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Copper: The intermediate cause of PET? - Caravaggio - 01-29-2019
In my previous hypothesis I claimed acetylcholine as the cause of PET but this is just one of 3 steps to the root cause.
Now I probably found the 2nd step: copper.
When acetylcholine is the train then copper is the damaged railway.
When you have a damaged railway you slow down the trains (stop drinking coffee because that raises ACh).
I don't know if this nerve damage is a cause of too low or too high copper but it's most likely a lack because copper is needed in the formation of myelin.
Quote:EFFECTS OF COPPER DEFICIT ON MYELINATION
J -M Matthieu, A W Zimmerman, R H Quarles & R O Brady
Pediatric Research volume 9, page 865 (1975)
https://www.nature.com/articles/pr1975325
You can imagine the nerve as a copper wire where myelin would be the plastic insulator.
https://beyondthedish.wordpress.com/2015/12/07/inhibition-of-gli1-enhances-remyelination-abilities-of-endogenous-stem-cell-populations/
https://commons.wikimedia.org/wiki/File:Leitungsende_Abisoliert_en.svg
Marekich [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons
https://www.rchsd.org/health-articles/bells-palsy-3/
Now you maybe remember that scientist Luigi Galvani that experimented with death frogs and electric current.
"The beginning of Galvani's experiments with bioelectricity has a popular legend which says that the Galvani was slowly skinning a frog at a table where he and his wife had been conducting experiments with static electricity by rubbing frog skin. Galvani's assistant touched an exposed sciatic nerve of the frog with a metal scalpel that had picked up a charge. At that moment, they saw sparks and the dead frog's leg kicked as if in life. The observation made the Galvanis the first investigators to appreciate the relationship between electricity and animation—or life."
https://en.wikipedia.org/wiki/Luigi_Galvani
A damaged myelin sheath in the area of the eustachian tube could innervate the levator veli palatini and/or tensor veli palatini muscle.
Like you would get an electric shock from a damaged electrical cable.
Copper and estrogen
There are many women who report worsened PET after taking a contraceptive pill containing estrogen (Ethinylestradiol for example).
Estrogen increases serum copper but it also seems to deplete liver copper which is the copper storage of the body.
Quote:Adv Exp Med Biol. 1989;258:155-62.
Effect of estrogen on serum and tissue levels of copper and zinc.
Mehta SW, Eikum R.
https://www.ncbi.nlm.nih.gov/pubmed/2626984
Quote:Eur J Clin Nutr. 1998 Oct;52(10):711-5.
Effect of oral contraceptive progestins on serum copper concentration.
Berg G, Kohlmeier L, Brenner H.
https://www.ncbi.nlm.nih.gov/pubmed/9805216
Quote:Contraception. 2013 Jun;87(6):790-800. doi: 10.1016/j.contraception.2012.10.006. Epub 2012 Nov 13.
Relevance of serum copper elevation induced by oral contraceptives: a meta-analysis.
Babić Ž, Tariba B, Kovačić J, Pizent A, Varnai VM, Macan J
https://www.ncbi.nlm.nih.gov/pubmed/23153894
There's also a steep rise in estrogen during pregnany.
http://www.johnyfit.com/estrogen-levels-during-pregnancy/
Copper and cortisol
Cortisol also seems to decrease copper.
It seems to lower ceruloplasmin, the copper transport protein while estrogen raises ceuloplasmin.
Quote:Indian J Med Sci. 2004 Apr;58(4):150-4.
Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress.
Ganaraja B, Pavithran P, Ghosh S.
https://www.ncbi.nlm.nih.gov/pubmed/15122050
Quote:Am J Med Sci. 1981 Sep-Oct;282(2):68-74.
Influence of synthetic corticosteroids on plasma zinc and copper levels in humans.
Yunice AA, Czerwinski AW, Lindeman RD.
https://www.ncbi.nlm.nih.gov/pubmed/7325187
Quote:Environ Toxicol Chem. 2003 May;22(5):1122-6.
