Objectives Vitamin A deficiency (VAD) has remained a leading cause of morbidity and mortality throughout the world for decades, however there are still challenges defining VA status because the most common biomarker, serum retinol, is regulated homeostatically except in extreme deficiency and affected by inflammation; therefore, more accurate biomarkers to define VAD are needed. Furthermore, the effects of VAD on metabolism are still being uncovered. The objective was to investigate whether serum metabolomics profiles differed between Zambian women with adequate versus deficient VA status measured by the gold-standard biomarker total liver VA reserves (TLR) whose serum retinol concentrations did not differ. Methods Retinol isotope dilution (RID) was used to estimate TLR in Zambian women in the Rufunsa district; serum aliquots were selected for metabolomics based on adequate (TLR > 0.1–1 μmol VA/g liver) or deficient (TLR < 0.1 μmol/g) VA status (n = 10/group). Serum retinol levels were indicative of adequacy (>0.7 μmol/L) and were not different between groups. Serum samples were analyzed by LC-MS using four metabolomics assays. Metabolomics data were covariate-adjusted for age and BMI. Results Ten metabolites were different between the adequate and deficient vitamin A groups (P < 0.05). Metabolites lower in the deficient group included multiple phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), as well as lipoxygenase (LOX)-derived oxylipins (9-HODE and 17-HDoHE), choline, and anthranilic acid. One cholestryl ester was elevated in the deficient group. Conclusions The study revealed numerous metabolites altered by RID-measured VAD and adequacy despite similarly adequate serum retinol levels in both groups. Future research is required to investigate the mechanisms by which phospholipids such as PCs and PEs, as well as LOX-derived oxylipins, are altered by VA status and the potential use of these metabolites as biomarkers of VAD. Funding Sources University of Wisconsin-Madison Global Health Institute visiting scholar fellowship (CK and SAT).

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