SIDE EFFECTS பக்க விளைவுகள்
PRODUCTS SIDE EFFECTS
Ephedra பக்க விளைவுகள்
Ephedra, a main ingredient in Herbalife, has been known to cause psychosis, tremors, kidney stones, high blood pressure, sweats, rapid heartbeat, and damage to the heart and other organs. It has been linked to strokes, seizures and death.
SINICA, MA HUANG)
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.
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 Report Ephedra
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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Liu LU, Schiano TD. Hepatotoxicity of herbal medicines, vitamins and natural hepatotoxins. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 733-54. (Review of hepatotoxicity of herbal and dietary supplements [HDS] published in 2007; Ma Huang has been linked to numerous instances of acute, clinically apparent liver injury presenting with an acute hepatitis, often with fever, resolving rapidly on stopping).
No authors listed. Ma huang: ephedra sinica. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007, pp 543-52. (Compilation of short monographs on herbal medications and dietary supplements).
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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 (33 year old woman developed nausea within days of starting Ma Huang for weight loss, followed at 3 weeks by jaundice [bilirubin 4.5 rising to 8 mg/dL, ALT 832 U/L, Alk P 178 U/L, ANA 1:160, asterixis], resolving within 4 weeks of stopping: Case 1).
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Borum ML. Fulminant exacerbation of autoimmune hepatitis after the use of Ma Huang. Am J Gastroenterol 2001; 96: 1654-5. PubMed Citation (58 year old woman developed jaundice 4 months after starting Ma Huang for weight loss [bilirubin 9.3 mg/dL, ALT 293 U/L, Alk P 320 mg/dL, protime 21.1 sec, SMA 1:320, ANA negative], developed ascites and was referred for transplant, but resolved spontaneously after stopping herbal).
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Pittler MH, Ernest E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther 2003; 18: 451-71. PubMed Citation (Systematic review of published cases of hepatotoxicity due to herbal medications, listing 52 case reports or case series, most common agents being celandine , chaparral , germander , Jin Bu Huan , kava , Ma Huang , pennyroyal , skullcap , Chinese herbs  and valerian ).
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Abourashed EA, El-Alfy AT, Khan IA, Walker L. Ephedra in perspective – a current review. Phytother Res 2003; 17: 703-12. PubMed Citation (Review of history, botany, chemistry, pharmacology, clinical efficacy and safety of ephedra; by the year 2000, the FDA had received 1000 injury reports, often attributed to misuse, abuse or mislabeling of the product; only one report of hepatitis).
Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. PubMed Citation (Among ~50,000 liver transplants reported to UNOS between 1990 and 2002, 270 [0.5%] were done for drug-induced acute liver failure, including 7 [5%] for herbal medications, one due to chaparral and one to kava; Ma Huang and ephedra not mentioned).
Nelson R. FDA issues alert on Ephedra supplements in the U.S.A. Lancet 2004; 363: 135. PubMed Citation (Report on FDA ruling that ephedrine alkaloids present an unreasonable risk of injury, after review of ~155 deaths blamed on ephedra).
Neff GW, Reddy R, Durazo FA, Meyer D, Marrero R, Kaplowitz N. Severe hepatotoxicity associated with the use of weight loss diet supplements containing Ma Huang or usnic acid. J Hepatol 2004; 41: 162-4. PubMed Citation (Review of 12 patients with hepatotoxicity due to herbal weight loss agents, 10 due to Ma Huang [ephedra] with onset within 6 months in all but one [bilirubin 9.9-45 mg/dL, ALT 664-10,265 U/L], 1 died and 2 underwent liver transplantation, remaining recovered within 4-8 weeks).
Skoulidis F, Alexander GJM, Davies SE. Ma huang associated acute liver failure requiring liver transplantation. Eur J Gastroenterol Hepatol 2005; 17: 581-4. PubMed Citation (57 year old woman developed nausea soon after starting Ma Huang and jaundice one week later [bilirubin 24.9 mg/dL, ALT 1061 U/L, Alk P 196 U/L], with progressive liver failure and transplantation, the explant showing massive collapse).