Effect of cortisol treatment and/or sublethal copper exposure on copper uptake and heat shock protein levels in common carp, Cyprinus carpio.
De Boeck G, De Wachter B, Vlaeminck A, Blust R.
https://www.ncbi.nlm.nih.gov/pubmed/12729223
The other way around a high copper level seems to raise the cortisol level.
Quote:OUTSIDE JEB
COPPER, CORTISOL AND THE COMMON CARP
Katherine A. Sloman
Journal of Experimental Biology 2003 206: 3309
http://jeb.biologists.org/content/206/19/3309
Quote:Aquat Toxicol. 2002 Feb;56(3):167-76.
Stress response to waterborne Cu during early life stages of carp, Cyprinus carpio.
Flik G, Stouthart XJ, Spanings FA, Lock RA, Fenwick JC, Wendelaar Bonga SE.
https://www.ncbi.nlm.nih.gov/pubmed/11792433
But too much estrogen raises cortisol which lowers ceruloplasmin.
Quote:Maturitas. 2008 Dec 20; 61(4): 330–333.
Effects of estrogen versus estrogen and progesterone on cortisol and interleukin-6
Kate M. Edwards, and Paul J. Mills
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663529/
Copper and soy isoflavones
The soy isoflavones could improve the PET by improving the absorption of copper through the ability of the isoflavones to reduce cupric (divalent) to cuprous (monovalent) copper.
Quote:Oxidative Medicine and Cellular Longevity
Isoflavones Reduce Copper with Minimal Impact on Iron In Vitro
Jana Karlíčková, Kateřina Macáková, Michal Říha, Liliane Maria Teixeira Pinheiro, Tomáš Filipský, Veronika Horňasová, Radomír Hrdina, and Přemysl Mladěnka
https://www.hindawi.com/journals/omcl/2015/437381/
Link between bariatric surgery copper and PET
(thanks to Matt Dawson at the FB group for pointing this out)
Bariatric (weight loss) surgery causes an impaired uptake of copper. And in patients with such a surgery there was a higher count of people getting PET.
I doubt it was just the weight loss that caused a diminishing of the Ostmann's pad of fat around the eustachian tube. Then most people with weight loss would have PET.
Quote:Obes Surg. 2016 Jun;26(6):1335-42.
Copper Deficiency after Gastric Bypass for Morbid Obesity: a Systematic Review.
Kumar P, Hamza N, Madhok B, De Alwis N, Sharma M, Miras AD, Mahawar KK.
https://www.ncbi.nlm.nih.gov/pubmed/27034062
Quote:Otolaryngol Head Neck Surg. 2010 Oct;143(4):521-4.
Patulous eustachian tube in bariatric surgery patients.
Muñoz D, Aedo C, Der C.
https://www.ncbi.nlm.nih.gov/pubmed/20869562
Quote:OBES SURG (2011) 21:1482–1483
Gastric Bypass and Copper Deficiency: A Possible Overlooked Consequence
Denis M. Medeiros
https://sci-hub.se/10.1007/s11695-011-0465-3
Quote:Obesity (Silver Spring). 2009 Apr; 17(4): 827–831.
Acquired Copper Deficiency: A Potentially Serious and Preventable Complication Following Gastric Bypass Surgery
Daniel P. Griffith, R.Ph., David Liff, M.D., Thomas R. Ziegler, M.D., Gregory J. Esper, M.D., and Elliott F. Winton, M.D.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712481/
So what is the root cause that causes this copper deficiency?
Excess estrogen (can exclude that for me as I'm not a woman and levels are normal)
Gene Mutation that causes low copper
Viral infection that causes low copper
Environmental factors (pesticides [Glyphosate], low copper in food)
Glyphosate can chelate metals and is probably in every non-organic food.
