A recent study has revealed that individuals with vitamin B12 levels at both the low and high ends of the normal range may still face risks of cognitive impairment. This finding prompts a reconsideration of what constitutes “healthy” vitamin B12 levels, particularly given the vitamin’s critical role in brain and nerve health.
Vitamin B12, also known as cobalamin, is essential for several bodily functions, including DNA synthesis, red blood cell production, nervous system health, and energy metabolism. It is primarily obtained from animal products such as meat, poultry, fish, dairy, and eggs. For those following vegetarian or vegan diets, B12 can be sourced from fortified foods.
Led by researchers at the University of California, San Francisco (UCSF), the study explored how seemingly normal blood levels of vitamin B12 could still negatively impact brain function and structure, particularly in older adults.
Dr. Ari Green, the study’s corresponding author from UCSF’s Weill Institute for Neuroscience, emphasized that earlier studies might have overlooked subtle effects associated with high or low B12 levels. “Revisiting the definition of B12 deficiency to include functional biomarkers could facilitate earlier intervention and potentially prevent cognitive decline,” he noted.
After vitamin B12 is absorbed, it binds to two carrier proteins in the bloodstream: haptocorrin (HC) and transcobalamin (TC). While HC binds to the majority of B12 in circulation, this form is considered biologically inactive because it is not readily available for use by the body. Conversely, TC binds to a smaller portion of B12, allowing cells to absorb the active form of the vitamin.
Measuring blood levels of B12 involves assessing both forms; however, the active B12 (Holo-TC) is what significantly impacts cellular function. Low levels of Holo-TC can lead to neurological symptoms, while inactive B12 (Holo-HC) primarily serves as a storage form in the liver. The study standardized the reference ranges for vitamin B12 across different countries, measured in picomoles per liter (pmol/L):
- United States: 148 to 748 pmol/L
- Australia: 135 to 650 pmol/L
- United Kingdom: 115 to 740 pmol/L
In this study, 231 healthy participants with a median age of 71 and a median B12 concentration of 414.8 pmol/L—above the lower recommended threshold—were recruited through the Brain Aging Network for Cognitive Health (BrANCH) study at UCSF. Researchers measured both total blood B12 and Holo-TC levels, calculating Holo-HC by subtracting Holo-TC from total B12.
The study investigated the relationship between B12 concentrations, cognitive performance, and myelin integrity—the protective sheath surrounding nerve fibers. Given the critical role of B12 in maintaining myelin, deficiencies can hinder the body’s ability to repair and sustain myelin health. MRI scans were employed to evaluate brain tissue health, revealing that lower levels of B12, especially the active form (Holo-TC), correlated with slower cognitive processing speeds. This effect intensified with age, indicating older adults with low Holo-TC faced greater cognitive challenges. Additionally, lower Holo-TC levels were associated with slower nerve signaling related to vision, and MRI results indicated that participants with reduced Holo-TC exhibited more white matter hyperintensities (WMH)—small areas of damage in the brain associated with aging and neurological diseases.
Surprisingly, the study found that higher levels of the inactive form of B12 (Holo-HC) correlated with elevated serum tau levels, a protein linked to brain cell degeneration and conditions like Alzheimer’s disease.
These findings carry significant implications for clinical practice and may inform changes in treatment strategies, particularly for older patients. “Clinicians should reconsider supplementation for older patients with neurological symptoms, even if their B12 levels appear normal,” advised co-lead author Alexandra Beaudry-Richard, a doctoral researcher at UCSF’s Department of Neurology.
By rethinking the definitions and thresholds surrounding vitamin B12 levels, we may enhance early detection and intervention for cognitive decline, ultimately improving outcomes for aging populations.
References:
- Beaudry-Richard, A., et al. “Cognitive decline risk could prompt rethink of ‘healthy’ vitamin B12 levels.” University of California, San Francisco.
- Green, A. “Revisiting the definition of B12 deficiency.” Weill Institute for Neuroscience, UCSF.
- National Institutes of Health. “Vitamin B12 Fact Sheet.” NIH
- Alzheimer’s Association. “Understanding tau.” Alzheimer’s Association
