• 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, 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.

Interesting results supplementing copper, but also side effects

Messages
31
After several months of taking/injecting b12 and failed attempts to use b1, my peripheral neuropathy didn't seem to go away, my histamine intolerance, tremors, cramps, circulatory and blood pressure just got worse plus my blood tests resulted in normal b1, 6 and 12.

As a last attempt I decided to supplement 2mg of copper gluconate, to my surprise on the sixth day my feet were 50% better, the cramps reduced, blood pressure normalized, no dizziness, nice energy levels and that feeling of agony and imminent panic attack reduced a lot! However, I noticed that I was much more irritable, my testicles smaller, my skin drier and it seems that my oral candida got worse, my gut too. I saw that some users reported treating copper deficiency with similar doses but I didn't see anyone with these side effects, any idea how to proceed? Thanks!
 

datadragon

Senior Member
Messages
404
Location
USA
Copper is required to be attached to ceruloplasmin to be usable by the body for this and its many other functions, otherwise you can have plenty of copper intake but still be deficient at the same time due to the lack of ceruloplasmin to make it usable. Most are not low in copper intake but low in being able to produce ceruloplasmin allowing both unbound copper and iron to build up and potential deficiency at the same time. Individuals lacking ceruloplasmin display iron overload in selected tissues, including liver, brain over time. Cp deficiency also impaired the behavioral ability of mice, including weakened exercise ability and reduced motor coordination. https://link.springer.com/article/10.1007/s12013-022-01061-9

Ceruloplasmin requires zinc, magnesium and Vitamin A to make our copper and iron bioavailable (usable).
Its also not generally known that under inflammation the cofactors for ceruloplasmin are depleted. The problem is again more that the zinc and Vitamin A become unavailable/deficient during inflammation/infection and so for most cases causing a deficiency of usable copper despite plenty of intake. It has been explained that it is kind of like being in the middle of the ocean surrounded by water, yet still starved of usable water to drink. Zinc deficiency further increases copper, again it all makes sense looking at it via just one part of the shift to an inflammatory state like a see saw. Its possible to check serum copper and serum ceruloplasmin (the usable copper) and can calculate free copper levels unbound to ceruloplasmin but this is a spot check at the time of the test only and does not reflect any long term accumulation in the tissues over time. https://web.archive.org/web/2021030...ients-families/lab-tracker-copper-calculator/

Ceruloplasmin, a copper-containing acute phase plasma protein, has been shown to be regulated by 13-cis retinoic acid, an active metabolite of Vitamin A in rats https://www.ncbi.nlm.nih.gov/pubmed/3655940 Ceruloplasmin and Vitamin A also require Zinc and thats where problems occur as under inflammation zinc availability and uptake/absorption is reduced. The cytokine interleukin 6 (IL6) and others induces the expression of Metallothionein and consequently reduces zinc availability. IL-6 is released during the acute phase of an inflammatory response. Interleukin-6 (IL-6) up-regulates the ZIP14 gene expression, which in turn, is responsible for an excess of intracellular zinc and, at the same time, for hypozincemia that accompanies the acute phase response to inflammation and infection. The cytokine interleukin 6 (IL6) induces the expression of Metallothionein and α2-macroglobulin (A2M) and consequently reduces zinc availability. IL-6 is released during the acute phase of an inflammatory response. This mechanism is beneficial to the acute immune response, however, a long-term decrease in zinc availability may contribute to pathological processes in conditions of chronic inflammation. https://www.pnas.org/content/102/19/6843

Its even been found that all trans retinoic acid at higher levels can even help with a genetic form of reduced ceruloplasmin found in Wilsons Disease. Ceruloplasmin secretion-based drug screening identified all-trans retinoic acid (ATRA) and other active Vitamin A metabolites as promising candidates for rescuing Ceruloplasmin secretion. ATRA also alleviated reactive oxygen species (ROS) production induced by lipid accumulation in Wilsons Disease-specific hepatocytes. In wilsons disease some people have genetics that cause this although I found it can happen just from excessive chronic inflammation. https://www.biorxiv.org/content/10.1101/2021.08.10.455792v1
https://forums.phoenixrising.me/thr...ons-disease-october-2-2023.90883/post-2445674 This is all more of a summary as I've omitted large amounts of the research to simplify.
 
