Vol. I pg. 226 FDA's Dr. Love:
"Texas and Ohio's data includes OTC drug products. This database does not. Where we identify a product afterwards as an OTC drug, we get a label, we find out that it's a drug, it's taken out of our database..."  (Emphasis added.)
     So it is not possible to compare the rate of adverse reactions reported for the ephedrine, pseudoephedrine, and phenylpropanolamine (which are the principal active ingredients in ephedra herb) containing OTCs as compared to the reports for ephedra herb containing dietary supplements.  FDA has wilfully removed OTC adverse reaction information from their database that is just as relevant to the  Committee's charge as is the adverse reaction information on the ephedra supplements.  In some respects, this OTC information that the FDA concealed from the Committee is better for determining safe dosage because it is less noisy; amounts per dose, instructions, and warnings are all specified in FDA OTC monographs.  FDA did not supply this important data on many ephedra dietary supplement adverse reaction reports.  One concludes that FDA is exhibiting its infamous bias against dietary supplements and in favor of more tightly regulated drugs.  FDA must withdraw its Rule and convene a new Committee that has access to all relevant information.


Vol. I pg. 240 Dr. Ziment:
"...I've got a report here of a "PrimeTime Live" television interview in which the CEO of the Los Angeles company that manufactures Herbal Ecstasy said that his firm alone sold 15 million units of this product. The amount sold in this country must be absolutely enormous. Is there any further details or extrapolation from this type of information to guess what the market is?"

Vol. I pg. 240 FDA's Dr. Love:
"I think generally FDA do not have this data and will have to defer to industry."

Vol. I pg. 75 Dr. Culmo:
"The most common traditional use for ma huang is to treat respiratory disorders. There is no evidence to show that it was prescribed or promoted for weight loss, athletic performance enhancement, stimulation, or euphoria, as is commonly practiced today."
     This is incorrect.  A Chinese law (over 2,000 years old) prohibits horse riders who are under the stimulating/euphoric influence of ephedra herb tea from galloping their steeds through villages.  This early DUI (driving under the influence) law shows that the Chinese have traditionally used (and sometimes misused) ephedra for more purposes than FDA and Dr. Culmo are aware of.


Vol. II pg. 68 Dr. McCausland:
"What changes is compromise. The facts don't change."
     Dr. McCausland is referring to the fact that the Committee's recommendations have changed drastically since the 1995 meeting without any significant changes in the scientific data.  This is science filtered through political considerations, which is not science at all.
Vol. II pg. 221 Dr. Ricaurte:
     "I think it's telling that just from October '95 until here we are 8, 9, 10 months later, we've already gone from an estimated safety level down 10-fold and I'm not quite sure on what basis we're doing that."


     The FDA proposes that a dietary supplement is adulterated if it contains 8 milligrams (mg.) or more of ephedrine alkaloids per serving or if its labeling suggests or recommends conditions of use that would result in intake of 8 mg. or more in a 6-hour period or a total daily intake of 24 mg. or more of ephedrine alkaloids and requires a label warning not to use the product for more than 7 days.  The transcript records of the 1996 Food Advisory Committee meeting showed no consensus for a limit on the daily dose of ephedrine alkaloid containing dietary supplements, which ranged from 0 mg. to 60 mg. of the alkaloids a day.
     The limit FDA now proposes is virtually the same limitation on the dose and length of use of ephedrine containing ephedra dietary supplements as Canada has recently done for OTC nasal decongestants containing ephedrine: 6 to 8 mg. of ephedrine per single dose repeated three to four times daily, used for no longer than 7 days.
     Dr. Micheline Ho, Chief of the Product Regulation Division, Bureau of Pharmaceutical Assessment, Vol. I pp. 106-122, appeared at the Food Advisory Committee meeting, but provided none of the data that led the Canadian government to decide on that dose.  Her presentation, however, may have influenced the final determination by FDA of the dosage limitation proposed in the rulemaking.  It also influenced some of the Committee members.  For example:
     Dr. Wang, Vol. II pg. 189, "...since in the OTC drugs ephedrine is allowed to consume, what, 150 milligrams per day on the sustained release product, maybe a 10-fold safety factor, following the Canadian way, is 15 milligrams per day for food, but again I am just pulling that as a figure." (emphasis added)
     Mr. Israelson, Vol. II pg. 223, "So, with that reservation that we're making decisions based on crucial cases without adequate evidence, I would repeat that the Canadian proposal as it's being used there is a reasonable model to follow. And my understanding  of that proposal is that it would be based on 6 to 8 milligrams of total alkaloids. That would give a daily value of 28 to 32 total alkaloids." (emphasis added)
     Dr. Fukagawa, Vol. II pg. 198, "...I would concur with the Canadian experience in that the safe level in dietary supplements would be anywhere between zero to 3.1 milligrams per day of the ephedra alkaloids, and then one can make the calculations after that with respect to ephedrine in terms of per-serving and per-day recommendations." (emphasis added)
     Mr. Israelson, Vol. II pg. 191, "...if we look at the Canadian levels, which were 6 to 8 milligrams 4 times daily, or 24 to 32 milligrams, without the addition of other stimulant materials and with good manufacturing practices, I think that that's something that the industry would be able and willing to support and comply with." (emphasis added)
     Mr. Israelson, Vol. II pg. 193, "Under DSHEA, we're able to have a lot of labeling that would essentially follow what the Canadian labeling would say, if that would be helpful to solve your concern." (emphasis added)

     The data used by the Canadian government to determine the dose and length of use were not presented at the Food Advisory Committee meetings of 1995 or 1996, nor were these data available for American public examination and comment.  The data that were presented at the 1995 and 1996 Food Advisory Committee  meetings provided no or very weak evidence to support the Canadian dose and length of use limits.  There was no Committee consensus on the dosage or duration of use limitations, yet the Canadian standard was chosen, perhaps because it was (relatively) politically safe and because Mr. Israelson, representing certain industry interests, urged the FDA to accept those limitations.
     Per the APA (Administrative Procedures Act), the Canadian standard cannot be adopted without examining the data used to establish this standard, putting these data into the public record, and permitting public comment on the data, the basis for how the standard was established.
     Under the APA, the ultimate regulation may remain controversial but at least the procedure ensures public access to the debate and identification of important issues and scientific evidence used in the agency's decisionmaking process.  If the FDA accepts the Canadian government's conclusion without further examination and critical analysis, the FDA will have bypassed the salutary purposes of notice-and-comment rulemaking.

