the good, the bad, & the banned
Written by Rebecca J. Anderson, PhD
In the 16th century, Paracelsus famously declared, “All things are poison…only the dose determines that a thing is not a poison.” Despite this edict, remedies derived from botanicals have long been considered not only “natural” but also wholesome and harmless. And consumers of pharmacologically active botanicals mistakenly think that “if some is good, more is better.” A case in point is ephedra: an herb that was used successfully for millennia, both as a natural folk medicine and a commercial pharmaceutical. But then it became so popular as an herbal remedy that it was abused, declared hazardous, and subsequently banned.
“All things are poison…only the dose determines that a thing is not a poison.” – Paracelsus
It started in China
When Carl Schmidt finished his internship at the University of Pennsylvania Hospital in August 1919, he became an instructor in pharmacology at the university.1 He soon took advantage of another opportunity: to spend two years teaching at the Peking Union Medical College under a Rockefeller Foundation fellowship. In the summer of 1922, he and his wife traveled by ship to China and then by train to Peking (now Beijing).
In parallel with Schmidt, Ko Kuei Chen received his PhD in biochemistry and physiology from the University of Wisconsin in 1923.2 He then returned to China to teach pharmacology at Peking Union Medical College.
Chen was interested in Chinese herbal medicines. There were about 4,000 medicinal substances in the Chinese pharmacopeia, and Chen and Schmidt worked together, hoping to discover some new, pharmacologically active compound.1,3 They tested a handful of the most popular traditional herbs, but the results were discouraging.1,2
Then, one day, Chen discussed the project with his uncle, who was a pharmacist. He asked for suggestions of native medicines that might possess “real” actions, and his uncle recommended a few, including ma huang.1,4
Ma huang refers to a preparation of plant material from Ephedra sinica (Chinese ephedra). The dried stems and leaves of the Ephedra plant could be prepared as capsules, tablets, tinctures, and teas.5 Peking shops sold ma huang in brownish-green sticks about 1 mm in diameter and 10–15 mm long.6
Known in the rest of the world as ephedra, ma huang had been used in traditional Chinese medicine as a stimulant and anti-asthmatic for more than 5,000 years.1–3,6,7 Various Ephedra plant species were also used in the Bronze Age Mediterranean (1050 BCE), by Greek physicians (50 CE), and in Russia (19th century), India, and Mexico.4,8 Native Americans and Mormon pioneers brewed other Ephedra species as a tea, called “Indian tea” and “Mormon tea,” respectively.2–4
Chen and Schmidt obtained a small supply of ma huang. In the fall of 1923, they tested it in an anesthetized dog, at the end of a student laboratory experiment.4 To their amazement, injection of the crude aqueous extract caused a prolonged rise in blood pressure, accelerated heart rate, and constricted kidney blood vessels.7
A few days later, Chen isolated and crystallized the active substance from ma huang and confirmed that it had the same effects as the crude extract.1,2,4 Searching the literature, Chen and Schmidt discovered that Nagayoshi Nagai, a professor at Tokyo University, had already crystallized this compound from ma huang in 1885.3,7 Nagai called it ephedrine, but his paper included only a few short notes regarding its biological properties.1,6,7
The first physiological investigations of ephedrine were conducted by other Japanese researchers in 1887. At the doses they used, ephedrine dilated the pupils, but it had toxic cardiovascular effects. Japanese manufacturers produced and marketed ephedrine, and clinicians briefly used it for dilating pupils. But they thought it was too toxic for other therapeutic uses.4
Ephedrine was first listed in E Merck’s Index in 1896. Interestingly, it was available for five years before the actions of the first adrenal extracts were reported and more than 12 years before adrenaline (epinephrine) was first isolated and identified by John Jacob Abel (the founder of ASPET) and Jokishi Takamine.4
In 1917, Japanese researchers reported that ephedrine’s actions were similar to epinephrine. They saw value in using ephedrine to treat only one condition, asthma, which was also relieved by epinephrine. Unfortunately, these clinical findings attracted little attention in the US and Europe.2,4
So, Chen and Schmidt embarked on a thorough investigation of ephedrine’s pharmacologic properties.1,4 In a nod to Paracelsus, Chen and Schmidt pointed out that simple adjustments in dose made all the difference between ephedrine’s reputation as a toxic substance and its therapeutic potential.
