Amazoniac
Member
When I searched for 'imaginary deficiency to blame any misfortune upon', manganese appeared. I realized the forum has relatively little information on it.
There are similar parts that weren't not excluded because sometimes authors express the same thing in different ways and usually add something else to it. Don't mind conflicting information since this mineral has no significance in health.
Manganese and Man
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http://www.traceelements.com/Docs/The Nutritional Relationships of Manganese.pdf
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Manganese in Health and Disease - Daiana Silva Avila, Robson Luiz Puntel, and Michael Aschner (there are others with the same title)
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Modern Nutrition in Health and Disease - Ross
ESPN: 978-1-60547-461-8
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Advanced Nutrition: macronutrients, micronutrients, and metabolism - Berdanier and Zempleni
978‑1‑4200‑5552‑8
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Trace Elements and Iron in Human Metabolism (1978) - Ananda Prasad
978-1-4684-0793-8
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Trace Elements in Human Health and Disease (1976) - Ananda Prasad again
0-12-564202-4
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https://www.intechopen.com/books/en...a-new-emerging-contaminant-in-the-environment
There are similar parts that weren't not excluded because sometimes authors express the same thing in different ways and usually add something else to it. Don't mind conflicting information since this mineral has no significance in health.
Manganese and Man
"The study of the micronutrients and their use in clinical medicine has been actively practiced by our group since 1967. Three micronutrients in particular, copper, zinc and manganese (Mn), have generated much research, especially concerning their roles in the schizophrenias. Heilmeyer et al. (1941) presented one of the earliest studies implicating excess copper in 32 of 37 schizophrenics. We continue to find similar blood serum copper elevations in our patients, particularly in the low histamine schizophrenic, depressives, epileptics, alcoholics, infectious diseases, and some cancer. The high copper level of many schizophrenics and other patients can be reduced by adequate dietary intake of zinc and Mn. Both Reiter of Denmark (1927) and English of Ontario (1929) found improvement in schizophrenic patients given manganese chloride. Manganese is similar to zinc in increasing urinary copper excretion. The combination of zinc and Mn is more effective than either alone.
One of our patients experienced skipped heart beats because of decreased conduction in the heart. The eating of tropical fruit high in Mn improved the heart rate. This effect, to regularize the heart, could be reproduced at will by an oral dose of five mg of Mn as the gluconate or by the ingestion of foods high in Mn."
"Using data of other workers, Schlage calculated that intakes of 0.035 to 0.070 mg per kg body weight and day would result in balanced Mn intakes and excretions. Ranges of Mn intakes for some age groups are as follows:
9 kg infant -- 0.32-0.63 mg Mn/day;
28 kg child -- 0.98-1.96 mg Mn/day;
54 kg female -- 1.89-3.78 mg Mn/day;
70 kg male -- 2.45-4.90 mg Mn/day."
However!
"For instance, an allergic patient with low blood Mn needed 300mg of Mn per day in order to start the slow rise of blood Mn toward normal. With this large dose of Mn he gained 10 pounds in needed body weight and could tolerate an oral zinc supplement for the first time (Brain Bio Center, 1979)."
"Apparent adequate dietary levels of Mn may not meet body needs due to the influence of other nutrients which affect Mn absorption. Manganese absorption depends upon body tissue levels of Mn, dietary calcium, zinc, phosphorus, iron, cobalt, choline and ethanol content in the diet. For example, Lassiter et al. (1974) have shown that 54Mn retention in low Mn baby calves was nine times greater than in Mn supplemented calves. Also in calves, Howes and Dyer (1971) have shown increased absorption of Mn under conditions of low Mn intakes and decreased absorption at higher Mn intakes in a manner reminiscent of iron absorption in iron deficiency.
Manganese competes with cobalt and iron for common binding sites at the mucosal cell surfaces. Within the intestinal mucosa, Mn and iron compete for a common carrier which has less affinity for Mn than for iron. Cruden (1979) has shown that for Mn supplemented diets the duodenal transport and retention of Mn is greater on an iron deficient diet compared with a diet much higher in iron content. This provides further evidence that the absorption of iron and Mn is interrelated and that the duodenal transport and absorption of iron and Mn are competitive.
Dietary calcium and phosphorus modify Mn metabolism. In birds it has been found that excess dietary calcium phosphate can aggravate Mn deficiency (Wilgus and Patton, 1939) probably by absorption of the Mn to the calcium phosphate in the gut, thereby preventing absorption. Therefore, a greater Mn intake would probably provide a margin of safety and cope with variations in calcium and phosphorus intakes.
Lassiter et al. (1972) have shown liver stable Mn to be one-third higher in rats given low calcium diets (.1 percent). Dietary calcium, however, may not be the explanation. King et al. (1979) round a skim milk diet increased liver Mn and contained the higher calcium level than the alternate Mn-free purified casein-dextrose diet. The calcium-phosphorus ratios in the two diets were also similar. One important difference between the two diets was a higher amount of lactose in the corn-skim milk diet. Fournier and Fournier (1972) suggest that lactose may increase Mn absorption.
An association between choline and Mn metabolism has been recognized for some years. In turkey poults, lack of choline has been shown to produce perosis, a Mn deficiency symptom (Jukes 1940, 1941). Choline deficient rats show lower liver Mn levels (Keefer et al., 1973). Ethanol metabolism in the gut causes an increase in hepatic Mn (Barak etal., 1971)."
"The excretory system for Mn is very efficient so the danger of causing Mn toxicity through the use of oral Mn supplements is minimal."
"Due to its poor absorption and rapid excretion, the differences in absorbability of various compounds of Mn may be important. In animals, Mn appears more rapidly in the blood if fed in the form of chelates rather than in the form of inorganic salts (Cotzias, 1958). At present, at the Brain Bio Center, we are measuring the change in blood Mn levels of subjects fed different forms of Mn: sulfate, orotate, chelate, gluconate, as well as food sources such as tea, whole grains, nuts and tropical fruits."
"With Mn deficiency likely in certain segments of the U.S. population, we must be aware of the possible consequences of Mn undernutrition. During growth, Mn deficiency would affect the development of bones and cartilage. Diabetes, hypoglycemia, arthritis, epilepsy and schizophrenia may be more serious consequences of low Mn intakes in later years."
"Why deficiency is likely
The richest food sources of Mn are nuts, whole grains, spices, legumes and tea leaves."
"Refined sugars, fresh and canned vegetables, fresh, dried, and canned fruits, meats, including organ meats, fish, eggs, milk products, and fats are relatively poor sources."
"Since Mn is involved in photosynthesis (Winget and Spector, 1980) Dr. Pfeiffer suggests that tropical fruits and nuts may be good sources of Mn. This appears so. Values for tea leaves, pineapple, macadamia nuts, dates, persimmon, and banana are 71.0, 2.76, 0.67, 0.53, 0.15, and 0.13 mg Mn/100 g respectively."
"Chondroitin sulfate is a major polysaccharide of cartilage and is the mucopolysaccharide most severely affected by Mn deficiency."
"The formation of bone occurs in the cartilage at the epiphysis, and skeletal maturation is notdiokineforsure if this process is inhibited in some manner. Research has focused on the organic matrix of the epiphyseal plate, an integrating part of the growth zone. The mucopolysaccharide and protein composition of the epiphyseal plate may be altered in Mn deficiency (Hidiroglou et al., 1979).
Chondroitin sulfate consists of a polypeptide backbone to which is attached a carbohydrate side chain composed of xylose and two molecules of galactose. To this is attached the main carbohydrate portion of the molecule, a repeating unit of glucuronate and N-acetyl-galactosamine. Leach (1971) has noted that Mn is a far more efficient divalent cation than magnesium in stimulating the incorporation of the various carbohydrates into this unit structure of cartilage. With xylose attached to the protein, the rest of the components are attached in a stepwise fashion."
"With the postulated role for Mn in chondroitin sulfate synthesis it is possible to see why Mn deficiency may cause problems in connective tissue synthesis. What develops then are disease of osteochondrosis such as Osgood Slatter disease and Perthes disease. At the Brain Bio Center we have had good results in treating these patients with zinc, Mn and vitamin B6."
"Generally the cause of the back problems centers around inadequate nutrition to the disc. There is 91 percent less Mn in the discs of dogs with degenerated discs. Manganese, as we know, is involved in the production of cartilage, the material which makes up the disc. The Mn content of the hair was significantly less in the afflicted dogs when compared to normal dogs."
