Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin

Abstract

This analysis was performed in Zambian children who had a high prevalence of hypervitaminosis A, defined as > 1.0 μmol retinol/g liver. Bone parameters included markers of bone formation (P1NP), bone resorption (CTX), parathyroid hormone, calcium, vitamin A, and vitamin D. Low dietary vitamin A intake increased P1NP.

Purpose: Vitamin A (VA) interacts with bone health, but mechanisms require clarification. In countries where multiple interventions exist to eradicate VA deficiency, some groups are consuming excessive VA. Bone metabolism and inflammatory parameters were measured in Zambian children who had high prevalence of hypervitaminosis A determined by 13C-retinol isotope dilution.

Methods: Children (n = 143), 5 to 7 years, were recruited into a placebo-controlled biofortified orange maize feeding study for 90 days. Bone turnover (P1NP and CTX) and inflammatory (C-reactive protein (CRP) and alpha-1-acid glycoprotein) biomarkers were measured in fasting blood samples before and/or after intervention with the following: (1) VA at the recommended dietary allowance (400 μg retinol activity equivalents/day (as retinyl palmitate)), (2) maize enhanced with the provitamin A carotenoid β-carotene (2.86 mg/day), or (3) a placebo. Parathyroid hormone, calcium, and 25(OH)-vitamin D were measured at end line.

Results: Bone formation, as measured by P1NP, increased (P < 0.0001) in the placebo group who consumed low preformed VA during the intervention. Bone resorption, measured by CTX, was not affected. P1NP and CTX were negatively associated with inflammation, most strongly with CRP. Serum calcium did not differ among groups and was low (7.29 ± 0.87 μg/dL). Serum 25(OH) D did not differ among groups (54.5 ± 15 nmol/L), with 91% < 75 nmol/L and 38% < 50 nmol/L.

Conclusions: Reduction of dietary preformed VA in Zambian children for 4 months improved bone formation. Chronic consumption of preformed VA caused hypervitaminosis A and may impair bone formation. In children, this could be associated with failure to accrue optimal peak bone mass.

Trial registration: The NIH Clinical Trial registry number is NCT01814891; https://ichgcp.net/clinical-trials-registry/NCT01814891 .

Keywords: CTX; Calcium; P1NP; PTH; Vitamin D; Vitamin a; Zambia.

Conflict of interest statement

Conflicts of Interest: Sherry Tanumihardjo, Bryan Gannon, Chisela Kaliwile, Justin Chileshe, and Neil Binkley declare that they have no conflicts of interest.

Figures

Figure 1

P1NP measurements in Zambian children (n = 71) at three timepoints displayed an effect of time (P < 0.0001), a trending treatment effect (P = 0.060), and a treatment by time interaction (P < 0.0001). The time interval between post-intervention and washout was three weeks and all children were on the same diet during this period. Data are predicted population margins ± standard errors; values without a common letter differ; a>b>c.