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Ephedra: A Dangerous Supplement

Author: Stan Reents, PharmD
Original Posting: 05/06/2007 06:51 AM
Last Revision: 12/23/2020 08:06 AM

In this article, I will summarize ephedra, and, some of the FDA actions regarding its regulation in the US. (NOTE: The FDA banned the sale of ephedra in the US on August 17, 2006. These supplements were banned in Canada in January 2002.)


Ephedra, also called "Ma huang," is one of the oldest and best known herbs in Chinese medicine. It is mentioned in the book Shen Nong Ben Cao Jing which dates to around 100 AD. Some sources claim that ephedra has been used for more than 5000 years.


The names "ephedra" and "ephedrine" should not be used interchangeably:

"Ephedra" refers to the plant or herbal products in their raw form. There are approximately 40 different species of ephedra plants. Biological names for two of the more commonly used plants are Ephedra sinica and Ephedra intermedia.

"Ephedrine" is one of several specific chemical ingredients obtained from ephedra plants (see below). An analogy is nicotine and tobacco: nicotine is one of many chemicals obtained from the tobacco plant. Further, note that ephedrine is a legitimate pharmaceutical drug while ephedra is sold as an herbal supplement.

Ephedra plants yield at least 6 chemicals: the first 2 below are major, while the other 4 are minor:

  • ephedrine (major)
  • pseudoephedrine (major): commonly known by the brand name "Sudafed®"
  • norephedrine (minor): a component of phenylpropanolamine (PPA)
  • norpseudoephedrine (minor): a controlled substance in the US; also known as "cathine"
  • methylephedrine (minor)
  • methylpseudoephedrine (minor)

Of these 6 chemicals, ephedrine and pseudoephedrine represent about 90% of the total alkaloid content in ephedra plants, with Ephedra sinica being a slightly better source than Ephedra intermedia.


While it is useful to know the chemical make-up of herbal ephedra, it is even more important to realize that its ingredients -- ephedrine, pseudoephedrine, etc. -- are related to amphetamine; the chemical structures of all these drugs are almost identical. Thus, it should not be surprising that the effects of herbal ephedra are similar to those of amphetamine. Fortunately, ephedrine is not as prone to addiction as amphetamines are. Nevertheless, in high doses, ephedrine has been shown to cause psychosis (see below).

As with epinephrine, the effects of herbal ephedra are mostly seen on the cardiovascular system. The alkaloids in ephedra cause a release of adrenalin (aka: epinephrine). This leads to an increase in heart rate and blood pressure. But, this is also the most likely explanation for why ephedra supplements have been associated with severe cases of cardiovascular and cerebrovascular toxicity.


• Use During Surgery: In controlled settings like an operating room, and with precise dosing, IV ephedrine is used therapeutically to increase blood pressure and heart rate during surgery.

• Use in Weight Loss: Herbal ephedra dietary supplements have been shown to be effective for weight-loss in obese subjects, however it appears that it does so only when administered either in high doses (Shekelle PG, et al. 2003), or in combination with caffeine (Astrup A, et al. 1992) (Lenz TL, et al. 2004). Unfortunately, combining ephedra (or ephedrine) with caffeine leads to more side effects (see below).

• Use in Sports: The February 2, 1998 issue of Sports Illustrated carried a story about the use (abuse) of pseudoephedrine (commonly known by the brand name Sudafed®) in the NHL. The article stated that, as players were being warned of the risks of pseudoephedrine, many were switching to herbal ephedra supplements to provide the same boost.

However, single oral doses of ephedrine had no effect on performance during cycling (40 mg dose; DeMeersman R, et al. 1987), or on muscle strength, endurance, reaction time, or hand-eye coordination (24 mg dose; Sidney KH, et al. 1977). An extensive review of herbal ephedra from the RAND Corporation, published in March 2003, concluded that solid proof that ephedra supplements improve athletic performance is dubious (Shekelle PG, et al. 2003).

