Rafael Lao Wai
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Feeling pretty good, better than when I wasn't eating raw liver.
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Manganese And Its Unimportance In Health
- Thread starter Amazoniac
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- manganese unimportantium
Rafael Lao Wai
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I think offal is great. Internal organs have more choline, b12, etc. than muscle meats.
Yes, liver is indeed much more than vitamin A, it's just one component of it, I was just emphasizing that component.
Beef kidney is also a great source of vitamin A, but I haven't found a place that sells it in my city. Also, kidney is really high in choline, I think only 100 grams of kidney has something like 500mg of choline.
But I don't avoid muscle meats, I think they are very valuable, as are other parts of the animal. Creatine is found in large quantitities in the muscle tissues, but not so much in the internal organs.
Rafael Lao Wai
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My thinking has been the same lately. Liver has a lot of copper, so maybe the copper is helping me utilize the vitamin A correctly.
Also, I heard that retinyl palmitate is toxic to the liver, because it bypasses a certain limiting pathway. Liver has retinol instead, which is subjected to such limitation, so even getting large amounts of vitamin A from things such as eggs, liver, kidney, etc. is probably safe. People usually use the "polar bear liver is toxic because of vitamin A" argument, but, as far as I know, there hasn't been one study showing that retinol from foods is damaging to any organ. What they haven't taken into account is that vitamin A isn't the only thing that is stored in the liver of polar bears. They also store toxic substances from algae that they may ingest and heavy metals as well, so the evidence seems to point to these substances being the culprit for the adverse reactions of consuming the liver of polar bears.
Cirion
Member
Yeah my digestion is FUBAR, so limited organ meat is all I can tolerate for meat lol.
The liverwurst I get from wellness meats has kidney in it also. Also heart.
Rafael Lao Wai
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Have you ever tried ground meat cooked in a pressure cooker? This yields the best results in terms of digestion for me.
Awesome. Beef heart is great, full of coenzyme Q10.
Cirion
Member
Yeah I think maybe I tolerate some organ meat precisely because it is richer in nutrients than muscle meat. Also I have to watch out for tryptophan and cystine. My limit for both is very low, about half a gram a day. Then of course I have to limit pufa, and just about everything else. Yeah. Being hypothyroid is such fun lol.
I have not tried a pressure cooker but I do have a slow cooker. Hmm, maybe I'll try slow cooked potatoes cooked in bone broth.... Walmart sells organic bone broth now which I just bought earlier today. Could be a fairly benign way to boost my protein without running into tryptophan/cystine issues.
Eliminating fluoride did not help or heal the thyroid condition?
What caused your hypothyroidism
OP
Amazoniac
Member
OP
Amazoniac
Member
- Impact of dietary manganese on experimental colitis in mice
- Innate Immune Cells Speak Manganese
"Micronutrient deficiencies have been, for decades, a major concern in the management of IBD as numerous studies have documented associations between IBD and deficiencies in trace minerals, such as Fe, Zn, and Se.[25] Fe deficiency is associated with the bleeding, malabsorption, or anemia that occurs in one-third of IBD patients,[26] while zinc deficiency is also common in patients with IBD (15 to 40% of the patient population).[27] Similarly, an inverse association has been reported for nutritional Se status and the occurrence of IBD.[28] These previous studies are reminiscent of the findings described here for Mn, as deficiencies in these other trace minerals also show effects on the intestinal barrier and immune functions.[25]"
"[..]low Mn levels have been reported in IBD patients. For example, a recent epidemiological survey measured hair micronutrient levels in pediatric patients newly diagnosed with Crohn's disease and ulcerative colitis from 2012 to 2016.[8] This study identified that Fe (P = .033), Se (P = .017), and Mn (P = .009) were significantly lower in patients with Crohn's disease and ulcerative colitis than in healthy controls, implicating insufficiency in these trace minerals, including Mn, as potential risk factors for IBD."
"This study provides the first evidence that dietary Mn deficiency exacerbates intestinal injury and inflammation in an experimental colitis model. Our results provide some mechanistic insights into IBD, as they revealed how dietary Mn can maintain the intestinal barrier integrity and limit the development of colitis during colon injury."
"Mn-deficient mice displayed an increased intestinal permeability and impaired expression of tight junction proteins when compared to Mn-adequate mice. Strikingly, even in the absence of DSS treatment, mice fed with a Mn-deficient diet displayed a 1.5-fold greater permeability and impaired expression of tight junction proteins when compared with mice fed a Mn-adequate diet (Figure 6). These data suggest that impairment of the intestinal barrier in response to a Mn-deficient diet makes the mice more susceptible to severe intestinal injury and inflammation following DSS administration."
"Interestingly, Fe, Zn, and Se are abundant in animal foods, such as red meats, seafood, and poultry, whereas Mn is essentially absent from these foods and must be obtained from plant sources. As society has become industrialized, foods associated with the typical Western diet, characterized by high intakes of red meat, sugary desserts, high-fat foods, and refined grains, have replaced traditional plant-based, and therefore, Mn-adequate diets, leading to consumption of foods low in Mn.[7] Epidemiological studies have revealed a >40% reduction in a dietary Mn consumption in the past 15 years in the United States[7,40,41] and a similar substantial decline in Mn consumption has been reported in China within the last 14 years[42,43] and in South Korea within the last 6 years.[44,45] These studies are congruent with an increasing incidence of IBD in developed countries[46] and they indicate that, despite the rarity of dietary Mn deficiency (ie, the lack of Mn) regardless of dietary lifestyle, a Mn insufficiency is prevalent. Our data clearly demonstrated that tissue Mn deficiency occurs in a rapid and robust manner. Therefore, we postulate that reductions in dietary Mn intake might be one of the contributing factors that would explain the observed worldwide increases in IBD incidence."
"The Institute of Medicine's Dietary Reference Intake for Mn cites ~2 mg/day as adequate for adults and 1.2-1.5 mg/day as adequate for children. The Dietary Reference Intake also lists 9-11 mg/day of Mn for adults and 2-6 mg/day for children as the upper tolerable limit likely to pose no risk of adverse effects.[48] However, the guidelines were set for healthy individuals and it remains unclear whether these numbers apply to the restoration of a severely injured gastrointestinal tract associated with low Mn in IBD patients."
"Our work suggests that the restoration of nutritional Mn status to the normal range could be useful in the prevention and/or abrogation of IBD. One might argue that Mn toxicity can be a concern for this type of strategy; however, most Mn toxicity is triggered by the inhalation of Mn dust in occupational settings, such as is reported in workers employed in Mn dioxide mines, smelters, steel manufacturing plants, and dry-cell battery factories.[9] Thus, no evidence of dietary Mn toxicity has been found in humans.[49] This is because the homeostatic regulation of dietary Mn levels is tightly controlled by intestinal absorption and hepatobiliary excretion of the nutrient.[50] Unlike dietary sources of Mn, airborne Mn circumvents the first-pass clearance mechanisms. Therefore, inhaled Mn is effectively transported across the air-brain barrier, thereby potentially leading to brain Mn accumulation. In our Mn supplementation study, we fed mice with 300 ppm Mn and found a slight protective effect against DSS-induced colitis. Previous mouse studies have shown that oral supplementation with Mn even at levels of ~2400 ppm does not cause toxicity.[51,52]"
"[..]low Mn levels have been reported in IBD patients. For example, a recent epidemiological survey measured hair micronutrient levels in pediatric patients newly diagnosed with Crohn's disease and ulcerative colitis from 2012 to 2016.[8] This study identified that Fe (P = .033), Se (P = .017), and Mn (P = .009) were significantly lower in patients with Crohn's disease and ulcerative colitis than in healthy controls, implicating insufficiency in these trace minerals, including Mn, as potential risk factors for IBD."
"This study provides the first evidence that dietary Mn deficiency exacerbates intestinal injury and inflammation in an experimental colitis model. Our results provide some mechanistic insights into IBD, as they revealed how dietary Mn can maintain the intestinal barrier integrity and limit the development of colitis during colon injury."
"Mn-deficient mice displayed an increased intestinal permeability and impaired expression of tight junction proteins when compared to Mn-adequate mice. Strikingly, even in the absence of DSS treatment, mice fed with a Mn-deficient diet displayed a 1.5-fold greater permeability and impaired expression of tight junction proteins when compared with mice fed a Mn-adequate diet (Figure 6). These data suggest that impairment of the intestinal barrier in response to a Mn-deficient diet makes the mice more susceptible to severe intestinal injury and inflammation following DSS administration."
"Interestingly, Fe, Zn, and Se are abundant in animal foods, such as red meats, seafood, and poultry, whereas Mn is essentially absent from these foods and must be obtained from plant sources. As society has become industrialized, foods associated with the typical Western diet, characterized by high intakes of red meat, sugary desserts, high-fat foods, and refined grains, have replaced traditional plant-based, and therefore, Mn-adequate diets, leading to consumption of foods low in Mn.[7] Epidemiological studies have revealed a >40% reduction in a dietary Mn consumption in the past 15 years in the United States[7,40,41] and a similar substantial decline in Mn consumption has been reported in China within the last 14 years[42,43] and in South Korea within the last 6 years.[44,45] These studies are congruent with an increasing incidence of IBD in developed countries[46] and they indicate that, despite the rarity of dietary Mn deficiency (ie, the lack of Mn) regardless of dietary lifestyle, a Mn insufficiency is prevalent. Our data clearly demonstrated that tissue Mn deficiency occurs in a rapid and robust manner. Therefore, we postulate that reductions in dietary Mn intake might be one of the contributing factors that would explain the observed worldwide increases in IBD incidence."
