by Aliza Becker, BA, MPS

Manganese is present throughout the body, including in the liver, pancreas, brain, and bone, and is an essential trace metal that functions as a cofactor for several enzymes to support a variety of biological processes.¹ Manganese was first discovered in 1774 as an element on the periodic table; however, its value to human health was not confirmed until the 1950s.²

How much do we need?

The recommended average daily amount of manganese varies according to age and sex. It is suggested that all children age 1 to 3 years consume 1.2mg/day and age 4 to 8 years 1.5mg/day, while boys 9 to 13 years of age should intake 1.9mg/day and girls 9 to 13 years of age should intake 1.6mg/day.³ This divergence continues into adulthood (men, 2.3mg/day vs. women, 1.8mg/day), though the daily concentration for women should be adjusted during pregnancy (2.0mg/day) and breastfeeding (2.6mg/day).³ Manganese may be ingested as a dietary supplement or in food, with certain shellfish (e.g., 3oz of blue cooked mussels, 5.8mg/serving) and nuts (e.g., 1oz of dry roasted hazelnuts, 1.6mg/serving) being particularly good sources; however, manganese may also be found at higher amounts in some grains (e.g., 0.5 cups of cooked medium-grain brown rice, 1.1mg/serving), vegetables (e.g., 0.5 cups of boiled spinach, 0.8mg/serving), and fruits (e.g., 0.5 cups of raw pineapple chunks, 0.8mg/serving).⁴ 

Certain characteristics may support better absorption of manganese, including female sex, young age (i.e., infants and children absorb greater proportions of manganese than adults), and lower plasma ferritin concentrations.⁴ Meanwhile, concurrent intake of other elements, such as calcium and phosphorus, may reduce the absorption of manganese,⁵ and manganese itself inhibits iron absorption.⁶

How does the body use it?

Functions. Manganese is a necessary cofactor in a range of processes within the body. Studies indicate it is essential in the synthesis of cartilage and bone collagen and in bone mineralization,⁷ and rat modeling indicates that supplementation with manganese may increase both bone mineral density and bone formation.⁸ Manganese may also boost the innate immune system by increasing numbers of myeloid cells and natural killer cell activity, although high levels of the metal can reduce lymphoid cell counts and impair the innate immune response.⁹ Different enzymes activated by manganese assist in the metabolism of carbohydrates, amino acids, protein, and cholesterol,¹⁰ and manganese deficiency can lead to abnormal glucose tolerance and alterations in lipid and carbohydrate metabolism.¹¹ Manganese is also a necessary component for manganese superoxide dismutase, an enzyme that helps to prevent mitochondrial dysfunction by reducing reactive oxygen species in the mitochondrial matrix.^11,12 Meanwhile, manganese is indirectly involved in reproduction by acting as a cofactor for enzymes necessary in the synthesis of cholesterol, which is a required precursor in the production of steroid hormones.¹³ In conjunction with vitamin K, manganese supports blood coagulation and hemostasis.¹⁰

Absorption. In humans, manganese from food or supplements is absorbed through the intestines, enters the bloodstream for transport to tissues via the liver, and is excreted from the body in the feces.⁵

Toxicity. A diagnosis of manganese toxicity includes consideration of the following factors: exposure history (e.g., occupational, environmental); the presence of idiopathic neurological defects, such as tremor, gait abnormalities, or dysfunctional speech; and/or psychiatric symptoms, such as hallucinations, psychosis, or memory impairment.¹ In the brain, high levels of manganese impair the regulation of neurotransmitters, such as dopamine, glutamate, and GABA, by inhibiting the activity of enzymes that regulate neurotransmitter levels.^14,15 Existing neuroprotective strategies include endogenous antioxidants, plant extracts, iron-chelating therapies, precursors of glutathione, and synthetic compounds.¹⁴ Overexposure to manganese may also result in cardiovascular and pulmonary complications.¹ Co-exposure of brain mitochondria to manganese and ammonia together leads to more visible mitochondrial impairment than exposure to either alone.¹⁶ Individuals receiving parenteral nutrition, those with liver failure or hepatic encephalopathy, and those with iron deficiency are also at risk for an overaccumulation of manganese in the body.¹⁷ 

Nonexperimentally induced manganese deficiency in humans is rare; however, previous research reported that men placed on manganese-depleted diets developed an erythematous rash on the torso, while women consuming a diet containing <1mg manganese/day experienced mood alterations and increased pain levels during the premenstrual phases of their estrous cycles.¹⁰ 

Certain conditions may result from impairments in manganese uptake or transport, such as Huntington’s disease.¹⁵ 

SOURCES

1. Evans GR, Masullo LN. Manganese toxicity. [Updated 2021 Jul 31]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022.

2. Emsley J. Manganese the protector. Nat Chem. 2013;5(11):978.

3. United States National Institutes of Health Office of Dietary Supplements. Manganese—fact sheet for consumers. https://ods.od.nih.gov/factsheets/Manganese-Consumer/. Accessed 14 May 2022. 

4. United States National Institutes of Health Office of Dietary Supplements. Manganese—fact sheet for health professionals. https://ods.od.nih.gov/factsheets/Manganese-HealthProfessional/. Accessed 14 May 2022. 

5. United States Institute of Medicine Panel on Micronutrients. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. 10. Manganese. Washington, DC: National Academies Press; 2001.

6. Rossander-Hultén L, Brune M, Sandström B, et al. Competitive inhibition of iron absorption by manganese and zinc in humans. Am J Clin Nutr. 1991;54(1):152–156. 

7. Rondanelli M, Faliva MA, Peroni G, et al. Essentiality of manganese for bone health: an overview and update. Nat Prod Commun. 2021:16(5).

8. Bae Y-J, Kim M-H. Manganese supplementation improves mineral density of the spine and femur and serum osteocalcin in rats. Biol Trace Elem Res. 2008;124(1):28–34.

9. Wu Q, Mu Q, Xia Z, et al. Manganese homeostasis at the host-pathogen interface and in the host immune system. Semin Cell Dev Biol. 2021;115:45–53.

10. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005;26(4-5):353–362.

11. Li L, Yang X. The essential element manganese, oxidative stress, and metabolic diseases: links and interactions. Oxid Med Cell Longev. 2018;2018:7580707.

12. Kitada M, Xu J, Ogura Y, et al. Manganese superoxide dismutase dysfunction and the pathogenesis of kidney disease. Front Physiol. 2020;11:755.

13. Studer JM, Schweer WP, Gabler NK, Ross JW. Functions of manganese in reproduction. Anim Reprod Sci. 2022;238:106924.

14. Peres TV, Schettinger MRC, Chen P, et al. Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies. BMC Pharmacol Toxicol. 2016;17(1):57.

15. Harischandra DS, Ghaisas S, Zenitsky G, et al. Manganese-induced neurotoxicity: New insights into the triad of protein misfolding, mitochondrial impairment, and neuroinflammation. Front Neurosci. 2019;13:654.

16. Heidari R, Jamshidzadeh A, Ommati MM. Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury. Clin Exp Hepatol. 2019;5(2):109–117.

17. Horning KJ, Caito SW, Tipps KG, et al. Manganese is essential for neuronal health. Annu Rev Nutr. 2015;35:71–108.