High-dose manganese: could it be an effective treatment for ME/CFS? (Ron Davis Research)

Hip

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In the light of the findings by Prof Ron Davis that manganese levels are low in the hair analysis of ME/CFS patients, I decided to look back in my journal to when I was experimenting with high-dose manganese, and I found some possible very positive results!

I often take 3 mg of manganese daily, as I find it has slight mood and enthusiasm-boosting effects (I think because manganese is a cofactor for making dopamine). If I go higher than about 3 mg, I notice some insomnia, even if I take the manganese in the morning. But I don't notice any benefits for my ME/CFS at this 3 mg dose level.

However, looking in my journal, in 2012 there was a period where I was taking manganese 40 mg daily for a short time (3 days), along with some other trace elements (zinc, molybdenum, vanadium, germanium, iodine selenium and silicon).

After taking 40 mg manganese daily for 3 days, I wrote some very positive results in my journal like:

"Very physically and energetically cleaning my room all evening" — this was written in my journal two days after the end of my 3 days of manganese supplementation at 40 mg daily.

And also, a complex mathematics project that I had abandoned since getting ME/CFS, I started working on again about 6 days after taking 40 mg manganese daily. I cannot normally do complex mathematics with my brain fog, so the fact I started working on a mathematical project is a strong indication of a positive effect.



I think there may be a fairly immediate effect from high-dose manganese, because 9 hours after my very first dose of manganese 40 mg, I wrote in my journal: "feeling quite clear headed mentally".

Then two days later, while still taking 40 mg daily, I wrote: "feeling quite relaxed and reasonably focused".

At this point, I seemed to have stopped taking manganese, perhaps because it was causing some insomnia (nothing is noted in my journal about why I stopped).

However, even though I stopped taking manganese, two days after stopping, I reported "very physically and energetically cleaning my room all evening". And 6 days after stopping, I started on the complex mathematical project, even though I had not taken manganese for the last 6 days. Several days after starting the mathematical project, my brain fog returned, and I was not able to continue.

So if these benefits are indeed from manganese, then the effects of high dose manganese seem to kick in within 9 hours; and even when you stop taking manganese, it appears the benefits remain for about a week or so.



The manganese supplement I took was Swanson Albion Manganese 40 mg, which contains manganese in the highly bioavailable form of manganese glycinate chelate.

I was also taking this high-dose manganese with the following trace minerals:

Trace Mineral Protocol:
Manganese 40 mg
Selenium (as selenomethionine) 200 mcg
Zinc 50 mg transdermal
Chromium (as chromium picolinate) 200 mcg
Molybdenum 150 mcg
Vanadyl sulphate 10 mg
Copper 2 mg transdermal
Germanium sesquioxide 100 mg
Iodine 11 mg
Horsetail herb (source of silicon) 600 mg

I am not sure if any of these other trace minerals were also helping, but since copper and selenium were found to be low in Ron Davis's hair mineral analysis of ME/CFS patients, these two minerals at least might be worth adding to the manganese.

(I take zinc and copper as crushed tablet powder, rubbed into the skin transdermally, as these two minerals often give me a stomach ache if I take them orally).



One has to be careful with long-term very high doses of manganese, though, because manganese can cause a Parkinson's-like disease called manganism, due to the manganese accumulating in the brain's basal ganglia.

I would definitely avoid trying intranasal manganese, because one article says "inhaled manganese is transported directly to the brain instead of first being metabolized by the liver".



I just need to figure out why manganese is causing me insomnia, so that I can try to find a workaround.

Apparently manganese competes with iron for absorption, and low iron can cause insomnia; so maybe when taking high-dose manganese, it may be an idea to take an iron tablet (but perhaps not at the same time, maybe take the iron 12 hours after the manganese). I will experiment to see if iron prevents the insomnia.



Anyway, today I am going to start further experiments with high-dose manganese, and have just now taken 20 mg of manganese, and will take this dose daily for the next few days. And I will take a 200 mg tablet of ferrous sulphate (contains 65 mg of iron) 12 hour after taking manganese each day.

