Manganese

Common Names: Manganese picolinate, Manganese gluconate

Clinical Name: Manganese

Summary

Manganese

chemical name: Mn

forms: Manganese picolinate, Manganese gluconate, Manganese sulfate

overview of interactions:
• nutrient affected by drug: Oral Contraceptives

chemistry/metabolism:
• Found particularly in mitochondria, manganese is a component of several enzymes, including glutamine synthetase, pyruvate carboxylase, and mitochondrial superoxide dismutase (SOD).
• Manganese is poorly absorbed. Less than 1% of dietary intake is used by the body. Citrate enhances absorption.
• Plasma uptake of manganese may be increased with concomitant ingestion of zinc, though some research has found a possible decrease in manganese absorption attributable to zinc.
• High doses of magnesium, calcium, iron, copper, and zinc may inhibit the absorption of manganese.

function:
• Manganese is needed for connective tissue and bone function, including skin integrity, skeletal development, and ear otolith development.
• Essential in skeletal development.
• Bone remodeling: Manganese may work with vitamin K by enhancing alpha c carboxylation of glutamate side chains. These are vital for the binding of calcium ions in the bone.
• Pancreatic and brain function.
• In mitochondria, manganese may protect the membranes from oxidative damage by acting with SOD.
• Activator of enzymes necessary for utilization of biotin, vitamin B1 and vitamin C.
• Formation of urea.
• Formation of thyroxin.

dietary sources:
• Rich food sources include nuts and whole grains, particularly the outer coating of nuts and grains (bran), especially those high in the germ moiety.
• Other good sources include egg yolks, seeds, green vegetables, spinach, beets, Brussel sprouts, blueberries, oranges, grapefruit, apricots, peas, and kelp.
• Meat poultry, fish, and dairy are generally considered poor sources.
• Estimated safe and adequate daily dietary intake (ESADDI) (1989): 2-5 mg per day.
• Average daily intake in the U.S.: 3 mg per day

deficiency:
• Manganese deficiencies are considered uncommon, even though most individuals do not consume the levels deemed safe and adequate.
• Magnesium can substitute for many manganese functions.
• Symptoms of deficiency include sterility, skeletal abnormalities, glucose intolerance, and ataxia. Other symptoms noted are temporary inflammations of the skin, nausea and vomiting.
• Decreased serum levels have been found in diabetics, epileptics, people with osteoporosis, and in people with pancreatic insufficiency.

known or potential therapeutic uses: Allergies, arthritis, bone repair, connective tissue damage, diabetes mellitus, epilepsy, hypoglycemia, multiple sclerosis, myasthenia gravis, schizophrenia, tardive dyskinesia

maintenance dose: While manganese may be considered an essential trace mineral, supplementation is usually not necessary. Optimal levels of intake have not been established. 20 mg per day has been suggested as a maintenance dose by some healthcare professional experienced in nutritional therapies.

therapeutic dose: 5-50 mg per day.

side effects: Side effects due to excessive doses are known but infrequent.

toxicity:
• Individuals who inhale manganese have been known to develop Parkinsons-like neurological symptoms. Other symptoms associated with manganese inhalation include psychiatric symptoms such as hallucinations and violent actions.
• There are few toxic symptoms associated with large ingested intakes of manganese. Over 100 mg per day may cause nausea
• Signs and symptoms of toxicity include: weakness, psychological and motor difficulties, irritability, impotence; generally seen only in industrial exposure to manganese dust.

contraindications: None known to date.



Interactions

nutrient affected by drug: Oral Contraceptives

• research: Though contradictory findings have been published, oral contraceptives may interfere with manganese absorption. The clinical implications of this potential interaction are uncertain at this time.
(Heese HD, et al. S Afr Med J 1988 Feb 6;73(3):163-165.)

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Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.


References

Freeland-Graves JH, Turnlund JR. Deliberations and evaluations of the approaches, endpoints and paradigms for manganese and molybdenum dietary recommendations. J Nutr. 1996 Sep;126(9 Suppl):2435S-2440S.

Freeland-Graves JH. Manganese: an essential nutrient for humans. Nutr Today 1989;23:13-19. (Review)

Freeland-Graves JH, et al. Metabolic balance of manganese in young men consuming diets containing five levels of dietary manganese. J Nutr. 1988 Jun;118(6):764-773.
Abstract: Five healthy men, ages 19-20, were fed a diet for 105 d to measure manganese balance during consumption of conventional foods. The study was divided into five periods of 21, 21, 38, 11 and 14 d, in which the daily dietary intakes of manganese (Mn) were 2.89, 2.06, 1.21, 3.79 and 2.65 mg, respectively. During the last 7 d of each dietary period, subjects resided in a metabolic unit and fasting blood samples were drawn on two mornings. Feces and urine were collected during the last 6 d and integumental losses were collected during the last 60 h of each period. The mean Mn balances for periods 1-5 were -0.083, -0.018, -0.088, +0.657 and +0.136 mg/d, respectively. Corresponding apparent retentions were -2.90, -0.88, -7.40, +17.33 and +5.12%. The mean sum of endogenous and exogenous losses when intake was theoretically zero was calculated to be 392 micrograms/d. When these total losses were combined with the mean positive retention, the theoretical mean dietary level of Mn required for positive balance for these male subjects was 3.5 mg/d or 50 micrograms/kg.

