Is Manganese the solution??

[LostPancake]

something kind of interesting - the dopamine-producing neurons are darkly colored due to having a lot of melanin in them (hence, substantia nigra, "black substance"). and apparently, "Melanin is able to effectively ligate metal ions through its carboxylate and phenolic hydroxyl groups, in many cases much more efficiently than the powerful chelating ligand ethylenediaminetetraacetate (EDTA). It may thus serve to sequester potentially toxic metal ions, protecting the rest of the cell." http://en.wikipedia.org/wiki/Melanin

so the melanin could be storing the manganese and magnesium ions (and other ionic cofactors) needed for dopamine production that get transported there.

also, the locus coeruleus ("blue body") is similar, with polymerized norepinepherine causing the blue color. it might also store the same ionic cofactors, since norepinepherine is just one reaction down from dopamine.
"The locus coeruleus is activated by stress, and will respond by increasing norepinephrine secretion, which in turn will increase cognitive function (through the prefrontal cortex), increase motivation (through nucleus accumbens)... " http://en.wikipedia.org/wiki/Locus_coeruleus

interestingly, another disease which can cause parkinsons is wilson's disease, which is an accumulation of copper in tissues, esp the brain.
"About half the patients with Wilson's have neurological or psychiatric problems. Most patients initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms then follow, often in the form of parkinsonism (increased rigidity and slowing of routine movements)... Psychiatric problems due to Wilson's disease may include behavioral changes, depression, anxiety and psychosis." http://en.wikipedia.org/wiki/Wilson's_disease

so, another case where too much metal can damage the dopaminergic (and maybe also noradrenergic) neurons.


so... since people with SA are more likely to develop parkinsons (i read that here a while back), it could be due to increased exposure to or storage of metal ions, which are transported to the substantia nigra, and locus coeruleus, which then get oxidative damage and start dying off, hence less dopamine and norepinephrine available. that's just a guess though. i mean, it seems like organisms should be good at dealing with metal ions, since it would encounter them a lot in the environment. so i dunno.

um, plus this - "A common finding in advanced Alzheimer's disease is almost complete loss of the norepinephrine producing pigmented neurons of the locus ceruleus". i remember reading a while back that aluminum might be implicated in alzheimers, which maybe causing the same loss of neurons.

[LostPancake]

some more info -

http://74.125.113.132/search?q=cache...7p544to553.pdf

Human Mn deficiency has been reported in patients on parenteral nutrition and in micronutrient studies. Mn toxicity has been reported through occupational (e.g. welder) and dietary overexposure and is evidenced primarily in the central nervous system, although lung, cardiac, liver, reproductive and fetal toxicity have been noted. Mn neurotoxicity results from an accumulation of the metal in brain tissue and results in a progressive disorder of the extrapyramidal system which is similar to Parkinson’s disease. In order for Mn to distribute from blood into brain tissue, it must cross either the blood–brain barrier (BBB) or the blood–cerebrospinal fluid barrier (BCB). Brain import, with no evidence of export, would lead to brain Mn accumulation and neurotoxicity. The mechanism for the neurodegenerative damage specific to select brain regions is not clearly understood. Disturbances in iron homeostasis and the valence state of Mn have been implicated as key factors in contributing to Mn toxicity. Chelation therapy with EDTA and supplementation with levodopa are the current treatment options, which are mildly and transiently efficacious. In conclusion, repeated administration of Mn, or compounds that readily release Mn, may increase the risk of Mn-induced toxicity.

The trace element manganese (Mn) is essential for normal development and body function across the life span of all mammals. Mn binds to and/or regulates many enzymes throughout the body. For example, Mn is a required co-factor for arginase, which is responsible for urea production in the liver, superoxide dismutase, which is critical to prevent against cellular oxidative stress, and pyruvate carboxylase, an essential enzyme in gluconeo-genesis. In brain, about 80% of Mn is associated with the astrocyte-specific enzyme glutamine synthetase

Interruption of Mn homeostasis has also been associated with a variety of disease states in humans. There are few reports of Mn deficiency in general human populations with self-selected diets, which contain 2–4 mg Mn daily.

It is suspected that the presence of neurological symptoms in epileptics may correlate with low brain Mn, which may result from a low blood Mn.