Manganese is best absorbed on an empty stomach. Same for iron.



Prof Ron Davis in this video says that manganese is involved in many of the enzymes that are known to be a problem in ME/CFS.

Regarding these enzymes, this article says:
Manganese is a cofactor for many enzymes, including manganese superoxide dismutase, arginase, and pyruvate carboxylase.

Through the action of these enzymes, manganese is involved in amino acid, cholesterol, glucose, and carbohydrate metabolism; reactive oxygen species scavenging; bone formation; reproduction; and immune response. Manganese also plays a role in blood clotting and hemostasis in conjunction with vitamin K
Pyruvate carboxylase might be important, as this mitochondrial enzyme converts pyruvate to oxaloacetate when acetyl CoA is available. This is a Krebs intermediate. See the green pathway in this diagram.

So pyruvate carboxylase facilitates anaplerotic replenishment of the Krebs cycle intermediates.


The article also says blood tests for manganese may not be that useful for measuring deficiency, because:
Manganese status is difficult to assess and not routinely measured in clinical practice. Normal whole blood concentrations of manganese range from 4 to 15 mcg/L, but they are highly variable, and their utility as a status indicator is unclear.
 
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BrightCandle

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After my hair test last year I started taking Manganese in fairly regularly although I stopped about 5 weeks ago as I was markedly improved and had been coming off various pills for a month or so thought I didn't appear to need anymore and these 3 having potential toxic effects at high amounts I started coming off them first. I started taking it in last Thursday again and I am slowly picking up. I have been taking 8mg of Manganese and 250ug of Copper and some iron as well.

My improvement periods also correlate with this supplement and my worsening periods without it from my records. Its an interesting idea given Rons update and what we know about these pathways being a problem and its a simple and cheap experiment to run for a few weeks, effect should be pretty quick. I'll try something similar see if I get a faster recovery and get to a good place doing it. Dose is set at 24mg tomorrow morning and I'll do my weeks drugs tomorrow afternoon so will maintain 24mg, so if I seem nicer this coming week you'll all know why!
 
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valentinelynx

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Interesting. I think I may have taken Mn supplements at some point in time. But, when I read that Borrelia (Lyme disease bacteria) requires lots of manganese to thrive, I decided to not supplement that mineral anymore, because I was concerned about having chronic Lyme at the time. Perhaps that was a mistake, or perhaps since I've likely had sufficient antibiotics for any Lyme disease, it's worth revisiting this?

https://www.livescience.com/28120-lyme-disease-manganese.html
 

pattismith

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I wish I could do a small trial with high manganese, but the iron interaction is a concern to me.

I need 200 mg a day of iron to maintain my ferritin!

People with iron deficiency like me seems at risk for higher manganese load so not sure if supplementation is a good idea...

Manganese | Linus Pauling Institute | Oregon State University

Nutrient interactions
Iron
Iron and manganese share common absorption and transport proteins, including the divalent metal transporter 1, the lactoferrin receptor, transferrin, and ferroportin (reviewed in 10). Absorption of manganese from a meal decreases as the meal's iron content increases (7). Iron supplementation (60 milligrams [mg]/day for four months) has been associated with decreased blood manganese concentrations and decreased MnSOD activity in leukocytes, 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 decreased when iron stores are elevated (i.e., high ferritin concentrations) (12). Small studies have found increased blood concentrations of manganese in iron-deficient infants (13) and children (14), and a national survey of adults residing in South Korea found men and women with low ferritin levels had higher blood concentrations of manganese compared to those with normal ferritin levels (15). In this analysis, anemia was associated with higher blood concentrations of manganese in women but not in men (15). Men generally absorb less manganese than women, which may be related to the fact that men usually have higher iron stores than women (16). Iron deficiency has also been shown to increase the risk of manganese accumulation in the brain (17).
 
