OptiZinc Does Not Lower Metallothionein—It Induces It
You have heard incorrectly: zinc supplementation (including OptiZinc, which is zinc monomethionine) does not lower metallothionein levels; rather, zinc induces and increases metallothionein production in both enterocytes and hepatocytes. 1
Mechanism of Zinc's Effect on Metallothionein
Zinc induces metallothionein synthesis, not degradation:
- Zinc supplementation induces enterocyte metallothionein, a cysteine-rich protein that acts as an endogenous metal chelator 1
- Zinc also induces hepatocellular metallothionein levels, which binds excess toxic metals (particularly copper) to prevent cellular injury 1
- Daily zinc supplementation (50 mg/day) increases erythrocyte metallothionein to a 7-fold maximum within 7 days in human subjects 2
The Actual Relationship Between Zinc and Metallothionein
Metallothionein levels rise and fall with zinc availability:
- When zinc intake is low (0.7 mg/kg diet for 8 days), erythrocyte metallothionein decreases significantly to 59% of initial levels 2
- Zinc deprivation can lead to amplification of the metallothionein gene locus as a compensatory survival mechanism under extreme zinc deficiency 3
- Metallothionein is fairly rapidly degraded when zinc is the primary bound metal, but this represents normal protein turnover, not zinc-induced lowering 4
Clinical Context: Wilson's Disease Treatment
The therapeutic use of zinc in Wilson's disease relies entirely on inducing metallothionein:
- The mechanism of zinc therapy is to induce enterocyte metallothionein, which preferentially binds copper (having greater affinity for copper than zinc) and prevents copper absorption 1
- Recommended dosing is 150 mg elemental zinc daily in three divided doses, 30 minutes before meals 1, 5
- This induced metallothionein traps copper in enterocytes, which is then lost in feces as enterocytes are shed during normal turnover 1
Important Caveat About Ammonium Tetrathiomolybdate
There is one agent that does remove copper FROM metallothionein:
- At low doses, ammonium tetrathiomolybdate (TM) removes copper from metallothionein, but this is a different mechanism entirely from zinc 1
- TM is an experimental therapy not commercially available and is not related to zinc supplementation 1
Bottom Line
OptiZinc and all other zinc formulations increase metallothionein production—this is their primary mechanism of action for copper management and cellular metal homeostasis. The claim that zinc lowers metallothionein contradicts the fundamental biochemistry and clinical application of zinc therapy. 1, 2