What about pseudoephedrine, the other major active ingredient in herbal ephedra? Pseudoephedrine demonstrated no performance-enhancing effects during cycling (Gillies H, et al. 1996) or treadmill running (Clemons JM, et al. 1993).

Because ephedrine and pseudoephedrine are the main alkaloids in herbal ephedra, these studies cast serious doubt on the performance-enhancing capabilities of herbal ephedra.

Complicating matters further, pretty much all substances classified as "stimulants" (aka: sympathomimetics) are banned by most sports governing organizations.

Olympic athletes Rick DeMont (swimming, 1972) and Andreea Raducan (gymnastics, 2000) lost gold medals due to consuming prescription drugs that contained ephedrine and pseudoephedrine. The herb ephedra also contains those ingredients.

The World Anti-Doping Agency (WADA) focuses on specific drugs and molecules and doesn't say much about herbal supplements in its Banned Substances List. However, the National Collegiate Athletic Association (NCAA) does include a section on "nutritional/dietary supplements" in its List. It warns that many "are contaminated with banned substances not listed on the label."

Herbal ephedra (not mentioned) same as
Not specifically listed,
however, a
blanket warning
is provided
Ephedrine prohibited if
urine concentration
exceeds 10 mcg/ml
same as
Pseudoephedrine prohibited if
urine concentration
exceeds 150 mcg/ml
same as
not banned


Between December 1993 and September 1995, the Texas Department of Health received approximately 500 reports of adverse events in persons who consumed dietary supplements containing ephedra. The reports described stroke, myocardial infarction, seizures, insomnia, dizziness, and 8 fatalities (MMWR 8/16/96).

Since then, at least 4 extensive evaluations of side effects to ephedra supplements have been published:

1) An analysis of 926 reports of possible ephedra toxicity received by the FDA between 1995 and 1997 revealed that 4% involved serious cardiovascular events: 11 sudden deaths, 16 strokes (3 deaths), and 10 myocardial infarctions (Samenuk D, et al. 2002).

2) In 2000, Haller and Benowitz reviewed 140 reports of adverse events involving ephedra supplements that were submitted to the FDA between June 1, 1997 and March 31, 1999. Hypertension and cardiac arrhythmias were common in these reports including ten deaths and 13 cases of permanent disability. They concluded that 31% were "definitely" or "probably" related to ephedra, and another 31% were "possibly" related (Haller CA, et al. 2000).

3) In an attempt to compare the rates of adverse reactions from ephedra supplements against other types of herbal supplements, investigators at UCSF analyzed adverse reactions to herbal products reported to the American Association of Poison Control Centers during 2001. They found that products containing ephedra accounted for 64% of the reports even though ephedra products represented less than 1% of total herbal sales (Bent S, et al. 2003).

4) In the most thorough analysis to date, the RAND Corporation, at the request of the US Department of Health and Human Services, performed a comprehensive search and review of published reports on ephedra. The investigators concluded that ephedrine and ephedra are associated with 2-3 times the risk of heart palpitations, autonomic symptoms, and psychiatric symptoms (Shekelle PG, et al. 2003).


In the US, dietary supplements are regulated under the DSHEA law, which was passed in 1994.

One major problem that DSHEA created when it was passed is that supplement manufacturers were not held to the same production standards that manufacturers of traditional pharmaceutical drugs are. In other words, when you buy a bottle of Tylenol® or Motrin®, you don't worry that the tablet might contain too much active ingredient.

Yet this is exactly the risk you have with dietary supplements. Prior to 2007, producers of dietary supplements did not always adhere to the Good Manufacturing Practice (GMP) standards that are required for the production of pharmaceutical drugs (Fontanarosa PB, et al. 2003). Not following GMP standards can lead to quality-control problems.

