dose for safety which, oh so surprisingly (he says dripping with sarcasm!), the media and FDA appear to have all but ignored.
Makes great ammo when some one informs you that according to Fox News, that ephedrine has been shown to be worse for you than crack cocaine!
..........
- Cantox Report Establishes Ephedra Upper Limit, Finds FDA AERs Unhelpful
December 21, 2000 12:00am Source: F-D-C Reports, Inc.
Up to 90 mg per day of ephedrine alkaloids, based on three daily doses of 30 mg, is the safe upper limit for intake at which no adverse events were observed, according to a Cantox Health Sciences International report released Dec. 20.
'Based on the available scientific data, a [No Observed Adverse Event Level] of 90 mg/day of ephedrine alkaloids in ephedra' can be established, the report notes. The intake level was determined taking into account several studies, including eight conducted on ephedra efficacy in the obese from 1985 to 2000.
The long-awaited Cantox report - 'Safety Assessment and Determination of a Tolerable Upper Limit for Ephedra' - comes after FDA had withdrawn its 24 mg/d and 8 mg per serving ephedrine alkaloid recommendation that was to be part of the ephedra proposed reg.
The General Accounting Office raised concerns that the limits initially proposed by FDA were based on a small amount of questionable adverse event data.
The Canadian firm's report - an analysis of clinical and non-clinical studies as well as animal and toxicological data - had been delayed for several months while researchers analyzed data from an obesity study led by Columbia University's Carol Boozer and Patricia Daly, MD, formerly of Harvard University.
The Cantox report also sets a Lowest Observed Adverse Event Level of 150 mg/day, based on an evaluation of the same eight clinical studies of obese individuals. The LOAEL is the threshold at which any AE was observed.
The report adds that most of the events experienced at those dosage levels in the referenced trials 'were expected, anticipated physiological responses to ephedrine.'
With safety identified as the primary endpoint of the Cantox analysis, FDA's adverse event monitoring system also was factored into the writing of the report. However, the agency's AERs 'are not conclusive and therefore are not an adequate basis for identifying appropriate limits,' according to a Dec. 20 letter to FDA from the Council for Responsible Nutrition.
CRN, which sponsored the Cantox study, reiterates doubt as to the utility of the agency's AERs. 'Many contain little information of reliable quality. Others lack critical information needed for any possible assignment of causality,' the association noted. 'Reliable dosage information is missing from most.'
Additionally, CRN found many AERs may be misleading based on existing conditions of patients and intake of other substances. 'The overall rate of adverse effects is low, considering the amount of ephedra sold and consumed' in the U.S., the council concluded.
CRN's interpretation of FDA's AERs run counter to an analysis published by University of California at San Francisco researchers in the Dec. 21 New England Journal of Medicine.
Christine Haller, MD, and Neal Benowitz, MD, found that although the reliability of self-reported AEs raise questions, 87 of 140 adverse events included in the agency's database 'definitely,' 'probably' or 'possibly' were related to use of ephedrine alkaloid supplements. The USCF researchers urged prompt regulatory action due to the 'severity' of the AEs.
The Cantox report places particular emphasis on the recently completed Harvard/Columbia clinical trial conducted by Boozer et al., largely basing the 90 mg/d ephedrine alkaloids intake on their study protocol and findings.
The study found supplements containing ephedra and caffeine were efficacious in promoting loss of body weight and body fat in healthy obese subjects, with only 'transient increases in blood pressure and heart rate,' Boozer commented at a Dec. 20 press conference releasing the Cantox data. FDA remains opposed to combination supplements containing ephedrine and caffeine.
CRN asks that the Cantox report be added to the public comments accepted by FDA in concluding a final rule on ephedra supplements. The Dec. 20 submission of the data comes after the agency first moved the comment deadline from May 18 to July 3, then to Sept. 30.