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.