[LostPancake]

the significantly lower incidence of Parkinson's in blacks than in whites has "prompt[ed] some to suggest that cutaneous melanin might somehow serve to protect the neuromelanin in substantia nigra from external toxins."

http://en.wikipedia.org/wiki/Melanin

or it could absorb excess metals?

[LostPancake]

continued from same source - http://74.125.113.132/search?q=cache...7p544to553.pdf

Serum concentration of Mn in healthy subjects is about 0.05–0.12mg/dl. After entering, or being injected into, blood, Mn rapidly distributes into other tissues.

Based on animal data, Mn distributes, under normal conditions, in brain regions in the following order: substantia nigra > striatum > hippocampus > frontal cortex

Once Mn enters the brain it persists there for a relatively long time.

it was found that the relative retention of Mn in the cerebrum increased, while its relative retentions in most other tissues examined remained fairly constant, suggesting a selective retention of Mn in the brain.

Studies conducted in rats indicate that Mn accumulates in the cerebrum during the first 4 days following dose administration; the levels did not decline at 34 or 64 days after dosing.

Currently, there is a significant concern about airborne Mn exposure from the fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT). Combustion of MMT releases Mn from the tailpipe, primarily as airborne Mn phosphates and sulfate. Increased use of Mn-containing products results in greater exposure of large populations to Mn. Mn intoxication has also been reported after ingestion of contaminated water.

Mn toxicity has also been reported by ingestion in patients receiving long-term parenteral nutrition containing about 1mg/day of parenteral Mn for adults or more than 40mg/kg/day for children (as reviewed in Dickerson). Interestingly, Mn deficiency has also been noted in patients on TPN. [Parenteral nutrition (PN) is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulas containing salts, glucose, amino acids, lipids and added vitamins. It is called total parenteral nutrition (TPN) when no food is given by other routes.]

(maybe because taking it orally a lot of it gets eliminated by the liver, but injecting it bypasses the liver?)

For Mn, the primary targeted brain regions are the globus pallidus and striatum of the basal ganglia, whereas the neurodegeneration in IPD (parkinson's) occurs mainly in the substantia nigra.

Based on our own study on 36 welders diagnosed with the symptoms of typical Mn poisoning in Beijing, the onset of symptoms is between 2 and 34 years (average 16.3 years), the welders having average working duration of 24.4 years (4–40 years).

Occupational exposure for an average of 7 years was associated with significant decrements in neurological function.

Chronic Mn overexposure causes Mn accumulation in brain regions, notably including the basal ganglia structures and, to a lesser extent, the caudate nucleus and putamen.

A number of studies have shown that Mn-elicited neurotoxicity may be related to the abnormal iron metabolism. High dietary Mn increased Fe uptake into rat brain, liver and kidneys. The excess accumulation of Fe in neurons may consequently produce the cellular oxidative stress that leads to neuronal damage.

The suggestion that transition metals contribute to the neurodegeneration observed in Parkinsonian syndromes is consistent with studies of the toxicity of different Mn valence states. As Mn can participate in Fenton reactions, it has the potential to increase reactive oxygen species, and subsequent oxidative damage, within cells. A recent human study further confirms the oxidative damage among welders exposed to airborne Mn.

Furthermore, 10 years after cessation of Mn exposure, the same patients continued to show progression in severity of symptoms.

i found this pretty interesting, as my grandfather was exposed to some things in his work environment (an oil refinery), and later developed high iron in his blood AND a parkinson-like tremor. he used to play guitar and paint, but had to give them up due to it.

[zomgz]

Hmm I heard it was in Blueberries and Pineapple. I like both of those. Also, I take 50mcg of manganese, wondering if that's too much?

[Beggiatoa]

LostPancake, excellent work. You know what's needed to make melanine? Tyrosine. Interesting as it's also needed to make dopamine. The dietary exposure you quoted above most likely referenced newborns who are fed soy formulas high in manganese. Since their biliary systems aren't fully developed, they can't excrete the manganese and thus, it becomes toxic to them. Again, I've seen no studies referencing Mn toxicity to diet. Some diets, I've seen referenced, contain in excess of 20 mg Mn per day without any adverse effect.

But what if, we supplement with the RIGHT amount?? The Upper limit of manganese is 11 mg. Right now I'm taking 20 but admit this feels to strong. There are formulas that offer 15 mg but I'm going to use one that gives 10 mg. Most minerals exert toxic effects at high dose. I read a report of a lady that died from magnesium overdose but she REALLY overdid it. I'm talking about grams...