"Rats, mice and guinea pigs, which have been deprived of Mn during gestation or have inherited the mutant gene, are unable to land on their feet during a fall. They cannot distinguish between up and down while swimming and have abnormal or no otoliths at all in the inner ear."
"in both Mn deficiency and genetic cases there is a common impairment in mucopolysaccharide synthesis in the otolithic matrix (Erway et al., 1966). The vestibular system and the delicate otoliths are the balance mechanism of the body. Information about our relation to gravity and the perception of movement all determine perception of the body in space and of body motion. Therefore, the vestibular system plays an early and vital role in how we think and feel about our bodies."
"Glucose Metabolism
Everson and Shrader (1968), in their studies on guinea pigs, have found that Mn deficiency produces:
1) aplasia or marked hypoplasia of all the cellular components of the pancreas,
2) smaller numbers of islet cells containing fewer and less intensely granulated beta cells,
3) a diabetic-like glucose tolerance curve.
Rubenstein (1962) has shown that Mn supplementation in deficient guinea pigs completely reverses the reduced utilization of glucose and, in some way, provides for normal glucose tolerance curves. The mechanism of this effect and manganese's role in the mechanism is not well established. The most likely explanation is the participation of Mn in enzymatic reactions. The glycosyltransferase enzymes have been discussed previously in relationship to mucopolysaccharide synthesis and collagen formation. The role of two other enzymes, pyruvate carboxylase and superoxide dismutase, in Mn deficiency are also important."
"Superoxide dismutase (SOD) is the second known manganoenzyme. SOD ensures the complete reduction of tissue oxygen to water. Partial reduction yields extremely toxic products, the superoxide radical, 0~2 and hydrogen peroxide, H2O2 (free radicals). Both products are highly reactive and potentially destructive to certain types of functional groups present in biomolecules capable of producing irreversible damage. Fridovich (1974) has found several types of SOD. One form occurs in the cytosol and requires copper and zinc for activity and another form requires iron. Still another form occurs in the mitochondria and requires Mn for activity. Without Mn the mitochondrial SOD would be inactive and accumulation of 0~2 and H2O2 would lead to membrane damage and damage to a variety of biological materials. Mitochondrial damage and impaired function have been established as one of the effects of Mn deficiency.
The protective action of superoxide dismutase and catalase, which decomposes H2O2, is probably supported by ascorbic acid, glutathione (a tripeptide of glutamic acid, cysteine, and glycine), and vitamin E, which readily accept electrons and may serve a backup function by scavenging free radicals."
"Manganese is important in the building and breakdown cycles of protein and nucleic acid. Hossenlopp et al. (1974) showed that a divalent cation was necessary for binding of calf thymus RNA polymerases to DNA and that Mn was a better effector of this reaction than magnesium. Nagamine et al. (1978) reported on the differences in the effects of Mn and magnesium on initiation and elongation in the RNA polymerase 1 reaction in RNA synthesis. The process of RNA synthesis consists of three major steps: initiation, elongation and termination. For RNA chain initiation, Mn"
"Manganese stimulates adenylate cyclase activity in brain tissue. This is of importance because cyclic-AMP plays a regulatory role in the action of several brain neurotransmitters. It acts as a second messenger within the cell to transmit the message of the hormone. Thus, Mn has an important role in brain function."
"Manganese chloride was first tested and found effective in treating schizophrenia by Reiter of Denmark (1927). This finding was confirmed by English of Brockville, Ontario (1929). A later study, however, found Mn ineffective (Hoskins, 1934). Both Reiter and English used manganese chloride intravenously while Hoskins used suspended manganese dioxide intramuscularly. Since then, little attention has been paid to the possibility of its therapeutic effects. When we discovered that zinc plus Mn was more effective in eliminating copper via the urinary pathway, we devised "ziman drops" which contained 10 percent zinc sulfate and 0.5 percent Mn chloride. The usual adult dose is six drops AM and PM. We further had multivitamin formulations prepared which contained zinc sulfate, USP 80mg, and Mn chloride, 4mg (Vicon-Plus or Ziman Fortified), with no copper. These preparations are popular but not perfect in that the Mn content is too low and many schizophrenic patients need less zinc and more Mn owing to the fact that zinc is well absorbed from the gut but Mn is poorly absorbed."
"all diagnostic categories can be harmed by large prolonged doses of zinc without Mn. With this new concept we have treated problem patients with large oral doses of Mn. In one severely allergic male, age 45, whom we had treated for 14 years, we suggested 50 mg of Mn as the gluconate morning and night. He felt somewhat better with this dose, so he cautiously increased the dose to 100 mg, three times per day. Before starting this dose his blood Mn was six ppb (11/7/79). After three months of the big dose, his blood Mn was 11 ppb (4/22/80). On 5/20/80 the level was 8.5 ppb. Normal is 10 to 20 ppb. Physical examination, blood pressure, pulse and chem-screen showed no abnormalities. During the period of 300 mg Mn orally per day he gained 11 needed pounds in body weight and was able to tolerate foods that normally caused depressive reactions.
In summary then, the high copper level of schizophrenics, arthritics and patients with psoriasis can be reduced by dietary intake of zinc and Mn. Manganese is more effective than zinc in increasing urinary copper excretion; a combination of zinc and Mn is more effective than either alone."
"We found Mn to be low in the hair of schizophrenics, and in males (but not in females) Mn decreased with age."
"Excesses of the polyvalent metal ions of Mn, mercury, copper, cadmium and lead all appear to cause malfunctions of the CNS in animals and man. Manganese is unusual among these ions since neurological abnormalities have been associated with both a deficiency and an excess of this metal."
"In oral doses Mn has not been found harmful, although in patients over 40 years of age it has occasionally elevated blood pressure. The elevated pressure returns to normal when Mn is discontinued and zinc alone is used. Zinc is effective in lowering the blood pressure of some hypertensive patients which is reminiscent of some of the early work of Schroeder and his co-workers."
"zinc, by antagonizing Mn, may lower the blood pressure of some hypertensives"
"zinc, when used to treat arthritic patients, should be carefully balanced with adequate Mn to sustain any beneficial effect."
"Mn deficiency also affects cerebral function. Hurley et al. (1963) demonstrated a relationship between seizure activity and Mn deficiency in rats. The seizure threshold was found to be significantly lower in Mn deficient animals."
"Both Mn and choline deficiencies are believed to interfere with membrane stability and this could be responsible for facilitating the propagation of seizure activity."
One of our patients experienced skipped heart beats because of decreased conduction in the heart. The eating of tropical fruit high in Mn improved the heart rate. This effect, to regularize the heart, could be reproduced at will by an oral dose of five mg of Mn as the gluconate or by the ingestion of foods high in Mn."
"Using data of other workers, Schlage calculated that intakes of 0.035 to 0.070 mg per kg body weight and day would result in balanced Mn intakes and excretions. Ranges of Mn intakes for some age groups are as follows:
9 kg infant -- 0.32-0.63 mg Mn/day;
28 kg child -- 0.98-1.96 mg Mn/day;
54 kg female -- 1.89-3.78 mg Mn/day;
70 kg male -- 2.45-4.90 mg Mn/day."
However!
"For instance, an allergic patient with low blood Mn needed 300mg of Mn per day in order to start the slow rise of blood Mn toward normal. With this large dose of Mn he gained 10 pounds in needed body weight and could tolerate an oral zinc supplement for the first time (Brain Bio Center, 1979)."
"Apparent adequate dietary levels of Mn may not meet body needs due to the influence of other nutrients which affect Mn absorption. Manganese absorption depends upon body tissue levels of Mn, dietary calcium, zinc, phosphorus, iron, cobalt, choline and ethanol content in the diet. For example, Lassiter et al. (1974) have shown that 54Mn retention in low Mn baby calves was nine times greater than in Mn supplemented calves. Also in calves, Howes and Dyer (1971) have shown increased absorption of Mn under conditions of low Mn intakes and decreased absorption at higher Mn intakes in a manner reminiscent of iron absorption in iron deficiency.
Manganese competes with cobalt and iron for common binding sites at the mucosal cell surfaces. Within the intestinal mucosa, Mn and iron compete for a common carrier which has less affinity for Mn than for iron. Cruden (1979) has shown that for Mn supplemented diets the duodenal transport and retention of Mn is greater on an iron deficient diet compared with a diet much higher in iron content. This provides further evidence that the absorption of iron and Mn is interrelated and that the duodenal transport and absorption of iron and Mn are competitive.
