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

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 ß-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://clinicaltrials.gov/ct2/show/NCT01814891 .

Hypercarotenodermia in Zambia: which children turned orange during mango season?

Vitamin A (VA) deficiency is a public health problem in many countries. The World Health Organization recommends high-dose VA supplements to children aged 6-59 months based on unequivocal evidence that supplements decreased mortality risk. VA supplements were meant as a temporary intervention until more sustainable approaches could be implemented. Fortification of processed foods with preformed VA is a means to improve VA status. The most recent addition of retinyl palmitate to cooking oil in countries that may also fortify margarine and milk will undoubtedly have a positive impact on VA status. However, quantitative measures have not been used to assess the underlying VA status of the groups who have adopted widespread fortification. The addition of preformed VA to otherwise adequate diets in VA may cause excessive total body stores. Monitoring population status will require accurate VA assessment to ensure that hypervitaminosis does not prevail. This perspective describes a cohort of rural Zambian children who have adequate diets in VA, mostly as provitamin A carotenoids; who were given high-dose VA supplements till the age of 5 years; who have access to VA-fortified sugar; and whose mothers had access to VA-fortified sugar throughout pregnancy and lactation. Many of these children turned orange during mango season, and this phenomenon occurred at estimated liver reserve concentrations >1 µmol retinol equivalents/g liver. It will be necessary to continue to monitor VA status, including all sectors of the population that have access to successful interventions, to optimize health with the intent to lower retinol content of fortified foods or better target VA supplementation to areas of most need.