05.02.16
FDA issued seven warning letters at the end of March to companies selling products that contain methylsynephrine (also known as oxilofrine) just before a study published in Drug Testing and Analysis on Apr. 7 indicated that 14 over-the-counter dietary supplement products (out of 27 brands tested) contained this unapproved pharmaceutical stimulant.
Oxilofrine (also known as methylsynephrine, p-hydroxyephedrine, oxyephedrine, 4-HMP and suprifen)—a pharmaceutical drug developed in Europe in the 1930s to stimulate the heart, increase blood pressure and improve oxygen exchange—has never been approved in the U.S.
Consumption of supplements containing oxilofrine may pose serious health risks. According to the published analysis, 26 adverse events have been reported in the Netherlands linked to supplements containing oxilofrine. These supplements were connected to nausea and vomiting, chest pain and cardiac arrest, according to reports. Oxilofrine is often referred to on labels as “methylsynephrine” or “extract of Acacia rigidula.”
Several professional athletes have been disqualified from sports due to testing positive for oxilofrine, which is banned by the World Anti-Doping Agency (WADA) and most major sports organizations.
According to the FDA, oxilofrine is an illegal dietary ingredient, which means products containing the drug are considered misbranded under the law. Warning letters were delivered to the following companies: Chaotic Labz, Line One Nutrition, Inc., m4 Nutrition Companies LLC, NutraClipse, Inc., Swagger Supps and Xcel Sports Nutrition, LLC.
Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), Washington, D.C., applauded FDA for taking action against companies breaking the law and potentially putting consumers at risk. “Responsible marketers and manufacturers of supplements who compose the mainstream dietary supplement industry are in lockstep with FDA when it comes to enforcing the law and protecting the safety of their consumers, and we strongly urge the companies that received these warning letters—and any others that may be selling this illegal ingredient—to heed the agency’s warning immediately.”
For the study published in Drug Testing and Analysis, researchers from Harvard Medical School (including lead author Dr. Pieter Cohen), NSF International, the National Center for Natural Products Research (NCNPR) at the University of Mississippi and the National Institute for Public Health and the Environment in the Netherlands (RIVM) designed their study to determine the presence and quantity of oxilofrine in dietary supplements sold in the U.S.
They analyzed 27 brands of supplements labeled as containing a synonym of oxilofrine (methylsynephrine) and found that oxilofrine was present in 14 different brands (52%) at dosages ranging from 0.0003 to 75 mg per individual serving. Of the supplements containing oxilofrine, 43% (6 of 14) contained pharmaceutical or greater dosages of oxilofrine. Following instructions on the label, consumers could ingest as much as 250 mg of oxilofrine per day. This dosage is twice the typical adult dosage prescribed by physicians in other countries where the drug is approved for use during anesthesia and for treating a variety of medical conditions.
Oxilofrine has been studied in animals and humans and found to cause effects on the heart similar to ephedrine, a compound banned by FDA in 2004 due to serious side effects. Since then, scientists at NSF International have discovered several unapproved and potentially dangerous replacement stimulants such as DEPEA, DMAA, DMBA and now oxilofrine in products marketed as dietary supplements.
“Adolescents who use these products might be placing themselves at risk of serious harm. The larger-than-adult doses we found might overstimulate their smaller, growing bodies,” said Dr. Cohen, an assistant professor of medicine at Harvard Medical School who has conducted extensive research on supplements. “In countries where oxilofrine is prescribed by doctors, the usual amount of the drug for adolescents is 24 mg or less. We found amounts in supplements of oxilofrine more than three times higher than the usual pediatric dose. Combined with physical activity and other stimulants commonly found in supplements, the consequences could be catastrophic.”
This is the fourth time in three years that the research team has found unapproved stimulants disguised in supplements as botanical ingredients. “This compound was found in 14 supplements which are used as either dieting aides or pre-workout supplements,” said John Travis, NSF International research scientist. “As a public health organization we want to warn consumers about these compounds that may harm instead of improve their health.”
Oxilofrine (also known as methylsynephrine, p-hydroxyephedrine, oxyephedrine, 4-HMP and suprifen)—a pharmaceutical drug developed in Europe in the 1930s to stimulate the heart, increase blood pressure and improve oxygen exchange—has never been approved in the U.S.
Consumption of supplements containing oxilofrine may pose serious health risks. According to the published analysis, 26 adverse events have been reported in the Netherlands linked to supplements containing oxilofrine. These supplements were connected to nausea and vomiting, chest pain and cardiac arrest, according to reports. Oxilofrine is often referred to on labels as “methylsynephrine” or “extract of Acacia rigidula.”
Several professional athletes have been disqualified from sports due to testing positive for oxilofrine, which is banned by the World Anti-Doping Agency (WADA) and most major sports organizations.
According to the FDA, oxilofrine is an illegal dietary ingredient, which means products containing the drug are considered misbranded under the law. Warning letters were delivered to the following companies: Chaotic Labz, Line One Nutrition, Inc., m4 Nutrition Companies LLC, NutraClipse, Inc., Swagger Supps and Xcel Sports Nutrition, LLC.
Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), Washington, D.C., applauded FDA for taking action against companies breaking the law and potentially putting consumers at risk. “Responsible marketers and manufacturers of supplements who compose the mainstream dietary supplement industry are in lockstep with FDA when it comes to enforcing the law and protecting the safety of their consumers, and we strongly urge the companies that received these warning letters—and any others that may be selling this illegal ingredient—to heed the agency’s warning immediately.”
For the study published in Drug Testing and Analysis, researchers from Harvard Medical School (including lead author Dr. Pieter Cohen), NSF International, the National Center for Natural Products Research (NCNPR) at the University of Mississippi and the National Institute for Public Health and the Environment in the Netherlands (RIVM) designed their study to determine the presence and quantity of oxilofrine in dietary supplements sold in the U.S.
They analyzed 27 brands of supplements labeled as containing a synonym of oxilofrine (methylsynephrine) and found that oxilofrine was present in 14 different brands (52%) at dosages ranging from 0.0003 to 75 mg per individual serving. Of the supplements containing oxilofrine, 43% (6 of 14) contained pharmaceutical or greater dosages of oxilofrine. Following instructions on the label, consumers could ingest as much as 250 mg of oxilofrine per day. This dosage is twice the typical adult dosage prescribed by physicians in other countries where the drug is approved for use during anesthesia and for treating a variety of medical conditions.
Oxilofrine has been studied in animals and humans and found to cause effects on the heart similar to ephedrine, a compound banned by FDA in 2004 due to serious side effects. Since then, scientists at NSF International have discovered several unapproved and potentially dangerous replacement stimulants such as DEPEA, DMAA, DMBA and now oxilofrine in products marketed as dietary supplements.
“Adolescents who use these products might be placing themselves at risk of serious harm. The larger-than-adult doses we found might overstimulate their smaller, growing bodies,” said Dr. Cohen, an assistant professor of medicine at Harvard Medical School who has conducted extensive research on supplements. “In countries where oxilofrine is prescribed by doctors, the usual amount of the drug for adolescents is 24 mg or less. We found amounts in supplements of oxilofrine more than three times higher than the usual pediatric dose. Combined with physical activity and other stimulants commonly found in supplements, the consequences could be catastrophic.”
This is the fourth time in three years that the research team has found unapproved stimulants disguised in supplements as botanical ingredients. “This compound was found in 14 supplements which are used as either dieting aides or pre-workout supplements,” said John Travis, NSF International research scientist. “As a public health organization we want to warn consumers about these compounds that may harm instead of improve their health.”
