Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats

Diabetologia. 1997 Dec;40(12):1416-24. doi: 10.1007/s001250050844.


An excess of reactive oxygen species (ROS) has been associated with the increased rate of congenital malformations in experimental diabetic pregnancy. Previous in vitro and in vivo studies show that antioxidants can protect the embryonic development in a diabetic environment. In the present investigation we examined the antiteratogenic capacity of vitamin C, an antioxidative agent not previously evaluated as a dietary supplement in diabetic pregnancy. Normal and streptozotocin diabetic rats were either fed a standard diet or a diet enriched with 0.9, 1.8 or 4% sodium ascorbate throughout pregnancy. On gestational day 20, the litters of normal and diabetic rats without vitamin C supplement contained 9 and 12% early resorptions, 2 and 17% late resorptions and 1 and 27% malformations, respectively. Vitamin C treatment reduced the rates of late resorptions and malformations in the diabetic groups in proportion to the dose administered. Thus, in the diabetic group with 4% ascorbate treatment we found unchanged numbers of early resorptions, but only 7% late resorptions (p < 0.05 vs untreated diabetic pregnancy) and 8% malformations (p < 0.05 vs untreated diabetic pregnancy). Maternal diabetes did not alter tissue levels of ascorbic acid in the fetuses at term, whereas vitamin C treatment caused accumulation of ascorbic acid in the placenta, maternal and fetal liver. Vitamin C supplementation yielded increased alpha-tocopherol concentration in the placenta and caused a reduction of the high concentrations of thiobarbituric acid reactive substances (TBARS) in serum of pregnant diabetic rats. Vitamin C treatment reduces the rates of congenital malformations and late resorptions, thereby supporting that ROS are involved in the embryonic dysmorphogenesis of diabetic pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / metabolism
  • Body Weight
  • Brain / embryology
  • Brain / metabolism
  • Congenital Abnormalities / etiology
  • Congenital Abnormalities / prevention & control*
  • Diabetes Mellitus, Experimental / complications*
  • Diet*
  • Female
  • Fetus / metabolism
  • Liver / embryology
  • Liver / metabolism
  • Organ Size
  • Placenta / anatomy & histology
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy in Diabetics / complications*
  • Rats
  • Rats, Sprague-Dawley
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Vitamin E / metabolism


  • Thiobarbituric Acid Reactive Substances
  • Vitamin E
  • Ascorbic Acid