zinc supplements WARNING.

Hmm... Perhaps I was misunderstanding at which part in the absorption the competitive inhibition was happening; or at least missing part of the story. The sucrosome is helping with the absorption across the intestinal lumen. However, he is claiming that then the sucrosome is broken down before entering serum, which then signals an increase in metallothioneins, which then sequesters the metals. I suppose that could be. I thought the sucrosome was staying intact THROUGH the mucosal cells and delivering to serum. I think I am wrong on that after reading a bit more. The sucrose ester on the outside of the lipid bilayer of the sucrosome signals for the intestinal lumen to open up, which allows the zinc to enter the mucosal cells. Then the zinc would enter serum like normal. I was also under the impression that the competitive inhibition was happening at the lumen, due to the statements from that study.

The competition between Zn and Cu may also take place at the brush border during the luminal phase of absorption, but the effects at this site have not been well characterized. The interaction between these two elements has therapeutic implications, since it has been demonstrated that the oral administration of Zn salts can reduce Cu accumulation in the liver in patients with Wilson's disease (8-11).

That does seem to be the case, too. However, that's not the end of the story. I am not sure why he is claiming that the luminal phase is not part of the problem, though. The things he quoted contradict his conclusion.

These experiments substantiate the hypothesis that the luminal phase of Cu absorption is modulated by the simultaneous presence of another trace element of similar chemical characteristics, molecular weight, and atomic radius, such as Zn. [bold: mine]

That contradicts his conclusion of:

As I suggested above, sucrosomal absorption targets the luminal phase and that isn't the problem.

Competition at the intestinal lumen is part of the problem. Zinc will compete with copper at the lumen. Bypassing that will avoid some of that issue. It might not be the whole issue, but it is part of the issue. The other part of the issue is inducing metallothioneins. Let's address that.

It is now accepted that Cu-Zn interplay is mediated through intracellular metallothioneins (MT), which are inducible by certain divalent cations, for whom they have the greatest affinity (5,6).

The sucrosomial zinc is not delivering divalent cations of zinc. It's delivering zinc oxide, which might not induce the metallothioneins. The data is saying elemental zinc cations cause a release of the metallothioneins, which then sequester copper. However, why are we making the jump to that applying to zinc oxide? Zinc oxide is not a divalent cation... Zinc oxide is not the same thing as elemental zinc. Zinc oxide should not induce metallothioneins like divalent cations of zinc would, or at least we can't make the jump to conclusions that they would, based of the data. Actually, the more I look at this, the more I think it doesn't. Hear me out.

So we know that zinc oxide increases serum levels of zinc, right? If zinc oxide was increasing metallothioneins like divalent cations of zinc, that would not be the case. The increase in metallothioneins would sequester both zinc and copper in the mucosal cells. That DOES happen with elemental zinc and elemental copper. However, the fact that ingesting elemental zinc doesn't lead to the same increase in serum zinc as taking zinc oxide does means that interaction at the metallothioneins is not taking place with the oxide form. Why is that? Well the metals have to be in divalent cation form to bind to the finger structures on the metal-regulatory transcription factor (MTF-1), which increases the expression of thionein, which increases metallothionein levels, which sequesters the copper. Zinc in oxide form doesn't bind to the finger structures on the metal-regulatory transcription factor (MTF-1).

The Essential Toxin: Impact of Zinc on Human Health

Elevated levels of free zinc ions can bind to zinc finger structures of the metal-regulatory transcription factor (MTF)-1, thus inducing the expression of thionein.

Here is the whole trigger. Binding to MTF-1 is what leads to the increase in metallothioneins, by increasing the expression of thionein in intestinal mucosal cells. This is happening by divalent cations of zinc and copper, not by the oxide forms. So the question then becomes where/when does zinc oxide become Zn2+? It seems to be in serum, due to interactions with albumin.