"In aquatic ecosystems, where both heavy metals and glyphosate can co-occur, glyphosate and Roundup can control both the toxicity and the bioavailability of heavy metals, e.g., Cd, Cu, Cr, Ni, Pb, Se, and Zn (Tsui et al. 2005)."
Quote:Environ Sci Pollut Res Int. 2018; 25(6): 5298–5317.
Glyphosate, a chelating agent—relevant for ecological risk assessment?
Martha Mertens, Sebastian Höss, Günter Neumann, Joshua Afzal, and Wolfram Reichenbecher
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823954/
RE: Copper: The intermediate cause of PET? - Matt - 01-30-2019
Great info! Can you clarify a few things...
Firstly, as the creator of the group, would you mind telling us of your situation...
- do you have PET, and if so can you give us some background?
- have you had your copper tested or tried supplementing?
Ok, questions...
You said this on the FB group:
Caffeine raises the neurotransmitter acetylcholine by inhibiting the enzyme acetylcholinesterase which breaks down acetylcholine. And acetylcholine gives skeletal muscle the signal to contract. So PET is a neuromuscular dysfunction of the muscles in the ear. That's probably why alcohol improves PET because alcohol increases dopamine which is in an equilibrium with acetylcholine and therefore lowers the latter.
So are we saying that acetylcholine, while usually an important neurotransmitter and great for improving memory, in our cases is causing muscular spasm and therefore PET?
Personally, I eat extremely healthy, but would be concerned if this is true, as my choline levels would be off the charts given I eat an abundance of most of the foods highest in choline - ie. eggs/dairy/meat/fish/avocado/nuts....
Re copper...
I'm in total agreement with the copper deficiency theory, and were we to look at raising our copper intakes naturally, then some of the best sources - liver, fish, avocados, nuts, seeds - are also all high in choline. So perhaps a dedicated copper supplement is a better option..?
Another thing I've learnt while researching - and this certainly applies to me - is "zinc-induced copper deficiency". I won't post medical links but there are many. Zinc is already known as a copper inhibitor, so taking high dose zinc supplements for more than a few weeks will by default, lower your copper levels. This is becoming more and more common as doctors/pharmacists/naturopaths prescribe zinc for a variety of ailments, all the while being unaware of the mineral imbalance it's causing.
Personally, I have tested at the bottom end of the range for serum copper and slightly below the acceptable range for ceruloplasmin. This wasn't surprising to me as I'm experiencing a number of other symptoms that would point to this, which I would expect others to have along with PET, were copper to be the cause. As such, I've started treating with copper bisglycinate (Thorne brand), 2-4mgs per day. I'm seeing a specialist in a few weeks to discuss this approach, amongst other things. Only possible side-effect so far is that it encourages too many bowel movements, but I can't say for sure it's the cause. My understanding is that it can take months to boost copper levels, even at 6-8mgs per day. Any thoughts on any of this are very welcome.
While my doctor doesn't see an issue with me being at the very low end or slightly below the range, it does pose the question "what is an ideal level?", especially in order to eliminate the symptoms of PET (assuming the correlation). I imagine it's different for everyone and perhaps only time will tell. I believe it's all about having optimum levels (of everything) - eg. you can be in the range for Vitamin D, but still feel poorly and be symptomatic as though you had a deficiency).
As I've mentioned previously, I'd encourage everyone with PET to get their serum copper and ceruloplasmin levels tested and share them here.
Cheers
Re supplementation...
Is there anything to suggest it's required, and going to be a better alternative than simply boosting our intake of high-copper foods?
Apparently even the tiniest serving of beef liver can give you 4mgs!
Does the body find it harder to absorb copper from food sources, compared to supplements?
Also, I'm interested in your post regarding the type of copper supplement to use....
I wouldn't recommend any blue copper (which smells like wet dog), one that definitely works is MitoSynergy MitoActivator Extra Strength, but that is extremely expensive. An alternative is Nature's Plus Copper 3 mg (green copper).
