Manganese

DEFICIENCY DISEASES
      Hypothyroidism, ataxia (muscle coordination failure), deafness, convulsions, chondrodystrophy, asthma, retarded growth, infertility, miscarriages, loss of libido in females and males, skeletal defects, disruption of fat and carbohydrate metabolism, joint problems (including TMJ, slipped tendon, repetitive motion syndrome, and carpal tunnel syndrome), osteoporosis, ringing in ears, dizziness, fatigue, myasthenia gravis, allergies, hypoglycemia, diabetes.

MANGANESE EXCESS SYMPTOMS
     Anorexia, ataxia, iron deficiency, copper deficiency, neurological symptoms, schizophrenia, criminal behavior

Manganese ion as a goitrogen in the female mouse.

Kawada J, Nishida M, Yoshimura Y, Yamashita K

Effects of manganese ions on thyroid function in rat.

Buthieau AM, Autissier N

 

: Endokrynol Pol 1993;44(1):57-63

[Effect of occupational environment containing manganese on thyroid function].

[Article in Polish]

Misiewicz A, Radwan K, Karmolinski M, Dziewit T, Matysek A

VI Katedra i Klinika Chorob Wewnetrznych Slaskiej AM, Katowicach.

Significantly lower blood serum concentrations of triiodothyronine (T3) and thyroxine (T4) accompanied by a significantly higher concentration of thyrotropin (TSH) have been found in workers exposed to the environmental presence of manganese, iron chromates and other agents as compared to the control group (differing with respect to the environmental exposure to manganese only)

The following study may be extremely significant for the understanding of Graves' disease and Graves' ophthalmopathy (TED). While I hesitate to jump to conclusions, this study seems to indicate that manganese superoxide (MnSOD), which is an antioxidant, may stimulate retroocular fibroblast growth which is the root of TED. The retroocular fibroblasts seem to grow in response to stimulation by the TSH receptor antisera (anti-p1). MnSOD has a similar structure to the TSH receptor peptide and apparently in Graves' there is an autoimmune response to MnSOD. Therefore it is possible that an excess amount of manganese in the diet causes excessive production of MnSOD which in turn causes and autoimmune response to MnSOD and this stimulates the retroocular fibroblasts. While this would be very interesting, I don't know if my interpretation of this is correct. However, this does fit in with the fact that manganese is a copper antagonist and high levels of manganese would suppress copper levels. Copper supplementation could, in turn, help reduce manganese levels and help suppress this autoimmune response.

Immunodetection of manganese superoxide dismutase in cultured human retroocular fibroblasts using sera directed against the thyrotropin receptor.

In the following study manganese is shown to be an effective inhibitor of bone loss in ovarectimized animals.  This indicates that post-menopausal women need adequate manganese to prevent osteoporosis.

 

Eur J Obstet Gynecol Reprod Biol 2000 May 1;90(1):97-101

Effects on bone loss of manganese alone or with copper supplement in ovariectomized rats. A morphometric and densitomeric study.

Rico H, Gomez-Raso N, Revilla M, Hernandez ER, Seco C, Paez E, Crespo E

Departamento de of Medicina, Universidad de Alcala de Henares, 28801, Madrid, Spain

[Record supplied by publisher]