Clark BM, Schofield RS. Dilated cardiomyopathy and acute liver injury associated with combined use of ephedra, gamma-hydroxybutyrate, and anabolic steroids. Pharmacotherapy 2005; 25: 756-61. PubMed Citation (40 year old man developed congestive heart failure and jaundice several months after starting anabolic steroids, ephedra and γ-hydroxybutyrate [bilirubin 3.9 mg/dL, ALT 2173 U/L, Alk P normal, INR 1.9], with slow recovery over next 18 months).
Elinav E, Pinsker G, Safadi R, Pappo O, Bromberg M, Anis E, Keinan-Boker L, et al. Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity. J Hepatol 2007; 47: 514-20. PubMed Citation (12 cases of liver injury attributed to Herbalife products in Israel, 11 women, 1 man, ages 32 to 78 years, onset after 2 to 35 months [mean peak bilirubin 9.1 mg/dL, ALT 1481 U/L, Alk P 282 U/L, 1 with ANA], on stopping, 11 recovered and one died of hepatitis B reactivation; 3 had a positive rechallenge).
Schoepfer AM, Engel A, Fattinger K, Marbet UA, Criblez D, Reichen J, Zimmermann A, Oneta CM. Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products. J Hepatol 2007; 47: 521-6. PubMed Citation (10 cases of hepatotoxicity due to Herbalife products in Switzerland; ages 30-69 years, 3 men and 7 women, with onset after 2 to 144 months, 9 with jaundice [bilirubin 0.4-28.2 mg/dL, ALT 4-50 times ULN, Alk P 1.1-6.5 times ULN], 2 with recurrence on rechallenge, 3 requiring liver transplant, 1 with sinusoidal obstruction syndrome, 1 with cirrhosis).
Stickel F. Slimming at all costs: Herbalife-induced liver injury. J Hepatol 2007; 47: 444-6. PubMed Citation (Editorial in reference to Schoepfer  and Elinay  discussing the difficulties in assigning causality and identifying the toxic component in herbal mixtures, many patients take multiple products and each includes multiple components).
Duque JM, Ferreiro J, Salgueiro E, Manso G. [Hepatotoxicity associated with the consumption of herbal slimming products]. Med Clin(Barc) 2007; 128: 238-9. Spanish. PubMed Citation (3 cases of hepatotoxicity attributed to Herbalife products, women ages 49-54 years, with onset of liver injury after 1, 6 and 36 months [bilirubin 0.7, 0.8, and 26.6 mg/dL, ALT 138, 505 and 1890 U/L, Alk P 112, 166 and 425 U/L], resolving in all 3 upon stopping).
Chao S, Anders M, Turbay M, Olaiz E, Mc Cormack L, Mastai R. [Toxic hepatitis by consumption Herbalife products: a case report]. Acta Gastroenterol Latinoam 2008; 38: 274-7. Spanish. PubMed Citation (63 year old woman developed jaundice and pruritus 2.5 months after starting Herbalife products [peak bilirubin 17.5 mg/dL, ALT 847 U/L, Alk P 3 times ULN], resolving within 5 months of stopping).
Manso G, López-Rivas L, Duque JM, Salgueiro E. Spanish reports of hepatotoxicity associated with Herbalife products. J Hepatol 2008; 49: 289-90; author reply 290-1. PubMed Citation (Discussion of 4 cases of Herbalife hepatotoxicity from Spain [3 reported by Duque 2007], 2 occurring in sisters, suggesting a genetic propensity and an idiosyncratic drug reaction).
Ignarro L, Heber D, Henig YS, Bejar E. Herbalife nutritional products and liver injury revisited. J Hepatol 2008; 49: 291-3; author reply 293-4. PubMed Citation (Comment on publications on Herbalife hepatotoxicity [Elinav and Schoepfer 2007] questioning whether their product was involved, as the product is used by millions).