"The Institute of Medicine's Dietary Reference Intake for Mn cites ~2 mg/day as adequate for adults and 1.2-1.5 mg/day as adequate for children. The Dietary Reference Intake also lists 9-11 mg/day of Mn for adults and 2-6 mg/day for children as the upper tolerable limit likely to pose no risk of adverse effects.[48] However, the guidelines were set for healthy individuals and it remains unclear whether these numbers apply to the restoration of a severely injured gastrointestinal tract associated with low Mn in IBD patients."
"Our work suggests that the restoration of nutritional Mn status to the normal range could be useful in the prevention and/or abrogation of IBD. One might argue that Mn toxicity can be a concern for this type of strategy; however, most Mn toxicity is triggered by the inhalation of Mn dust in occupational settings, such as is reported in workers employed in Mn dioxide mines, smelters, steel manufacturing plants, and dry-cell battery factories.[9] Thus, no evidence of dietary Mn toxicity has been found in humans.[49] This is because the homeostatic regulation of dietary Mn levels is tightly controlled by intestinal absorption and hepatobiliary excretion of the nutrient.[50] Unlike dietary sources of Mn, airborne Mn circumvents the first-pass clearance mechanisms. Therefore, inhaled Mn is effectively transported across the air-brain barrier, thereby potentially leading to brain Mn accumulation. In our Mn supplementation study, we fed mice with 300 ppm Mn and found a slight protective effect against DSS-induced colitis. Previous mouse studies have shown that oral supplementation with Mn even at levels of ~2400 ppm does not cause toxicity.[51,52]"
- Innate Immune Cells Speak Manganese
OP
Amazoniac
Member
- Relationship among manganese, arginase, and nitric oxide in childhood asthma
"Asthma is a respiratory disease characterized by increased airway responsiveness, inflammation, and variable airflow obstruction (1). Inflammatory cells infiltrating the airways produce several mediators that modulate the inflammatory response (2). Reactive nitrogen species might play an important role in the modulation of airway inflammation. Nitric oxide (NO), a highly reactive and unstable reactive nitrogen species, is synthesized from L-arginine by deoxygenases, known as nitric oxide synthases (NOS). It might play a role in the pathogenesis of asthma on the basis that expression of inducible NOS (iNOS) occurs in airway cells of asthmatics (3). Research demonstrated that asthmatic patients have a higher level of NO in plasma and exhaled air (4–6)."
"Arginase (L-arginine amidinohydrolase, E.C. 3.5.3.1) hydrolyses L-arginine to urea plus L-ornitine and plays a critical role in nitrogen metabolism (7). It is well known that arginase and NOS compete for the same substrate, L-arginine (8). It has been shown that arginase can limit arginine substrate for NO synthesis (9). Arginase requires manganese (Mn) for its catalytic activity and stability, although its oligomeric composition remains obscure (10). There is only one case-control study investigating the role of Mn in asthma. This study concluded that the lowest intakes of Mn were associated with more than a fivefold increase in bronchial reactivity (11). However, this association had not been explained yet. We suspect that a low level of plasma Mn could be associated with a decrease in arginase activity and an increase in NO with a reciprocal pathway in asthmatic patients."
"As shown in Table 2, plasma Mn and plasma arginase activities of patients with childhood asthma were significantly lower (p<0.05, p<0.01, respectively), whereas plasma NO level was significantly higher (p<0.01) than that of control subjects."
"The increased NO levels in asthmatic subjects can be explained in two ways. First, NOS can be induced in epithelial cells by exposure to proinflammatory cytokines such as tumor necrosis factor-α (TNF-α, and interleukin- 1β (IL-1β, secreted by macrophages and interferon-γ (IFN-γ) secreted by Th1 cells (24). In asthmatic subjects, NOS protein is upregulated in the airway epithelium through transcriptional regulation (25). Second, it is reported that the deficiency of Mn reduces arginase activity and that reduced arginase activity increases NOS activity (26). Because NO is synthesized from L-arginine by the catalytic action of NOS and strong interactions between the L-arginine-metabolizing enzymes, a competition between arginase and NOS is clearly demonstrated and they control each other’s level (27). L-Arginine is the substrate for NO synthesis in mammalian cells and is also metabolized to L-ornithine and urea by the action of arginase (28)."
"Arginase (L-arginine amidinohydrolase, E.C. 3.5.3.1) hydrolyses L-arginine to urea plus L-ornitine and plays a critical role in nitrogen metabolism (7). It is well known that arginase and NOS compete for the same substrate, L-arginine (8). It has been shown that arginase can limit arginine substrate for NO synthesis (9). Arginase requires manganese (Mn) for its catalytic activity and stability, although its oligomeric composition remains obscure (10). There is only one case-control study investigating the role of Mn in asthma. This study concluded that the lowest intakes of Mn were associated with more than a fivefold increase in bronchial reactivity (11). However, this association had not been explained yet. We suspect that a low level of plasma Mn could be associated with a decrease in arginase activity and an increase in NO with a reciprocal pathway in asthmatic patients."
"As shown in Table 2, plasma Mn and plasma arginase activities of patients with childhood asthma were significantly lower (p<0.05, p<0.01, respectively), whereas plasma NO level was significantly higher (p<0.01) than that of control subjects."
"The increased NO levels in asthmatic subjects can be explained in two ways. First, NOS can be induced in epithelial cells by exposure to proinflammatory cytokines such as tumor necrosis factor-α (TNF-α, and interleukin- 1β (IL-1β, secreted by macrophages and interferon-γ (IFN-γ) secreted by Th1 cells (24). In asthmatic subjects, NOS protein is upregulated in the airway epithelium through transcriptional regulation (25). Second, it is reported that the deficiency of Mn reduces arginase activity and that reduced arginase activity increases NOS activity (26). Because NO is synthesized from L-arginine by the catalytic action of NOS and strong interactions between the L-arginine-metabolizing enzymes, a competition between arginase and NOS is clearly demonstrated and they control each other’s level (27). L-Arginine is the substrate for NO synthesis in mammalian cells and is also metabolized to L-ornithine and urea by the action of arginase (28)."
Kingpinguin
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- Aug 14, 2019
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- 586
@Amazoniac
Hi! Asking for your opinion regarding Manganese.
I had previous problems with zinc, copper and iron.
Manganese never occured to me as also being a vital player in the trio of those minerals.
Long story short I used high dose zinc. I ended up with low copper and many strange symptoms along with it. I did focus on copper foods and took a supplement. Eventually I became I would say about 75% better. I had according to blood test semi low iron. So I used iron bisglycinate and that helped even further. I would say with iron supplementation I feel I’m around 90% restored in overall symptoms. But the weird thing is even though my iron now is quite high if i discontinue iron it takes a week or two and symptoms start reoccuring slowly. Sorta addicted to iron now which seems both strange and undesirable since the ill effects of having too much of it. So finally I started reading about manganese and eventually thought it might be the missing link. since manganese and iron share many of their properties and only differ in one atom number but still have different biological effects. Im now thinking I actually have a manganese deficiency and that my increased need for iron is just a masking of my manganese deficiency. I can relate to many of the manganese deficiency things you mentioned in this post like fatigue, joint problems and also a sense of spatial disorientation. Like I easily get dizzy coz it can feel like my world is upside down.
Ive read about manganism though. And I can feel my symptoms are low dopamine related. Although I did find a study about manganese involvement in tyrosine hydroxylase just like iron. That would also explain low dopamine symptoms I have. Also me not getting manganese if I’m taking iron even if both are very reactive seems counterproductive to mitochondria health. Since iron causes superoxide formation and and manganese SOD counters that. I would believe you need manganese and iron combined. Instead of high iron low manganese or low iron and high manganese?
I bought 15mg manganese bisglycinate supplement. I did read that upper limit is 11mg per day. You think I should worry about toxicity? Or is the toxicity from oral supplements overblown? What is the maximum oral dose one could try daily? My pill bottle says take 3 as in 45mg per day. But I’m gonna start low and build up.
Whats your opinion in the matter and my condition. I would appreciate it so much since you actually done the reading on manganese. BTW I have read this whole thread.
You also have any knowledge about zinc, copper and iron affecting manganese levels in the body. I read zinc lowers copper, manganese lowers copper, iron lowers manganese. But the whole interplay and action between them seems confusing. Wouldnt suprise me if the effects fall over to other transition metals such as chromium and cobalt/B12.
Just looking for guidiance as I would like to fix my mineral problems and get to be able to stop them all together. But my symptoms never fully dissappeared. Hoping manganese would help and actually me trying to lower my iron a bit now to see if manganese would be the missing link that my iron was trying to take its place.
another thing I could relate to your post is that I get bad reaction from taking zinc. According to your thread manganese seemed important for proper zinc metabolism?
