Manganese And Its Unimportance In Health

[Amazoniac]

@paymanz Yes, bioaccessibility, I guess the term wasn't well defined in my head. Possibly it still isn't, but I was just trying to reconcile that. From my new understanding it seems that bioaccessibility is what is available for absorption in the GI but not what is necessarily absorbed. Bioavailability is sort of what I was thinking it read as, and that is what enters into circulation. Correct me if I am wrong! Analytical Methods for Determining Bioavailability and Bioaccessibility of Bioactive Compounds from Fruits and Vegetables: A Review

@Amazoniac Point taken!

So what I would like to know is, when they define the amount of a nutrient we are supposed to obtain in the diet, is absorption taken into consideration for the most part? So if it is said that we need 3mg a day of manganese (or whatever), I assume, based on my new understanding that in reality only a very small amount is actually absorbed, that it's simply 3mg of dietary manganese and not necessarily bioaccessible manganese let alone bioavailable? In other words, the actual amount we need absorbed is just something like 3% of 3mg?

If I'm not wrong, our fate-determiners usually deplete gurus then replete them while monitoring what they consider good markers for the nutrient status. When they suggest people to consume a certain amount of a nutrient, the absorption from foods isn't the main accounted factor. It's the specific amount of a nutrient that restores balance, regardless of the availability. It only factors in later when they consider what are the main sources of the nutrient, the supplement used, the possible interactions, etc; so that they can adjust the recommendation in a safer way.

 

[paymanz]

@schultz yes bioavailability and bioaccessible sound like same concept.

But from most articles i read ,human body highly regulates manganese absorption to prevent excess manganese from entering circulation.

So just a few percent of that bioavailable manganese is absorbed.

 

[paymanz]

The more phosphorus the less absorption of manganese, especially phytates....

.Absorption of 54Mn from MnCl2 (8.90%) was greater than from lettuce (5.20%), spinach (3.81%), wheat (2.16%) or sunflower seeds (1.71%),

 

[Nathan777]

Maple syrup has a ton of manganese in it right? I find quality maple syrup to be a great addition to milk.

 

[InChristAlone]

Yeah maple syrup, pineapple, berries, grape juice, bananas, potatoes, cinnamon!

 

[YourUniverse]

molasses

 

[mayweatherking]

i asked ray about this

"Ray Peat" wrote:
Once a week is more than enough.
>
> Ray,
>
> What do you think of Manganese? I noticed it is not high in dairy, but I know it is stored by the pancreas. I did notice it's in oysters. Would you say oysters a few times a week is enough to get it?

 

[paymanz]

i asked ray about this

"Ray Peat" wrote:
Once a week is more than enough.
>
> Ray,
>
> What do you think of Manganese? I noticed it is not high in dairy, but I know it is stored by the pancreas. I did notice it's in oysters. Would you say oysters a few times a week is enough to get it?

I really surprised by that.

Balance studies show we need 3-3.5 mg a day.

Maybe very high levels of manganese in some sea foods is why ray thinks like that.

 

[InChristAlone]

Hmmm.. oysters can be your source? You'd have to eat over 1 cup canned, to get the daily required. Not happening in my family!

 

[lollipop]

Very good my friend. Mention you too as well and God's glory be with you

Hey @Such_Saturation have you been microdosing some nootropics? Just kidding...

 

[Amazoniac]

i asked ray about this

"Ray Peat" wrote:
Once a week is more than enough.
>
> Ray,
>
> What do you think of Manganese? I noticed it is not high in dairy, but I know it is stored by the pancreas. I did notice it's in oysters. Would you say oysters a few times a week is enough to get it?

I think he had zinc in mind, it would make more sense, for manganese it doesn't.

I suppose he would be mentioning pineapples more often if it wasn't for the idea that they are a source of serotonin. This is questionable and the bad reaction probably comes from something else. Sometimes it's not easy to find great pineapfels, the harsh ones are often opaque with a white pulp (a mere coincidence, I'm not implying that everything that's white out there is inferior). The mild ones are clear with a yellow coloration.

 

[Such_Saturation]

Hey @Such_Saturation have you been microdosing some nootropics? Just kidding...

