Are Current Vitamin B12 Guidelines Putting Brain Health at Risk?

Recent research indicates that the current reference values for vitamin B12 may not be sufficiently protective of brain health in older adults. Individuals with B12 levels considered “normal” but on the lower end show subtle signs of cognitive decline and brain structural changes, according to a study published in Annals of Neurology. ¹

What the Study Found

Researchers from the University of California, San Francisco (UCSF) enrolled 231 healthy adults (average age ≈ 71) without diagnoses of dementia or mild cognitive impairment. They measured biologically active B12 (often holo-transcobalamin) rather than only total serum B12, as it reflects the amount usable by the body.

After adjusting for factors like age, sex, education, cardiovascular risk, and more, they found that participants with lower active B12—even though their levels were still within the traditionally accepted “normal” range—performed worse in tests of processing speed and visual reaction time.

MRI scans also revealed increased white matter lesions (areas of damage in the brain’s connecting fibers) in these lower-B12 individuals compared to higher-B12 counterparts.

The mean total B12 level in the cohort was 414.8 pmol/L — well above the U.S. standard minimum of 148 pmol/L — yet even within that range, variation correlated with neurological outcomes.

Implications: Why “Normal” May Be Misleading

According to senior author Dr. Ari J. Green, previous definitions of B12 deficiency may “miss subtle functional manifestations” affecting brain health, even in absence of overt blood or nerve symptoms. The authors suggest that functional biomarkers (such as MRI findings, cognitive testing, biologically active B12) should supplement or perhaps redefine thresholds for deficiency.

Supporting Evidence & Contrasting Views

Earlier literature has long recognized B12 deficiency as a cause of neurological problems (e.g. demyelination, peripheral neuropathy, cognitive impairment).² But evidence on whether supplementing beyond deficiency levels improves cognition is mixed. For example, a review by the NIH Office of Dietary Supplements notes that B12 supplementation in older adults with normal B12 status did not show clear benefits on memory, executive function, or processing speed in several trials.

A related 2025 meta-analysis looked at B12 deficiency and cognitive impairment, finding that individuals with deficient B12 had a roughly 1.5× higher risk of cognitive decline. This supports that low B12 is a risk factor, though it does not directly address whether raising “low-normal” levels confers benefit.

What This Means for Guidelines & Practice

The findings provoke reconsideration of how B12 deficiency is defined and addressed:

• Thresholds for “normal” B12 may be too low to protect brain health in aging populations.

• Functional and structural biomarkers, in addition to blood B12 levels, might be useful to detect early brain impact.

• Clinicians might consider evaluating older patients who present with cognitive complaint, even if their B12 is “within normal limits,” especially if they have brain imaging or other risk factors.

• Any potential benefit of supplementation in people with “low-normal” B12 needs rigorous testing in controlled trials.

Further large-scale, longitudinal, and interventional studies are needed to clarify whether revising B12 guidelines or recommending supplementation will reduce risks of brain decline, cognitive impairment, or dementia.

References

1. Beaudry-Richard, Alexandra, Praneet K. Gupta, Brian J. Morris, Zoe Y. Wang, Gabrielle R. Smith, Michael L. Jones, et al. “Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults.” Annals of Neurology (2025). https://doi.org/10.1002/ana.27200.

2. “Vitamin B12: A Review of Evidence for Cognitive Function.” PMC / Health Quality Ontario, 2013. Accessed [date you accessed]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874776/

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