Normal vitamin B12 levels may still pose risk for cognitive decline, UCSF study finds

A groundbreaking study led by researchers at UC San Francisco (UCSF) has found that meeting the minimum recommended levels of vitamin B12 may not be sufficient to prevent cognitive decline, especially in older adults. The findings, published in the Annals of Neurology, suggest that current B12 recommendations may need revision to better protect brain health.

Vitamin B12 is essential for DNA synthesis, red blood cell formation, and nerve function. However, the study found that older adults with lower—yet still ‘normal’—B12 levels exhibited greater brain white matter damage, slower cognitive processing, and delayed visual responses compared to those with higher B12 levels.

Study Highlights the Hidden Risks of ‘Normal’ B12 Levels

Led by senior author Dr. Ari J. Green, MD, of UCSF’s Departments of Neurology and Ophthalmology, the study analyzed 231 healthy participants from the Brain Aging Network for Cognitive Health (BrANCH) study. The average age was 71 years, and none of the participants had dementia or mild cognitive impairment at the start of the research.

Key findings include:

• Lower active B12 levels correlated with slower cognitive processing speeds and delayed responses to visual stimuli.
• MRI scans revealed increased white matter lesions, which are linked to cognitive decline, dementia, and stroke.
• Older participants were more vulnerable to B12-related neurological deficits, suggesting age amplifies its impact.

Despite having an average B12 level of 414.8 pmol/L—well above the U.S. minimum of 148 pmol/L—participants with lower biologically active B12 showed significant brain function impairments.

A Call for Updated B12 Guidelines and Supplementation

Dr. Green emphasized that current B12 deficiency definitions may be outdated, as they fail to account for subtle neurological effects that occur before traditional symptoms appear.

“Revisiting the definition of B12 deficiency to incorporate functional biomarkers could lead to earlier intervention and prevention of cognitive decline,” said Dr. Green.

Co-first author Alexandra Beaudry-Richard, MSc, of UCSF’s Department of Neurology, highlighted the wider implications of the study:

“These findings suggest that lower B12 levels could impact a much larger proportion of the population than previously believed,” she said. “Clinicians should consider B12 supplementation for older patients with neurological symptoms—even if their levels are within the ‘normal’ range.”

The study underscores the urgent need for further research into the biology of B12 insufficiency and its potential role in preventable cognitive decline.