     The adoption of another government's determination that is made without meetings open to the American public for examining the data underlying the determination are a violation of FACA (Federal Advisory Committee Act).

     Moreover, the Congress has delegated to the FDA the authority to make determinations on safety issues concerning dietary supplements. It did not and cannot delegate this authority to the Canadian government.  The FDA does not have the constitutional authority to redelegate the rulemaking authority given them by Congress to the Canadian or any other extragovernmental entity. Hence, the use of the Canadian standard is unconstitutional.  This same issue was part of a 1992 decision by the 11th U.S. Circuit Court of Appeals in which the court considered the propriety of OSHA's incorporation of the standards and findings of outside organizations (e.g., not part of OSHA, not part of the United States government and not subject to U.S. law concerning open meetings, etc.). In that case, the court vacated a "generic" OSHA rulemaking to set permissible exposure limits for 428 substances identified by the agency as air contaminants.  The court found that while OSHA may "rely on the recommendations and documentation" of outside organizations (such as the 'threshold limit values' established by the American Conference of Governmental Industrial Hygienists), the outside body's findings "did not relieve OSHA of the responsibility for making detailed findings, with adequate explanations, for all statutory criteria. (See AFL-CIO v. Occupational Safety and Health Administration. 965 F.2d 962, 984 (11th Cir. 1992)

.fo Version 12 August, 1997 4:30PM PDT;      page #

                FDA's Labeling Power Is Limited

     "[N]o one disputes the proposition that [t]he Constitution created a Federal Government of limited powers") (New York v. United States, 505 U.S. ___,___(1992) (slip op., at 7) quoting [several citations deleted]. The powers granted under the Constitution to the federal government are outlined in the Constitution (the enumerated powers) and interpreted by the U.S. Supreme Court.  The Bill of Rights describes further limits to the powers of the federal government.

     The First Amendment of the US Constitution absolutely prohibits the FDA from banning labeling that is neither misleading nor deceptive.  Indeed, Pearson & Shaw, et. al, have a First Amendment lawsuit against the FDA Commissioner before the U.S. District Court for the District of D.C. at this very moment.  (Civil Action No. 95-1865 (EGS), District Court for the District of Columbia)  If the FDA proceeds with its proposed Rule, it is asking for another lawsuit.

     The Commissioner of the U.S. Food and Drug Administration promises, in his oath of office, to "protect, defend, and uphold" the U.S. Constitution.  Unless we are to suppose that the oath of office is simply a ritual devoid of meaning and that the taking of the oath incurs no obligations, then the FDA Commissioner is obligated to seriously consider the constitutionality of his rules before it proposes them.  There can be no excuse that it is somebody else's responsibility.

     The U.S. Supreme Court has made it clear that the First Amendment does not permit government to keep information from the public in order to manipulate public choices.  That includes, for example, information on the published peer reviewed clinical trials of ephedrine as a weight loss aid.  It also includes information on the adverse effects reports received by the FDA from consumers using OTC products containing the same alkaloids as in ephedra: ephedrine, pseudoephedrine, and phenylpropanolamine (which is racemic norephedrine, the principal metabolite of ephedrine in humans.)
       If there are political factors involved in the FDA's decisionmaking, then the public has a right to know what they are.  Though the disclosure of this information may be deemed an embarrassment or inconvenient to the agency, the Constitution trumps the agency's embarrassment or inconvenience.

Quotes from the U.S. Supreme Court decision in 44 Liquormart v. Rhode Island (1996 WL 241709 (U.S.))
     "...a State's paternalistic assumption that the public will use truthful, nonmisleading commercial information unwisely cannot justify a decision to suppress it."  (at 8)
     "It is precisely this kind of choice, between the dangers of suppressing information, and the dangers of its misuse  if it is freely available, that the First Amendment makes for us." (quoting from Pittsburgh Press Co. v. Pittsburgh Comm'n on Human Relations, 413 U.S. 376, 93 S.Ct. 2553, 37 L.Ed.2d. 770 (1973)
     "In case after case following Virginia Pharmacy Bd., the Court, and individual Members of the Court, have continued to stress the importance of ... the impropriety of manipulating consumer choices or public opinion through the suppression of accurate 'commercial' information..." (J. Thomas, concurring, at 21)

                          AND COMMENTS
                 Food Advisory Committee Meeting
                       August 27-28, 1996

Vol. II pg. 12 James Prochnow, an attorney with Patton Boggs
"...a dietary supplement manufacturer is able to inform each consumer of how a supplement or one of its ingredients affects the function and structure of the human body as long as it is not promoted to prevent, diagnose, mitigate or treat or cure a disease. As a result, a statement that a particular dietary supplement is effective for weight loss, mental alertness or clarity or for just plain energy does not make that related product a drug as defined by the Federal Food, Drug and Cosmetic Act."

Vol. II pg. 262 Dr. Ricaurte
"...I'm surprised at the fact that a number of potential uses and why these compounds, products, have been distributed have been taken off the table..."
     It's no surprise. The FDA has instructed the Committee members that no use benefits may be considered in evaluating the risk/benefit of ephedra use, which requires that any mention of uses be eliminated.  Prohibiting label mention of uses is unconstitutional as well as being a gross disservice to the customer.  Note that the most common uses are ones where the consumer is able to judge whether they are receiving the promised benefits: satisfaction or reduction of appetite, weight loss, mental alertness and energy.  Note further, DSHEA does not give authority to FDA to exclude benefits of a supplement from their Committee considerations.

     Double blind placebo controlled peer reviewed published studies of the safety and effectiveness of 20 mg. ephedrine three times per day (e.g., Astrup, et al) were referred to several times during the meeting.  FDA is not ignorant of this.  FDA even officially admits "Other actions of ephedrine include stimulation of oxygen uptake and thermogenesis (heat or energy production)."  (page 15 of the proposed Rule notice.)  FDA's prohibition on the consideration of any benefits from ephedra dietary supplements is yet another example of FDA's bias against nutrient supplements, and is arbitrary, capricious, and contrary to fact.  FDA must withdraw the proposed Rule, re-convene the Committee, refrain from forbidding the members from considering all relevant facts, and develop a new rule.

