Repeated High-dose Vitamin A Supplements, Standard of Care for Treating Xerophthalmia, leads to Hypervitaminosis A in Piglets

Abstract

BackgroundVitamin A (VA) deficiency and excess negatively affect development, growth, and bone health. The WHO’s standard of care for xerophthalmia due to VA deficiency, is three high-dose VA supplements of 50,000-200,000 IU, based on age, which may cause hypervitaminosis A in some individuals. ObjectivesThis study measured VA status following three VA doses in two piglet studies. MethodsIn Study 1, five groups of piglets (n = 10/group) were weaned 10 d post-birth to VA-free feed and orally administered 0; 25,000; 50,000; 100,000; or 200,000 IU VA ester on d 0, 1, and 7. On d 14-15, the piglets underwent the modified relative dose response (MRDR) test for VA deficiency, and were killed. Tissues were collected for HPLC analysis. Study 2 used the same design in three groups (n = 13/group) weaned at 16 d and administered 0; 25,000; and 200,000 IU doses. ResultsIn Study 1 (final weight: 3.6 + 0.7 kg), liver VA concentration was hypervitaminotic in 40, 90, and 100% of 50,000; 100,000; and 200,000 IU groups. The 25,000 IU group was 100% adequate, and the placebo group was 40% deficient. In Study 2 (final weight: 8.7 + 0.8 kg), where 200,000 IU could be prescribed to infants with a similar body weight, 31% of the piglets were hypervitaminotic, the 25,000 IU group was 100% VA adequate, and the placebo group was 100% deficient. The MRDR test measured deficiency in 50% and 70% of the placebo group in each study but had three false positives among hypervitaminotic piglets in Study 1. ConclusionsRepeated high-dose VA may cause hypervitaminosis, indicating dose sizes may need reduction. The MRDR resulted in false positives in a hypervitaminotic state during malnutrition and should be paired with serum retinyl ester evaluation to enhance VA status assessment in populations with overlapping interventions.