A recent study published in the Annals of Neurology highlights hidden neurological risks associated with vitamin B12 even within what is considered ‘normal’ range.
Study: Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults
Vitamin B12, also known as cobalamin, is crucial for numerous bodily functions. It can be sourced from animal products like fish and beef, certain fruits such as bananas and mangoes, nutritional yeast, and fortified cereals.
Deficiency in vitamin B12 leads to blood cell abnormalities including megaloblastic anemia, while also affecting the neurological system with symptoms like subacute combined degeneration of the spinal cord (SACD). This can cause sensory ataxia, paresthesia and weakness. The myelin sheath’s breakdown causes white matter destruction and vacuolization in the spinal cord.
Vitamin B12 deficiency is also linked to cognitive impairment, memory loss, dementia and psychosis. However, vitamin B supplementation has shown effectiveness in reducing brain atrophy among older adults with mild cognitive impairment (MCI).
In the United States, a blood level below 148 pmol/L defines vitamin B12 deficiency — three standard deviations below average. Due to disagreement on defining this threshold, clinical features are often used for supplementation recommendations.
B12 is absorbed from food and bound by transport proteins in the bloodstream like haptocorrin (HC) and transcobalamin (TC). Only B12 attached to TC forms the bioactive Holo-TC. Conversely, B12 bound to HC remains inactive as it cannot be taken up by cells.
About the Study
Visual evoked potentials (VEP) provide a sensitive and non-invasive method for early detection of myelin function alterations in the visual pathway. This study used multifocal VEP (mfVEP) to evaluate how low B12 levels affect neurological health.
A total of 231 healthy individuals aged around 71 years, part of the Brain Aging Network for Cognitive Health (BrANCH) at the University of California, San Francisco’s Memory and Aging Center were included in the study. All participants underwent annual tests on neurologic function, cognitive performance and MRI to detect signs like inflammation or amyloid-related disease.
Study Findings
The median blood B12 concentration among this cohort was 415 pmol/L, with Holo-TC and Holo-HC medians of 93 and 298 pmol/L respectively. Vitamin B12 levels were divided into categories above or below the geometric mean value of 408 pmol/L.
Lower B12 levels, particularly low bioavailable Holo-TC, correlated with neurological dysfunction. mfVEP was observed to be 0.04 slower at lower B12 levels indicating reduced nerve impulse conduction in the brain. Lower Holo-TC values were inversely related to latency and illustrated how inadequate B12 availability leads to higher nerve conduction latencies.
Low vitamin B12 was associated with decreased spatial processing speed, suggesting that less total B12 or Holo-TC, but not necessarily lower levels of inactive Holo-HC, were linked to brain dysfunction. This negative association appeared age-dependent and perhaps older individuals are more prone to low bioavailable B12 leading to poorer cognitive function at younger ages.
Increasing Holo-HC correlated with higher serum tau protein and ubiquitin C-terminal hydrolase L1 (UCH-L1) levels. Vitamin B12 prevents the formation of tau fibrils, a precursor to neurofibrillary tangles in Alzheimer’s disease. High non-bioavailable B12 thus pointed towards increased markers of neurodegeneration.
Lower blood B12 was associated with higher white matter hyperintensities (WMH), indicating damage. This occurred even within the limits considered normal for total B12 levels; however, reduced Holo-TC values were linked to greater WMH burden.
Implications
Inadequate bioavailable vitamin B12 can lead to white matter injury in the spinal cord. While this mechanism is unclear, high homocysteine levels secondary to low B12 may be involved. Hematological symptoms often resolve with supplementation but neurological issues persist despite normal blood B12.
Overall, these findings underscore the importance of establishing optimal vitamin B12 levels and call for a broader review of nutritional guidelines.