Manganese comes in some uncommon sources

 

[Mossy]

Interesting that the Linus Pauling Therapy would suggest to "Reduce manganese intake", for heart health.

But, it also recommends to "Eliminate ordinary sugar...avoid supplemental calcium...supplement with arginine...supplement with melatonin...".

I always find it challenging, and interesting, when two respected minds (Peat and Pauling) have such opposing views.

For the record, I realize manganese is not as much of, if not at all, a Peatism.

 

[Amazoniac]

- Manganese Superoxide Dismutase: Guardian of the Powerhouse

"Manganese superoxide dismutase (MnSOD) is the major ROS detoxifying enzyme of cells because of its localization to mitochondria. Altered function or expression of MnSOD can have remarkable consequences on mitochondrial function and the overall health of cells due to oxidative damage to various mitochondria-localized metabolic processes, leading to the development of different diseases [27,28]."

"Mitochondria are the main source of ROS (particularly superoxide radicals) in the cell due, in part, to the oxygen metabolism that occurs at this organelle [29,30]. Multiple enzymes in the electron transport chain are responsible for superoxide production [31], with complexes I (NADH-ubiquinone oxidoreductase) [32,33] and III (ubiquinol-cytochrome c oxidoreductase) [34] as major sites of superoxide production." "Complex II also adds to the total amount of superoxide radicals produced by mitochondria." "Other enzymes within the mitochondria not directly tied to the electron transport chain are also sources of mitochondrial ROS."

"Superoxide radicals contribute to the production of other reactive oxygen species that further damage mitochondria. Mitochondria possess many proteins with iron-sulfur centers that are susceptible to attack by superoxide, resulting in the release of free iron cations into the mitochondria. Iron cations participate in the production of hydroxyl radicals from hydrogen peroxide through the Haber-Weiss reaction [52–55]. Superoxide radicals also react with mitochondrial nitric oxide to produce peroxynitrite, a reactive nitrogen species (RNS) [56]. Peroxynitrite can modify various amino acids in proteins, including oxidation of sulfhydryl groups on proteins [57] and the nitration of tyrosine residues [58]. Mitochondrial enzymes are no exception to attack by peroxynitrite [59], with such diverse targets as electron transport chain components complex I [60–63], complex II [61,63], and complex V [61], as well as glutathione peroxidase [64], aconitase [65,66], and MnSOD."

"Because of the deleterious effects of ROS, the cell is equipped with several enzyme systems to detoxify ROS produced throughout the cell [67,68]. Superoxide dismutases are the major ROS detoxifying enzymes of the cell [69] and catalyze the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen [70]. Glutathione peroxidase [71,72], peroxiredoxins [73], and catalase [74] decompose hydrogen peroxide generated by SODs to water. Three types of SOD are expressed by cells, encoded by separate genes (reviewed in [75]). Copper- and zinc-containing SOD (CuZnSOD, SOD1) is a homodimer primarily localized to the cytoplasm [76], though, small amounts of CuZnSOD have been identified in the intermembrane space of mitochondria [77,78]. Extracellular SOD (ECSOD, SOD3) shares significant amino acid homology with CuZnSOD (40–60%), contains both copper and zinc in its active site, but is localized to the extracellular region of the cell [79,80]. MnSOD is a homotetramer [81–83] localized exclusively in the mitochondrial matrix [77,78] and is found in multiple organisms, including Saccharomyces cerevisiae [82], the red alga Porphyridium cruentum [84], Escherichia coli B [85], and chicken liver mitochondria [78]."

"Numerous studies in different model systems demonstrate the indispensable role for MnSOD in protecting aerobic life from the deleterious effects of oxygen." "Complete knockout of MnSOD has no effect on embryonic development, but leads to death shortly after birth."

"Interestingly, a 100% increase in cancer incidence was observed in MnSOD heterozygous knockout mice compared to wild-type controls. In a study by Copin et al. [104], mice were generated that simultaneously overexpressed CuZnSOD and were deficient in MnSOD. Overexpression of CuZnSOD did not compensate for the neonatal lethality caused by decreased MnSOD expression, suggesting that localization of the antioxidant enzymes is vital to oxidative-stress related cellular damage."

