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

Abstract

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.

Keywords: Heavy metals; manganese; neurotoxicity; nutrition; parenteral nutrition; trace elements.

Figure 1.

The differences in Mn handling after oral (A) and intravenous (B) administration. Orally administered Mn is absorbed in the duodenum and jejunum. Intestinal Mn absorption is also regulated by dietary factors that may reduce Mn bioavailability. Once absorbed, Mn enters the enterohepatic circulation and approximately 97% of the absorbed Mn is excreted through bile, thus only 3% Mn enters the systemic circulation with subsequent transport as albumin-, transferrin- or citrate-bound Mn to target tissues, including brain. As a result of intravenous injection, Mn enters directly into the bloodstream with 100% bioavailability, as this route of exposure in contrast to dietary intake lacks limiting factors such as intestinal absorption, and the influence of other dietary factors and biliary excretion. Altogether, these factors result in higher brain Mn accumulation, thus increasing the risk of neurotoxicity resulting from intravenous Mn administration