Last edited:
Messages
31
But i think my neuropathy was aggravated by 30mg zinc + 1g vitamin C over the years plus 3 months of 1200mg NAC, of course low b12 over the years also contributed, but there was a huge worsening of symptoms after the combination of zinc, vitamin c and NAC.
My biggest fear now is copper messing with my liver, gallbladder, gut, hormones and kidneys, but the great improvement in neuropathy cheered me up!
 

datadragon

Senior Member
Messages
404
Location
USA
But i think my neuropathy was aggravated by 30mg zinc + 1g vitamin C over the years plus 3 months of 1200mg NAC,
It sounds like you may have induced a true copper deficiency with high dose zinc and Vitamin C which you can check into. NAC has been shown to have metal-chelating capabilities including copper and zinc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696987/

I was just also explaining that some people who are dealing with chronic inflammation can experience a copper deficiency even as they supplement normal copper also. Or dont have one of the cofactors available as well to utilize it. Someone without inflammation may have great results from the copper while the person under inflammation would obviously have a much worse result. Thats why beef liver for example has high copper but also the cofactors so it works well as a copper source that is bioavailable but only need a very small amount not the big doses some say to take. Hopefully there will also be more attempts at copper that is bioavailable as a drug/supplement.


I guess taking zinc or copper without the other can cause problems, or else one of the other things. It can be hard to figure out how they fit together and its different for everyone.

Yes they are like a see saw. Many people however who have chronic health problems sometimes find they have chronic inflammation which then would suggest unavailability and lowered absorption of zinc, copper deficiency yet a high unbound copper at the same time that starts accumulating in the tissues over time. Its at least testable so you dont have to guess.
 
Last edited:
Messages
31
@datadragon

And every time I tried to take zinc, vitamin C, rutin, hisperidin or anything that affects copper, I felt needles in my feet on the same day, as well as feeling very sick and worsening other symptoms, very similar to a b12 deficiency( which was the first suspicion), the subsequent months of NAC and b1 also coincide with the worsening of my histamine intolerance, I had to stop using boulardii and reuterii after this incident and medications that used to make me sleep like Trazodone now cause me allergic attacks that keep me up all night, it's really brutal and I'm running out of things, I'm only sleeping with Ambien and 4 hours a night!

Something that caught my attention about copper is that it supposedly has antimicrobial actions but the impression I have is that it completely worsened my gut, is it possible that it killed the good bacteria?
 

datadragon

Senior Member
Messages
404
Location
USA
Copper is also anti fungal and that is also reliant on ceruloplasmin production requiring zinc to make the copper bioavailable (usable by the body). Under typical prolonged inflammation/infection as the zinc availability and absorption lowers, this can therefore also cause copper to become in a non usable (non bio available) state and instead start to accumulate in the tissues and would not therefore be able to provide its role to help control fungi and yeast/candida in the gut. Zinc is also involved in Vitamin A metabolism (and vice versa). In addition to ceruloplasmin, Vitamin A is crucial to a very sophisticated bi-directional mechanism that takes place in the digestive system and leads to immune tolerance across the entire gut lining. Moderate levels of vitamin A in the intestine prevent the immune system from becoming overactive. https://www.medicalnewstoday.com/articles/324066 https://www.clinicaleducation.org/resources/reviews/vitamin-a-the-key-to-a-tolerant-immune-system/

When hydrochloric acid (HCl) is low which also requires zinc, the healthy gut flora are weakened. HCl helps kill off pathogens and is required for the absorption of nutrients such as calcium, iron, and various vitamins. Reduced digestive enzyme production occurs and the intestine becomes overly alkaline, giving a nice home which allows candida, fungi, yeast, parasites and bacteria to flourish.