Vol. I pg. 153 Dr. Ziment
"...the patients who are taking herbal medicines rather than the standard drug produced by an ethical pharmaceutical firm, that individual is looking for magic. And if somebody's looking for magic, they're not going to be bound down by scientific recommendations. So even if we limit the amount of ephedra alkaloids in the drug, a person who's looking for a particular effect is simply going to take enough of the drug to give them that effect."  "I think we're really expecting some sort of scientific control over the way people exercise free behavior, and that's not going to be easy."
     And its not constitutional, either.

Vol. II pg. 245 Dr. Benedict
"And the cat, frankly, is already out of the bag. We can remove all of the labels regarding weight loss and all of the other things and people are still going to know that this is something that they think will work."
     The FDA has required this committee to disregard any evidence for efficacy of ephedra in weight loss and anything else, but they cannot prevent that information from reaching the public.  When the public has information which they think the government (FDA) is trying to keep from them, their respect for the FDA as a source of information plummets until it is all but ignored.

     "In the May 1995 FMI [Food Marketing Institute] survey, 45% of consumers trust no one and rely on themselves for assuring the nutritional value of the food they eat, up 6% from last year [1994].  Manufacturers followed at 23%, government 13%, food stores 5% and consumer groups fell dead last at 3%.  A major shift has occurred at the expense of government, which led the list five years ago [1990]. Today, twice as many look to industry as government for assuring nutritious foods." (data from Food Marketing Institute, 1995. Trends in the United States Consumer Attitudes and the Supermarket 1995, Washington, DC, p. 57, as quoted from pg. 69 of Sloan and Stiedemann, "Guaranteed Success: How to Make Products Consumers Really Want" in J. of Nutraceuticals, Functional & Medical Foods (Haworth Press) Vol. 1 No. 1, 1997.) (emphasis added)
     The authors report in the same article that they have recently conducted proprietary research to determine what motivates consumers to purchase products in health food stores. They found (pg. 72) that 62% purchase supplements to prevent disease; 54% for increased energy; 40% to improve fitness; 31% to increase alertness; 27% to reduce stress; 25% to treat medical problems; and 21% to fight depression.  As the authors note, "...the diet and disease connection with supplements has come a long way in just a few short years."
     It is clear, from the above, that the government has suffered a decline in the extent to which the public relies upon it for nutritional information.  If the FDA continues its practice of attempting to mold consumer dietary supplement choices by limiting information (such as prohibiting uses on labels) or by providing disinformation (such as mandating bogus time limits for use), the government's public credibility will decline further until it will cease to be of any relevance whatever in the area of nutritional information.  The FDA's proposed Rule will cause great consumer harm because it will cause loss of credibility in all label warnings, not just FDA mandated bogus ones.  All this is in addition to the insurmountable constitutional problems posed by the FDA's proposed Rule.

Vol. II pg. 37 Adam Gissen
" of the most telling things has been the desire to limit the use of products like this to some duration of time. This is in spite of a complete lack of scientific information indicating that this makes the product safer or more effective."
     "In fact, ...all of the studies that have been done on ephedra have been done over a duration significantly longer than one week."
     Millions of people have used ephedra dietary supplements for periods of time far in excess of one week.  FDA's proposed Rule requiring the label to state a one week limit on duration of use will backfire in a very serious manner.  A warning that 99% of the customers know is false or misleading will reduce the credibility of the real pharmacologically justified warnings (e.g., contraindications such as cardiac arrhythmias and hypertension) thereby making the FDA directly responsible for an increase in adverse reactions and deaths.

Vol. I pg. 42 Dr. Larsen
The working group "agreed that the ephedrine alkaloid limit should be below that for currently marketed OTC drugs, and label instructions should advise consumers that more frequent use or using more than instructed does not increase effectiveness."            This is patently false and will reduce consumer confidence in label warnings.  Instructions ought to advise consumers that more frequent use or using more than instructed increases risk of adverse reactions, not the obviously bogus statement that it does not increase effectiveness.  FDA seems to believe that dietary supplement consumers are all idiots.  This is untrue; market surveys have repeatedly shown that dietary supplement customers average considerably above the general population in formal education and intelligence.  The FDA's Rule mandates label disinformation, and serious adverse consequences will inevitably occur unless the proposed Rule is withdrawn, new Committee meetings held, and a modified scrupulously honest Rule subsequently re-issued.

Vol. 1 pg. 280 Dr. Jones
"Finally, if the above is not sufficient, one extra line on the label will certainly kill the herbal street drug look-alike market: Warning -- exceeding the maximum permitted intake may result in temporary impotence."
"Those who understand the roles of the catecholamines in mammalian physiology will appreciate the scientific rationale for this cautionary statement."
     Dr. Jones is entirely correct.  His statement is not a bogus warning; it is truthful, not misleading, useful, and likely to be very effective.

     The FDA does have a constitutionally legitimate role in assuring that dietary supplements sold in interstate commerce have adequate warnings.  No warnings or inadequate warnings were found on a disproportionate number of products associated with adverse reactions:

Vol. I pg. 31 Ms. Binzer
(From 1995 working group meeting): Approximately 15 percent of all the dietary supplements collected in the review did not bear warning statements of any kind; 85 percent of the dietary supplements bore warning statements ranging from very general states, such as "consult your physician before beginning any nutritional or exercise program" to more specific warning statements, which tended to include recommendations not to use the product if consumers suffers from various medical conditions, experiences certain adverse effects, is taking certain medications, or is under a certain age.

Vol. I pg. 91 Frank Wickham
"...we've had this death of this young man due to a toxic level of ephedrine, taking it, of course, not having any idea that the product was dangerous..."  (emphasis added)
     Apparently there were no warnings on the label.  This is certainly a legitimate and useful area for FDA action -- so long as the FDA mandated warnings are truthful and not misleading, rather than the proposed disinformation which will reduce credibility of all label warnings to the consumer.

Vol. I pg. 121 Ms. Ho (Canadian official)
"Subsequently, perhaps due to misuse or the fact that as a food the product did not contain any of the warning statements present in drug labeling, and because consumers may have exceeded recommended usage directions, two serious adverse reactions were reported in 1993"  "Although as in most cases of adverse event reporting cause-and-effect relationship are not firmly established..."  (emphasis added)
     On the basis of misuse and/or a lack of important warnings, Canada now disallows the inclusion of ephedra as a non-medicinal ingredient in traditional herbal remedies and its use as food is no longer permitted rather than mandating appropriate warning labels.  Canada does not have a U.S. Constitution, DSHEA (Dietary Supplement Health and Education Act), a FACA (Federal Advisory Committee Act), nor an APA (Administrative Procedure Act) and hence can not be used as a model for FDA action.

