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

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Abstract

Summary

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

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Fig. 1

Abbreviations

RID:

Retinol isotope dilution

VA:

Vitamin A

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Acknowledgments

The authors would like to thank Kiersten Olsen and Michael Grahn for analyzing samples and Devika Suri for assistance with statistical evaluation. HarvestPlus (www.harvestplus.org) is a global alliance of agriculture and nutrition research institutions working to increase the micronutrient density of staple food crops through biofortification.

Funding

The work was supported by HarvestPlus contract number 8256. HarvestPlus provided funding on the basis of study design and recommended additional assays to perform. Other support was from an endowment to Tanumihardjo entitled, “Friday Chair for Vegetable Processing Research” and Global Health Funds at the University of Wisconsin-Madison.

Author information

Author notes

  1. B. M. Gannon

    Present address: Cornell University, Ithaca, NY, USA

  2. S. A. Tanumihardjo and B. M. Gannon contributed equally to this work.

Authors and Affiliations

  1. Department of Nutritional Sciences, University of Wisconsin-Madison, 1415 Linden Dr., Madison, WI, 53706, USA

    S. A. Tanumihardjo & B. M. Gannon

  2. National Food and Nutrition Commission of Zambia, P.O. Box 32669, Lusaka, Zambia

    C. Kaliwile

  3. Tropical Diseases Research Center, Ndola, Zambia

    J. Chileshe

  4. Osteoporosis Clinical Research Program, University of Wisconsin-Madison, Madison, WI, USA

    N. C. Binkley

Authors
  1. S. A. Tanumihardjo
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  2. B. M. Gannon
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  3. C. Kaliwile
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  4. J. Chileshe
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  5. N. C. Binkley
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Corresponding author

Correspondence to S. A. Tanumihardjo.

Ethics declarations

The Tropical Disease Research Center’s Ethics Review Committee in Ndola, Zambia approved the study. The consent form and related materials were translated into English and the University of Wisconsin-Madison’s Health Sciences Human Subjects’ Institutional Review Board approved the study.

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Tanumihardjo, S.A., Gannon, B.M., Kaliwile, C. et al. Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin. Arch Osteoporos 14, 72 (2019). https://doi.org/10.1007/s11657-019-0617-y

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