Objective: The aim of this study was to examine the effect of manganese (Mn) alone and with the addition of copper (Cu) in the inhibition of osteopenia induced by ovariectomy (OVX) in rats. Study conditions: Four lots of 100-day-old female Wistar rats were divided into experimental groups of 15 each. One group received a diet supplemented with 40 mg/kg of Mn per kilogram of feed (OVX+Mn). The second group received the same diet as the first, but with an additional 15 mg/kg of copper (OVX+Mn+Cu). The third group of 15 OVX and the fourth group of 15 Sham-OVX received no supplements. At the conclusion of the 30-day experiment, the rats were slaughtered and their femurs and fifth lumbar vertebrae were dissected. Femoral and vertebral length were measured with caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone density (BMD) of the femur (F-BMC, mg and F-BMD, mg/cm(2)) and the fifth lumbar vertebra (V-BMC, mg and V-BMD, mg/cm(2)) were measured separately with dual energy X-ray absorptiometry. Results: The F-BMD, mg/cm(2) was lower in the OVX than in the Sham-OVX group (P<0.0001) and in the other two groups receiving mineral supplements (P<0.005 in both). F-BMC, mg was significantly lower in the OVX group than in the other three (P<0.0001 in all cases). Calculations for V-BMC, mg and V-BMD, mg/cm(2) are similar to findings in the femur. Conclusions: These data show that a Mn supplement is an effective inhibitor of loss of bone mass after OVX, both on the axial and the peripheral levels, although this effect is not enhanced with the addition of Cu.

The following study indicates that manganese blocks the action of calcium ions. This may mean that excessive levels of manganese might interfere with calcium metabolism, requiring a person to need to supplement with more calcium and magnesium.

 

Nippon Yakurigaku Zasshi 1982 Aug;80(2):93-104

[Actions of manganese and lanthanum on smooth muscles].

[Article in Japanese]

Sunano S

Effects of Mn2+ and La3+ on the excitation, contraction, ion movement, and biochemistry of smooth muscles were reviewed. Both Mn2+ and La3+ block the action potential of smooth muscles without affecting membrane resting potential. However, depolarization or hyperpolarization by these ions and slow discharges which are not affected by these ions have also been reported in some smooth muscles. Mn2+ and La3+ inhibit the spontaneous contraction and high-K-induced contracture, although these ions can also initiate slow tension development in some preparations. The drug-induced contractions are relatively insensitive to these ions. Mn2+ blocks Ca influx, and La3+ blocks both Ca influx and efflux. However, La-resistant Ca movements such as Na-Ca exchange or active Ca extrusion have also been reported. La3+ also shows effects on the movement of other ions. In biochemical experiments, La3+ shows effects on Ca movement of the membraneous and microsomal fractions of smooth muscles, with variations among the smooth muscles. Thus, we should be careful of using these ions as mere Ca blockers.

 

The following study shows that manganese exposure on a low protein diet will result in a significant increase in dopamine and norepinephrine levels. Norepinephrine is one of the catecholamine stress hormones and high levels can induce hypertension. I wish that the authors had looked at chromium levels. A low protein diet usually means a high carbohydrate diet which will deplete chromium. Since chromium is an antagonist of manganese, it is possible that the effect is not due per se to low protein but to a combination of high manganese with low chromium.

Neurobehav Toxicol Teratol 1985 Sep-Oct;7(5):427-31

Effect of low protein diet on manganese neurotoxicity: III. Brain neurotransmitter levels.

Ali MM, Murthy RC, Mandal SK, Chandra SV

The effect of concurrent low protein (10% casein) diet and manganese (Mn) exposure (3 mg/ml drinking water) on brain levels of dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were investigated in Fo-growing (90 days exposure), Fo-diet rehabilitated (low----normal protein diet-28 days) and F1-weaned rats. Mn exposure in either diet group resulted in a significant increase in the DA and NE levels but a decrease in the 5-HT level. These effects were more pronounced in the rats fed the low protein diet, especially in the F1-offsprings. Diet rehabilitation reduced the effects of Mn exposure.

 

 

: FEBS Lett 1997 Oct 13;416(1):69-71

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells.