Dietary calcium and phosphorus modify Mn metabolism. In birds it has been found that excess dietary calcium phosphate can aggravate Mn deficiency (Wilgus and Patton, 1939) probably by absorption of the Mn to the calcium phosphate in the gut, thereby preventing absorption. Therefore, a greater Mn intake would probably provide a margin of safety and cope with variations in calcium and phosphorus intakes.
Lassiter et al. (1972) have shown liver stable Mn to be one-third higher in rats given low calcium diets (.1 percent). Dietary calcium, however, may not be the explanation. King et al. (1979) round a skim milk diet increased liver Mn and contained the higher calcium level than the alternate Mn-free purified casein-dextrose diet. The calcium-phosphorus ratios in the two diets were also similar. One important difference between the two diets was a higher amount of lactose in the corn-skim milk diet. Fournier and Fournier (1972) suggest that lactose may increase Mn absorption.
An association between choline and Mn metabolism has been recognized for some years. In turkey poults, lack of choline has been shown to produce perosis, a Mn deficiency symptom (Jukes 1940, 1941). Choline deficient rats show lower liver Mn levels (Keefer et al., 1973). Ethanol metabolism in the gut causes an increase in hepatic Mn (Barak etal., 1971)."
"The excretory system for Mn is very efficient so the danger of causing Mn toxicity through the use of oral Mn supplements is minimal."
"Due to its poor absorption and rapid excretion, the differences in absorbability of various compounds of Mn may be important. In animals, Mn appears more rapidly in the blood if fed in the form of chelates rather than in the form of inorganic salts (Cotzias, 1958). At present, at the Brain Bio Center, we are measuring the change in blood Mn levels of subjects fed different forms of Mn: sulfate, orotate, chelate, gluconate, as well as food sources such as tea, whole grains, nuts and tropical fruits."
"With Mn deficiency likely in certain segments of the U.S. population, we must be aware of the possible consequences of Mn undernutrition. During growth, Mn deficiency would affect the development of bones and cartilage. Diabetes, hypoglycemia, arthritis, epilepsy and schizophrenia may be more serious consequences of low Mn intakes in later years."
"Why deficiency is likely
The richest food sources of Mn are nuts, whole grains, spices, legumes and tea leaves."
"Refined sugars, fresh and canned vegetables, fresh, dried, and canned fruits, meats, including organ meats, fish, eggs, milk products, and fats are relatively poor sources."
"Since Mn is involved in photosynthesis (Winget and Spector, 1980) Dr. Pfeiffer suggests that tropical fruits and nuts may be good sources of Mn. This appears so. Values for tea leaves, pineapple, macadamia nuts, dates, persimmon, and banana are 71.0, 2.76, 0.67, 0.53, 0.15, and 0.13 mg Mn/100 g respectively."
"Chondroitin sulfate is a major polysaccharide of cartilage and is the mucopolysaccharide most severely affected by Mn deficiency."
"The formation of bone occurs in the cartilage at the epiphysis, and skeletal maturation is notdiokineforsure if this process is inhibited in some manner. Research has focused on the organic matrix of the epiphyseal plate, an integrating part of the growth zone. The mucopolysaccharide and protein composition of the epiphyseal plate may be altered in Mn deficiency (Hidiroglou et al., 1979).
Chondroitin sulfate consists of a polypeptide backbone to which is attached a carbohydrate side chain composed of xylose and two molecules of galactose. To this is attached the main carbohydrate portion of the molecule, a repeating unit of glucuronate and N-acetyl-galactosamine. Leach (1971) has noted that Mn is a far more efficient divalent cation than magnesium in stimulating the incorporation of the various carbohydrates into this unit structure of cartilage. With xylose attached to the protein, the rest of the components are attached in a stepwise fashion."
"With the postulated role for Mn in chondroitin sulfate synthesis it is possible to see why Mn deficiency may cause problems in connective tissue synthesis. What develops then are disease of osteochondrosis such as Osgood Slatter disease and Perthes disease. At the Brain Bio Center we have had good results in treating these patients with zinc, Mn and vitamin B6."
"Generally the cause of the back problems centers around inadequate nutrition to the disc. There is 91 percent less Mn in the discs of dogs with degenerated discs. Manganese, as we know, is involved in the production of cartilage, the material which makes up the disc. The Mn content of the hair was significantly less in the afflicted dogs when compared to normal dogs."
"Rats, mice and guinea pigs, which have been deprived of Mn during gestation or have inherited the mutant gene, are unable to land on their feet during a fall. They cannot distinguish between up and down while swimming and have abnormal or no otoliths at all in the inner ear."
"in both Mn deficiency and genetic cases there is a common impairment in mucopolysaccharide synthesis in the otolithic matrix (Erway et al., 1966). The vestibular system and the delicate otoliths are the balance mechanism of the body. Information about our relation to gravity and the perception of movement all determine perception of the body in space and of body motion. Therefore, the vestibular system plays an early and vital role in how we think and feel about our bodies."
"Glucose Metabolism
Everson and Shrader (1968), in their studies on guinea pigs, have found that Mn deficiency produces:
1) aplasia or marked hypoplasia of all the cellular components of the pancreas,
2) smaller numbers of islet cells containing fewer and less intensely granulated beta cells,
3) a diabetic-like glucose tolerance curve.
Rubenstein (1962) has shown that Mn supplementation in deficient guinea pigs completely reverses the reduced utilization of glucose and, in some way, provides for normal glucose tolerance curves. The mechanism of this effect and manganese's role in the mechanism is not well established. The most likely explanation is the participation of Mn in enzymatic reactions. The glycosyltransferase enzymes have been discussed previously in relationship to mucopolysaccharide synthesis and collagen formation. The role of two other enzymes, pyruvate carboxylase and superoxide dismutase, in Mn deficiency are also important."
"Superoxide dismutase (SOD) is the second known manganoenzyme. SOD ensures the complete reduction of tissue oxygen to water. Partial reduction yields extremely toxic products, the superoxide radical, 0~2 and hydrogen peroxide, H2O2 (free radicals). Both products are highly reactive and potentially destructive to certain types of functional groups present in biomolecules capable of producing irreversible damage. Fridovich (1974) has found several types of SOD. One form occurs in the cytosol and requires copper and zinc for activity and another form requires iron. Still another form occurs in the mitochondria and requires Mn for activity. Without Mn the mitochondrial SOD would be inactive and accumulation of 0~2 and H2O2 would lead to membrane damage and damage to a variety of biological materials. Mitochondrial damage and impaired function have been established as one of the effects of Mn deficiency.
The protective action of superoxide dismutase and catalase, which decomposes H2O2, is probably supported by ascorbic acid, glutathione (a tripeptide of glutamic acid, cysteine, and glycine), and vitamin E, which readily accept electrons and may serve a backup function by scavenging free radicals."
"Manganese is important in the building and breakdown cycles of protein and nucleic acid. Hossenlopp et al. (1974) showed that a divalent cation was necessary for binding of calf thymus RNA polymerases to DNA and that Mn was a better effector of this reaction than magnesium. Nagamine et al. (1978) reported on the differences in the effects of Mn and magnesium on initiation and elongation in the RNA polymerase 1 reaction in RNA synthesis. The process of RNA synthesis consists of three major steps: initiation, elongation and termination. For RNA chain initiation, Mn"
"Manganese stimulates adenylate cyclase activity in brain tissue. This is of importance because cyclic-AMP plays a regulatory role in the action of several brain neurotransmitters. It acts as a second messenger within the cell to transmit the message of the hormone. Thus, Mn has an important role in brain function."
"Manganese chloride was first tested and found effective in treating schizophrenia by Reiter of Denmark (1927). This finding was confirmed by English of Brockville, Ontario (1929). A later study, however, found Mn ineffective (Hoskins, 1934). Both Reiter and English used manganese chloride intravenously while Hoskins used suspended manganese dioxide intramuscularly. Since then, little attention has been paid to the possibility of its therapeutic effects. When we discovered that zinc plus Mn was more effective in eliminating copper via the urinary pathway, we devised "ziman drops" which contained 10 percent zinc sulfate and 0.5 percent Mn chloride. The usual adult dose is six drops AM and PM. We further had multivitamin formulations prepared which contained zinc sulfate, USP 80mg, and Mn chloride, 4mg (Vicon-Plus or Ziman Fortified), with no copper. These preparations are popular but not perfect in that the Mn content is too low and many schizophrenic patients need less zinc and more Mn owing to the fact that zinc is well absorbed from the gut but Mn is poorly absorbed."
