Vitamin D Supplementation and the Effects on Glucose Metabolism During Pregnancy: A Randomized Controlled Trial

Randomized controlled trial conducted at a single institution in Sydney, Australia, enrolling pregnant women with singleton pregnancies who started supplementation before 20 weeks' gestation and had low baseline vitamin D status. The active intervention groups included 89 randomized to 5,000 IU/day and 90 randomized to 400 IU/day; most participants also used a pregnancy multivitamin during the study.

Pregnant participants received oral vitamin D3 capsules daily until delivery: high dose 5,000 IU/day versus low dose 400 IU/day. The trial compared high-dose supplementation with standard-dose vitamin D3 in women with low baseline vitamin D status.

High-dose vitamin D3 did not improve maternal glucose metabolism during pregnancy compared with 400 IU/day. At 26-28 weeks, fasting glucose was 75 (7) mg/dL vs 75 (6) mg/dL, 2-hour glucose was 108 (25) mg/dL vs 111 (28) mg/dL, HOMA-IR was 1.0 (1.3) vs 0.8 (1.6), and gestational diabetes occurred in 7 (8%) vs 12 (13%) participants, P = 0.25. High-dose supplementation did increase neonatal cord blood 25OHD to 46 (19) ng/mL versus 29 (12) ng/mL and reduced cord plasma 25OHD <20 ng/mL to 5 (10%) versus 11 (24%). The authors concluded that 5,000 IU/day safely improved vitamin D status and reduced neonatal deficiency, but did not change glucose outcomes.

The trial was not powered to detect differences in gestational diabetes incidence, limiting inference for that outcome. It was conducted at a single center and relied on a relatively short treatment window through pregnancy. Widespread pregnancy multivitamin use and the possibility that prepregnancy vitamin D status influenced response may also complicate interpretation.