If you can find more information like the one you posted, share some links. I'd like to read up on it some more. Maybe this way, we can figure out what's wrong with us.

I read a book on google books that said daily manganese excretion in bile is 4 mg per day. the RDA for Mn is set for 2-2.5. Hmm.m......

[LostPancake]

Originally Posted by zomgz

Hmm I heard it was in Blueberries and Pineapple. I like both of those. Also, I take 50mcg of manganese, wondering if that's too much?

not at all - mcg is micrograms, so that's only 0.05 mg!

Originally Posted by Beggiatoa

LostPancake, excellent work. You know what needed to make melanine? Tyrosine. Interesting as it's also needed to make melanin. The dietary exposure you quoted above most likely referenced newborns who are fed soy formulas high in manganese. Since their biliary systems aren't fully developed, they can't excrete the manganese and thus, it becomes toxic to them. Again, I've seen no studies referencing Mn toxicity to diet. Some diets, I've seen referenced, contain in excess of 20 mg Mn per day without any adverse effect.

But what if, we supplement with the RIGHT amount?? The Upper limit of manganese is 11 mg. Right now I'm taking 20 but admit this feels to strong. There are formulas that offer 15 mg but I'm going to use one that gives 10 mg. Most minerals exert toxic effects at high dose. I read a report of a lady that died from magnesium overdose but she REALLY overdid it. I'm talking about grams...

If you can find more information like the one you posted, share some links. I'd like to read up on it some more. Maybe this way, we can figure out what's wrong with us.

I read a book on google books that said daily manganese excretion in bile is 4 mg per day. the RDA for Mn is set for 2-2.5. Hmm.m......

thanks! yeah, i wonder about that monkey study - maybe they were injecting the manganese, for it to be toxic at only ~30mg/day? i'll have to read the article.

whoa, i'd seen the RDA as being 9mg - maybe that was an old reference. but yeah it looks like it's now at 2-2.3mg. http://en.wikipedia.org/wiki/Reference_Daily_Intake

here's an interesting paper from 1994 - http://www.springerlink.com/content/...ext.pdf?page=1

Manganese (Mn) is assumed to be an essential nutrient for
humans because numerous animal studies have shown that
deficiencies produce abnormalities in brain function...

However, a formal recommended dietary allowance
(RDA) has not been set for this nutrient because of a lack
of sufficient data. Currently, the estimated safe and adequate
intake for Mn is 2.5-5.0 mg/day [2]. This recom-
mendation was made, based on metabolic studies that
showed equilibrium or accretion of Mn in adult human
subjects fed diets containing 2-5 rag/day or more, and
negative balance on an intake of 0.7 rag/day. Recent studies
have reported negative Mn balance in subjects fed diets
containing 2.3-17.3 mg/day [5-10]. This wide range
suggests that the precise requirement for Mn remains to
be determined.
...the present study was undertaken to assess the dietary intake for this
country and to compare data with the estimated safe and
adequate dietary intake (2-5 mg) recommended by the
Food and Nutrition Board of the National Research Council
of the USA [14].

so they evaluated what people typically ate and found it to be around 3mg manganese a day.

but it's interesting that there was such a range that produced a negative Mn balance. maybe some people are better at excreting it than others, and might end up being deficient in it?

anyway, given that accretion (ie being accumulated in tissues) can happen at 5mg a day, i'd be wary about taking too much for too long. but again, i'm paranoid...

[Beggiatoa]

Aside from all this toxicity talk, Mn is also needed without loss, for so many functions.

Manganese is needed for T4 production in the thyroid, It's also needed for insulin, dopamine, acetylcholine, superoxide dismutase, Nitric Oxide and on and on. This is all very interesting.

Another thing, my sugar cravings and hypoglycemia problems have completely stopped. I have NO cravings for sweets which was a big problem for me.

I know we should be getting all these things from foods. But somehow, we are not. Even so, the daily requirement is setup to avoid deficiency and it's related problems. To have a therapeutic effect, as in healing, etc., you need higher doses. That's why the upper limit is established. Maybe we have a condition that calls for more manganese??

I don't generally pay much attention to supplement review on Iherb, but I found this one interested. This was for a manganese supplement of 50 mg.