"Ikegami et al. developed a MnSOD flox mouse, and used this mouse to develop a liver-specific MnSOD knockout model. The researchers found that knockout of MnSOD in the liver had no effect on morphology and there was no increase in oxidative damage as determined by lipid peroxidation, suggesting that either the liver contains compensatory mechanisms to protect from oxidative stress or the liver is susceptible to systemic oxidative stress [107]."

"[..]overexpression of the antioxidant enzymes CuZnSOD, catalase, or a combination of CuZnSOD with either catalase or MnSOD does not increase the life span of mice [113]."

"[As mentioned, complexes] I, II, and III are sources of superoxide [] and potential victims of the very superoxide they produce, in part, due to the presence of iron-sulfur centers in key subunits of all three complexes [115–120]. These complexes are also susceptible to oxidative modification of key amino acids by superoxide and other ROS/RNS [reactive oxygen/nitrogen species], which can affect their activities. For example, in a study by Chen et al. on the complex I subunit NADH dehydrogenase, Cys206 and Tyr177 were two amino acids susceptible to oxidative modification, causing a decrease in the electron transport function of complex I [121], and this type of auto-oxidation of complex I may be involved in Parkinson’s disease [122]."

Rosacea, inflammation, and aging: The inefficiency of stress
"mitochondrial Complex-I, NADH-ubiquinone reductase, is probably the most easily damaged part of the mitochondrion, and it is protected by vitamin K"​

"MnSOD is important for the scavenging of superoxide generated by the electron transport chain complexes and may be important in preventing ROS-induced inactivation of these complexes."

"The TCA cycle (also known as the Krebs cycle) is a vital metabolic pathway in mitochondria, providing reducing equivalents that are fed into the electron transport chain for ATP production and generating substrates used in a variety of cellular processes. Altered activity of various enzymes in the TCA cycle has been linked to different neurological diseases and cancer [9,149].

Aconitase, the enzyme that catalyzes the conversion of aconitate to isocitrate [9], contains iron-sulfur centers and is susceptible to deactivation by superoxide [65,150,151] leading to release of Fe(II) from the enzyme (reviewed in [152])."

"The mitochondrion is vital for proper iron handling and utilization [158] and is the site of two important iron-consuming processes: the synthesis of iron-sulfur centers [159] and heme [7]. Mitochondria are also important for intracellular iron storage by virtue of the presence of a mitochondria-specific ferritin (reviewed in [160]). Improper sequestration and use of iron can lead to iron-induced oxidative damage [161] and is associated with several disorders" "Altered expression or mutations of MnSOD can have dramatic effects on cellular iron handling."

"[..]studies suggest that decreased MnSOD expression or activity causes accumulation of iron in cells, specifically within mitochondria. Increased MnSOD expression or activity may prove valuable for the treatment of iron toxicity caused by numerous diseases." "[..]iron metabolism and MnSOD expression are tightly regulated, that a feedback mechanism is present in cells to carefully balance iron metabolism and oxidative stress, and diseases can result from an upset of this balance."

"Several mechanisms have been implicated in MnSOD protection from apoptosis. [Temporary?] MnSOD overexpression protects from mitochondrial dysfunction and loss of mitochondrial membrane potential caused by various agents that induce apoptosis, including ionizing radiation [187], as well as Fe(II), amyloid β-peptide, NO generating agents [188], and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) [189]. MnSOD also prevents the release of various proteins from mitochondria that carry out apoptosis, such as cytochrome c [187] and Smac/DIABLO [189]."

"MnSOD also affects apoptosis stimulated by inflammatory cytokines."

"Tumor necrosis factor (TNF) induces apoptosis, in part, by stimulating mitochondrial ROS production [192]. MnSOD expression is stimulated by TNF and may act as an adaptive response to protect cells from further exposure to TNF [193]. As a demonstration of this concept, overexpression of MnSOD confers protection of a variety of cell lines against apoptosis induced by tumor necrosis factor (TNF) [194]. This adaptive response may protect cells from apoptosis caused by other toxic agents."

