Copper dysregulation

[Thewonders92]

I am asking if you have any evidence for your statement



The reference you linked, which talks about the 5 different ways in which histidine can complex with copper, is simply characterising an isolated histidine-copper complex in vitro.

I don't see how it is relevant to the function you claim in this quote, namely that histidine shuttles bio-available copper around the body.

I would like to know what the evidence is for this purported role of histidine, or is this more speculation on your part?

Also could you clarify do you mean the amino acid histidine is doing the shuttling or do you mean histidine as part of some protein (which?) is doing the shuttling.

Speculation is fine but I think you should make it clearer when you are speculating and when there are studies to support your statements.

Did you read the articles I mentioned?

I dont have my masters degree in molecular biology as you'd imagine given that this is a forum dedicated to people who for the most part are mentally and physically disabled. I would need to spend probably 5 years even if I were a molecular biologist just to understand the role of histidine related to maybe one or two forms of copper in the body.

I, like most others on this forum am more concerned with results than figuring out why. Take any enzyme in the body and you could either figure out in layman's terms how it functions so that you might proceed, or you could do the actual deep research and come up with 10,000 functions related to this, with another 10,000 for each of them and have spent 10 years withering away. I dont see how that would be effective.

What I do know, is that histidine does carry complexes of copper in the body, that many have been detected and the function isn't necessarily clear, that in vitro studies have been somewhat accurate in vivo, I'm assuming you didn't read the literature I passed on, if you want an in vivo replication of copper transport by histidine, there is one through dialysis. If introducing histidine increases the function of copper in the body while decreasing ceruloplasmin, I have to kind of go with that logically to dig deeper into that implication rather than spinning my wheels figuring out at exactly which terminals histidine acts upon, and at what pH it functions etc.

If histidine improves copper dependent enzymatic function, I'm only concerned with the why to the extent that I can understand its implication.

I'm assuming you are a lot more well educated on molecular biology than I am, so I passed on the studies where I got my information from, you could shed a lot more light on those studies than I can.

Also it's histidine as part of an unknown compound through albumin, I believe in the third study I linked this is mentioned and investigated. It's currently not known.

 

[alicec]

Did you read the articles I mentioned?

I skimmed those links which worked (one didn't).

I didn't find them particularly relevant to this shuttling role for histidine - (which you now clarify is part of some unknown protein) independently of ceruloplasmin and metallothionine.

The first one talks about a copper binding domain in the N-terminus of the CuZnSOD of a couple of pathogenic bacteria (not all bacteria) which is additional to the metal-binding active site of the enzyme. The authors speculate that this domain might bind copper under starvation conditions and pass it to the active site of the enzyme or to other molecules.

The second talks about the observed copper-binding properties of prion protein (PrP) and whether it plays a role in copper metabolism. Contrary to studies by others, these authors concluded that PrP is NOT a major copper binding protein and it does not shuttle copper to SOD.

The third also deals with PrP and simply characterises the copper-binding domain of the protein.

The fourth looks at the use of the amino acid histidine as a chelating agent to bind copper from serum.

I couldn't access the fifth reference.

I am not questioning the important role that histidine plays as part of the active site of metalloproteins. There is no doubt about that. I am questioning some of the speculative claims you have made which appear to be based on little or no evidence.

 

[NotThisGuy]

so @Thewonders92 any updates on your carnosine experiment?

 

[Thewonders92]

so @Thewonders92 any updates on your carnosine experiment?

I backed off the carnosine to experiment with the Tryptophan Kynurenine idea, saw a lot of promise in it.

Kidney function is completely normal now, don't need to balance my electrolytes anymore. Depression 80% gone and with drastic efficacy, didn't realize I could feel okay without the screaming highs, lymph nodes at least 50% down, arrythmia gone, body temperature fluctuations gone, normal bowel movements, joint and muscle pain at least 50% down, anxiety is gone, my vision and hearing have improved drastically.

All I can figure is that the antimicrobial properties of copper further aggravated my impaired gut biome, mega dosing probiotics has brought me to about 60% remission alone, haven't even begun with Jiaogulan, Reuteri, Berberine and prebiotics. 15+ years of misery gone over 3 days, pretty impressive but not surprising considering there are antibiotics in and on every single morsel of food we eat and the water we drink.

The antibiotic Tryptophan/Kynurenine, CFS is rooted at the gut theory doesn't fly much around here but I see almost no possibility beyond cancer where it is not the cause. I'll continue to share information as I collect it, so possibly someone will consider nothing short of therapeutic probiotic treatment can counter the massive influx of antibiotics we've consumed and are still consuming.

But yeah experiments in the future will likely be to get a boost rather than life or death shots in the dark, I feel better now than I have in probably 20 years, I know that technically means I didn't have CFS to begin with as I've seen stated time and time again here, but hey, it's sure nice not to be living in that nightmare anymore.

