Amino Acid Complexed Zinc Has Higher Bioavailability Than Hydroxy Acid Complexed Zinc

Poor zinc absorption causes zinc deficiency, leading to skin, gut, and immune pathologies, and psychiatric changes, and are potentially life threatening in infants and children. This can be caused by dietary deficiencies, but also inherited mutations of the ZIP4 gene. Objective Although zinc complexed with organic molecules have previously been shown to have better uptake, we hypothesized that bonding the zinc to the amino group would be less liable to breakdown in the gut than zinc complexed to hydroxy acids, leading to higher bioavailability. Methods We treated wild‐type and mice with inducible universal knockout of one copy of the ZIP4 gene with reduced zinc diet (15 ppm) ad libitum, either in the form of amino acid complexed (CSK18271) or hydroxy acid complex (CSK18273) zinc in an otherwise nutritionally complete diet. Weight was measured at weekly intervals, and mice placed in metabolic phenotyping chambers for a week near the end of the trial. Results We found that ZIP4 +/− mice fed CSK18271 had weight gain comparable to wild‐type mice; wild‐type mice fed CSK18273 had lower weight gain, indicating bioavailability was lower even with intact zinc transporter. Zip4 +/− mice fed CSK18273 had the worst overall weight gain. Metabolic phenotyping chambers found an increase in respiratory exchange rate (RER) and water intake in the Zip4 +/− mice, indicating reduced kidney function in the heterozygous knockout mice, which was compensated for functionally by CSK18271 diet. Conclusions Zinc complexed to the amine group has higher bioavailability than zinc complexed to the hydroxyl group in amino acids, likely because of increased resistance to degradation in the gut. This results in improved weight gain in both wild‐type and Zip4 +/− animals. Support or Funding Information The work was funded by Vanderbilt University Medical Center internal funds.