And quality-control issues were demonstrated for ephedra supplements:

In 2000, researchers at the University of Arkansas analyzed two separate lots of 10 commercially available ephedra supplements (Gurley BJ, et al. 2000.). Brands such as Metabolife, Ripped Fuel, and Xenadrine, to name a few, were included. Nineteen of 20 products contained measurable amounts of ephedrine, the major alkaloid found in herbal ephedra. But the amount of ephedrine ranged from 1.09 to 15.33 mg/capsule. Pseudoephedrine was identified in 16 of these 20 products; quantities ranged from 0.16 to 9.45 mg per capsule.

When 2 brands that each claimed 150 mg of herbal ephedra per capsule were compared, one contained only 3.0 mg ephedrine while the other contained 14.2 mg ephedrine. This does not suggest these products were intentionally mislabeled. Rather, it is simply an example of how much an ingredient in an herbal substance can vary. Different manufacturers will obtain their raw material from different suppliers. In this case, even though both products used the same amount of raw material (150 mg), the amount of active ingredient (ephedrine) varied by nearly 5-fold. In another report, researchers from UCSF revealed that 31% of the products they tested contained more than 110% of the amount stated on the product's label (Haller CA, et al. 2004).

Even more worrisome is a lack of consistency between 2 lots of the same brand:

When the University of Arkansas researchers compared different lots of the same brand, variations in ephedrine content differed by as much as 260% (Gurley BJ, et al. 2000). Again, this can be explained by normal variation in the amount of active ingredient in an herbal substance, or, by the manufacturer changing the source of their raw material. Thus, consumers are unknowingly subjected to unpredictable amounts of substances they ingest, even if they purchase the same brand each time.

Some athletes abuse ephedrine (Gruber AJ, et al. 1998) and pseudoephedrine. This behavior is concerning enough when the amount of active ingredient per dosage unit is known and consistent. However, when the amount of active ingredient varies from batch to batch, or, worse, is higher than what is stated on the label, serious side effects are possible. Even "normal" doses of pseudoephedrine have been associated with cardiac arrhythmias (Bright TP, et al. 1981).

This is the side of the story that consumers need to be aware of. Ephedra is a potentially dangerous herb; even more so when you can't be certain what amount you are actually ingesting.


Prior to the death of Anne Marie Capati in 1998 (see table below), ephedra-containing herbal supplements had been linked to more than 3 dozen deaths. By December 2003, the FDA stated it was aware of 155 deaths linked to ephedra.

The risks of ephedra increase when combined with caffeine. This combination is not only dangerous, but potentially deadly. When dogs were given high doses of guarana (an herbal source of caffeine) with ephedra, 17% died or had to be euthanized (Ooms TG, et al. 2001).

Nevertheless, some researchers argue that caffeine and ephedrine have been used together successfully as a weight loss aid in obese subjects without problems. Several studies from Copenhagen show that chronic administration of caffeine and ephedrine together does not produce severe side effects (Astrup A, et al. 1992) (Astrup A, et al. 1993) (Toubro S, et al. 1993).

Yet, an equally compelling argument can be made against the use of supplements that combine herbal ephedra with caffeine:

Numerous studies have investigated the effects of caffeine during exercise. Most of them state that caffeine did not affect sweat rates or temperature regulation (Armstrong LE, et al. 2007). But, in almost all of these studies, so few subjects were included it's difficult to draw reliable conclusions. In some studies, caffeine did increase body temperature (Ely BR, et al. 2011) (Falk B, et al. 1990) and affect sweat rate (Dunagan N, et al. 1998) during exercise. Several alkaloids in ephedra cause vasoconstriction, which could inhibit heat loss. Thus, these 2 actions aren't a good combination for the cardiovascular system.

