my low manganese diet - my success so far

percyval577

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I want to tell about and discuss one of two components. The weighting ratio remains unclear so far.


I started my low-manganese diet in August 2015. Slowly but steadily (sometimes chaotic) my missfeelings lessend, and now I even feel good sometimes.

On the other hand my ability to think is worse, and the faster my feelings grow good the more I get shaked - sometimes without being prepared for that horror, "He is crazy." But this can be understood and (my confidence truly tells me) will not last. Sometimes I am already going to be souvereign now (but not often).

As far as I can see I will recover completly.


There might be a second component, a somehow serious infection. It would be thinkable that this component differs from person to person or from region to region, but the first component seems to be common: there are hints enough from good science. I summed them up (for the first time?).

The weighting ratio remains unclear so far.


It is common known that manganes-rich food is not necessary. In respect of low-manganese food I can tell from my experiences:
  • Meet from non-mammals do increase the need for manganese (arginase). I don´t eat them more often than once a week. Otherwise I sometimes had got problems with coordination (glutaminsynthase).
  • Milk, yoghurt and cheese do increase the manganes-uptake strongly. I only consume milk and yoghurt very very isolated (if at all). Otherwise I got to states of mind that you will not bear for some longer time.
  • No physician critisized my food. And until now I cannot detect any damage, but I do not suffer from any other sickness.

In some detail then (it´s in principle about epigenetics):
  • The direct sources of what I think is one of the mainpoints
  • What the reason for the Mn-dependency of the iNOS could be
  • The indirect sources of what I think is one of the mainpoints
 
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percyval577

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Do you need manganese to make Mn-SOD to get rid of superoxide molecules made by mitochondria as they produce ATP?

Yes, you do. This obviously is to think about at first rate. There exists a genetic mutation, where Mn-SOD does not work. People tend to get a faty liver when they proceed in getting older. The cause were ROS. I will try to refind the source.

In issues like this I was interessted right at the beginning. Well, I´ve to say, I had come from a state of feeling, where I would have given at least one leg. In respect of Mn-SOD absence I expected something to find like getting cancer. I surched only for three times.
I found this very thought but I also found the thought that goes right the other direction: ROS would damage cancer cells as well as other cells, and might be even a help. But as far as I got across, there are still no proofs for any of the possibilities. (Cancer is an illness of the DNA-care, not an illness of the DNA itself, as there are everytime damages.)


Furthermore, the mitochondria hypothesis is of interesst. Nitrosative stress would cause mitochondrial disfunction. Now there could arise already two problems for mitochondria: less Mn-SOD and to much nitric oxide.

With Q10 (helping mitochondria) I detected an effect that lasts for 25 minutes, quit detectable in a combination of Doxcycline 25 mg (which al to soon lost his very good effect) and Resveratrol (which did only in combination with Doxcycline). Doxcycline and Resveratrol both inhibit nitric oxide production, so the goal could be completly the same.

But I experienced sudden clearences of my fog, with many a power all over (this good experience appeared only seldom). So I think that mitochondrial disfunction is nor a lasting problem nor the major one. I think that nitric oxide is the major problem, and yes, it does target not only nerves but also mitochondria indeed:
(In my opinion not only synapses do come and go, but mitochondria as well.)
 
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percyval577

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Which SOD SNP are you referring to?
Your first question might be more precise than my answer was meant.

There are two possibilties how metal-enzymes can work, if I am remembering right:
  • the metal stays inside the molecule (or where ever it may be)
  • the metal comes and goes when the enzyme acts
I already do not know if there is an enzyme Mn-SOD that can not take up his requested manganese,
or if there is an enzyme Mn-SOD that does not exist because of the damage to be build.

And I don´t know, which genetic defects in detail are already have been found that can make Mn-SOD to fail.
I only thought: Well, without enough manganese, there could arise a problem with mitochondria or ROS.
But with any genetic drop out for Mn-SOD - what happens?
The only answer I´ve found was: not to much (a faty liver perhaps).
So, if I suffered from such genetic defect, no change in this respect should occure.
If I didn´t suffer from such a defect, it will still work at least a little bit.
(But until now, 30 months later, nothing else seems to take place, so far.)


Of course, it can not be ruled out that there could be more causes for such state of mind we are talking about.
When my symptoms in 2010 suddenly became strong again, very strong, I could not lift up things of some weight for about nine days. I thought already: This is caused by dysfunction of the nerves, despite it feels like a dysfunction of muscles. Well, mitochondria are affected, but as far as I can tell about me, not serious as it seems.

