title: The use of animal models in homeopathic research--a review of 2010-2014 PubMed indexed papers.
abstract: BACKGROUND
  In the 1990s, a study was performed on the effects of highly diluted thyroxine on frog metamorphosis. This model represented one of the most discussed examples of the biological effects of high dilutions over the next two decades. In 2010, another critical conceptual review of the use of animal models in homeopathy and high-dilution research was published. The main contribution of these studies was the elucidation of the biological features and phenomenology of the effects of high dilutions on living systems, representing an important step forward in our understanding of the mechanisms of action of homeopathic medicines.
  
  
  METHODS
  We performed a further review of this line of investigation using the same methods. Fifty-three articles that were indexed in the PubMed database and used 12 different animal species were systematically evaluated. Only a fraction of the studies (29/53) reported herein were performed with "ultra high" dilutions. The other studies were performed with dilutions in ranges below 10(-23) (14/53 articles) or commercial complexes (10/53 articles).
  
  
  RESULTS
  Only two articles reported negative results; both used in vivo protocols to test commercial complexes, one in fish and one in bees. The quality of the employed techniques improved in 2010-2014 compared with the studies that were reviewed previously in 2010, with the inclusion of more ethically refined protocols, including in vitro primary cell cultures and ex vivo studies (10/53 articles), often with three or more replicates and analyses of epigenetic mechanisms that were previously unknown in 2010.
  
  
  CONCLUSIONS
  In our updated review of the past 5 years, we found further demonstrations of the biological effects of homeopathy using more refined animal models and in vitro techniques.
authors.affiliation: Paulista University UNP, São Paulo, Brazil. Electronic address: leonibonamin@unip.br.
authors.forename: Leoni Villano
authors.initials: LV
authors.lastname: Bonamin
authors.affiliation: Paulista University UNP, São Paulo, Brazil.
authors.forename: Thayná Neves
authors.initials: TN
authors.lastname: Cardoso
authors.affiliation: Paulista University UNP, São Paulo, Brazil.
authors.forename: Aloísio Cunha
authors.initials: AC
authors.lastname: de Carvalho
authors.affiliation: Paulista University UNP, São Paulo, Brazil.
authors.forename: Juliana Gimenez
authors.initials: JG
authors.lastname: Amaral
mesh_terms: D000818:Animals; D001516:Bees; D006705:Homeopathy / Q000379:methods*; D023421:Models, Animal; D008962:Models, Theoretical; D012107:Research Design
keywords: Animal models; High dilutions; Homeopathy; Review