 

[NotThisGuy]

I dont understand. What made the you better?
Kidney function etc. is improved after few days carnosine? Or something else?
What kind of probiotic did u take?

 

[Thewonders92]

I dont understand. What made the you better?
Kidney function etc. is improved after few days carnosine? Or something else?
What kind of probiotic did u take?

Carnosine had the same effect as copper in increasing urinary output for a day (excessive, urinating 5 minutes after drinking water), to very little and dark colored urine by day two.

500 billion CFU probiotics per day, for 3 days. Brand (http://www.renewlife.com/ultimate-flora-extra-care-probiotic-100-billion.html)

By day two my kidney function of 1 month, and electrolyte imbalance of 5 or 6 years. Depression and anxiety of 15 years and progressively worsening fatigue of 15 years have improved substantially, most importantly for me kidney function is completely back to normal as far as urine output, color and frequency go.

Probiotics can be dangerous when someone is chronically ill, but I decided to roll the dice after the reading I've been doing.

The 60% I'm estimating is probably even lower as I'm getting better each day, and am questioning what the upper limit of feeling better or normal actually is.

There are side effects, after 3 days I dropped to 100 billion (yesterday) to make sure I don't throttle it too hard, and I plan to do rotations of 500 billion for 2 or 3 days every week, and 100 billion every day regardless. Side effects were weakened muscles on the third day (possibly d-lactate, which berberine and jiaogulan control, I don't have them yet though), itchy nose and face, and irritability without a drop in mood on day 4. Day 5 I've been totally fine and am waiting for my prebiotics and reuteri/tryptophan to come in.

Once I'm able to take 1-2 trillion CFU per day without side effects I will maintain 150 billion CFU indefinitely same brand but with 40 strains including reuteri.

I would imagine at least for me, I've been over consuming powerful antibiotics (glyphosate being one of them) for a very long time, had 5 rounds of antibiotics as a young child without probiotics and I believe I've been compromised ever since, the additional antibiotics on all the food I've been eating the past 20 years since further aggravated the situation.

 

[Little Bluestem]

I've been over consuming powerful antibiotics (glyphosate being one of them) for a very long time

Glyphosate is a herbicide, sold as Roundup in the US. It is an organophosphorus compound. If you had been consuming very much of it for a very long time, you would be dead.

 

[Thewonders92]

Glyphosate is a herbicide, sold as Roundup in the US. It is an organophosphorus compound. If you had been consuming very much of it for a very long time, you would be dead.

So you're more in agreement with Monsantos third party studies than the independent ones?

Ah well, let's agree to disagree.

 

[Tigger]

Awesome conversation @Thewonders92 ! Your issues match mine to a T. I've recently started taking L-Carnosine as well with the most positive results I've had in a long time. Any idea how the Acetyl form would change things? I was just considering given the amount of neurological functions impacted with bio-available/un-available copper.

 

[Thewonders92]

Awesome conversation @Thewonders92 ! Your issues match mine to a T. I've recently started taking L-Carnosine as well with the most positive results I've had in a long time. Any idea how the Acetyl form would change things? I was just considering given the amount of neurological functions impacted with bio-available/un-available copper.

Carnosine has the ability to cross the BBB so the added benefit usually seen with acetyl grouped amino acids is lost there.

The benefit to using acetyl-carnosine is that it prevents degradation by the carnosinase enzyme into histidine and beta alanine allowing more carnosine to build up. This can be bypassed through supplementing greater than 1gram of carnosine per day as this inhibits carnosinase and allows for the storage of carnosine, so that it may be used as carnosine, and also broken down to beta alanine and histidine by carnosinase over time.

I mostly see acetylcarnosine used in glaucoma treatment, which makes sense as only small amounts can be put into eye droppers. Carnosine in dosages exceeding 1 gram will have the same effect.

Acetylcarnosine is also substantially more expensive.

 

[Thewonders92]

I should also mention I stopped taking carnosine.

I was having severe panic attacks, tachycardia, respiratory depression and histamine issues.

This was either due to the histamine, or to carnosine in the presence of too much hydrogen peroxide (which anyone with a lot of oxidative stress will have in abundance when given antioxidants) histidine in the presence of hydrogen peroxide causes double DNA strand breaks.

It could have also been the magnesium malate I was taking in large doses, high amounts of malic acid cause issues. But I'm not going to be able to figure that out because I'm not willing to risk heart failure to try carnosine again on its own to find out.

I will say carnosine was the most effective anti depressant I'd ever tried, but contrary to the anxiolytic effects largely claimed I was having massive panic attacks which I've never had before, and was suffocating most of the time.
I can't attribute it directly to carnosine though so take it with a grain of salt.

