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

[BrightCandle]

How much manganese is safe to try?

In researching this the presumed safe dose is about 11mg orally. I know from myself 8mg is not of much help so this is really a test to see if we need a lot more than that to move the needle.

 

[Strawberry]

In researching this the presumed safe dose is about 11mg orally. I know from myself 8mg is not of much help so this is really a test to see if we need a lot more than that to move the needle.

If 11 mg is the only safe amount , how is it @Hip has 40 mg pills? Are there different forms? What are we to try?

 

[Hip]

This source says the NOAEL for manganese is 0.14 mg/kg/day, so 10.5 mg for a 75 kg person.

I have now been taking 20 mg of manganese daily for the last 8 days, and have not noticed any improvements in my ME/CFS.

 

[BrightCandle]

If 11 mg is the only safe amount , how is it @Hip has 40 mg pills? Are there different forms? What are we to try?

I can't speak to Hip's supplements they may just be older before "safe" ranges were set, but honestly when it comes to supplements we rarely know the proper safe range. I have found most of the supplements are in the 8 - 14mg range of elemental manganese. I am currently using an 8 + 14 for a total of 22mg, but I have been taking 8mg for maybe 9 months with some gaps already so I know the lower end of dosing is unlikely to do much.

People have taken manganese before and not seen dramatic effects or we would know about it so the question based on Ron's research is whether there is an amount that we can take where we get an effect and if there is an interesting area for us that is relatively straightforward. 22mg is unnoticeable to me, I do feel a little better but its within usual range, so far nothing positive or negative to say but doing another week at this dose and I'll probably do a complete month before I drop back.

Based on my own experience if this has an impact its got to be more than 22mg or it takes a while to have an effect.

 

[GlassCannonLife]

There is a 50 mg supplement on iherb

 

[Alvin2]

There is not a lot of manganese in the body, this source says 20mg, another source i had found last week (but forgot to bookmark) said 50-75mg.
So its not wise to take too much. I am going to try 5mg tablets twice a week when i can find a store that has them in stock.
https://www.livestrong.com/article/520170-taking-too-much-manganese/

 

[Hip]

I am not sure what dose level of manganese is safe, but when I got these dramatic improvements in brain fog, I took 40 mg of elemental manganese for 4 days in a row (and then stopped taking it), so that the total dose of manganese was just 4 x 40 mg.

For my latest test this week, I took 20 mg of elemental manganese for 8 days in a row, but unfortunately did not notice any improvements.

It may be that any benefits from manganese only appear at a certain highish dose level. This is what I observed with selenium: I found that 400 mcg of selenium daily substantially improves my ME/CFS symptoms (I have a thread about this here). But if I reduce the selenium dose to 200 mcg, I lose a lot of the benefits. So for selenium, it seems that high daily dose is necessary for it to work as an ME/CFS treatment.

 

[Hip]

Regarding safety:

When you look at NOAEL calculations (the No Observed Adverse Effect Level), these calculations often factor in a large safety margin.

I happened to be looking at a NOAEL calculation the other day, and in this calculation, they came to a dose level which had no adverse effects at all. But then to add a further safety margin, they decreased that already safe dose level by an additional factor of 3.

 

[Alvin2]

Two things to bear in mind, if we are low then we only need to normalize our levels, not super saturate.
If only super saturating has an effect then either there is an absorption/utilization problem or its a drug effect instead of a normalization effect its having.

Second point, the permanent damage it can cause is substantial, you can google manganese toxicity to learn more (not to mention the link i posted above).
https://www.sciencedirect.com/topics/medicine-and-dentistry/toxicity-of-manganese

 

[GlassCannonLife]

Two things to bear in mind, if we are low then we only need to normalize our levels, not super saturate.
If super saturating has an effect then either there is an absorption/utilization problem or its a drug effect instead of a normalization effect its having.

Second point, the permanent damage it can cause is substantial, you can google manganese toxicity to learn more (not to mention the link i posted above).
https://www.sciencedirect.com/topics/medicine-and-dentistry/toxicity-of-manganese

Good point! I'll be less aggressive with supplementation, thank you.

I just got the liposomal multi from solaray (? IIRC) that has liposomal forms of all of the minerals so hopefully that will be helpful..

 

[Inez]

Is it possible that antigens are cleaving manganese from the blood and stopping it from entering our cells properly?
https://www.sciencedaily.com/releas...utrient,process known as nutritional immunity.

Could 'nutritional immunity' be the link between the low manganese found and the hypothesis of hidden chronic infections in patients?

