Ephedra (Ephedra sinica) / Ma huang

Ephedra (Ephedra sinica) / Ma huang

Background

Note : On December 30, 2003, U.S. federal officials announced plans to ban the sale of dietary supplements containing ephedra, due to continued and growing health concerns. The FDA notified more than 60 companies that market ephedra products, and issued a consumer warning. U.S. officials stated that within several weeks, a regulation would be issued, after which it will become illegal after 60 days to sell products containing ephedra. Prior to this announcement, sales of ephedra had already been banned in several U.S. states, including New York, Illinois, and in Florida to minors.

Ephedra sinica , a species of ephedra (Ma huang), contains the alkaloids ephedrine and pseudoephedrine, which have been found to induce central nervous system stimulation, bronchodilation, and vasoconstriction. In combination with caffeine, ephedrine appears to elicit weight loss (in trials of 1-12 months duration). However, studies of ephedra or ephedrine monotherapy have been equivocal. The majority of human trials of weight loss have been small with methodological weaknesses including large dropout rates due to adverse effects, and incomplete reporting of blinding or randomization. Numerous trials have documented the efficacy of ephedrine in the management of asthmatic bronchoconstriction and hypotension. However, commercial preparations of non-prescription supplements containing ephedra have not been systematically studied for these indications.

Major safety concerns have been associated with ephedra or ephedrine use, including hypertension, tachycardia, CNS excitation, arrhythmia, myocardial infarction, and stroke. In 1997, due to over 800 U.S. reports of serious toxicity (and many more worldwide) including at least 22 deaths in adolescents and young adults, the U.S. Food and Drug Administration (FDA) adopted a policy that ephedra-containing products must: (1) be labeled with all possible adverse effects, including death; (2) contain no more than 8mg of ephedrine per serving; and (3) be used for no more than seven days. The FDA also proposed a maximum daily dose of 24mg, and a ban on ephedra-caffeine combination products (these proposed limits were subsequently withdrawn).

In 2002, Samenuk et al. identified 926 cases of possible ephedra toxicity reported to the Adverse Reaction Monitoring System of the FDA between 1995-1997. In 37 patients, use of ephedra was temporally related to stroke (16 patients), myocardial infarction (10), or sudden death (11). Autopsies performed in patients who experienced sudden death showed a normal heart in one, coronary atherosclerosis in three, and cardiomyopathies in three. In 36 of the 37 patients, use of ephedra was reported to be within the manufacturers' dosing guidelines.

In 2003, a report was prepared by Shekelle et al. on behalf of the RAND Southern California Evidence-based Practice Center for the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. This study reviewed available clinical trials, as well as more than 1,500 adverse event reports to the FDA and adverse event reports to the manufacturer Metabolife. Although most prospective trials were not sufficiently large and most adverse event reports were not sufficiently detailed, the authors identified three deaths, two myocardial infarctions, two cerebrovascular accidents, one seizure, and three psychiatric cases that were considered to be "sentinel events" (i.e., strongly tied to ephedra use within 24 hours without other plausible explanations). In addition, 50 other possible sentinel events were identified.

A 2003 analysis by Bent et al. in Annals of Internal Medicine found that products containing ephedra account for 64% of all adverse reactions to herbs in the United States, but only represent 0.82% of herbal product sales. The relative risk for an adverse reaction in a person using ephedra compared with other herbs was extremely high, ranging from 100 (95% CI, 83 to 140) for kava to 720 (95% CI, 520 to 1100) for Ginkgo biloba . It was concluded that ephedra use poses a greatly increased risk of adverse reactions compared with other herbs. A 2003 analysis published in Neurology also found increased risk of stroke associated with ephedra-containing products.

Despite widely publicized safety concerns and mounting public pressure, and the highly publicized 2003 death of a U.S. major league baseball pitcher thought to be related to ephedra, 14% of individuals using non-prescription weight-loss products in the U.S. continued to take ephedra or ephedrine-containing products.

