Sex-related differences in within-subject biological variation estimates for 22 essential and non-essential amino acids

Background: Measurement of serum amino acid (AA) concentrations is important in particular for the diagnosis and monitoring of inborn errors of AA metabolism. To ensure optimal clinical interpretation of AAs, reliable biological variation (BV) data are essential. In the present study, we derived BV data for 22 non-essential, conditionally essential, and essential AAs and assessed differences in BV of AAs related to sex. Methods: Morning blood samples were drawn from 66 subjects (31 males and 35 females) once a week for 10 consecutive weeks. All samples were analyzed in duplicate using liquid chromatography-tandem mass -spectrometry. The data were assessed for outliers, trends, normality and variance homogeneity analysis prior to estimating within-subject (CVI) and between-subject (CVG) BV. Results: CVI estimates ranged from 9.0 % for histidine (male) to 33.0 % for taurine (male). CVI estimates in males and females were significantly different for all AAs except for aspartic acid, citrulline and phenylalanine, in most cases higher in females than in males. Apart from for arginine, CVG estimates in males and females were similar. Conclusions: In this highly powered BV study, we provide updated BV estimates for 22 AAs and demonstrate that for most AAs, CVI estimates differ between males and females, with implications for interpretation and use of AAs in clinical practice.