Background
Manganese is a naturally occurring transition metal and an important trace element in the body. Manganese chemical symbol is Mn and the atomic number is 25. In the body, manganese is a cofactor of many important enzymes that are involved in the synthesis of polysaccharide, fatty acids, and urea from ammonia, regeneration of red blood cells, the reproductive cycle, and chondroitin synthesis in bone matrix (1). Despite several health benefits, excessive exposure to manganese in an extended period of time can lead to manganese induced neurotoxicity, which can present as physical and/or psychological disorders (2,3,4).
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In nature, manganese is a chemical element that is often found in mineral combination with iron or as oxides. Manganese compounds have many industrial applications and can be found in:
- Steel industry uses manganese as an alloying constituent to improve forging qualities
- Alloying agent for aluminum to increase resistance to corrosion
- Alloying agent for copper to improve its mechanical strength
- Batteries
- Chemical industry (e.g. purifying drinking water, medicine)
- Coloring of ceramics and glass
- Agricultural fungicide
Lithium-manganese dioxide cell
Manganeses is also an important trace element that can be found in many types of food:
- Whole grains
- Nuts
- Leafy greens
- Soybean
- Oysters
- Clams
- Coffee
- Tea
- Many spices
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A small amount of manganese can also be found in daily drinking water with concentration ranging from 1 to 100 mcg/L (5).
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Toxicokinetics
There has been no evidence showing that high dietary manganese intake can result in toxicity. However, chronic exposure to manganese dust through inhalation has been reported to cause neurotoxicity, especially in the welding and mining industry (4,6).
According to the CDC, the extend of inhaled manganese absorption is based on the particle size. Smaller particles of manganese can be deposited in the lower airways and be absorbed into the blood and lymph fluids. On the other hand, larger particles can be deposited in the nasal mucosa and be transported to the brain by the olfactory or trigeminal nerves (7). Circulating manganese particles are distributed throughout the body with the highest levels found in the pancreas, liver, and kidneys (7).
Manganese – Occupational and Environmental Exposure
Carcinogenicity
Manganese and its inorganic compounds are considered to have low carcinogenic risks compared to other heavy metals. Studies have shown that manganese demonstrated weak mutagenic risk in vitro with unknown mechanisms of action. Evidence has remained insufficient to conclude that manganese can increase cancer risks in animals and humans. However, one should be cautious when being exposed to manganese chronically with respect to the impact on the central nervous system and potential harm to the fetus (8,9).
Mechanism of Action
The mechanism of action of manganese in producing neurotoxicity has not been proved yet. The most commonly reported manganese toxicity is neurotoxicity. However, inhaled manganese can also cause adverse health effects on respiratory function, reproductive system, and development in children (10). One of the hypothesized mechanisms of manganese toxicity involves the effects on cholinergic signaling.
Overview of Manganese (Mn) effects on cholinergic signaling. a Mn promotes an increase in reactive oxygen species production through of mitochondrial dysfunction. In addition, Mn impairs the synthesis of precursors for acetylcholine neurotransmitter production. b Mn induces up-regulation of nicotinic and muscarinic receptors. c Mn has a controversial effect on acetylcholinesterase since it is able to increase, reduce or not alter the activity of this enzyme across diferent models of Mn exposure
Target organs
Manganese particles are widely distributed throughout the body and can be found in:
- Brain – Basal ganglia: Target for toxicity
- Pancreas
- Liver
- Kidneys
Signs and Symptoms
Manganese can accumulate in the body and exhibit clinical signs and symptoms slowly over months or years. It can cause a permanent neurological disorder known as manganism and present as:
- Irritability
- Aggressiveness
- Hallucinations
- Tremors
- Muscle spasms
- Tinnitus, hearing loss
- Mania
- Insomnia
- Depression
- Delusions
- Anorexia
- Headaches
- Changes in mood and short-term memory
- Altered reaction times
- Reduced hand-eye coordination
- Parkinson’s-like symptoms
Besides, inhaled manganese can cause damages to the respiratory system such as lung inflammation and impaired lung function.
Routes of exposures (7)
- Inhalation – Predominant route of exposure for occupational populations
Minor route of exposure for the general population:
- Oral – Predominant route of exposure for the general population.
- Dermal – Minor route of exposure.
Biomarkers
Manganese is often present in blood and urine samples. The urinary excretion level of manganese is considered the most indicative of the most recent manganese exposure. Thus, blood and urine levels can be used to detect manganese levels that are above the normal ranges, which are 4–15 μg/L in blood, 1–8 μg/L in urine, and 0.4–0.85 μg/L in serum (10).
Essentiality and deficiency
Manganese is needed in the body for (11):
- Amino acid, cholesterol, glucose, and carbohydrate metabolism
- Reactive oxygen species scavenging
- Bone formation
- Reproduction
- Immune response
- Blood clotting and hemostasis in conjunction with vitamin K
Deficiency in manganese is rare but may lead to (11):
- Bone demineralization
- Poor growth in children
- Skin rashes
- Hair depigmentation
- Decreased serum cholesterol and increased alkaline phosphatase activity in men
- Altered mood and increased premenstrual pain in women
- Altered lipid and carbohydrate metabolism, causing abnormal glucose tolerance
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Reference
- Molina-Poveda, C. (2016). Nutrient requirements. In Aquafeed Formulation (pp. 75-216). Academic Press.
- Buchman AR. Manganese. In: A. Catharine Ross BC, Robert J. Cousins, Katherine L. Tucker, Thomas R. Ziegler ed. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:238-44.
- Nielsen FH. Manganese, Molybdenum, Boron, Chromium, and Other Trace Elements. In: John W. Erdman Jr. IAM, Steven H. Zeisel, ed. Present Knowledge in Nutrition. 10th ed: Wiley-Blackwell; 2012:586-607.
- National Institute for Occupational Safety and Health. Welding and Manganese.
2015 - Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med 2005;26:353-62. [PubMed abstract]
- Finley JW, Penland JG, Pettit RE, Davis CD. Dietary manganese intake and type of lipid do not affect clinical or neuropsychological measures in healthy young women. J Nutr 2003;133:2849-56. [PubMed abstract]
- ToxGuide for Manganese – Mn. ATSDR. October 2012
- Assem, F. L., Holmes, P., & Levy, L. S. (2011). The mutagenicity and carcinogenicity of inorganic manganese compounds: a synthesis of the evidence. Journal of Toxicology and Environmental Health, Part B, 14(8), 537-570.
- Gerber, G. B., Leonard, A., & Hantson, P. H. (2002). Carcinogenicity, mutagenicity and teratogenicity of manganese compounds. Critical reviews in oncology/hematology, 42(1), 25-34.
- Manganese – Fact Sheet for Health Professionals. NIH