Nishida S, Nakano T, Kimoto S, Kusunoki T, Suzuki K, Taniguchi N, Murata K, Tomura TT

Department of Biochemistry and Oncology, Kinki University School of Medicine, Osakasayama, Osaka, Japan. nishida@med.kindai.ac.jp

Alterations in the superoxide dismutase (SOD) content of thyroid tissues occurring in association with thyroid dysfunction have been reported. In this study, the Mn-SOD content was found to increase in thyroid tissues of rats administered thyroid stimulating hormone (TSH) and in thyrocytes cultured in medium supplemented with TSH. Furthermore, in the thyroid glands of rats whose serum TSH level was elevated by inhibiting the synthesis of T3 and T4 by 6-methyl-2-thiouracil, the Mn-SOD increased as the TSH concentration increased. In the cultured thyrocytes, the increase in Mn-SOD induced by TSH was inhibited by the C-kinase inhibitor H7. These findings suggest the induction of Mn-SOD by TSH in thyroid cells and point to a role of C-kinase in this process, thereby indicating that a close relationship exists between the serum TSH level and the change in Mn-SOD content in thyrocytes with thyroid dysfunction.

 

Acta Endocrinol (Copenh) 1993 Dec;129(6):573-8

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Localization of Cu/Zn and Mn superoxide dismutase in various thyroid disorders.

Iwase K, Nagasaka A, Kato K, Ohtani S, Tsujimura T, Inagaki A, Jimbo S, Nakai A, Masunaga R, Hamada M, et al

Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan.

The intracellular localization of Cu/Zn- and Mn-superoxide dismutase (SOD), which catalyze the dismutation of superoxide radicals (O2-) to O2 and H2O2, was studied in the thyroid tissue of various thyroid disorders by an immunohistochemical technique. The concentrations of both SODs in those tissues were measured also by a sandwich enzyme immunoassay technique. Copper/zinc-SOD in thyroid tissues were identified by immunocytochemical staining in most cases of papillary carcinoma and in some cases of other thyroid disorders. In normal follicular cells this enzyme is localized in the perinuclear cytoplasm, whereas in thyroid tumor or hyperplastic follicular cells it exists homogeneously in cytoplasm. Manganese-SOD stained strongly in papillary carcinoma and papillary-growing cells in the thyroid tissue of adenoma and Graves' disease. The concentrations of Cu/Zn-and Mn-SOD in thyroid tumor tissues and hyperplastic follicular disorders were significantly higher than those in normal thyroid tissue when they were compared as a function of protein or deoxyribonucleic acid contents. The ratio of Mn-SOD to Cu/Zn-SOD was significantly higher only in papillary carcinoma, except for other thyroid disorders as compared with that in the normal thyroid. In conclusion, SOD seems to be related to cell proliferation and differentiation in the thyroid follicular cell because Cu/Zn-SOD changes its localization in tumor and hyperplastic follicular cells and because the Mn-SOD concentration is increased in papillary carcinoma or papillary-growing cells.

 

 

J Toxicol Clin Toxicol 1999;37(2):293-307

Manganese.

Barceloux DG

dgbarcelou@aol.com

Manganese is a very hard, brittle metal, which is used to increase the strength of steel alloys. Absorption from the gastrointestinal tract occurs in the divalent and tetravalent forms. Permanganates, which are strong oxidizing agents, have a +7 valence. The principal organomanganese compound is the anti-knock additive, methylcyclopentadienyl manganese tricarbonyl. Manganese is a ubiquitous constituent of the environment comprising about 0.1% of the earth's crust. For the general population, food is the most important source of manganese with daily intake ranging from 2-9 mg Mn. Combustion of gasoline containing methylcyclopentadienyl manganese tricarbonyl releases submicron particles of Mn3O4 that are potentially respirable. Biomagnification of manganese in the food chain probably does not occur. The lungs and gastrointestinal tract absorb some manganese, but the relative amounts absorbed from each site are not known. Homeostatic mechanisms limit the absorption of manganese from the gastrointestinal tract. Elimination of manganese occurs primarily by excretion into the bile. Animal studies indicate that manganese is an essential co-factor for enzymes, such as hexokinase, superoxide dismutase, and xanthine oxidase. However, no case of manganese deficiency in humans has been identified. Manganism is a central nervous system disease first described in the 1800s following exposure to high concentrations of manganese oxides. Manganese madness was the term used to describe the initial psychiatric syndrome (compulsive behavior, emotional lability, hallucinations). More commonly, these workers developed a Parkinson's-like syndrome. Currently, the risks of exposure to low concentrations of manganese in the industrial and in the environmental settings (e.g., methylcyclopentadienyl manganese tricarbonyl in gasoline) are being evaluated with regards to the development of subclinical neuropsychological changes. The American Conference of Governmental and Industrial Hygienists recently lowered the TLV-TWA for manganese compounds and inorganic manganese compounds to 0.2 mg Mn/m3.

