Metylmalonic acid (MMA) and homocysteine (HCY) are important biomarkers in the assessment of cobalamin and folate metabolism. Correct interpretation of patient results benefit from knowledge of biological variation. The aim of the present study was to determine within-subject (CVI) and between-subject (CVG) biological variations of serum MMA and HCY in healthy women. We collected blood samples from 12 healthy volunteers (33-61 years) on the same weekday for 10 consecutive weeks. Samples were stored at -80 °C until analysis in duplicate in a single analytical run in random order. The CVI and CVG biological variations were estimated by CV-ANOVA after the data were first subjected to outlier and homogeneity analysis. The CVI (95% CI) for MMA and HCY were 7.2% (6.1-8.5) and 7.4% (6.5-8.5), respectively. The corresponding CVG were 21.1% (14.0-32.2) and 24.2% (16.2-36.8). The index of individuality (II) was 0.34 for MMA and 0.31 for HCY and the reference change value (RCV) was -17.7; 21.0 (% decrease; increase) for MMA and -16.2; 19.4 for HCY. We provide within- and between-subject biological variation estimates for MMA and HCY in healthy women using an updated protocol. The results will contribute to a better clinical interpretation of these biomarkers and be of aid when setting analytical performance specifications.
Keywords: Methylmalonic acid; biological variation; healthy volunteers; homocysteine; humans; index of individuality; reference change value; women.