Vol. I pg. 133 Dr. Chassy
"You seem to have set national policy in Canada, if I heard you correctly, on the basis of two serious cases, and this committee is being asked to address itself to the issue of association versus scientific evidence of causality that the ephedrine alkaloids cause serious consequences. Could you share with us those serious cases and how you reached the determination, which you obviously did, that there was a causal relationship?"

Vol. I pg. 133 Ms. Ho (Canadian government representative)
"I don't have a lot of details about the two cases. I know that one was related to cardiovascular effects in a middle-aged male, I think, with a predisposing heart condition. The other one was a teenager who abused the drug product."  "People were being told ignore label directions and, yes, do take ten tablets instead of two tablets today if you want the product to be effective or if you want to lose weight faster."  (emphasis added)
     If the FDA limits dosage to the Canadian rule of 8 mg. ephedra alkaloids three times per day for a maximum of one week instead of the usual informal industry standard dose of 20 mg. ephedra alkaloids three times per day without time limit, the above is exactly what will happen in the U.S.  The FDA's ill designed proposed Rule is about to destroy the integrity and credibility of the ephedra dietary supplement warning and instruction labels and thereby increase the incidence of adverse reactions.  This is not a theory; it has already happened in Canada and FDA cannot plead ignorance of the consequences.

Vol. I pg. 157 Dr. David Kessler
"We have two very real cases that the medical examiners have at least associated with the use of the products, the compounds under discussion. We need to reduce those risks. You're never going to reduce it to zero. You're never going to have somebody not do something very stupid that you can't predict. You can't safeguard against everything in this world. But I am convinced that those two individuals died needlessly because the information wasn't communicated to them about the hazards associated with these products."  (emphasis added)
     Dr. Kessler is correct.  However, he did not state here what the labels on these products actually say about doses and about warnings. Were there no or inadequate warnings on the labels or did the individuals misuse the products?

Vol. I pg. 169 Constance Hardy (referring to FDA's second market review in April 1966, which identified 125 different dietary supplement products containing ephedrine alkaloids, some being duplicates (not necessarily the same formulation) of products collected in the first market review)
"Product labels, however, did not necessarily specify the form of the botanical source of ephedrine alkaloids, that is, whether it was an extract, a concentrate, or raw herb."  "In some cases where the ingredient was listed as ma huang or ephedra without any further clarifying terms such as an extract or a concentrate, the ephedrine analytical values found on the products were higher than could be expected for the range of ephedrine alkaloids known to be present in the natural herb."
Vol. I pg. 174 Hardy
"...26 products had no warning statements at all; a general statement was noted on 14; disease or condition states were on 86 products; drug interaction statements were on 37; adverse effects noted were on 25 products; maximum daily use imperative--that's something to the effect 'Do not exceed'--you know, it specifically has the word 'exceed.'  That was on 35 of the products, and age restrictions was 35."

Vol. I pg. 205 Dr. Love
Death of a 20 year old male college student who took eight tablets of an ephedra-containing "street drug alternative" although the label instructions were to take four and not to exceed four in a 24 hour period.  The coroner's report stated (pg. 206) that the cause of death was "cardiac arrhythmia due to the synergistic effects of ephedrine, pseudoephedrine, phenylpropanolamine, and caffeine."
     Dosage information was not given by Dr. Love; however, this is clearly a case of drug abuse, not use in accord with the label.  We agree with FDA that labeling that promotes an ephedra dietary supplement as a street drug look-alike (e.g., Herbal Ecstasy) is false and misleading and can and should be prohibited in interstate commerce.

Vol. I pg. 275 Jones
"In the United States, our market surveillance covers over 300,000 users of ephedra herb with a particular range of products and has failed to reveal any serious adverse effects. We have had occasional minor complaints, but these were generally associated with failure to follow label instructions -- in other words, failing to start with a low intake and building up to a comfortable level...taking it too late and being kept awake at night--and these complaints did not occur in those who followed label instructions."  "...the products concerned are manufactured under GMP conditions to a strict specification, and we analyzed both incoming raw materials and the finished product for ephedrine alkaloids and alkaloid pattern."

Vol. II pg. 37 Adam Gissen
"...these products have negative tolerance when looking at their effects on the central nervous system."
     "And that's one of the things that makes something like ephedra a real poor alternative to speed. People develop tolerance, very very rapidly to the effects of ephedra on the central nervous system, especially used responsibly, in other words, starting at a low dose and slowly building up to some recommended level."
     Tolerance develops very rapidly to the cardiovascular effects of ephedrine, too.  Several members of the Committee agreed that slowly increasing the dose over a few days would reduce the risks of adverse reactions.  We agree with this, and believe that it should be part of the label instructions.  Unfortunately, FDA's proposed rule requiring labeling to state a maximum use period of seven days makes that impossible, and hence this labeling requirement should be withdrawn.  Instructions recommending a slow build-up to a full dose over a period of a few days to several days will reduce the adverse reactions far more effectively than a seven day limit which will be almost universally ignored.

     Commenters Pearson & Shaw license formulations containing approximately 1.8 grams per dose of ground ephedra herb (the amount being adjusted on the basis of lot analyses to contain a total of 20 mg. of ephedra alkaloids).  No ephedra extracts are used in this product, there is no caffeine or other methylxanthines, and it contains no synthetic ephedrine, pseudoephedrine, or phenylpropanolamine.  Here are the label instructions:

"DIRECTIONS: Add 4 ounces of hot or cold water to one heaping tablespoon of mix. Stir briskly. Allow the mixed tea to stand for a couple of minutes. DO NOT EXCEED THREE SERVINGS A DAY! Keep in a cool, dry place. Keep lid tightly closed when not in use."
"SUGGESTED USAGE: For first three days, drink one serving in the morning as soon as you wake up. For the next three days, drink a second serving before lunch. From then on, drink a third serving one hour before dinner."