"Mitochondria are important for the initiation of immune responses." "[..]studies suggest a role for autophagy for the removal of damaged mitochondria, which prevents the activation of innate immunity through inflammasome formation. When autophagy is inhibited, damaged mitochondria accumulate, resulting in increased basal levels of mitochondrial ROS and increased inflammasome formation. These studies also suggest exciting possibilities for mitochondrial antioxidant enzymes, particularly MnSOD, in the regulation of innate immunity and inflammatory diseases through both inflammasome-dependent and -independent mechanisms."

Koch wrote:

"In the muscular dystrophies, the thymus is the essential deficient tissue upon which the muscle deficiency depends. In both the thyroid and in the complete thymus deficiencies, the inability to accept energy into the functional mechanisms is evident in the hyperplasia of the gland, and the increased use of oxygen and higher basal metabolism rate. In the thyroid case, the BMR was as high as 104%, but in complete thymus deficiency cases it is very much less elevated, though enough to indicate the inability to use the energy of ATP. It is also evident that the thymus defect may not be complete, but may depend on the inability to use its specific trace element, manganese, as a thyroid case may not use iodine, or an anemia case may not use cobalt. So one must provide a concept of how the thymus gland works as we have for diabetes, especially, because orthodoxy has no solution.

There are a few facts that can be organized for a practical pattern of its function. Alpha tocopherol is essential to its function as well as manganese. The spent product of tocopherol appearing in the urine is in the form of the hydroquinone of tocopherol. Therefore, our Thesis is simply that tocopherol is oxidized to the quinone, which on performing its task, is reduced to the hydroquinone. In other words, the manganese is used by the thymus Hassall’s cells as a co-factor, possibly as the trioxide, to oxidize tocopherol to its quinone and the quinone serves as an oxidizing agent (hydrogen or electron acceptor) in the further function of the gland, as in the production of a substance for the development and function of the muscles, and of the reproductive system. In this latter function, the use of ATP is required and when the FCG of energy acceptance of the Hassall’s cells cannot accept this energy because of a block via an integrated pathogen; thus the thymus and muscle deficiencies are complete until the block is removed. Many years ago we used the serial system of Carbonyl groups and those as activated in Benzoquinone, to accomplish the liberation of the FCG.

But the deficiency in the thymus may not be complete and may involve the simple oxidation of manganese to its trioxide. The supply of fair but non-toxic amounts of manganese to the tissues in general Josephson (8) found would correct such cases. Evidently the chain of subsequent processes was unimpeded and the body cells in general oxidized the manganese. But when the FCG of energy acceptance is integrated with a pathogen, the use of the Reagent given to the thyroid cases, is also required to reverse the disease picture in Parkinson’s disease, myasthenia gravis, and some other forms of muscular dystrophy, as reported by our collaborators."​

"mtDNA [mitochondrial] is susceptible to damage induced by a variety of agents, including ultraviolet [228] and ionizing radiation [229], as well as ROS [127,228,229]." "Cortopassi and Wang found that mtDNA sequences that encode various Complex I subunits are statistically more susceptible to damage, which may contribute to increased superoxide production and age-related diseases [231]."

"A vicious cycle [can be] set in motion in which mtDNA damage results in altered mitochondrial function, leading to increased ROS production, which causes more mtDNA damage [234]."

"Polγ is susceptible to oxidative stress-mediated inactivation, which may affect mtDNA replication and repair."
..and she also wants a cracker.

"MnSOD plays an important role in protecting mtDNA from ROS-induced damage."

"Oxidative mtDNA damage increases with age in mice, but this damage is much greater in the livers of MnSOD heterozygous knockout mice compared to wild-type controls [103]. MnSOD expression is increased in peripheral blood mononuclear cells from type 2 diabetic patients as an adaptive response to increased oxidative mtDNA damage in these cells [237]. In bovine retina endothelial cells, overexpression of MnSOD or treatment with a MnSOD mimetic inhibits oxidative mtDNA damage caused by high glucose, resulting in an increase in the expression of various electron transport chain components compared to cells treated with glucose alone [238]. Overexpression of MnSOD also protects mtDNA from oxidative damage induced by exposure to UV radiation [228], as well as mtDNA damage and depletion caused by acute ethanol exposure [129,239]. MnSOD has been identified as part of the nucleoid complex, where it interacts with mtDNA, Polγ, and glutathione peroxidase and may play a role in protecting mtDNA from oxidative stress-induced damage [240]."