Chitturi S, Farrell GC. Hepatotoxic slimming aids and other herbal hepatotoxins. J Gastroenterol Hepatol 2008; 23: 366-73. PubMed Citation (Review of hepatotoxicity of herbal medications focusing upon those used for weight loss including nitrosofenfluramine, usnic acid, ephedra, germander, skullcap and green tea).
Dara L, Hewett J, Lim JK. Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 2008; 14: 6999-7004. PubMed Citation (Two women ages 33 and 40 years with onset of symptoms 1 and 4 weeks after starting Hydroxycut [bilirubin 0.7 and 20.9 mg/dL, ALT 1150 and 934 U/L, Alk P 299 and 112 U/L], resolving rapidly, ingredients including green tea but not ephedra; review of liver injury due to weight loss supplements including Ma Huang, Lipokinetix, Kava, green tea, Shou Wu Pian, germander and usnic acid).
García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. [Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry]. Rev Esp Enferm Dig 2008; 100: 688-95. Spanish. PubMed Citation (Among 521 cases of drug-induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals but none were attributed to ephedra or Ma Huang).
Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network(DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. PubMed Citation (Among 300 cases of drug-induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications).
Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 29: 373-82. PubMed Citation (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; specific discussion of Herbalife and traditional Chinese herbal medicines).
Chen GC, Ramanathan VS, Law D, Funchain P, Chen GC, French S, Shlopov B, et al. Acute liver injury induced by weight-loss herbal supplements. World J Hepatol 2010; 2: 410-5. PubMed Citation (Three women, ages 31, 37 and 53 years, taking Hydroxycut or Herbalife for weight loss developed jaundice 3, 4 and 12 months after starting product [bilirubin 15.3, 29.9, and 18.2 mg/dL, ALT 1227, 2068 and 983 U/L, Alk P 268, 185 and 292 U/L], resolving within 2-3 months of stopping).
Fong TL, Klontz KC, Canas-Coto A, Casper SJ, Durazo FA, Davern TJ 2nd, Hayashi P, et al. Hepatotoxicity due to hydroxycut: a case series. Am J Gastroenterol 2010; 105: 1561-6. PubMed Citation (Details of 17 US cases of hepatotoxicity due to Hydroxycut in the United States between 2002-9, latency to onset 2 to 12 weeks [2 outliers at 1 and 2 years], hepatocellular pattern of injury, often severe, 4 were fatal or led to liver transplantation).
Jóhannsson M, Ormarsdóttir S, Olafsson S. [Hepatotoxicity associated with the use of Herbalife]. Laeknabladid 2010; 96: 167-72. Icelandic. PubMed Citation (Five cases of Herbalife hepatotoxicity found in a survey in Iceland; 4 women, 1 man, ages 29 to 78 years, after 1 to 7 months of use, 4 with hepatocellular injury [bilirubin 1.5 to 18.2 mg/dL, ALT 456 to 2637 U/L, Alk P 149 to 712 U/L], all resolving upon stopping).
Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute
liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. PubMed Citation. (Among 1198 patients with acute liver failure enrolled in a U.S. prospective study between 1998 and 2007, 133 [11%] were attributed to drug induced liver injury of which 12 [9%] were due to herbals including usinic acid , thermoslim , ma huang , horny goat weed , black cohosh , hydroxycut  and unspecified herbals ).
Molleston JP, Fontana RJ, Lopez MJ, Kleiner DE, Gu J, Chalasani N: Drug-induced Liver Injury Network. Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study. J Pediatr Gastroenterol Nutr 2011; 53: 182-9. PubMed Citation. (Among 30 children with suspected drug-induced liver injury, only one case was attributed to an herbal; hydroxycut).
