Am J Clin Nutr. 2022 Jan 14:nqab422. doi: 10.1093/ajcn/nqab422. Online ahead of print.
ABSTRACT
BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children.
OBJECTIVES: We evaluated the relationship of VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort.
METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z-scores]; serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)]; and inflammation defined as C-reactive protein (CRP ≥ 5 mg/L) and/or α1-acid glycoprotein (AGP ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. (Registered at Clinicaltrials.gov NCT02915731).
RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001) while formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each timepoint was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements.
CONCLUSIONS: Excessive TLRs due to dietary vitamin A intake and supplementation is associated with lower anthropometric measures and bone resorption decreased after supplementation. Vitamin A supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A.The Clinical Trial Registry number is NCT02915731: https://clinicaltrials.gov/ct2/show/NCT02915731.
PMID:35030234 | DOI:10.1093/ajcn/nqab422