Methylmalonic acid and vitamin B12 in patients with heart failure

Vitamin B12 deficiency among patients with heart failure (HF) may have been underestimated. High serum levels of methylmalonic acid (MMA) have been identified in several studies as an early indicator of vitamin B12 deficiency. Furthermore, MMA seems to constitute a biomarker of oxidative stress and mitochondrial dysfunction. There are scarce data regarding vitamin B12 and MMA in patients with HF. The aim of this study was to investigate vitamin B12 and MMA serum levels in patients with HF.

One hundred five consecutive patients admitted to our hospital with symptoms and signs of acute decompensated HF were included in the study. Demographic and clinical characteristics as well as comorbidities and medical treatment before hospital admission were recorded. Transthoracic echocardiography was performed in all patients. Blood samples were collected during the first 24 hours of hospitalization and measured for complete blood count, biochemical profile, vitamin B12, N-terminal prohormone of brain natriuretic peptide, and MMA levels. Finally, 51 healthy individuals constituted the control group.

A total of 43.8% of patients with HF had elevated MMA levels, but only 10.5% had overt vitamin B12 deficiency, defined as serum cobalamin levels below 189 pg/ml. Mean MMA level was higher in patients with HF than in controls (33.0 ± 9.6 vs. 19.3 ± 6.3 ng/ml; p < 0.001). This difference remained significant when adjusted for age, sex, vitamin B12, and folate serum levels and kidney function (B = 14.7 (9.6-19.7); p < 0.001). MMA levels were higher in patients with acutely decompensated chronic HF than in those with newly diagnosed acute HF (34.7 ± 10.5 vs. 30.7 ± 7.8 ng/ml; p = 0.036). Correlation analysis revealed significantly negative correlation between MMA and vitamin B12 levels only in patients without comorbidities.

Patients with HF have elevated MMA levels, independent of age, gender, HF category, or comorbidities, possibly indicating subclinical vitamin B12 deficiency. Further research is needed to investigate subclinical vitamin B12 deficiency in patients with HF and/or to clarify whether MMA constitutes a biomarker of oxidative stress.