Zinc deficiency also leads to the leaky gut and changes in the microbiome composition and function toward a more inflammatory state including the reduction in lactobacillus population as part of that, increased propionate and decreased butyrate, and alongside that within the brain are signs of neuroinflammation all from the recent research. Heres just one of them. Acute zinc-deficient mice have an altered composition of gastro-intestinal (GI) microbiota. These changes were accompanied by alterations in markers for GI permeability and within the brain signs of neuroinflammation. Zinc deficiency alters gut microbiota composition and function. Zinc deficiency induces significant taxonomic alterations and decreases overall species richness and diversity, establishing a microbial profile resembling that of various other pathological states, along with concomitant decreases in beneficial short chain fatty acids. https://www.ncbi.nlm.nih.gov/pubmed/31849598

Pathogens must acquire trace minerals in order to replicate and cause disease. However, during infection, the host sequesters key nutrients restricting access to these nutrients as a part of a process known as nutritional immunity. Its part of the normal response to infection but can be problematic if prolonged. https://www.yeastinfectionadvisor.com/zinc.html and https://pubmed.ncbi.nlm.nih.gov/27242763/
 
Last edited:

linusbert

Senior Member
Messages
1,246
for copper one might try out 100% pure cocoa or dark chocolate 100%.
like 25g serve already the daily requirements and even more. there is a study where they treated successfully copper deficiency with cocoa. in about 4-6 weeks timeframe.

i cannot tolerate any copper supplement, i get nausea and dizziness like if i had a bad alcohol hangover.
but i can eat dark chocolate/cocoa.

for zink, it might be beneficial to supplement a zink-histidine complex... but they must be bound together as molecule and not a supplement with both 2 separate zink + l-histidine. histidine is the natural protein to transport zink in the body like coeruloplasmin is for copper and iron. its much better bio available and i guess much less side effects due to bound to transport protein already.

lactoferrin is a transport protein for iron. it also has a bit of capacity for copper.
lactoferrin is available as supplement and some say its better to treat iron deficiency with lactoferrin with or without iron because it increases bioavailability of iron.
i could imagine that it helps with copper metabolism too, because if less coeruloplasmin is needed for iron transport more is available for copper - but thats a guess of mine, not sure if this is how it works.
 

datadragon

Senior Member
Messages
404
Location
USA
Personally I tried some things like this ancestral beef liver which would be a good bioavailable form due to including the cofactors, only taking one capsule for example rather than a full dose for me as Im not naturally a fan of beef liver https://www.amazon.com/Ancestral-Supplements-Grass-Liver-Desiccated/dp/B01MSBZYQW/

Copper supplements otherwise may work much better again when not dealing with high inflammation or infection which creates a problem with the cofactors needed for ceruloplasmin in order to utilize copper and then iron and thats mainly where much of the problem lies as its part of the shift to an inflammatory state. Low usable copper will then also affect iron causing unbound iron to build up and can also cause a deficiency of iron at the same time. Copper in an inorganic form however is best avoided whenever possible. In drinking water samples from 280 households about a third of these samples had levels above 0.1 ppm copper, the level causing AD-type toxicity in animal models. Another third were at intermediate copper levels of unknown toxicity, and only one-third were at a level we consider completely safe, that is 0.01 ppm or less and also linked to the increase in inorganic copper ingested through water piping, copper sulfate sprayed on crops, copper iud, some copper supplements, and copper is also passed down through the placenta. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030141/ I had briefly mentioned here https://forums.phoenixrising.me/thr...lock-il-6-trans-signalling.90433/post-2438840
 
Last edited:
Messages
31
I'll have to stop using copper for a bit because I think ursodiol is making my gallbladder worse instead of better, when it's not one thing it's another! If I return to take copper I will return with information, thank you all!
 
Messages
31
Copper is required to be attached to ceruloplasmin to be usable by the body for this and its many other functions, otherwise you can have plenty of copper intake but still be deficient at the same time due to the lack of ceruloplasmin to make it usable. Most are not low in copper intake but low in being able to produce ceruloplasmin allowing both unbound copper and iron to build up and potential deficiency at the same time. Individuals lacking ceruloplasmin display iron overload in selected tissues, including liver, brain over time. Cp deficiency also impaired the behavioral ability of mice, including weakened exercise ability and reduced motor coordination. https://link.springer.com/article/10.1007/s12013-022-01061-9