Green copper tends to be more cuprous (monovalent) while blue copper tends to be more cupric (divalent). The body can use both forms but monovalent copper is easier to absorb by the intestinal transporter CTR1. If it is divalent it has to be reduced by another electron donator. The isoflavones are probably able to donate an electron as does niacin, that's why the only available cuprous copper supplement is a combination of niacin and copper.
I've just noticed that the Thorne product I'm using has clear capsules and the contents are distinctly blue.
So if this is just a case of bioavailability, then could one simply take it with soy milk (as suggested on the group)?
RE: Copper: The intermediate cause of PET? - Caravaggio - 01-30-2019
Hey Matt,
I have PET since 2000/2001, but currently I only have it during exercise and when consuming caffeine.
Back then it was much worse with autophony during class e.g. From the infamous sniffing habit of PET sufferes I actually got an eardrum perforation. The vacuum from the sniffing causes a permanent moving of the eardrum which makes it thinner till it tears.
I got nosedrops and antibiotics and the hole in the eardrum healed eventually. But the PET stayed.
I only had ceruloplasmin tested, it wasn't below the range but on the lower side.
Bute regarding these articles blood values of copper are not very useful anyway:
http://www.unveilingthem.com/CopperTheMalignedMineral.htm
http://www.unveilingthem.com/CopperDefiningTheHumanRequirement.htm
Please ignore the other articles on this site though, they are from some tin foil hat guy.
Regarding ACh I don't think we should avoid ACh or supplements that raise it (acetylcholinesterase inhibitors), ACh is not the bad guy we are just more sensitive to it than normal people.
From my experience regular choline doesn't really raise ACh much, because Choline does not easily pass the blood-brain-barrier. Centrophenoxine, Alpha-GPC and CDP-Choline are better for that.
Here's a video from Christopher Shade, I know he's more of a salesman than a scientist but I think he's right about the Phosphatidylcholine:
I definitely agree with too much zinc being a problem. I took 50 mg/day for years and I think it gave me additional symptoms like lower leg alopecia, red hair follices on lower legs and very dry skin on the ankles.
It didn't even seem to raise zinc much, I had a blood level of 1.0 mg/l with a range of 0.6-1.5 mg/l. Before the results I was actually scared I could have like very high levels from overdosing.
In a heavy metal urine test I was almost at the upper range with 1159 µg/g Creatinine and a range of 250-1200 µg/g Creatinine, so I was basically peeing out the zinc.
This woman had the same experience with zinc and copper:
So without copper it's useless to take zinc and it's probably lowering copper furthermore. I also have exactly the same vertical ridges on my fingernails and I hope that they will also go away from supplementing copper.
Copper sulphate (CuSO4) is given to animals as a food additive and is blue so the color probably doesn't matter. I just assumed that green is better because for example reducing divalent copper chloride to monovalent copper chloride changes it from blue to green.
Here's video:
The whole fear of too much copper is probably based on two anecdotal studies:
https://scholar.google.com/scholar?cites=8984004657111542333&as_sdt=2005&sciodt=0,5&hl=en
Micronodular cirrhosis and acute liver failure due to chronic copper self-intoxication - Released in the European Journal of Gastroenterology & Hepatology in 1993.
This study is cited by 41 articles.
https://scholar.google.com/scholar?cites=12071494746637947392&as_sdt=2005&sciodt=0,5&hl=en
A case of adult chronic copper self-intoxication resulting in cirrhosis. - Released in the European Journal of Medical Research in 1999.
This study is cited by 20 articles.
Strangely I couldn't find a copy of these articles. For the first study I couldn't even find the Volume 5, July 1993, Issue 7 where it must be contained.
If somebody has a copy of these articles please provide them to us.
And then there's this study where adult capuchin monkeys got a dose of 7.5 mg copper per kg per day, that equals 525 mg a day for a 70 kg human. Though a capuchin monkey only weighs 3-4 kg which would be a dose of 22.5 to 30 mg of copper.
