Week-to-week biological variation of methylmalonic acid and homocysteine in healthy women

Abstract

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 (CV_I) and between-subject (CV_G) 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 CV_I and CV_G biological variations were estimated by CV-ANOVA after the data were first subjected to outlier and homogeneity analysis. The CV_I (95% CI) for MMA and HCY were 7.2% (6.1–8.5) and 7.4% (6.5–8.5), respectively. The corresponding CV_G 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
• homocysteine
• biological variation
• reference change value
• index of individuality
• healthy volunteers
• women
• humans

Acknowledgments

The skilled technical assistance of Mona Maagerø and Janne Myrsve Solheim is gratefully acknowledged. We also thank the volunteers who provided the blood specimens for the study.

Disclosure statement

The authors report no conflicts of interest.