Examining the Clinical Usefulness of Urine Methylmalonic Acid for Diagnosis of Vitamin B-12 Deficiency in Older Adults: A Pilot Study.

AIM: Vitamin B-12 deficiency is common among older adults and can lead to irreversible neurological damage and severe complications if not treated early. Despite its clinical significance, effective management remains challenging due to the absence of simple and sensitive biomarkers for early detection and for monitoring treatment response.

PURPOSE: This pilot study evaluated the feasibility and potential of the urinary methylmalonic acid (uMMA)/creatinine ratio as a biomarker of vitamin B-12 deficiency in older adults, while exploring clinical responses following supplementation.

PARTICIPANTS AND

METHODS

A 3-month quasi-experimental pre-post study was conducted with 53 community-dwelling adults aged ≥70 years. Participants provided 4 monthly fasting urine samples to enable tandem mass spectrometry analysis of the uMMA/creatinine ratio before and after 1200 µg/day of peroral vitamin B-12 supplementation. Balance (Berg Balance Scale, Activities-specific Balance Confidence Scale), cognitive function (Montreal Cognitive Assessment), and neurophysiological markers (motor evoked potentials [MEP] latency) were assessed before and after supplementation.

RESULTS

All urine filter paper samples were successfully received and analyzed, with most participants (n = 45) maintaining a supplementation adherence rate of 95% or higher. Supplementation led to a statistically significant reduction in uMMA/creatinine levels, accompanied by significant improvements in both balance and cognitive performance. A significant correlation was observed between the reduction in the uMMA/creatinine ratio and cognitive improvement. No significant changes were detected in MEP latency.

CONCLUSION

Urinary methylmalonic acid is a promising biomarker for assessing vitamin B-12 deficiency and treatment response in older adults. Larger, well-designed studies with extended supplementation periods are needed to confirm its clinical utility and better evaluate the impact of prolonged supplementation on balance, cognitive and neurophysiological outcomes.