Synonyms

Amsania, brigham tea, budshur, cao Ma huang (Chinese), chewa, Chinese ephedra, Chinese joint fir, desert herb, E. altissima, E. americana, E. anti-syphilitica, E. distacha, E. distachya, E. equisetina (Mongolian Ephedra) , E. geradiana, E. helvetica, E. intermedia (intermediate ephedra), E. major, E. nevadensis, E. shennungiana, E. trifurca, E. viridis, E. vulgaris, Ephedraceae (family), Ephedrae herba, epitonin, European ephedra, herba ephedrae, horsetail, hum, huma, Indian joint fir, intermediate ephedra, joint fir, khama, mahoàng, máhuáng, "Mao" (Chinese), mao-kon, mahuuanggen, Mexican tea, môc tac ma hoàng, Mongolian ephedra, Mormon tea, mu-tsei-ma-huang, muzei mu huang, natural ecstasy, phok, popotillo, san-ma-huang, sea grape, shrubby, soma, song tuê ma hoàng, squaw tea, teamster's tea, trun aa hoàng, tsao-ma-huang, tutgantha, yellow astringent, yellow horse, zhong Ma huang.

Note : There are approximately 40 species of ephedra.

Multi-ingredient preparations containing ephedra: Acceleration, AllerClear, AllerPlus, Andro Heat, Better BodyEnergy for Life, Bio Trim, Biovital Plus, Bladderwrack-Dandelion Virtue, Breathe-Aid Formula, Breath Easy, Cordephrine XC, Diet Fuel, Dymetadrine Xtrem, EPH-833, Ephedra Plus, Thermogen, Guarana-Gotu Kola Virtue, Herba Fuel, Herbal Decongestant Expectorant Capsules, Herbalife - Thermojetics Original Green, Metabolife 356, Metabolift, Metaboloss, MetaboTRIM, Naturafed, Naturally Ripped, Naturatussin 1, Nettle-Reishi Virtue, Power Thin, ProLab Stoked, Pro-Ripped Ephedra, Respa-Herb, Respiratory Support Formula, Ripped Fuel, SinuCheck, SinuClear, SnoreStop, Thermadrene, Thermic Blast, Thermicore, Thermo Cuts, ThermoDiet, Ultra Diet Pep, Xenadrine RFA-1.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Weight loss
Ephedra contains the chemical ephedrine, which appears to cause weight loss when used in combination with caffeine, based on the available scientific evidence. The results of research on ephedrine alone without caffeine are unclear. The amounts of ephedrine in commercially available products has widely varied.

A

Bronchodilator (asthma)
Ephedra contains the chemicals ephedrine and pseudoephedrine which are bronchodilators (expand the airways to assist in easier breathing). It has been used and studied to treat asthma and chronic obstructive pulmonary disease in both children and adults. Other treatments such as beta-agonist inhalers (for example, albuterol) are more commonly recommended due to safety concerns with ephedra or ephedrine.

B

Low blood pressure
Chemicals in ephedra can stimulate the heart, increase heart rate, and raise blood pressure: Ephedrine, a component of ephedra, is sometimes used in hospitals to help control blood pressure. However, the effects of over-the-counter ephedra supplements taken by mouth are not well described in this area.

C

Allergic nasal symptoms (used as a nose wash)
One study suggests that ephedrine nasal spray, a chemical in ephedra, may help treat symptoms of nasal allergies. Additional research is needed before a recommendation can be made.

C

Sexual arousal
One small study suggests that ephedra may increase sexual arousal in women. Further well designed research is needed to confirm these results.

C

* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acute coryza (rhinitis), anaphylaxis (a severe allergic reaction), anti-inflammatory, appetite suppressant, athletic performance enhancer, bed-wetting, body building, chills, colds, congenital myasthenic syndrome, cough, decongestant, depression, diuretic, dyspnea (shortness of breath), edema, energy enhancer, euphoria, fevers, flu, gonorrhea, gout, hay fever, hives, increased sweating, joint pain, kidney disease, lack of perspiration, metabolic enhancement, myasthenia gravis, narcolepsy, nasal congestion, nephritis, obesity, performance enhancement, runny nose, shortness of breath, stimulation of energy, syphilis, stimulant, upper respiratory tract infections, urticaria (rash), uterine stimulant, water retention.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. There is wide variability in the alkaloid content of different preparations of ephedra. A 1998 study by Gurley et al. examined the pseudoephedrine and ephedrine content of nine commercially available nutritional supplements containing Ephedra sinica . Significant variations in content were found for pseudoephedrine ranging from 0.52-9.46mg and for ephedrine from 1.08-13.54mg per recommended dose. A 1992 study by Liu et al. was conducted by collecting 22 different ephedra products from herbal shops throughout Taiwan. A four-fold difference was found in the amounts of the various alkaloids, ranging from 0.536-2.308%. Average ephedra supplement content is 1% of the crude plant.

