The study identified 60 metabolites and the metabolic patterns associated with vitamin D deficiency (VDD) in early pregnancy, providing new proof of vitamin D’s beneficial effect on pregnant women’s lipid levels and offering insights into the underlying mechanisms.
Published in Nutrients, the study identified metabolite changes unreported in earlier investigations. Specifically, VDD was linked with upregulated benzenoids, organic acids and organic oxygen compounds, suggesting it may disturb aromatic compound metabolism and broader energy-related pathways.
“This study provides new metabolomic evidence for the linkage between vitamin D and maternal lipid levels during pregnancy, along with clues about the mechanisms,” the report stated.
Vitamin D deficiency in pregnancy
Vitamin D is a fat-soluble vitamin with diverse physiological functions beyond skeletal health, including roles in immune regulation and metabolic processes.
Deficiency of the vitamin is a widespread global public health issue, with an even higher prevalence among pregnant women.
There is growing evidence that vitamin D status is linked to dyslipidemia—referring to abnormal levels of lipids in the bloodstream—in pregnant women.
A prospective cohort study of pregnant women previously linked lower levels of 25(OH)D in early pregnancy to higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).
While previous research largely concentrated on how vitamin D’s antioxidant and anti-inflammatory mechanisms may affect lipid metabolism, underlying mechanisms have remained unexplored, according to the authors of the current study.
Assessing deficiency related metabolites
The study drew from the Zhoushan Pregnant Women Cohort (ZPWC), a long-term, prospective study initiated in 2011 at the Zhoushan Maternal and Child Care Hospital in China.
A total of 44 women with VDD (25(OH)D < 20 ng/mL), and 44 controls (≥20 ng/mL) were matched 1:1 using propensity scores based on age, pre-pregnancy BMI, gestational week and calendar year at blood sampling.
The researchers measured untargeted metabolomics of first-trimester maternal plasma and identified 60 metabolites connected to VDD. They analyzed associations between VDD-related metabolite components and lipid levels in mid-pregnancy using linear regression models.
A total of 26 metabolites—primarily glycerophospholipids and fatty acyls—were found in smaller amounts in the VDD group.
Lineolic acid (an essential omega-6 polyunsaturated fatty acid) and derivatives were negatively associated with total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C).
Glycerophosphocholines were negatively associated with TC, TG, and high-density lipoprotein cholesterol (HDL-C).
“The level of linoleic acid in the mother is very important for the growth and development of the fetus,” the researchers wrote.
“Studies have shown an inverted U-shaped connection among the birth weight of the offspring and the mother’s consumption of linoleic acid. Additionally, linoleic acid and its derivatives can influence placental function and fetal neurodevelopment by modulating inflammatory cytokines and cellular signaling pathways."
They suggested this metabolic pathway to infant health warrants further in-depth and systematic investigation.
A total of 34 metabolites—mainly benzenoids, organic acids and derivatives—were elevated in the VDD group.
“These findings suggest that vitamin D status may exert broader effects beyond classical lipid and energy metabolism pathways, potentially influencing biochemical clearance processes and host–microbiome homeostasis," the study stated. “For example, low vitamin D levels have been linked to downregulated expression and activity of key cytochrome P450 enzymes, which may slow the metabolism of various drugs and organic compounds, leading to their accumulation in the body.”
Study limitations noted included its cross-sectional nature, meaning that causal correlations cannot be established, and the small sample size. The researchers noted that including mid-pregnancy lipid data for longitudinal analysis would better assess the impact of vitamin D on lipid levels and help elucidate the underlying mechanisms.
Source: Nutrients, doi: 10.3390/nu17193096 (registering doi). “Alterations in the Metabolic and Lipid Profiles Associated with Vitamin D Deficiency in Early Pregnancy”. Qiu, Y. et al.
