Scientists Found a Major Problem With Vitamin B12 Guidelines, and Your Brain Might Be at Risk

When “Normal” Vitamin B12 May Not Be Enough

By University of California - San Francisco

Meeting the standard daily requirement for vitamin B12, which is essential for making DNA, red blood cells, and nerve tissue, may not provide enough protection for the brain, particularly in older adults. In fact, falling within the “normal” range could still increase the risk of cognitive problems.

Researchers at UC San Francisco studied healthy older adults and discovered that participants with lower B12 levels, even though still considered normal, showed neurological and cognitive weaknesses. 

These individuals had more damage in the brain’s white matter (the network of nerve fibers that allows different regions of the brain to communicate) and scored lower on tests measuring cognitive speed and visual processing compared with those who had higher B12 levels.

The study was published in Annals of Neurology.

Rethinking Vitamin B12 Guidelines

According to senior author Ari J. Green, MD, of UCSF’s Departments of Neurology and Ophthalmology and the Weill Institute for Neurosciences, the results raise concerns about whether current B12 recommendations are sufficient and suggest that guidelines may need to be revised.

“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.”

Low B12, Slower Thinking, and 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 general slower brain conductivity.

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

Implications for Prevention and Future Research

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.

“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.

A version of this article was originally published in February 2025.

Since the February 2025 publication, the findings have sparked wide discussion among researchers and clinicians. Several reviews have reinforced the link between low-normal vitamin B12 and subtle neurological damage, pointing out that current guidelines may underestimate the brain’s true requirements.

Commentators have called for raising the cutoff for deficiency and shifting toward measuring biologically active B12 (holo-transcobalamin) rather than total serum levels, as even “healthy” amounts may leave older adults vulnerable to cognitive decline and white matter damage. Early reports also highlight associations between low active B12 and elevated neurodegeneration markers such as tau protein, strengthening the case for redefining what counts as adequate.