Your brain might not be getting enough B12 — even if your levels are considered “normal.”

 Normal B12 Levels Still Linked to Brain Deficiency

By University of California - San Francisco

Getting the recommended amount of vitamin B12 is essential for making DNA, red blood cells, and nerve tissue. But new research suggests that meeting the minimum requirement may not be enough — especially for older adults. In fact, having lower B12 levels, even within the normal range, could increase the risk of cognitive impairment.

A study led by researchers at the University of California, San Francisco found that healthy older adults with lower B12 levels showed signs of neurological and cognitive decline. These individuals had more damage to the brain’s white matter — the nerve fibers that enable different parts of the brain to communicate — and performed worse on tests measuring cognitive and visual processing speeds compared to those with higher B12 levels.

The study was published in Annals of Neurology on February 10.

Rethinking B12 Guidelines for Brain Health

Senior study author Dr. Ari J. Green, from UCSF’s Departments of Neurology and Ophthalmology and the Weill Institute for Neurosciences, says the findings raise concerns about current B12 recommendations.

“Previous studies that defined healthy amounts of B12 may have missed subtle functional manifestations of high or low levels that can affect people without causing overt symptoms,” said Green, noting that clear deficiencies of the vitamin are commonly associated with a type of anemia. “Revisiting the definition of B12 deficiency to incorporate functional biomarkers could lead to earlier intervention and prevention of cognitive decline.”

Lower B12 Correlates with Slower Processing Speeds, Brain Lesions

In the study, researchers enrolled 231 healthy participants without dementia or mild cognitive impairment, whose average age was 71. They were recruited through the Brain Aging Network for Cognitive Health (BrANCH) study at UCSF.

Their blood B12 amounts averaged 414.8 pmol/L, well above the U.S. minimum of 148 pmol/L. Adjusted for factors like age, sex, education, and cardiovascular risks, researchers looked at the biologically active component of B12, which provides a more accurate measure of the amount of the vitamin that the body can utilize. In cognitive testing, participants with lower active B12 were found to have slower processing speed, relating to subtle cognitive decline. Its impact was amplified by older age. They also showed significant delays responding to visual stimuli, indicating slower visual processing speeds and generally slower brain conductivity.

Cognitive Decline Could Affect More People Than Expected

MRIs revealed a higher volume of lesions in the participants’ white matter, which may be associated with cognitive decline, dementia or stroke.

While the study volunteers were older adults, who may have a specific vulnerability to lower levels of B12, co-first author Alexandra Beaudry-Richard, MSc, said that these lower levels could “impact cognition to a greater extent than what we previously thought, and may affect a much larger proportion of the population than we realize.” Beaudry-Richard is currently completing her doctorate in research and medicine at the UCSF Department of Neurology and the Department of Microbiology and Immunology at the University of Ottawa.

Rethinking B12 Deficiency and Supplementation

“In addition to redefining B12 deficiency, clinicians should consider supplementation in older patients with neurological symptoms even if their levels are within normal limits,” she said. “Ultimately, we need to invest in more research about the underlying biology of B12 insufficiency, since it may be a preventable cause of cognitive decline.”

Reference: “Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults” by Alexandra Beaudry-Richard, Ahmed Abdelhak, Rowan Saloner, Simone Sacco, Shivany C. Montes, Frederike C. Oertel, Christian Cordano, Nour Jabassini, Kirtana Ananth, Apraham Gomez, Azeen Keihani, Makenna Chapman, Sree Javvadi, Shikha Saha, Adam Staffaroni, Christopher Songster, Martin Warren, John W. Boscardin, Joel Kramer, Bruce Miller, Joshua W. Miller, Ralph Green and Ari J. Green, 10 February 2025,Annals of Neurology.
DOI: 10.1002/ana.27200

Authors: Co-first author is Ahmed Abdelhak, MD, PhD, of the UCSF Department of Neurology and the Weill Institute for Neurosciences. For a full list of authors, please see the study.

Funding and Disclosures: Westridge Foundation and the Canadian Institutes of Health and Research. There are no conflicts of interest to report.