Manganese in human parenteral nutrition: Considerations for toxicity and biomonitoring

Abstract

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.

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

“…Patients with hepatic impairment and those receiving TPN, especially newborns, are susceptible to Mn accumulation [9, 17–19]. Infants and children are particularly vulnerable to inappropriate supplementation of Mn, which in some cases may lead to hypermanganesemia, dependent upon the duration of the treatment [17, 18, 20, 21]. Additionally, Mn is present at levels considered excessive in children’s formula [17].…”

Developmental exposure to manganese induces lasting motor and cognitive impairment in rats

“…Of particular importance, the hepatic mechanisms responsible for Mn excretion are not completely developed in newborns. This combined with the high bioavailability of the metal in TPN leads to Mn accumulation (Boggio Bertinet et al, 2000;Dobson et al, 2004;Santos et al, 2014).…”

Trace Element Status (Zinc, Copper, Selenium, Iron, Manganese) in Patients with Long-Term Home Parenteral Nutrition

“…Enforced reduction of the daily dose carries the risk of giving rise to a deficit of other trace elements; otherwise there is a risk of a toxic effect. Such a dilemma has been repeatedly reported in the literature in connection with the substitution of Mn during long-term HPN in the past years [3,4]. Preparation of substitution mixtures with lower content of Mn and/or its complete exclusion from complex formulas were suggested [5].…”

“…While the balance of fluid, energy, basic nutrients and biogenic elements in the form of all-in-one bags does not cause any greater problems, a personalized bag for each patient containing different essential trace elements is somewhat problematic [3,4]. In a long-term parenteral nutrition, trace elements are mostly supplied by widely used commercial pharmaceutical supplements (Addamel®, Tracutil®, Elotrace®) with their indicated but fixed content.…”