Can't live without it., May 19, 2009
From Florida
I was always tired my head shook like Parkinson's, back and neck hurt, ears infected, just sick all the time and could not work. I used to take the pill and wanted to illiminate the copper from it . I replaced line in fridge, got rid of copper pots and pans illiminated chlorine with filters in shower, sinks and a salt pool. Started taking a mineral supplement with low copper and also this product. My health problems are gone my chronic fatigue, and pain is gone, my thyroid is doing great. I could not live without Country Life chelated manganese. I take it seperate from other minerals to insure complete absorption. It is my little miracle.

[Beggiatoa]

Wow, I had missed that completely. There's no set RDA based on evidence. They just guessed. Hmmmm...

I think manganese deserves more attention.

[LostPancake]

Originally Posted by Beggiatoa

I know we should be getting all these things from foods. But somehow, we are not. Even so, the daily requirement is setup to avoid deficiency and it's related problems. To have a therapeutic effect, as in healing, etc., you need higher doses. That's why the upper limit is established. Maybe we have a condition that calls for more manganese??

yeah, the RDA is for the average person, but there are apparently significant variations. it does sound like it needs more study. or maybe it's been done? needs more googling...

Can't live without it., May 19, 2009
From Florida
I was always tired my head shook like Parkinson's, back and neck hurt, ears infected, just sick all the time and could not work. I used to take the pill and wanted to illiminate the copper from it . I replaced line in fridge, got rid of copper pots and pans illiminated chlorine with filters in shower, sinks and a salt pool. Started taking a mineral supplement with low copper and also this product. My health problems are gone my chronic fatigue, and pain is gone, my thyroid is doing great. I could not live without Country Life chelated manganese. I take it seperate from other minerals to insure complete absorption. It is my little miracle.

wow, i hadn't thought about this - copper lines used in plumbing? especially in light of the thing about wilson's disease -

interestingly, another disease which can cause parkinsons is wilson's disease, which is an accumulation of copper in tissues, esp the brain.
"About half the patients with Wilson's have neurological or psychiatric problems. Most patients initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms then follow, often in the form of parkinsonism (increased rigidity and slowing of routine movements)... Psychiatric problems due to Wilson's disease may include behavioral changes, depression, anxiety and psychosis." http://en.wikipedia.org/wiki/Wilson's_disease

so... maybe in modern society we get exposed to more metals (in the shower? vehicle exhaust? water supply?), which get accumulated in the dopamine and norepinephrine producing neurons, which damages them, leading to SA, and then increased chances of parkinson's?

consider that most metals were locked away in ores until we learned how to extract them. now they're everywhere. we even cook with them. i remember the aluminum link with alzheimers being thought to be from this. our genes wouldn't know how to deal with them properly.

it's funny how we're focusing on the different ends of the spectrum, but they would both lead to the same thing - low amounts of dopamine (and presumably norepinephrine).

i don't normally think in terms of medical causes of SA, but it's interesting to think about.

[killergowri]

i am not sure on providing solution for you

[proximo20]

1) Manganese-Insulin Relation

a) These findings indicate that dietary Mn deficiency can result in impaired insulin secretion producing impaired carbohydrate metabolism; however, the timing of the deficiency may be a critical factor in the expression of this abnormality.

from http://jn.nutrition.org/cgi/content/abstract/114/8/1438

b) 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 (17). However, urinary manganese excretion tended to be slightly higher in 185 diabetics compared to 185 non-diabetic controls (18 ).

http://lpi.oregonstate.edu/infocente...als/manganese/

2) Insulin-Dopamine Relation

a) The results are some of the first to link insulin status and dopaminergic brain function and hold several implications for human health and disease.

The findings suggest that ADHD risk may have an insulin-dependent component and that control of insulin levels and response to the hormone may be an important determinant of amphetamine efficacy in patients with ADHD.

These experiments show that there is likely a strong interplay between these important dopamine neurotransmitter systems and insulin signaling mechanisms, which we know are altered in diabetes.

http://www.sciencedaily.com/releases...1017090131.htm

------------------------------------------------------

So if you have MN deficiency you produce less insulin and if you have inadequate insulin your dopamine system does not work properly.