Stickel F, Kessebohm K, Weimann R, Seitz HK. Review of liver injury associated with dietary supplements. Liver Int 2011; 31: 595-605. PubMed Citation. (Review of current understanding of liver injury from herbals and dietary supplements focusing upon herbalife and hydroxycut products, green tea, usnic acid, Noni juice, Chinese herbs, vitamin A and anabolic steroids).
Sunday, November 11, 2012
What is Ephedrine, Ephedra and Ma Huang?
These terms are used to refer to the same substance derived from the plant Ephedra. (There are many common names for these evergreen plants, including squaw tea and Mormon tea.) Ephedra is a shrub-like plant that is found in desert regions in central Asia and other parts of the world. The dried greens of the plant are used medicinally. Ephedra is a stimulant containing the herbal form of ephedrine, an FDA-regulated drug found in over-the-counter asthma medications.
In the United States, ephedra and ephedrine are sold in health food stores under a variety of brand names. Ephedrine is widely used for weight loss, as an energy booster, and to enhance athletic performance. These products often contain other stimulants, such as caffeine, which may have synergistic effects and increase the potential for adverse effects. Ephedra is often touted as the "herbal fen-phen."
Ephedra's main active medical ingredients are the alkaloids ephedrine and pseudoephedrine. The ephedras also contain various tannins and related chemicals.The stem contains 1-3% total alkaloids, with ephedrine accounting for 30-90% of this total. The concentrations of these alkaloids depends upon the particular species of ephedra used.
Ephedrine alkaloids are amphetamine-like compounds used in OTC and prescription drugs with potentially lethal stimulant effects on the central nervous system and heart. The FDA has received more than 800 reports of adverse effects associated with use of products containing ephedrine alkaloid since 1994. These serious adverse effects, include hypertension (elevated blood pressure), palpitations (rapid heart rate), neurophathy (nerve damage), myopathy (muscle injury), psychosis, stroke, memory loss, heart rate irregularities, insomnia, nervousness, tremors, seizures, heart attacks, and death. The agency has proposed to prohibit the marketing of dietary supplements containing 8 milligrams or more of ephedrine alkaloids per serving.
Ephedra is one of the most dangerous of the dietary supplements
Over 800 injuries have been reported by users and doctors to the FDA and various state medical bodies, including more than 50 deaths.
Most of these cases involve the heart attacks or high blood pressure leading to bleeding in the brain or stroke.
Recent studies sho wthat many people are seriously injured by the use of ephedrine. They are often unaware that ephedrine suppliers are can make wide ranging health claims about the product that have no scientific basis. Nor is there any mention of the potential for dangerous side effects. Because the industry was lobbyed to pass a law deregulating these products in l994, the FDA has been unable to regulate these products.
|FDA statement on street drugs containing botanical
FDA is warning consumers not to purchase or consume ephedrine-containing dietary supplements with labels that often portray the products as apparent alternatives to illegal street drugs such as "ecstasy." Possible adverse effects of ephedrine range from clinically significant effects such as heart attack, stroke, seizures, psychosis, and death, to clinically less significant effects that may indicate the potential for more serious effects (for example, dizziness, headache, gastrointestinal distress, irregular heartbeat, and heart palpitations). Ingredient panels on these products may list ma huang, Chinese ephedra, ma huang extract, ephedra, Ephedra sinica, ephedra extract, ephedra herb powder, or epitonin, all of which indicate a source of ephedrine.
The Food and Drug Administration proposed to reduce risks associated with dietary supplement products containing ephedrine alkaloids by limiting the amount of ephedrine alkaloids in products and requiring labeling and marketing measures that give adequate warning and information to consumers.
Ephedrine alkaloids are amphetamine-like compounds with potentially powerful stimulant effects on the nervous system and heart. Hundreds of consumer illnesses and injuries associated with the use of these products have been reported.
The proposal would not ban dietary supplements that contain ephedrine alkaloids.
"Consumers should be aware that just because a product is labeled 'natural' or from an herbal source it is not guaranteed to be safe," said Dr. Michael Friedman, Deputy Commissioner of Food and Drugs. "The effects of ephedrine alkaloids are potentially powerful ones. We urge people to talk to their doctors before using dietary supplements containing ephedrine alkaloids, and to always use them with caution."