 

[Consul]

Hmm maybe the rabbit cells cant make MnSOD when Mn-transporters are inactive so that the resulting increase in SO is killing the virus before it kills the rabbit cell? Probably not though

 

[Replenished]

I bought Manganese along with a load of other mineral supplements after my own hair analysis also showed low Manganese. I never took very high doses or took it consistently but I still have it in the cupboard so I'll give this a go.

How much is too much Manganese?

 

[Hip]

Just an update: in the last few days, I have been feeling terrible, much more tired, brain fogged, substantially more depressed, mentally frail, I have more anhedonia and I am even physically a little more weak.

Whether this is due to the 20 mg of manganese I have taking daily, I am not sure because I have generally been feeling worse since getting COVID two month ago.

However, there is a good chance it is due to the manganese.

When I took a similar total dose of ME/CFS back in 2012, I experienced a great improvement in brain fog. But at the moment, I am feeling substantially worse. I've stopped taking manganese now.

So maybe 20 mg a day is too high. I regularly take 3 mg of manganese daily, as I find this actually boosts my mood and enthusiasm a little, and I do not experience adverse effects from 3 mg daily.

 

[Wishful]

Just an update: in the last few days, I have been feeling terrible, much more tired, brain fogged,

Me too! I wasn't taking manganese though. I think in my case it was from retesting oats.

The number of possible factors for what makes us feel worse at any time sure makes figuring it out difficult, even without the brainfog.

 

[GlassCannonLife]

For the record @Hip I've been taking 10 mg manganese every 2nd day for over 18 months and tested with undetectable levels.. Also had been supplementing 100 % rda molybdenum for 6 months and have undetectable levels.. So I'm not sure where they are going but not into our cells it seems..

There's a chance your supplementation caused the symptoms but it'd surely be a transient effect and not toxic build up.? Unless we all have different transport etc issues

 

[Hip]

There's a chance your supplementation caused the symptoms but it'd surely be a transient effect and not toxic build up.?

It did occur to me that the worsening of my symptoms that I got from manganese might just be the immune system activating to kill pathogens, and the fatigue I feel might just be from this immune response.

It says in this paper that:

Manganese appears to potently boost the innate immune system by increasing myeloid cells and NK cell activity, thereby facilitating the host's defense against infection

Some other excepts from the same paper:

Manganese, iron, and copper catalyze the conversion of hydrogen peroxide (H2O2) into oxygen radical species via the Fenton reaction. Thus, excessive levels of manganese, iron, and copper can cause cellular toxicity, leading to oxidative stress, genotoxicity, membrane perturbations, and protein dysfunction

And this might explain the low level of manganese in ME/CFS patients with chronic infections, since the body tries to hide minerals like manganese, so that pathogens, especially bacteria, cannot utilise them:

Organisms have developed a variety of defense strategies designed to prevent invading pathogens from acquiring metal ions such as Mn2+. One such well-known strategy is known as “nutritional immunity”.

Although circulating levels of manganese ions can reach 3.6 ng/mL, large amounts of metal ion‒binding proteins—primarily calprotectin, which is produced by neutrophils—are synthesized and secreted into the microenvironment in order to sequester essential metals from pathogens.

As a result, significantly reduced levels of manganese in the serum and tissues have been observed in patients with various types of infections.

Maybe taking high doses of manganese can actually increase bacteria growth, and that could be another possible explanation of why I felt worse on 20 mg of manganese daily.

 

[Wishful]

The 'nutritional immunity' strategy is interesting. I wonder if there's any way for GlassCannonLife to check for it, since that might explain his undetectable levels (which is otherwise odd).

 

[Alvin2]

It did occur to me that the worsening of my symptoms that I got from manganese might just be the immune system activating to kill pathogens, and the fatigue I feel might just be from this immune response.

It says in this paper that:



Some other excepts from the same paper:



And this might explain the low level of manganese in ME/CFS patients with chronic infections, since the body tries to hide minerals like manganese, so that pathogens, especially bacteria, cannot utilise them:


Maybe taking high doses of manganese can actually increase bacteria growth, and that could be another possible explanation of why I felt worse on 20 mg of manganese daily.

I know that anemia of chronic disease is the body sequestering iron to keep bacteria from accessing it, but didn't know manganese was in the same boat.
Is there a complete list somewhere of what the body can sequester during an infection?

 

[GlassCannonLife]

The 'nutritional immunity' strategy is interesting. I wonder if there's any way for GlassCannonLife to check for it, since that might explain his undetectable levels (which is otherwise odd).

I thought Ron Davis showed many pwME have the same deficiencies as I reported (perhaps not quite so many though!). I am definitely dealing with some EBV/CMV/HHV-6 (not sure exactly which to what proportion) reactivation at the moment so that might also be why..? But is that the case for most pwME?