Supplementation of high doses of vitamin D during the gestational period do not cause reproductive, teratogenic and genotoxic damage in mice

• Published in: Food and chemical toxicology 2024-11, Vol.193, p.115007, Article 115007
• Main Authors: Neves, Silvia Cordeiro das, Auharek, Sarah Alves, Gomes, Roberto da Silva, Vilela, Marcelo Luiz Brandão, Nascimento, Valter Aragão do, Coelho, Henrique Rodrigues Scherer, Arunachalam, Karuppusamy, Antoniolli-Silva, Andréia Conceição Milan Brochado, Oliveira, Rodrigo Juliano
• Format: Article
• Language: English
• Subjects: Animals; Cholecalciferol; Dietary Supplements; DNA damage; DNA Damage - drug effects; Dose-Response Relationship, Drug; Embryonic Development - drug effects; Female; Fetal Development - drug effects; Male; Malformations; Mice; Pregnancy; Reproduction - drug effects; Teratogens - toxicity; Vitamin D; Vitamin D - administration & dosage
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.115007

Vitamin D deficiency during pregnancy may have adverse effects on embryo-fetal and postnatal development. Indeed, vitamin D supplementation has been indicated for pregnant women. However, there are no studies that indicate the safe dose of this supplementation during the gestational period. Therefore, the present study assessed the effects of high doses of vitamin D and vitamin D combined with calcium on reproductive performance, embryo-fetal development, and DNA integrity in Swiss mice. A total of 140 pregnant female mice treated with vitamin D and vitamin D combined with calcium were analyzed in two experiments. In one experiment, mice received intramuscular supplementation at doses of 600,000, 6,000,000, or 60,000,000 IU of vitamin D. These same doses were also associated with the dose of 8.56 mg/kg of calcium. In the other experiment, mice received a single oral dose of 6,000, 60,000, or 600,000 IU of vitamin D. These same doses were also associated with the dose of 8.56 mg/kg of calcium. The treatments were always carried out in the 10th gestational day. The results show that neither intramuscularly nor orally administered vitamin D and vitamin D combined with calcium affected reproductive performance, embryo-fetal development, or DNA integrity at the different doses tested. These pioneering results confirm the safety of using this type of high doses of supplementation, including during pregnancy. •High-dose vitamin D did not impact reproductive performance, embryo-fetal development, or DNA integrity in mice.•Both intramuscular and oral administration of high doses of vitamin D were assessed for safety during pregnancy.•The study suggests that high doses of vitamin D, including during pregnancy, may be safe based on the results in mice.•Human studies are needed to validate the findings and provide evidence on the safety of high-dose vitamin D pregnancy.