Duration of Metallothionein Activation After Zinc Intake
Metallothionein remains activated and functional as long as zinc intake continues, with enterocyte turnover occurring approximately every 2-6 days, at which point the copper-metallothionein complex is shed into fecal contents. 1
Mechanism and Timeline
Zinc induces enterocyte metallothionein synthesis, which then preferentially binds copper over zinc due to its higher affinity for copper. 1 The key temporal aspects are:
- Metallothionein induction occurs within 18 hours of zinc administration 2
- The protein persists throughout the lifespan of the enterocyte (approximately 2-6 days in normal turnover) 1
- Once bound to copper, the metallothionein-copper complex is lost into fecal contents as enterocytes are naturally shed 1
Clinical Implications for Dosing
For therapeutic efficacy, zinc must be taken at least twice daily, though three times daily is preferred (150 mg elemental zinc divided into three doses for adults >50 kg). 1 This frequent dosing requirement exists because:
- Metallothionein activation is not a one-time event but requires continuous zinc presence 1
- Taking zinc with food interferes with absorption and reduces effectiveness 1, 3
- Optimal absorption requires taking zinc 30 minutes before meals 3
Important Caveats
The relationship between metallothionein and zinc absorption is dose-dependent and bidirectional:
- Low-dose zinc induction (0.2-0.5 μmol) increases zinc absorption 2
- High-dose zinc induction (2 μmol) paradoxically decreases zinc absorption efficiency by sequestering zinc in the mucosa 4, 2
- Metallothionein levels are inversely related to serum zinc concentration after oral dosing 4
Zinc also induces hepatocellular metallothionein, providing a secondary mechanism for copper management beyond the intestinal effect. 1