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My problem is the paradoxical copper issues a lot of people have discussed on older threads on PR. Also when I reesarched this it advised taking each mineral seperately due to bio competition, which is annoying.

Josh's protocol has a TON of chelators in it. I easily get 300mg r-ala per day and 3g nac per day and I prob have other chelators tbh.

I've tried the fancy pants bio available trace mineral supps, which give me a temperature and make me feel unwell. Haven't really got the patience to try that long term as it also seems to fog my brain right up. So I am taking centrum in the AM instead, on an empty stomach. Supposedly minerals must be taken on an empty stomach for decent absorption.

No idea if it will help me but stress and a virus I picked up last week are kicking my arse at the moment. Just getting over the virus today but it's not fully gone yet. Felt very similair to covid tbh but the pcr I had was negative and so were all the lfts I did.

Josh's protocol reduced the symptoms of the virus every time I took a dose. I know his latest protocol has focussed on trace minerals and low dose lithium for a few months now: https://bornfree.life/experimental-treatment-methodology/7/v3-45u-preview/42/
However it bothers me that he moves away from driving pathogen reduction via reishi and oat bran, to concentrating on trace minerals, in my particular case I don't think that would help me much. Still b vitamins and trace minrals fog me up as I say - even if I take them long term. Even b12 does that to me now so I just don't think that's my issue.
 

max_yazhbin

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In the light of the findings by Prof Ron Davis that manganese levels are low in the hair analysis of ME/CFS patients, I decided to look back in my journal to when I was experimenting with high-dose manganese, and I found some possible very positive results!

I often take 3 mg of manganese daily, as I find it has slight mood and enthusiasm-boosting effects (I think because manganese is a cofactor for making dopamine). If I go higher than about 3 mg, I notice some insomnia, even if I take the manganese in the morning. But I don't notice any benefits for my ME/CFS at this 3 mg dose level.

However, looking in my journal, in 2012 there was a period where I was taking manganese 40 mg daily for a short time (3 days), along with some other trace elements (zinc, molybdenum, vanadium, germanium, iodine selenium and silicon).

After taking 40 mg manganese daily for 3 days, I wrote some very positive results in my journal like:

"Very physically and energetically cleaning my room all evening" — this was written in my journal two days after the end of my 3 days of manganese supplementation at 40 mg daily.

And also, a complex mathematics project that I had abandoned since getting ME/CFS, I started working on again about 6 days after taking 40 mg manganese daily. I cannot normally do complex mathematics with my brain fog, so the fact I started working on a mathematical project is a strong indication of a positive effect.



I think there may be a fairly immediate effect from high-dose manganese, because 9 hours after my very first dose of manganese 40 mg, I wrote in my journal: "feeling quite clear headed mentally".

Then two days later, while still taking 40 mg daily, I wrote: "feeling quite relaxed and reasonably focused".

At this point, I seemed to have stopped taking manganese, perhaps because it was causing some insomnia (nothing is noted in my journal about why I stopped).

However, even though I stopped taking manganese, two days after stopping, I reported "very physically and energetically cleaning my room all evening". And 6 days after stopping, I started on the complex mathematical project, even though I had not taken manganese for the last 6 days. Several days after starting the mathematical project, my brain fog returned, and I was not able to continue.

So if these benefits are indeed from manganese, then the effects of high dose manganese seem to kick in within 9 hours; and even when you stop taking manganese, it appears the benefits remain for about a week or so.



The manganese supplement I took was Swanson Albion Manganese 40 mg, which contains manganese in the highly bioavailable form of manganese glycinate chelate.

I was also taking this high-dose manganese with the following trace minerals:

Trace Mineral Protocol:
Manganese 40 mg
Selenium (as selenomethionine) 200 mcg
Zinc 50 mg transdermal
Chromium (as chromium picolinate) 200 mcg
Molybdenum 150 mcg
Vanadyl sulphate 10 mg
Copper 2 mg transdermal
Germanium sesquioxide 100 mg
Iodine 11 mg
Horsetail herb (source of silicon) 600 mg

I am not sure if any of these other trace minerals were also helping, but since copper and selenium were found to be low in Ron Davis's hair mineral analysis of ME/CFS patients, these two minerals at least might be worth adding to the manganese.

