INTERNATIONAL OBESITY MEDICAL JOURNAL PUBLISHES IMPORTANT, LONG-TERM CLINICAL DATA ON EPHEDRA’S SAFETY AND BENEFITS

Overweight men and women seeking healthier lifestyles through proper nutrition, exercise and use of herbal supplements just received good news about dietary supplements containing Ephedra. The most comprehensive study on Ephedra to date, conducted by researchers at the prestigious Harvard and Columbia Universities, confirms the safety and benefits of Ephedra dietary supplements in healthy Americans when used as directed. The study reiterates the need for appropriate serving limits, warnings, and precautions for Ephedra dietary supplements that responsible industry manufacturers and distributors are using and advocating.

Doctors Boozer and Daly concluded in their published study that

“…herbal ephedrine/caffeine herbal supplements, when used as directed by healthy overweight men and women in combination with healthy diet and exercise habits, may be beneficial for weight reduction without significantly increased risk of adverse events.”

The new study on Ephedra safety and effectiveness is published in the May issue of The International Journal of Obesity, a respected British medical journal. Study authors, Dr. Boozer and Dr. Patricia Daly (formerly from Beth Israel-Deaconess Medical Center, Harvard Medical School), tested 167 subjects in a double-blind placebo controlled clinical trial. Participants took an herbal combination of Ma Huang (Ephedra) and Kola Nut (a source of caffeine) at a daily serving level of 90/192 mg (ephedrine alkaloids/caffeine, two tablets, three times a day) for a period of six months and were counseled on proper nutrition and exercise.

The study further concluded that

“extrapolation of the present findings to usage by individuals with medical complications (diabetes, heart disease, etc) is unwarranted and usage by such individuals is contra-indicated on labels of commercial products.”

“Losing 11 to 12 pounds, as this study accomplished, can have a dramatic effect on reducing the serious health risks of being overweight. This new study is important not only because it showed increased weight loss over diet and exercise alone, but because its results are consistent with those of previous studies. Beneficial effects on body composition and cholesterol levels were produced without causing significant adverse events. This study helps confirm that otherwise healthy Americans have choices to help them lose weight,”

concluded Steven Dentali, PhD., vice president for Scientific & Technical Affairs, American Herbal Products Association.

6 Quick Facts About Ephedra

FACT #1: Ephedra (Ma Huang) is an herbal ingredient found in dietary supplements. Dietary supplements containing Ephedra include ephedrine alkaloids, which are complex combinations of nitrogen and oxygen.

FACT #2: Based on surveys conducted in 1999, between 12 and 17 million Americans consume more than three billion servings of Ephedra products every year.

FACT #3: Existing data—from consumption patterns to clinical research— establish that Ephedra is safe and effective when used as directed. Clinical studies are accepted as the gold standard for establishing safety and benefits.

FACT #4: The only indication of side effects comes from a small number of adverse event reports (AERs), which even critics of Ephedra concede do not provide scientific proof that Ephedra causes adverse events. A conservative risk assessment based by Cantox Health Sciences International shows that Ephedra is safe when taken as directed.

FACT #5: For years, Ephedra manufacturers have urged the Food and Drug Administration to mandate consumer labeling and manufacturing safeguards to reduce the risk of consumer misuse. The FDA response has been to do nothing, thereby leaving behind a cloud of confusion and doubt about Ephedra products.

FACT #6: With obesity reaching epidemic levels in our nation, weight-loss products like Ephedra have never been more valued by consumers or needed to combat the public health costs associated with weight-related health problem.

Serving Limits, Warnings and Precautions for Taking Ephedra Products

1. Do not take more than 25 mg ephedrine alkaloids per serving and not more than 100 mg per day.
2. Consult a health care professional before consuming an Ephedra-containing dietary supplement if you have heart disease, thyroid disease, diabetes, high blood pressure, depression or other psychiatric condition, glaucoma, difficulty in urinating, prostate enlargement, or seizure disorder, if you are using a monoamine oxidase inhibitor (MAoI) or any other prescription drug, or you are using an over-the-counter drug containing ephedrine, pseudoephedrine or phenylpropanolamine (ingredients found in certain allergy, asthma, cough/cold and weight control products).
3. Do not use Ephedra products if you are under the age of 18. Do not use Ephedra products if you are pregnant or nursing.
4. Discontinue use and call a health care professional immediately if you experience rapid heartbeat, dizziness, severe headache, shortness of breath, or other similar symptoms.
5. Exceeding recommended serving will not improve results and may result in serious adverse health effects