Because ephedrine alkaloids are heart and nervous system stimulants, certain individuals including those with hypertension, heart conditions and neurologic disorders, should avoid their use. Pregnant women, too, should avoid the use of dietary supplements with ephedrine alkaloids.
The proposal would prohibit the marketing of dietary supplements containing 8 milligrams or more of ephedrine alkaloids per serving. Labeling that recommends or suggests conditions of use that would result in an intake of 8 mg or more in a 6-hour period or a total daily intake of 24 mg or more also would not be allowed.
In addition, the proposal would require label statements instructing consumers not to use the product for more than 7 days, and would not allow label claims for uses for which long-term intake would be necessary to achieve the purported effect. These safety measures are based on the fact that long-term intake of ephedrine alkaloids increases the likelihood of serious adverse events.
Another measure in the proposal would apply to products with claims that encourage short-term excessive intake to enhance the claimed effect, such as energy enhancement. Such products would be required to bear a labeling statement that "Taking more than the recommended serving may result in heart attack, stroke, seizure or death."
The proposal also would prohibit the use of other stimulant ingredients such as botanical sources of caffeine with ephedrine alkaloids because the combination increases the stimulant effects of ephedrine alkaloids and the chance of consumer injury.
Dietary supplement products containing ephedrine alkaloids are currently sold for a variety of purposes including weight loss, increased energy and body building.
Since 1994, the agency has received and investigated more than 800 reports of adverse events associated with the use of these products. Reported adverse events range from episodes of high blood pressure, irregularities in heart rate, insomnia, nervousness, tremors and headaches, to seizures, heart attacks, strokes and death. Most events occurred in young to middle aged, otherwise healthy adults using the products for weight control and increased energy.
Ephedrine alkaloids in dietary supplements are usually derived from one of several species of herbs of the genus Ephedra, sometimes called Ma huang, Chinese Ephedra and epitonin. Other botanical sources include Sida cordifolia.
The proposed measures were developed based on the FDA's review of its adverse event reports, the scientific literature, and public comments reviewed by the agency, including comments generated by an October 1995 advisory working group public meeting and an August 1996 public meeting of the FDA's Food Advisory Committee. These experts suggested a number of steps the agency might take to reduce injuries associated with use of dietary supplements containing ephedrine alkaloids.
Lack of FDA Regulation
People are unaware that suppliers of ephedra products are virtually free to make health claims about the substances that have no scientific basis. People are also unaware of the potentially deadly side effects of these products. Dietary supplements are routinely marketed without undergoing a safety review by FDA.
A law known as the Dietary Supplements Health and Education Act or "DSHEA," prevents the FDA from regulating these products. Prior to the DSHEA, dietary supplements were in regulatory limbo. The FDA claimed it had the power to regulate them and tried to make the manufacturers and suppliers prove their safety claims for their products.
The DSHEA reduced the FDA's and federal control over these products, compared with food and drugs, which are subjected to strict regulation and compliance mointering by the FDA. Under the DSHEA, dietary supplements like ephedrine are loosely defined as products intended to supplement the diet. These supplements contain herbs, minerals, amino acids, vitamins and combinations of these things. The supplement industry can sell any product that meets that definition in stores and its supplier can make claims about its alleged healthful qualities.
Herbal usage in the United States has increased dramatically since the passage of the DSHEA. In 1997, 60 million Americans spent $3.24 billion on herbs for reasons such as migraines, hypertension, depression, weight loss, and sexual stamina. An estimated 15 million adults are at risk for potential herb-drug interactions.
