Study: Vitamin B12 Levels Within "Normal" Range Linked to Cognitive Decline in Older Adults

The current minimum vitamin B12 recommendations may be insufficient for older adults, as new research published by investigators in Annals of Neurology reveals that cognitive impairment was linked to levels within the ‘normal range,’ with the presence of white matter damage and slower cognitive processing.^1,2

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Vitamin B12 is crucial in red blood cell formation, cell metabolism, nerve function, and the production of DNA, according to Mayo Clinic. The current recommended daily amount of vitamin B12 for adults is 2.4 mcg, which is often obtained through diet. Foods rich in vitamin B12 include poultry, meat, fish, and dairy products; however, supplementation is available for individuals that cannot reach the recommended amount in the foods they eat.³

Although vitamin B12 deficiency is relatively uncommon in the US, older adults and individuals with digestive absorption issues are more susceptible. Untreated B12 deficiency can result in serious health problems, including anemia, fatigue, muscle weakness, intestinal issues, nerve damage, and mood disturbances.³ Additionally, B12 deficiency can cause various neurological issues, including peripheral neuropathy, cognitive impairment, and gait disturbances.⁴

The current study led by researchers from The University of California, San Francisco (UCSF), aimed to determine if vitamin B12 levels, even those considered within the normal range, could be linked to neurological damage or impaired function in healthy older individuals.¹

“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,” Ari J. Green, MD, of the UCSF Departments of Neurology and Ophthalmology and the Weill Institute for Neurosciences, said in a news release. “Revisiting the definition of B12 deficiency to incorporate functional biomarkers could lead to earlier intervention and prevention of cognitive decline.”¹

A total of 231 healthy individuals without dementia or mild cognitive impairment were recruited in the study from the Brain Aging Network for Cognitive Health (BrANCH) at the UCSF. The individuals had an average age of 71, with a median blood concentration of about 414.8 pmol/L.^1,2

To evaluate neurological status, researchers conducted multifocal visual evoked potential testing, processing speed assessments, and magnetic resonance imaging. Additionally, they measured serum biomarkers related to neuroaxonal injury, astrocyte activity, and amyloid pathology. Factors like age, sex, education, and cardiovascular risks were assessed to provide an accurate measure of the amount of vitamin the body could consume.^1,2

Results from cognitive testing revealed that individuals with lower levels of active vitamin B12 demonstrated slower processing speeds, causing subtle cognitive decline, which was more pronounced in older individuals. Additionally, older individuals displayed significant delays in responding to visual stimuli, indicating slower visual processing and overall reduced brain conductivity.^1,2

Further results from MRIs revealed that individuals with lower transcobalamin (Holo-TC), or active B12, had a higher amount of white matter hyperintensities, which indicates brain damage. The investigators also observed that higher levels of the inactive form of B12 were linked with an increased T-Tau protein in the blood, which is a sign of neurodegeneration.^1,2

The findings suggest that the current recommended levels of vitamin B12 might not be sufficient to protect against neurological decline, particularly among older adults.^1,2

“In addition to redefining B12 deficiency, clinicians should consider supplementation in older patients with neurological symptoms even if their levels are within normal limits,” Alexandra Beaudry-Richard, MSc, co-first author, said in a news release. “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.”¹

REFERENCES

1. Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults. Annals of Neurology. News release. February 10, 2025. Accessed April 1, 2025. https://onlinelibrary.wiley.com/doi/full/10.1002/ana.27200

2. ‘Healthy’ vitamin B12 levels not enough to ward off neuro decline. EurekAlert!. News release. February 18, 2025. Accessed April 1, 2025. https://www.eurekalert.org/news-releases/1074161

3. Mayo Clinic. Vitamin B-12. News release. June 28, 2024. Accessed April 1, 2025. https://www.mayoclinic.org/drugs-supplements-vitamin-b12/art-20363663

4. Vitamin B12-Associated Neurological Diseases. Medscape. News release. Updated February 4, 2025. Accessed April 1, 2025. https://emedicine.medscape.com/article/1152670-overview?form=fpf