They first confirmed the Japanese scientists’ observations that ephedrine mimicked the actions of epinephrine: pupil dilation, bronchodilation, increased blood pressure and heart rate, uterine contraction, and relaxation of gut smooth muscle.4,6,7 In their follow up experiments, they showed that ephedrine produced the same effects in cats and rabbits, as they had seen in dogs.6
Ephedrine was less potent than epinephrine. And unlike epinephrine, ephedrine was orally active and had a much longer duration of action.4,6 It was also more stable in solution.
Although they had limited equipment available at that time, they demonstrated that ephedrine’s mechanism of action was a direct effect on the heart, blood vessels, and lung. The effects were comparable to the “fight-flight” response produced by adrenaline or to stimulation of sympathetic nerves.6,7
Chen and Schmidt reported the results of their first series of experiments in 1924.6,7
Clinical acceptance
Ephedrine’s oral bioavailability and longer duration of action indicated that it might be more useful clinically than epinephrine. Chen and Schmidt conducted the initial clinical studies on patients in the wards at the Hospital of Peking Union Medical College, as well as on themselves. They found that ephedrine produced “uniformly favorable results; no untoward symptoms of any kind.”6
When sufficient supplies were available, Chen and Schmidt sent the compound to T. G. Miller at the University of Pennsylvania and L. G. Rowntree at the Mayo Clinic. Their results in patients were also favorable.4
The first clinical reports were published in 1925–1926 and led to ephedrine’s approval by the Council of Pharmacy and Chemistry of the American Medical Association in 1926.2,4 Prior to the Food, Drug, and Cosmetic Act of 1938, there was no mechanism for review of new drugs by the federal government.2 Recognition by the AMA Council was the equivalent of FDA approval.
Several manufacturers in Europe, Asia, and North America marketed ephedrine, and it was “made available to clinicians in general, as rapidly as possible.” 4
In 1930, Chen and Schmidt published a 130-page monograph on the chemistry, pharmacology, and therapeutics of ephedrine and related ephedra alkaloids.4 The monograph discussed the routes of administration, dosage, absorption, and pharmacokinetics of ephedrine. Pharmacologically, it is an alpha- and beta-adrenergic agonist.
Based on the findings reported by numerous clinical investigators, Chen and Schmidt proposed a host of therapeutic uses including asthma, hay fever, bronchitis, emphysema, whooping cough, spinal anesthesia, hypotension, shock, nasal congestion, mydriasis, hives, menstrual cramps, and as an antidote for narcotic drugs.4
From the AMA’s acceptance in 1926 until well into the 1950s, ephedrine was one of the most widely used drugs in Western medicine.1,2
Ephedrine’s bronchodilator action made it useful to treat asthma, whooping cough, and bronchitis, at a time when the only other available bronchodilator was theophylline.2,4 It was also useful as a nasal decongestant for the common cold and for various allergic disorders, such as rhinitis.4 Many combination products containing ephedrine were marketed as well.2
As a powerful central nervous system stimulant, ephedrine was used to treat morphine and barbiturate overdose, narcolepsy, and catalepsy.2 Its cardiovascular uses included intravenous injection to bolster blood pressure during spinal anesthesia and, as an oral drug, to treat chronic hypotensive states and postural hypotension.2,4
Like all drugs, ephedrine’s usefulness had its limits. As early as 1930, Chen and Schmidt said, “It is now quite certain that ephedrine, in spite of its present popularity, is far from ideal.”4 The side effects reported by patients included headache, palpitations, sweating and thirst, giddiness, nausea, difficulty urinating, muscle weakness, tremors, restlessness, and insomnia.4
The toxic effects seen in animals included accelerated heart and respiratory rates, convulsions, and death from cardiac and respiratory failure. But at appropriately chosen clinical doses, Chen and Schmidt said, the benefits outweighed the side effects.4
Ephedrine isomers
Because there are two chiral centers, the molecule can be configured into four separate stereoisomers. The most potent isomer has been designated “ephedrine” and can account for up to 90% of the total Ephedra alkaloid content in the plant material.9
In 1889, chemists at E. Merck in Germany isolated one of the other isomers from European Ephedra plants and called it “pseudoephedrine.”4,6,7 Pseudoephedrine can account for up to 27% of total Ephedra alkaloid content.9 The other isomers include phenylpropanolamine and cathine.