"all diagnostic categories can be harmed by large prolonged doses of zinc without Mn. With this new concept we have treated problem patients with large oral doses of Mn. In one severely allergic male, age 45, whom we had treated for 14 years, we suggested 50 mg of Mn as the gluconate morning and night. He felt somewhat better with this dose, so he cautiously increased the dose to 100 mg, three times per day. Before starting this dose his blood Mn was six ppb (11/7/79). After three months of the big dose, his blood Mn was 11 ppb (4/22/80). On 5/20/80 the level was 8.5 ppb. Normal is 10 to 20 ppb. Physical examination, blood pressure, pulse and chem-screen showed no abnormalities. During the period of 300 mg Mn orally per day he gained 11 needed pounds in body weight and was able to tolerate foods that normally caused depressive reactions.
In summary then, the high copper level of schizophrenics, arthritics and patients with psoriasis can be reduced by dietary intake of zinc and Mn. Manganese is more effective than zinc in increasing urinary copper excretion; a combination of zinc and Mn is more effective than either alone."
"We found Mn to be low in the hair of schizophrenics, and in males (but not in females) Mn decreased with age."
"Excesses of the polyvalent metal ions of Mn, mercury, copper, cadmium and lead all appear to cause malfunctions of the CNS in animals and man. Manganese is unusual among these ions since neurological abnormalities have been associated with both a deficiency and an excess of this metal."
"In oral doses Mn has not been found harmful, although in patients over 40 years of age it has occasionally elevated blood pressure. The elevated pressure returns to normal when Mn is discontinued and zinc alone is used. Zinc is effective in lowering the blood pressure of some hypertensive patients which is reminiscent of some of the early work of Schroeder and his co-workers."
"zinc, by antagonizing Mn, may lower the blood pressure of some hypertensives"
"zinc, when used to treat arthritic patients, should be carefully balanced with adequate Mn to sustain any beneficial effect."
"Mn deficiency also affects cerebral function. Hurley et al. (1963) demonstrated a relationship between seizure activity and Mn deficiency in rats. The seizure threshold was found to be significantly lower in Mn deficient animals."
"Both Mn and choline deficiencies are believed to interfere with membrane stability and this could be responsible for facilitating the propagation of seizure activity."
__
http://www.traceelements.com/Docs/The Nutritional Relationships of Manganese.pdf
"Manganese is located largely in the mitochondria. It activates numerous enzymes —such as hydrolases, transferases, kinases, and decarboxylases— and is a constituent of some enzymes. One of the most well known manganese metaloenzyme is pyruvate carboxylase, which catalyzes the conversion of pyruvate to oxalo-acetate.2 Other enzymes include arginase, which is involved in the conversion of the amino acid arginine to urea, and mitochondrial superoxide dismutase (SOD). The structure and function of the mitochondria are therefore particularly affected by manganese status. Manganese activates enzymes associated with fatty acid metabolism and protein synthesis,3 and is involved in neurological function."
"The liver regulates manganese via excretion in the bile; however, if the liver excretory route is blocked or if overloading occurs, pancreatic excretion increases. Tissue manganese levels are directly related to availability in the diet. Alcohol increases the hepatic manganese level and apparently doubles its absorption."
"Manganese is required for normal thyroid function and is involved in the formation of thyroxin.7 Tissue mineral analysis (TMA) studies have revealed low manganese levels in hypothyroid patients. Due to the antagonistic effect of insulin, parathyroid hormone (PTH), and estrogen on thyroid function, absorption or utilization of manganese may be impaired when levels of these hormones are elevated.8,9 The adrenal hormones are known to affect the tissue distribution of manganese as well as to alter its metabolism."
"Manganese is involved in cholesterol synthesis; therefore, a deficiency can be related to a lack of this precursor for normal hormonal production. Manganese also shows a synergistic relationship with choline. A deficiency of either or both may lead to abnormal mitochondrial and cell membrane integrity.15 The liver mitochondria isolated from manganese deficient mice revealed abnormalities of the cristae and a lowered oxidation rate.16"
"Disturbances in carbohydrate metabolism is due to abnormal glycosyltransferase activity. Abnormality of the pancreas resulting in poor glucose utilization suggests that manganese may be involved with insulin formation or activity.17"
"Human manganese deficiency has been described in which manganese was inadvertently omitted from a purified diet. The symptoms included hypocholesterolemia, decreased triglycerides and phospholipids, weight loss, transient dermatitis, and intermittent nausea."
"Since prothrombin is a glycoprotein and manganese activates transferases, it is possible that manganese may be required for prothrombin synthesis."
"Epileptics were found to have lowered blood concentrations of manganese.20"
"Other manganese related conditions include intrauterine malformations and osteoporosis."
"Patients with drug-induced and non-drug induced lupus have been reported to benefit from manganese administration.23 Since manganese is required for the conversion of ammonium ions to urea, a deficiency may lead to a ammonium toxicity."
"Elevated levels have been associated with multiple sclerosis, learning disabilities; and Parkinson's disease."
"In TMA testing, Trace Elements has commonly found low manganese levels in the hair of patients with hypoglycemia, hypothyroidism, adrenal insufficiency, and diabetes."
"As mentioned previously, manganese compounds are substituting for lead as an anti-knock additive in unleaded gasoline. Excess manganese is also often seen in conjunction with iron toxicity. In this case the manganese is not a toxin per se, but is a secondary elevation due to excess iron retention. In this case the elevation may be due to the body's attempt to decrease the effects of iron toxicity by increasing manganese retention, or the excess iron may be displacing manganese from storage tissues."
"The liver regulates manganese via excretion in the bile; however, if the liver excretory route is blocked or if overloading occurs, pancreatic excretion increases. Tissue manganese levels are directly related to availability in the diet. Alcohol increases the hepatic manganese level and apparently doubles its absorption."
"Manganese is required for normal thyroid function and is involved in the formation of thyroxin.7 Tissue mineral analysis (TMA) studies have revealed low manganese levels in hypothyroid patients. Due to the antagonistic effect of insulin, parathyroid hormone (PTH), and estrogen on thyroid function, absorption or utilization of manganese may be impaired when levels of these hormones are elevated.8,9 The adrenal hormones are known to affect the tissue distribution of manganese as well as to alter its metabolism."
"Manganese is involved in cholesterol synthesis; therefore, a deficiency can be related to a lack of this precursor for normal hormonal production. Manganese also shows a synergistic relationship with choline. A deficiency of either or both may lead to abnormal mitochondrial and cell membrane integrity.15 The liver mitochondria isolated from manganese deficient mice revealed abnormalities of the cristae and a lowered oxidation rate.16"
"Disturbances in carbohydrate metabolism is due to abnormal glycosyltransferase activity. Abnormality of the pancreas resulting in poor glucose utilization suggests that manganese may be involved with insulin formation or activity.17"
"Human manganese deficiency has been described in which manganese was inadvertently omitted from a purified diet. The symptoms included hypocholesterolemia, decreased triglycerides and phospholipids, weight loss, transient dermatitis, and intermittent nausea."
"Since prothrombin is a glycoprotein and manganese activates transferases, it is possible that manganese may be required for prothrombin synthesis."
"Epileptics were found to have lowered blood concentrations of manganese.20"
"Other manganese related conditions include intrauterine malformations and osteoporosis."
"Patients with drug-induced and non-drug induced lupus have been reported to benefit from manganese administration.23 Since manganese is required for the conversion of ammonium ions to urea, a deficiency may lead to a ammonium toxicity."
"Elevated levels have been associated with multiple sclerosis, learning disabilities; and Parkinson's disease."
"In TMA testing, Trace Elements has commonly found low manganese levels in the hair of patients with hypoglycemia, hypothyroidism, adrenal insufficiency, and diabetes."
"As mentioned previously, manganese compounds are substituting for lead as an anti-knock additive in unleaded gasoline. Excess manganese is also often seen in conjunction with iron toxicity. In this case the manganese is not a toxin per se, but is a secondary elevation due to excess iron retention. In this case the elevation may be due to the body's attempt to decrease the effects of iron toxicity by increasing manganese retention, or the excess iron may be displacing manganese from storage tissues."
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Manganese in Health and Disease - Daiana Silva Avila, Robson Luiz Puntel, and Michael Aschner (there are others with the same title)
"In living tissue, Mn has been found as Mn 2+, Mn3+, and possibly as Mn4+, while Mn5+, Mn6+, Mn7+, and other complexes of Mn at lower oxidation states, are not observed in biological materials [3,4]."