Ceruloplasmin requires zinc, magnesium and Vitamin A to make our copper and iron bioavailable (usable).
Its also not generally known that under inflammation the cofactors for ceruloplasmin are depleted. The problem is again more that the zinc and Vitamin A become unavailable/deficient during inflammation/infection and so for most cases causing a deficiency of usable copper despite plenty of intake. It has been explained that it is kind of like being in the middle of the ocean surrounded by water, yet still starved of usable water to drink. Zinc deficiency further increases copper, again it all makes sense looking at it via just one part of the shift to an inflammatory state like a see saw. Its possible to check serum copper and serum ceruloplasmin (the usable copper) and can calculate free copper levels unbound to ceruloplasmin but this is a spot check at the time of the test only and does not reflect any long term accumulation in the tissues over time. https://web.archive.org/web/2021030...ients-families/lab-tracker-copper-calculator/

Ceruloplasmin, a copper-containing acute phase plasma protein, has been shown to be regulated by 13-cis retinoic acid, an active metabolite of Vitamin A in rats https://www.ncbi.nlm.nih.gov/pubmed/3655940 Ceruloplasmin and Vitamin A also require Zinc and thats where problems occur as under inflammation zinc availability and uptake/absorption is reduced. The cytokine interleukin 6 (IL6) and others induces the expression of Metallothionein and consequently reduces zinc availability. IL-6 is released during the acute phase of an inflammatory response. Interleukin-6 (IL-6) up-regulates the ZIP14 gene expression, which in turn, is responsible for an excess of intracellular zinc and, at the same time, for hypozincemia that accompanies the acute phase response to inflammation and infection. The cytokine interleukin 6 (IL6) induces the expression of Metallothionein and α2-macroglobulin (A2M) and consequently reduces zinc availability. IL-6 is released during the acute phase of an inflammatory response. This mechanism is beneficial to the acute immune response, however, a long-term decrease in zinc availability may contribute to pathological processes in conditions of chronic inflammation. https://www.pnas.org/content/102/19/6843

Its even been found that all trans retinoic acid at higher levels can even help with a genetic form of reduced ceruloplasmin found in Wilsons Disease. Ceruloplasmin secretion-based drug screening identified all-trans retinoic acid (ATRA) and other active Vitamin A metabolites as promising candidates for rescuing Ceruloplasmin secretion. ATRA also alleviated reactive oxygen species (ROS) production induced by lipid accumulation in Wilsons Disease-specific hepatocytes. In wilsons disease some people have genetics that cause this although I found it can happen just from excessive chronic inflammation. https://www.biorxiv.org/content/10.1101/2021.08.10.455792v1
https://forums.phoenixrising.me/thr...ons-disease-october-2-2023.90883/post-2445674 This is all more of a summary as I've omitted large amounts of the research to simplify.

My blood tests came back and my copper levels are back to normal even though I only took 2mg every 5 days (any more than that and I felt a lot of side effects, but I managed it on two occasions maintain 2mg for 5 consecutive days) but my ceruloplasmin is still low!

I am thinking about supplementing Vitamin A to increase ceruloplasmin, what would be the recommended dose?

I don't know if I should give vitamin C a second chance, I read that there is a big difference between fruit-based vitamin C supplements and ascorbic acid, which is what I was taking when I caused my copper deficiency, is it worth trying to supplement with a natural source of vitamin C to increase my ceruloplasmin? Thank you again!
 

linusbert

Senior Member
Messages
1,246
I don't know if I should give vitamin C a second chance, I read that there is a big difference between fruit-based vitamin C supplements and ascorbic acid, which is what I was taking when I caused my copper deficiency, is it worth trying to supplement with a natural source of vitamin C to increase my ceruloplasmin? Thank you again!
red pepper has like 120-150mg each, kiwi is around 50mg and gold kiwi around 100.
or acerola direct juice (when the juice is directly pressed into a bottle and not dried as powder extract and then mixed with water).

supplements are flawed, you might try different formulations and vendors.
 

datadragon

Senior Member
Messages
404
Location
USA
My blood tests came back and my copper levels are back to normal even though I only took 2mg every 5 days (any more than that and I felt a lot of side effects, but I managed it on two occasions maintain 2mg for 5 consecutive days) but my ceruloplasmin is still low!