In the late 1920s, chemists at E. Merck were able to resolve and separate the isomers, but they marketed the synthetic racemic mixture and called it Ephetonin. American manufacturers preferred to prepare ephedrine by extracting it from Ephedra plants.4
Chen and Schmidt’s 1930 monograph included an exploration of several of the alkaloids’ stereoisomers. From their research results, they concluded that pseudoephedrine and the other alkaloids found in Ephedra plants were “distinctly less useful” than ephedrine.4
Moving on
Carl Schmidt returned to the US in 1924 to resume his post as an assistant professor of pharmacology at the University of Pennsylvania. He rose through the ranks to department chairman in 1939.1 Schmidt served as editor of Circulation Research (1958–1962) and managing editor of the Journal of Pharmacology and Experimental Therapeutics (1940–1942). In 1962, he was appointed research director of the Naval Air Development Center and then served as clinical professor of pharmacology at the University of South Florida College of Medicine in Tampa (1970–1982).
In addition to ephedrine, Schmidt conducted research on respiratory and circulatory reflexes, cerebral blood flow, renal circulation, and aviation and space medicine. He was considered a pioneer in the field of clinical pharmacology.1 In 1949 and 1950, Schmidt served as president of ASPET.
K. K. Chen also returned to the US and was awarded an MD from Johns Hopkins University in 1927. In 1929, he was appointed director of pharmacological research at Eli Lilly & Company and became a highly respected figure in new drug discovery.2 After retiring from Lilly in 1963, he shifted from a part-time position to the full-time faculty at Indiana University School of Medicine, where he taught until 1968.
In addition to ephedrine, Chen is credited with discovering a successful treatment for cyanide poisoning, the structure-activity relationships of cardiac glycosides, and synthetic methadone-analgesic drugs. He followed Schmidt as president of ASPET in 1952. In 1969, Chen published a monograph, The First Sixty Years (1908–1969) of ASPET.
Over-the-counter use
When chemically synthesized, ephedrine and pseudoephedrine are regulated by the Food and Drug Administration (FDA) as drugs.10 Synthetic ephedrine has been approved by the FDA to treat hypotension during anesthesia. Although it is still sometimes prescribed off-label for myasthenia gravis and respiratory conditions such as bronchial asthma, ephedrine has largely been replaced by superior and more selective drugs.2,11
On the other hand, pseudoephedrine continued to be popular as an over-the-counter (OTC) nasal decongestant in products such as Sudafed.9
The Food, Drug & Cosmetic Act of 1938 required manufacturers to submit a New Drug Application with data that demonstrated the drug’s safety before market approval could be granted. To deal with the vast number of OTC drugs that were already on the market before this requirement, the FDA created a system to review and classify OTC products as “generally recognized as safe and effective” (GRAS/E). Those drugs could remain on the market, if they conformed to the FDA’s OTC guidelines for dosage, labeling, and warnings. Pseudoephedrine, phenylpropanolamine, and phenylephrine were among the GRAS/E-designated drugs.12
In 2005, FDA removed the GRAS/E status for phenylpropanolamine, because data showed it was causing hundreds of strokes per year in adults over 50.12
Pseudoephedrine also came under scrutiny in 2005.12 Because a simple synthetic step can transform pseudoephedrine into methamphetamine, Congress passed the Combat Methamphetamine Epidemic Act. This new law required pharmacists to move medicines containing pseudoephedrine “behind the counter.” They are still sold without a prescription, but consumers must provide ID and are limited in the amounts of the product that they can buy.12
Many drug makers voluntarily replaced pseudoephedrine with phenylephrine, which they could still sell over-the-counter without restrictions. Phenylephrine is an alpha-adrenergic agonist, and it constricts blood vessels. It had been used medically since the 1930s and enjoyed GRAS/E status.12,13
Unfortunately, when phenylephrine is taken orally, it is quickly metabolized by MAO enzymes to inactive compounds.