Do you know if zinc depletes manganese if taken high doses alone?
Hi! Asking for your opinion regarding Manganese.
I had previous problems with zinc, copper and iron.
Manganese never occured to me as also being a vital player in the trio of those minerals.
Long story short I used high dose zinc. I ended up with low copper and many strange symptoms along with it. I did focus on copper foods and took a supplement. Eventually I became I would say about 75% better. I had according to blood test semi low iron. So I used iron bisglycinate and that helped even further. I would say with iron supplementation I feel I’m around 90% restored in overall symptoms. But the weird thing is even though my iron now is quite high if i discontinue iron it takes a week or two and symptoms start reoccuring slowly. Sorta addicted to iron now which seems both strange and undesirable since the ill effects of having too much of it. So finally I started reading about manganese and eventually thought it might be the missing link. since manganese and iron share many of their properties and only differ in one atom number but still have different biological effects. Im now thinking I actually have a manganese deficiency and that my increased need for iron is just a masking of my manganese deficiency. I can relate to many of the manganese deficiency things you mentioned in this post like fatigue, joint problems and also a sense of spatial disorientation. Like I easily get dizzy coz it can feel like my world is upside down.
Ive read about manganism though. And I can feel my symptoms are low dopamine related. Although I did find a study about manganese involvement in tyrosine hydroxylase just like iron. That would also explain low dopamine symptoms I have. Also me not getting manganese if I’m taking iron even if both are very reactive seems counterproductive to mitochondria health. Since iron causes superoxide formation and and manganese SOD counters that. I would believe you need manganese and iron combined. Instead of high iron low manganese or low iron and high manganese?
I bought 15mg manganese bisglycinate supplement. I did read that upper limit is 11mg per day. You think I should worry about toxicity? Or is the toxicity from oral supplements overblown? What is the maximum oral dose one could try daily? My pill bottle says take 3 as in 45mg per day. But I’m gonna start low and build up.
Whats your opinion in the matter and my condition. I would appreciate it so much since you actually done the reading on manganese. BTW I have read this whole thread.
You also have any knowledge about zinc, copper and iron affecting manganese levels in the body. I read zinc lowers copper, manganese lowers copper, iron lowers manganese. But the whole interplay and action between them seems confusing. Wouldnt suprise me if the effects fall over to other transition metals such as chromium and cobalt/B12.
Just looking for guidiance as I would like to fix my mineral problems and get to be able to stop them all together. But my symptoms never fully dissappeared. Hoping manganese would help and actually me trying to lower my iron a bit now to see if manganese would be the missing link that my iron was trying to take its place.
another thing I could relate to your post is that I get bad reaction from taking zinc. According to your thread manganese seemed important for proper zinc metabolism?
Do you know if zinc depletes manganese if taken high doses alone?
Last edited:
OP
Amazoniac
Member
Toxicity from ingestion within the range that you mentioned is a minor concern..
- Manganese And Its Unimportance In Health
- Manganese And Its Unimportance In Health (last paragraph)
- Manganese And Its Unimportance In Health (last paragraph)
..but imbalances are not. It's not difficult to obtain from diet, I would avoid supplementation because the body should be capable of adjusting over time on lower intakes, the priority is to eliminate what's preventing it from doing this.
If you were exceeding on iron without needing, manganese absorption was probably enhanced (on meals that had no competition) while excretion decreased, there's an experiment in rats where elimination was abolished in these conditions. It can be substituted by other minerals in some enzyme functions, sparing it further. It's better to draw blood, make sure that the diet contains plenty, and investigate other causes.
It may inhibit other minerals as well. If you respond to dietary manganese, this step should be working normally.
Might interest you:
- Handbook Of Vitamins, Minerals And Hormones - Roman J. Kutsky
Kingpinguin
Member
- Joined
- Aug 14, 2019
- Messages
- 586
Thank you so much! Very grateful for your time and information.
I’ll defo have a read on the handbook!
Its hard to find proper information about suboptimal manganese or deficiency as all studies done is mostly about toxicity. But interesting enough I found this website about a woman with chronic iron deficiency that was treated with 10mg manganese daily for more than a year succesfully restored her symptoms. Gonna stay on my 15mg pill bottle of manganese till its empty and see if I can achieve any results.
43 POSITIVE INFLUENCE OF SUPPLEMENTAL MANGANESE ON IRON INCORPORATION IN BRAIN AND RED BLOOD CELLS.
43 POSITIVE INFLUENCE OF SUPPLEMENTAL MANGANESE ON IRON INCORPORATION IN BRAIN AND RED BLOOD CELLS.
- S. Gupta,
- G. M. Stroh,
- H. Hassouna
Abstract
Structural, biochemical, and physiologic similarities make it possible for manganese to directly interact with iron on enzymes and proteins that require iron as a cofactor in their catalytic center. Elegant in vitro studies by Li et al (Toxicology and Applied Pharmacology 2005;205:188-200) demonstrate that manganese treatment alters the transcriptional but not translational level of the transferrin receptor (Tfr) expression and significantly augments the influx of Fe to the choroid plexus at the blood-CSF barrier. Transferrin bound diferric iron interacts with Tfr to undergo receptor-mediated endocytosis into erythroid precursors, hepatocytes, and brain endothelial cells, and proteolytic cleavage of the extracellular Tfr segment provides an index of the iron tissue levels. Although manganese toxicity is well documented, a beneficial role for manganese on iron homeostasis in the blood and the brain has never been reported. We present a lifelong iron deficiency microcytic anemia associated with symptoms suggestive of neurotransmitter dysregulation and perceptual size distortion in a 54-year-old white female. She had a total absence of sweating, severe constipation, and intolerance to heat and cold and episodes of oculomotor bias with size underestimation lasting 15 to 20 minutes. The anemia and symptoms resolved with daily administration of 10 mg over-the-counter oral manganese supplement (manganese). Premanganese levels for haptoglobin, direct bilirubin, and immunoglobulin were within the normal range. Erythrocyte sedimentation rate and platelet and white cell counts were within the normal range. Erythropoietin levels were 11 mU/mL (ref 4-21 mU/mL). Blood transfusions but not oral iron improved her symptoms but not the red cell indices and a consistently low reticulocyte count (0.6%). She had been off oral iron for a few months prior to her visit. Manganese was started in May 2005, discontinued December to February 2006 (‡), and resumed from then until the present. Manganese-induced changes in her hematologic profile and iron status from April 2005 to November 2006 are presented in Table 1. Studies performed in March and April in 2005 show iron studies consistent with appropriate iron absorption from the gut and inefficient incorporation of iron in the erythron, possibly from decreased TfR expression. Her tissue iron stores measured by ferritin levels were negligible. Manganese significantly increased her Hgb levels and corrected the MCV but not the soluble transferrin receptor levels that remain consistently above normal, an indication of deficient iron tissue storage. She started perspiring, and her ocular symptoms did not recur. On August 6, 2006, she had significant blood loss (§) that decreased her red blood cell count to 2.8 mill/μg and created a normochromic normocytic anemia with a reticulocyte count rising to 2%, a surprising consequence of manganese. We postulate that manganese, by positively influencing Tfr expression, reversed the underlying microcytic hypochromic iron deficiency anemia and related symptoms.
OP
Amazoniac
Member
There are members consuming a diet (similar to the one described below) that's low in manganese, increasing bile release, ingesting plenty of fiber and under stress. It's a recipe for death.
- Manganese: An essential nutrient for humans
- Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women
- Nutrition for the Women:
- Manganese: An essential nutrient for humans
"Although gross deficiencies have not been observed in free-living populations, cases of suboptimal status of manganese have been found in selected populations. These populations include children with inborn errors, such as phenylketonuria, maple syrup urine disease, galactosemia and methylmalonic acidemia; children and adults with epilepsy; and patients with exocrine pancreatic insufficiency, active rheumatoid arthritis or hydralazine syndrome.[4] Individuals with these conditions may have special needs for this trace element."
"Biochemical reasons for the dermatitis observed in [] experimentally-induced deficiencies could be related to the requirement of manganese for the activity of enzymes that are necessary in maintenance of skin integrity. The first group of enzymes, glycosyltransferases, functions in the synthesis of glycosaminoglycans, compounds which are components of the mucopolysaccharides of collagen in the skin as well as other tissues."
"[One of the consequences] of the manganese-deficient diet fed to our subjects was a decline in total and high-density lipoprotein-serum cholesterol. The hypocholesterolemia that was observed may be related to the requirement of manganese at five sites in the biosynthesis of cholesterol. [That's likely how Stephanie Seneff got into manganese: cholesterol sulfate.] Since both a fleeting, finely scaling rash and hypocholesterolemia were found in both our study and that by Doisey, it seems probable that these may be clinical symptoms of a manganese deficiency in humans."
"Perhaps the most provocative finding of our study were the observed increases in serum calcium and phosphorus and enhanced activity of alkaline phosphatase. Similar findings of elevated serum calcium and phosphorus were observed in rats that were fed Mn-deficient diets for 12 months.[8] The bones in the Mn-deficient animals were low in manganese and exhibited an osteoporotic condition. The alteration observed in both the human and animal studies suggest that stores of manganese were being mobilized as a consequence of the manganese deficiency. Dissolution of bone to release manganese would also release calcium and phosphorus in the blood. Whether or not continued manganese depletion would eventually lead to osteopororis is an area which demands further investigation."
