• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Methionine Synthase

Messages
69
There appears to be overwhelming evidence that (MS) is in fact a cuproenzyme, leaving me kind of scratching my head at its exclusion or antagonism in any methylation programs, specifically those involving B12/Folate.

Keep in mind that a long standing copper deficiency results in copper toxicity by nature of coppers role in the body. Blood tests are inconclusive on this matter as high copper in blood serum can be an indicator of any level of inflammation, infection or oxidative stress in the body. A liver biopsy is the only reliable method of determining copper status in the body.

https://www.ncbi.nlm.nih.gov/pubmed/10350650

Copper deficient rats saw a 21% reduction in (MS) activity.
Copper deficient rats saw elevated hepatic 5-methyltetrahydrofolate and homocysteine concentrations.

https://www.ncbi.nlm.nih.gov/pubmed/17513393
Copper deficient rats saw a significant decrease in plasma homocysteine.
Copper deficient rats saw down regulation in BHMT function (MS shortcut).
Trimethylglycine (Betaine) lowers homocysteine substantially.
Copper deficient rats saw increased amounts of gluathione.
This is in contrast to longstanding copper deficiency which eventually leads to increased homocysteine. Shortterm loss of homocysteine through the transulfuration will lead to longterm (MS) dysfunction.

https://www.ncbi.nlm.nih.gov/pubmed/18472229
Copper deficient myleopathy is strikingly similar to subacute combined degeneration (SCD) of which B12 is involved.

http://m.pnas.org/content/101/12/4234.full
There is indication in a rare case of s-adenosyl-homocysteine hydroylase deficiency that copper dysregulation exists between homocysteine to methinionine, and not pre-homocysteine.
Ceruloplasmin and copper levels were found to be normal in the case of 30 and 150x fold increases to AdoMet and AdoHcy respectively.
A lowered demand for homocysteine recycling appears to spare copper.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076209
Homocysteine directly antagonizes serum copper levels, preventing the healthy functioning of cuproenzymes.

Copper, as it appears to be essential to the functioning of methinione synthase, could in a time of infection or stress, be spread far too thin in the body to adequately break down homocysteine, leading to an eventual antagonism of copper, creating a deficiency state alongside a toxic state. Inadequate copper supply will hinder the (MS) enzyme, preventing the breakdown of homocysteine, further increasing the need for copper to break down homocysteine, further impairing cuproenzyme activity until eventually (MS) has lost function creating an exponentially worsened state of copper deficiency in the body.

Ceruloplasmin is copper dependant and is required to remove copper from the body (histidine seems to serve this same function very well), in cases where ceruloplasmin is impaired, copper will build up in tissues. Increasing the demand for Zinc to create (MT), impairing zinc functions throughout the body, eventually lowering CuZnSOD and causing extreme oxidative stress throughout the body, depleting essential minerals everywhere through a cascading effect.

In a histidine deficient state, our secondary carrier and eliminator of copper from the body is also impaired, thus a copper and histidine deficient state over a period of time eventually guarantees high oxidative stress, impaired copper function, copper deficiency and toxic levels of copper in the body, impaired zinc function, and overall incredibly impaired methylation cycle.

Lacking Histidine (powerful metal carrier) SOD, MT and Cp will allow heavy metals to run rampant the body, leading to increased accumulation. These metals also antagonize copper and zinc.

It seems to me that if a person has been on a methylation protocol for several months and isn't getting better they should consider what methinionine synthase is fundamentally.

Supplementing or refeeding copper will not correct this deficiency and is incredibly dangerous, as it will reactivate many enzymatic functions that have been shut down or slowed down over time, resulting in an even higher need for copper without any adequate way of removing it afterwards. I'm doing research on carnosine, that's in the general forum if you'd like to these a look, but I've been curious about it in regards to methylation for a while and figured I'd do a quick bit of research on it in regards to methylation.

My current idea for rebalancing copper and zinc in the body is through the use of Carnosine (histidine is absolutely required for all essential mineral functioning and transportation in the body, including MT, SOD and ceruloplasmin, as well as the chelation of free copper from the body), a balanced diet including copper at adequate levels, TMG at dosages ranging from 3-12 grams per day to temporarily offset the need of copper in (MS) when TMG can do a good enough job meanwhile, and obviously plenty of water and rest.

I don't believe driving (MS) with folate and b12 is safe in as copper deficient state, though I'm not giving treatment advice here, just outlining my current research.
 