"CAUTION: KEEP OUT OF REACH OF CHILDREN. Not for use by children, pregnant or lactating women. May cause insomnia in sensitive individuals, especially if taken too soon before bedtime. Consult your physician if you are taking asthma medications, anorectic (appetite suppressing) drugs, antidepressants, or cardiovascular medications. Do not consume this tea if you are pregnant or lactating or have high blood pressure, cardiovascular disease (especially cardiac arrhythmia), diabetes, prostatic hypertrophy, glaucoma (angle closure), hyperthyroidism, psychosis, thyroid disease, or Wilson's disease. Do not drink this tea within 14 days after taking MAO (monoamine oxidase) inhibitor drugs. If symptoms of allergy develop, discontinue use. Avoid the use of antacids containing aluminum with this product."

     The label also discloses that the ingredients include ephedra herb powder.  We wanted to put "contains 20 mg. ephedra alkaloids (primarily ephedrine)" on the label but were advised by one of our attorneys (who worked for the FDA for many years) that we should not do it because the FDA might use this statement as the basis for declaring our formulation to be a new unapproved drug.  We believe that all ephedra herb containing products should disclose that information on the labels, stating the total amount per dose of ephedra alkaloids.

     Note that these instructions increase the dose from the initial dose of 20. mg. ephedra alkaloids once per day to the final 20 mg. three times per day over a period of seven days.  This very conservative rate of daily dose increase will be made unfeasible by the FDA's proposed rule mandating a labeled maximum use period of seven days; only one day of full dose and full effect would be allowed, hence rendering a product with these instructions ineffective and uncompetitive.  For all practical purposes, the FDA may as well prohibit all labeling that instructs the customer to slowly increase their dose over a period of several days.

     FDA has not met DSHEA's burden of proof for their requirement that the labeling limit use to seven days. A number of comments by Committee members and consultants also expressed doubts about the basis for such a limit. FDA's primary interest in the seven day limit appears to be their use of it to prohibit any labeling which would suggest uses which would require longer than seven days.  (See pg. 36 of the Proposed Rule notice, "a. Claims that promote long-term use.")  FDA thereby attempts an end run around the First Amendment, believing that their seven day rule may receive more judicial leniency than the strict scrutiny that would apply to a prior restraint on such truthful non-misleading speech as labeling suggesting weight loss benefits when used for longer periods of time (eg. longer than a week).

     In order to keep the label information-free regarding possible weight loss benefits, FDA ignores the increased risk to consumer safety.  FDA is well aware that the development of tolerance to both the CNS and cardiovascular effects of ephedra alkaloids reduces the risk of these adverse reactions.  They even admit this when they say on pg. 48 of the proposed Rule Notice, "FDA requests comments on whether the warning statement should disclose the possibility of increasing the risk of adverse events by a pattern of stopping and starting use."  This is another iatrogenic risk created by the FDA's proposed 7 day use limit, which will cause those consumers who heed it to repeatedly start and stop taking the supplement.

     FDA proposes to require that labels say "Taking more than the recommended serving may cause heart attack, stroke, seizure, or death."  While it is true that taking too much of anything (including oxygen and water) can cause death, FDA has not met its DSHEA burden of proof that a warning of this severity is appropriate for their proposed label Rule specifying less than 8 mg. ephedra alkaloids three times a day for a week maximum.  With such a low permitted dose, most consumers will continue to take more than 8 mg. TID, just as consumers have been doing for many years.  Unfortunately, consumers won't get any information from labels on how much more it is reasonable to take.  Those who take 2 to 3 times the label dose will be receiving about the same amount of ephedra alkaloids per dose that consumers have been taking for years.  Those who know that the FDA has drastically reduced the dose -- but not by exactly how much -- may take much more, thereby being subject to an increased risk of adverse reactions or even death.

     The application of the FDA's above Rule warning to such a low dose (8 mg. TID) will be considered bogus by essentially all consumers who have previous experience with ephedra supplements, thereby casting unwarranted doubt on real and truly justified warnings such as "Don't take this product if you have hypertension or a cardiac arrhythmia."  The FDA's above proposed warning would make much more sense if applied to a product containing 20 mg. of ephedra alkaloids or more, that is, if it applied to doses of the size of those that have been widely used for many years.  There will be a serious cost involved if FDA requires the arbitrary and capricious use of inappropriately severe warnings -- a cost in increased adverse reactions and death due to loss of consumer confidence in fully justified warnings.

     On page 47 of the 100 page proposed Rule notice, FDA proposes to require the statement "Larger quantities may not be more effective."  As we have commented above, this is not only misleading (since larger quantities may also be more effective), it is so obviously deceptive (particularly with respect to the most common use, weight loss) that the credibility of all warnings on the label will be seriously reduced.

     FDA then disinforms both the people of the United States and the Congress by saying "The agency is not aware of any data or other information that establishes that there are benefits from the use of dietary supplements containing ephedra alkaloids."  (See pg. 47 of the proposed Rule Notice.)  This is a lie.  Ephedrine is the principal ephedra alkaloid.  The transcripts of the meetings show that the FDA Committee is well aware of reputable peer reviewed published double blind placebo controlled clinical trials with ephedrine (though not necessarily on the same amount of the same compound when contained in the herb) that show that it can be effective for weight loss.  Indeed, (inconsistently) these studies are even discussed on pg. 17-19 of the proposed Rule Notice.  An advertisement that was equally misleading would be illegal.

     In any case, FDA's attempt to require more severe warnings on ephedra dietary supplement labels than on OTC (over the counter, no prescription required) drugs containing larger doses of the same alkaloids contained in ephedra supplements is arbitrary, capricious, contrary to reason, and is a further indication of FDA's bias against dietary supplements and in favor of more heavily regulated OTC drugs.

     On pg. 51 of the proposed Rule Notice, FDA says:
"The agency considered the applicability of OTC drug data and tentatively concluded that these data, which involve use in a restricted population (physician-diagnosed mild asthmatics) under limited directions for use (i.e., not to exceed 12.5 to 25 mg. every 4 hours, not to exceed 150 mg. in 24 hours) and with warnings and contraindications for use, has no application here. The determination of safety for drugs is based on a weighing of the proven benefits of the use of the product against the risks. This approach may not be used with foods under section 402(a) of the act. The only question for food use under this section is whether it will cause harm or not. While the concept of "unreasonable risk" as stated in section 402(f)(1)(A) of the act, may imply that some evaluation of effects, including risks and benefits, is appropriate for dietary supplements, it is not necessary to reach that question here, because, as stated above, there are no demonstrated benefits for ephedrine alkaloids.  Moreover, the risks attendant on consuming dietary supplements containing levels of ephedrine permitted in oral bronchodilator drugs (12.5 to 25 mg. ephedrine per dose) are manifest."