"Lipids, especially polyunsaturated lipids, are susceptible to attack by ROS. A variety of compounds resulting from lipid peroxidation have been identified, such as 4-hydroxynonenal and malondialdehyde, as well as products derived from the oxidative attack of cholesterol, cholesterol esters, and sphingholipids [242]. Lipids are also vulnerable to attack by RNS to form different oxidation and nitration products [243–246], and these RNS-derived lipid peroxidation products may have importance in such diverse functions as inflammation [243] and ischemia/reperfusion injury [247].

Altered MnSOD expression or activity can also have consequences on total cellular, and mitochondrial, lipid integrity. Heterozygous MnSOD knockout mice have substantially more lipid peroxidation (as determined by immunohistological staining for 8-isoprostane, a marker of lipid peroxidation) at day 10 after birth compared to wild-type counterparts [248]."

"Since MnSOD contains manganese in its active site [85], factors that affect manganese availability can also have a marked effect on lipid peroxidation. Manganese deficiency significantly reduces age-related increases in MnSOD activity compared to manganese-sufficient rats, correlating with a 5-fold increase in lipid peroxidation in manganese-deficient rat liver compared to a 3-fold increase in rats receiving adequate amounts of manganese [251]. Malecki and Greger found that lipid peroxidation was greater in rat heart mitochondria in animals deficient in Mn compared to rats receiving adequate amounts of manganese, which inversely correlated with MnSOD activity [252]. Manganese deficiency has been identified in patients with sundry diseases, including epilepsy [253], diabetes mellitus [254], and patients receiving hemodialysis [255]. Future studies of how this manganese deficiency correlates with MnSOD activity and lipid peroxidation in these, and other, diseases may provide important insights into mechanisms of disease development."

"Cardiolipin is a tetra-acylated glycerophospholipid composed of two phosphotidyl groups linked by glycerol, resulting in a lipid with four hydrocarbon chains and three chiral centers [256] Cardiolipin is found almost entirely in the inner mitochondrial membrane [257]. Altered levels and composition of cardiolipin is associated with various diseases involving mitochondrial dysfunction, including ischemia/reperfusion injury, diabetes, heart failure [258,259], aging [260,261], and cancer [262–264]."

"Cardiolipin is vital for the proper function of many mitochondrial activities. For example, cardiolipin is important for the initiation of apoptosis [269–275]. Peroxidation of cardiolipin leads to the release of cytochrome c from mitochondria [270,276] and opening of the permeability transition pore (PTP) by inactivation of the adenine nucleotide translocator (ANT) [270]. Cardiolipin is vital for the activities of individual components of the electron transport chain [277] and the assembly of these components into supramolecular complexes [278,279]. Cardiolipin is susceptible to peroxidation by ROS [261,280,281], and ROS-mediated inactivation of different complexes of the electron transport chain parallel oxidative damage of cardiolipin."

"[..]studies imply a potential mechanism for MnSOD in protecting mitochondria from ROS-induced damage by preventing cardiolipin peroxidation."​

- Mitochondrial Dysfunction Due to Lack of Manganese Superoxide Dismutase Promotes Hepatocarcinogenesis

"Mitochondrial dysfunction, one of the hallmarks of tumor cells, is associated with an imbalance of the antioxidant defense and an increased production of reactive oxygen species (ROS) resulting in oxidative stress. Among the first line of defense against oxidative stress is the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen by superoxide dismutases (SODs); in mitochondria, this task is carried out by manganese superoxide dismutase (MnSOD).