"Based on regression analysis of manganese intake versus balance, the theoretical point of equilibrium was 3.55 mg/day (Figure 2). Thus, our suggestion is that a lower limit of 3.5 mg be set for adult men eating typical foods. However, notice in Figure 2 that there are still a number of studies tha reported negative balances with consumption of dietary intakes of manganese that are above this level. This suggests that, under some dietary conditions, intakes as great as 5 mg/day may be necessary to produce positive balances."
"Determination of human requirements of manganese is complicated by the fact that excretion[/retention], rather than absorption, is believed to be the regulator of homeostatic control."
"Studies in cattle, swine and poultry have shown that high intakes of calcium or a combination of excessive calcium and phosphorus in the diet intensifies the dietary requirement for manganese. Conversely, rats fed a high dietary level of manganese developed rickets due to negative calcium and phosphorus balances. In humans, the plasma uptake of manganese was greatly reduced by a concomitant load of 800 mg of calcium, whereas a similar amount of phosphorus had no effect.[11] Thus, the routine use of [killcium supplements] may be increasing the amount of manganese required."
"The negative influence of both fiber and phytate on manganese bioavailability was illustrated by Schwartz et al.[10] In their study, the consumption of three bran muffins per day produced negative manganese balance despite dietary levels of 13.9 mg of Mn/day."
"Pectin has a somewhat greater inhibitory effect on the plasma uptake of manganese than cellulose, followed by a slight suppression by phytate."
"Sugar is another dietary component that has been reported to promote deficiencies of some trace elements. In metabolic balance study of adult men and women,[13] the substitution of simple sugars for complex carbohydrates resulted in negative balances of manganese despite dietary levels of 4.4 to 5.9 mg/day. However, it was unclear whether the negative balances were due to the lower levels of manganese in the high sugar versus the high fiber diet (6.2 to 8 mg Mn/day) or were the result of interactions with other trace elements. Nonetheless, the impact of simple sugars on manganese balance should be pursued further since sugar is such an integral part of the American diet."
"High manganese levels in the diets of British, Canadian and Indian diets have been associated with consupmtion of tea, a beverage which is exceptionally rich in this mineral. However, the inclusion of tea in diets did not improve the retention of the mineral, suggesting that other constituents in the beverage (i.e., polyphenols) interfere with its absorption.[16] Other foods that provide significant amounts of manganese are nuts, seeds and whole grains; leafy green vegetables are fair sources (Table 2)."
"Poor food sources of manganese include meats, eggs, mil, sugar and refined foods. A diet containing a variety of nuts, seeds and whole grains may contain about 8 to 17 mg of Mn/day, whereas one based on meats, dairy products, sugary and refined foods may contain from 2 to 2.7 mg/day. Thus, dietary intakes of the mineral were much higher in the past when whole grains were an essential component of daily diets. The larger proportion of meats and refined fast foods in our current diets is presumably responsible for low dietary intakes of manganese."
"[Nevertheless,] having dietary intakes well above normal levels may not ensure optimal manganese status. Bioavailability of manganese (and other trace elements) is dependent on the sum of all the components in the diet, not just the absolute value of the total intake. Our current method of assessing nutritional adequacy of diets by comparing intakes to percent RDAs [] is inappropriate for most nutrients since it ignores the abundance of inhibitory and acceleratory factors found in foodstuffs. We must remember that people eat meals, not just nutrients."
"Biochemical reasons for the dermatitis observed in [] experimentally-induced deficiencies could be related to the requirement of manganese for the activity of enzymes that are necessary in maintenance of skin integrity. The first group of enzymes, glycosyltransferases, functions in the synthesis of glycosaminoglycans, compounds which are components of the mucopolysaccharides of collagen in the skin as well as other tissues."
"[One of the consequences] of the manganese-deficient diet fed to our subjects was a decline in total and high-density lipoprotein-serum cholesterol. The hypocholesterolemia that was observed may be related to the requirement of manganese at five sites in the biosynthesis of cholesterol. [That's likely how Stephanie Seneff got into manganese: cholesterol sulfate.] Since both a fleeting, finely scaling rash and hypocholesterolemia were found in both our study and that by Doisey, it seems probable that these may be clinical symptoms of a manganese deficiency in humans."
"Perhaps the most provocative finding of our study were the observed increases in serum calcium and phosphorus and enhanced activity of alkaline phosphatase. Similar findings of elevated serum calcium and phosphorus were observed in rats that were fed Mn-deficient diets for 12 months.[8] The bones in the Mn-deficient animals were low in manganese and exhibited an osteoporotic condition. The alteration observed in both the human and animal studies suggest that stores of manganese were being mobilized as a consequence of the manganese deficiency. Dissolution of bone to release manganese would also release calcium and phosphorus in the blood. Whether or not continued manganese depletion would eventually lead to osteopororis is an area which demands further investigation."
"Based on regression analysis of manganese intake versus balance, the theoretical point of equilibrium was 3.55 mg/day (Figure 2). Thus, our suggestion is that a lower limit of 3.5 mg be set for adult men eating typical foods. However, notice in Figure 2 that there are still a number of studies tha reported negative balances with consumption of dietary intakes of manganese that are above this level. This suggests that, under some dietary conditions, intakes as great as 5 mg/day may be necessary to produce positive balances."
"Determination of human requirements of manganese is complicated by the fact that excretion[/retention], rather than absorption, is believed to be the regulator of homeostatic control."
"Studies in cattle, swine and poultry have shown that high intakes of calcium or a combination of excessive calcium and phosphorus in the diet intensifies the dietary requirement for manganese. Conversely, rats fed a high dietary level of manganese developed rickets due to negative calcium and phosphorus balances. In humans, the plasma uptake of manganese was greatly reduced by a concomitant load of 800 mg of calcium, whereas a similar amount of phosphorus had no effect.[11] Thus, the routine use of [killcium supplements] may be increasing the amount of manganese required."
"The negative influence of both fiber and phytate on manganese bioavailability was illustrated by Schwartz et al.[10] In their study, the consumption of three bran muffins per day produced negative manganese balance despite dietary levels of 13.9 mg of Mn/day."
"Pectin has a somewhat greater inhibitory effect on the plasma uptake of manganese than cellulose, followed by a slight suppression by phytate."
"Sugar is another dietary component that has been reported to promote deficiencies of some trace elements. In metabolic balance study of adult men and women,[13] the substitution of simple sugars for complex carbohydrates resulted in negative balances of manganese despite dietary levels of 4.4 to 5.9 mg/day. However, it was unclear whether the negative balances were due to the lower levels of manganese in the high sugar versus the high fiber diet (6.2 to 8 mg Mn/day) or were the result of interactions with other trace elements. Nonetheless, the impact of simple sugars on manganese balance should be pursued further since sugar is such an integral part of the American diet."
"High manganese levels in the diets of British, Canadian and Indian diets have been associated with consupmtion of tea, a beverage which is exceptionally rich in this mineral. However, the inclusion of tea in diets did not improve the retention of the mineral, suggesting that other constituents in the beverage (i.e., polyphenols) interfere with its absorption.[16] Other foods that provide significant amounts of manganese are nuts, seeds and whole grains; leafy green vegetables are fair sources (Table 2)."
"Poor food sources of manganese include meats, eggs, mil, sugar and refined foods. A diet containing a variety of nuts, seeds and whole grains may contain about 8 to 17 mg of Mn/day, whereas one based on meats, dairy products, sugary and refined foods may contain from 2 to 2.7 mg/day. Thus, dietary intakes of the mineral were much higher in the past when whole grains were an essential component of daily diets. The larger proportion of meats and refined fast foods in our current diets is presumably responsible for low dietary intakes of manganese."
"[Nevertheless,] having dietary intakes well above normal levels may not ensure optimal manganese status. Bioavailability of manganese (and other trace elements) is dependent on the sum of all the components in the diet, not just the absolute value of the total intake. Our current method of assessing nutritional adequacy of diets by comparing intakes to percent RDAs [] is inappropriate for most nutrients since it ignores the abundance of inhibitory and acceleratory factors found in foodstuffs. We must remember that people eat meals, not just nutrients."
- Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women
"We longitudinally evaluated changes in MnSOD activity and other indices of manganese and iron status in 47 women during a 124-d supplementation study. Subjects received one of four treatments: placebo, 60 mg iron, 15 mg manganese, or both mineral supplements daily."
- Nutrition for the Women:
"Manganese is needed to synthesize thyroxin, so a deficiency can interfere with thyroid function (coffee is a major source of manganese, and caffeine also stimulates the thyroid)."
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The Role of Lead, Manganese, and Zinc in Autism Spectrum Disorders (ASDs) and Attention-Deficient Hyperactivity Disorder (ADHD): a Case-Control Study on Syrian Children Affected by the Syrian Crisis.
Hawari I1, Eskandar MB2, Alzeer S3.