     COMMENT:  The FTC concludes "tentatively" that the OTC drug data on ephedra alkaloid containing products has no application here.  The FDA argues that the OTC data apply to a restricted population with directions for limited use and with warnings and contraindications.  However, OTC drugs may be purchased freely by anyone (not just a restricted population) and used for any length of time and at any dosage their purchasers may choose.  Adverse events resulting from abuse and improper use of the OTC drugs may provide valuable data for evaluating the adverse events resulting from the abuse and misuse of the dietary supplements containing ephedra alkaloids.  We reviewed published reports of adverse events of individuals taking ephedrine, phenylpropanolamine, and pseudoephedrine containing products that are exhibits to the FDA's proposed rulemaking (exhibits 56, 60, 62, 63, 67, 68, 69, 70, 71, 73, 100, and 128). Our review indicates that most of the adverse events were a result of abuse or misuse of the products.

     The FDA argues that the safety for drugs is based on a weighing of the proven benefits of the use of the product against the risks and that benefits may not be considered for foods, only whether they will cause harm or not.  The FDA admits that the concept of "unreasonable risk" (as stated in section 402(f)(1)(A) of the act) may imply that "some evaluation of effects, including risks and benefits, is appropriate for dietary supplements, it is not necessary to reach that question here because...there are no demonstrated benefits for ephedrine alkaloids." There are a number of published peer-reviewed studies indicating that ephedrine has a thermogenic effect that helps with weight loss.  But, in the final analysis, it is consumers using these dietary supplements who are the judge of whether they are getting benefits or not.  In the case of weight loss or energy, a consumer is quite capable of evaluating whether he or she has lost weight or gained energy.  If the FDA is going to assume that nothing has a "demonstrated" benefit other than those very few dietary supplements for which it has approved "health claims," then nearly all dietary supplements will be denied a risk/benefit analysis.  This is unreasonable, arbitrary, and capricious.
     The FDA then states that "the risks attendant on consuming dietary supplements containing levels of ephedrine permitted in oral bronchodilator drugs (12.5 to 25 mg. ephedrine per dose) are manifest."  A number of comments during the Food Advisory Committee meeting by consultants and Committee members who were experienced in their practices with the use of ephedrine for bronchodilation indicated that when used according to label instructions, these risks are not great.  The real problem, with both OTC and dietary supplements containing ephedra alkaloids, is abuse and misuse by careless consumers.

.fo Version of 12 August, 1997 4:50 PM PDT;       page #
                     AND TOTAL DOSE PER DAY

                          AND COMMENTS

     Although we have already made several comments as to why the FDA should not limit ephedra alkaloid to 8 mg. per dose with a total dose of 24 mg. per day, but instead should set the limit at 20 mg. per dose, 60 mg. per day, we hereby provide further reasons for this conclusion.

     The most fundamental reason that the FDA has not met the DSHEA burden of proof on their dose limits is that ephedra dietary supplements are already much safer than food in common form.  This is true even though the doses found in current products are given by the FDA as having a median of 17 mg. per dose with a mean of 30 mg. per dose (standard deviation = +-31 mg.).  Unless FDA is allowed to set far higher standards of safety for dietary supplements than for food in common form (which is not allowed by DSHEA), a 20 mg. dose cannot be considered unreasonably unsafe when used as directed.  We believe that a dose limit is needed (we consider a 110 mg. dose to be grossly irresponsible), and that 20 mg. total ephedra alkaloids per dose is reasonable as demonstrated by the current safety record.  A 20 mg. per dose limit with a total dose of 60 mg. per day is realistic and will be accepted by consumers; the FDA's proposed limits will be generally ignored by consumers, thereby reducing the credibility of the other label warnings and instructions, and causing consumers to take multiple doses -- sometimes too many multiples -- thereby causing avoidable adverse reactions and harm.

Vol. I pg. 206 Dr. Love
In a summary of the FDA analyses on products associated with adverse event reports "where we had information on how the consumer used the product so that we could calculate the milligrams per consumer use," the products range from one product at 0 all the way up to over 50.  The mean dosage was approximately 30 mg. plus or minus 31. (!!) One of the supposedly ephedra-containing products associated with an adverse event had zero ephedra alkaloids in it.  What were the rest of the ingredients??  FDA doesn't say.

Vol. II pg. 234 Dr. Askew
"From the information that has been presented to me, I've been impressed by the amount of people that are actually consuming this product without having adverse reactions, and I draw more my conclusions as to its relative safety from that than from the adverse incidence reports which are very difficult to deal with because of the nature of the reports."

Vol. I pg. 153 Dr. Ziment
"...the patients who are taking herbal medicines rather than the standard drug produced by an ethical pharmaceutical firm, that individual is looking for magic. And if somebody's looking for magic, they're not going to be bound down by scientific recommendations. So even if we limit the amount of ephedra alkaloids in the drug, a person who's looking for a particular effect is simply going to take enough of the drug to give them that effect."  "I think we're really expecting some sort of scientific control over the way people exercise free behavior, and that's not going to be easy."

     A second major reason why FDA cannot set their dose limits at 8 mg. per dose and 24 mg. per day is that OTC drugs are readily available to anyone for any purpose at any supermarket that contain 24 mg. of ephedrine and 120 mg. of theophylline, a caffeine like stimulant methylxanthine, with a 150 mg. per day of ephedrine label limit.  FDA's Rule dose is not only arbitrarily and capriciously far lower, but it lacks reason; no increase in safety will occure if current ephedra supplement customers switch to an OTC product with higher doses of ephedrine and methylxanthenes than the typical ephedra herb dietary supplement.