Latest FDA Reports Consistent with Previous Findings, No Association Between Ephedra Consumption and Serious Adverse Events

Experts who reviewed the most recent Food and Drug Administration (FDA) reports on Ephedra confirmed their conclusion, based on the totality of evidence, that these reports do not demonstrate an association between Ephedra consumption and serious adverse events (AERs). This conclusion is consistent with recent clinical data showing that Ephedra is safe and beneficial for weight loss, and with the previous findings of Cantox Health Sciences International’s quantitative risk analysis, and of a multidisciplinary expert panel sponsored by the Ephedrine Education Council (EEC).

As part of an ongoing effort to work with the FDA and other federal and state agencies to establish responsible standards for dietary supplements containing Ephedra, the dietary supplement industry has obtained from FDA the most recent AERs for Ephedra products. AERs cannot be viewed as scientific “data,” and it is not possible to use AERs to establish whether an event is attributable to Ephedra or whether Ephedra increases the risk of adverse events. Nonetheless, industry has agreed to review all new AERs that FDA receives for Ephedra products in an effort to help monitor whether the current national standard for these products is working, and in order to foster a more cooperative approach with FDA concerning the regulation of these products.

“The review of the most recent AERs is consistent with the written comments of the Expert Panel of the Ephedra Education Council submitted to FDA in October 2000, which stated that ‘available information does not demonstrate an association between the use of dietary supplements containing ephedrine alkaloids and serious adverse events’ when consumed according to the national standard,” said Dr. Stephen Kimmel, Chairman of the EEC’s Expert Panel.

“These conclusions are also consistent with a quantitative risk study submitted to FDA in December 2000 by Cantox Health Sciences International, and with data from clinical studies on ephedrine and Ephedra products, including the recently published abstract of the Harvard and Columbia study,” Dr. Kimmel added.

Researchers at the prestigious Harvard and Columbia Universities, who recently published data in abstract form in the FASEB Journal and Obesity Research, found that herbal Ephedra, when combined with caffeine, lowered body weight, fat and body mass index. There were no significant adverse events in this 6-month study, and rigorous testing of cardiac function showed little or no effect on heart rate or blood pressure. In addition, data published last month in The International Journal of Obesity also showed that the combination of Ephedra and Guarana in healthy, overweight subjects produced significant weight and fat loss.

As with past reports, the most recent batch of AERs shows why frequent media reporting of the raw number of AERs is meaningless and only confuses consumers. The new AERs include many that bear no relationship to Ephedra consumption. This includes reports on products that did not contain Ephedra, reports where no adverse event is listed, and cases where the event occurred well prior to any Ephedra consumption. Also included were cases medically unrelated to Ephedra, such as gallstones, small bowel obstruction and fat feet, as well as ludicrous reports such as that of a married woman who had an affair with a student, for which she has been criminally prosecuted. The only experts who have reviewed the entire FDA collection of AERs have consistently found that the AERs, when considered in the context of scientific data from clinical studies, do not represent a public health concern when Ephedra products are consumed according to current standards – a total dose of 100mg per day at 25mg four times a day.

Most important, the enormous potential benefits of Ephedra products for millions of consumers must be considered. According to the Centers for Disease Control, more than 60% of Americans are obese or overweight, and obesity results in 300,000 preventable deaths each year in the United States. Because of the clinical data showing safety and efficacy, leading experts in obesity have urged FDA to permit continued access to Ephedra products, one of the few useful tools that consumers have to help them lose weight.

Consumer Reports: Not Objective About Ephedra

We felt it critical to point out serious inaccuracies and deficiencies within the Consumer Reports June 2001 article on Sports Supplements entitled, “Sports-Supplement Dangers: Some Products Supposedly Increase Muscle or Energy. But They Could Cause Serious Harm.”

Consumer Reports prides itself on being an objective provider of information to the public. It has a reputation of providing well-researched information on the products that it reviews and providing both the pros and cons of reviewed products. Thus, it is especially disturbing to see Consumer Reports fail to provide both sides of an issue that is important to the health of the American public. Consumer Reports also failed to provide the most current and accurate information.

