Vitamin A Antagonizes the Action of Vitamin D in Rats

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Abstract
Interactions between vitamin A and vitamin D have been suggested for several decades but have not been established. In particular, vitamin A has been proposed to intensify the severity of the bone mineralization disease, rickets and inhibit the ability of vitamin D to cure this disease. To investigate this hypothesis, weanling Holtzman rats were fed a 1.2% calcium, 0.1% phosphorus diet and 15.5 ng ergocalciferol (vitamin D2) every 3 d for 21 d in the presence of increasing amounts of retinyl acetate (0 μg to 8621 μg/d). The increasing amounts of retinyl acetate produced a progressive and significant decrease in total bone ash (P < 0.001) and an increase in epiphyseal plate width (P < 0.001). The same experiment conducted with increasing amounts of vitamin D2 (0 to 645 ng/d) indicated that the antagonism by retinyl acetate could be demonstrated at all vitamin D2 dosages. To further investigate this antagonistic relationship, weanling Holtzman rats were fed a 0.47% calcium, 0.3% phosphorus diet and 15.5 ng vitamin D2 every 3 d for 33 d in the presence of increasing retinyl acetate (0 to 3448 μg/d). In the absence of retinyl acetate, these rats maintained a normal serum calcium level (2.34 mmol/L). Increasing retinyl acetate, however, eliminated the ability of vitamin D2 to elevate the level of serum calcium (1.35 mmol/L). These results illustrated in vivo antagonism of vitamin D2 action on intestine and bone by retinyl acetate.