I say this while I am knowing, genetics from mitochondria-"cells" (prokaryontic) are more vulnerable than genetics of other human cells (eukaryontic). And yes, that´s a danger for all animals and us.
(Therefore, al lot of genetics for mitochondria are stemming already from our eukaryontic cells.)
 
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Learner1

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As a stage 3 cancer survivor homozygous for all of the SOD2 SNPs, I'm very thankful you brought this topic up. I've tested low in manganese, high in iron, and there's something wrong with my mitochondrial function.

SOD2 uses MnSOD in the mitochondria.

Obviously, as with too much of anything, too much manganese can be toxic, but it doesn't seem wise to be low in it either.

Poor mitochondrial function is implicated in most diseases of aging. Optimizing mitochondrial function seems prudent.
 

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percyval577

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As a stage 3 cancer survivor ... I've tested low in manganese, high in iron, and there's something wrong with my mitochondrial function. -- SOD2 uses MnSOD in the mitochondria.
-- ... too much manganese can be toxic, but it doesn't seem wise to be low in it either. -- Poor mitochondrial function is implicated in most diseases of aging. ...
I want to replie quit soon. In cancer cells manganese is high, but in the tissue about (fibro-xy, how is it called?) it differs. For example, in pancreas cancer it´s low as it is in all of that kind (say I). But in other cancer-enviroments (say II) it´s high (I don´t remember which ones).

So, if you were suffering from a cancer type (II), you could even try low manganese. Well, to have been tested with low manganese, it might be much to bold to say, all the cancer cells are feeding up their telomerase or what ever with your manganese.
On the other hand, suffering from cancer type (I) does not allow any advise so far (if you would have wanted).


About aging I would roughly say: Most of the animals die after a few years. This is necessary, because the world changes quickly. And, sorry, they are to stupid to adopt. Genetic must do it. Therefore they die early.
But some, intelligent enough for their enviroment, whales for example, can get very old, up to 400 years. So getting old is genetic.
 
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percyval577

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Thanks, I am cancer free and hope to remain so. Having adequate nutrients, including manganese is a part of the strategy my doctor has recommended.
I wish you for shure the best.

My point would be, that high manganese implicates high nitric oxide,
at least at some circumstances (infection, what strong ever it would be).

I will continue this thought soon.
 

Learner1

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I had low manganese, high peroxynitrites, and plenty of infections. Likely this all needs to be looked in context. There are many variables. Looking forward to more info. ;)
 

percyval577

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I had low manganese, high peroxynitrites, and plenty of infections. ...
Without knowing any great deals from other sicknesses I would list from a logical point of view the following sentences, which contain both nitric oxide (NO) and reactive oxygene species (ROS), both of which affect mitochondria. I would claim, that this is not by accident but made and still makes sence, in respect of mitochondria, round about since 600.000.000 years or so.

iNOS..............Mn-SOD​
1. lower manganese....->...lower NO......higher ROS.
2. higher manganese...->...higher NO......lower ROS


Peroxynitrite (ONOO-) builts up from NO, see for example above Finocchietto, Franco et al. 2009.
With an infection, there is more NO from iNOS (inducible Nitric Oxide Synthase), thus more ONOO-.
If you suffer with ME/CFS it´s a good hypothesis, that you have to much NO
(maybe without a realy serious infection).
ONOO- is only one example of reactive nitrogene species (RNS), but a serious one.

It would be possible that in your brain manganese is not low, and ONOO- ... well I don´t know.
 
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Learner1

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The papers I shared might provide insight.

The approach I'm taking which seems to be helping is taking high dose B12, C, and folate (and co factors like B6 and magnesium), ensuring RBC minerals are adequate, taking lipid replenishment for mitochondrial membranes in the form of NT Factor, and feeding mitochondria with NAD+, B2, CoQ10, and PolyMVA.

Any other thoughts?
 

percyval577

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B12, C, and folate (and co factors like B6 and magnesium), ... NAD+, B2, CoQ10, and PolyMVA.
I agree, I take the most of them as well. I didn´t know about PolyMVA, about NAD+ I knew, but I´ve forgotten to surch for (I forget a lot of things).

If you like, one of my goals is indeed to reduce peroxynitrite!!
 
