Population Reference Values for Serum Methylmalonic Acid Concentrations and Its Relationship with Age, Sex, Race-Ethnicity, Supplement Use, Kidney Function and Serum Vitamin B12 in the Post-Folic Acid Fortification Period

Serum methylmalonic acid (MMA) is elevated in vitamin B-12 deficiency and in kidney dysfunction. Population reference values for serum MMA concentrations in post-folic acid fortification period are lacking. Aims of this study were to report the population reference values for serum MMA and to evaluate the relation between serum MMA and sex, age, race-ethnicity, kidney dysfunction and vitamin B-12. We used data from three National Health and Nutrition Examination Surveys, 1999-2000, 2001-2002 and 2003-2004 conducted after folic acid fortification commenced (n = 18,569). Geometric mean MMA was approximate to 22.3% higher in non-Hispanic white compared to non-Hispanic black (141.2 vs. 115.5 nmol/L) and was approximate to 62.7% higher in >70 years old persons compared to 21-30 years old persons (196.9 vs. 121.0 nmol/L). Median serum MMA was approximate to 28.5% higher in the 1st the quartile of serum vitamin B-12 than in the 4th quartile of serum vitamin B-12 and was approximate to 35.8% higher in the 4th quartile of serum creatinine than in the 1st quartile of serum creatinine. Multivariate-adjusted serum MMA concentration was significantly associated with race-ethnicity (p < 0.001) and age (p < 0.001) but not with sex (p = 0.057). In this large US population based study, serum MMA concentrations presented here reflect the post-folic acid fortification scenario. Serum MMA concentrations begin to rise at the age of 18-20 years and continue to rise afterwards. Age-related increase in serum MMA concentration is likely to be due to a concomitant decline in kidney function and vitamin B-12 status.