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Abstract
Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are two developmental disorders that affect children worldwide, and are linked to both genetic and environmental factors. This study aims to investigate the levels of lead, manganese, and zinc in each of ASD, ADHD, and ASD with comorbid ADHD in Syrian children born or grown during the Syrian crisis. Lead and manganese were measured in the whole blood, and zinc was measured in the serum in 31 children with ASD, 29 children with ADHD, and 11 children with ASD with comorbid ADHD (ASD-C) compared with 30 healthy children, their ages ranged between 3 and 12 years. Blood lead levels were higher in the groups of ASD-C (245.42%), ASD (47.57%), and ADHD (14.19%) compared with control. Lead levels were significantly higher in children with ASD in the age of 5 or less compared with control, and they were also higher in the male ASD compared with females (P = 0.001). Blood manganese levels were lower in the groups of ASD-C (10.35%), ADHD (9.95%, P = 0.026), and ASD (9.64%, P = 0.046). However, serum zinc levels were within the reference range in all groups of study. Lead and manganese were positively correlated with each other (P = 0.01). Lead increase and manganese decrease may associate with the incidence of ASD, ADHD, or the co-occurrence of both of them together. Further studies are needed to examine the relationship between metal levels and the co-occurrence of ASD and ADHD together.
The Role of Lead, Manganese, and Zinc in Autism Spectrum Disorders (ASDs) and Attention-Deficient Hyperactivity Disorder (ADHD): a Case-Control Stu... - PubMed - NCBI
Hawari I1, Eskandar MB2, Alzeer S3.
Author information
Abstract
Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are two developmental disorders that affect children worldwide, and are linked to both genetic and environmental factors. This study aims to investigate the levels of lead, manganese, and zinc in each of ASD, ADHD, and ASD with comorbid ADHD in Syrian children born or grown during the Syrian crisis. Lead and manganese were measured in the whole blood, and zinc was measured in the serum in 31 children with ASD, 29 children with ADHD, and 11 children with ASD with comorbid ADHD (ASD-C) compared with 30 healthy children, their ages ranged between 3 and 12 years. Blood lead levels were higher in the groups of ASD-C (245.42%), ASD (47.57%), and ADHD (14.19%) compared with control. Lead levels were significantly higher in children with ASD in the age of 5 or less compared with control, and they were also higher in the male ASD compared with females (P = 0.001). Blood manganese levels were lower in the groups of ASD-C (10.35%), ADHD (9.95%, P = 0.026), and ASD (9.64%, P = 0.046). However, serum zinc levels were within the reference range in all groups of study. Lead and manganese were positively correlated with each other (P = 0.01). Lead increase and manganese decrease may associate with the incidence of ASD, ADHD, or the co-occurrence of both of them together. Further studies are needed to examine the relationship between metal levels and the co-occurrence of ASD and ADHD together.
The Role of Lead, Manganese, and Zinc in Autism Spectrum Disorders (ASDs) and Attention-Deficient Hyperactivity Disorder (ADHD): a Case-Control Stu... - PubMed - NCBI
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- Manganese Is Essential for Neuronal Health
- The impact of manganese on neurotransmitter systems
- Manganese in diet: bioaccessibility, adequate intake and neurotoxicological effects
- 2. Nutritional Requirements for Manganese | Manganese in Health and Disease (978-1-78262-238-3)
- Low Dietary Manganese Levels Exacerbate Experimental Colitis in Mice
- Impact of Dietary Manganese on Intestinal Barrier and Inflammatory Response in Broilers Challenged with Salmonella Typhimurium
- The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men
- Daily Copper and Manganese Intakes and Their Relation to Blood Pressure in Normotensive Adults
"Adults are able to absorb 8% of the Mn from human milk, but only 2% from cow’s milk, and <1% from soy-based formulas (63)."
"Radiolabeled 54Mn uptake studies show differential uptake of Mn based on gender; for a meal containing 1 mg Mn, adult males absorb 1.35 ± 0.51%, whereas adult females absorb 3.55 ± 2.11% (67, 93)."
"Younger individuals absorb and retain higher levels of Mn than adults (146, 312), most likely because their requirements for Mn are much higher than those for adults. This is especially true for infants."
"The mechanism by which Mn enters the bloodstream upon exiting the GI tract is poorly understood; however, it is known that distribution to tissues by plasma is quick. The estimated half-life for Mn to leave plasma is 1 min (162). Mn is distributed from plasma to the liver (30% of total Mn), kidney (5%), pancreas (5%), colon (1%), urinary system (0.2%), bone (0.5%), brain (0.1%), erythrocytes (0.02%), and the remaining 58.18% to the remaining soft tissues (162). The liver, pancreas, bone, kidney, and brain retain Mn more than other tissues and have the highest Mn concentrations in the body (10). This is likely due to the essential nature of Mn in energy production and the high energy demands of these tissues."
"Mn speciation is important in influencing how Mn is bound and transported in the blood (225, 305). Mn can exist in 11 different oxidation states; the most commonly ingested forms include Mn2+ and Mn3+. Mn2+ is the most predominant form found in the human body, although the exact percentage of the total Mn pool that consists of Mn3+ is unknown (243). Mn3+ is highly reactive and will undergo disproportionation to Mn2+ and Mn4+ unless stabilized in a complex with a ligand (305). Interestingly, Mn2+ can be oxidized in the blood to Mn3+ by ceruloplasmin (141). Mn2+ is bound by several species in the blood for transport and distribution. These include albumin (84% of total Mn2+), hexahydrated ion (6%), bicarbonate (6%), citrate (2%), and transferrin (Tf) (1%) (128, 200). Albumin is the major protein bound to Mn2+ (99, 217), with a KD of 0.63 × 10^(−4) M^(−1). Tf is a circulating Fe-binding protein that has affinity for Mn in both the Mn2+ and Mn3+ states (64). Tf-mediated transport of Mn3+ allows for delivery of Mn3+ to neuronal tissues similar to Fe3+Tf transport, though Mn3+Tf transport is noticeably slower and occurs to a lesser degree than other Mn transport processes (123)."
"Metabolic stress may alter Mn distribution in tissues, as suggested by a recent study that found decreased levels of Mn in the brain stem and frontal lobe after strenuous exercise relative to control conditions and moderate exercise (83). Dietary iron levels may have an impact on levels of Mn accumulation in the brain (96). Ceruloplasmin, a plasma protein involved in the oxidation and mobilization of iron, may also affect the distribution of Mn in brain tissues (141). These studies point to related mechanisms of Mn and Fe homeostasis."
"Arginase is an Mn-dependent enzyme that catalyzes the hydrolysis of arginine to ornithine in the urea cycle. The two isozymes of arginase, ARG1 and ARG2, have the same function but differ in their expression. ARG1, which has been found at higher levels in the brain, is found primarily in the cytoplasm, whereas ARG2 is found primarily in the mitochondria (307). ARG2 is expressed in neurons and glial cells of most brain structures, with particularly high levels of expression found in the neocortex, corpus callosum, putamen, and ventral striatum (29). Whereas metal requirements for arginases may differ between species, optimal catalytic function of human ARG1 specifically depends upon Mn2+ (60, 144). Arginase is expressed in endothelial cells, where it controls the production of nitric oxide by mediating the bioavailability of arginine (22, 303). The function of arginase in the brain has not been fully characterized, although studies suggest neuroprotective effects." "Arginase also plays a role in the neural immune response, contributing to neuronal protection and regeneration through microglial activation pathways (48) and polyamine synthesis pathways (71, 155)."
"Overexpression of MnSOD in AD-model brains has been shown to reduce oxidative stress (79)."
"No known neurological conditions have been medically established to be due to Mn insufficiency. However, recent research on Huntington’s disease (HD) has identified a deficiency in neuronal Mn handling associated with decreased neuronal Mn levels under both basal and elevated Mn exposure conditions (28, 178, 266, 276, 291, 293, 294). Although additional studies are needed to establish the relationship between alterations in Mn homeostasis and HD pathogenesis, several lines of evidence point to a potential role. For example, many critical Mn-dependent enzymes of the brain show diminished levels of activity in HD patients and other models of HD (36, 44, 45). Of particular note, intracellular Mn levels are reduced in the striatum of HD patients and other HD models (234). Mn-dependent activation of ATM signaling is impaired in both mouse and human neuronal models of HD and rescued by restoration of intracellular Mn levels (276). Also, impairment of ATM-dependent repair pathways of DNA double-strand breaks have been reported in irradiated HD human fibroblasts, suggesting that ATM may be implicated in HD pathology (90). Consistent with the hypothesis of decreased Mn transport, HD cells have an increased tolerance to Mn toxicity (294). The mechanism by which mutant Huntingtin (HTT) protein impairs Mn transport is unknown. However, the change of Mn levels in one cellular model of HD has been shown to be independent of Tf or DMT1 activity, despite the known alterations of iron homeostasis in HD (293). Of note, expression of ferroportin is increased and Tf decreased in the cortex and striatum in mouse models of HD (42). Taking into consideration how iron concentrations are elevated in striatal neurons in HD, this may be a compensatory mechanism."