First, Consumer Reports magazine fails to point out the dangers of obesity itself. According to the Centers for Disease Control, more than 60% of Americans are obese or overweight, and obesity results in 300,000 preventable deaths each year in the United States. As a result, it is important to note that Ephedra is a popular dietary supplement used both safely and effectively by millions of Americans as an aid to weight loss – something Consumer Reports magazine failed to report.

Second, Consumer Reports magazine failed to report any of the research that has taken place with respect to Ephedra over the last 2 years. Research conducted at the prestigious Harvard and Columbia Universities, and recently published in abstract form in the FASEB Journal and Obesity Research, showed that dietary supplements containing Ephedra and caffeine are safe and effective as an aid to weight loss. The data from the Harvard and Columbia study also confirm the results of numerous other clinical studies, including a separate, short-term study conducted by some of the same Harvard and Columbia researchers and recently published in the International Journal of Obesity.

Further, Consumer Reports neglected to report that Cantox Health Sciences International, an internationally known and respected scientific research organization, reviewed the data held by Food and Drug Administration (FDA). Cantox analyzed over 19 clinical studies and numerous scientific articles about Ephedra and its chemistry, reviewing that data according to a standard set by the National Academy of Sciences. That analysis showed that Ephedra products, when consumed according to voluntary standards set by industry and codified as law in several states, are safe. Those standards have been submitted to FDA yet FDA has failed to respond.

One of the most glaring examples of the Consumer Reports article’s failure to fully evaluate, or fairly present all of the available information, is Consumer Reports’ reference to a University of California, San Francisco review by Christine Haller and Neil Benowitz, published last year. While Consumer Reports presents the information from this review that supported the negative tone of the article, Consumer Reports fails to mention that Haller and Benowitz recently conceded in a letter to the New England Journal of Medicine that their report “does not prove causation, nor does it provide quantitative information with regard to risk.”

Moreover, had Consumer Reports done a thorough job of researching the facts for this article, it would have discovered that Haller and Benowitz’s findings represent old information that had already been reviewed and rejected by scientific and medical experts. The information was rejected because it conflicted with more relevant and reliable data from clinical studies, which are regarded as the “gold standard” for establishing product safety and benefits. In August 2000, a panel of medical and scientific experts reviewed the same information reviewed by Haller and Benowitz, as well as the published clinical and other data that Haller and Benowitz did not consider, and found that there was no association between Ephedra and serious adverse events when it is taken as directed. Haller and Benowitz’s findings are based on anecdotal adverse event reports (AERs) received by FDA. The use of AERs to demonstrate product risk is not an accepted scientific method. Therefore, FDA’s use of AERs for this very purpose was found to be scientifically deficient by the United States General Accounting Office, causing FDA to have to take the embarrassing step of withdrawing a substantial portion of the proposed regulation.

Finally, the Consumer Reports article also incorrectly compares Ephedra to Methamphetamine. Dr. Edgar Adams, an internationally-recognized expert in addiction and drug abuse data, has reviewed the available data on Ephedra on two occasions and has submitted public statements to the FDA and the Department of Health and Human Services (HHS) establishing that, unlike Methamphetamine which is highly addictive and widely abused, there is no significant abuse of Ephedra despite its widespread use.

As stated above, obesity is an epidemic in this country. Ephedra products represent a viable alternative for many Americans looking for products to assist them in losing and managing their weight. Several national experts in obesity testified at a HHS public meeting in August 2000 to urge FDA to continue to allow consumers to have access to ephedra products because of the promise that these products offer in the fight against obesity. The Consumer Reports article unfairly creates an unfounded fear of these products, and does not provide the balance consumers have a right to expect from Consumer Reports magazine.

Response to Consumer Reports Article about Sports Dietary Supplements Ephedra

In Response to the June 2001 edition of Consumer Reports:

Overwhelming scientific and medical evidence directly conflicts with Consumer Reports’ unfavorable statements about Ephedra contained in an article on sports supplements. The facts are that Ephedra dietary supplements are safe and effective when marketed according to industry standards. Specifically, research conducted at the prestigious Harvard and Columbia Universities, and recently published in abstract form in the FASEB Journal and Obesity Research, showed that dietary supplements containing Ephedra and caffeine are safe and effective as an aid to weight loss. The data from the Harvard and Columbia study confirm the results of numerous other clinical studies, including a separate, short-term study conducted by some of the same Harvard and Columbia researchers and recently published in the International Journal of Obesity.