"The versatile chemical properties of Mn have enabled its industrial usage in iron and steel production, manufacture of dry cell batteries, production of potassium permanganate and other chemicals, as oxidant in the production of hydroquinone, manufacture of glass and ceramics, textile bleaching, as an oxidizing agent for electrode coating in welding rods, adhesives, paint, matches and fireworks, and tanning of leather. Organic compounds of Mn are also present in fuel additive, methyl-cyclopentadienyl manganese tricarbonyl (MMT) as well as in several fungicides. Moreover, considering that Mn is a paramagnetic metal, namely that it has unpaired electrons in its outer d shell, it can also be detected with magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) [1,5]. These techniques allow for the tracking of Mn dynamics repeatedly in the same subject in vivo [1,6]"
"in the mammalian brain, small amounts of Mn are required for brain development, cellular homeostasis, and for the activity of multiple enzymes [28–30]. Additionally, Mn is believed to be involved in the stellate process production in astrocytes, as well as in the metabolism of brain glutamate to glutamine, a step carried out by glutamine synthetase (GS)."
"few occurrences of Mn deficiencies have been reported in humans, with symptoms including dermatitis, slowed growth of hair and nails, decreased serum cholesterol levels, decreased levels of clotting proteins, increased serum calcium and phosphorus concentrations, and increased alkaline phosphatase activity [25,33,34]"
"during Fe deficiency the number of transporters in enterocyte membranes is increased in order to maximize Fe absorption [47]. This will inevitably result in increased Mn absorption, particularly in the absence of Fe."
"About 3–5% of dietary Mn is absorbed in the gastrointestinal tract as Mn2+ and Mn4+ [29]. Mn2+ is oxidized to Mn3+ by liver and plasma ceruloplasmin and transported through the blood [51,52]. Mn tends to form tight complexes with other ligands [4]. Accordingly, a variety of plasma proteins or ligands have been implicated as specific Mn carrier proteins, including transglutaminase, beta-globulin, albumin, and Tf [53,54]. As a result, its free plasma and tissue concentrations tend to be extremely low [55]."
"The physiological half-life of Mn in the adult rat and primate brain is approximately 51 to 74 days [52,55,73,79]. The main excretion mechanism for Mn depends on normal liver function. Indeed, blood Mn concentrations are increased during the active phase of acute hepatitis as well as in post hepatic cirrhosis, and a significant correlation exists between blood Mn and the activities of liver enzymes in patients with hepatitis and cirrhosis [80,81]"
"Although Cu and Mg can substitute for Mn as a cofactor for some enzymes, there is a subset of enzymes with roles in neuron and/or glial that are strictly dependent upon the presence of Mn. These discrete Mn-binding proteins (manganoproteins) include glutamine synthetase, superoxide dismutase 2 (SOD2), arginase, pyruvate decarboxylase, and serine/threonine phosphatase [87–89]."
"Glutamine synthetase is the most abundant manganoprotein [in brain]; it is predominantly expressed in astrocytes, where it converts glutamate to glutamine. Because GS contains four Mn ions per octamer [90], Mn has been proposed to regulate GS activity. In fact, insufficient Mn increases glutamate trafficking, glutamatergic signaling, and excitotoxicity [91]. Furthermore, it has been proposed that the increased susceptibility to seizures observed in individuals with Mn deficiency may be due to diminished GS levels and/or activity [92].
Arginase regulates elimination of ammonia from the body by converting L-arginine, synthesized from ammonia, to L-ornithine and urea as part of the urea cycle. Moreover, in the brain, L-arginine is converted to nitric oxide by neuronal nitric oxide synthetase. Proper regulation of arginase promotes neuronal survival by impairing nitric oxide signaling [93,94].
Pyruvate carboxylase is an essential enzyme required for glucose metabolism that interacts with Mn to generate oxaloacetate, a precursor of the tricarboxylic acid (TCA) cycle [95]. Interestingly, in the brain, pyruvate carboxylase is predominantly expressed in astrocytes [58,96]. Protein phosphatase-1 is essential for glycogen metabolism, cell progression, regulation synthesis, and release of neurotrophins, which promote neuronal survival and synaptic membrane receptors and channels [97].
Finally, SOD2 is a mitochondrial enzyme that detoxifies superoxide anions through the formation of hydrogen peroxide. Although the concentration of Mn within neurons is low (<10^[−5] M), their high mitochondrial energy demands is correlated with a propensity for increased SOD2 in neurons compared to glia [28,42]. Furthermore, loss of SOD2 activity increases the susceptibility to mitochondrial inhibitor induced toxicity and causes oxidative stress [98].
Thus, Mn deficiencies, although not frequently reported in humans, may result in several biochemical and structural defects [35,99,100]. Accordingly, taking into account the Mn-dependent enzymatic processes, it is clear that inadequate daily supply of this metal may be associated with a variety of health repercussions [31,32]."
From now on, going awry (mostly toxicity):
"Manganism (also referred to as locura manganica) has been known for 150 years and it is caused by the preferential accumulation of Mn in brain areas rich in dopaminergic (DAergic) neurons (caudate nucleus, putamen, globus pallidus, substantia nigra, and subthalamic nuclei) [79,141,142]. Mn can readily oxidize catecholamines,211 including dopamine (DA), altering homeostasis in these areas [70]. Perturbation in striatal DA levels likely explains the biphasic syndrome experienced by patients with manganism. An initial phase of increased DA production is associated with psychotic episodes commonly observed in psychiatric patients [143]. As Mn poisoning progresses, catecholamine levels decrease, most likely due to the loss of nigrostriatal DAergic neurons and, consequently, the parkinsonian-like symptoms ensue [1,13,70]."
"Mn-induced DA oxidation is a complex process involving several steps in which semiquinone, aminochrome intermediates, L-cysteine or copper and NADH are implicated [158,182,193]. Mechanisms underlying semiquinone and aminochrome-induced damage in the Mn-induced neurodegenerative process likely include: (i) NADH or NADPH depletion; (ii) inactivation of enzymes by oxidizing thiol groups or essential amino acids; (iii) formation of ROS; and (iv) lipid peroxidation. It is noteworthy that neither Mn2+ nor Mn3+ can generate hydroxyl radicals from hydrogen peroxide and/or superoxide via Fenton-type or Haber-Weiss-type reactions, while Mn2+ can scavenge and detoxify superoxide radicals [3,188]."
"The ability of Mn to enhance oxidative stress is due to the transition of its oxidative state +2 to +3, which increases its pro-oxidant capacity [192]. Superoxide produced in the mitochondrial electron transport chain may catalyze this transition through a set of reactions similar to those mediated by SOD and thus lead to the increased oxidant capacity of the metal [195]. Since Mn3+ has greater pro-oxidant potential than Mn2+, its production in the mitochondria may accentuate oxidative damage [197]."
"Mn can directly impair mitochondrial function by inhibiting the mitochondrial electron transfer chain [21,88,198], resulting in a reduced ATP production, increased leakage of electrons, and increased O·2− production [199]. Although, Mn3+ is more potent at inhibiting complex I [3,197], Mn2+ is the predominant species within cells and is largely bound to ATP [196,197]. Notably, Mn in biological media in any of the oxidation states will spontaneously generate Mn3+. Interestingly, even trace amounts of Mn3+ can cause formation of ROS [200]. The involvement of ROS in Mn-induced mitochondrial dysfunction is also supported by observations on the efficacy of antioxidants in attenuating its effects [201]."
"Mn also interferes with Ca2+ homeostasis in mitochondria by inhibiting its efflux [202,203]"
"Unlike neurons, astrocytes concentrate Mn to levels at least 50-fold higher than the culture media, thus functioning as the major homeostatic regulators and storage site for Mn [213,214]."
"The versatile chemical properties of Mn have enabled its industrial usage in iron and steel production, manufacture of dry cell batteries, production of potassium permanganate and other chemicals, as oxidant in the production of hydroquinone, manufacture of glass and ceramics, textile bleaching, as an oxidizing agent for electrode coating in welding rods, adhesives, paint, matches and fireworks, and tanning of leather. Organic compounds of Mn are also present in fuel additive, methyl-cyclopentadienyl manganese tricarbonyl (MMT) as well as in several fungicides. Moreover, considering that Mn is a paramagnetic metal, namely that it has unpaired electrons in its outer d shell, it can also be detected with magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) [1,5]. These techniques allow for the tracking of Mn dynamics repeatedly in the same subject in vivo [1,6]"
"in the mammalian brain, small amounts of Mn are required for brain development, cellular homeostasis, and for the activity of multiple enzymes [28–30]. Additionally, Mn is believed to be involved in the stellate process production in astrocytes, as well as in the metabolism of brain glutamate to glutamine, a step carried out by glutamine synthetase (GS)."
