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Juice Plus or Toxicity Plus

  • Aung Naing
    Correspondence
    Requests for reprints should be addressed to Aung Naing, MD, FACP, Assistant Professor, Department of Investigational Cancer Therapeutics, Unit 455, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, PO Box 301402, Houston, TX 77030-1402
    Affiliations
    The University of Texas MD Anderson Cancer Center, Houston, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program)
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  • Joann Aaron
    Affiliations
    The University of Texas MD Anderson Cancer Center, Houston, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program)
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  • Razelle Kurzrock
    Affiliations
    The University of Texas MD Anderson Cancer Center, Houston, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program)
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      To the Editor:
      The increasing popularity and widespread use of complementary and alternative medicine is based on its perceived effectiveness in treating and preventing disease, the belief that such treatments are “natural” and therefore safe, and patients' perceptions that they are actively participating in controlling their disease and its management.
      • Stickel F.
      • Patsenker E.
      • Schuppan D.
      Herbal hepatotoxicity.
      • Ernst E.
      The role of complementary and alternative medicine in cancer.
      However, there also can be unforeseen side effects from complementary and alternative medicine, including liver damage and interference with allopathic therapies.

      Clinical Summary

      A 51-year-old woman with endometrial cancer whose condition progressed with prior treatments was referred to the MD Anderson Cancer Center Phase I Clinical Trials clinic for treatment with an investigational agent. Initial assessment showed normal liver function test results, although aspartate aminotransferase, alanine aminotransferase, and bilirubin levels were elevated on repeat blood tests several days later. Peak total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels were 4.0 mg/dL, 302 IU/L, and 91 IU/L, respectively (Figure). The patient felt well with no fever or change in diet. She had icteric sclera and mild tenderness on palpation of a lower abdominal/pelvic mass. Computed tomography and ultrasound showed no extrahepatic or intrahepatic biliary obstruction, hepatomegaly, or liver metastases. The patient's regular medications included ramipril, calcium/vitamin D, ciprofloxacin, hydrocodone/acetaminophen, and ibuprofen. She had started taking Juice Plus+ a few days before her initial visit to the MD Anderson Cancer Center. Viral hepatitis serology, ceruloplasmin, anti-smooth muscle antibody, and antimitochondrial antibody test results were negative. Liver biopsy results showed no carcinoma, but focal hepatocellular degenerative changes and steatosis with mild sinusoidal dilatation against a background of mild cholestasis, minimal lobular, and portal acute and chronic inflammation were findings most consistent with a drug effect. On the basis of the timing of her elevated liver function test results, the Juice Plus+ supplement was deemed the most likely causative agent of the patient's liver injury, and it was discontinued. Liver function test results peaked and improved, followed shortly by a second lesser peak, and then normalized over 4 weeks.
      Figure thumbnail gr1
      FigureLiver enzyme values: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin.

      Discussion

      Juice Plus+ is a dietary supplement containing concentrated vegetable and fruit extracts fortified with added nutrients and vitamins, advertised as reducing oxidative stress. Urticaria and gastrointestinal distress were reported in some clinical studies.
      • Houston M.C.
      • Cooil B.
      • Olafsson B.J.
      • Raggi P.
      Juice powder concentrate and systemic blood pressure, progression of coronary artery calcium and antioxidant status in hypertensive subjects: a pilot study.
      The use of complementary and alternative medicine by patients with cancer is highly prevalent. In the United States, a study showed that 34% of patients (72/212) with advanced cancer who were planning to enroll in phase I trials took biologically based complementary and alternative medicine, and an additional 30% had considered taking complementary and alternative medicine.
      • Hlubocky F.J.
      • Rattain M.J.
      • Wen M.
      • Daugherty C.K.
      Complementary and alternative medicine among advanced cancer patients enrolled on phase I trials: a study of prognosis, quality of life, and preferences for decision making.
      Because most herbal products are considered to be dietary supplements, they are not required to meet specified US Federal Food, Drug, and Cosmetic Act requirements. The only requirement is to meet the standards set forth in the 1994 Dietary Supplement and Health Education Act.
      • De Smet P.A.
      Herbal remedies.
      Although most supplements are safe, some such as Chinese herbal tea, the African Remedy, and clove oil have been shown to cause liver toxicity.
      • Chitturi S.
      • Farrell G.C.
      Herbal hepatotoxicity: an expanding but poorly defined problem.

      Conclusions

      Our patient had hepatotoxicity related to the use of complementary and alternative medicine. The injury was reversible after discontinuation of the drug. As clinicians, it is important for us to investigate our patients' use of complementary and alternative medicine, as well as prescription drugs, in the event of an abnormal liver injury or otherwise deleterious clinical event.

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        • Patsenker E.
        • Schuppan D.
        Herbal hepatotoxicity.
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        • Ernst E.
        The role of complementary and alternative medicine in cancer.
        Lancet Oncol. 2000; 1: 176-180
        • Houston M.C.
        • Cooil B.
        • Olafsson B.J.
        • Raggi P.
        Juice powder concentrate and systemic blood pressure, progression of coronary artery calcium and antioxidant status in hypertensive subjects: a pilot study.
        Evid Based Complement Alternat Med. 2007; 4: 455-462
        • Hlubocky F.J.
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        Herbal remedies.
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        Herbal hepatotoxicity: an expanding but poorly defined problem.
        J Gastroenterol Hepatol. 2000; 15: 1093-1099