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
• nutrition
• neurotoxicity
• parenteral nutrition
• trace elements
• manganese

Article highlights

• The diet is the major source of Mn intake for humans. Mn is required for several normal physiological functions that support development, growth, and neuronal function in the brain. Nevertheless, overexposure to this metal induces toxic effects, primarily neurotoxicity

• The mechanism(s) that leads to Mn-induced neurotoxicity is not entirely understood. Some proposed mechanisms include oxidative stress, mitochondrial dysfunction, transporter dysregulation, metal imbalances, neuroinflammation, and protein trafficking pathway dysregulation

• PN is used when an individual has clinical conditions that could inhibit enteral nutrition and adequate gastrointestinal uptake. Mn can be found as a contaminant in parenteral solutions, leading to accumulation in brain and developing neurotoxicity.

• Neuroimaging studies in children and adults reported that Mn accumulation in basal ganglia after PN was associated with neurological symptoms, such as movement disorders, tremor, rigidity, and seizures

• The challenge to the scientific community is to define clinical biomarkers for Mn toxicity in general as well as by PN, identifying new effective agents to treat Mn-neurotoxicity and development of new guidelines and practice safeguards to protect hospitalized children and adults from excessive Mn exposure in PN are urgently needed.

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Declaration of interest

Authors AB Bowman and M Aschner serve as members of the scientific advisory board to American Regent, Inc related to the TRALEMENT(TM) PN product. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Institute of Environmental Health Sciences (NIEHS) R01ES07331 and R01ES10563 to MA and ABB. R01 ES024756 (EL), and R01 ES031282 (EL).