"While ephedra might be more dangerous than, say, a multivitamin, its risks, which stem

mainly from stimulating the cardiovascular system, are well within the range considered

acceptable for OTC [over-the-counter] drugs. The FDA, the medical establishment and the

pharmaceutical industry all want to prevent the emergence of an alternative drug market in which

consumers can obtain cheap, effective and reasonably (though not completely) safe products

without permission from the government's gatekeepers." —Jacob Sullum, The Washington Post

Basic Facts about Ephedrine/Ephedra

Ephedrine is classified as a sympathomimetic drug and central nervous system stimulant.

Its ability to suppress appetite and increase thermogenesis (production of heat) has led to its use

in weight loss/fat loss. Ephedrine alone isn’t very effective as a fat-loss agent; however, caffeine

clearly enhances its effectiveness. It’s been estimated that about 80 percent of weight loss from a

ephedrine/caffeine mixture is due to the appetite suppressing and 20 percent is due to a

thermogenic effect. There’s also evidence that ephedrine spares muscle mass and prevents a

drop in the resting metabolic rate associated with calorie restriction.

In addition, ephedrine is used as a performance-enhancing substance (ergogenic aid).

For example, Jacobs and colleagues reported that ephedrine ingestion, either alone or in

combination with caffeine, can lead to a significant increase in the number of repetitions that can

be performed and the total amount of weight that can be lifted during weight training. In fact, the

magnitude of the ergogenic effect is highly significant for gym rats since only 90 minutes after

ingesting caffeine plus ephedrine a 16 percent improvement in bench press performance was

reported.

In most dietary supplements, ephedrine used to appear as an extract from one of two

sources: ephedra or ma huang. Although the ephedra species have a long tradition of use (more

than 5,000 years) for respiratory ailments, in 2004, the U.S. Food and Drug Administration (FDA)

decided to ban ephedra-containing supplements. According to Health and Human Services

Secretary Tommy G. Thompson, "This FDA rule reflects what the scientific evidence shows—

that ephedra poses an unreasonable risk to those who use it."

Some feel ephedra extract is safer than pharmaceutical ephedrine based on the fact that

the LD50, which refers to the amount of a material that causes death in 50 percent of test

animals, is lower for the botanical extract (5.4 grams per kilogram of bodyweight) as compared to

the LD50 for pharmaceutical ephedrine (64.9 milligrams per kilogram). Nevertheless, the FDA

didn’t ban ephedrine. This decision may have something do with fact that the FDA has strong

financial connections with the pharmaceutical industry.

The history of ephedrine as a weight-loss/fat-loss agent is rather interesting. In 1972, Dr.

Erikson, a Danish general practitioner in Elsinore, Denmark, noted unintentional weight loss when

he prescribed a compound containing ephedrine, caffeine and Phenobarbital to patients he was

treating for asthma. By 1977, over 70,000 patients were taking the "Elsinore Pill," and one Danish

pharmaceutical house was reportedly producing one million tablets a week!

As you may know, MD Publisher and Editor-in-Chief Steve Blechman is a former

TwinLab

(Ripped Fuel), which was extremely popular among serious gym rats simply because it worked

and had few, if any, adverse effects when used as directed. Indeed, numerous well-controlled

clinical studies support this contention. The latest study was just published in the International, a leading peer-reviewed scientific journal in the area of obesity research.

Journal of Obesity

The purpose of the recent study by Hackman and co-workers at the University of

California was to determine the safety and efficacy of a low-dose ephedrine/caffeine mixture in 61

overweight/obese women. This study was a nine-month, double-blind, randomized control study

comparing the efficacy and safety of a dietary supplement containing ephedra, caffeine

(guarana), high potency vitamins and minerals, omega-3 fatty acids and a host of other botanical

extracts to a control supplement (i.e., a inactive fake supplement containing only some

vitamins/minerals). The active supplement provided 40 milligrams per day of ephedrine and 100

milligrams per day of caffeine.

As expected, women receiving the ephedra/caffeine mixture lost significantly more

bodyweight (7.18 kilograms) and body fat (5.33 kilograms) than the control group (2.25 and 0.99

kilograms, respectively) and showed significant improvements in blood lipids. Furthermore, the

ephedra/caffeine group reported more energy and decreased appetite compared to controls and

scored higher on a quality of life domain assessing vitality. Importantly, the ephedrine/caffeine

mixture didn’t cause any major adverse side effects. However, minor symptoms included dry

mouth, insomnia, nervousness and palpitations. The incidence of dizziness and headache were

similar between groups. The authors concluded that "a low-dose of ephedra alkaloids and

caffeine combined with a broad spectrum multinutrient supplement and other botanical extracts

may be a useful option to help physicians and patients with safe and effective weight loss."

As pointed out by the authors, the mean weight loss in the group of women taking the

ephedrine/mixture in this study was similar to the mean weight loss found in obese patients

treated with orlistat in addition to calorie restriction. In other words, this study clearly

demonstrated that the ephedra/caffeine mixture is a more effective fat-loss agent than orlistat, a

prescription drug approved by the FDA. Orlistat blocks the absorption of almost one-third of

ingested fat. The side effects of orlistat are rather annoying: flatulence, increased defecation,

fecal urgency, fatty/oily stool, etc. So, if you’ve just started to date some hot babe, orlistat is

clearly not your drug of choice. I would rather have a dry mouth than excessive gas in the

alimentary canal!