As support for their stance on Ephedra, Consumer Reports specifically references a University of California, San Francisco study by Christine Haller and Neil Benowitz, published last year. It is important to point out that Haller and Benowitz recently conceded in a letter to the New England Journal of Medicine that their report

does not prove causation, nor does it provide quantitative information with regard to risk.

Moreover, Haller and Benowitz’s findings represent old information that has already been reviewed and rejected by scientific and medical experts because it conflicts with more relevant and reliable data from clinical studies that prove Ephedra’s efficacy. In August 2000, a panel of medical and scientific experts reviewed the same information reviewed by Haller and Benowitz and found that there was no association between Ephedra and serious adverse events when it is taken as directed.

And finally, what Consumer Reports fails to point out is that obesity itself results in 300,000 preventable deaths each year in the United States, and that millions of Americans are benefiting from Ephedra dietary supplements as an aid to weight loss.

Ephedra Found Safe And Effective In Combating Excessive Weight By Researchers At Harvard And Columbia

Study Published in The International Journal of Obesity Also Reveals Significant Weight Loss in Subjects.

Popular Ephedra dietary supplements, taken by more than 12 million Americans for weight loss, are safe and effective according to conclusions reached by researchers at the prestigious Harvard and Columbia Universities. The data, generated from the most comprehensive study of Ephedra’s safety and efficacy to date, were officially published in abstract form recently in the FASEB Journal and Obesity Research. In addition, the International Journal of Obesity published a double-blind trial performed by some of the same researchers on a similar dietary supplement containing Ephedra and Guarana, finding that it was effective in weight loss.

The findings, presented by researchers from Harvard and Columbia Universities, found that herbal Ephedra, when combined with caffeine, lowered body weight, fat and body mass index. Additionally, data published in the International Journal of Obesity found that the combination of Ephedra and Guarana revealed that healthy, overweight subjects experienced significant weight and fat loss. The study called for additional research into Ephedra’s safety.

It is important to note that other respected studies have recently been completed, including the conclusions of a comprehensive science-based risk analysis performed by Cantox Health Sciences International. Cantox assessed all available scientific information, focusing on 19 clinical trials, and found that Ephedra was both safe and beneficial for weight loss at the 90mg per day dosage. In August 2000, a seven-member panel of experts completed a multidisciplinary review of Ephedra and concluded that there is no association between serious adverse events and Ephedra when consumed as directed.

Ephedra, also known as Ma Huang, is an herb that has a long history of being used both safely and responsibly. Conservative estimates indicate that over three billion servings of Ephedra products are consumed each year as an aid to weight loss and improved health.

Safe Use Of Ephedra Diet Pills Established

Scientific and medical experts announced today that the popular dietary supplement Ephedra is safe at a total daily dosage of 90mg, divided into smaller doses of up to 30mg. This finding is based on the conclusions of a comprehensive science based risk analysis performed by Cantox Health Sciences International, a world-renowned, independent scientific consulting firm. Cantox assessed all available scientific information — focusing on 19 clinical trials, including the critical data from a recent Harvard and Columbia trial that found Ephedra both safe and beneficial for weight loss at the 90mg per day dosage, as well as other key data including adverse event reports (AERs) collected by the Food and Drug Administration (FDA).

“The information reported here today is a win for consumers, a win for regulators and a win for industry. Consumers can continue to use Ephedra supplements for weight management; FDA has a credible scientific basis for implementing sound regulatory policy on Ephedra; and the industry is committed to continuing self-regulatory initiatives that benefit consumers,” said John Cordaro, President and Chief Executive Officer of the Council for Responsible Nutrition. CRN had commissioned Cantox to perform the risk assessment analysis.

John Hathcock, Ph.D., Vice President of Nutritional and Regulatory Science for CRN, explained the three conditions for safe Ephedra supplement use identified in the Cantox Report: dosage limits, effective labeling and post-market monitoring.

“A dosage of 90mg of Ephedra per day, taken in divided doses of 30mg, caused no observed adverse effects—the No Observed Adverse Effect Level (NOAEL). The report also identified a 150mg total daily dosage as the lowest level at which moderate adverse effects were first observed—the Lowest Observed Adverse Effect Level (LOAEL),” explained Hathcock.

In reviewing data on both Ephedra and ephedrine, Cantox analyzed in detail clinical trials, AERs from FDA, case reports and published articles, including data on both human and animal studies. Its exhaustive study revealed no serious concerns dealing with toxicity or other potentially harmful effects. This comprehensive database was analyzed in the context of the U.S. National Academies’ Food and Nutrition Board Upper Limit methodology, which is well established and broadly accepted.

