1.
Sources and Composition
1.1
Sources and Composition
Sources of manganese in the diet tend to be grains (37% of dietary manganese), tea (20%), and vegetable products (18%).[1]
Manganese is present in water, as it normally exists in running water (due to being prominent in the earth's crust) but industries using manganese in production could also contaminate local water supplies;[2] ambient concentrations of manganese vary between sea water (0.4-10µg/L; average of 2µg/L[3][4]), fresh water (highly variable between 1-200µg/L[4]), and in the US some river testing has noted various concentrations from below 11µg/L to above 51µg/L.[3][2] In regards to drinking water, it is estimated that 20µg of manganese is ingested daily from drinking water assuming an intake of 2 liters of water with the median concentration of 10µg/L[2] which is significantly less than estimated dietary intake of manganese (between 0.7mg and 10.9mg daily[5]) and approximately 1/100th the adequate intake (AI) for adults.
While manganese is present in the drinking water supply, it is at a small enough concentration that is likely doesn't play a major role in human health and nutrition (for better or worse)
1.2
Physicochemical Properties
Manganese is a mineral that can exist in 11 oxidative states with Mn2+ being the most relevant to human nutrition. It can be found in various forms as the natural pure form (manganese) is rare due to rapid decomposition as more common forms being manganese sulfate (MnSO4), manganese chloride (MnCl2), and potassium permanganate (KMnO4) as examples.[2]
1.3
Biological Significance
Manganese has a primary role in the body as a component of an antioxidant enzyme known as superoxide dismutase (SOD), but specifically a variant known as manganese superoxide dismutase (MnSOD)[6] which is different from the variant dependent on copper and zinc to function known as copper,zinc-superoxide dismutase (Cu,Zn-SOD); they have similar functions but differ in cellular locations.[7]
Other enzymes that manganese is a known component of include pyruvate carboxylase[8] and glutamine synthetase located in the cytoplasm of glial cells where it converts glutamate (neurotransmitter) into glutamine.[9]
1.4
Recommended Intake
Manganese has been stated to have an adequate intake (AI) value of:
- 3μg a day for infants less than six months of age, increasing to 600μg (0.6mg) for infants between six and twelve.[10] This difference is explained to be due to a relatively low amount of manganese in breast milk of nourished mothers (average daily production of 1.6-1.9μg a day[11]) relative to food ingested by infants in the 6-12 month age group (estimated 700-720μg daily[10] from 71-80μg/kg bodyweight estimates[12])
- For children, an AI of 1.2mg a day until the age of three increasing to 1.5mg a day until the age of 8[10]
- For preadolescents up to 13 years of age, the AI differs between boys (1.9mg) and girls (1.6mg) and during adolescense the AI is increased in boys (2.2mg) while being maintained at 1.6mg in girls[10]
- Adult recommendations remain constant above the age of 19, being maintained at 1.8mg for women and 2.3mg for men[10]
The AI for manganese is increased slightly to 2mg a day for pregnant women of all ages but increased further to 2.6mg a day in lactating women of all ages.[10] These are estimates, as at this moment in time there has never been a manganese deficiency reported in pregnancy (assessed by potential fetal defects noted in other species) or in lactating women.[10]
2.
Pharmacology
2.1
Absorption
Diets containing high levels of manganese (12-17.7mg daily) are associated with a bioavailability of 7.7% with high variance (+/-6.3%)[13] which was similar to the absorption rate of 2.5mg manganese (as manganese sulfate) in adult men (8.4+/-4.7%).[14] These high bioavailability values may be due to supplement forms, as elsewhere ingestion of manganese chloride was greater (8.9%) than food sources including lettuce (5.20%), spinach (3.81%), wheat (2.16%), or sunflower seeds (1.71%)[15] with retention being similar between sources.[15]
2.2
Transportation in Serum
Manganese has a physiological concentration of around 4-15μg/L (4-15ng/mL) in whole blood and a concentration of 0.4-0.85μg/L (0.4-0.85ng/mL) in serum until normal nourished conditions; average values listed here[3] collected from multiple direct studies.[16][17][18] People exposed to manganese in the workplace may have higher serum and salivary manganese, 46% higher than controls in areas of normal airborne manganese content.[19]
Supplementation of 15mg manganese for one week trends to increase serum levels in otherwise healthy nourished subjects.[18]
2.3
Neurological Distribution
Amongst brain organs, the basal ganglia appears to accumulate the greatest amount of manganese during instances of toxicity with the pallidum (subset of basal ganglia) potentially accumulating more than either the putamen or caudate nucleus.[20][21] Other brain regions can accumulate manganese in instances of toxicity such as the substantia nigra and the subthalamic nucleus,[22][23] and after chronic toxicity dopamine concentrations in these brain regions may decrease.[24]
3.
