Supplement Performance - The Ephedra Ban: The Truth

Before we start to analyze the scientific basis of the ephedra ban, let me

tell you an interesting story on health politics outside of the bodybuilding world.

In 1874, a smart German cookie named Othmar Zeidler first produced a

substance called DDT, but he did not suggest any use for it. However, 60 years

later, Paul Muller discovered the chemical’s enormous insecticidal (destroys

insects) potential and he received a Nobel Prize in 1948.

Clearly, DDT has been effective in controlling humankind’s worst insect

pests, including mosquitoes. Also, well-controlled studies have indicated that

the purported adverse effects are false, or at least grossly exaggerated. In his

final 113-page report decision, issued in 1974, Hearing Examiner Edmund

Sweeney stated: “DDT is not a carcinogenic, mutagenic, or teratogenic hazard

to man. The uses under regulations here do not have deleterious effects on

freshwater fish… and other wildlife… and there is a present need for essential

uses of DDT.”

This scientifically-based decision was, however, overruled by EPA

Administrator William Ruckelshaus, who never attended a single day of the

seven months of DDT hearings. In his Final Opinion, this not-so-smart cookie

omitted scientific data, misnamed many chemicals and even recommended

substituting parathion (a deadly chemical) for DDT. To look at the evidence and

go away unconvinced is one thing. To not look at the evidence and be

convinced against it nonetheless, is another thing. But that’s not science, so

Ruckelshaus apparently didn’t do his homework. Oddly enough, he later even

wrote, “In such decisions the ultimate judgement remains political.”

Certainly, there are politics involved in the current ephedra debate, too. As

this Manninen dude (me) is a politically incorrect maverick by nature, you will

now read the truth, the whole truth and nothing but the truth— without political

baloney.

Basic Facts About Ephedra/Ephedrine

Ephedrine is classified as a sympathomimetic drug and central nervous

system stimulant. Its ability to act as a sympathetic agonist and increase

thermogenesis (production of heat) has led to its use in weight loss/fat loss. In

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

two herbs: ephedra or Ma Huang.

Although 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 is higher for the botanical extract (5.4 grams per

kilogram of bodyweight [g/kg]) as compared to the LD50 for pharmaceutical

ephedrine (64.9 mg/kg). (LD50 refers to the amount of a material that causes

death in 50 percent of test animals). Nevertheless, the FDA did not ban

ephedrine. This decision may have something do with fact that the FDA has

strong financial connections with the pharmaceutical industry (“big pharma”).

FDA and its Big Brother

The muscular hand of big pharma is felt at all levels of government. In

fact, it has by far the largest lobby in Washington. For example, in 2002, big

pharma employed 675 lobbyists at a cost of over $91 million. Thus, it’s not

surprising that Congress has put the FDA on the big pharma´s payroll. In 1992,

it enacted the Prescription Drug User Fee Act, which authorized drug

companies to pay user fees to the FDA. According to Dr. Marcia Angell, a

former editor-in-chief of The New England Journal of Medicine, fees originally

amounted to about $310,000 per new drug application. However, in 2002, the

fees were increased to about $576,000 per new drug application. Obviously,

that makes the FDA dependent on an industry it supposedly regulates.

Further, the FDA is subject to big pharma propaganda through its 18

standing “advisory committees” on drug approvals. As expected, many

members of these committees have financial ties to interested companies.

Although there are conflict-of-interest rules that prohibit participation in such

cases, the FDA regularly waives them on the ridiculous grounds that someone’s

advice is indispensable. Nonsense. Nobody is indispensable. Not surprisingly,

members of the FDA “advisory committees” command ridiculously high

consulting fees from big pharma.

In the summer of 2003, The New York Times reportedly obtained

confidential documents from PhRMA (big pharma´s trade association) that

details its plans to buy influence in the coming fiscal year. According to the

report, spending for that purpose would increase to $150 million. Interestingly,

expenditures would include a $5 million lobby to the FDA. So, it must be clear

that the FDA cannot always be trusted.

Was the Ephedra Ban Based on Science?

According to the Final Rule Declaring Dietary Supplements Containing

Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk

(Federal Register, February 11, 2004), “We [the FDA] have concluded that

dietary supplements containing ephedrine alkaloids pose a risk of serious

adverse events, including heart attack, stroke and death, and that these risks

are unreasonable in light of any benefits that may result from the use of these

products under their labeled conditions of use, or under ordinary conditions of

use if the labeling is silent.”

It appears this conclusion was mainly based on the Boozer study,

which compared the effects of a combination of ephedra and caffeine (from kola

nut) with placebo (fake supplement) over a six-month period in a population of

obese and overweight individuals. Dr. C.N. Boozer and colleagues measured

sitting blood pressure in the clinic using the cuff method for all six months of the

study. Also, they measured changes in blood pressure throughout the day at

weeks one, two and four using an automated blood pressure monitoring device

(this method is purportedly better able to evaluate blood pressure effects over

time).

