Semin Liver Dis 2008; 28(2): 226-231
DOI: 10.1055/s-2008-1073122
DIAGNOSTIC PROBLEMS IN HEPATOLOGY

© Thieme Medical Publishers

Cholestatic Liver Injury Associated with Whey Protein and Creatine Supplements

Kerry N. Whitt1 , Stephen C. Ward2 , Kemal Deniz2 , Lawrence Liu1 , Joseph A. Odin1 , Lihui Qin2
  • 1Department of Medicine, Division of Liver Diseases, The Mount Sinai Medical Center, New York, New York
  • 2The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, The Mount Sinai Medical Center, New York, New York
Further Information

Publication History

Publication Date:
02 May 2008 (online)

ABSTRACT

We present a case of acute cholestatic liver injury associated with the combination of whey protein and creatine supplements. The difficulty of diagnosing drug-induced liver injury is emphasized. The patient is a healthy, 27-year-old man who presented with painless jaundice. He had no occupational exposures to solvents, was not taking prescription medications, and did not use recreational drugs or alcohol. He was an enthusiastic weight-lifter and had been taking creatine for 8 to 9 months and whey protein supplements for 4 weeks prior to the development of symptoms. Laboratory tests revealed elevated total bilirubin (54.7 mg/dL) and alkaline phosphatase (436 U/L), minimally elevated transaminases, and a creatinine of 3.1 mg/dL. Serologic work-up was negative for viral hepatitis and autoimmune liver disease, and Wilson's disease was ruled out. Magnetic resonance cholangiopancreatogram was unremarkable, but a liver biopsy showed marked cholestasis with ductular proliferation. He had dramatic clinical improvement with intravenous fluids and discontinuation of the nutritional supplements. In patients with acute liver injury, clinicians should inquire about dietary supplement usage and consider immediate discontinuation of all unnecessary products. We describe a case of profound jaundice related to a commonly used and reportedly safe combination of such supplements.

REFERENCES

  • 1 Sgro C, Clinard F, Quazir F et al.. Incidence of drug-induced hepatic injuries: a French population-based study.  Hepatology. 2002;  36 451-455
  • 2 Ostapowicz G, Fontana R J, Schiødt F V et al.. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.  Ann Intern Med. 2002;  137 947-954
  • 3 Navarro V J, Senior J R. Drug-related hepatotoxicity.  N Engl J Med. 2006;  354 731-739
  • 4 Andrade R J, Lucena M I, Fernandez M C et al.. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period.  Gastroenterology. 2005;  129 512-521
  • 5 Kessler R C, Davis R B, Foster D F et al.. Long-term trends in the use of complementary and alternative medical therapies in the United States.  Ann Intern Med. 2001;  135 262-268
  • 6 Seeff L B. Herbal hepatotoxicity.  Clin Liver Dis. 2007;  11 577-596
  • 7 Favreau J T, Ryu M L, Braunstein G et al.. Severe hepatotoxicity associated with the dietary supplement LipoKinetix.  Ann Intern Med. 2002;  136 590-595
  • 8 Gunawan B K, Kaplowitz N. Mechanisms of drug-induced liver disease.  Clin Liver Dis. 2007;  11 459-475
  • 9 Andrade R J, Luceni M I, Kaplowitz N et al.. Outcome of acute, idiosyncratic drug-induced liver injury: long-term follow-up in a hepatotoxicity registry.  Hepatology. 2006;  44 1581-1588
  • 10 Zimmerman H J. Hepatotoxicity. 2nd ed. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 61-109
  • 11 Pauli-Magnus C, Meier P J. Hepatobiliary transporters and drug-induced cholestasis.  Hepatology. 2006;  44 778-787
  • 12 Sebagh M, Yilmaz F, Karam V et al.. The histologic pattern of “biliary tract pathology” is accurate for the diagnosis of biliary complications.  Am J Surg Pathol. 2005;  29 318-323
  • 13 Handharyani E, Ochiai K, Iwata N, Umemura T. Immunohistochemical and ultrastructural study of Ito cells in response to extrahepatic bile duct ligation in broiler chickens.  J Vet Med Sci. 2001;  63 547-552
  • 14 Bronfenmajer S, Schaffner F, Popper H. Fat-storing cells (lipocytes) in human liver.  Arch Pathol. 1966;  82 447-453
  • 15 Shao A, Hathcock J N. Risk assessment for creatine monohydrate.  Regul Toxicol Pharmacol. 2006;  45 242-251
  • 16 Kume H, Okazaki K, Sasaki H. Hepatoprotective effects of whey protein on D-galactosamine-induced hepatitis and liver fibrosis in rats.  Biosci Biotechnol Biochem. 2006;  70 1281-1285
  • 17 Watanabe A, Okada K, Shimizu Y et al.. Nutritional therapy of chronic hepatitis by whey protein (non-heated).  J Med. 2000;  31 283-302
  • 18 Volek J S, Rawson E S. Scientific basis and practical aspects of creatine supplementation for athletes.  Nutrition. 2004;  20 609-614
  • 19 Kreider R B, Melton C, Rasmussen C J et al.. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes.  Mol Cell Biochem. 2003;  244 95-104
  • 20 Tarnopolsky M A, Bourgeois J M, Snow R et al.. Histological assessment of intermediate and long-term creatine monohydrate supplementation in mice and rats.  Am J Physiol Regul Integr Comp Physiol. 2003;  285 R762-R769
  • 21 Kafrouni M I, Anders R A, Verma S. Hepatotoxicity associated with dietary supplements containing anabolic steroids.  Clin Gastroenterol Hepatol. 2007;  5 809-812

Kerry N WhittM.D. 

Department of Medicine, Division of Liver Diseases, The Mount Sinai Medical Center

One Gustave L. Levy Place, New York, NY 10029

Email: kerry.whitt@mssm.edu

    >