Observational studies find that vitamin A status, as measured by serum concentrations of retinol, retinoic acid, or retinyl esters, is associated with several health conditions. For example, lower serum vitamin A concentrations are found in people with asthma compared to healthy controls,[1] and low serum vitamin A concentrations are associated with a greater risk of stroke.[2] Other studies find complicated relationships. For example, a U-shaped relationship exists between vitamin A status and the risk of hip fracture: both lower-than-normal and higher-than-normal serum concentrations are correlated with a greater risk of fracture.[3] Furthermore, vitamin A status has been associated with cardiometabolic diseases like cardiovascular disease, obesity, and type 2 diabetes, but the direction of association varies depending on which vitamin A metabolite is measured.[4]
Consequently, it is difficult to determine causality from such observations. Furthermore, the measurement of vitamin A metabolites in the blood is not a good biomarker for bodily vitamin A stores or dietary intake.[5][6][7][8][9] The better approach is the retinol isotope dilution method, which is considered the gold standard since it correlates strongly with liver stores and indicates vitamin A status in deficiency and in excess.[10] However, this method is not used in the above-described observational studies. Therefore, further research, ideally with dose-response and/or randomized controlled trial designs, is needed to clarify the causal effect of vitamin A status on health conditions.