Neurology
3.1
Neurogenesis
In industrial settings where manganese is present in high concentrations in the air (and can be absorbed from the lungs and nasal mucosa via inhalation[25]) it is known as an industrial toxin due to its neurodegenerative effects and the condition arising from this toxicity known as 'Manganism'.[26]
Despite causing Parkinson's like symptoms, manganism does not appear to greatly reduce dopamine transporter activity (the putamen being measured[27]).
4.
Peripheral Organ Systems
4.1
Eyes
Mn-superoxide dismutase is present in mitochondria of various eye regions including the retina, lens, and cornea.[28]
5.
Nutrient-Nutrient Interactions
5.1
Iron
Women have been noted to have higher manganese absorption rates in some studies when compared to men[29] later noted to be correlated with the ferritin content as those with a good ferritin content (greater than 50μg/L) had an absorption rate of 0.97%[30] (many studies suggest around 5% absorption or less in nourished subjects[31][15]) and those with ferritin less than less than 15μg/L absorbed nearly 5-fold the amount (4.86%).[30] This observation may not be gender exclusive as one study noting a group average of 8.4% bioavailability had one outlier with iron-deficiency anemia absorbing 45.5% of the same oral dose manganese.[14]
It seems subjects with low iron status, assessed by low ferritin stores, have a relatively increased absorption rate of manganese from the diet
6.
Safety and Toxicology
6.1
General
Manganese is known to be able to be absorbed via the nasal and lung membranes, underlying how it can enter the body via inhalation[25] and is a potential industrial toxin in industries that use manganese (steel industries primarily).[3][4] Excessive industrial exposure leads to a condition known as Manganism which features Parkinson's like symptoms[reference|url=http://www.atsdr.cdc.gov/toxprofiles/tp151.pdf|title=TOXICOLOGICAL PROFILE FOR MANGANESE[4] secondary to the neurotoxicity it can promote in this context,[26] primarily manifesting as cognitive deficit[32] and decreased brain volumes[33] although some impairment may exist even without apparent symptoms of neurodegeneration.[34]
In the context of industrial usage of manganese, where it can be inhaled in the air, chronic exposure can promote neurodegeneration. Due to this, manganese (despite being an essential mineral) is an industrial toxin.
References
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- ^Manganese in Drinking-water
- ^TOXICOLOGICAL PROFILE FOR MANGANESE
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- ^Greger JLNutrition versus toxicology of manganese in humans: evaluation of potential biomarkersNeurotoxicology.(1999 Apr-Jun)
- ^Manganese superoxide dismutase, MnSOD and its mimics
- ^Liochev SI1, Fridovich ICarbon dioxide mediates Mn(II)-catalyzed decomposition of hydrogen peroxide and peroxidation reactionsProc Natl Acad Sci U S A.(2004 Aug 24)
- ^Baly DL, Keen CL, Hurley LSPyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in developing rats: effect of manganese deficiencyJ Nutr.(1985 Jul)
- ^Prohaska JRFunctions of trace elements in brain metabolismPhysiol Rev.(1987 Jul)
- ^Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
- ^Casey CE1, Neville MC, Hambidge KMStudies in human lactation: secretion of zinc, copper, and manganese in human milkAm J Clin Nutr.(1989 May)
- ^Dietary trace metal intake of some Canadian full-term and low birthweight infants during the first twelve months of infancy
- ^Schwartz R, Apgar BJ, Wien EMApparent absorption and retention of Ca, Cu, Mg, Mn, and Zn from a diet containing branAm J Clin Nutr.(1986 Mar)