Quote:Administration of High Doses of Copper to Capuchin Monkeys Does Not Cause Liver Damage but Induces Transcriptional Activation of Hepatic Proliferative Responses
Magdalena Araya Héctor Núñez Leonardo Pavez Miguel Arredondo Marco Méndez Felipe Cisternas Fernando Pizarro Walter Sierralta Ricardo Uauy Mauricio González
The Journal of Nutrition, Volume 142, Issue 2, 1 February 2012, Pages 233–237
https://academic.oup.com/jn/article/142/2/233/4630792
"We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg−1 . d−1) and adult (7.5 mg Cu · kg−1 . d−1) capuchin monkeys would induce detectable liver damage. "
"After 36 mo, the liver copper concentration was 4–5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage."
"Their diets consisted of fresh foods plus vitamin and mineral supplementsfollowing the norms of the Primate Center, as previously published (25).Copper dosing was set at 5.5 mg and 7.5 mg/d (as copper gluconate) in 1 or2 doses to avoid acute manifestations (mainly salivation and loose stools)"
I don't really know if they now used 7.5 mg per day or 7.5 mg per kg per day. But interesting that they mention loose stool as a side-effect on high doses, that matches your experience. But I didn't notice that even at 9-12 mg per day.
But if a 3 kg monkey can take 7.5 mg a day without any liver damage that would equal 175 mg copper for a 70 kg human. Very strange if you keep in mind that there is no RDA and the recommended daily intake is 1.5 to 3 mg per day.
You could get the impression that there's a copper conspiracy.
Regarding your last question I don't think that supplements are better than foods, it's more likely that we have less copper in the food or too much zinc in the food.
Fructose and Vitamin C are also diminishing copper.
"The minimal amount of fructose that increases the severity of Cu
deficiency has received little attention. Rats fed Cu-deficient diets «1
mg Cu/kg diet) with as little as 20% fructose had more severe signs of Cu
deprivation than those fed 0% fructose (Johnson, 1988; Kays and Johnson,
1988). In this study, fructose decreased hemoglobin, cytochrome c oxidase
activity, Fe absorption, liver Cu, and liver Cu,Zn-superoxide dismutase in
a dose-dependent manner."
Constance Kies (auth.), Constance Kies (eds.) - Copper Bioavailability and Metabolism (1990, Springer US)
Quote:J Nutr. 1987 Dec;117(12):2109-15.
Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men.
Jacob RA, Skala JH, Omaye ST, Turnlund JR.
https://www.ncbi.nlm.nih.gov/pubmed/3694287
Quote:J Nutr. 1981 Nov;111(11):1964-8.
A postabsorption effect of L-ascorbic acid on copper metabolism in chicks.
Disilvestro RA, Harris ED.
https://www.ncbi.nlm.nih.gov/pubmed/6117609
I wouldn't recommend taking more than 500 mg Vitamin C a day.
RE: Copper: The intermediate cause of PET? - Matt - 01-31-2019
Wow, I thought I'd stumbled onto something important when you first mentioned the word copper in the fb group a few weeks ago, but this whole copper thing is becoming quite ridiculous, spooky even. You only need to spend time researching (plus now with your amazing input), and the number of conditions that are a result of copper deficiency is incredible. It's almost like all my unexplained health issues are now making sense. Fingers crossed anyway.
Re Fructose... I've always been a fructose malabsorber, so I'm on the low-FODMAP diet (for 10+yrs), so my intake would be limited, but it was interesting what she says in the video about excess fructose in the gut...
Re Vit C... I don't eat much fruit, but I do eat very healthy so could cut back a little on some vegetables... I basically never supplement, but I did in Nov/Dec when I was sick (2000mg+) and that clearly hasn't helped my situation.
Re Vertical ridges on fingernails... I don't think it will surprise you to learn I also have this, and always have! Naturally, it was a mystery.