Vol. II pg. 104 Dr. Ziment
"If we say ma huang and ephedra products in dietary supplements are unacceptable does this create the concept that people who want to take these drugs have to buy orthodox ephedrine over-the-counter or would it give the message that we think people should go to MDs and have them evaluate the patient and then prescribe the ephedra products?" (emphasis added)

     A third major reason that the FDA cannot impose the Rule doses is that it is far lower than the doses traditionally used in ephedra herb teas.  FDA is legally required to allow the marketing of grandfathered products in traditional doses provided the labels are unchanged.  It would be regrettable if FDA forced the industry to take this route because the original labels had few if any warnings and no drug interaction precautions.  If this occurred, it would be harm caused by the FDA's proposed Rule, not harm inherent in the herb.

Vol. II pg. 105 Dr. Croom
"If you take the Chinese pharmacopeia the range of ma huang or ephedra that you can use is 1.5 to 9 grams. Actually most of the formulas used by practitioners that I've seen range around 6 grams but there is a ma huang tong that is based on a 9-gram dose."  "If you take the more moderate, 5 to 6 grams, and you say the Japanese pharmacopeia is the only official source that sets a minimum, which is .6 percent, if you take in commerce, no matter what these range of values you've seen, the average is probably 1.2 percent.  Then you will find that if you took 5 grams, which is approximately two tablespoons -- I have cut it and weighed it myself -- that you will find that at a .6 to a 1.2 that you are getting 15 to 30 milligrams per tablespoon in ma huang tea for the minimum concentration of .6 to an average of 1.2  If you take the two tablespoons, therefore, you are at the same dose that we found most physicians using, between 25 and 50 for the pure compounds." (emphasis added)
     The USP standard for ephedra herb is at least 1.2% ephedra alkaloids.  Our own extensive experience is that most of the herb available on the US market is between 1.2 and 1.8%, in agreement with the observations of Dr. Croom.

Vol. II pg. 172 Dr. Croom
"The Chinese herb itself has between generally 1 and 2 percent [ephedrine alkaloids].  An average dose of the herb is 6 grams. That means you have between 6 and 12 milligrams of alkaloids there. So I'm taking traditional long-term use, what do we know from others, not to justify the use, but to say for safety where are the numbers..."
     Incorrect math.  The 6 grams of herb contains between 60 and 120 milligrams of alkaloids.

Vol. II pg. 219 Dr. Fong
Here, Dr. Fong states that the German Commission E dosage [no prescription required] is 1 to 6 grams per dose and that the "Japanese and the Chinese pharmacopeia of ephedrine alkaloid content in ephedra of 0.7 and 0.8 percent, not less than."
     This calculates to a range of 7 milligrams to 48 milligrams a serving, though Dr. Fong refers only to the 7 milligrams.  With a more likely ephedrine content, it calculates to 12 mg. to 72 mg. per dose.

Vol. I pg. 44 Ms. Bowen
"...we published a proposal in 1995 to remove ephedrine-containing products for bronchodilator use from the marketplace due to three events, one being diversion and difficulty containing that by the DEA under their current rulemakings, and also some evidence [emphasis added] in our adverse event reporting system of misuse of the products"        Removal was not proposed because after 50 years or so of use these products were suddenly found to be unreasonable unsafe when used as directed.  What evidence of misuse of products is in the adverse event reporting system?  FDA deleted all OTC data from their database and refused to supply it to Committee members even though Committee members asked for it.  Note, too, that while the FDA mentions this previously proposed (and failed) removal of the ephedrine alkaloid containing bronchodilators in the Rule Notice, FDA deceptively leaves the false impression that this previous proposed removal was for safety reasons, not because ephedrine was being diverted for use as a precursor of illicit blackmarket methamphetamine.

Vol. I pg. 45 Ms. Bowen
"over the counter bronchodilators has single dose of 12.5 to 25 mg. of ephedrine, not to exceed 150 mg. a day."
     Primatene tablets, containing 24 mg. ephedrine plus 120 mg. theophylline, are still on the market.  So are products containing pseudoephedrine (the second major ephedra alkaloid) and phenylpropanolamine (a racemic version of norephedrine, the principal human metaabolite of ephedrine.  The maximum dose of OTC pseudoephedrine is 60 mg., and the maximum OTC dose of phenylpropanolamine is 120 mg.

Vol. I pg. 46 Dr. Jasinski (the drug abuse expert)
"Most of the concern of the DEA is not with ephedrine at a retail level."

Vol. I pg. 72 Dr. Askew
"Now, also the question has been raised as to whether or not the OTC drugs are experiencing the same incidence of adverse reaction reports as the food products are, and I think this is probably a fair question."

Vol. I pg. 73 Dr. Culmo
"TDH [Texas Dept. of Health] provided oral and written comments in October 1995 to the committee's working group on ma huang. At that time, we indicated that TDH had collected 900 reports of adverse reactions to ephedrine-containing products for Texas citizens; that was 400 from over-the-counter or OTC drug products and 500 from food products. We now have substantially more than a thousand reports of injuries or adverse events."  (emphasis added)

Vol. I pg. 162 Dr. Ziment (expert on the use of ephedrine in asthma and other respiratory diseases)
"As somebody who has been treating asthma for a long time, I regard ephedrine as an asthma drug. And I think I know that the dose is something between 50 and 60 mg. three or four times a day. And I rarely have changed those dosages in treating patients, whatever their underlying or secondary condition may be. So I think we should use those dosages as a starting dose of what is safe and reasonable, and make the equivalent dose of ma huang equated to those dosages of pure ephedrine." (emphasis added)

Vol. II pg. 165 Dr. Ziment
"...this implication that more than seven days could be hazardous, as opposed to less than seven days in some sort of long-term fashion. I just don't see the evidence for that."

Vol. II pg. 240 Dr. Katz
"When I looked at this question, I had to divorce my experience as a physician with ephedrine since as a practicing pediatric pulmonologist back in the late '70s and early '80s we used a lot of ephedrine for children with asthma. It has been supplanted by obviously much better drugs, but we saw very few serious adverse effects."

Vol. II pg. 105 Dr. Croom
"One of the things that we discussed in the committee [1995 working group] was certainly that when you set the level at 25 total ephedrine alkaloids, but ephedrine being seen as the most cardioactive and potentially the largest side effect being lower at 20, was one of the things that was discussed."  "...there was also consensus certainly between Dr. Tyler and I and this was also forwarded to the charman, that if things were used in combination with things like caffeine that we were both in agreement that ratio--this is individual dose--should be a 10/15 level, not a 20/25, because of what was unknown we felt like in the lack of data, even though there is some data." (emphasis added)
     We agree with Dr. Croom and Dr. Tyler: 20 mg. ephedrine in 25 mg. total ephedra alkaloids per dose if there is no caffeine or other methylxanthines, 10/15 mg. per dose if the product contains caffeine or other methylxanthines, with a maximum of three doses per day.