Less than 1% of the oral dose is absorbed unmetabolized, whereas 55–75% of pseudoephedrine (despite a similar structure) reaches the bloodstream unchanged.12
FDA conducted a comprehensive review of all available data on the safety and efficacy of oral phenylephrine. This included historical data that had been used 30 years earlier to support the initial use of phenylephrine as a nasal decongestant, as well as newer clinical data on the pharmacokinetics and metabolism of orally administered phenylephrine.14
In September 2023, FDA’s Nonprescription Drug Advisory Committee reviewed this accumulated data and unanimously agreed that phenylephrine does not work when it is taken orally.12,14 On November 7, 2024, FDA proposed removal of phenylephrine as an active ingredient in OTC oral nasal decongestant products.14
However, the FDA proposal excluded phenylephrine nasal sprays from its recommendation. Phenylephrine via nasal spray reaches the nose without being metabolized and remains effective as a nasal decongestant. But those nasal spray products can increase blood pressure and are not recommended for individuals with essential hypertension.12,14
Deregulating supplements
In the 1980s and early 1990s, health foods and dietary supplements grew in popularity. They were sold not only in pharmacies but also in grocery stores, health food stores, and over the internet.15 Their popularity triggered a grassroots effort to limit FDA oversight. In response to consumer pressure, Congress passed the Dietary Supplement Health and Education Act (DSHEA) of 1994, which substantially limited the FDA’s role in regulating these products.2,15
According to this legislation, dietary supplements, including herbs, are not “drugs” and are not required to have FDA approval or be registered with FDA before they are produced and marketed.15 Because FDA lacks the authority to review safety and efficacy data, the agency cannot provide dosing information or monitoring advice.14
Regulators also do not verify the amounts of ingredients listed on the label and do not ensure the identity, purity, quality, composition, or strength of those ingredients.15,16 Instead, dietary supplement companies establish their own manufacturing guidelines.5,15 Not surprisingly, manufacturers and distributors often promoted their products by claiming unsubstantiated benefits and rarely mentioned potential hazards.
Once a dietary supplement is on the market, FDA officials can take regulatory action against it, but they must demonstrate unequivocally that the product is unsafe.2,15 Unfortunately, that safety assessment is handicapped, because FDA does not require supplement makers to report adverse events or consumer complaints.16
Ephedra supplements
Among the most notable dietary supplements were herbal products containing ephedra. Manufacturers aggressively promoted them, claiming the products aided weight loss and boosted sports performance and energy.9,10 The weight loss effect was thought to be due to enhanced metabolism—so-called “fat burners.”17 The performance enhancement allegedly came from ephedrine’s adrenaline-like properties.
The FDA has never approved ephedra or synthetic ephedrine for weight loss or to enhance athletic performance.9
By the 1990s, FDA officials grew concerned about the seriousness and increasing number of adverse reactions associated with ephedra.17 Everyone knew that ephedra raised blood pressure and could stress the circulatory system. But the FDA’s particular concern was that the ephedra adverse events were not only reported in individuals with co-morbidities such as hypertension, but also in young and otherwise healthy individuals. There were also reports that children and teenagers who used ephedra products exhibited a “stimulant overdose syndrome.”17
In June 1997, FDA issued its first proposed rule concerning ephedra use. Dietary supplement manufacturers were asked to include a labeling statement, warning that ephedra-containing products may be hazardous and should not be used for more than 7 days.10,11,18
The FDA also proposed restrictions on the amount of ephedra alkaloids in those products, and manufacturers were urged to avoid combining ephedra with other ingredients known to have stimulant effects.16 Caffeine, a mild stimulant, was commonly combined with ephedra, and that likely amplified the ephedrine effects on the cardiovascular and central nervous systems.11,16 The heart and brain could be further stressed, when those who took ephedra/caffeine-containing products also consumed large quantities of caffeine in coffee, tea, and soft drinks.
In 2000, FDA modified its proposed rule, in response to a review of 140 adverse event reports that had been submitted to the agency between 1997 and 1999.10,11 FDA asked Christine Haller and Neal Benowitz at the University of California, San Francisco, to conduct an independent review of those adverse event reports, all of which concerned ephedra supplements.