"Dietary Mn deficiency has been found to decrease arginase activity and increase the activity of nitric oxide synthases (31, 82). Intracellular depletion of arginine by arginase may be neuroprotective (86, 160). Whereas inhibition of ARG1 leads to increased NO production, which contributes to neuronal death, inhibition of NO by ARG1 contributes to neuronal survival, as demonstrated by a surviving subpopulation of motor neurons deprived of trophic factors (87). Altered arginase activity (dependent on Mn as described above) has been implicated in the progression of HD. A urea cycle deficiency has been reported in HD. Increased ammonia and citrulline levels point to decreased arginase activity in these models (45). Neuronal nitric oxide synthase and dietary L-arginine, the NO precursor, have been shown to mediate the time of symptom onset in HD (68,69). Diminished GS activity has also been observed in HD brain (20, 40). Interestingly, decreased astrocytic GS expression and activity have been observed in the AD brain, especially in late stages of the disease (153, 205, 229)."
"Radiolabeled 54Mn uptake studies show differential uptake of Mn based on gender; for a meal containing 1 mg Mn, adult males absorb 1.35 ± 0.51%, whereas adult females absorb 3.55 ± 2.11% (67, 93)."
"Younger individuals absorb and retain higher levels of Mn than adults (146, 312), most likely because their requirements for Mn are much higher than those for adults. This is especially true for infants."
"The mechanism by which Mn enters the bloodstream upon exiting the GI tract is poorly understood; however, it is known that distribution to tissues by plasma is quick. The estimated half-life for Mn to leave plasma is 1 min (162). Mn is distributed from plasma to the liver (30% of total Mn), kidney (5%), pancreas (5%), colon (1%), urinary system (0.2%), bone (0.5%), brain (0.1%), erythrocytes (0.02%), and the remaining 58.18% to the remaining soft tissues (162). The liver, pancreas, bone, kidney, and brain retain Mn more than other tissues and have the highest Mn concentrations in the body (10). This is likely due to the essential nature of Mn in energy production and the high energy demands of these tissues."
"Mn speciation is important in influencing how Mn is bound and transported in the blood (225, 305). Mn can exist in 11 different oxidation states; the most commonly ingested forms include Mn2+ and Mn3+. Mn2+ is the most predominant form found in the human body, although the exact percentage of the total Mn pool that consists of Mn3+ is unknown (243). Mn3+ is highly reactive and will undergo disproportionation to Mn2+ and Mn4+ unless stabilized in a complex with a ligand (305). Interestingly, Mn2+ can be oxidized in the blood to Mn3+ by ceruloplasmin (141). Mn2+ is bound by several species in the blood for transport and distribution. These include albumin (84% of total Mn2+), hexahydrated ion (6%), bicarbonate (6%), citrate (2%), and transferrin (Tf) (1%) (128, 200). Albumin is the major protein bound to Mn2+ (99, 217), with a KD of 0.63 × 10^(−4) M^(−1). Tf is a circulating Fe-binding protein that has affinity for Mn in both the Mn2+ and Mn3+ states (64). Tf-mediated transport of Mn3+ allows for delivery of Mn3+ to neuronal tissues similar to Fe3+Tf transport, though Mn3+Tf transport is noticeably slower and occurs to a lesser degree than other Mn transport processes (123)."
"Metabolic stress may alter Mn distribution in tissues, as suggested by a recent study that found decreased levels of Mn in the brain stem and frontal lobe after strenuous exercise relative to control conditions and moderate exercise (83). Dietary iron levels may have an impact on levels of Mn accumulation in the brain (96). Ceruloplasmin, a plasma protein involved in the oxidation and mobilization of iron, may also affect the distribution of Mn in brain tissues (141). These studies point to related mechanisms of Mn and Fe homeostasis."
"Arginase is an Mn-dependent enzyme that catalyzes the hydrolysis of arginine to ornithine in the urea cycle. The two isozymes of arginase, ARG1 and ARG2, have the same function but differ in their expression. ARG1, which has been found at higher levels in the brain, is found primarily in the cytoplasm, whereas ARG2 is found primarily in the mitochondria (307). ARG2 is expressed in neurons and glial cells of most brain structures, with particularly high levels of expression found in the neocortex, corpus callosum, putamen, and ventral striatum (29). Whereas metal requirements for arginases may differ between species, optimal catalytic function of human ARG1 specifically depends upon Mn2+ (60, 144). Arginase is expressed in endothelial cells, where it controls the production of nitric oxide by mediating the bioavailability of arginine (22, 303). The function of arginase in the brain has not been fully characterized, although studies suggest neuroprotective effects." "Arginase also plays a role in the neural immune response, contributing to neuronal protection and regeneration through microglial activation pathways (48) and polyamine synthesis pathways (71, 155)."
"Overexpression of MnSOD in AD-model brains has been shown to reduce oxidative stress (79)."
"No known neurological conditions have been medically established to be due to Mn insufficiency. However, recent research on Huntington’s disease (HD) has identified a deficiency in neuronal Mn handling associated with decreased neuronal Mn levels under both basal and elevated Mn exposure conditions (28, 178, 266, 276, 291, 293, 294). Although additional studies are needed to establish the relationship between alterations in Mn homeostasis and HD pathogenesis, several lines of evidence point to a potential role. For example, many critical Mn-dependent enzymes of the brain show diminished levels of activity in HD patients and other models of HD (36, 44, 45). Of particular note, intracellular Mn levels are reduced in the striatum of HD patients and other HD models (234). Mn-dependent activation of ATM signaling is impaired in both mouse and human neuronal models of HD and rescued by restoration of intracellular Mn levels (276). Also, impairment of ATM-dependent repair pathways of DNA double-strand breaks have been reported in irradiated HD human fibroblasts, suggesting that ATM may be implicated in HD pathology (90). Consistent with the hypothesis of decreased Mn transport, HD cells have an increased tolerance to Mn toxicity (294). The mechanism by which mutant Huntingtin (HTT) protein impairs Mn transport is unknown. However, the change of Mn levels in one cellular model of HD has been shown to be independent of Tf or DMT1 activity, despite the known alterations of iron homeostasis in HD (293). Of note, expression of ferroportin is increased and Tf decreased in the cortex and striatum in mouse models of HD (42). Taking into consideration how iron concentrations are elevated in striatal neurons in HD, this may be a compensatory mechanism."
"Dietary Mn deficiency has been found to decrease arginase activity and increase the activity of nitric oxide synthases (31, 82). Intracellular depletion of arginine by arginase may be neuroprotective (86, 160). Whereas inhibition of ARG1 leads to increased NO production, which contributes to neuronal death, inhibition of NO by ARG1 contributes to neuronal survival, as demonstrated by a surviving subpopulation of motor neurons deprived of trophic factors (87). Altered arginase activity (dependent on Mn as described above) has been implicated in the progression of HD. A urea cycle deficiency has been reported in HD. Increased ammonia and citrulline levels point to decreased arginase activity in these models (45). Neuronal nitric oxide synthase and dietary L-arginine, the NO precursor, have been shown to mediate the time of symptom onset in HD (68,69). Diminished GS activity has also been observed in HD brain (20, 40). Interestingly, decreased astrocytic GS expression and activity have been observed in the AD brain, especially in late stages of the disease (153, 205, 229)."
- The impact of manganese on neurotransmitter systems
- Manganese in diet: bioaccessibility, adequate intake and neurotoxicological effects
"Plant-based foods are the major sources of Mn in the diet, as plants require uptake Mn from soil for their physiological processes and growing[24]."
"There are several food sources that have high Mn levels (~30 mg Mn/kg), for example, rice, nuts and, whole grains[3]."
"Mn levels have also been reported in fruits - pineapple (90.8 mg/kg), acai (145 to 1197 mg/kg)
, strawberry (4.9 mg/kg), banana (10.747 mg/kg)[40-43]."
"Oliveira et al. (2018)[41] demonstrated that acai (a native South American tropical fruit) which contains high amount of essential elements, including Mn and the percent of bioaccessible Mn ranges from 39-55% and bioavailability of 8% to 17% of total Mn concentration. Other berry fruits, such as strawberry, blackberry, raspberry, blueberry, grape and cherry are also important sources of Mn. The bioavailability of Mn in these fruits was reported by Pereira et al. (2018), showing that the bioaccessible fractions are approximately 35% of the total concentration of Mn present, where strawberry was the fruit with higher bioaccessibility (52%) and blueberry samples had lower value of the Mn (10%) than other fruits analyzed."
"In conditions associated with disturbances in enteral nutrition, where the gastrointestinal tract is no longer intact resulting in the loss of uptake of nutrients as macro and microelements, parenteral nutrition is used to replace the recommended dietary intake of essential elements as Mn. Parenteral nutrition is commonly used in ill infants and upon surgical resections[3, 84]. However, solutions administered in parenteral nutrition may contain higher levels of Mn and in some cases may lead to hypermanganesemia, which is a condition where occurs accumulation of excess Mn in tissues by decreased biliary excretion[85-87]. It should be noted that when administered intravenously, Mn in parenteral nutrition is 100% bioavailable while upon enteral nutrition only 3–5% is bioavailable[3, 88]."