Re Food vs supplements... yes I think that unless you have absorption issues, there shouldn't be much difference re copper availability... I've temporarily stopped the supplement until my gut/bowels clear up (I've long had issues in this area and need to work out why I've always eaten like a horse and struggle to maintain weight - and I doubt it's entirely metabolism-based)... that said, I had beef liver tonight for the first time, only 50g, which is about 7.3mg of copper. So we'll see how that goes down.
Re my symptoms... after taking zinc for about 4 months a few years ago, can't remember exact dosage but was prob similar to you, I developed MS-like neurological symptoms; numbness/tingling/weakness mainly in lowers legs and forearms. My copper was 9 at the time, now it's 11 (range is 11-22). Similar symptoms have recently returned to a lesser degree as I (stupidly) took zinc along with the VitC a few months ago. My research at the time led me to believe it was a B12 deficiency, but my levels were fine. My clueless doctor never suggested testing for copper. It could've saved me from much suffering and potentially PET. He was of course keen to talk about SSRIs.
This is a list of potential copper deficiency symptoms via google... (and I'm sure there's plenty more - eg. fingernails)
* the ones I have are in italics *
- fatigue or low energy levels
- paleness
- low body temperature / sensitivity to cold
- anemia / neutropenia
- weak, brittle bones (osteopenia/orosis)
- balding/thinning/greying hair
- unexplained weight loss
- inability to gain weight
- skin inflammation
- weakened immune system
- MS type symptoms
- muscle soreness
- joint pain
- high cholesterol
- PET?!
My neutrophils were down on a recent blood test, my cholesterol is too high for someone who eats so healthily, and out of the blue last week, my chiropractor, after looking at my spinal xray, tells me I'm showing obvious signs of osteopenia! In my 40s! WTF?!
So basically, I'm the poster-child for copper deficiency. I would lol but feeling unwell for this long is too serious.
I'll also be very interested to see if copper plays a role in weight loss / high metabolism. Do you know of any research/links?
Would you mind talking about your copper supplementation... what you're taking, for how long, dosage, findings? And obviously how it's affected your PET?
Have you ever had your copper retested?
The evidence suggests 10mg/day is the limit if you're going to supplement consistently, so I think 4-6mgs is perfectly fine.
Btw what the hell is that unveilingthem website?! He sounds like a genius and a nutter all in one. Hard to know how much to believe.
On the other hand, that YouTube lady (Vita?) is my new favourite person... behind you of course.
PS. What's the 3rd factor in the cause of PET? Or is that in the members only paid subscription area?
RE: Copper: The intermediate cause of PET? - Caravaggio - 01-31-2019
I'm curious how your blood fatty acid profile looks like.
I did one and almost every fatty acid was low except for linoleic acid (18:2) which was high. If you have low fatty acids in your blood it's clear that you won't become fat.
That probably has to do with the role of copper in fatty acid metabolism.
Quote:The Role of Copper as a Modifier of Lipid Metabolism
By Jason L. Burkhead and Svetlana Lutsenko
https://www.intechopen.com/books/lipid-metabolism/the-role-of-copper-as-a-modifier-of-lipid-metabolism
Quote:Food Nutr Res. 2017; 61(1): 1348866.
Effect of dietary copper addition on lipid metabolism in rabbits
Liu Lei, Sui Xiaoyi and Li Fuchanga
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510220/
Quote:UBMB Life. 2017 Apr; 69(4): 263–270.
The role of insufficient copper in lipid synthesis and fatty-liver disease
Austin Morrell, Savannah Tallino, Lei Yu, and Jason L. Burkhead
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619695/
But it must be dependant on more factors, there are thin and overweight people with copper deficiency.
I also had muscles twitches from the high zinc intake, probably nerve damage, already thought if it could be multiple sclerosis.
On your symptoms list I could also check 9 symptoms. I think I found an explanation for the vertical ridges on the nails. There are thiol oxidase (sulfhydryl oxidase) enzymes which are resposible for disulfide-bond formation.