(I take zinc and copper as crushed tablet powder, rubbed into the skin transdermally, as these two minerals often give me a stomach ache if I take them orally).



One has to be careful with long-term very high doses of manganese, though, because manganese can cause a Parkinson's-like disease called manganism, due to the manganese accumulating in the brain's basal ganglia.

I would definitely avoid trying intranasal manganese, because one article says "inhaled manganese is transported directly to the brain instead of first being metabolized by the liver".



I just need to figure out why manganese is causing me insomnia, so that I can try to find a workaround.

Apparently manganese competes with iron for absorption, and low iron can cause insomnia; so maybe when taking high-dose manganese, it may be an idea to take an iron tablet (but perhaps not at the same time, maybe take the iron 12 hours after the manganese). I will experiment to see if iron prevents the insomnia.



Anyway, today I am going to start further experiments with high-dose manganese, and have just now taken 20 mg of manganese, and will take this dose daily for the next few days. And I will take a 200 mg tablet of ferrous sulphate (contains 65 mg of iron) 12 hour after taking manganese each day.

Manganese is best absorbed on an empty stomach. Same for iron.



Prof Ron Davis in this video says that manganese is involved in many of the enzymes that are known to be a problem in ME/CFS.

Regarding these enzymes, this article says:


Pyruvate carboxylase might be important, as this mitochondrial enzyme converts pyruvate to oxaloacetate when acetyl CoA is available. This is a Krebs intermediate. See the green pathway in this diagram.

So pyruvate carboxylase facilitates anaplerotic replenishment of the Krebs cycle intermediates.


The article also says blood tests for manganese may not be that useful for measuring deficiency, because:
wonder if its the horsetail helping get the minerals in the right places, very interesting
 

borko2100

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If Manganase does help I'm pretty sure we would need a pretty significant dose (otherwise multivitamins etc. would help too). Yes there is a risk of toxicity, but usually toxicities like this take months or even years of excessive intake to manifest. Therefore I believe a trial of 3 weeks up to a month would be safe, even with a high dose. I am going to try this myself when I run out of my selenium supps. I'd try it sooner but for precautionary reasons I don't want to take 2 minerals at huge doses at same time.
 
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I'm also taking the horsetail but I haven't had much luck with trace minerals when I take Thorne biomins I get a temperature and feel a bit sick. Maybe it does indeed help though.
 

BrightCandle

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So far I don't have much to report. Taking in 14+8 mg a day and am seeing marginal improvements in energy but its well within normal tolerance. Had a bad set of headaches yesterday but its passed today and that happens sometimes. Nothing of note has happened positively or negatively so far. Continuing on, will likely do it for a month in all, that is my usual trial period.

I found it interesting that we don't really know what low Manganese causes. Its not like Vitamin D or C where we have a nice name for the disease and a treatment plan. Its associated with a bunch of chronic conditions, but whether its casual really hasn't been established.

I have quite a few other things stacked up ready to try at the moment like the Lysates (CBIS theory) just appearing unexpectedly and Syrian Rue (Quinolinic acid experiment on kyurenine pathway theory) and this experiment I don't want to run parallel with any of those given the reasoning for starting. If its not shown something in a month its likely not going to.
 
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Took 8mg manganese tonight. Was wondering why I felt so good. But it looks like my ebv which had already reactivated earlier in the day appears to have done so again with the manganese. I still don't know why most things reactivate ebv like this. But they do. There are a huge list of things that do not. But there's also a list of things I've noticed that do.

I had got rid of the sore throat earlier today by taking valtrex. So I figure it's just over stretched me.

I do feel good though. I guess someone without ebv issues would be ok?