Freeland-Graves JH, Lin PH. Plasma uptake of manganese as affected by oral loads of manganese, calcium, milk, phosphorus, copper, and zinc.J Am Coll Nutr. 1991 Feb;10(1):38-43.
Abstract: Six adult subjects were administered a series of manganese (Mn) tolerance tests to investigate the influence of various minerals on Mn plasma uptake. Oral loads given to all six subjects included 40 mg manganese alone, or with 800 mg calcium (Ca) as either calcium carbonate (CaCO3) or 545 ml 2% milk. Four of the subjects also received loads of 800 mg phosphorus (P), 2 mg copper (Cu), and 50 mg zinc (Zn) with the 40 mg Mn. Baseline Mn tolerance tests for all subjects produced a rapid increase in plasma Mn, followed by return to baseline. The addition of Ca as either CaCO3 or 2% milk to the oral Mn essentially blocked the plasma uptake of Mn. No significant differences were found between the source of Ca in its inhibitory effect. Plasma Ca uptake was lower when Mn was simultaneously administered, but the results were not significantly different. Ionized levels of plasma Ca did not change significantly. The addition of Cu to the Mn load decreased the area under the curve for plasma Mn by about half, but it was not significantly different in the four subjects. In contrast, the addition of Zn to the Mn produced a significant increase in plasma Mn. Phosphorus has no influence on plasma uptake of Mn. These results indicate that the plasma uptake of Mn is greatly reduced by concomitant ingestion of Ca but may be increased by an oral load of Zn.

Friedman BJ, Freeland-Graves JH, Bales CW, Behmardi F, Shorey-Kutschke RL, Willis RA, Crosby JB, Trickett PC, Houston SD. Manganese balance and clinical observations in young men fed a manganese-deficient diet. J Nutr. 1987 Jan;117(1):133-143.
Abstract: A balance study was conducted to determine the minimum requirement for manganese (Mn) and to examine the effects of Mn depletion. Seven male subjects, age 19-22, were fed a Mn-adequate diet of conventional foods (2.59 mg Mn/d, 135 mg cholesterol, and P:S ratio of 0.86) for 3 wk to establish base-line data. Then a purified diet containing 0.11 mg Mn/d was fed for 39 d (depletion), followed by two 5-d periods of 1.53 and 2.55 mg Mn/d (repletion). Diets, feces, urine, and integument were analyzed for Mn, and blood was analyzed for Mn, cholesterol, and other constituents. Plasma levels of cholesterol decreased from 170 to 152 mg/dL during the base-line period, and then to 142 mg/dL at the end of depletion, but did not respond to 10 days of repletion. A fleeting dermatitis, Miliaria crystallina, developed in five of the seven subjects at the end of depletion, but disappeared as repletion began. The minimum requirement for Mn on this purified diet, calculated by the factorial method using Mn balance at three levels of intake was 0.74 mg/d. This requirement would be increased to 2.11 mg/d if the obligatory loss was combined with the lowest individual percentage of retention.

Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988 Feb 6;73(3):163-165.
Abstract: Reference serum selenium and manganese concentrations were established for healthy nulliparas aged 18-23 years resident in Cape Town. Measurements were determined for selenium in 100 female students who had been taking low-dosage triphasic contraceptive medication for a minimum of 3 months and in 100 female students who were not on contraceptive therapy. Manganese concentrations were determined for 25 female students from each group. The mean serum selenium concentrations were 0.988 +/- 0.189 micrograms/l (78 +/- 15 micrograms/dl) and 0.925 +/- 0.177 mumol/l (73 +/- 14 micrograms/l) respectively for females taking and not taking oral contraceptives. The corresponding concentrations for manganese were 21.84 +/- 9.82 nmol/l (1.20 +/- 0.54 micrograms/l) and 21.66 +/- 7.64 nmol/l (1.19 +/- 0.42 micrograms/l) respectively. The differences in selenium were statistically significant (P = 0.0231) but not for manganese (P = 0.910).

Holt GA. Food and Drug Interactions. Chicago: Precept Press, 1998.

Krieger D, Krieger S, Jansen O, Gass P, Theilmann L, Lichtnecker H. Manganese and chronic hepatic encephalopathy. Lancet. 1995 Jul 29;346(8970):270-274.
Abstract: Clinical observations and animal studies have raised the hypothesis that increased concentrations of manganese (Mn) in whole blood might lead to accumulation of this metal within the basal ganglia in patients with end-stage liver disease. We studied ten patients with liver failure (and ten controls) by magnetic resonance imaging (MRI) and measurement of Mn in brain tissue of three patients who died of progressive liver failure (and three controls) was also done. Whole blood Mn concentrations in patients with liver cirrhosis were significantly increased (median 34.4 micrograms/L vs 10.3 micrograms/L in controls; p = 0.0004) and pallidal signal intensity indices correlated with blood Mn (Rs = 0.8, p = 0.0058). Brain tissue samples reveal highest Mn concentrations in the caudate nucleus, followed by the quadrigeminal plate and globus pallidus. Mn accumulates within the basal ganglia in liver cirrhosis. Similarities between Mn neurotoxicity and chronic hepatic encephalopathy suggest that this metal may have a role in the pathogenesis of chronic hepatic encephalopathy. Further studies are warranted because the use of chelating agents could prove to be a new therapeutic option to prevent or reverse this neuropsychiatric syndrome.

Marz R. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.

Raloff J. Reasons for boning up on manganese. Science Sep 1986, 199. (Review)

Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold, 1989.

Roe DA. Drug-induced Nutritional Deficiencies. 2nd ed. Westport, CT: Avi Publishing, 1985.

USDA: Composition of Foods. USDA Handbook #8. Washington DC, ARS, USDA, 1976-1986.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997. (Review).