The deception occurs when the supplements industry selects brand names or uses wording on labels such as "fat burner" or "detoxifies" or "natural viagra" or the "#1 rated herbal" for impotence or "herbal fen-phen" to suggest the impossible. Under DSHEA, a herbal product label can state the way the product is intended to affect "the structure or function" of the body but cannot claim its use for a specific disease. Manufacturers use creative borderline language that complies technically with the law, but is generally confusing and deceptive. For example, one manufacturer claims its product "promotes regularity" instead of "treats constipation." How many consumers can discern the difference? Rather than stating Echinaeu "treats the flu" one manufacturer deftly says its product "promotes wellness during the flu season." These types of misleading claims are apparently permissible under the new laws and mislead consumers into believing these products are safe, when many clearly can have serious side effects.
Some companies have named their ephedrine tablets after illegal street drugs such as "Ecstasy" and "Black Beauties," as well as brand names such as Easy Trim, Advocare, Metabolite, Metab-Rx Ultar, Epitonin, Chinese Ephedra, Metabolife 356 and Ripped Fuel. Other manufacturers have taken a more subtle approach to sell their ephedrine products. These companies make representations that they are vitamin or nutrition companies that sell only "natural" diet supplements. Drug companies have taken advantage of the current status of ephedrine and have attempted to produce a "legal"
amphetamine by mixing ephedrine with other stimulants such as caffeine. Ephedrine use is highly popular among college students and people who work out. Most remain completely unaware of the potential dangers of these products.
People continue to believe that because herbs are "natural" they are therefore, harmless. However, many herbal remedies are dangerous. Many can interact with prescription medication. Some herbs become toxic if taken with certain drugs, and fatal herb-drug interactions can occur.
"Herbs are not regulated the same as other dietary supplements," says Donald D. Hensrud, M.D., a consultant in preventive medicine and endocrinology at Mayo Clinic in Rochester, Minn. "This means they can be misidentified, contaminated or contain multiple ingredients. There is no quality control for herbs."
"Patients electing to use herbal supplements for a serious disease in place of proven therapy are truly taking their lives in their own hands," says Thomas P. Moyer, Ph.D., director of the toxicology laboratory at Mayo Clinic, Rochester. "The growing trend of self-therapy is very concerning."
Excerpts from an article on the dangers of herbal supplements from
Journal of The New England Journal of Medicine
Now, with the increased interest in alternative medicine, we see a reversion to irrational approaches to medical practice, even while scientific medicine is making some of its most dramatic advances. Exploring the reasons for this paradox is outside the scope of this editorial, but it is probably in part a matter of disillusionment with the often hurried and impersonal care delivered by conventional physicians, as well as the harsh treatments that may be necessary for life-threatening diseases.
Fortunately, most untested herbal remedies are probably harmless. In addition, they seem to be used primarily by people who are healthy and believe the remedies will help them stay that way, or by people who have common, relatively minor problems, such as backache or fatigue. Most such people would probably seek out conventional doctors if they had indications of serious disease, such as crushing chest pain, a mass in the breast, or blood in the urine. Still, uncertainty about whether symptoms are serious could result in a harmful delay in getting treatment that has been proved effective. And some people may embrace alternative medicine exclusively, putting themselves in great danger. In this issue of the Journal, Coppes et al. describe two such instances.
Also in this issue, we see that there are risks of alternative medicine in addition to that of failing to receive effective treatment. Slifman and her colleagues report a case of digitalis toxicity in a young woman who had ingested a contaminated herbal concoction. Ko reports finding widespread inconsistencies and adulterations in his analysis of Asian patent medicines. LoVecchio et al. report on a patient who suffered central nervous system depression after ingesting a substance sold in health-food stores as a growth hormone stimulator, and Beigel and colleagues describe the puzzling clinical course of a patient in whom lead poisoning developed after he took an Indian herbal remedy for his diabetes. These are without doubt simply examples of what will be a rapidly growing problem.