"Mn and Ca2+ [] share transporters in the mitochondria and Golgi complex and changes in Ca2+ levels might result in impairments in ER-Golgi trafficking and mitochondrial function[127]."
"There are several food sources that have high Mn levels (~30 mg Mn/kg), for example, rice, nuts and, whole grains[3]."
"Mn levels have also been reported in fruits - pineapple (90.8 mg/kg), acai (145 to 1197 mg/kg)
, strawberry (4.9 mg/kg), banana (10.747 mg/kg)[40-43].""Oliveira et al. (2018)[41] demonstrated that acai (a native South American tropical fruit) which contains high amount of essential elements, including Mn and the percent of bioaccessible Mn ranges from 39-55% and bioavailability of 8% to 17% of total Mn concentration. Other berry fruits, such as strawberry, blackberry, raspberry, blueberry, grape and cherry are also important sources of Mn. The bioavailability of Mn in these fruits was reported by Pereira et al. (2018), showing that the bioaccessible fractions are approximately 35% of the total concentration of Mn present, where strawberry was the fruit with higher bioaccessibility (52%) and blueberry samples had lower value of the Mn (10%) than other fruits analyzed."
"In conditions associated with disturbances in enteral nutrition, where the gastrointestinal tract is no longer intact resulting in the loss of uptake of nutrients as macro and microelements, parenteral nutrition is used to replace the recommended dietary intake of essential elements as Mn. Parenteral nutrition is commonly used in ill infants and upon surgical resections[3, 84]. However, solutions administered in parenteral nutrition may contain higher levels of Mn and in some cases may lead to hypermanganesemia, which is a condition where occurs accumulation of excess Mn in tissues by decreased biliary excretion[85-87]. It should be noted that when administered intravenously, Mn in parenteral nutrition is 100% bioavailable while upon enteral nutrition only 3–5% is bioavailable[3, 88]."
"Mn and Ca2+ [] share transporters in the mitochondria and Golgi complex and changes in Ca2+ levels might result in impairments in ER-Golgi trafficking and mitochondrial function[127]."
- 2. Nutritional Requirements for Manganese | Manganese in Health and Disease (978-1-78262-238-3)
"The primary sources of Mn in the diet are whole grains and cereals. Other good sources are brown rice, pineapples, green leafy vegetables, dried legumes, nuts and tea. For example, the Mn content in one cup of tea ranges from 0.4 to 1.3 mg, and one-half cup of pineapple contains 0.77 mg. In contrast, meats, fat, sugar and white flour are poor sources of this mineral, as illustrated in Figure 2.1."
"In the past, diets were based on abundant amounts and varieties of whole grains and cereals, foods that are rich in Mn. But the nutrition transition that occurred in the United States (US) and other developed countries has shifted diets more towards those high in processed meats and energy-dense, high-fat foods, all of which are low in this element. Thus, the quantity of Mn in the diet has been reduced substantially in recent years."
"The Mn content in human breast milk is 3–8 mg/L, but this amount is much less than that present in infant formulas containing either cow’s milk (50–100 mg/L) or soy (200–300 mg/L).[8] [How appropriate to the values above!?] Cockell and Belonjea (2004)[9] also reported Mn levels in milk protein formulas (90±50 mg/L) to be less than in those which are soy based (310±80 mg/L). It has been postulated that the elevated levels of Mn found in soy formula may increase the susceptibility of an infant to Mn toxicity."
"The distribution of Mn in the body is dependent on the mitochondrial content of tissues, with the greatest deposition in mitochondrial-rich tissues such as bone, liver, kidneys, pituitary gland, and pancreas.[3]"
"Excretion of Mn from the urine is of less significance, and appears to be independent of dietary intake.[19]"
"Manganese acts as an activator for mevalonate kinase and farnesyl pyrophosphate synthase; the latter initiates the formation of a cholesterol precursor, squalene, in the biosynthesis of cholesterol.[49] In 2011, Bae and colleagues explored the influence of Mn on cholesterol synthesis in Ca-deficient ovariectomized rats. In animals fed a low-Ca diet for 12 weeks, Mn counteracted the effects of decreased cholesterol and low-density lipoprotein levels in blood.[53]"
"The recommendations for Mn across different countries vary considerably, as shown in Table 2.3."
"Numerous factors affect the bioavailability of Mn, including dietary components such as fiber, phytate, Fe, calcium, cadmium, fats, proteins, and polyphenols."
"Both soluble and insoluble fiber, as well as phytate, negatively influence the bioavailability of Mn. An example of the diminished absorption or enhanced excretion from the inclusion of these components is seen with consumption of vegetarian diets. The total Mn content of these diets is high owing to the abundance of plants, nuts and seeds that are naturally rich in this trace element. Despite high intakes of 2.9 to 4.6 mg per day, negative Mn balances (0.4 to 1.1 mg per day) have been documented in vegetarians(see Table 2.1)."
"Presumably, the negative amounts are the result of a reduced bioavailability of the mineral.[110] However, greater quantities of dietary Mn (7 mg per day) in vegetarian diets increased mean Mn balance to a positive 3.34 mg per day.[22] In 1998 Hunt et al. systematically investigated the effects of lacto-ovovegetarian or omnivorous diets in young women for 8 weeks in a crossover design. Although the lacto-ovovegetarian diet had double the amount of Mn when compared with the meat-based one (5.9 vs. 2.5 mg per day), the respective Mn balances (0.6 vs. 0.1 mg per day) did not differ significantly.[111]" "However, some studies have not demonstrated significant changes in Mn balance in humans consuming high-fiber diets.[110,113]"
"In rats, the addition of soluble fiber to the diet improved the viscosity of gut content, which enhanced fermentation and the formation of volatile fatty acids in the cecum.[115] In turn, these effects increased serum enteroglucagon concentrations, gastric emptying time and absorption of numerous minerals including Mn. Thus, the amount of Mn absorbed and retained may depend on whether the fiber is soluble or insoluble, naturally present in the diet, or supplemented."
"[..]soluble fibers may have quite different effects on Mn; these fibers include pectins, gums, resistant starches, lactulose, oligofructose and inulin."
"The author of this chapter found similar results when measuring the Mn plasma intake in response to an isolated insoluble fiber, alpha cellulose. In a Mn-tolerance test, a significant reduction in the plasma levels of the mineral was observed one-hour post dose (Figure 2.5). It is possible that isolated fibers exhibit effects on minerals that differ from those present in foods naturally abundant in fiber, such as wheat, bran, sunflower and vegetables.[116]"
"Phytate (the salt of insoluble hexa bisphosphate) is the storage form of phosphorus in plant tissues such as bran and seeds. This compound binds a variety of minerals via chelation to the oxygen in the phosphate moiety.[117] Davidsson et al. (1995) documented the influence of phytate and ascorbic acid on Mn absorption using labeled 54Mn in 16 young adults fed a dephytinized diet. The removal of phytate significantly increased Mn absorption from 0.7% to 1.6% (p<0.05), but this percentage absorption was still quite low. The doubling of the amount of ascorbic acid in the phytinized diet from 625 mmol/L to 1250 mmol/L had no influence on Mn absorption.[118] Therefore, despite the fact that whole grains, nuts and seeds are excellent sources of dietary Mn, the presence of fiber and phytates may limit bioavailability to a substantial degree."
"A variety of mineral interactions significantly affect both manganese requirements and metabolism. Minerals reported to exert adverse effects when ingested concomitantly with Mn include Fe, Ca and cadmium (Cd)."
"In a series of plasma tolerance tests in young adults, the addition of Ca, as either calcium carbonate (CaCO3) or in milk, diminished Mn absorption in plasma.[116] LikeTerma, the administration of 40 mg Mn as manganese chloride essentially blocked the uptake of 800 mg Ca, as shown in Figure 2.6. The concomitant administration of 2 mg Cu depressed Mn uptake a great deal, but the change was not significant. In contrast the provision of 50 mg Zn with the 40 mg Mn produced a rapid rise in the area under the curve (124%, p<0.05) for plasma Mn."
"In subjects with heartburn, Ca [carbonate] supplements elevated esophageal pH, producing an alkaline environment in the gastrointestinal tract which may have subsequently diminished Mn absorption.[127] However, Johnson et al. reported no differences in Mn absorption in young women who consumed diets consisting of 587 or 1336 mg Ca per day.[128] Thus, the impact of Ca on Mn uptake may be dependent on dose and pharmacological administration."
"The effect of dietary fat on mineral utilization was investigated by Kies et al. (1988), who provided a diet with two levels of total fat (30% and 40% of total calories), and cholesterol (300 and 600 mg per day) to 30 subjects. The Mn absorption was less negative when participants received the moderately high-fat diet (−28.63% to −30.60%), as compared to the low-fat (−7.11% to −7.80%) group. Thus, fat was believed to enhance Mn absorption,[131] perhaps due to the increased viscosity which created a slower transport through the intestine.[115]"
"[..]it appears that dietary protein is not a significant factor influencing Mn absorption."
