Vitamin A deficiency remains a problem for more than 200 million preschool children and reproductive age women. In areas of the world where vitamin A deficiency remains despite supplementation programs, multiple interventions have been employed. As a result, there is a possibility that overlapping intervention programs have exposed some individuals to the potential for excessive vitamin A intake. Sowa and colleagues conducted a study to explore this possibility and report the results of their work in the November 2020 issue of The Journal of Nutrition.

Two experiments using gerbils were conducted that evaluated the impact of combined supplement regimens on liver retinol stores. In the first experiment, animals were provided diets containing white maize and white carrots along with vitamin A (50% of estimated needs) as controls, or with high b-carotene maize, orange carrots and vitamin A (2 x 2 x 2 factorial). In the second study, only orange carrots were used with dietary vitamin A levels at 100 or 200% of estimated needs (2 x 3 factorial). The expression of genes for the b-carotene absorption scavenger and oxygenases involved in the conversion to vitamin A were also measured in the second experiment.

Supplementing with either orange carrots or orange maize increased liver retinol concentrations relative to baseline levels, and when compared with the controls using white carrots and maize. The vitamin A supplement alone did not induce an increase in liver retinol in either experiment. However, adding in orange carrots in the second study also led to elevated liver retinol concentrations. Elevations in liver retinol were associated with lower expression of the carotenoid scavenger protein and b-carotene 15,15’-dioxygenase genes. These observations led the authors to conclude that biofortified carrots and maize were sufficient to prevent vitamin A deficiency, but that the addition of preformed vitamin A led to excess liver retinol storage even though it caused down regulation of key carotenoid absorption and cleavage gene expressions.

In a commentary on this article, Lietz outlines two questions that must be addressed based on the results described. The first one asks if provitamin A can lead to excessive liver retinol levels based on our existing knowledge about its conversion to vitamin A, then are provitamin A carotenoids “safe”. The second question addresses the possibility that the definition of an upper intake level for vitamin A may need to be modified to include provitamin A carotenoids. He concludes that more work is needed to establish what truly constitutes hypervitaminosis A and whether provitamin A carotenoids need to be included in intake measures to accurately assess safety of vitamin A interventions.


Sowa M, Mourao L, Sheftel J, Kaeppler M, Simons G, Grahn M, Davis CR, von Lintig J, Simon PW, Pixley KV, Tanumihardjo SA. Overlapping vitamin A interventions with provitamin A carotenoids and preformed vitamin A cause excessive liver retinol stores in male Mongolian gerbils. The Journal of Nutrition, Volume 150, Issue 11, November 2020, Pages 2912–2923,

Lietz G. Overlapping vitamin A intervention programs: Should we be concerned with excessive intakes? The Journal of Nutrition, Volume 150, Issue 11, November 2020, Pages 2849 – 2851,

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