Hypertensive Retinopathy Associated With Use of the Ephedra-Free Weight-Loss Herbal Supplement Hydroxycut

Scott L. Willis, MD; Fouad J. Moawad, MD; Joshua D. Hartzel; Melissa Iglesias, DO; William L. Jackson, MD

Disclosures

September 28, 2006

Discussion

To our knowledge, the patient described above represents the first reported case of hypertensive retinopathy associated with the use of Hydroxycut. The patient had no previous history of hypertension, and his symptoms resolved following the discontinuation of Hydroxycut. His retinal findings were consistent with grade 3 retinopathic changes. The presence of deep and flare retinal hemorrhages is typically seen in more acute or severe hypertension.[7] The patient also had arteriovenous-crossing changes (or nicking), which are classically associated with chronic hypertension but can be seen in early and severe cases of hypertension.[8] The patient's history suggests that his retinopathy was acute in nature and his retinal exam supports this conclusion.

Hydroxycut is an "ephedra-free" dietary supplement designed to enhance weight loss and improve performance by increasing metabolism.[4] The original formulation contained the ephedra-type alkaloid, ma huang, a sympathomimetic with a serious side-effect profile that is known to include seizures, hepatitis, and myocarditis.[1] In 2004, the US Food and Drug Administration banned the use of ephedra as a dietary supplement.[9] As a consequence of that decision, Hydroxycut, along with most other dietary and herbal supplements, has been reformulated to exclude ephedra.

The safety of the new formulation is being challenged as case reports of adverse events are now being reported. A recent association with hepatotoxicity was reported with the new formulation.[4] Stevens and colleagues[4] reported the cases of 2 men, ages 27 and 30, who presented with acute liver injury following the administration of Hydroxycut for 5 weeks and 5 days, respectively. The former developed a severe transaminitis with an aspartate aminotransferase level of 1969 U/L and an alanine aminotransferase level of 3962 U/L. The latter presented with a cholestatic liver pattern with a serum bilirubin level of 7.8 mg/dL and an alkaline phosphatase level of 530 U/L. Both patients underwent a thorough work-up that included viral serologies (hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus), antinuclear and antismooth muscle antibodies, acetaminophen level, and toxicology screening. The work-up for these other etiologies was negative, and both patients recovered with supportive treatment and discontinuation of Hydroxycut.

It is unclear which ingredient in Hydroxycut might be responsible for the increased blood pressure and retinal changes that were seen in our patient. Presumably, the causative agent has sympathomimetic effects. Caffeine is a major ingredient in Hydroxycut and has known hypertensive effects.[10] At recommended daily doses Hydroxycut has a caffeine content of 600 mg, which is equivalent to 6 cups of coffee.[11]

A recent study evaluated the effects of 2 weight-loss supplements, one of which was caffeine-based (Xenadrine EFX) and the other synephrine-based (Advantra Z). The researchers found that the caffeine-based product significantly increased blood pressure by 9.6 mm Hg and heart rate by 16.7 beats per minute, whereas the synephrine-based product did not, again, suggesting that caffeine may be playing a significant sympathomimetic role in these supplements.[12] It is important to note that the caffeine-based product also contained a small amount of synephrine (5.5 mg). This raises the possibility that caffeine may be working synergistically with synephrine to cause the elevations in blood pressure that are seen with Xenadrine EFX, but this relationship has not been studied.

Xenadrine EFX has also been implicated in a case of exercise-induced syncope associated with QT prolongation.[5] Nasir and colleagues[5] reported the case of a 22-year-old woman who experienced a syncopal episode after her second dose of Xenadrine. An electrocardiogram showed significant QT prolongation that resolved within 24 hours upon discontinuation of Xenadrine. The active ingredient of this supplement is caffeine, although it contains a host of other plant extracts and amino acids, as previously stated.[13] Of interest, Xenadrine contains 239 mg of caffeine, whereas Hydroxycut contains nearly 3 times that amount.

With respect to Hydroxycut, it is unclear whether caffeine alone is the causative agent, or whether caffeine is working synergistically with one of the other active ingredients (Garcinia cambogia, Gymnema sylvestre, glucomannan, guarana extract, green tea, or willow bark). A Medline search failed to reveal any information about the hemodynamic effects of caffeine mixed with these other agents. Unlike Xenadrine, Hydroxycut does not contain synephrine or any other ingredients with known sympathomimetic or vasoactive effects, with the exception of caffeine.

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