"few occurrences of Mn deficiencies have been reported in humans, with symptoms including dermatitis, slowed growth of hair and nails, decreased serum cholesterol levels, decreased levels of clotting proteins, increased serum calcium and phosphorus concentrations, and increased alkaline phosphatase activity [25,33,34]"
"during Fe deficiency the number of transporters in enterocyte membranes is increased in order to maximize Fe absorption [47]. This will inevitably result in increased Mn absorption, particularly in the absence of Fe."
"About 3–5% of dietary Mn is absorbed in the gastrointestinal tract as Mn2+ and Mn4+ [29]. Mn2+ is oxidized to Mn3+ by liver and plasma ceruloplasmin and transported through the blood [51,52]. Mn tends to form tight complexes with other ligands [4]. Accordingly, a variety of plasma proteins or ligands have been implicated as specific Mn carrier proteins, including transglutaminase, beta-globulin, albumin, and Tf [53,54]. As a result, its free plasma and tissue concentrations tend to be extremely low [55]."
"The physiological half-life of Mn in the adult rat and primate brain is approximately 51 to 74 days [52,55,73,79]. The main excretion mechanism for Mn depends on normal liver function. Indeed, blood Mn concentrations are increased during the active phase of acute hepatitis as well as in post hepatic cirrhosis, and a significant correlation exists between blood Mn and the activities of liver enzymes in patients with hepatitis and cirrhosis [80,81]"
"Although Cu and Mg can substitute for Mn as a cofactor for some enzymes, there is a subset of enzymes with roles in neuron and/or glial that are strictly dependent upon the presence of Mn. These discrete Mn-binding proteins (manganoproteins) include glutamine synthetase, superoxide dismutase 2 (SOD2), arginase, pyruvate decarboxylase, and serine/threonine phosphatase [87–89]."
"Glutamine synthetase is the most abundant manganoprotein [in brain]; it is predominantly expressed in astrocytes, where it converts glutamate to glutamine. Because GS contains four Mn ions per octamer [90], Mn has been proposed to regulate GS activity. In fact, insufficient Mn increases glutamate trafficking, glutamatergic signaling, and excitotoxicity [91]. Furthermore, it has been proposed that the increased susceptibility to seizures observed in individuals with Mn deficiency may be due to diminished GS levels and/or activity [92].
Arginase regulates elimination of ammonia from the body by converting L-arginine, synthesized from ammonia, to L-ornithine and urea as part of the urea cycle. Moreover, in the brain, L-arginine is converted to nitric oxide by neuronal nitric oxide synthetase. Proper regulation of arginase promotes neuronal survival by impairing nitric oxide signaling [93,94].
Pyruvate carboxylase is an essential enzyme required for glucose metabolism that interacts with Mn to generate oxaloacetate, a precursor of the tricarboxylic acid (TCA) cycle [95]. Interestingly, in the brain, pyruvate carboxylase is predominantly expressed in astrocytes [58,96]. Protein phosphatase-1 is essential for glycogen metabolism, cell progression, regulation synthesis, and release of neurotrophins, which promote neuronal survival and synaptic membrane receptors and channels [97].
Finally, SOD2 is a mitochondrial enzyme that detoxifies superoxide anions through the formation of hydrogen peroxide. Although the concentration of Mn within neurons is low (<10^[−5] M), their high mitochondrial energy demands is correlated with a propensity for increased SOD2 in neurons compared to glia [28,42]. Furthermore, loss of SOD2 activity increases the susceptibility to mitochondrial inhibitor induced toxicity and causes oxidative stress [98].
Thus, Mn deficiencies, although not frequently reported in humans, may result in several biochemical and structural defects [35,99,100]. Accordingly, taking into account the Mn-dependent enzymatic processes, it is clear that inadequate daily supply of this metal may be associated with a variety of health repercussions [31,32]."
From now on, going awry (mostly toxicity):
"Manganism (also referred to as locura manganica) has been known for 150 years and it is caused by the preferential accumulation of Mn in brain areas rich in dopaminergic (DAergic) neurons (caudate nucleus, putamen, globus pallidus, substantia nigra, and subthalamic nuclei) [79,141,142]. Mn can readily oxidize catecholamines,211 including dopamine (DA), altering homeostasis in these areas [70]. Perturbation in striatal DA levels likely explains the biphasic syndrome experienced by patients with manganism. An initial phase of increased DA production is associated with psychotic episodes commonly observed in psychiatric patients [143]. As Mn poisoning progresses, catecholamine levels decrease, most likely due to the loss of nigrostriatal DAergic neurons and, consequently, the parkinsonian-like symptoms ensue [1,13,70]."
"Mn-induced DA oxidation is a complex process involving several steps in which semiquinone, aminochrome intermediates, L-cysteine or copper and NADH are implicated [158,182,193]. Mechanisms underlying semiquinone and aminochrome-induced damage in the Mn-induced neurodegenerative process likely include: (i) NADH or NADPH depletion; (ii) inactivation of enzymes by oxidizing thiol groups or essential amino acids; (iii) formation of ROS; and (iv) lipid peroxidation. It is noteworthy that neither Mn2+ nor Mn3+ can generate hydroxyl radicals from hydrogen peroxide and/or superoxide via Fenton-type or Haber-Weiss-type reactions, while Mn2+ can scavenge and detoxify superoxide radicals [3,188]."
"The ability of Mn to enhance oxidative stress is due to the transition of its oxidative state +2 to +3, which increases its pro-oxidant capacity [192]. Superoxide produced in the mitochondrial electron transport chain may catalyze this transition through a set of reactions similar to those mediated by SOD and thus lead to the increased oxidant capacity of the metal [195]. Since Mn3+ has greater pro-oxidant potential than Mn2+, its production in the mitochondria may accentuate oxidative damage [197]."
"Mn can directly impair mitochondrial function by inhibiting the mitochondrial electron transfer chain [21,88,198], resulting in a reduced ATP production, increased leakage of electrons, and increased O·2− production [199]. Although, Mn3+ is more potent at inhibiting complex I [3,197], Mn2+ is the predominant species within cells and is largely bound to ATP [196,197]. Notably, Mn in biological media in any of the oxidation states will spontaneously generate Mn3+. Interestingly, even trace amounts of Mn3+ can cause formation of ROS [200]. The involvement of ROS in Mn-induced mitochondrial dysfunction is also supported by observations on the efficacy of antioxidants in attenuating its effects [201]."
"Mn also interferes with Ca2+ homeostasis in mitochondria by inhibiting its efflux [202,203]"
"Unlike neurons, astrocytes concentrate Mn to levels at least 50-fold higher than the culture media, thus functioning as the major homeostatic regulators and storage site for Mn [213,214]."
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Modern Nutrition in Health and Disease - Ross
ESPN: 978-1-60547-461-8
"The human body contains approximately 10 to 20 mg of Mn, with 25% to 40% present in bone and 5 to 8 mg turned over on a daily basis. The biologic half-life of Mn ranges from approximately 12 to 40 days (4)."
"Mn is essential as a cofactor for the metalloenzymes superoxide dismutase (SOD), xanthine oxidase, arginase, galactosyltransferase, and pyruvate carboxylase (5). It functions as a constituent of these metalloenzymes or as an enzyme activator. SOD activity is depressed in Mn-deficient animals (6). SOD protects the cell against antioxidant processes, including injury associated with radiation, chemicals, and ultraviolet light. Mn binding to arginase has significant importance in nitrogen metabolism through the ornithine cycle (7). It hydrolyzes L-arginine to urea and L-ornithine. Decreased arginase results in increased plasma ammonia in rats (8)." "Mn also activates numerous enzymes including various decarboxylases, glutamine synthetase, hydrolases, kinases, and transferases such as glycosyltransferases, the last of which are involved in polysaccharide biosynthesis (10)."
"Mn deficiency can result in defective cartilage formation in animals."