Haller and Benowitz found that 47% of the adverse events involved cardiovascular symptoms (i.e., hypertension, palpitations, stroke) and 18% involved the brain (e.g., seizures). There were 10 deaths, and 13 adverse events resulted in permanent disability. These findings heightened the FDA’s concerns about the risks of ephedra-containing supplements.11
Haller and Benowitz noted that unlike vitamins and minerals, ephedra-containing supplements are not essential for proper nutrition. “People who take these products to increase their exercise capacity or to lose weight place themselves at risk without a substantial likelihood of benefit.”11
In 2002, in addition to the adverse event reports received by the FDA, several clinicians published articles in the medical literature, where they raised serious concerns about the safety of dietary supplements containing ephedra.11,19 The Annals of Internal Medicine noted that, although products containing ephedra made up less than 1% of dietary supplement sales, they accounted for 64% of the serious adverse events that had been reported.29,21
Because dietary supplement makers were not required to report consumer complaints, industry critics believed there were likely thousands of ephedra side effect cases that the FDA never heard about.16
The RAND review
Realizing that the FDA-reported cases were not sufficient to assess the products’ safety, the Department of Health and Human Services (HHS) commissioned the Southern California Evidence-based Practice Center of the RAND Corporation to conduct an independent scientific review.9,10,19,22
In June 2002, RAND experts were charged with reviewing the adverse events associated with ephedra alkaloids (particularly in dietary supplements), assess causation, and determine the level of risk that ephedra posed to consumers.11 The report was due by the spring of 2003.2,10
The RAND reviewers’ comprehensive 300-plus page technology assessment and evidence report found that ephedra and ephedrine, both alone and in combination with caffeine, could induce a modest weight loss.9,22 But in the few well-designed studies, the largest weight loss associated with ephedra was only about eight pounds, and the effect lasted less than six months.15,22
In contrast, various FDA-approved weight-loss products available at that time produced a greater and more sustained effect. For example, phentermine, an amphetamine-like appetite suppressant, produced an average 16-pound weight loss.22
RAND found no studies that assessed the effect of ephedra-based botanicals on athletic performance. The reviewers concluded, “We did not find sufficient evidence to support the use of ephedra for enhancing athletic performance.”22
More disturbing, the RAND reviewers found that ephedra and ephedrine, alone and in combination with caffeine, were associated with 2–3 times the risk of nausea, vomiting, psychiatric symptoms (such as anxiety and mood changes), autonomic hyperactivity, upper gastrointestinal symptoms, and heart palpitations.9,22
Also, the RAND meta-analysis suggested that ephedra and ephedrine increased the risk of serious adverse events including profound psychiatric illnesses, heart attacks, strokes, seizures, and death.9
Throughout the early 2000s, isolated reports of high school and college athlete deaths had been linked to ephedra-containing dietary supplements.16 The National Collegiate Athletic Association, the National Football League, and the International Olympic Committee had all banned ephedra.23,24
In addition, the deaths of servicemen and women, who were in their early 20s to early 30s and in good health, prompted the US Army, Navy, Marine Corps, and Air Force military exchanges and commissaries worldwide to stop selling ephedra products.25
But ephedra was still allowed and in common use among Major League Baseball players.24
The case of Steve Bechler not only made headlines but also prompted early release of the RAND report.
The Bechler case
In February 2003, a promising young pitcher, Steve Bechler, 23, reported to spring training, determined to make the Baltimore Orioles’ team roster.2,23 He was out of shape, 40 pounds overweight, and unaccustomed to the heat and humidity in Ft. Lauderdale, FL.23,24
To lose weight, Bechler had been decreasing his food intake, consuming primarily liquids and semi-liquids.24 On the morning of February 16, he skipped breakfast and took 3 capsules of the dietary supplement, Xenadrine RFA-1 (3-times the recommended dose), right before his all-important qualifying workout.20,23 During the 2-lap run, Bechler collapsed and was rushed to the hospital.23
He had a fever of 108°F, high blood pressure, and was bloated from fluid retention. Several times throughout the day, Bechler suffered a cardiac arrest. Each time, the hospital staff was able to revive and stabilize him, but on the following morning, he was totally unresponsive. His wife agreed to take him off life support, and Bechler was pronounced dead at 10:12 am on February 17, 2003.23
The Broward County medical examiner concluded that Bechler died from heatstroke, followed by multi-organ failure. Contributing factors included a pre-existing liver abnormality, borderline hypertension, his excessive weight, Florida’s heat and humidity, and low food consumption.20,23
The toxicology report confirmed that Bechler’s body contained “significant amounts” of ephedra, the active ingredient in Xenadrine RFA-1.24 Joshua Perper, the medical examiner, said that “the toxicity of ephedra played a significant role in the death of Mr. Bechler.”23
Shortly after Bechler’s death, Baseball Commissioner Bud Selig began pushing for stricter drug policies, including on dietary supplements.23,24
Ephedra had been implicated in at least 100 deaths, many of them high school, college, and professional athletes, as well as more than 17,000 nonfatal adverse events.2,16 But the publicity surrounding Bechler’s death marked a turning point.