Last edited:
Messages
69
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671677/
A study involving the dangers of copper deficiency alongside elevated homocysteine.
They actually seem to be working under the high serum copper=/=Copper deficiency model, but the results are still the same. They did note that it was interesting how the results came in, I don't really understand the disconnect.

A copper deficient diet alongside high homocysteine results in high pressure aortic ruptures, copper repletion in rats at the human equivalent of 6mg daily has been shown to significantly treat heart disease in mice.

Homocysteine also antagonizes and lowers the functioning of cuproenzymes, understanding this makes the idea of forcing methylation through high dose folate and b12, without adequate copper to sustain (MS) function, as well as impaired health globally and lack of cuproenzymatic function could result in severe heart problems. Noted are prolonged QT intervals, arrythmia and pressure buildup damaging arterial lining. I have noticed that some folks who are pushing their methylation cycle end up with general heart issues, or even have to quit because of it, I'm not sure if anyone involved with methylation protocols has had a heart attack though.

But the danger is there, pushing a cuproenzymes (MS) function to the limit in a copper deficient state will further increase homocysteine and further deplete bioavailable copper, increasing more of a buildup of oxidized copper and oxidative stress without bioavailable copper to manufacture CuZnSOD.

I want to remind everyone that as simple a source as wikipedia will show you that copper serum testing is pointless and could be taken either way, though for whatever reason this isn't getting through to the majority of medical researchers and family Doctors.
 

aquariusgirl

Senior Member
Messages
1,732
Interesting stuff...& I have only skim read....you should probably email DR Richard Deth @ Nova Southeastern University....world expert in the MS enzyme.


He always responds .

I gave thought for a long time that copper & iron dysregulation is at the root of this disease but the testing is lacking
 
Last edited:

aquariusgirl

Senior Member
Messages
1,732
Also I personally think based on my experience that Mitosynergy copper gets around the issues you are talking about but I would never encourage anyone else to supplement copper.,,,we just don't know enough.


But I don't think carnosine & TMG is going to do much of anything..,,

Also did you see my earlier posts ..,Dr Cohen on copper in biofilm? Professor Cooper's copper chelation?
 
Last edited:

NotThisGuy

Senior Member
Messages
312
Also I personally think based on my experience that Mitosynergy copper gets around the issues you are talking about but I would never encourage anyone else to supplement copper.,,,we just don't know enough.


But I don't think carnosine & TMG is going to do much of anything..,,

Also did you see my earlier posts ..,Dr Cohen on copper in biofilm? Professor Cooper's copper chelation?

did u ever take normal copper supplements? or did u start with mitosynergy?
 
Messages
69
Also I personally think based on my experience that Mitosynergy copper gets around the issues you are talking about but I would never encourage anyone else to supplement copper.,,,we just don't know enough.


But I don't think carnosine & TMG is going to do much of anything..,,

Also did you see my earlier posts ..,Dr Cohen on copper in biofilm? Professor Cooper's copper chelation?

I did yes, I will attempt to make contact with him.

This does seem very interesting, Mito-synergy I mean, the Niacin binding has me very curious as Niacin is always implicated in overmethylation.

I'll give it a shot and some research and review it.

But I'm not really sure how you figure Carnosine will have no result on copper dysregulation. Histidine is required to manufacture most cuproenzymes as well as most mineral dependant enzymes in the body, regardless of whether or not methinionine synthase is a cuproenzyme I would say that carnosine would have some effect on copper metabolism given its metabolite is necessary for copper functioning in the body.

There's overwhelming evidence to support histidine as both an essential carrier of minerals especially copper, and to chelate and remove them afterwards. I don't know if evidence is even the right word, it's an established medical fact.
 
Messages
69
Only MitoSynergy

It's a 50/50 chance that you're not in the same boat as myself and Notthisguy in that case, as we are both experiencing pretty severe health effects revolving around copper supplemanation.

I will try mitosynergy though regardless, it does seem very interesting to me. I'm going to do some research into B3 status and copper, perhaps it's a lack of binding to niacin or some related mechanism that's causing the issues.
 

aquariusgirl

Senior Member
Messages
1,732
Yeah I mean I have so much copper stashed away that I will have to chelate. Need heavy hitting solutions
 
Messages
69
Yeah I mean I have so much copper stashed away that I will have to chelate. Need heavy hitting solutions

I'm going to order some today.

Coincidentally before looking into mitosynergy, I did actually take niacin for the first time today in a few months and have had improved kidney function all day, it's the first time in a week. This does seem very promising.
 

