A recent study published in Annals of Neurology has explored vitamin B12 levels within what are currently considered ‘normal’ ranges, revealing potential hidden neurological risks among older adults. This research delves into the relationship between B12 levels and biomarkers indicative of central nervous system injury.
Vitamin B12, or cobalamin, is a crucial dietary nutrient primarily found in animal products such as meat, eggs, dairy products, certain dry fruits like nori and nutritional yeast, and fortified foods. Deficiency can result in blood disorders like megaloblastic anemia and neurological impairments including subacute combined degeneration of the spinal cord (SACD). Symptoms associated with SACD include sensory ataxia, paresthesia, and muscle weakness.
Pathological studies have shown that SACD is linked to myelin sheath degeneration in the spinal cord, leading to white matter destruction and vacuolization. Vitamin B12 deficiency also correlates with cognitive decline, memory loss, dementia, and even psychosis. However, supplementation with vitamin B has been demonstrated to slow brain atrophy in older individuals experiencing mild cognitive impairment (MCI).
In the United States, a blood level of less than 148 pmol/L is defined as deficiency, three standard deviations below average population levels. The lack of consensus on what constitutes low B12 often leads clinicians to rely more on clinical symptoms for supplementation recommendations.
Vitamin B12 absorbed from food binds with transport proteins in the blood such as haptocorrin (HC) and transcobalamin (TC). Only the B12-TC complex, or Holo-TC, is bioactive; that bound to HC, known as Holo-HC, remains inactive.
About the study
Visual evoked potentials (VEP), which offer a sensitive and non-invasive method for detecting early myelin function alterations in the visual pathway, were used in this research. A multifocal VEP technique was employed to assess the impact of low B12 on neurological health. The study included 231 healthy individuals aged around 71 years from the Brain Aging Network for Cognitive Health (BrANCH) at UCSF Memory and Aging Center.
In addition to measuring vitamin B12 levels, participants were annually assessed for cognitive performance, neurological function, and MRI scans to identify signs of inflammation, axonal damage, or amyloid-related diseases.
Study findings
The study cohort had a median blood B12 concentration of 415 pmol/L. Holo-TC and Holo-HC levels were respectively measured at medians of 93 and 298 pmol/L. The participants’ vitamin B12 levels were stratified into above or below the geometrical mean value of 408 pmol/L.
Results showed that lower bioavailable B12, especially Holo-TC, was associated with neurological dysfunction. At low B12 concentrations, mfVEP latency increased by 0.04 milliseconds, indicating slower nerve impulse conduction in the brain. The inverse correlation between Holo-TC levels and latency suggests that inadequate B12 bioavailability is responsible for greater nerve conduction delays.
Participants with lower vitamin B12 levels exhibited decreased spatial processing speed, a finding attributed to reduced total B12 and Holo-TC, not influenced by Holo-HC. The negative association appeared age-dependent, possibly because older individuals are at higher risk of low bioavailable B12 or suboptimal cognitive performance.
Increased serum levels of non-bioavailable B12 (Holo-HC) correlated with tau protein and ubiquitin C-terminal hydrolase L1 (UCH-L1), markers associated with neurodegeneration. Since vitamin B12 prevents the formation of tau fibrils, higher Holo-HC predicted increased neurodegenerative biomarkers.
Low B12 levels were also linked to white matter hyperintensity burden in spinal cord MRI scans, despite blood levels remaining within ‘normal’ limits. This correlation was absent with total B12; however, lower Holo-TC was associated with higher WMH load.
Implications
The study highlights that even when blood vitamin B12 levels are in the normal range, low bioavailable B12 can lead to white matter injury in the spinal cord. The specific mechanisms of this damage remain unclear but may involve elevated homocysteine levels due to B12 deficiency.
While hematological symptoms typically resolve with B12 supplementation, neurological issues often persist even when blood levels are ‘normal’. This suggests that subtle neurologic dysfunction could be undetected without measuring bioavailable B12.
The findings underscore the necessity for establishing optimal vitamin B12 levels and advocate for a broader reconsideration of nutritional guidelines.