 

[Tigger]

Good to hear about its ability to cross the BBB and subsequent savings in cost.

And I'm sorry to hear that. Just out of curiosity, what did the panic attacks feel like and what were the triggers if any? I've suffered from what I believe are histamine-triggered panic attacks my whole life triggered by just about any stressor, particularly social.

 

[NotThisGuy]

@Thewonders92

I was having severe panic attacks, tachycardia, respiratory depression and histamine issues.

Those are exactly mine histamine triggered panic attacks. Also by mold, too much oxalates or salycilates. So maybe a methylation problem or mitochondrial problem.

So now to the interresting part:
I had this kind of symptoms (the ones u had from carnosine) to a new degree after I supplemented B1 for a while. (anti-gylcation)
My friend had this symptoms with carcinine supplementation after a while. (anti-glycation)

So this symptoms seems to appear after a while of anti-glycation supplements.

Right know I'm starting to believe that this is a methylcobalamin deficiency.
At least for my friend those symptoms went away with methylB12. He had some PEM issues with methylB12 but mitoQ pretty much stopped the PEM and after 3 days everything was back to normal. Also his thyroid was quite a mess after carcinine.

I think the solution for me might be B12, too. I switched from the liquid B12 to sublingual and noticed in the past it wasn't as effective. I'm going back to the liquid B12 soon, so then I'll know for sure.

 

[NotThisGuy]

Also interestingly. ALA gives me and my friend glaucoma like symptoms. Didn't know carnosine cures glaucoma.
Maybe all anti-glycation supplements have to be taken together instead isolated?

 

[salam]

Which Carnosine form is better to supplement with orally For MAO-A deficient and undermethylator with high blood pressure, N-Acetyl-Carnosine or L-Carnosine?

 

[Chocolove]

@Thewonders92 What kind of copper supplement were you taking? Not oligo amounts?

 

[Gondwanaland]

Also interestingly. ALA gives me and my friend glaucoma like symptoms. Didn't know carnosine cures glaucoma.
Maybe all anti-glycation supplements have to be taken together instead isolated?

Could you please describe the symptoms? I get eye issues too (pain - dr. said I have epithelial dystrophy in the cornea and prescribed hyaluronic acid drops which cause me photophobia + ingestion of linseed oil which I will start tonight).
I suspect glycine deficiency might be playing a role since it is one of the main constituents of eye tissues.
B5 worsens it dramatically (B5 is a known antagonist of taurine, bile acids, probably also glycine?).

Which Carnosine form is better to supplement with orally For MAO-A deficient and undermethylator with high blood pressure, N-Acetyl-Carnosine or L-Carnosine?

Carnosine is a MAOI, and even though I am +/+MAO-A, I have low serotonin probably due to +/+MTHFR 1298, and Carnosine did wonders for my mood.

Now something important about copper is that polyphenol oxidase from foods might be binding lots of copper, and giving false higher results than what can actually be absorbed for those who use cronometer to track micronnutrient intake.
https://en.wikipedia.org/wiki/Polyphenol_oxidase
+ enclosed pdf file

 

[Gondwanaland]

Subcutaneous copper-histidine is the treatment for Menkes disease (genetic copper deficiency)

Carnosine in the presence of too much hydrogen peroxide (which anyone with a lot of oxidative stress will have in abundance when given antioxidants)

I got a lot of H2O2 from carcinine

I will say carnosine was the most effective anti depressant I'd ever tried

Ditto from carcinine. I think this is not only from MAO blocking, but also from increased gluathione production and improved sulfation with fast hormone, phenol, sulphite etc breakdown

I was having massive panic attacks which I've never had before, and was suffocating most of the time.

I got hyperthyroid from it = iodine and B1 depletion. I think it will also deplete molybdenum.

Right know I'm starting to believe that this is a methylcobalamin deficiency.
At least for my friend those symptoms went away with methylB12. He had some PEM issues with methylB12 but mitoQ pretty much stopped the PEM and after 3 days everything was back to normal. Also his thyroid was quite a mess after carcinine.

Add B12 to the list.

Also interestingly. ALA gives me and my friend glaucoma like symptoms. Didn't know carnosine cures glaucoma.
Maybe all anti-glycation supplements have to be taken together instead isolated?

I think they do. Lipothiamine contains a small amount of ALA. @Asklipia got huge gains with carcinine + B1 megadosing.

I think it is safe to say that anti-glycation supps remove the metabolism roadblocks and deplete all vitamins, minerals and aminoacids.

 

[Gondwanaland]

@Thewonders92 could you please update us on your health?

 

[Gondwanaland]

I have taken Mitosynergy copper & I *think* it helped

Do you have an update for us?