title: Multi-ingredient, caffeine-containing dietary supplements: history, safety, and efficacy.
abstract: OBJECTIVE
  Our objective was to review the history, safety, and efficacy of caffeine-containing dietary supplements in the United States and Canada.
  
  
  METHODS
  PubMed and Web of Science databases (1980-2014) were searched for articles related to the pharmacology, toxicology, and efficacy of caffeine-containing dietary supplements with an emphasis on Ephedra-containing supplements, Ephedra-free supplements, and energy drinks or shots.
  
  
  RESULTS
  Among the first and most successful dietary supplements to be marketed in the United States were those containing Ephedra—combinations of ephedrine alkaloids, caffeine, and other phytochemicals. A decade after their inception, serious tolerability concerns prompted removal of Ephedra supplements from the US and Canadian markets. Ephedra-free products, however, quickly filled this void. Ephedra-free supplements typically contain multiple caffeine sources in conjunction with other botanical extracts whose purposes can often be puzzling and their pharmacologic properties difficult to predict. Ingestion of these products in the form of tablets, capsules, or other solid dosage forms as weight loss aids, exercise performance enhancers, or energy boosters have once again brought their tolerability and efficacy into question. In addition to Ephedra-free solid dosage forms, caffeine-containing energy drinks have gained a foothold in the world market along with concerns about their tolerability.
  
  
  CONCLUSIONS
  This review addresses some of the pharmacologic and pharmaceutical issues that distinguish caffeine-containing dietary supplement formulations from traditional caffeine-containing beverages. Such distinctions may account for the increasing tolerability concerns affiliated with these products.
authors.affiliation: Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, College of Pharmacy, Little Rock, Arkansas. Electronic address: gurleybillyj@uams.edu.
authors.forename: Bill J
authors.initials: BJ
authors.lastname: Gurley
authors.affiliation: Education and Reference Services, University of Arkansas for Medical Sciences Library, Little Rock, Arkansas.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Steelman
authors.affiliation: Education and Reference Services, University of Arkansas for Medical Sciences Library, Little Rock, Arkansas.
authors.forename: Sheila L
authors.initials: SL
authors.lastname: Thomas
mesh_terms: D000470:Alkaloids / Q000009:adverse effects; D002110:Caffeine / Q000009:adverse effects / Q000494:pharmacology*; D002170:Canada; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D019587:Dietary Supplements / Q000009:adverse effects / Q000266:history; D004338:Drug Combinations; D061215:Energy Drinks / Q000009:adverse effects / Q000266:history; D029789:Ephedra / Q000009:adverse effects / Q000737:chemistry; D004809:Ephedrine / Q000737:chemistry; D049673:History, 20th Century; D006801:Humans; D057053:Safety-Based Medical Device Withdrawals; D014481:United States
chemical_list: D000470:Alkaloids; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D002110:Caffeine; D004809:Ephedrine
keywords: Ephedra; Ephedra-free; caffeine; dietary supplements; energy drinks