The ephedrine-caffeine combo did not show a difference in the blood

pressure measurements taken at the clinic, but did show statistically significant

higher average blood pressure measurements over 24 hours at week four, as

measured by automated blood pressure monitoring (about 4 mm Hg for both

systolic and diastolic blood pressure) when compared to placebo treated

subjects. Dr. Boozer and colleagues concluded, “Herbal treatment produced

small changes in blood pressure variables ( 3 to -5 mm Hg, P< or =0.05), and

increased heart rate (4 /-9 vs. -3 /-9 bpm, P<0.001), but cardiac arrhythmias

were not increased (P>0.05)… In this six-month placebo-controlled trial, herbal

ephedra/caffeine (90/192 milligrams per day) promoted bodyweight and body

fat reduction and improved blood lipids without significant adverse events.”

Obviously, the FDA didn’t agree with this conclusion, as the Final Rule

paper stated, “The ABPM [automated blood pressure monitoring] data are

important because they demonstrate that the effect of the ephedrine alkaloids,

including dietary supplements containing ephedrine alkaloids, on blood

pressure is not transient, but is still evident after one month of continued

exposure (when measured by ABPM) and therefore, would be expected to

persist long term… The Boozer et al. (2002) study (Ref. 49) was reviewed at

our request by three outside scientific experts, Norman M. Kaplan, MD (Ref.

50), Richard L. Atkinson, MD (Ref. 51) and Mark Espeland, PhD (Ref. 52).

These experts were asked to give their independent, scientific opinion of

whether the study provides adequate data to assess the safety of ephedrine

alkaloids and caffeine for weight loss— considering, among other things, the

design and duration of the trial and subject selection— and whether further

studies are needed. In general, the experts concluded that the safety of

ephedrine alkaloid and caffeine-containing products could not be established by

this study because the study used a highly selected population (i.e., carefully

screened by medical history and medical evaluation to eliminate cardiovascular

and other acute or chronic disorders) and had relatively few subjects.”

I was not able to get these expert opinion documents that were

prepared for the FDA. However, opinion statements do not prove anything.

Opinions are just that: opinions. The Final Rule states, “Dr. Kaplan, one of the

reviewers, raised the concern that the size of the change in blood pressure

observed with ABPM, when applied to a large population, could translate into a

significant increase in the incidence of strokes and heart attacks.” Of course,

this statement is purely speculative. More importantly, it seems the FDA ignored

expert opinions prepared by Drs. Atkinson and Espeland. Maybe they were not

negative enough. What does “in general, the experts concluded…” mean? Well,

there were three expert opinions, and if they all agreed that ephedra is as

dangerous as the FDA claims, then there´s no reason to say “in general.” So,

we can assume that at least one expert opinion disagreed with the FDA.

True, the Boozer study had relatively few subjects: The placebo group

had 84 subjects and herbal treatment had 83 subjects. However, the fact that

the Boozer study screened by medical history and medical evaluation to

eliminate cardiovascular and other acute or chronic disorders is irrelevant, since

ephedra product labels state, “Consult a health care professional before using

this product if you have heart disease, thyroid disease, diabetes, high blood

pressure...” so nobody is suggesting that individuals with acute or chronic

disorders use ephedra-caffeine products without medical supervision.

Clearly, the Boozer study does not prove that an ephedra-caffeine

combo is completely safe. Rather, this study indicates the ephedra-caffeine

combo has a small effect on blood pressure. Certainly, we cannot have the best

of the both worlds; there is no such thing as “very effective and perfectly safe.”

However, a more important question is: Does this study prove that an

ephedra-caffeine combo poses a risk of serious adverse events, including

heart attack, stroke and death, and are these risks unreasonable in light of

fat loss benefits that may result from the use of these products under

their labeled conditions of use? I don’t think so.

U.S. Distinct Judge Tena Cambell apparently agrees with me, as she

recently stated, “There is not sufficient evidence in the administrative record to

establish that the risks identified by the FDA are associated with the intake of

low-dose [ephedrine-alkaloid dietary supplements].” However, the FDA took that

to mean it could still ban the supplement in higher doses, as the agency

recently restated its case by saying all doses of ephedra above 10 milligrams

are still illegal. Obviously, the FDA feels it’s above the law and can just ban any

dietary supplement it wants without evidence that it poses unreasonable risks.

Yet, the FDA keeps certain highly toxic (but extremely profitable) prescription

drugs perfectly legal. Talk about the tyranny of the pharma-FDA complex!

Finally, let´s examine what the recent report by the Institute of

Medicine, titled Weight Management: State of the Science and Opportunities for

Military Programs (Committee on Military Nutrition Research, 2003), said about

ephedra and caffeine. The Committee admits that ephedrine alone or in

combination with caffeine has been associated with cardiovascular and other

symptoms in adverse events reports (AERs do not prove anything), but they

also pointed out that prospective studies using healthy individuals doesn’t

support the concept that there are major adverse events with ephedrine and

caffeine, citing studies by Boozer et al. and Kalman et al. Thus, it appears the

Committee on Military Nutrition Research, which is supported by the U.S. Army

Medical Research and Material Command, disagrees with the FDA.

Summing Up

Contrary to the belief supported by the FDA, there is no scientific

evidence suggesting that an ephedra-caffeine combo, when used as directed,

poses unreasonable risks. The suggestion that the effect of this combo on blood

pressure would be expected to persist long term was based on speculations,

i.e., the FDA was not able to provide any evidence supporting this contention. In

summary, the risks of an ephedra-caffeine combo are relatively small and must

be balanced against the real and established risk of continued obesity.