These enzymes are copper-dependent. So if you lack copper then the enzymes will create less disulfide-bonds which are for example a part of keratin (hair, nails). As a side effect I think it's possible that you could get an excess of sulphur (could this be the yellow/brown ring in the inner iris? Or green eyes when in fact you have blue eyes)
Quote:"Steely" wool caused by copper deficiency.
Agricultural Gazette of New South Wales 1947 Vol.58 pp.99; 106
https://www.cabdirect.org/cabdirect/abstract/19471402845
The copper I take is 3x3 mg (analysis says 4 mg, it always varies) Nature's Plus because this is chelated with soy amino acids, has the advantage of several different amino acids plus the additional isoflavones.
That resembles more of a natural food, although I asked the producer (Biotron Laboratories) and it's divalent copper.
Food is usually a mix of monovalent (Cu+) and divalent (Cu++) copper.
Quote:Ceko, M.J., Aitken, J.B., Harris, H.H.
Speciation of copper in a range of food types by X-ray absorption spectroscopy
Food Chemistry (2014)
https://sci-hub.se/10.1016/j.foodchem.2014.05.018
The 3rd step is to find the actual cause of the copper deficiency.
My best bet is it's either a genetic disorder where we can't convert enough Cu++ (transport version) to Cu+ or it's a viral infection where the virus either modified DNA to protect it from the macrophages' copper bursts or the macrophages simply shot all their copper and are depleted.
"The macrophage copper burst
When macrophages encounter pathogens, they can engulf and contain the microbe within a compartment known as the phagolysosome. This extremely hostile environment contains high ROS and reactive nitrogen, low pH and proteases, which are all designed to kill the microbe. With certain infectious agents, the phagolysosome can also accumulate high copper which, together with phagolysosomal ROS, can attack microbes through Fenton chemistry or through other pathways as described above. The high copper of macrophage phagolysosomes was first described for infection with Mycobacterium species including the M. tuberculosis pathogen for tuberculosis [33]. Since then, macrophage copper has been shown to be important in killing E. coli [34] and inducing copper toxicity stress for Salmonella [35, 36]. Even fungi such as Candida albicans show symptoms of high copper exposure during encounters with macrophages [37]. The mechanism by which macrophages accumulate this high copper is believed to involve a combination of increasing copper uptake by the high affinity copper transporter CTR1 and by activating the copper ATPase ATP7A, which can directly pump copper into the phagolysosome [34, 36, 38]."
Quote:J Biol Inorg Chem. 2016 Apr; 21(2): 137–144.
The Yin and Yang of Copper During Infection
Angelique N. Besold, Edward M. Culbertson, and Valeria C. Culotta
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535265/
It would be interesting to know if there are any couples that both have PET, would speak for a viral cause, or a very rare coincidence where both partners have the same gene defect.
RE: Copper: The intermediate cause of PET? - Matt - 02-01-2019
Ok, well plenty of commonalities with us re symptoms...
So you take 9mg of copper per day? How long have you been supplementing at these levels? Surely you have noticed a change/improvement, and if not, are you thinking your body just isn't utilising it properly..?
I tend to think I had a virus in 2017 when a lot of my problems started. I took a bunch of supplements (incl zinc) and also ended up taking herbal antimicrobial tonics for a few months later that year - all this was an attempt to clean up my gut which was clearly overwhelmed by bad bacteria/pathogens/candida/etc. While my gut health improved dramatically after all that, it has recently flared up again, possibly due to taking ibuprofen along with the high dose zinc and VitC. I do wonder whether my microbiome was permanently altered after all the concoctions I took, and now affects the way I process nutrients..... but I'm only guessing.
Either way, sounds like we're screwed if our bodies are simply incapable of utilising copper anymore.
