Neurotoxicities in Infants Seen With the Consumption of Star Anise Tea Diego Ize-Ludlow, MD*; Sean Ragone, MD‡; Isaac S. Bruck, PhD§; Jeffrey N. Bernstein, MD‡; Michael Duchowny, MD; and Barbara M. Garcia Pen ˜ a, MD, MPH¶ ABSTRACT. Chinese star anise (Illicium verum Hook f.) is a well-known spice used in many cultures. Many populations use it as a treatment for infant colic. Japa- nese star anise (Illicium anisatum L), however, has been documented to have both neurologic and gastrointestinal toxicities. Recently, concern has been raised regarding the adulteration of Chinese star anise with Japanese star anise. We report 7 cases of adverse neurologic reactions in infants seen with the home administration of star anise tea. In addition, we have found evidence that Chi- nese star anise has been contaminated with Japanese star anise. More strict federal regulation of the import of star anise into the United States is warranted. Star anise tea should no longer be administered to infants because of its potential danger in this population. Pediatrics 2004; 114:e653–e656. URL: www.pediatrics.org/cgi/doi/10.1542/ peds.2004-0058; star anise, neurotoxicity, colic, infants. ABBREVIATION. GC-MS, gas chromatography–mass spectroscopy. C hinese star anise (Illicium verum Hook f.) is a well-known spice used in many cultures. Ca- ribbean and Latino populations typically use a tea infusion of its 8-pointed stellate fruit (Fig 1) as a carminative and sedative for the treatment of infant colic. Because of its long history of herbal and culi- nary uses, Chinese star anise has been commonly regarded as being safe and nontoxic. A closely re- lated species, Japanese star anise (Illicium anisatum L, syn. I japonicum Sieb, syn. I religiosum Sieb et Zucc), has been well documented to cause both neurologic and gastrointestinal toxicities. 1–5 All Illicium species contain sesquiterpene lactone compounds, 6–12 a large and diverse group of biolog- ically active plant chemicals, most containing a num- ber of secondary metabolite products related to ani- satin, neoanisatin, and pseudoanisatin, the potent neurotoxins found in Japanese star anise. 13,14 Al- though Chinese star anise is considered safe for con- sumption, this species also contains toxic com- pounds named veranisatins A, B, and C. 15 Although these veranisatins are not as potent as anisatin itself, neurologic symptoms are observed at higher doses. 15 Anisatin compounds are thought to act as potent noncompetitive -aminobutyric acid antagonists. 16–20 Concern has been raised regarding the adultera- tion of I verum with I anisatum and has led to recalls of these products in other countries, including Spain, France, Scotland, China, Japan, and Netherlands. 21–23 In this communication, we report 7 cases of adverse neurologic reactions associated with the home ad- ministration of star anise tea to young infants seen during the past 2 years at Miami Children’s Hospital. In addition, we have discovered adulteration of sev- eral of the Chinese star anise samples with I anisatum. METHODS Clinical Cases Over a 2-year period, infants with signs and symptoms of star anise intoxication were identified in the emergency department of Miami Children’s Hospital. Miami Children’s Hospital is a large, urban, pediatric teaching hospital with an emergency department that sees 87 000 patients per year. Signs and symptoms of star anise intoxication include jitteriness, hyperexcitability, nystagmus, vomiting, myoclonic movements, and seizures. We included pa- tients who experienced an otherwise unexplainable acute onset of 1 or more signs of star anise intoxication after the ingestion of star anise tea. Analysis of Samples Samples were obtained and analyzed from 3 of the patients (5, 6, and 7) to determine whether readily available herbal packages of I verum had been contaminated with the toxic I anisatum. Sam- ples from the remaining 4 patients were not available for analysis. Three samples of Chinese star anise were also purchased from local stores for comparative morphologic and chemical analysis. All fruits were inspected for the defining structures of I verum and I anisatum. The volatile fraction from each sample was then examined by gas chromatography–mass spectroscopy (GC-MS) techniques for the presence of safrole and eugenol, compounds found in all toxic Illicium species but not in I verum. 24–28 The samples were also examined for the presence of anethole, found in I verum in con- centrations of 72% to 92%. 24–28 Other Illicium species typically have anethole concentrations 40%. 29,30 The isolation and charac- terization of anisatin and neoanisatin 31–33 using liquid chromatog- raphy–mass spectroscopy techniques was also performed. The method of the liquid chromatography–mass spectroscopy and GC-MS analyses are described elsewhere. 34 RESULTS Clinical Cases Seven cases of infants who were aged 2 to 12 weeks and had signs of acute star anise intoxication were identified over a 2-year period. The cases are presented in Table 1. Symptoms included seizures, jitteriness, irritability, hyperexcitability, emesis, ver- From the *Department of Pediatrics, Miami Children’s Hospital, Miami, Florida; ‡Florida Poison Control Center, Jackson Memorial Hospital, Uni- versity of Miami School of Medicine, Miami, Florida; §Center for Ethno- biology and Natural Products, Florida International University, Miami, Florida; Department of Neurology, Miami Children’s Hospital and the University of Miami School of Medicine, Miami, Florida; and ¶Division of Emergency Medicine, Miami Children’s Hospital, Miami, Florida. Accepted for publication May 25, 2004. doi:10.1542/peds.2004-0058 Reprint requests to (B.M.G.P.) Division of Emergency Medicine, Miami Children’s Hospital, 3100 SW 62nd Ave, Miami, FL 33155. E-mail: barbara.pena@mch.com PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad- emy of Pediatrics. www.pediatrics.org/cgi/doi/10.1542/peds.2004-0058 PEDIATRICS Vol. 114 No. 5 November 2004 e653 by guest on June 12, 2020 www.aappublications.org/news Downloaded from