"The addition of large doses of Mn (four to eight times the AI) leads to a decrease in iron absorption by approximately one third (26). Mn supplementation leads to decreased iron absorption in iron-deficient animals, although this effect has not been demonstrated in humans (27). Investigators have also suggested that Mn absorption is enhanced in iron sufficiency and is decreased in iron deficiency (28). Therefore, Mn may possibly be recognized by the intestinal iron transport mechanism, and factors that regulate iron absorption may also then regulate Mn absorption."
"Adding calcium (Ca) to human milk and increasing dietary phytate have been shown to reduce Mn absorption (29, 30)."
"Dietary Mn is absorbed by a diffusion mechanism and a transport mechanism that are rapidly saturable (32, 33). Approximately 6% to 16% of dietary Mn is absorbed (mean, 9%), with a retention half-life of 8 to 33 days (19, 34, 35). Mena (36) found that retention was 15.4% in premature infants at 10 days, but only 8.0% in term newborns and 1.0% to 3.0% in adults. The better absorption from human milk than from bovine milk or soy-based formula may be related to the decreased concentration of Mn in human milk or the increased binding of Mn in human milk to lactoferrin, the increased Ca content of bovine milk, and, for soy-based formula, the relatively large amounts of phytic acid (37, 38). No other dietary factors are known to affect Mn absorption, including ascorbic acid. [?]"
"Absorption is increased in patients with hemochromatosis (34), as well as in patients with iron deficiency (36). Mn absorption is decreased in the presence of a large Ca load (40). Mn sulfate is the most soluble salt and is therefore the form found in most nutritional supplements (41). After absorption into the portal circulation, Mn may remain either free or bound preferably to transferrin (42), but also to diokineguaranteed2-macroglobulin (43, 44) and albumin (45) to a lesser extent, all three of which are rapidly taken up by the liver."
"Metabolically active tissues with high numbers of mitochondria as well as pigmented structures appear to have greater Mn concentrations (6)."
"Excretion occurs primarily through the bile, and, as such, nearly all Mn is excreted in the feces (31). Studies in the rat indicated that approximately 11% of intravenously infused Mn that is excreted into the biliary system is reabsorbed in the intestine, although some variation may exist among species."
"Mn is essential as a cofactor for the metalloenzymes superoxide dismutase (SOD), xanthine oxidase, arginase, galactosyltransferase, and pyruvate carboxylase (5). It functions as a constituent of these metalloenzymes or as an enzyme activator. SOD activity is depressed in Mn-deficient animals (6). SOD protects the cell against antioxidant processes, including injury associated with radiation, chemicals, and ultraviolet light. Mn binding to arginase has significant importance in nitrogen metabolism through the ornithine cycle (7). It hydrolyzes L-arginine to urea and L-ornithine. Decreased arginase results in increased plasma ammonia in rats (8)." "Mn also activates numerous enzymes including various decarboxylases, glutamine synthetase, hydrolases, kinases, and transferases such as glycosyltransferases, the last of which are involved in polysaccharide biosynthesis (10)."
"Mn deficiency can result in defective cartilage formation in animals."
"The addition of large doses of Mn (four to eight times the AI) leads to a decrease in iron absorption by approximately one third (26). Mn supplementation leads to decreased iron absorption in iron-deficient animals, although this effect has not been demonstrated in humans (27). Investigators have also suggested that Mn absorption is enhanced in iron sufficiency and is decreased in iron deficiency (28). Therefore, Mn may possibly be recognized by the intestinal iron transport mechanism, and factors that regulate iron absorption may also then regulate Mn absorption."
"Adding calcium (Ca) to human milk and increasing dietary phytate have been shown to reduce Mn absorption (29, 30)."
"Dietary Mn is absorbed by a diffusion mechanism and a transport mechanism that are rapidly saturable (32, 33). Approximately 6% to 16% of dietary Mn is absorbed (mean, 9%), with a retention half-life of 8 to 33 days (19, 34, 35). Mena (36) found that retention was 15.4% in premature infants at 10 days, but only 8.0% in term newborns and 1.0% to 3.0% in adults. The better absorption from human milk than from bovine milk or soy-based formula may be related to the decreased concentration of Mn in human milk or the increased binding of Mn in human milk to lactoferrin, the increased Ca content of bovine milk, and, for soy-based formula, the relatively large amounts of phytic acid (37, 38). No other dietary factors are known to affect Mn absorption, including ascorbic acid. [?]"
"Absorption is increased in patients with hemochromatosis (34), as well as in patients with iron deficiency (36). Mn absorption is decreased in the presence of a large Ca load (40). Mn sulfate is the most soluble salt and is therefore the form found in most nutritional supplements (41). After absorption into the portal circulation, Mn may remain either free or bound preferably to transferrin (42), but also to diokineguaranteed2-macroglobulin (43, 44) and albumin (45) to a lesser extent, all three of which are rapidly taken up by the liver."
"Metabolically active tissues with high numbers of mitochondria as well as pigmented structures appear to have greater Mn concentrations (6)."
"Excretion occurs primarily through the bile, and, as such, nearly all Mn is excreted in the feces (31). Studies in the rat indicated that approximately 11% of intravenously infused Mn that is excreted into the biliary system is reabsorbed in the intestine, although some variation may exist among species."
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Advanced Nutrition: macronutrients, micronutrients, and metabolism - Berdanier and Zempleni
978‑1‑4200‑5552‑8
"Biochemical abnormalities were hard to document because many of the requirements for manganese as a cofactor in a number of enzymatic reactions could be met by magnesium. Nonetheless, bone and connective tissue growth are abnormal in manganese deficient animals. Few cases of human manganese deficiency have been reported."
"Manganese, like magnesium, is a transition element. It can exist in 11 oxidation states. However, in mammalian systems, it usually exists in either the +3 or +2 state. In the +2 state it is less easily chelated than in the +3 state. The +3 state is one which interacts with the ferric ion (Fe+++); it is also the state needed for service as a cofactor in the Mn superoxide dismutase enzyme."
"Manganese is poorly absorbed through the gut. Between 2 and 15% of that ingested in the food appears in the blood. This has been traced using radioactive 54Mn. As with many minerals, the route of excretion is via resecretion into the small intestine. That which is unabsorbed appears in the feces as does that which is excreted from the body via the bile."
"Manganese is present in the bone as part of the mineral apatite, and in the lactating gland, and liver to a greater extent than in other tissues.114 However, no tissue is free of this mineral. The turnover of manganese in the body varies depending on location. It is very short (~3-min half-life) in hepatic mitochondria and, in bone, its half life is about an hour."
"Evidence has been reported that manganese deficiency in experimental animals causes the downregulation of the mitochondrial manganese-containing superoxide dismutase (SOD) at the level of the activation of transcription of the gene that encodes this protein.115,119 Superoxide dismutases are a class of metalloproteins that catalyze the dismutation of the superoxide radical (O–2) [Travisord, if you're reading this, I know it made you itch] to oxygen (O2) and hydrogen peroxide (H2O2). These enzymes play a critical role in protecting cells against oxidative stress, particularly that produced by drugs (see Figure 12.7). Most mammalian cells contain two forms of this enzyme: one in the cytosol requiring iron or zinc and copper, and the other requiring manganese. It is generally thought that the latter, present in the mitochondria, protects that organelle from potential damage by the superoxide radical that could possibly be produced through the activity of the respiratory chain."
"Rich food sources include nuts, whole grains, and leafy vegetables. Meats, milk, seafood, and other animal products are poor sources. The germ of grains can contain up to 14 ppm. The average diet consumed in the United States contains about 3–4 mg/d. The range of intakes suggested by the National Academy of Sciences is from 2–11 mg/d, depending on the age and life stage of the consumers (see Table 12.1)."
"Manganese, like magnesium, is a transition element. It can exist in 11 oxidation states. However, in mammalian systems, it usually exists in either the +3 or +2 state. In the +2 state it is less easily chelated than in the +3 state. The +3 state is one which interacts with the ferric ion (Fe+++); it is also the state needed for service as a cofactor in the Mn superoxide dismutase enzyme."
"Manganese is poorly absorbed through the gut. Between 2 and 15% of that ingested in the food appears in the blood. This has been traced using radioactive 54Mn. As with many minerals, the route of excretion is via resecretion into the small intestine. That which is unabsorbed appears in the feces as does that which is excreted from the body via the bile."
"Manganese is present in the bone as part of the mineral apatite, and in the lactating gland, and liver to a greater extent than in other tissues.114 However, no tissue is free of this mineral. The turnover of manganese in the body varies depending on location. It is very short (~3-min half-life) in hepatic mitochondria and, in bone, its half life is about an hour."
