In this patient, the temporal relationship between the initiation of the supplement and the onset of symptoms was consistent with a diagnosis of ischemic colitis caused by decreased vascular flow to the gastrointestinal tract and resultant ischemic insult. Ischemic colitis has been associated with the use of vasoconstrictive drugs known to decrease splanchnic blood flow, such as cocaine, ma huang (ephedra), and pseudoephedrine.
- Dowd J
- Bailey D
- Moussa K
- Nair S
- Doyle R
- Culpepper-Morgan JA
Ischemic colitis associated with pseudoephedrine: four cases.
According to the manufacturer, each capsule of the supplement our patient was taking contained 5 active ingredients—bitter orange (334 mg), Garcinia cambogia (300 mg), L
-carnitine (250 mg), chitosan (250 mg), and chromium arginate (200 μg)—and the recommended dosage was 3 capsules once a day by mouth to achieve optimal weight loss. Bitter orange (Citrus aurantium
), also known as sour orange, Seville orange, or zhi shi, has been shown to increase mean arterial pressure and decrease portal blood flow in rat studies.
- Huang YT
- Wang GF
- Chen CF
- Chen CC
- Hong CY
- Yang MC
Fructus aurantii reduced portal pressure in portal hypertensive rats.
This effect may be mediated by synephrine, a key active compound found in the C aurantium
plant. Synephrine, an indirect β-sympathomimetic agent and sympathomimetic α-adrenergic agonist, has effects on the cardiovascular system similar to those of ephedra.
Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids.
None of the other 4 active ingredients in NaturalMax Skinny Fast have been shown to have sympathomimetic properties. Furthermore, none of the 4 ingredients have been known to cause any gastrointestinal adverse effects other than L
-carnitine, which can cause diarrhea if consumed in high doses. We attributed our patient's ischemic colitis to the action of bitter orange and did not perform toxicologic or pharmacological analysis. It is plausible that the supplement may have contained a contaminant that could have caused the patient's symptoms. Nevertheless, we believe that bitter orange was the likely agent responsible for the adverse effects.
Several reports of toxic effects associated with bitter orange have appeared in the literature. The recent case report by Gange et al
- Gange CA
- Madias C
- Felix-Getzik EM
- Weintraub AR
- Estes III, NAM
Variant angina associated with bitter orange in a dietary supplement.
described the occurrence of variant angina in an individual who was taking a bitter orange-containing weight-loss drug, and use of bitter orange has also been associated with acute myocardial infarction
- Nykamp DL
- Fackih MN
- Compton AL
Possible association of acute lateral-wall myocardial infarction and bitter orange supplement.
and exercise-induced syncope with QT prolongation in a young woman.
- Nasir JM
- Durning SJ
- Ferguson M
- Barold HS
- Haigney MC
Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine [published correction appears in Mayo Clin Proc. 2004;79:1591].
Additionally, a case of ischemic colitis, similar to that in our patient, was reported in a woman taking supplements that contained both ephedra and bitter orange.
- Ryan CK
- Reamy B
- Rochester JA
Ischemic colitis associated with herbal product use in a young woman.
In this latter case, ischemic colitis may have been caused by either agent or may have been attributable to the combined effects of ephedra and bitter orange. Our patient was taking a weight-loss supplement that was “ephedra free” and thus contained only bitter orange.
As bitter orange increases in popularity and consumption, more individuals may be at risk of adverse effects. Consumers should be aware of the potential harm that these dietary supplements can cause, and health care professionals should report these adverse events to the FDA. MedWatch is an FDA program that allows both health care professionals and consumers to report serious problems that they suspect are associated with the medical products they prescribe, dispense, or use. Such reports, along with follow-up investigations, can help to identify important safety concerns (see www.fda.gov/medwatch/
for more information or to report an event online).