Ephedra has been used in traditional Chinese medicine (known as Ma Huang) for centuries as a stimulant and antiasthmatic agent, and was recently introduced into use in the United States and Europe as a weight loss agent and aid in body building. Ephedra has been linked to multiple potentially severe side effects including clinically apparent liver injury and has been banned from sale in the United States and elsewhere.
Ephedra is prepared from the aerial parts of plants belonging to the genus Ephedra, family Ephedraceae. The 45 species of Ephedra are found worldwide, but Ephedra sinica is used predominantly and is native to China where it was first used therapeutically. Ephedra is an herbaceous perennial with a strong pine odor and astringent taste which accounts for its Chinese name – Ma Huang – which can be translated as “yellow astringent” or “yellow hemp.” Ephedra is purported to increase mental acuity and to improve sexual performance, increase circulation, and decrease weight through an increase in sympathetic nervous system activity and thermogenesis. It is also used for allergies, allergic rhinitis, colds, flu, fever, chills, nasal congestion, bronchospasm and asthma. The active ingredient of ephedra appears to be ephedrine and other related sympathomimetic alkaloids, which probably account for its therapeutic efficacy as well as its adverse effects. Ephedra was a component of many herbal weight loss and body-building preparations, including Ma Huang, Herbalife, Hydroxycut and others. The typical dose is 1.5 to 9 grams of the decocted herb daily or as herbal tea prepared by boiling dried green stems in water. Side effects are not uncommon and include nervousness, anxiety, palpitations, tachycardia, gastrointestinal upset, nausea, diarrhea, headache, and dizziness. Ephedra has also been implicated in an increased risk for myocardial infarction, stroke and sudden death and was banned from sale in the United States in April 2004.
Despite its apparent safe use for centuries in Chinese traditional medicine, ephedra has been linked to many serious and potential fatal side effects since its wide-scale use in Western countries for weight loss. The major reported serious adverse events were cardiovascular, including hypertension, palpitations, myocardial infarction, seizures, transient ischemic attacks, cerebrovascular accidents and sudden death. Ephedra preparations have also been implicated in more than a dozen instances of clinically apparent, acute liver injury. The time to onset has ranged from a few weeks to more than 6 months, but averages 12 weeks, presenting with symptoms of fatigue, nausea and abdominal discomfort followed by jaundice. The serum enzyme elevations are typically hepatocellular and the clinical syndrome resembles acute viral hepatitis. Immunoallergic features (rash, fever and eosinophilia) are uncommon as are autoantibodies. Recovery occurs within 1 to 6 months of stopping the ephedra preparation, but instances with acute liver failure and death or need for emergency liver transplantation have been reported.
Mechanism of Injury
Ephedra extracts contain multiple compounds including the sympathomimetic alkaloids ephedrine, pseudoephedrine, methylephedrine and norephedrine. The cardiovascular side effects and complications of ephedra use have been attributed to these sympathomimetic constituents. The liver injury has been attributed to ephedrine as well, but other constituents may be responsible for this idiosyncratic liver injury.
Outcome and Management
The severity of liver injury due to ephedra ranges from mild,
asymptomatic elevations in serum enzymes to clinically apparent acute
liver injury and to acute liver failure. Chronic use of ephedra has
been linked to a chronic hepatitis-like syndrome, but recovery is prompt
when ephedra is stopped. There have been no instances of vanishing
bile duct syndrome attributed to ephedra. Recurrence of liver injury is
typical when ephedra is restarted, and rechallenge should be avoided.
There is no apparent cross sensitivity to liver injury between ephedra
and other weight loss agents or herbal preparations, but ephedra was
previously found in many commercial herbal preparations.
Other names: Ma Huang, belcho, Chinese ephedra, desert herb,
ephedrine, heral ecstasy, Joint fir, Mongolian ephedra, Pakistani
ephedra, popotillo, sea Grade, Teamster’s tea, yellow astringent, yellow
Drug Class: Herbals and Dietary Supplements
Other drugs within this class:
Case 1. Acute hepatitis due to Ma Huang.
[Modified from: Nadir A, Agrawal S, King PD, Marshall JB. Acute
hepatitis associated with the use of a Chinese herbal product, ma-huang.
Am J Gastroenterol 1996; 91: 1436-8. PubMed Citation]
A 33 year old woman developed nausea and abdominal discomfort a few days after starting Ma Huang for weight loss. She continued taking the product for another 3 weeks when she noted jaundice and sought medical attention. She had no history of liver disease, alcohol abuse or risk factors for viral hepatitis and liver tests were known to be normal two years earlier. She was taking no other medications. Initially, she did not reveal that she was taking an herbal product. On examination, she was jaundiced and had hepatic tenderness but no fever, rash or signs of chronic liver disease. Laboratory tests showed raised serum bilirubin (4.5 mg/dL) and prominent elevations in serum aminotransferase levels (ALT 832 U/L, AST 376 U/L), with minimal increase in alkaline phosphatase (178 U/L). Tests for hepatitis A, B and C and a monospot were negative. Autoantibodies were present in moderate titers with ANA 1:160 and SMA 1:80. Ultrasound and computerized tomography of the liver were normal. She was initially thought to have viral hepatitis and sent home. She restarted Ma Huang but quickly felt worse, stopped and returned to the hospital where liver tests were found to be worse (Table). A liver biopsy showed changes of acute hepatitis with occasional eosinophils and plasma cells suggestive of drug-induced liver disease. She stopped taking Ma Huang and when seen four months later, all liver tests were again normal.
|Medication:||Ma Huang (Ephedra: unknown dose)|
|Severity:||3+ (Jaundice, hospitalization)|
|Recovery:||Within 16 Weeks|
|Time After Starting||Time After Stopping||
|Total Bilirubin (mg/dL)||Other|
|Ma Huang taken for 3-4 weeks|
|Ma Huang restarted for a few days|
|5 weeks||0||1586||175||8.0||Protime 13.2 seconds|
|5 months||4 months||40||51||0.5|
A typical case of an acute hepatitis due to Ma Huang. The time to onset was difficult to assess, because she reported having nausea and abdominal discomfort “soon after” starting Ma Huang, but the time to jaundice was about 4 weeks. The clinical presentation was similar to acute viral hepatitis, which was the initial diagnosis, because the patient did not admit to using an herbal product (and this was the first report of Ma Huang related acute liver injury). The finding of autoantibodies might suggest an autoimmune drug-induced hepatitis. Immunoglobulin levels and serial ANA titers were not provided, but the liver histology did not suggest autoimmune hepatitis. Moderate levels of autoantibodies are not infrequent in cases of acute liver injury due to Ma Huang, but autoimmune features (hyperglobulinemia, prolonged course, response to corticosteroids) are not found.
SUMMARY & LABELING
REPRESENTATIVE TRADE NAMES
Ephedra – Generic
Ephedra – Generic
Herbals and Dietary Supplements
Herbals and Dietary Supplements
CHEMICAL FORMULA AND STRUCTURE
|DRUG||CAS REGISTRY NUMBER||MOLECULAR FORMULA||STRUCTURE|
|Ephedra||ID: OM54525000||Herbal mixture||Not applicable|
References Last Updated: 10 March 2012
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