"Evidence has been reported that manganese deficiency in experimental animals causes the downregulation of the mitochondrial manganese-containing superoxide dismutase (SOD) at the level of the activation of transcription of the gene that encodes this protein.115,119 Superoxide dismutases are a class of metalloproteins that catalyze the dismutation of the superoxide radical (O–2) [Travisord, if you're reading this, I know it made you itch] to oxygen (O2) and hydrogen peroxide (H2O2). These enzymes play a critical role in protecting cells against oxidative stress, particularly that produced by drugs (see Figure 12.7). Most mammalian cells contain two forms of this enzyme: one in the cytosol requiring iron or zinc and copper, and the other requiring manganese. It is generally thought that the latter, present in the mitochondria, protects that organelle from potential damage by the superoxide radical that could possibly be produced through the activity of the respiratory chain."
"Rich food sources include nuts, whole grains, and leafy vegetables. Meats, milk, seafood, and other animal products are poor sources. The germ of grains can contain up to 14 ppm. The average diet consumed in the United States contains about 3–4 mg/d. The range of intakes suggested by the National Academy of Sciences is from 2–11 mg/d, depending on the age and life stage of the consumers (see Table 12.1)."
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Trace Elements and Iron in Human Metabolism (1978) - Ananda Prasad
978-1-4684-0793-8
"Manganese is also required for cholesterol synthesis, probably at a step between acetate and mevalonate (Olson, 1965). In addition, manganese is required for the enzyme farnesyl pyrophosphate synthetase. Farnesyl-pyrophosphate is needed for squalene, which is a precursor of cholesterol; thus, a decrease in the activity of farnesyl pyrophosphate synthetase due to manganese deficiency may decrease the serum cholesterol level."
"In view ofthe competition that exists among manganese, copper, iron, and magnesium at the cellular level, it is conceivable that disorders of manganese metabolism do exist in human subjects, perhaps in association with certain disease states."
"Calcium and phosphorus affect the absorption of manganese adversely."
"It appears that manganese homeostasis is regulated at the excretory level, rather than at the site of absorption. The key tissue in this regulation is the liver, with the bile serving as an important route of excretion. Although biliary excretion is important in adjusting to a manganese load, the bile is not the only route of manganese excretion. Biliary ligation does not halt manganese excretion by the intestinal tract (Leach, 1976)."
"The retina is rich in its manganese content."
"The similarity between the symptoms of chronic manganese poisoning and Parkinson's disease encouraged the study of a possible relationship between manganese and biogenic amines. Subjects with parkinsonism and chronic manganese poisoning have decreased concentration of striatal dopamine. Mena et al. (1970) reported that administration of L-dopa (dihydroxy-phenylalanine), an immediate precursor of dopamine, to patients with chronic manganese toxicity resulted in a disappearance of rigidity and hypokinesia in addition to an improvement of postural reflexes and restitution of balance. This compound (L-dopa) has also been shown to be of great benefit in alleviating some ofthe symptoms ofParkinson's disease (Cotzias et al., 1971; Leach, 1976)."
"Papavasiliou et al. (1968) proposed that cyclic adenosine monophosphate (cyclic 3' ,5'-AMP) is the link between biogenic amines and manganese metabolism. In these reports, the substances that altered cyclic AMP also altered manganese metabolism, as shown by increased liver retention accompanied by decreased biliary excretion."
"Liver mitochondria isolated from deficient mice demonstrate a normal phosphate esterified to oxygen consumption ratio (P : O), but show a reduced oxygen uptake (Hurley et al., 1970). Abnormalities, including elongation and reorientation of cristae, are revealed by examination of the ultrastructure, and Ben and Hurley (1973) observed that the ultrastructural changes associated with manganese deficiency occur in other tissues as well. An tissues examined revealed alterations in the integrity of their cell membranes as well as changes in the endoplasmic reticulum. It was therefore proposed that the morphological changes observed in the mitochondria might explain the lowered oxidation rate observed in their previous study (Leach, 1976)."
"Some other defects in carbohydrate metabolism were observed with manganese deficiency. Several of the guinea pigs with a congenital deficiency have short survival times and exhibit aplasia or hypoplasia of pancreatic tissue. Moreover, these studies revealed that those animals that survive to adult age show abnormal tolerance to intravenously administered glucose (Shrader and Everson, 1968; Everson and Shrader, 1968)."
"In view ofthe competition that exists among manganese, copper, iron, and magnesium at the cellular level, it is conceivable that disorders of manganese metabolism do exist in human subjects, perhaps in association with certain disease states."
"Calcium and phosphorus affect the absorption of manganese adversely."
"It appears that manganese homeostasis is regulated at the excretory level, rather than at the site of absorption. The key tissue in this regulation is the liver, with the bile serving as an important route of excretion. Although biliary excretion is important in adjusting to a manganese load, the bile is not the only route of manganese excretion. Biliary ligation does not halt manganese excretion by the intestinal tract (Leach, 1976)."
"The retina is rich in its manganese content."
"The similarity between the symptoms of chronic manganese poisoning and Parkinson's disease encouraged the study of a possible relationship between manganese and biogenic amines. Subjects with parkinsonism and chronic manganese poisoning have decreased concentration of striatal dopamine. Mena et al. (1970) reported that administration of L-dopa (dihydroxy-phenylalanine), an immediate precursor of dopamine, to patients with chronic manganese toxicity resulted in a disappearance of rigidity and hypokinesia in addition to an improvement of postural reflexes and restitution of balance. This compound (L-dopa) has also been shown to be of great benefit in alleviating some ofthe symptoms ofParkinson's disease (Cotzias et al., 1971; Leach, 1976)."
"Papavasiliou et al. (1968) proposed that cyclic adenosine monophosphate (cyclic 3' ,5'-AMP) is the link between biogenic amines and manganese metabolism. In these reports, the substances that altered cyclic AMP also altered manganese metabolism, as shown by increased liver retention accompanied by decreased biliary excretion."
"Liver mitochondria isolated from deficient mice demonstrate a normal phosphate esterified to oxygen consumption ratio (P : O), but show a reduced oxygen uptake (Hurley et al., 1970). Abnormalities, including elongation and reorientation of cristae, are revealed by examination of the ultrastructure, and Ben and Hurley (1973) observed that the ultrastructural changes associated with manganese deficiency occur in other tissues as well. An tissues examined revealed alterations in the integrity of their cell membranes as well as changes in the endoplasmic reticulum. It was therefore proposed that the morphological changes observed in the mitochondria might explain the lowered oxidation rate observed in their previous study (Leach, 1976)."
"Some other defects in carbohydrate metabolism were observed with manganese deficiency. Several of the guinea pigs with a congenital deficiency have short survival times and exhibit aplasia or hypoplasia of pancreatic tissue. Moreover, these studies revealed that those animals that survive to adult age show abnormal tolerance to intravenously administered glucose (Shrader and Everson, 1968; Everson and Shrader, 1968)."
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Trace Elements in Human Health and Disease (1976) - Ananda Prasad again
0-12-564202-4
"In contrast to intestinal absorption, where there appears to be some interaction between iron and manganese, the pathway of manganese within the body appears to be very specific. It was found that only manganese would accelerate the exit of radiomanganese from the body.
Administration of a variety of other elements did not increase excretion, indicating that there was not an interaction between manganese and other elements of similar chemical properties as is observed with many other trace elements.
In spite of this apparent lack of interaction, there are several substitutions between manganese and other elements that have been reported. Several investigators (Borg and Cotzias, 1958b; Hancock and Fritze, 1973) have reported the isolation of manganese-containing porphyrins. Also, Scrutton et al. (1972) found magnesium to substitute for manganese in pyruvate carboxylase, a manganese metalloprotein."
Administration of a variety of other elements did not increase excretion, indicating that there was not an interaction between manganese and other elements of similar chemical properties as is observed with many other trace elements.
In spite of this apparent lack of interaction, there are several substitutions between manganese and other elements that have been reported. Several investigators (Borg and Cotzias, 1958b; Hancock and Fritze, 1973) have reported the isolation of manganese-containing porphyrins. Also, Scrutton et al. (1972) found magnesium to substitute for manganese in pyruvate carboxylase, a manganese metalloprotein."
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https://www.intechopen.com/books/en...a-new-emerging-contaminant-in-the-environment
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