Manganese

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1Sources 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]


2Pharmacology

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]


3Neurology

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]).


4Peripheral Organ Systems

4.1. Eyes

Mn-superoxide dismutase is present in mitochondria of various eye regions including the retina, lens, and cornea.[28]


5Nutrient-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


6Safety 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[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.

Scientific Support & Reference Citations

References

  1. Pennington JA1, Young BE Total diet study nutritional elements, 1982-1989 . J Am Diet Assoc. (1991)
  2. Manganese in Drinking-water
  3. TOXICOLOGICAL PROFILE FOR MANGANESE
  4. Barceloux DG Manganese . J Toxicol Clin Toxicol. (1999)
  5. Greger JL Nutrition versus toxicology of manganese in humans: evaluation of potential biomarkers . Neurotoxicology. (1999)
  6. Manganese superoxide dismutase, MnSOD and its mimics
  7. Liochev SI1, Fridovich I Carbon dioxide mediates Mn(II)-catalyzed decomposition of hydrogen peroxide and peroxidation reactions . Proc Natl Acad Sci U S A. (2004)
  8. Baly DL, Keen CL, Hurley LS Pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in developing rats: effect of manganese deficiency . J Nutr. (1985)
  9. Prohaska JR Functions of trace elements in brain metabolism . Physiol Rev. (1987)
  10. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
  11. Casey CE1, Neville MC, Hambidge KM Studies in human lactation: secretion of zinc, copper, and manganese in human milk . Am J Clin Nutr. (1989)
  12. Dietary trace metal intake of some Canadian full-term and low birthweight infants during the first twelve months of infancy
  13. Schwartz R, Apgar BJ, Wien EM Apparent absorption and retention of Ca, Cu, Mg, Mn, and Zn from a diet containing bran . Am J Clin Nutr. (1986)
  14. Sandström B, et al Manganese absorption and metabolism in man . Acta Pharmacol Toxicol (Copenh). (1986)
  15. Johnson PE1, Lykken GI, Korynta ED Absorption and biological half-life in humans of intrinsic and extrinsic 54Mn tracers from foods of plant origin . J Nutr. (1991)
  16. Rükgauer M1, Klein J, Kruse-Jarres JD Reference values for the trace elements copper, manganese, selenium, and zinc in the serum/plasma of children, adolescents, and adults . J Trace Elem Med Biol. (1997)
  17. Minoia C1, et al Trace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood and serum of Italian subjects . Sci Total Environ. (1990)
  18. Greger JL1, et al Intake, serum concentrations, and urinary excretion of manganese by adult males . Am J Clin Nutr. (1990)
  19. Wang D1, Du X, Zheng W Alteration of saliva and serum concentrations of manganese, copper, zinc, cadmium and lead among career welders . Toxicol Lett. (2008)
  20. Rose C1, et al Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction . Gastroenterology. (1999)
  21. Newland MC1, et al Visualizing manganese in the primate basal ganglia with magnetic resonance imaging . Exp Neurol. (1989)
  22. Eriksson H1, et al Effects of manganese oxide on monkeys as revealed by a combined neurochemical, histological and neurophysiological evaluation . Arch Toxicol. (1987)
  23. Yamada M, et al Chronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brain . Acta Neuropathol. (1986)
  24. Bird ED, Anton AH, Bullock B The effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkey . Neurotoxicology. (1984)
  25. Dorman DC1, et al Nasal toxicity of manganese sulfate and manganese phosphate in young male rats following subchronic (13-week) inhalation exposure . Inhal Toxicol. (2004)
  26. Racette BA1, et al Pathophysiology of manganese-associated neurotoxicity . Neurotoxicology. (2012)
  27. Huang CC1, et al Dopamine transporter binding in chronic manganese intoxication . J Neurol. (2003)
  28. Behndig A1, et al Superoxide dismutase isoenzymes in the human eye . Invest Ophthalmol Vis Sci. (1998)
  29. Finley JW1, Johnson PE, Johnson LK Sex affects manganese absorption and retention by humans from a diet adequate in manganese . Am J Clin Nutr. (1994)
  30. Finley JW Manganese absorption and retention by young women is associated with serum ferritin concentration . Am J Clin Nutr. (1999)
  31. Manganese and calcium absorption and balance in young women fed diets with varying amounts of manganese and calcium
  32. Roels HA1, et al Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity . Neurotoxicology. (2012)
  33. Chang Y1, et al Decreased brain volumes in manganese-exposed welders . Neurotoxicology. (2013)
  34. Chang Y1, et al High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders . Neurotoxicology. (2009)
  35. Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, et al Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial . JAMA. (2015)
  36. Taylor MJ1, et al Folate for depressive disorders . Cochrane Database Syst Rev. (2003)
  37. Godfrey PS1, et al Enhancement of recovery from psychiatric illness by methylfolate . Lancet. (1990)
  38. Kushwaha S1, Chawla P1, Kochhar A1 Effect of supplementation of drumstick (Moringa oleifera) and amaranth (Amaranthus tricolor) leaves powder on antioxidant profile and oxidative status among postmenopausal women . J Food Sci Technol. (2014)