Accordingly, carcinogenesis may be expected to be associated with a dysregulation in the expression of antioxidant enzymes such as MnSOD. Indeed, first reports showed low levels or absence of MnSOD in many tumor types (3, 47), whereas forced expression of MnSOD could prevent the tumorigenic phenotype in melanoma, breast cancer, and glioma cells (8, 38, 57, 70). In addition, recent studies have reported that reduced MnSOD expression in primary tongue squamous cell carcinoma is associated with lymph node metastasis (40). In contrast, increased levels of MnSOD were found in progressive and metastatic breast, pancreatic, gastric, colorectal prostate, and lung carcinomas (12, 42), and findings from mouse experiments propose that MnSOD expression switches between early and advanced stages of skin cancer (13)."

"Interestingly, the direct role of MnSOD in hepatocellular carcinoma has not been widely addressed, although from all organs investigated so far, MnSOD activity was shown to be highest in the [human] liver (32). Recent studies indicate that MnSOD promoter mutations may contribute to the carcinogenic process in hepatocarcinoma cells (65), and studies in mice suggested that lack of MnSOD may affect liver development (25, 36), likely without affecting the integrity of mitochondrial the NA (10)."

"First evidence that MnSOD deficiency contributes to carcinogenesis and malignancy came from numerous reports showing a relative reduction of MnSOD in many solid tumors (54, 66). In addition, two MnSOD variants (23), showing either reduced mitochondrial translocation or enzyme activity (2, 55), were associated with a higher incidence of cancer (44, 62), which points to the role of MnSOD as a tumor suppressor, and of oxidative stress as a promoter of liver tumors."

"Although the ROS generated due to MnSOD deficiency do not necessarily need to be carcinogenic, they can initiate or participate in reactions that contribute to transformation of cells and to a carcinogenic process. The concept that loss of MnSOD leads to a transformed cell type is supported by our findings from hepatocyte-specific MnSOD-KO mice displaying an enhanced number of GST-P-[placental glutathione S-transferase, a member of the GST family known as a reliable marker for hepatocarcinogenesis (52)] and GS[glutamine synthetase]-positive cells. Enhanced levels of GST isoenzymes as precancerosis markers were also found in hepatic preneoplastic nodules (7), suggesting that hepatocyte-specific loss of MnSOD induces development of hepatocellular carcinomas."

"MnSOD deficiency in the livers of male humans and rodents has been associated with nonalcoholic fatty liver disease (NAFLD) (35). While NAFLD does not necessarily lead to liver cancer, it is a known cause of chronic liver disease, which possesses a risk for progression to cirrhosis and hepatic carcinogenesis (43). Although not enough epidemiological data are available to show whether loss of MnSOD is cause or consequence of NAFLD, our findings provide a link indicating that loss of MnSOD may be carcinogenic."​

Unimportant publications:

- https://www.tandfonline.com/doi/abs/10.1080/10715760100300281
- The Interaction of Mitochondrial Iron with Manganese Superoxide Dismutase
- https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(18)30007-2
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859767/
- https://link.springer.com/chapter/10.1007/978-3-319-30705-3_3
- https://www.hindawi.com/journals/er/2011/387176/
- https://www.liebertpub.com/doi/abs/10.1089/152308604773934242

Unimportant posts:

- https://raypeatforum.com/community/...otoxin-edwardjedmonds.6448/page-3#post-310134
- https://raypeatforum.com/community/...ineapples-and-tomatoes.836/page-3#post-310169

 

[smith]

Is anything known to chelate labile manganese particularly well out of other heavy metals?
That would be useful for synthetic fungal infections which produce toxic amounts of manganese oxide in the brain.

 

[ddjd]

Whenever I take manganese my lymph nodes flare up

 

[paymanz]

However!

Lol what is that?!

 

[Amazoniac]

Is it possible that lack of manganese leads to adverse effects to (red) light? There are various posts from members complaining about it.
- My Log On EMF At Home Investigation

Lol what is that?!

paymanz, you've been looking like Gadsie and Stryker, but don't worry because you're special, in sui genesis.

 

[methylenewhite]

Manganese encephalopathy is kinds scary thing. There are lots cases of manganism in Russia caused by illicit methcathinone production using manganese permanganate as an oxidiser. Are manganese supps really safe?

 

[BigChad]

@Amazoniac I don't understand, you are saying manganese is not important for health in both your post and the title. You posted a lot of studies showing it is beneficial. Should we not be supplementing with manganese