What about the FDA? Shouldn't it be monitoring the safety and efficacy of these remedies? Not any longer, according to the U.S. Congress. In response to the lobbying efforts of the multibillion-dollar "dietary supplement" industry, Congress in 1994 exempted their products from FDA regulation. (Homeopathic remedies have been exempted since 1938. Since then, these products have flooded the market, subject only to the scruples of their manufacturers. They may contain the substances listed on the label in the amounts claimed, but they need not, and there is no one to prevent their sale if they don't. In analyses of ginseng products, for example, the amount of the active ingredient in each pill varied by as much as a factor of 10 among brands that were labeled as containing the same amount. Some brands contained none at all.
Herbal remedies may also be sold without any knowledge of their mechanism of action. In this issue of the Journal, DiPaola and his colleagues report that the herbal mixture called PC-SPES (PC for prostate cancer, and spes the Latin for "hope") has substantial estrogenic activity. Yet this substance is promoted as bolstering the immune system in patients with prostate cancer that is refractory to treatment with estrogen. Many men taking PC-SPES have thus received varying amounts of hormonal treatment without knowing it, some in addition to the estrogen treatments given to them by their conventional physicians.
The only legal requirement in the sale of such products is that they not be promoted as preventing or treating disease. To comply with that stipulation, their labeling has risen to an art form of doublespeak (witness the name PC-SPES). Not only are they sold under the euphemistic rubric "dietary supplements," but also the medical uses for which they are sold are merely insinuated. Nevertheless, it is clear what is meant. Shark cartilage (priced in a local drugstore at more than $3 for a day's dose) is promoted on its label "to maintain proper bone and joint function," saw palmetto to "promote prostate health," and horse-chestnut seed extract to "promote... leg vein health." Anyone can walk into a health-food store and unwittingly buy PC-SPES with unknown amounts of estrogenic activity, plantain laced with digitalis, or Indian herbs contaminated with heavy metals. Caveat emptor. The FDA can intervene only after the fact, when it is shown that a product is harmful.
Ephedra Containg Products
Ephedrine products are sold under dozens of brand names, to the right are some of the more popular brands.
The products are sold for a variety of reasons: ranging from weight loss to engery for work outs.
Many consumers may not be aware of the ephedra in the products or the levels or potency of the products.
If you have taken one of these products and have been injured you may want to Contact Ephedra Injury Lawyers
Metabolife 356® (Metabolife International)
Ripped Fuel (TwinLab Laboratories)
Extreme Ripped Force (American Bodybuilding)
Diet Fuel (Twin Laboratories)
GH Fuel (TwinLab Laboratories)
Herba Fuel (TwinLab Laboratories)
MetaboLift (TwinLab Labortories)
ThermiCare® (Met-Rx USA)
ETA Stack® (Nutra Sport)
Xenadrine RFA-1® (Cytodyne Technologies)
Ultimate Orange (Next Nutrition, Inc)
Vasopro (Mega Pro International)
Adipokinex (Syntrax Innovations, Inc)
Thermogenic Power (Nature's Herbs)
Chinese Ephedra (Frontiers, Inc.)
Chinese Ma Huang (Gaia Herbs, Inc)
Lipokinetix (Syntrax Innovations, Inc)
Clenbutrx (Vital Pharm, Inc)
BetaLean HP (EAS)
Diet Pep (Natural Balance, Inc)
Diurlean (ISS Research)
Dyma-Burn Xtreme (Dymatize Nutrition)
If your doctor has directed you to use this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Many people have had serious (sometimes fatal) side effects with this medication. Discuss the risks and benefits of this medication with your doctor or pharmacist.
Tell your doctor immediately if any of these serious side effects occur: mental/mood changes (e.g., anxiety, difficulty concentrating, irritability), dry mouth, increased thirst, muscle pain, flushing/tingling, difficult/painful urination.
Seek immediate medical attention if any of these very serious side effects occur: chest pain, dizziness/fainting, fast/irregular/pounding heartbeat, severe/pounding headache, severe mental/mood changes (e.g., confusion, hallucinations), seizure, swelling ankles/feet, tiredness, slurred speech, change in amount of urine, weakness on one side of the body.
A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.