Re my fatty acid profile... just looking at some results from 18 months ago (before any treatment), long chain fatty acids were 1.5 (range 1-23), short chain fatty acids were 92 (they should be >13... though elevated levels may indicate bacterial overgrowth). Not sure what that all means, but may prove your point about low levels and being slim.
Would be nice if boosting our copper levels helped with weight gain, but as you say, overweight people have low copper too.
I still need to read those articles you linked to for a better understanding.
As much as I hope that copper is a huge part of the fix for PET, there are some aspects of the condition that are simply mystifying and seemingly unrelated to something like copper. The one that stands out for me is hydration.
We've all heard people go on and on about staying hydrated, electrolytes, etc... but personally it never seems to help me.
In fact, drinking water (it's basically all I drink), is pretty much guaranteed to trigger my PET if my tubes are closed at the time.
Generally it takes anywhere from 2-10 minutes for my tubes to open after drinking, and it doesn't seem to matter how much I drink (as long as it's more than a sip).
What could this possibly be doing to my body to cause this?
And on the flip side, if I abstain from drinking anything, my tubes can stay closed for hours at a time.
This was most evident on a very hot day recently when I was outside in the heat and became very dehydrated, and yet my ears felt perfectly normal for an entire afternoon.
I have 4 theories on this...
1. I know that I suffer from silent reflux, so water may well be a trigger for me (especially on an empty stomach), thus causing the refluxate to find its way into my throat and ETs, which is common in LPR
2. The water is having some weird imbalancing effect on my system, causing the tubes to open (I only started drinking plenty of water a few years ago, prior to that all I drank was tea)
3. The act of swallowing is causing the muscles responsible for closing the ETs to malfunction
4. I'm an alien and as such, my body has no need for water, in fact it acts as a poison
Point 3 makes no sense to me, as when I eat/chew/swallow food during a meal, my tubes often close.
This could of course be related to the chewing action, but you see my point.
Clearly it's hard to see a copper link to any of these.
Btw I tend to think it's number 1 (or 4).
Thoughts?
* btw what timezone are you in? i'm guessing Europe somewhere? *
RE: Copper: The intermediate cause of PET? - Caravaggio - 02-01-2019
There must to be a connection between sodium and copper. It seems sodium helps with the absorption of copper.
So if you drink too much water you dilute the sodium and decrease copper absorption.
If you drink water with salt you probably won't notice the PET trigger.
Quote:Proc Soc Exp Biol Med. 1987 Jul;185(3):277-82.
Intestinal absorption of copper: effect of sodium.
Wapnir RA, Stiel L.
https://www.ncbi.nlm.nih.gov/pubmed/3601948
Interesting that you mention silent reflux, I also suspected having that but two ENTs and one gastroenterologist couldn't find anything in my esophagus and stomach although I had even blood in my sputum for some time.
But what can you expect from ENTs that can't even diagnose PET, I diagnosed it myself. And I just found out the gastroenterologist probably retired because he is no more listed on the doctor's office homepage. That was probably not a positive factor for motivation.
I think it has to do with zinc and stomach acid. Zinc is needed to produce stomach acid, the imbalance of zinc to copper could be the cause.
I don't think we have too much stomach acid because without enough copper we can't even raise zinc above a certain threshold. So I hope the copper will also fix this.
I'm in the GMT+1 timezone.
RE: Copper: The intermediate cause of PET? - Matt - 02-01-2019
Interesting, I have tried adding salt in the past, including electrolyte tablets, but don't remember it making a difference.
I get that sodium decreases copper absorption, but in the case of simply drinking water (ie. no copper is involved), I'm not sure I see the connection.
Perhaps if water diluted the copper already in our bodies, then that would become problematic.
I totally agree about the ENTs, but I did have two tell me my throat showed obvious signs of reflux. I plan to treat this separately with the IQoro device btw.
I do like the zinc theory regarding stomach acid, and the obvious copper tie in. Makes an awful lot of sense. It's a wonder no one has suggested this before.