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percyval577

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The direct sources of what I think is one mainpoint

Manganese is referred to mostly in terms of intoxination from fume. But we should use the insights in respect to non-toxic levels as well, if it makes sence. Two publications have come to the same conclusion:
more manganese (Mn) means more nitric oxide (NO).


Filipov et al. 2005 - "Manganese potentiates In Vitro Production of inflammatory Cytokines and Nitric Oxide by Microglia Through a Nuclear Factor kappa B-dependent Mechanism."

"In the absence of LPS, Mn moderatley increased interleukin-6 and tumour necrosis factor alpha (TNF-alpha) production only at higher Mn concentrations, which were cytotoxic. At all LPS doses, however, proinflammatory cytokine production was dose-depently increased by Mn. Similarly, LPS-induced NO production and iNOS expression were substantially enhanced by Mn."

And there are of course every second many small LPS (bacterial fragments) in the brain.


Chen et al. 2006 - "Manganese modulates proinflammatory gene expression in activated microglia."

"Within the assayed concentration, manganese was unable to induce tumour necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression, whereas it potentiated iNOS and TNF-alpha gene expression by lipopolysaccharide/interferon-gamma-activated glia cells. The enhencement was accompanied by elevation of free manganese, generation of oxidative stress, activation of mitogen-activated protein kinases, and increased NF-kappaB and AP1 binding sites. The potential degradation of inhibitory molecule IkappaB was one of the underlying mechanisms for the increased activation of NF-kappaB by manganese."

It is easily thinkable that after a long time or after a strong infection epigenetics for NO have become changed,
and produce much NO now.



So, we would like to rechange epigenetics.
 
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percyval577

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What the reason for the Mn-dependency of the iNOS could be
(attempt)​

As a matter of fact there are living many bacterias from, with and even for us in our body.
Every second their LPS and what ever will stimulate microglia to produce NO. That´s normal.
The purpose of iNOS was to slower the gene expression (or something like that) from pathogenes, by NO.
But the nerves use NO as well.
Drinking to much alcohol, and you stop to produce NO from the nerves (nNOS), you can´t remember things (this is so far a good, known guess in respect of alcohol).

Now, if this nNOS is that important, the normal iNOS must adopt to the purposes of the nerves.
Therefore it should adjust his NO-production, if there is any further dependence.

The iNOS is acting at once (but the other ones - nNOS, eNOS - should be prepared for there action).
Now, NO is only produced from arginine.
Arginine is very very important in the liver: the enzyme arginase needs it for avoiding ammonia-poisening.
[While acting the arginase changes arginine to ornithine, and get it to some extent back, to act once more.]
And the arginase uses manganese as cofactor. [As a cofactor Mn might/should come and go.]

So the activity of the enzyme-molecule is a function of the blood (and/or tissue) concentration of these two substances. They need to match from the fast blood stream.
roughly:
activity of arginase = arginine + manganese...............(concentrations in the blood)
.................... same = 1+4............................................. for example
.....................same = 4+1............................................. and so on.

Well, this should be imitated by the iNOS-enzyme-molecule, for the purpose not to confuse the nerves when the very very important arginase deals with different manganese levels.
And here the arginase must be safe, whereas the iNOS remains more flexible, as it is neccesary to react against pathogenes and even to make sickness behaviour, if needed. If not necessary the iNOS should not be prepared for higher and very high (toxic) Mn-levels which could arise from something, that would have occured in the process of evolution only quit recently.

The adoption of the iNOS to manganese might have two aspects:
1. An animal might consume different amounts of manganese. This should be averaged from epigenetic, over some time.
2. This mechanism should serve for the evolution, to create easily new animals with new nutrition (with different amounts of manganese).


I think it could be true, but a mathmatician should rethink it.
 
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percyval577

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The indirect sources of what I think is one mainpoint

If one looks at the effects that both manganese or nitric oxide exert, one can not deny that it is in principle the same.
I only looked via internet:

NO->
NMDAR elevated (Neitz, Mergia 2014); Kainatreceptors lowered (Banach, Piskorska 2011); Glutamine elevated (Neitz, Mergia 2011); voltage gated kalium channels changed (Steinert, Robinson 2011); GABAR lowered (Nijs, Sujatha 1999); Taurine lowered (), Acetylchline with positive feedback (Prast, Tran 1998 + Xu, Tong 1996); Norepinephren with negative feedback (Kolo, Westphal 2004 + Russo, Westphal 2004); Dopamine reuptakeinhibited (Kiss, Zsilla 2004) - > more changing in combination with the Norepinephren-effect.