[Please insert a cartoon pic of fat bastard wearing Orlistat t-shirt and having major

problems with excessive gas in his alimentary canal! :D ]

It’s worth noting that the formula used by Hackman et al., also contains hydroxycitric acid

(HCA), which is a popular ingredient in fat-loss supplements, but studies on its fat-loss enhancing

effects are controversial. In a recent study by Drs. van der Haar and co-workers, the effects of

three different HCA-containing preparations (Regulator, Citrin K, CitriMax

bodyweight were studied in rats. The conclusion was that these commercially available HCA

preparations exert striking differences in efficacy in inhibiting voluntary food intake in rats.

Specifically, Regulator and Citrin were potent suppressants of food intake, whereas CitriMax

exerted much smaller effects on food intake.

In a comprehensive study by Blechman and colleagues at the New York of School of

Medicine and City and County of San Francisco Hall of Justice, the investigators reviewed all

autopsies in their medical examiners’ jurisdictions, from 1994 to 2001, where ephedrine or any of

its isomers were detected. Toxicology testing results were tabulated and anatomic findings in

ephedra cases were compared to those in a control group of drug-free trauma victims.

Of 127 ephedra cases, 33 were due to trauma, i.e., an injury caused by an extrinsic

(outside of a body) agent. Furthermore, more than 88 percent (113/127) of the decedents also

tested positive for other drugs, the most common being cocaine and morphine. The authors

stated, "What is most surprising about the results of this study is that of the cases where only

ephedrine alkaloids were detected, only one possible case of ephedrine toxicity occurred in San

Francisco from 1994 to mid-1999. This data contradicts the recent, well-publicized case reports

suggesting that large numbers of ephedrine-related deaths were occurring and that only a fraction

are being reported to the FDA."

More recently, Ray and co-workers reported that the ingestion of an ephedrine/caffeine

mixture (plus other herbal extracts and omega-3 fatty acids) for one year doesn’t significantly alter

normal blood chemistry or induce any irreversible histological changes in the mouse heart, even

though their study employed up to 10 times the normal human consumption dose of ephedra.

Collectively, these studies suggest that the adverse effects of ephedra are greatly exaggerated.

In contrast, some clinicians feel that ephedra may pose significant risk. Andrews and coworkers

at the Beth Israel Medical Center reviewed the available literature and concluded that

more stringent oversight by regulatory authorities is required to minimize the incidence of adverse

events. The authors rightly stated, however, that, "No clinical trial has reported major adverse

cardiovascular events (stroke, myocardial infarction, or malignant arrhythmias) associated with

the use of ephedra alkaloids for weight loss."

They also cited numerous case reports purportedly showing that adverse cardiovascular

and cerebrovascular effects, including stroke, myocardial infarction and sudden death, are related

to ephedra use. Many of these case reports are very dubious and some of them had nothing to

do with ephedra products. For example, Andrews et al., stated, "Myocardial ischemia has also

been reported when ephedra alkaloids are combined with other medications that cause increased

adrenergic tone, such as bupropion," citing the case report by Pedersen. In reality, the patient’s

medication history revealed recent commencement of bupropion (Zyban

and pseudoephedrine as a non-prescription influenza remedy. In sum, the review paper by

Andrews et al., was poorly peer reviewed.

Surprisingly, there’s a recent study showing that a single dose of an ephedra/caffeine

supplement can produce significant increases in blood pressure and resting heart rate in healthy

young adults. Call me a skeptic, but this report smells like old fish. You see, the first and third

authors of this paper have served as "expert witnesses" in litigation involving manufacturers of

dietary supplements that contain ephedra. These authors are outspoken critics of ephedrine

supplements and just happen to be the authors of the only published study purportedly showing

that a single dose of ephedra/caffeine (taken in recommended doses) can produce significant

cardiovascular and metabolic changes. However, some 20 percent of patients have blood

pressures significantly higher in the doctor’s office than at home ("white coat hypertension")

simply because emotions increase the cardiac output and peripheral resistance and thus arterial

pressure. Thus, one can’t draw any conclusions based on such a single-dose study.

Finally, the purpose of the recent "study" by Dr. Woof and colleagues was to compare

toxicity from botanical products containing ephedra to non-ephedra products. They utilized the

Toxic Exposure Surveillance System (TESS; a national poison center database) to determine the

number and outcomes of cases involving botanical products reported from 1993-2002. The

authors concluded, "Hazard rate analysis suggests poison center-reported events involving

ephedra-containing botanical products were much more likely to result in severe medical

outcomes than those involving nonephedra-containing botanical products."

These well-meaning authors apparently didn’t read the comment published in the Annalsin 2003 blasting another ephedrine-related TESS study. In their comment,

of Internal Medicine

researchers at the PROSAR International Poison Control Center and International Toxicology

Consultants stated, "The TESS report does not provide the percentages of individual products or

categories in which the exposure is coded as unrelated, rendering the results presented in Bent

and colleagues’ work invalid. Furthermore, Bent and colleagues don’t make clear that most of the

ephedra cases described in TESS involve botanicals with many active ingredients. There’s no

consideration of severity, ephedrine dose, duration of use, purity, contaminants, underlying health

status, or other substances contemporaneously consumed. Comparing ephedrine with ‘other

herbs,’ the actions and indications of which are distinct, is toxicologic nonsense." In other words,

such TESS-studies can’t be taken seriously.

A low-dose ephedra/caffeine mixture is an effective and reasonably safe fat-loss agent.

However, ephedra isn’t for everyone and must be used responsibly. It's very important to read

product labels, warnings and cautions and follow the directions. Someone should never, under

any circumstances, use ephedra-containing supplements with heart disease or high blood

pressure. Remember, you can’t have the best of the both worlds; there’s no such thing as "very

effective and perfectly safe." It’s all about the risk-to-benefit ratio. You have to decide whether

potential fat loss benefits outweigh potential adverse effects.

The author of this article has no financial relationship with companies selling fat loss

supplements.