 

 

 

Subj: MANGANESE AND NOREPI
Date: 10/19/00 6:31:04 PM Pacific Standard Time
From: BU 007
To: BU 007

Subj: Re: Rigidity
Date: 10/19/00 8:05:33 AM Pacific Daylight Time
From: docv@COX-INTERNET.COM (kirk vestal)
Sender: WILSONS-LIST@LISTSERV.ACSU.BUFFALO.EDU (Wilson's Disease Discussion Group)
Reply-to: WILSONS-LIST@LISTSERV.ACSU.BUFFALO.EDU (Wilson's Disease Discussion Group)
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mn and mo may be antaganists to cu in someone without wilsons disease. they would be lethal if used solely for treatment in someone with wd in about 6 months to a year! mo is required in 3 enzymes. mo inhibits copper containing enzymes and ceruloplasmin which is a carrier of cu normally. wd people need all the normal copper containing enzymes and ceruloplasmin possible to prevent damage like oxidation causing arthritis, kidney damage, liver damage, basal ganglia damage, etc. the trouble in wd is free cu in the blood getting absorbed at various sites causing damage thru mostly oxidation of surrounding molecules and the lack of normal cu containing enzymes like superoxide dismutase which helps stop oxidative damage. manganese, atomic number 25, is different from magnesium, atomic number 12. i cant find where mn may have an antagonistic effect on cu? mn is required for at least 12 or 15 processes. it is essential to all higher forms of life above a bacteria as it is used in ATP production, an energy metabolite. too much mn or chronic mn poisoning has been described. this occurs in miners, foundry workers, welders, drug manufacturers, potters, glass, ceramic, varnish workers, and food additive workers. the symptoms are schizophrenia and parkinsons like! it is thought mn is required for norepinephrine synthesis and hence, dopamine synthesis. mn intoxication has also been found in chronic liver falure victims. i got this data from Tietz textbook of clinical chemistry 1999 edition. tietz is more authoritative and safer to rely upon than some natural foods book. drv

 

 

Compr Psychiatry 1991 May-Jun;32(3):229-37

Abnormalities in hair trace elements as indicators of aberrant behavior.

Gottschalk LA, Rebello T, Buchsbaum MS, Tucker HG, Hodges EL.

Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine 92717.

There are long-standing viewpoints that impulsive and violent behavior may stem from brain dysfunction or damage secondary to head injury, disease, or toxic chemical substances. This research has aimed to examine the relationship between potentially toxic metals and aberrant behavior, especially violent activity, through the nonintrusive technique of hair analysis for trace elements. In an initial study, phase I, it was not possible to replicate findings of others who reported high levels of lead, cadmium, and copper in violent offenders. However, high levels of manganese were found in prison versus control groups. In phase II, the possibility of artifactual results arising from prison cooking utensils was controlled for by sampling early after incarceration. Phase III was included to substantiate the initial post hoc findings in an additional jail population. In both latter phases, significantly elevated manganese levels were found in the hair of violent versus nonviolent subjects (P less than .0001). A review of the effects of manganese at deficient and toxic levels does not provide a simple answer as to why manganese levels are elevated in the hair of individuals who have been incarcerated for violent behavior. Our study does not implicate the prison environment or soaps and shampoos used in California prisons. Other factors, such as alcohol, dietary, or psychosocial factors, might influence manganese levels in hair, or any of these factors might function in combination with mild manganese toxicity to contribute to aberrant behavior.