Safety of bitter orange documented in scientific review

Safety of bitter orange documented in scientific review

A new scientific review has concluded that bitter orange and bitter orange extract are safe in normal use as foods and ingredients in dietary supplements.[1] The extensively peer-reviewed safety evaluation was just published in HerbalGram, the quarterly journal of the American Botanical Council.

A new scientific review has concluded that bitter orange and bitter orange extract are safe in normal use as foods and ingredients in dietary supplements.[1] The extensively peer-reviewed safety evaluation was just published in HerbalGram, the quarterly journal of the American Botanical Council, an independent nonprofit research and education organization.

The safety review was conducted by two medicinal plant experts, Sidney J. Stohs, PhD, Dean Emeritus of the Creighton University School of Pharmacy and Health Professions, and Harry G. Preuss, MD, Professor of Medicine and Pathology at Georgetown University Medical Center.

Bitter orange—also known as Seville orange (Citrus aurantium)—and its peel have long been used as a food. It is the primary ingredient in orange marmalade throughout Europe. The dried immature fruits of bitter orange have various medicinal uses in Traditional Chinese Medicine, particularly for gastrointestinal disorders, including indigestion, diarrhea and dysentery, constipation, and use as an expectorant.

Bitter orange extracts increased in popularity in herbal dietary supplements circa 2004 after the US Food and Drug Administration banned the controversial herb ephedra (Ephedra sinica), also known in Chinese as ma huang. Because bitter orange contains the a chemical known as p-synephrine, many writers and regulators incorrectly assumed that bitter orange was potentially unsafe, as a chemical type of synephrine—m-synephrine, which is not found in bitter orange—can have pronounced effects on the cardiovascular system.

Drs. Stohs and Preuss emphasize the difference between these two chemical types of synephrine. First, m-synephrine, a synthetic form of the chemical which is also known as the drug neosynephrine, can produce adverse cardiovascular effects. However, bitter orange peel contains a natural type of synephrine called p-synephrine which has a slightly different chemical structure, producing different biological activity.

The HerbalGram safety review documents the scientific and human clinical research on bitter orange which has confused the 2 different types of synephrine, often leading to erroneous and misleading conclusions in medical and lay literature about the overall safety of bitter orange and its extracts.

For example, the September 2010 issue of Consumer Reports stated that bitter orange has been “linked by clinical research or case reports to serious side effects.”[2]

The Consumer Reports article states that bitter orange “contains synephrine, which is similar to ephedrine, banned by the FDA in 2004.”

After critically reviewing the available published chemical, pharmacological, toxicological, and clinical data available on bitter orange and its extracts, the authors of the HerbalGram safety review concluded that there is confusion in the medical literature that has caused misinformation among health professionals, journalists, and others:

“In summary,” they write, “based on current research as well as the extensive ingestion of bitter orange and p-synephrine in the form of dietary supplements as well as fruits, juices, and other citrus food products, the data demonstrate that bitter orange extract is safe for human consumption. No credible adverse events have been directly attributed to bitter orange, or its primary protoalkaloid, p-synephrine, in association with oral ingestion.”

“Due to the widespread confusion about the relative safety of bitter orange, we employed an extra level of peer review for this article,” said Mark Blumenthal, founder and executive director of the American Botanical Council and editor of HerbalGram. “We normally use 3 expert peer reviewers for articles in HerbalGram,” he noted, “but for this article we went an extra few miles by having additional expert reviewers comment on and check the accuracy of all of the information in this safety review. This included experts who have published on bitter orange and synephrine in pharmacology and medical journals.”

The entire peer-reviewed safety review of bitter orange, which is published in HerbalGram 89, is available on the American Botanical Council website.

About the American Botanical Council

Founded in 1988, the American Botanical Council is a leading international nonprofit organization addressing research and educational issues regarding herbs and medicinal plants. ABC’s members include academic researchers and educators; libraries; health professionals and medical institutions; government agencies; members of the herb, dietary supplement, cosmetic, and pharmaceutical industries; journalists; consumers; and others within over 80 countries. The organization occupies a historic 2.5-acre site in Austin, Texas where it publishes the quarterly journal HerbalGram, the monthly e-publication HerbalEGram, HerbClips (summaries of scientific and clinical publications), reference books, and other educational materials. ABC also hosts HerbMedPro, a powerful herbal database, covering scientific and clinical publications on more than 225 herbs, including organization and links of over 150 published papers on bitter orange. ABC also co-produces the "Herbal Insights" segment for Healing Quest, a television series on PBS.

ABC is tax-exempt under section 501(c)(3) of the IRS Code.


1. Stohs SJ, Preuss HG. The Safety of Bitter Orange (Citrus aurantium) and p-Synephrine. HerbalGram 2011;89:34-39.
2. Anon. Dangerous Supplements. Consumer Reports. September, 2010:16-20.

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