Mn ->
NMDAR elevated (Brouillet, Shinobu, 1993); Glutamate elevated (Takeda, Sotokaku 2002); GABAR lowered (Brouillet, Shinobu 1993; Takeda, Sotogaku 2003), or elevated (Fordahl, Anderson 2010); Taurine lowered (Fordahl, Anderson 2010); Acetylcholine elevated (Santos, Milatovic 2012); Mn makes subtoxic levels of L-DOPA toxic (Serra, Esposito 2000), and Dopamine lowered (Brouillet, Shinobu 1993).


Furtheron, this would be a description of symptoms. The nerves come easier at action.
 
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Learner1

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From the Linus Pauling Institute website:
Manganese is a mineral element that is both nutritionally essential and potentially toxic. The derivation of its name from the Greek word for magic remains appropriate, because scientists are still working to understand the diverse effects of manganese deficiency and manganese toxicity in living organisms (1).

Function
Manganese (Mn) plays an important role in a number of physiologic processes as a constituent of multiple enzymes and an activator of other enzymes (2).

Antioxidant function
Manganese superoxide dismutase (MnSOD) is the principal antioxidant enzyme in the mitochondria. Because mitochondria consume over 90% of the oxygen used by cells, they are especially vulnerable to oxidative stress. The superoxide radical is one of the reactive oxygen species produced in mitochondria during ATP synthesis. MnSOD catalyzes the conversion of superoxide radicals to hydrogen peroxide, which can be reduced to water by other antioxidant enzymes (3).

Metabolism
A number of manganese-activated enzymes play important roles in the metabolism of carbohydrates, amino acids, and cholesterol (4). Pyruvate carboxylase, a manganese-containing enzyme, and phosphoenolpyruvate carboxykinase (PEPCK), a manganese-activated enzyme, are critical in gluconeogenesis — the production of glucose from non-carbohydrate precursors. Arginase, another manganese-containing enzyme, is required by the liver for the urea cycle, a process that detoxifies ammonia generated during amino acid metabolism (3). In the brain, the manganese-activated enzyme, glutamine synthetase, converts the amino acid glutamate to glutamine. Glutamate is an excitotoxic neurotransmitter and a precursor to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA) (5, 6).

Bone development
Manganese deficiency results in abnormal skeletal development in a number of animal species. Manganese is the preferred cofactor of enzymes called glycosyltransferases; these enzymes are required for the synthesis of proteoglycans that are needed for the formation of healthy cartilage and bone (7).

Wound healing
Wound healing is a complex process that requires increased production of collagen. Manganese is required for the activation of prolidase, an enzyme that functions to provide the amino acid, proline, for collagen formation in human skin cells (8). A genetic disorder known as prolidase deficiency results in abnormal wound healing among other problems, and is characterized by abnormal manganese metabolism (7). Glycosaminoglycan synthesis, which requires manganese-activated glycosyltransferases, may also play an important role in wound healing (9).

Nutrient interactions
Iron
Although the specific mechanisms for manganese absorption and transport have not been determined, some evidence suggests that iron and manganese can share common absorption and transport pathways (10). Absorption of manganese from a meal decreases as the meal's iron content increases (7). Iron supplementation (60 mg/day for four months) was associated with decreased blood manganese levels and decreased MnSOD activity in white blood cells, indicating a reduction in manganese nutritional status (11). Additionally, an individual's iron status can affect manganese bioavailability. Intestinal absorption of manganese is increased during iron deficiency, and increased iron stores (ferritin levels) are associated with decreased manganese absorption (12). Men generally absorb less manganese than women; this may be related to the fact that men usually have higher iron stores than women (13). Further, iron deficiency has been shown to increase the risk of manganese accumulation in the brain (14).

Magnesium
Supplemental magnesium (200 mg/day) has been shown to slightly decrease manganese bioavailability in healthy adults, either by decreasing manganese absorption or by increasing its excretion (15).

Calcium
In one set of studies, supplemental calcium (500 mg/day) slightly decreased manganese bioavailability in healthy adults. As a source of calcium, milk had the least effect, while calcium carbonate and calcium phosphate had the greatest effect (15). Several other studies have found minimal effects of supplemental calcium on manganese metabolism (16).

