(OR08-04-24) Repeated High-Dose Vitamin A Supplements, Standard of Care for Treating Xerophthalmia, Leads to Hypervitaminosis A in Piglets

Objectives: Two trials were conducted to test the impact of administering three high dose vitamin A (VA) supplements, used for recovery from severe VA deficiency in children, on VA status in a piglet model.

Methods: In 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), but these pigs were weaned at 16 d to prevent weight stagnation due to low feed intake that was observed in Study 1. Study 2 piglets were administered 0; 25,000; and 200,000 IU doses.

Results: In Study 1 (final weight: 3.6 ± 0.7 kg), 40, 90, and 100% of piglets in the 50,000; 100,000; and 200,000 IU treatment groups had hypervitaminosis A as determined by liver concentration (≥1 µmol VA/g). The 25,000 IU group was 100% adequate (0.1 to 1.0 µmol VA/g), and the placebo group was 40% deficient (≤ 0.1 µmol VA/g). 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 predicted deficiency in 50% and 70% of the placebo groups in Study 1 and 2, respectively, but there were three false positives among hypervitaminotic piglets in Study 1.

Conclusions: Repeated high-dose VA may cause hypervitaminosis A, indicating dose sizes should be scaled-back. The MRDR test resulted in false positives in a hypervitaminotic state during malnutrition (i.e., low bodyweight in Study 1), and should be paired with serum retinyl ester evaluation to enhance VA status assessment in populations with overlapping interventions.

Funding Sources: This work was supported by USDA Hatch WI 1022808, and the Louis and Elsa Thomsen Wisconsin Distinguished Graduate Fellowship, a Graduate Student Research Award from the University of Wisconsin-Madison Global Health Institute.