A recent study published in the Annals of Neurology on February 10, 2025, suggests that levels of vitamin B12 considered within lab-normal values may be too low to prevent cognitive decline in healthy older adults [1].
What is Vitamin B12?
Vitamin B12, also known as cobalamin, is a water-soluble vitamin found in foods of animal origin, including fish, meat, poultry, eggs, and dairy products. It is essential for the proper functioning of the central nervous system, as well as for the formation of healthy red blood cells, and the synthesis of DNA.
Vitamin B12 is absorbed in the gastrointestinal (GI) tract, however, a deficiency may result due to inadequate dietary intake in those following a vegan or vegetarian diet, and from conditions which impair its absorption in the GI tract, including decreased intrinsic factor (IF). IF is a protein secreted in the stomach that enables vitamin B12 to be absorbed from food, and which generally decreases with age due to lower amounts of stomach acid production [2].
Vitamin B12 Deficiency Symptoms
If left untreated, vitamin B12 deficiency can lead to health complications, including megaloblastic anemia (where red blood cells are too large), fatigue, muscle weakness, gastrointestinal problems, nerve damage, and mood disturbances. It can also cause neurological issues, including peripheral neuropathy, cognitive decline, and gait (walking) abnormalities [1].
Findings of the Study
The study was led by researchers at the University of California, San Francisco (UCSF) who investigated whether vitamin B12 levels, despite falling within the lab normal range, might still be associated with neurological damage or impaired function in healthy older adults [1].
The study included 231 healthy individuals, all without dementia or mild cognitive impairment, who were recruited from the Brain Aging Network for Cognitive Health (BrANCH) at UCSF. Participants had an average age of 71, with a median blood vitamin B12 concentration of approximately 414.8 pmol/L.
To assess neurological status, researchers used multifocal visual evoked potential testing, cognitive processing speed evaluations, and magnetic resonance imaging (MRI) and measured serum biomarkers associated with neuroaxonal injury, astrocyte activity, and amyloid pathology. To accurately estimate the body’s capacity to utilize vitamin B12, variables such as age, sex, education level, and cardiovascular risk factors were factored in.
Cognitive testing revealed that individuals with lower levels of active vitamin B12 exhibited slower processing speeds, indicating subtle cognitive decline, an effect more pronounced with advancing age. Older participants also showed significant delays in responding to visual stimuli, suggesting slower visual processing and reduced overall brain conductivity.
MRI results showed that individuals with lower levels of transcobalamin (Holo-TC), the active form of vitamin B12, had greater volumes of white matter hyperintensities—an indicator of brain damage. Additionally, researchers found that elevated levels of the inactive form of B12 were associated with increased concentrations of T-Tau protein in the blood, a biomarker linked to neurodegeneration.
Findings of the Study
The findings of this study suggest that the current recommended levels of vitamin B12 may be insufficient to protect against neurological decline, especially in older adults.
Final Thoughts…
Ensuring sufficient B12 intake can be difficult for older adults who consume less food overall, eat fewer animal-based foods, or have reduced levels of intrinsic factor due to aging.
While taking a supplement may seem like a relatively straightforward solution to ensure adequate vitamin B12 levels, most B12 supplements available on the market contain types of cobalamin that are not able to be used by people who have the relatively common MTHFR genetic variation which affects their ability to convert folate (vitamin B9) and other B vitamins, including B12 into their active form.
Another factor that needs to be considered is that long-term use of Metformin to manage blood sugar is, by itself, significantly associated with low vitamin B12 levels [4]. Since many older adults are prescribed this medication, and vitamin B12 levels may already be set too low for healthy older adults not taking any medication, the need for assessing and monitoring vitamin B12 status in older adults is essential.
Further complicating the issue, low iron levels lead to smaller-than-normal red blood cells, while low B12 levels cause them to become larger. When both deficiencies are present, which is not uncommon in individuals with low intake of animal-based foods, they can offset each other, causing red blood cells to appear normal in size and potentially masking the underlying problem. A dietary assessment can help identify these risks, while blood tests can determine the extent to which these nutrients may be sub-optimal, guiding appropriate dietary changes and supplementation.
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References
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- Beaudry-Richard, A., Abdelhak, A., Saloner, R., et al (2025), Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults. Ann Neurol. https://doi.org/10.1002/ana.27200
- National Institutes of Health (NIH) Office of Dietary Supplements, B12, https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
- Vitamin B12-Associated Neurological Diseases. Medscape. News release. Updated February 4, 2025. Accessed April 1, 2025. https://emedicine.medscape.com/article/1152670-overview
- Atkinson M, Gharti P, Min T. Metformin Use and Vitamin B12 Deficiency in People with Type 2 Diabetes. What Are the Risk Factors? A Mini-systematic Review. touchREV Endocrinol. 2024 Oct;20(2):42-53. doi: 10.17925/EE.2024.20.2.7. Epub 2024 Jul 12. PMID: 39526048; PMCID: PMC11548349.
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