Deficiency
Manganese deficiency has been observed in a number of animal species. Signs of manganese deficiency include impaired growth, impaired reproductive function, skeletal abnormalities, impaired glucose tolerance, and altered carbohydrate and lipid metabolism. In humans, demonstration of a manganese deficiency syndrome has been less clear (2, 7). A child on long-term total parenteral nutrition (TPN) lacking manganese developed bone demineralization and impaired growth that were corrected by manganese supplementation (17). Young men who were fed a low-manganese diet developed decreased serum cholesterol levels and a transient skin rash (18). Blood calcium, phosphorus, and alkaline phosphatase levels were also elevated, which may indicate increased bone remodeling as a consequence of insufficient dietary manganese. Young women fed a manganese-poor diet developed mildly abnormal glucose tolerance in response to an intravenous (IV) infusion of glucose (16). Overall, manganese deficiency is not common, and there is more concern for toxicity related to manganese overexposure (see Safety).

Osteoporosis
Women with osteoporosis have been found to have decreased plasma or serum levels of manganese and also an enhanced plasma response to an oral dose of manganese (19, 20), suggesting they may have lower manganese status than women without osteoporosis. Yet, a more recent study in postmenopausal women with and without osteoporosis did not find any differences in plasma levels of manganese (21). A study in healthy postmenopausal women found that a supplement containing manganese (5 mg/day), copper (2.5 mg/day), and zinc (15 mg/day) in combination with a calcium supplement (1,000 mg/day) was more effective than the calcium supplement alone in preventing spinal bone loss over a two-year period (22). However, the presence of other trace elements in the supplement makes it impossible to determine whether manganese supplementation was the beneficial agent for maintaining bone mineral density.

Diabetes mellitus
Manganese deficiency results in glucose intolerance similar to diabetes mellitus in some animal species, but studies examining the manganese status of diabetic humans have generated mixed results. In one study, whole blood manganese levels did not differ significantly between 57 diabetics and 28 non-diabetic controls (23). However, urinary manganese excretion tended to be slightly higher in 185 diabetics compared to 185 non-diabetic controls (24). A case-control study of 250 diabetic and non-diabetic individuals found that type 2 diabetic individuals had higher serum manganese levels than non-diabetics (25). However, a more recent study in 257 type 2 diabetics and 166 non-diabetic controls found lower blood levels of manganese in the diabetic patients (26). Additionally, a study of functional manganese status found the activity of the antioxidant enzyme, MnSOD, was lower in the white blood cells of diabetics than in non-diabetics (27). Neither 15 mg nor 30 mg of oral manganese improved glucose tolerance in diabetics or non-diabetic controls when given at the same time as an oral glucose challenge (28). Although manganese appears to play a role in glucose metabolism, there is little evidence that manganese supplementation improves glucose tolerance in diabetic or non-diabetic individuals.

Epilepsy (seizure disorders)
Manganese deficient rats are more susceptible to seizures than manganese sufficient rats, and rats that are genetically prone to epilepsy have lower than normal brain and blood manganese levels. Certain subgroups of humans with epilepsy reportedly have lower whole blood manganese levels than non-epileptic controls. One study found blood manganese levels of individuals with epilepsy of unknown origin were lower than those of individuals whose epilepsy was induced by trauma (e.g., head injury) or disease, suggesting a possible genetic relationship between epilepsy and abnormal manganese metabolism. While manganese deficiency does not appear to be a cause of epilepsy in humans, the relationship between manganese metabolism and epilepsy deserves further research (7, 29).
 

percyval577

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What I would like to say is that there might be the chance to get rid of our desease to some extent,
because there is some evidence
for a possible hypersensitive immunesystem
out of its adjustment (nitric oxide) to manganeselevels (averaged over time and infections).

If anybody would try a strong low manganese diet, what I did to some extent (not all consequent)
or if anybody would stop to eat high manganese foods, or whatever,
is up to every person himself (and his condition, his preferences, and what ever).

I am no physician, whose task would be indeed to care over xy.
But one can say, that there aren´t any common problems with lacks of manganese as they are commonly known from some other essential elements (if I got it right in the past). That does not mean manganese was unimportant -> Surely, all this would be in order of a good health management something to be investigated further and to look after.

Well, I talked about the onliest chance I can see for myself.
And even if I would fear serious sideeffects, I had nothing to loose, and I still have nothing to loose.
Of course, I could not complain if anything would apper.
Joke of life would be to have get rid of it, but then some other desease arrives.
But brainsickness is worst, isn´t it?
 
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