Immediate response
On February 28, 2003, and partly prompted by Bechler’s death, HHS Secretary Tommy Thompson and FDA Commissioner Mark McClellan held a press conference.2,15 They hurriedly released the findings of the RAND report and announced that FDA was taking enforcement actions against firms that made unsubstantiated claims about enhanced athletic performance with ephedra-containing products.2,10
Even before the FDA could take official action under the cumbersome DSHEA regulations, Commissioner McClellan said, “Do not take these products. They are simply too risky.” 10
In March 2003, FDA sent warning letters to firms that promoted ephedra products, instructing them to either remove their products’ unproven claims or to substantiate those claims, especially related to athletic performance. The FDA also proposed a “black box” warning label on all products containing ephedra, to note that serious adverse events and deaths had been reported after ephedra use.15 Many firms complied.10
DSHEA permitted FDA to remove a dietary supplement from the market if it presented “a significant or unreasonable risk of illness or injury.”10 To comply with this requirement, FDA officials conducted an exhaustive and highly resource-intensive evaluation of all of the relevant scientific evidence.11,26
In addition to the adverse event reports it had received and the independent RAND analysis, the FDA reviewed the well-known pharmacology of ephedra and ephedrine and the peer-reviewed scientific literature on the effects of ephedra.10,11,27 FDA also solicited information from the general public about ephedra-associated health risks and received tens of thousands of comments.10,15
On December 30, 2003, FDA officials announced plans to ban dietary supplements containing ephedra.21 They concluded from their comprehensive review that ephedra was linked to significant adverse health outcomes, including heart attack and stroke.10
FDA determined that products containing ephedra did, indeed, meet the DSHEA requirement of “an unreasonable risk of illness or injury.” 21
FDA notified 62 marketers of the planned ban and also issued a consumer alert, warning the public to stop buying and consuming ephedra products immediately.21 On February 11, 2004, FDA published the final rule prohibiting the sale of dietary supplements containing ephedra alkaloids.10,18,26,27 When this final rule became effective on April 12, 2004, it was the first time that FDA’s series of proposed rules on ephedra could, finally, be enforced.27
In fact, it was the first time that government officials had blocked the sale of any dietary supplement.21 FDA, in conjunction with the Federal Trade Commission and the Department of Justice, conducted injunctions, seizures, and joint enforcement actions against non-compliant firms.10,18,19 In some cases, non-compliant companies and individuals were prosecuted.19
On November 23, 2004, FDA intensified its efforts to protect consumers by taking enforcement action against dietary supplements containing ephedra that claimed to treat serious diseases and conditions.18 US Attorneys filed charges against a supplement supplier that claimed its ephedra product could be used for “poison release” and “ischemic injury of myocardium,” among other things. Acting FDA Commissioner Lester Crawford said, “We’ve issued a rule banning ephedra-containing products, and we’re sparing no effort to stop their manufacture and distribution.”10
Challenging the rule
In 2005, one manufacturer successfully challenged the legality of the ephedra ban in the District Court of Utah. But in August 2006, the US Court of Appeals for the 10th Circuit in Denver reversed that decision and upheld FDA’s final rule.26
The 3-judge panel cited the 133,000 pages of evidence that the FDA had compiled and reaffirmed that ephedra posed an unreasonable risk of illness or injury, especially for those suffering from heart disease and high blood pressure. Based on this mountain of evidence, the judges said, the FDA had acted correctly in banning ephedra as a dietary supplement.26 That court decision essentially ended US production and marketing of ephedra products.
In subsequent years, the FDA worked closely with US Customs and Border Protection, Immigration and Customs Enforcement, and the Drug Enforcement Agency to monitor imports of ephedra-containing products, which mostly came from Asia. Imported ephedra raw materials and finished products were seized by US Marshals.26
Associate FDA Commissioner Dara Corrigan said, “We will continue to take enforcement action that prevents potentially harmful products from reaching consumers and endangering their health.”28
The constraints imposed by DSHEA required FDA officials to expend considerable time and effort to accumulate sufficient safety data, not only to draw unambiguous scientific conclusions but also to withstand the scrutiny of the federal courts. In the meantime, numerous consumers had suffered serious side effects, and some had died.
In 2003, the editors of the Journal of the American Medical Association said, “The most important lessons from the new information on ephedra are demonstration of the inadequate nature of the current system of regulation of dietary supplements and recognition that much more rigorous oversight of these biologically active agents is necessary to protect the health and safety of the public.”15
The FDA’s ban under DSHEA was the final chapter of a pharmacologically active herb whose benefits vs. risks depended, not surprisingly, on dose. Over many centuries, ephedra moved from an effective herbal medicine to a widely used therapeutic drug, to a popular but misleadingly labeled dietary supplement, and, finally, to official banishment.
For those seeking to lose weight, it’s unfortunate that the GLP-1 drugs did not come along sooner. But that’s another story.
