The stimulant oxilofrine has been banned by the World Anti-Doping Agency, the National Football League, Major League Baseball, and various other organizations. Numerous once-admired athletes are now forever barred from competition for using it. Across the globe, health professionals warn against taking oxilofrine, citing the various adverse effects of the substance.

This article discusses the background of oxilofrine, including biological and historical information. Further, the article examines the criticisms surrounding the use of oxilofrine.

Background

baseballThe prescription name used for hydroxyephrine, oxyephrine, and methylsynephrine, also called “synephrine,” oxilofrine is an ephedra-like substance that is developed, marketed and sold as a nutritional supplement. Companies that market and sell oxilofrine products often classify it as a “fat-burner” or “energy-booster.”

A once-popular nutritional supplement, oxilofrine, is a natural component of Citrus aurantium (C. aurantium), or “bitter orange,” a natural ingredient found in certain citrus plants. The mechanisms of oxilofrine are similar to the currently-banned supplement ephedrine, but oxilofrine is less potent.

Uses

Pharmacologic uses for C. aurantium include the following: antibacterial, anti-inflammatory, antifungal, and antispasmodic. It is also used as a eupeptic, tonic, tranquilizer, demulcent, cholagogue, and vascular stimulant. Most studies conducted on C. aurantium focus on the safety and effectiveness of the stimulant’s weight-loss properties.

The history of C. aurantium dates back to the 14th century, when the Portuguese and the Spanish transported bitter oranges to America. During this time, the plant was commonly used as a tonic to treat dyspepsia, or indigestion. People also used the dried variety of bitter orange to treat ptosis and several disorders of the uterus and anus.

In other parts of the world, the plant has been used to treat a variety of conditions, including cancer, gout, gastrointestinal (GI) problems, nervousness, anxiety, and insomnia. Other, less common uses have also been reported.

Perhaps the most widespread use of bitter orange is as a flavoring ingredient. The product has been used to flavor a multitude of consumables, including alcoholic and non-alcoholic drinks, baked goods, gelatins, meat products, candies, and other condiments.

The most recent usage of bitter orange is as an ephedra alternative. Ephedra was a widely-used and widely-promoted supplement due to its weight-loss and energy-promoting properties. However, several adverse side effects caused ephedra to be banned by the U.S. Food and Drug Administration (FDA) in 2004.

An increased risk of cardiovascular, psychiatric, and gastrointestinal problems are commonly cited as predominant reasons for the FDA ban of ephedra. Other serious conditions, including diabetes, cardiovascular disease, and kidney disease were also reported. The ingredient’s side effects included high blood pressure, heart damage, anxiety, heart palpitations, stomach irritation, psychosis, and tremors.

Side effects of oxilofrine are purportedly similar to ephedra, with an emphasis on nausea and vomiting, chest pain, cardiac arrest, and tachycardia (irregular, rapid heart rate). Proliferation of these and other side effects caught the eye of United States health agencies, including the FDA.

Criticism and Response

footballResearchers have paid particular attention to adolescents who consume the substance. Dr. Pieter Cohen, an assistant professor of Medicine at Harvard University Medical School states, “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.” As a result, the FDA and other agencies, along with medical professionals, are critical of the substance’s presence on the market.

Recently, a research team from the public health and safety group NSF International discovered the presence of oxilofrine in 14 supplement products currently for-sale in the U.S. In cohort with Harvard Medical School, 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), NSF International published the findings in the journal Drug Testing and Analysis.

The ingredient was reportedly mislabeled, according to NSF: “This compound was found in 14 supplements which are used as either dieting aids or pre-workout supplements. As a public health organization we wanted to warn consumers about these compounds that may harm instead of improve their health,” states John Travis, a research scientist at NSF International.

On March 31, 2016, the FDA sent warning letters to seven different manufacturers, all of which allegedly mislabeled oxilofrine as a dietary ingredient. According to the FDA, “methylsynephrine is not a concentrate, metabolite, constituent, extract, or combination of the preceding substances…methylsynephrine is not a vitamin, a mineral, an herb or other botanical or amino acid.” The letter concludes with demands that the manufacturer cease the distribution of the misbranded, unapproved product.

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