Zinc Orotate and Zinc Depletion
Zinc orotate does not deplete zinc levels; rather, it is recommended as a form of zinc supplementation due to its better tolerability compared to inorganic zinc compounds. 1, 2
Zinc Orotate as a Zinc Supplement
Zinc orotate is one of several organic zinc compounds used for supplementation, alongside zinc gluconate and zinc histidinate. According to the ESPEN micronutrient guidelines, these organic compounds show better tolerability than inorganic forms like zinc sulfate and zinc chloride 1. This makes zinc orotate a preferred option for zinc supplementation rather than a cause of zinc depletion.
The recommended dosage for zinc supplementation using organic compounds such as zinc orotate is 0.5-1 mg/kg per day of elemental zinc for 3-4 months 1, 2. This recommendation is specifically made for treating acquired zinc deficiency.
Mechanism of Action
Zinc orotate functions as a zinc delivery system. Orotate (orotic acid) itself is a molecule involved in pyrimidine biosynthesis and is found naturally in milk and dairy products 3. When combined with zinc, it forms a complex that allows for zinc supplementation.
The zinc component:
- Induces enterocyte metallothionein, a protein that binds metals
- Interferes with copper uptake from the gastrointestinal tract
- Can generate a negative copper balance when used therapeutically 1
Clinical Applications of Zinc Orotate
Zinc orotate has been used in various clinical contexts:
- For treating acquired zinc deficiency 1
- As part of treatment protocols for Wilson's disease 1
- For immune support and appetite stimulation 2
In Wilson's disease treatment, zinc (including zinc orotate) works by:
- Inducing enterocyte metallothionein which has greater affinity for copper than zinc
- Binding copper in enterocytes and preventing its absorption
- Creating a negative copper balance to help remove stored copper 1
Administration Considerations
For optimal absorption of zinc orotate:
- Take on an empty stomach, at least 30 minutes before meals 2
- Avoid taking with foods high in phytates or with other mineral supplements, especially iron and calcium 2, 4
- Be aware that gastric irritation is a common side effect 1, 2
Potential Adverse Effects
While zinc orotate does not deplete zinc, excessive zinc supplementation (regardless of form) can lead to:
- Gastric irritation (common) 1, 2
- Copper deficiency with prolonged high-dose use, leading to anemia and neutropenia 5
- Impaired immune function with excessive intake 5
- Adverse effects on lipid profiles (LDL/HDL ratio) 5
- Elevations in serum lipase and/or amylase 1
Conclusion
Based on current clinical guidelines, zinc orotate is considered a form of zinc supplementation rather than a cause of zinc depletion. It is specifically recommended as a preferred organic compound for zinc supplementation due to its better tolerability compared to inorganic zinc forms 1, 2.