“The Cantox dietary supplement assessment report is invaluable to establishing regulatory policy. CRN urges FDA to objectively analyze the conclusions and findings and to work with industry on appropriate implementation,” Cordaro added.

In addition to introducing the Cantox findings, CRN’s Cordaro, Hathcock and John Cardellina, Ph.D. were joined by Carol Boozer, D.S.C., Patricia Daly, M.D., the principal investigators of the Columbia/Harvard clinical study. George Bray, M.D. addressed Ephedra’s benefits in weight management.

Founded in 1973, The Council for Responsible Nutrition (CRN) represents 105 companies in the dietary supplement industry, including ingredient suppliers and manufacturers. CRN members adhere to a strong Code of Ethics, comply with dosage limits and manufacture dietary supplements to high quality standards under good manufacturing practices.

Obesity: A National Epidemic

Obesity is one of our nation’s foremost health problems and is directly link to numerous other diseases, including heart disease, hypertension and diabetes. In December 2001, the U.S. Surgeon General sounded the alarm, releasing a “Call to Action to Prevent and Decrease Overweight and Obesity.” The Call to Action included some frightening obesity statistics:

• Nearly 40 million American adults are obese
• The national obesity average jumped from 12% in 1991 to 19.8% in 2000
• Some 300,000 Americans die from obesity-related diseases every year — making obesity second only to smoking as a leading cause of premature death in the U.S.

Drs. Roland Sturm of Rand and Kenneth Wells of Rand also studied our national obesity epidemic and discovered that the health risks associated with obesity are greater than those associated with smoking, drinking or poverty. According to the study, the findings suggest that weight reduction should be an urgent public health priority.

By stimulating weight loss, Ephedra products can be a valuable weapon in the battle against excess weight , and as research shows, weight loss helps cut the risk of other health problems. It is very important that you read products labels, warnings and cautions and follow the directions. Ephedra is not for everyone and must be used responsibly.

You can determine whether or not Ephedra products can help you in your overall health program by first calculating your Body Mass Index (BMI). BMI is a tested method to determine if you should be concerned about your weight. Of course, you should contact your physician or other health care professional to obtain specific information and advice concerning your weight and health.

Concerns Over PPA Are Not Relevant To Ephedra

The public health concerns that led FDA to ask all companies to discontinue marketing drug products that contain phenylpropanolamine (PPA) are not relevant to the ongoing review of the benefits and safety of dietary supplements that contain ephedra.

FDA’S DECISION ON PPA

• PPA has been marketed for decades as an over-the-counter ingredient in widely consumed cold medications and appetite suppressants, at individual doses of up to 25 mg taken 6 times per day (excluding extended release formulations, which use higher amounts).
• FDA has requested that companies cease marketing products containing PPA based on the availability of alternative ingredients, FDA’s perception that benefits of PPA for colds and appetite suppression are extremely limited, and the agency’s belief, based on a controversial study and a relatively small number of reports of possible adverse events, that PPA may cause a slight increase in hemorrhagic stroke – a serious adverse effect that is not associated with alternatives to PPA.
• FDA’s request at this time is for voluntary industry action – FDA has yet to issue a proposed rule that establishes a valid scientific basis for the agency’s request, and there is considerable question as to whether FDA can provide support for such a regulation.

PPA IS NOT RELEVANT TO EPHEDRA

• PPA is a natural but very minor constituent found in some, but not all, dietary supplements containing ephedra.
• When present at all, PPA is present in amounts that are approximately 100-fold or more lower than the amount of PPA found in popular OTC cold products.
• In addition, small amounts of the naturally occurring ephedrine that is present in supplements that contain ephedra may be converted to PPA in the body, but current data suggest that the conversion is no more than 4 to 6 percent, which would result in approximately 0.5 to 1.5 mg of PPA per serving from this source.
• FDA has not questioned the safety of OTC ephedrine, which contains more ephedrine (resulting in more consumer exposure to PPA) than found in ephedra products, presumably because the amounts from metabolic conversion are so small as to be insignificant.
• These facts show that any exposure to PPA from consuming ephedra products is minimal at most.
• This minimal exposure led a seven-member expert panel, which in July through September of this year subjected ephedra products to the most comprehensive review of ephedra ever, to conclude that PPA is not relevant to ephedra safety.