Manganese in human parenteral nutrition: Considerations for toxicity and biomonitoring

• Hypermanganesemia and neurotoxicity are associated with the duration of Mn supplementation.
• Whole blood Mn levels are not well correlated with Mn-induced neurotoxicity.
• This review addresses various approaches for biomonitoring Mn exposure and neurotoxic risk.

The iatrogenic risks associated with excessive Mn administration in parenteral nutrition (PN) patients are well documented. Hypermanganesemia and neurotoxicity are associated with the duration of Mn supplementation, Mn dosage, as well as pathological conditions, such as anemia or cholestasis. Recent PN guidelines recommend the biomonitoring of patients if they receive Mn in their PN longer than 30 days. The data in the literature are conflicting about the method for assessing Mn stores in humans as a definitive biomarker of Mn exposure or induced-neurotoxicity has yet to be identified. The biomonitoring of Mn relies on the analysis of whole blood Mn (WB Mn) levels, which are highly variable among human population and are not strictly correlated with Mn-induced neurotoxicity. Alterations in dopaminergic (DAergic) and catecholaminergic metabolism have been studied as predictive biomarkers of Mn-induced neurotoxicity. Given these limitations, this review addresses various approaches for biomonitoring Mn exposure and neurotoxic risk.