Establishing Reference Intervals for Fat-Soluble Vitamins in Healthy Chinese Adults: Study Protocol for a...

Fat-soluble vitamins (FSVs)-vitamins A, D, E, and K-are essential micronutrients involved in key physiological processes. Both deficiency and excess can influence nutritional assessment and disease risk. In China, clinical evaluation of FSVs often relies on reference intervals (RIs) derived from Western populations, and no large-scale study has comprehensively evaluated all 4 FSVs in healthy Chinese adults.

The aim of this study is to establish population-specific RIs for vitamins A, D, E, and K in healthy Chinese adults, thereby supporting more accurate clinical assessment of vitamin status and the prevention of related diseases.

This ongoing multicenter cross-sectional study aims to recruit 100,000 adults (≥18 y) from 20 hospitals across China. Participants undergo a standardized questionnaire, physical examination, and blood sample collection. FSV concentrations are quantified using liquid chromatography-tandem mass spectrometry. Group differences are assessed using the chi-square test or Fisher exact test. Nested ANOVA evaluates variation across subgroups. RIs will be established using parametric or nonparametric percentile methods following rigorous outlier removal to accurately determine the 2.5th and 97.5th percentile limits.

As of October 2025, 13,545 adults have been enrolled, and 1690 participants have met the inclusion criteria. Recruitment began on 1 July 2024 and is expected to conclude by 30 June 2026.

This study will generate the first large-scale, population-specific RIs for FSVs in healthy Chinese adults. The findings are expected to be published in 2027 and will provide an important evidence base for clinical nutrition assessment and disease prevention in China.