10/1/98Anne Marie Capati, 37:
After taking Thermodrene
and other supplements for several months,
she suffered a stroke and died.
She had hypertension
and was receiving blood pressure drugs.
• ephedra 20 mg
•caffeine 80 mg
• guarana 150 mg
9/3/02Sean Riggins, 16:
Suffered a heart attack and died.
He had been taking Yellow Jackets.
Yellow Jackets:
• ephedra
• kola nut
2/17/03Steve Bechler, 23:
Baltimore Orioles pitcher collapsed
during spring training in Ft. Lauderdale.
His body temp was 108.
He died the following day.
He had been taking Xenadrine RFA-1.
Xenadrine RFA-1:
• ephedra 10 mg/cap
• caffeine 100 mg/cap
Citrus aurantium 62 mg/cap

(*these dietary supplements also contain other ingredients)


Another problem with DSHEA is that it puts the burden of proving a dietary supplement is unsafe on the shoulders of the FDA, not the manufacturer, as is required before traditional pharmaceutical drugs are approved. This means that dietary supplements can be marketed before safety issues are thoroughly investigated.

The FDA had been trying to ban the sale of ephedra for years. Here is a chronological summary of some of the major legal/regulatory events affecting the sale of ephedra supplements:

• June 4, 1997: FDA proposes limiting the amount of ephedra in dietary supplements. At that time, they had received more than 800 reports of adverse events in people taking this supplement. The restrictions would have limited use to no more than 8 mg in a 6-hr period, or, 24 mg in a 24-hr period. FDA also proposed putting warning labels on containers. This generated an outcry from lawmakers and industry groups. They claimed that FDA did not have enough evidence to support these restrictions.

• October 1, 1998: Anne Marie Capati, 37, a known hypertensive, suffers a stroke and dies after working out while taking Thermadrene, which had been recommended by her personal trainer. On June 28, 1999, her family files a $320 million dollar lawsuit against Crunch Fitness (source: NY Times, June 29, 1999).

• August 4, 1999: A GAO report states that the FDA did not have enough evidence to justify their proposal to limit individual and daily doses of ephedra.

• March 31, 2000: FDA reluctantly withdraws its proposed restrictions on the sale of herbal ephedra supplements.

• December 21, 2000: The New England Journal of Medicine publishes a summary of 140 adverse reactions to ephedra (Haller CA, et al. 2000). Though not intentional, this article seemed to vindicate and validate the efforts of the FDA.

• September 5, 2001: Public Citizen files a petition to FDA requesting a ban on the manufacture and sale of all ephedra-containing dietary supplements.

• January 2002: Health Canada bans the sale of ephedra supplements in Canada.

• September 3, 2002: 16-yr old Sean Riggins, a high-school football player in Lincoln, IL, suffers a seizure and dies after taking the OTC herbal supplement Yellow Jackets.

• October 7, 2002: FDA halts the importation of Yellow Jackets.

• October 8, 2002: The American Medical Association and Sidney Wolfe, MD of Public Citizen testify at a House Committee on Government Reform in favor of banning the sale of ephedra in the US. HHS Secretary Tommy Thompson asks the FDA to evaluate the scientific evidence available and recommend the "strongest possible mandatory warning label possible for ephedra products."

• February 17, 2003: Baltimore Orioles pitcher Steve Bechler collapses from heat stroke while practicing in Florida. His body temperature was reported to be 108 degrees F. He was taking Xenadrine-RFA-1, a weight-loss supplement. He dies the following day.

• March 2003: FDA again proposes putting warning labels on ephedra. At that time, the FDA was aware of at least 100 reports of deaths linked to ephedra and a report, co-authored by Representative Henry Waxman, documenting 13,000 adverse reactions to ephedra was ready.

• July 2003: Kiley Bechler, widow of Steve Bechler, files a $600 million dollar lawsuit against Nutraquest (formerly Cytodyne Technologies), the manufacturer of Xenadrine RFA-1.

• October 21, 2003: Nutraquest Inc. files for bankruptcy.

• December 30, 2003: The FDA succeeds in categorizing ephedra products as "adulterated" under the FD&C act due to their unreasonable risk of adverse reactions.

• January 5, 2004: FDA issues a ban on the sale of ephedra supplements.

