Copper: The intermediate cause of PET?

[Caravaggio]

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.

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...pulations/


https://commons.wikimedia.org/wiki/File:...ert_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.

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

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

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-...pregnancy/

Copper and cortisol

Cortisol also seems to decrease copper.

It seems to lower ceruloplasmin, the copper transport protein while estrogen raises ceuloplasmin.

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

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

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.

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

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.

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.

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.

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

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

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

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)."

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/