THE TERATOGENIC METABOLITES OF VITAMIN-A IN WOMEN FOLLOWING SUPPLEMENTS AND LIVER

1 Ten healthy female volunteers were given 5 doses of retinol as the p almitate; 50 and 150 mg retinol as an oral supplement, 50 and 150 mg a s fried calf liver (50 and 150 g) and 3, 9 or 30 mg by intra-muscular injection, 2 Plasma concentrations of retinyl palmitate were higher af ter 50 mg retinol given as an oral supplement compared with 50 mg as l iver; there was no significant difference between the 150 mg doses. Pl asma concentrations of retinol showed only small increases. 3 The peak plasma concentrations (C(max)) of all-trans-retinoic acid, the princi pal teratogenic metabolite of retinol, and the area under the concentr ation-time curve (AUC) were up to 20-times higher after supplements co mpared to the same dose as liver. Plasma concentrations of all-trans-4 -oxo-retinoic acid, 13-cis-retinoic acid and 13-cis-4-oxo-retinoic aci d showed smaller differences between supplements and liver. 4 Intra-mu scular administration of 30 mg retinol gave retinyl palmitate concentr ations similar to those found after the oral doses but did not increas e circulating concentrations of the acid metabolites. 5 Based on the f ormation of all-trans-retinoic acid, liver and supplements are not of equivalent teratogenic potential. Advice to pregnant women on the cons umption of liver based on the reported teratogenicity of vitamin A sup plements should be reconsidered.