Zn2+ release from zinc and zinc oxide particles in simulated uterine solution

So the zinc oxide in our Micromag passes through the intestinal mucosal cells without interacting with metallothioneins, due to the oxide preventing it from binding to the finger structures on the metal-regulatory transcription factor (MTF-1), then enters the serum and is converted to Zn2+ by interacting with human serum albumin. That Zn2+ then goes on to act in the body as we would expect. The main issue with supplementing zinc oxide IS the competition for the transporter at the intestinal lumen, which is bypassed by the sucrosome. It's also the solubility issues of zinc oxide, but that's another story. The metallothionein sequestering of copper inside the mucosal cells is not a factor with zinc in oxide form, due to the inability of it to bind to the finger structures of MTF-1. This was my whole reasoning for saying that sucrosomial zinc doesn't affect copper levels, because it is bypassing the competition at the transporter of the intestinal lumen. I was then thinking (I think incorrectly) that the sucrosome then delivered the zinc oxide into serum directly. This would bypass the whole metallothionein issue altogether. Now that I research a bit more, I think the sucrosome is releasing the zinc oxide just after the lumen. However, the issue of copper sequestration doesn't seem to be an issue anyway, due to it being in oxide form. The zinc oxide then passes into serum where it is converted and bound to serum albumin. He says that bypassing the metallothionein mechanism is dangerous because it would lead to too much free zinc flying around in serum. However, that doesn't appear to be the case. Serum albumin binds to the zinc and releases it as needed. This regulates the zinc once it is in serum. We don't need to rely on intestinal mucosal metallothionein activity for that. The 1981 study he referenced above uses zinc sulfate to study the interactions with copper, which is an ionically bound salt. It will dissociate into free Zn2+, which will interact with metallothionein activity. That would be why they found copper sequestration. Zinc oxide is a covalently bonded molecule, though. It will not act like zinc sulfate.

Zinc and copper: proposed fortification levels and recommended zinc compounds

Minerals with similar physical and chemical properties and electronic structure will act antagonistically to each other.

Zinc oxide is not similar in chemical properties and electronic structure to Cu2+. It's not going to interact with the transporter or metallothioneins like free divalent cations of Zn2+ and Cu2+ would. Moreover, they state that a negative effect of typical zinc intake on copper absorption has not even been established. I can't find a single study showing that zinc oxide supplementation adversely affected copper levels.

So to recap, the competition at the metal transporter of the intestinal lumen is the main issue with supplementing metals in elemental or oxide form, compounded by the solubility issues. Supplementing regular zinc forms would prevent copper from absorbing through the intestinal lumen. This is bypassed with zinc in a sucrosome, as that bypasses the metal transporter and delivers zinc oxide into intestinal mucosal cells. Zinc in sucrosome forms will not compete with copper for transport at the intestinal lumen. Once inside the mucosal cells, the zinc oxide will not cause an increase in metallothioneins, because it will not bind to the finger structures on MTF-1. Because the zinc oxide won't bind to MTF-1, we will not have an increase in metallothionein sequestering copper. The zinc oxide will pass into serum where it will be bound to serum albumin and released as needed. Because serum albumin will bind to the zinc and regulate its release, we don't need to worry about bypassing metallothioneins causing a toxicity issue.

As always I could be wrong or missing something. I am not claiming to be the absolute arbiter of truth here. At no point am I trying to promote "propaganda" or mislead people. This is what I actually think, based off the data I have available. I've gone through this for many hours with my research team now as well. If we are missing something, which is entirely possible, I would love to update my understanding of the situation. Also, this whole discussion is centered on absorption. Once the zinc is in serum, I am sure there are mechansisms and interactions with metallothioneins and copper in other areas. I just don't think it is a significant issue in general at reasonable doses anyway.

https://www.hindawi.com/journals/ijad/2013/586365/

They are using 150mg of zinc acetate per day. That's a salt, so it will dossociate and result in increases in metallothioneins in intestinal mucosal cells. It's also delivering ~53mg of zinc per day, since zinc is ~35% of the molecular mass. That dose lowered serum free copper from 37.0μg/dL to 30.8μg/dL after 6 months of daily dosing. Our Microzinc is giving 8.4mg zinc, and it's not in salt form; so copper lowering is not an issue, even if I am proven wrong on the whole zinc oxide metallothionein thing.