Vitamin D3 kinetics in nonpregnant and pregnant women after a single oral dose of trideuterated vitamin D3

Authors: BEST, CORA - Cornell University; SHERWOOD, ROBERT - Cornell University; Novotny, Janet; ZHANG, SHENG - Cornell University; PRESSMAN, EVA - Cornell University; O’BRIEN, KIMBERLY - Cornell University

Submitted to: The Journal of Steroid Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/2021
Publication Date: 11/26/2021
Citation: Best, C.M., Sherwood, R., Novotny, J.A., Zhang, S., Pressman, E.K., O’Brien, K.O. 2021. Vitamin D3 kinetics in nonpregnant and pregnant women after a single oral dose of trideuterated vitamin D3. The Journal of Steroid Biochemistry and Molecular Biology. 216:1-8. 106034. https://doi.org/10.1016/j.jsbmb.2021.106034.
DOI: https://doi.org/10.1016/j.jsbmb.2021.106034

Interpretive Summary: During pregnancy, the blood pool of the active form of vitamin D is increased throughout most of the pregnancy period. Why or how this phenomenon occurs, but it likely represents an important adaptation to the health of the growing child. Stable isotopes are special “tags” that can be added to vitamins (or other molecules) to allow scientists to follow the movement of the vitamins through the body and are safe for pregnant women. Therefore, we tagged vitamin D with a stable isotope called deuterium to learn more about vitamin D metabolism in pregnant and nonpregnant women. We also developed new lab methods to measure the amount of the tagged vitamin forms in the body. It was found that the women in the study had marked variability in their vitamin D metabolism, and that a protein called “vitamin D binding protein” had the greatest influence on the vitamin D metabolism. Pregnant women had higher levels of vitamin D binding protein, which in part explains their difference in handling vitamin D compared to nonpregnant women. The new method developed in this work will allow further studies of vitamin D metabolism in various populations, including pregnant and nonpregnant women. This work will be used primarily by scientists.

Technical Abstract: The plasma pool of the hormone 1,25-dihydroxyvitamin D (1,25(OH)2D) is increased throughout most of human pregnancy. Mechanisms behind this adaptation are unclear, in part due to limited data on vitamin D kinetics during pregnancy. Stable isotopes make it possible to study vitamin D kinetics in vulnerable study populations like pregnant women. We conducted a pilot study of vitamin D kinetics in nonpregnant and pregnant women. We evaluated a clinical protocol and developed analytical methods to assess the serum appearance and disappearance of trideuterated vitamin D3 (d3-vitamin D3) and trideuterated 25-hydroxyvitamin D3 (d3-25(OH)D3) after a single oral dose of 25 µg of [6,19,19-2H]-vitamin D3 (d3-vitamin D3). Blood was collected at baseline and 2, 4, 6, 24, 168, 264, and 456 hours post-dosing. We then described the serum kinetic profiles of d3-vitamin D3 and d3-25(OH)D3 in nonpregnant and pregnant women. Serum kinetic profiles of d3-vitamin D3 and d3-25(OH)D3 followed a time course in line with previous pharmacokinetic studies. There was marked variability between participants in the area under the concentration-time curve (AUC) of d3-25(OH)D3 over the 20-day study period. This AUC of d3-25(OH)D3 was positively correlated with the serum vitamin D binding protein (DBP) concentration, which was higher in pregnant compared with nonpregnant women. The mean serum half-life of 25(OH)D3 was longer but not significantly different in pregnant women (18.8 days) compared with nonpregnant women (13.6 days). Our pilot study demonstrated that a single oral dose of 25 µg of d3-vitamin D3 can be used to study vitamin D kinetics. Serum DBP concentration is an important predictor of vitamin D kinetics, and more research is needed to fully understand the significance of elevated DBP concentration during pregnancy.