Don't think it as severe manganese deficiency, there is also something called suboptimal levels. Also as you can see how much you need depends on how much you excrete. But I would still be cautious because a different mechanism or another problem might be causing the dopamine problem.

[GSH]

Originally Posted by Beggiatoa

Is Manganese the solution??

No

[Beggiatoa]

Originally Posted by GSH

No

I love your simplistic and minimalistic nature but could you please elaborate on that?

[Beggiatoa]

Did I mention, manganese is THE mineral for connective tissue. It's needed as a cofactor for collagen, elastin and the mucopolyssacharides like hyaluronic acid, glucosamine and chondroitin.

I've always had a problem with my connective tissue. I wrote about this before, from a mitral valve prolapse, dilated aorta, hernias, lumbar hernia, to gynecomastia and saggy skin in my abdomen and face. I've been on Mn for a month now and at least what's visible on the outside, the elasticity is improving all over, noticeably. I'm curious to see what's happening on the inside.

[Beggiatoa]

Originally Posted by proximo20

1) Manganese-Insulin Relation

So if you have MN deficiency you produce less insulin and if you have inadequate insulin your dopamine system does not work properly.

Don't think it as severe manganese deficiency, there is also something called suboptimal levels. Also as you can see how much you need depends on how much you excrete. But I would still be cautious because a different mechanism or another problem might be causing the dopamine problem.

Close. Simply put, manganese is needed for BOTh insulin and dopamine production. It's as simple as that. Maybe what these patients had in common was insufficient Mn intake.

As for me, I have a dopamine problem. I've also noticed over the years that my fasting glucose levels have risen from the 70's to the upper 90's. At this rate, I'll be diabetic in a few years EVEN THOUGH I take awsome care of myself, eat healthy and exercise. This didn't seem to be enough.

I must note, since on Mn, a lack of motivation has not been a problem. In fact, I'm going out every single night. I'm leaving for a roadtrip in a few hours and I've been making more friends in the last month than I had in the last year living abroad. That's how awsome I feel.

[SAgirl]

How much does Manganese cost? Are you taking it in pill form?

[Beggiatoa]

Originally Posted by SAgirl

How much does Manganese cost? Are you taking it in pill form?

I was using this:

http://www.iherb.com/Chelated-Mangan...ets/13270?at=0

but just switched to this:

http://www.iherb.com/Twinlab-Mangane...ules/2383?at=0

[Beggiatoa]

un4td,

They used 20 or 40 mg Mn in rats. Let's say the biggest rat weighed 1 pound of body weight. For me, which I weight 200 lbs, that's the equivalent of consuming 4 grams at 20 mg per pound, or 8 grams at 40 mg per pound of Mn. The established upper limit is 11 mg so it's not too difficult to figure out why at these HIGH doses, Mn was toxic. Manganism is seen in welders who aspirated while working with Mn. It's also seen in other very specific conditions. With that in mind, Mn is needed as a cofactor for the production of dopamine.

dopamine production has an inverse U-curve. Add Mn up to a certain levels and D levels are augmented. As you increase the Mn concentration, these levels plateau and eventually start dropping. The key here is staying within the correct dose.

[Beggiatoa]

un4td,

They used 20 or 40 mg Mn in rats. Let's say the biggest rat weighed 1 pound of body weight. For me, which I weight 200 lbs, that's the equivalent of consuming 4 grams at 20 mg per pound, or 8 grams at 40 mg per pound of Mn. The established upper limit is 11 mg so it's not too difficult to figure out why at these HIGH doses, Mn was toxic. Manganism is seen in welders who aspirated while working with Mn. It's also seen in other very specific conditions. With that in mind, Mn is needed as a cofactor for the production of dopamine.

dopamine production has an inverse U-curve. Add Mn up to a certain levels and D levels are augmented. As you increase the Mn concentration, these levels plateau and eventually start dropping. The key here is staying within the correct dose.

Also, it doesn't say how the Mn was administered. If it was given in the form of manganese sulfate, then it was likey injected. Magnesium sulfate is used in the hospital setting and this is injected directly into the veins. So, a little weeee rat was given 4 or 40 grams Mn every day IV. This dose overcame the excretory speed of the liver and bile system and the body simply couldn't get rid of it fast enough so it accumulated in the dopamine producing areas of the brain. Mn has high affinity here BECAUSE it is required for normal brain function. I really doubt 10 or 20 mg will have this effect.