NotThisGuy

Senior Member
Messages
312
I think I'm gonna order it soon, too.
Im still left with copper damage, but maybe mitosynergy can resolve this.
 

NotThisGuy

Senior Member
Messages
312
I'm going to order some today.

Coincidentally before looking into mitosynergy, I did actually take niacin for the first time today in a few months and have had improved kidney function all day, it's the first time in a week. This does seem very promising.

Its really bad that u split those threads thewonders92.
It would be easier if everything is in one thread.
 

Violeta

Senior Member
Messages
2,895
I am looking at copper toxicity/biounavailability again because of post herpetic neuralgia, and I am trying beta alanine and taurine combination, along with small amounts of MegaFood zinc. It's helping the fatigue more than the neuralgia so far. I didn't read this whole thread, I'll do that this evening.
 

Violeta

Senior Member
Messages
2,895
One controls copper and the other controls zinc, for some reason. I am sorry to be so vague, but every since coming down with shingles my brain is mush.

Might I ask to all in this thread, I don't know anything about ME, but I just started taking selenomethionine a couple of days ago, I am fairly sure I need selenium, and I had seen that it can be related to sulfur metabolism, but I actually forget what I was going to ask about it. I am rushing to get ready for my first day back at work. If there is anything input that anyone can add, I would be interested.
 

Gondwanaland

Senior Member
Messages
5,092
If there is anything input that anyone can add, I would be interested.
Selenium is needed to convert T4 into T3, and so is copper.

ETA
http://www.acu-cell.com/ses.html
Some people - because of media hype (more is better) - take several hundred mcg of selenium a day, but I usually advise my own patients against higher amounts - not so much because of selenium toxicity (although that does become a concern at higher amounts), but because of its antagonism to chromium, magnesium, zinc and other nutritional factors. Long-term excessive intake of selenium increases the potential risk of triggering shingles, or developing trabecular osteoporosis, cystadenoma (usually in the throat), an enlarged prostate, reduced glucose tolerance / diabetes, neurological disturbances, or other negative consequences.
 
Last edited:

Gondwanaland

Senior Member
Messages
5,092
Last edited:

Gondwanaland

Senior Member
Messages
5,092
http://www.acu-cell.com/crcu.html
Copper shares many attributes with calcium, whereby both can become bio-unavailable at high levels and result in symptoms of deficiency!Some practitioners, being unaware of the underlying copper excess, and lacking the resources to test intracellular levels of copper, get temporary results by having a patient supplement more copper. Despite the initial improvement, this can have disastrous long-term effects on a patient's physical and mental health.

The correct approach consists of making copper (or calcium) more bioavailable by supplementing the proper co-factors, with the best choice being those whose levels are lowest ratio-wise to copper - and as mentioned above - may include Vitamin C, chromium, sulfur (MSM), molybdenum, nickel, or (rarely) zinc. The avoidance of foods high in copper is important as well. This will take care of the medical conditions a practitioner was originally consulted for, and at the same time prevents the potential development of new medical problems elsewhere related to excessive copper intake.

Chromium has to be considered first when trying to normalize copper, since it is its associated trace element. Many aches and pains, arthritis, slow-healing fractures, sciatica and other back problems, various infections, etc, can be relieved with chelated chromium (not GTF chromium), provided:
a) they conform to the left side-specific receptor requirements,
b) calcium and magnesium are close to normal, since they are also involved with various disorders of the musculoskeletal system, and
c) potassium levels are not below normal, since chromium is a potent potassium antagonist.

Following a close second is Sulfur, usually supplemented in the form of MSM, whose main action in addition to helping restore cartilage formation is the lowering of copper! So again, it is the high copper levels which created a need for sulfur to help reverse joint degeneration. Originally, glucosamine sulfate (another copper-lowering sulfur compound) had been the non-drug treatment of choice for joint problems, however its blood sugar raising potential has considerably reduced its popularity in individuals with blood sugar disturbances (e.g. diabetes), so MSM has become the preferred choice instead.

Copper works synergistically with potassium and calcium, so when patients do exhibit low copper levels, then calcium and potassium are frequently on the low side as well.

Supplementing 3 mg of copper for one to two weeks, or less, is all that is needed for an adult to normalize any copper deficiency, but then it should be discontinued or reduced, otherwise copper may go too high.
.....
Copper Synergists:
Calcium, potassium, iron, Vitamin E.

Copper Antagonists / Inhibitors:
Sulfur, molybdenum, zinc, nickel, chromium, tin,
Vitamin B6, Vitamin C, hesperidin, insoluble fiber.