• February 5, 2004: FDA seizes nearly 1000 bottles of ephedra-containing supplements from (NOTE: this web site has since been shut down) based on erroneous claims of enhanced athletic and muscular performance.

• April 12, 2004: Effective date for the January 5, 2004 ban.

• April 13, 2005: In response to a protest filed by a Park City, UT corporation (Nutraceutical Corp.), Judge Tena Campbell strikes down the FDA ban stating that FDA did not prove that ephedra was unsafe at low doses.

• June 13, 2005: FDA informs the court of its intent to appeal this decision.

• August 16, 2006: Utah District Court (Judge Tena Campbell) decision is reversed by a federal appeals court in Denver.

• May 14, 2007: In response to another protest filed by Nutraceutical Corp. (Park City, UT), the Supreme Court rejected the protest outright. This appears to be the end of the road for ephedra supplements in the US marketplace.


Lack of quality-control: "Natural" does not mean "safe". The alkaloids found in the herb ephedra can increase heart rate and blood pressure. Combined with the issue of uncertainty regarding the amounts of these ingredients in different batches and different brands of ephedra supplements, consumers put themselves at risk...even if they take the dose recommended on the label.

Interaction with caffeine: Caffeine increases the toxicity of ephedra. A large majority of the population drinks caffeinated beverages regularly. Thus, it seems inevitable that use of herbal ephedra by large populations increases the likelihood of adverse reactions. The FDA was concerned enough by this drug interaction in 1982 to ban drug products that combined caffeine with ephedrine and phenylpropanolamine (PPA).

Herbal ephedra contains ingredients that the FDA has already banned: In August 1982, FDA banned drug products containing the triple combination of caffeine-ephedrine-PPA stating that the combination was irrational and presented a potential health hazard (Federal Register, 1982). In addition, the decongestant PPA was removed from US and Canadian markets in 2000 due to the risk of stroke. Australia removed PPA products in 2001. Norephedrine is found in PPA and in the herb ephedra. If PPA is so risky, and, if ephedra contains a compound similar to PPA, ephedra also deserves to be banned.

The risks far exceed its potential benefits: Even though it is true that ephedra and ephedrine assist in promoting weight-loss, the impact is minimal. In 2003, JAMA published an extensive review of the scientific literature on ephedra and ephedrine conducted by the RAND group. They found that, by itself, ephedrine increased the rate of weight-loss by only 0.6 kg/month; when ephedrine or ephedra was combined with caffeine, the rate was still only 1.0 kg/month better than placebo (Shekelle PG, et al. 2003).

BITTER ORANGE (Citrus aurantium): "EPHEDRA 2.0"?

Another herb could replace ephedra: it's called "bitter orange". The botanical name is "Citrus aurantium". In fact, it has already appeared in some weight-loss supplements. In 2003, it was included in Xenadrine RFA-1. In 2005, herbal ephedra was removed but Citrus aurantium remained when it was renamed to Xenadrine EFX (Haller CA, et al. 2005).

As with herbal ephedra, bitter orange contains several active molecules (Gougeon R, et al. 2005):

  • synephrine
  • hordenine
  • octopamine
  • tyramine
  • N-methyltyramine

The chemical structure of synephrine is almost identical to ephedrine. So, it's not surprising that synephrine can also increase blood pressure and heart rate. Synephrine appears to have less potent BP-elevating actions than ephedrine, however those actions are magnified when combined with caffeine (Haller CA, et al. 2005).


As mentioned above, the FDA banned the sale of supplements containing ephedra in 2004. This became final in August 2006 after a series of legal challenges. Nevertheless, it's possible that ephedra supplements could still be purchased via the Internet. If that occurs, then athletes, dieters, and other consumers are urged to consider the following:

Guidelines for Athletes:

Athletes should avoid ephedra for the following reasons:

Ephedra is a stimulant; stimulants are banned from sports competition.

