Evaluating the risk of manganese-induced neurotoxicity of parenteral nutrition: review of the current literature

Airton C. Martins, Silvana Ruella Oliveira, Fernando Barbosa, Alexey A. Tinkov, Anatoly V. Skalny, Abel Santamaría, Eunsook Lee, Aaron B. Bowman, Michael Aschner

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


Introduction: Several diseases and clinical conditions can affect enteral nutrition and adequate gastrointestinal uptake. In this respect, parenteral nutrition (PN) is necessary for the provision of deficient trace elements. However, some essential elements, such as manganese (Mn) may be toxic to children and adults when parenterally administered in excess, leading to toxic, especially neurotoxic effects. Areas covered: Here, we briefly provide an overview on Mn, addressing its sources of exposure, the role of Mn in the etiology of neurodegenerative diseases, and focusing on potential mechanisms associated with Mn-induced neurotoxicity. In addition, we discuss the potential consequences of overexposure to Mn inherent to PN. Expert opinion: In this critical review, we suggest that additional research is required to safely set Mn levels in PN, and that eliminating Mn as an additive should be considered by physicians and nutritionists on a case by case basis in the meantime to avoid the greater risk of neurotoxicity by its presence. There is a need to better define clinical biomarkers for Mn toxicity by PN, as well as identify new effective agents to treat Mn-neurotoxicity. Moreover, we highlight the importance of the development of new guidelines and practice safeguards to protect patients from excessive Mn exposure and neurotoxicity upon PN administration.

Original languageEnglish (US)
Pages (from-to)581-593
Number of pages13
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number5
StatePublished - 2021


  • Heavy metals
  • manganese
  • neurotoxicity
  • nutrition
  • parenteral nutrition
  • trace elements

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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