I am thinking about supplementing Vitamin A to increase ceruloplasmin, what would be the recommended dose?

I don't know if I should give vitamin C a second chance, I read that there is a big difference between fruit-based vitamin C supplements and ascorbic acid, which is what I was taking when I caused my copper deficiency, is it worth trying to supplement with a natural source of vitamin C to increase my ceruloplasmin? Thank you again!
Vitamin A and ZInc are both necessary for ceruloplasmin production, but during ongoing inflammation or infection the zinc can become unavailable to utilize fully as it is brought into the cell during that time setting off a see saw switch to an inflammatory state instead. The itaconate shunt is just part of that switching by zinc. So lowering inflammation and supplementing zinc may be helpful to restore zinc metabolism when its just inflammation related and not infection caused. A low dose of retinol Vitamin A would also suffice as it would become inflammatory instead if zinc is not available for Vitamin A metabolism helping convert Vitamin A to active forms and where you can get into toxicity problems with retinol Vitamin A intake. Copper is not stored in the blood by the way for testing long term accumulation such as why wilsons patients have buildup in tissues etc over time, however copper is another that would become inflammatory due to the low ceruloplasmin caused from unavailable zinc again like a see saw switch the body makes to go into an inflammatory state. In other words taking copper or Vitamin A without fixing the inflammation or zinc issue can just increase inflammation. Even Vitamin D and B6 as well as butyrate I found will also become more inflammatory when you take them with unavailable zinc during chronic inflammation or infection states as zinc is involved in all of their metabolism(s). Other effects such as BH4 becomes low as well due to the zinc switch which increases inflammatory INOS instead. Zinc normally regulates that switch as I've covered before.

Vitamin C whole food forms are apparently not going to lower ceruloplasmin so thats one reason its helpful in that state, but its possible based on the limited research that ascorbic acid can lower ceruloplasmin so something to likely avoid (as ascorbic acid) during chronic inflammation or infection (ongoing use). You can try a natural whole food source if you wish to try to benefit without potentially having an effect on ceruloplasmin.
 
Last edited:
Messages
31
Vitamin A and ZInc are both necessary for ceruloplasmin production, but during ongoing inflammation or infection the zinc can become unavailable to utilize fully as it is brought into the cell during that time setting off a see saw switch to an inflammatory state instead. The itaconate shunt is just part of that switching by zinc. So lowering inflammation and supplementing zinc may be helpful to restore zinc metabolism when its just inflammation related and not infection caused. A low dose of retinol Vitamin A would also suffice as it would become inflammatory instead if zinc is not available for Vitamin A metabolism helping convert Vitamin A to active forms and where you can get into toxicity problems with retinol Vitamin A intake. Copper is not stored in the blood by the way for testing long term accumulation such as why wilsons patients have buildup in tissues etc over time, however copper is another that would become inflammatory due to the low ceruloplasmin caused from unavailable zinc again like a see saw switch the body makes to go into an inflammatory state. In other words taking copper or Vitamin A without fixing the inflammation or zinc issue can just increase inflammation. Even Vitamin D and B6 as well as butyrate I found will also become more inflammatory when you take them with unavailable zinc during chronic inflammation or infection states as zinc is involved in all of their metabolism(s). Other effects such as BH4 becomes low as well due to the zinc switch which increases inflammatory INOS instead. Zinc normally regulates that switch as I've covered before.

Vitamin C whole food forms are apparently not going to lower ceruloplasmin so thats one reason its helpful in that state, but its possible based on the limited research that ascorbic acid can lower ceruloplasmin so something to likely avoid (as ascorbic acid) during chronic inflammation or infection (ongoing use). You can try a natural whole food source if you wish to try to benefit without potentially having an effect on ceruloplasmin.
Thanks! My zinc levels are normal too, I took zinc for several years but after my bad experience with NAC and thiamine which triggered MCAS/Histamine Intolerance I have difficulty taking zinc, even in a small dose of 10mg my neuropathy returns on the same day, I'm going to risk just Vitamin A, I hope it has a positive impact on ceruloplasmin and doesn't trigger my MCAS!
 
Back