Ephedra can produce serious side effects, which are somewhat unpredictable: Even though some research shows that ephedra alkaloids don't increase HR or BP during aerobic exercise very much, don't be misled by this. It is risky to consume herbs with the potential for increasing blood pressure prior to, or during strenuous exercise. This would be especially true for weight-lifting, which can produce enormous, though brief, increases in blood pressure. In one study, the blood pressure in a body-builder performing leg press reached an astounding 480/350 mmHg (MacDougall J, et al. 1985).

Ephedra-caffeine supplements can also affect heat management during exercise, as in the case of Steve Bechler.

Lack of performance-enhancing effects. It's hard to understand why athletes use (abuse) ephedra in the first place. It appears that the performance-enhancing effects are minimal, if they exist at all.

Guidelines for Dieters:

Resorting to the use of stimulants for weight-loss is a poor choice. Many different stimulants have been used over the past several decades in an attempt to facilitate weight loss. Generally, this doesn't work long-term. Stimulants exert their effects by decreasing appetite, not by burning more calories. Further, attempting to lose weight by taking drugs or supplements does not achieve the other health benefits that exercise provides, namely, a stronger heart, lower blood pressure, increased bone density, and a lower risk of cardiovascular disease. Exercise is a better choice. In fact, exercise lowers blood pressure and lowers the risk of cardiovascular disease in obese people even if they remain obese (Barlow CE, et al. 1995) (Lee CD, et al. 1999).


The best source of scientific information on herbal ephedra can be found in the Natural Medicines database, published by TRC Healthcare: (

The January 2004 issue of Consumer Reports contained a review of ephedra.

Readers may also be interested in these topics:


Stan Reents, PharmD, is available to speak on this and many other exercise-related topics. (Here is a downloadable recording of one of his Health Talks.) He also provides a one-on-one Health Coaching Service. Contact him through the Contact Us page.


Armstrong LE, Casa DJ, Maresh CM, et al. Caffeine, fluid-electrolyte balance, temperature regulation, and exercise-heat tolerance. Exercise Sport Sci Rev 2007;35:135-140. Abstract

Astrup A, Breum L, Toubro S, et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. Int J Obes Relat Metab Disord 1992;16:269-277.  Abstract

Astrup A, Toubro S. Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man. Int J Obes Relat Metab Disord 1993;17 suppl 1:S41-S43.  Abstract

Barlow CE, Kohl HW, Gibbons LW, et al. Physical fitness, mortality and obesity. Int J Obes Rel Metab Disord 1995;19(suppl 2):S41-S44.  Abstract

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Chait LD. Factors influencing the reinforcing and subjective effects of ephedrine in humans. Psychopharmacol (Berl) 1994;113:381-387.  Abstract

Clemons JM, Crosby SL. Cardiopulmonary and subjective effects of a 60 mg dose of pseudoephedrine on graded treadmill exercise. J Sports Med Phys Fit 1993;33:405-412.  Abstract

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Gougeon R, Harrigan K, Tremblay J-F, et al. Increase in the thermic effect of food in women by adrenergic amines extracted from Citrus aurantium. Obesity Research 2005;13:1187-1194. Abstract

Gruber AJ, Pope HG. Ephedrine abuse among 36 female weightlifters. Am J Addict 1998;7:256-261.  Abstract

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Toubro S, Astrup AV, Breum L, et al. Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine/caffeine mixture. Int J Obes Relat Metab Disord 1993;17 suppl 1:S69-S72.  Abstract

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Stan Reents, PharmD, is a former healthcare professional. He has been a member of the American College of Lifestyle Medicine (ACLM) and a member of the American College of Sports Medicine (ACSM). In the past, he has been certified as a Health Fitness Specialist by ACSM, as a Certified Health Coach by ACE, as a Personal Trainer by ACE, and as a tennis coach by USTA. He is the author of Sport and Exercise Pharmacology (published by Human Kinetics) and has written for Runner's World magazine, Senior Softball USA, Training and Conditioning and other fitness publications.

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