Different ephedra species, yielding markedly different quantities of active alkaloids, are all sold as Ma huang in China, leading to difficulties for consumers trying to find standardized products. Ephedra sinica plants grown in northern China often have a different morphology and alkaloid content from the same species grown in southern China.

Adult Dosing (18 years or older):

Note : The United States Federal Government announced on Tuesday December 30, 2003 that it is banning the sale of ephedra early in 2004. Consumers are urged to stop using the herbal weight control supplement immediately as it has been linked to numerous adverse health effects including death.

Controversy Regarding Dosing : There is disagreement regarding the optimal form and dose of ephedra. Traditionally, herbalists have recommended a wide range of doses, which are typically higher than U.S. Food and Drug Administration (FDA) recommendations. In the past, the FDA has recommended a maximum of 8mg up to every six hours (total daily dose of 24mg) for up to seven days. However, doses up to 25mg of total ephedra alkaloids four times daily have been recommended by some experts, and doses in some studies have been as high as 50-100mg of ephedra three times daily. Over-the-counter drugs containing ephedra generally contain warning labels advising adults to take 12.5-25mg every four to six hours, and not to exceed 150mg in 24 hours.

Weight Loss : In the past, the FDA has recommended no greater than 8mg every six hours for up to seven days. Doses used in some clinical trials have been 25-50mg three times daily.

Pediatric Dosing (younger than 18 years):

Ephedrine is not recommended in children due to the risk of toxicity and death. Purified ephedrine has been given to children older than 2 years of age in doses of 2-3mg/kg/day divided into 4-6 daily doses in hospital settings.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Persons with a known allergy to ephedra, ephedrine or pseudoephedrine (Sudafed®) should avoid ephedra.

Side Effects and Warnings

The FDA has collected thousands of reports of serious toxicity (including over 100 deaths). On December 30, 2003, U.S. federal officials announced plans to ban the sale of dietary supplements containing ephedra, due to continued and growing health concerns. The FDA notified more than 60 companies that market ephedra products, and issued a consumer warning. U.S. officials stated that within several weeks, a regulation would be issued, after which it will become illegal after 60 days to sell products containing ephedra.

Some people may experience abdominal discomfort (nausea, vomiting, diarrhea, loss of appetite, constipation), anxiety, dizziness, headache, tremor, insomnia, dry mouth, delirium, or fainting. Ephedra may also cause irritability, euphoria, hallucinations, seizures, or stroke, as well as low potassium levels in the blood, exaggerated reflexes, weakness, muscle aches, muscle damage, or Parkinson's disease-like symptoms. Persons with prior strokes or transient ischemic attacks (TIAs/"mini-strokes"), tremor, or insomnia should avoid ephedra. Individuals with a history of a psychiatric illness, especially if treated with monoamine oxidase inhibitors (MAOIs), must first discuss ephedra with a qualified healthcare provider before taking supplements. Examples of MAOIs include isocarboxazid (Marplan®), phenelzine (Nardil®), and tranylcypromine (Parnate®).

Ephedra can cause chest tightness, irregular heart rhythms, damage to the heart muscle, high blood pressure, heart attack, inflammation of the heart, fluid retention in the lungs, breathing difficulties, or cardiac arrest. Ephedra should be used with extreme caution in persons with a history of heart disease, heart rate disorders, or high blood pressure. Other side effects may include liver damage, kidney stones, difficulty passing urine or pain when urinating, increased urine production, or contractions of the uterus. These potential effects may limit the use of ephedra by people with kidney disease or enlarged prostate. Individuals with thyroid gland disorders or glaucoma should use ephedra cautiously. In theory, ephedra may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a qualified healthcare provider, and medication adjustments may be necessary.

When used for prolonged periods, even at recommended doses, ephedra may lead to weight loss, difficulty sleeping, anxiety, high blood pressure, dry mouth, irregular heart rhythms, and heart damage.

Pregnancy & Breastfeeding

Ephedra should not be used during pregnancy, due to risks to the mother and fetus. Ephedrine crosses the placenta, and has been found to increase fetal heart rate. Ephedra may induce uterine contractions.

Ephedra should not be used during breastfeeding, due to risks to the mother and child. Ephedrine crosses into breast milk and has been associated with irritability, crying, and insomnia in infants.

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January 01, 2004