For unknown reasons, the highest incidence of osteoporosis is found in nort
hern Europe. In these populations, the sunlight exposure is limited and the
vitamin A intake is high. The interaction between vitamin A and D has been
the subject of several in vitro and animal studies. We have studied the ac
ute effects of vitamin A and D on calcium homeostasis in 9 healthy human su
bjects. We compared the effect of (i) 15 mg of retinyl palmitate, (ii) 2 mu
g of 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], (iii) 15 mg of retinyl pal
mitate plus 2 mug of 1,25(OH)(2)D-3, and (iv) placebo in a double-blind cro
ssover study. The subjects took vitamin preparations at 10:00 p.m. and the
following day blood samples were collected five times from 8:00 a.m. to 4:0
0 p.m. Serum levels of 1,25(OH)(2)D-3 and retinyl esters increased (1.7-fol
d and 8.3-fold, respectively; p < 0.01). As expected, serum calcium (S-calc
ium) increased (2.3%; p < 0.01) and S-parathyroid hormone (PTH) decreased (
-32%,; p < 0.05) after 1,25(OH)(2)D-3 intake. In contrast, retinyl palmitat
e intake resulted in a significant decrease in S-calcium. when taken alone
(-1.0%; p < 0.05) and diminished the calcium response to 1,25(OH)(2)D-3 aft
er the combined intake (1.4%; p < 0.01). S-PTH was unaffected by retinyl pa
lmitate. No significant changes in serum levels of the degradation product
of C-telopeptide of type I collagen (CrossLaps), or U-calcium/creatinine le
vels were found. In conclusion, an intake of vitamin A corresponding to abo
ut one serving of liver antagonizes the rapid intestinal calcium response t
o physiological levels of vitamin D in man.