- ^Sandström B, Davidsson L, Cederblad A, Eriksson R, Lönnerdal BManganese absorption and metabolism in manActa Pharmacol Toxicol (Copenh).(1986)
- ^Johnson PE1, Lykken GI, Korynta EDAbsorption and biological half-life in humans of intrinsic and extrinsic 54Mn tracers from foods of plant originJ Nutr.(1991 May)
- ^Rükgauer M1, Klein J, Kruse-Jarres JDReference values for the trace elements copper, manganese, selenium, and zinc in the serum/plasma of children, adolescents, and adultsJ Trace Elem Med Biol.(1997 Jun)
- ^Minoia C1, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini M, Nicolaou G, Alessio L, Capodaglio ETrace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood and serum of Italian subjectsSci Total Environ.(1990 Jun)
- ^Greger JL1, Davis CD, Suttie JW, Lyle BJIntake, serum concentrations, and urinary excretion of manganese by adult malesAm J Clin Nutr.(1990 Mar)
- ^Wang D1, Du X, Zheng WAlteration of saliva and serum concentrations of manganese, copper, zinc, cadmium and lead among career weldersToxicol Lett.(2008 Jan 4)
- ^Rose C1, Butterworth RF, Zayed J, Normandin L, Todd K, Michalak A, Spahr L, Huet PM, Pomier-Layrargues GManganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunctionGastroenterology.(1999 Sep)
- ^Newland MC1, Ceckler TL, Kordower JH, Weiss BVisualizing manganese in the primate basal ganglia with magnetic resonance imagingExp Neurol.(1989 Dec)
- ^Eriksson H1, Mägiste K, Plantin LO, Fonnum F, Hedström KG, Theodorsson-Norheim E, Kristensson K, Stålberg E, Heilbronn EEffects of manganese oxide on monkeys as revealed by a combined neurochemical, histological and neurophysiological evaluationArch Toxicol.(1987)
- ^Yamada M, Ohno S, Okayasu I, Okeda R, Hatakeyama S, Watanabe H, Ushio K, Tsukagoshi HChronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brainActa Neuropathol.(1986)
- ^Bird ED, Anton AH, Bullock BThe effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkeyNeurotoxicology.(1984 Spring)
- ^Dorman DC1, McManus BE, Parkinson CU, Manuel CA, McElveen AM, Everitt JINasal toxicity of manganese sulfate and manganese phosphate in young male rats following subchronic (13-week) inhalation exposureInhal Toxicol.(2004 Jun)
- ^Racette BA1, Aschner M, Guilarte TR, Dydak U, Criswell SR, Zheng WPathophysiology of manganese-associated neurotoxicityNeurotoxicology.(2012 Aug)
- ^Huang CC1, Weng YH, Lu CS, Chu NS, Yen TCDopamine transporter binding in chronic manganese intoxicationJ Neurol.(2003 Nov)
- ^Behndig A1, Svensson B, Marklund SL, Karlsson KSuperoxide dismutase isoenzymes in the human eyeInvest Ophthalmol Vis Sci.(1998 Mar)
- ^Finley JW1, Johnson PE, Johnson LKSex affects manganese absorption and retention by humans from a diet adequate in manganeseAm J Clin Nutr.(1994 Dec)
- ^Finley JWManganese absorption and retention by young women is associated with serum ferritin concentrationAm J Clin Nutr.(1999 Jul)
- ^Manganese and calcium absorption and balance in young women fed diets with varying amounts of manganese and calcium
- ^Roels HA1, Bowler RM, Kim Y, Claus Henn B, Mergler D, Hoet P, Gocheva VV, Bellinger DC, Wright RO, Harris MG, Chang Y, Bouchard MF, Riojas-Rodriguez H, Menezes-Filho JA, Téllez-Rojo MMManganese exposure and cognitive deficits: a growing concern for manganese neurotoxicityNeurotoxicology.(2012 Aug)
- ^Chang Y1, Jin SU, Kim Y, Shin KM, Lee HJ, Kim SH, Ahn JH, Park SJ, Jeong KS, Weon YC, Lee HDecreased brain volumes in manganese-exposed weldersNeurotoxicology.(2013 Jul)
- ^Chang Y1, Kim Y, Woo ST, Song HJ, Kim SH, Lee H, Kwon YJ, Ahn JH, Park SJ, Chung IS, Jeong KSHigh signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic weldersNeurotoxicology.(2009 Jul)