Vitamin B12, essential for DNA synthesis, red blood cell formation, and maintaining healthy nerve tissue, may not be adequately addressed by current guidelines, particularly for older adults. A study led by researchers at the University of California, San Francisco (UCSF) indicates that healthy older individuals with lower levels of B12, even within the accepted normal range, exhibited subtle neurological and cognitive issues.
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The research published in the *Annals of Neurology* analyzed older adults without dementia or mild cognitive impairment. It found that lower levels of biologically active B12 correlated with slower thinking processes, reduced visual processing speeds, and increased visible injury in brain white matter, which is crucial for communication between different brain regions.
Ari J. Green, MD, senior author of the study, highlighted a potential flaw in how B12 deficiency is defined. He noted that existing thresholds may overlook early functional changes in the nervous system. "Previous studies that defined healthy amounts of B12 may have missed subtle functional manifestations that can affect individuals without overt symptoms," Green remarked. He emphasized the need to consider functional biomarkers in redefining deficiency, which could facilitate earlier interventions to prevent cognitive decline.
The study involved 231 healthy participants from the Brain Aging Network for Cognitive Health study at UCSF, with an average age of 71. Their average blood B12 level was 414.8 pmol/L, significantly higher than the U.S. minimum of 148 pmol/L. However, focusing on the active form of the vitamin revealed that those with lower active B12 levels performed poorer on cognitive assessments, particularly as age increased. Additionally, MRI scans indicated that lower levels of active B12 were associated with a greater volume of white matter lesions, linked to cognitive decline and higher stroke risks.
According to co-first author Alexandra Beaudry-Richard, MSc, these findings suggest that lower but technically normal B12 levels might have broader cognitive effects than previously thought, potentially impacting a larger segment of the population. She recommended that clinicians consider supplementation for older patients displaying neurological symptoms, even when their B12 levels appear normal.
Further studies have added depth to the discussion surrounding B12. A comprehensive review in 2025 indicated that B12 deficiency is a modifiable risk factor for neurological and cognitive issues, especially in high-risk groups like older adults and vegetarians. Although supplementation with B vitamins showed limited benefits for cognitive function among older adults, the need for improved biomarkers and brain imaging to detect issues early was emphasized.
While the UCSF study does not establish a direct cause-and-effect relationship between lower active B12 levels and cognitive decline, it raises critical questions about the adequacy of current testing methods for identifying affected individuals. For clinicians, the findings suggest the importance of considering active B12 levels, particularly in older patients with neurological symptoms. For patients, it underscores that a normal lab result may not always represent complete health, especially if subtle cognitive changes are already in evidence.