"Tea is an excellent source of Mn; however, its bioavailability is diminished with the great abundance of polyphenolic compounds naturally present. An investigation of the Mn intake of tea drinkers reported intakes of 5.5–10 mg per day, as compared to 3.2 mg per day in non-tea drinkers.[134] However, indices of Mn status such as whole blood and plasma Mn, and superoxide dismutase expression, did not vary between the two groups. Thus, the abundant quantities of Mn in tea did not appear to translate to increased absorption and/or retention by tea drinkers, presumably owing to the presence of polyphenolic compounds."
"In the past, diets were based on abundant amounts and varieties of whole grains and cereals, foods that are rich in Mn. But the nutrition transition that occurred in the United States (US) and other developed countries has shifted diets more towards those high in processed meats and energy-dense, high-fat foods, all of which are low in this element. Thus, the quantity of Mn in the diet has been reduced substantially in recent years."
"The Mn content in human breast milk is 3–8 mg/L, but this amount is much less than that present in infant formulas containing either cow’s milk (50–100 mg/L) or soy (200–300 mg/L).[8] [How appropriate to the values above!?] Cockell and Belonjea (2004)[9] also reported Mn levels in milk protein formulas (90±50 mg/L) to be less than in those which are soy based (310±80 mg/L). It has been postulated that the elevated levels of Mn found in soy formula may increase the susceptibility of an infant to Mn toxicity."
"The distribution of Mn in the body is dependent on the mitochondrial content of tissues, with the greatest deposition in mitochondrial-rich tissues such as bone, liver, kidneys, pituitary gland, and pancreas.[3]"
"Excretion of Mn from the urine is of less significance, and appears to be independent of dietary intake.[19]"
"Manganese acts as an activator for mevalonate kinase and farnesyl pyrophosphate synthase; the latter initiates the formation of a cholesterol precursor, squalene, in the biosynthesis of cholesterol.[49] In 2011, Bae and colleagues explored the influence of Mn on cholesterol synthesis in Ca-deficient ovariectomized rats. In animals fed a low-Ca diet for 12 weeks, Mn counteracted the effects of decreased cholesterol and low-density lipoprotein levels in blood.[53]"
"The recommendations for Mn across different countries vary considerably, as shown in Table 2.3."
"Numerous factors affect the bioavailability of Mn, including dietary components such as fiber, phytate, Fe, calcium, cadmium, fats, proteins, and polyphenols."
"Both soluble and insoluble fiber, as well as phytate, negatively influence the bioavailability of Mn. An example of the diminished absorption or enhanced excretion from the inclusion of these components is seen with consumption of vegetarian diets. The total Mn content of these diets is high owing to the abundance of plants, nuts and seeds that are naturally rich in this trace element. Despite high intakes of 2.9 to 4.6 mg per day, negative Mn balances (0.4 to 1.1 mg per day) have been documented in vegetarians
"Presumably, the negative amounts are the result of a reduced bioavailability of the mineral.[110] However, greater quantities of dietary Mn (7 mg per day) in vegetarian diets increased mean Mn balance to a positive 3.34 mg per day.[22] In 1998 Hunt et al. systematically investigated the effects of lacto-ovovegetarian or omnivorous diets in young women for 8 weeks in a crossover design. Although the lacto-ovovegetarian diet had double the amount of Mn when compared with the meat-based one (5.9 vs. 2.5 mg per day), the respective Mn balances (0.6 vs. 0.1 mg per day) did not differ significantly.[111]" "However, some studies have not demonstrated significant changes in Mn balance in humans consuming high-fiber diets.[110,113]"
"In rats, the addition of soluble fiber to the diet improved the viscosity of gut content, which enhanced fermentation and the formation of volatile fatty acids in the cecum.[115] In turn, these effects increased serum enteroglucagon concentrations, gastric emptying time and absorption of numerous minerals including Mn. Thus, the amount of Mn absorbed and retained may depend on whether the fiber is soluble or insoluble, naturally present in the diet, or supplemented."
"[..]soluble fibers may have quite different effects on Mn; these fibers include pectins, gums, resistant starches, lactulose, oligofructose and inulin."
"The author of this chapter found similar results when measuring the Mn plasma intake in response to an isolated insoluble fiber, alpha cellulose. In a Mn-tolerance test, a significant reduction in the plasma levels of the mineral was observed one-hour post dose (Figure 2.5). It is possible that isolated fibers exhibit effects on minerals that differ from those present in foods naturally abundant in fiber, such as wheat, bran, sunflower and vegetables.[116]"
"Phytate (the salt of insoluble hexa bisphosphate) is the storage form of phosphorus in plant tissues such as bran and seeds. This compound binds a variety of minerals via chelation to the oxygen in the phosphate moiety.[117] Davidsson et al. (1995) documented the influence of phytate and ascorbic acid on Mn absorption using labeled 54Mn in 16 young adults fed a dephytinized diet. The removal of phytate significantly increased Mn absorption from 0.7% to 1.6% (p<0.05), but this percentage absorption was still quite low. The doubling of the amount of ascorbic acid in the phytinized diet from 625 mmol/L to 1250 mmol/L had no influence on Mn absorption.[118] Therefore, despite the fact that whole grains, nuts and seeds are excellent sources of dietary Mn, the presence of fiber and phytates may limit bioavailability to a substantial degree."
"A variety of mineral interactions significantly affect both manganese requirements and metabolism. Minerals reported to exert adverse effects when ingested concomitantly with Mn include Fe, Ca and cadmium (Cd)."
"In a series of plasma tolerance tests in young adults, the addition of Ca, as either calcium carbonate (CaCO3) or in milk, diminished Mn absorption in plasma.[116] LikeTerma, the administration of 40 mg Mn as manganese chloride essentially blocked the uptake of 800 mg Ca, as shown in Figure 2.6. The concomitant administration of 2 mg Cu depressed Mn uptake a great deal, but the change was not significant. In contrast the provision of 50 mg Zn with the 40 mg Mn produced a rapid rise in the area under the curve (124%, p<0.05) for plasma Mn."
"In subjects with heartburn, Ca [carbonate] supplements elevated esophageal pH, producing an alkaline environment in the gastrointestinal tract which may have subsequently diminished Mn absorption.[127] However, Johnson et al. reported no differences in Mn absorption in young women who consumed diets consisting of 587 or 1336 mg Ca per day.[128] Thus, the impact of Ca on Mn uptake may be dependent on dose and pharmacological administration."
"The effect of dietary fat on mineral utilization was investigated by Kies et al. (1988), who provided a diet with two levels of total fat (30% and 40% of total calories), and cholesterol (300 and 600 mg per day) to 30 subjects. The Mn absorption was less negative when participants received the moderately high-fat diet (−28.63% to −30.60%), as compared to the low-fat (−7.11% to −7.80%) group. Thus, fat was believed to enhance Mn absorption,[131] perhaps due to the increased viscosity which created a slower transport through the intestine.[115]"
"[..]it appears that dietary protein is not a significant factor influencing Mn absorption."
"Tea is an excellent source of Mn; however, its bioavailability is diminished with the great abundance of polyphenolic compounds naturally present. An investigation of the Mn intake of tea drinkers reported intakes of 5.5–10 mg per day, as compared to 3.2 mg per day in non-tea drinkers.[134] However, indices of Mn status such as whole blood and plasma Mn, and superoxide dismutase expression, did not vary between the two groups. Thus, the abundant quantities of Mn in tea did not appear to translate to increased absorption and/or retention by tea drinkers, presumably owing to the presence of polyphenolic compounds."
- Low Dietary Manganese Levels Exacerbate Experimental Colitis in Mice
- Impact of Dietary Manganese on Intestinal Barrier and Inflammatory Response in Broilers Challenged with Salmonella Typhimurium
- The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men
- Daily Copper and Manganese Intakes and Their Relation to Blood Pressure in Normotensive Adults
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Homo Consumericus
Member
The last time I ate liver was a 400 gram portion of lamb liver in one sitting. After digestion I experienced a strong headache, full body inflamation beyond what occurs from weighted exercise, and sharp pain around the molars farthest back in my mouth. This last issue was worst, as the gums swole up around the teeth to the point where they were partially hidden and bled a constant trickle. I was convinced that either the A vitamin, copper, or iron were to blame because no foods had previously had such effect. Not sure what I was reading at the time, but I took 16-24 milligrams of manganese (2-3 tablets from Solgar). Short while later all three issues had died down.
Never had the courage to eat ruminant liver again. My gums have never swollen up again since.
OP
Amazoniac
Member
- Role of some Critical Minerals in Nutrient Metabolism (uploaded as is in case the article disappears)
- Category:Manganese enzymes - Wikipedia
- BRENDA - Information on EC 2.1.1.12 - methionine S-methyltransferase
- Category:Manganese enzymes - Wikipedia
- BRENDA - Information on EC 2.1.1.12 - methionine S-methyltransferase
OP
Amazoniac
Member
Going crazy on manganese:
I might refine it later, include more inedible items and create a separate thread.
Heart of palm was a surprise, let's deforestate this world.
Cronometer was used.
- Manganese Content of Foods | Whole Food Catalog
I might refine it later, include more inedible items and create a separate thread.
Heart of palm was a surprise, let's deforestate this world.
Cronometer was used.
- Manganese Content of Foods | Whole Food Catalog
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EMF Mitigation - Flush Niacin - Big 5 Minerals