Vol. II pg. 57 Gordon Peterson
"And I then decided I would look at what is considered the pharmacological bible, Goodman's and Gilman's, in their book, Pharmacological Basis of Therapeutics, and found ephedrine listed as follows and I quote:  'The usual oral dose is 25 to 50 milligrams repeated every three to four hours for a 150 to 300 milligrams per day dose.'  "I then ... looked in the American Hospital Association's Hospital Formulary which recommends the following:  'The usual adult dosage is 25 to 50 milligrams every three to four hours.'"  "Another quote from this American Hospital Association's Formulary is... 'For self medication in children 12 years old and older, the usual dosage is 12.5 to 25 milligrams every four hours.'"  "It goes on....'For children 6 to 12 years of age, ephedrine is safe at 6.25 to 12.5 milligrams every four hours.'"

Vol. II pg. 58 Mr. Peterson
"Another study. This one comes from the International Journal of Obesity 1993, and I quote:  'We conclude that the ephedrine/caffeine combination is safe and effective in long-term treatment in improving and maintaining weight loss.'" "'The side effects are minor and transient and no clinically relevant withdrawal symptoms have been observed.'"

Vol. II pg. 75 Mr. Appler
"I find it difficult to believe on any scientific or toxicological basis that my ingestion by inhalation [sic, this should be per oral] in a health compromised population, 25 milligrams single dose, 150 a day, is safe as declared by FDA and its experts. But that oral ingestion at the levels you recommended last October [1995 working group] 20 milligrams of ephedrine alkaloids, 25 total alkaloids, AD/100 per day, is possibly the hazard that FDA has tried to present it as."
"If that were so, we would be seeing literally thousands of injuries among the tens of millions of daily users of bronchodilator products. Needless to say, despite the far more sophisticated system FDA has for capturing drug reactions, no such substantial reports for bronchodilator use have appeared."
     Not only that, but Primatene tablets containing ephedrine are available OTC, meaning that anyone can walk into a supermarket or drug store and buy them and then use or misuse them any way they wish.  If significant adverse reactions were occuring in users (rather than high dose abusers) of Primatene tablets, the lawsuits alone would have driven Primatene tablets off the market long ago.

Vol. II pg. 16 Mr. Prochnow
This testimony concerns an approved protocol for a clinical study of ephedrine:  "The Institutional Review Boards of Harvard and Vanderbilt on a preliminary test they go through would not probably have approved the protocol for these studies unless they felt that there was a good possibility or probability that the levels of ephedrine that were going to be tested, about 25 milligrams per dosage... was an appropriate safe level. ... the parameters of the protocol included at least 30 milligrams of caffeine per serving size and at least 25 milligrams of ephedrine alkaloids per serving size."

Vol. II pg. 111 Dr. Ricaurte
"What I'm puzzled by is the apparent disconnect between the data on the products we've been discussing the last day and a half and what several members of the committee has said is our 50-year long experience with OTC ephedrine-containing products." "...the issues of some of the adverse effects, certainly they haven't loomed as major concerns with OTC products contained in the ephedra alkaloids.  Is it the reporting system?  ...if we are going to use, as was suggested by the Special Working Group before [1995], as a benchmark or a starting point on dosage issues, prior experience with OTC products containing the ephedra alkaloids, then I think the issue of why the apparent disconnect exists is critical."

Vol. II pg. 111 Dr. Love
"Of course, the reporting systems are different and the products are very different."
     The FDA is focusing on ephedrine and other ephedra alkaloids. Thus, it is reasonable to compare adverse reactions with other products containing ephedrine and other ephedra alkaloids.  The admission by Dr. Love that the reporting systems are different may be pertinent in that there has been no FDA publicity concerning alleged dangers of the use of the OTC ephedrine, pseudoephedrine, and phenylpropanolamine products during the period when FDA has been publicizing the alleged dangers of dietary supplements containing those alkaloids.

Vol. II pg. 112 Dr. Love
"The product from one manufacturer containing ephedrine plus these other ingredients cannot be compared necessarily to a product from another manufacturer that may be listed as containing the same ingredients.  You don't know what their source is, you don't know what their potency or anything else is. And because there can be natural variations, even the products from a single manufacturer can have lot-to-lot and batch-to-batch variability that may well affect their safety profile."
     This is a good reason for doing a competent followup on reports of adverse reactions, to find out what the consumer actually ingested.  The FDA cannot just say "we don't know anything so let's just ban all products containing ingredients that may have (but we don't know) been involved."

Vol. II pg. 115 Dr. Ziment
"I want to follow-up what Dr. Ricaurte was referring to. I still don't feel that I understand what the reported and recognized dangers are of taking either over-the-counter ephedrine or even pseudoephedrine or phenylpropanolamine. And I certainly  have prescribed agents of this nature. And I feel there is a disconnect in that we are hearing a lot about the dangers of ma huang and ephedrine without knowing the dangers of comparable orthodox drugs." (emphasis added)

Vol. II pg. 116 Dr. Ziment
"Well, Dr. Love, perhaps can give us a little bit more information on the side effects that are actually recorded, even on a year-to-year basis in adverse drug reports on the legitimate ephedrine products."

Vol. II pg. 116 Dr. Love
"I don't have that data and I will defer to people from Drugs on that."  (emphasis added)
     However, no people from Drugs appeared at this meeting to inform the committee members on these data.  It is appalling that the FDA did not provide this clearly very relevant, very important information that is indispensable to making a scientific judgment on the risks in using products containing ephedrine alkaloids, particularly when this data was identified as important and requested by Committee members.

Vol. II pg. 116 Dr. Weintraub
"...there are no serious adverse effects within the dose range that is printed on the label. There are some adverse effects that occur due to taking of products with different names which may mislead the public or be sort of fanciful names that would indicate a different indication other than bronchial dilation.  So, but, as bronchial dilator, used as a bronchodilator there are no major adverse effects." (emphasis added)

Vol. II pg. 134 Dr. Kessler
"...the question about safety that we're asking you today is safety in the c

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator