Research

In this exciting new study, the authors (several of them being CluB-12 members) enrolled 231 healthy elderly volunteers (median age 71.2 years old) with a median B12 blood concentration of 414.8 pmol/L (as measured by automated chemiluminescence assay). They performed a variety of evaluations, including multifocal visual evoked potential testing, processing speed testing, and magnetic resonance imaging to assess neurological status. They also measured serum biomarkers of neuroaxonal injury, astrocyte involvement, and amyloid pathology.

Their main findings were:
Low B12, especially decreased holo-transcobalamin (sometimes called 'active B12', as this is the form of B12 that can be taken up into the brain), was associated with visual evoked potential latency delay, processing speed impairment (in an age-dependent manner), and larger volumes of white matter hyperintensities on MRI. High levels of holo-haptocorrin (the biologically inactive fraction of B12) correlated with serum levels of Tau, a biomarker of neurodegeneration.

In a press release, the authors wrote: "The current threshold to consider B12 deficiency as a diagnosis and to supplement with vitamin B12, is currently set at 148 pmol/L and is successful at treating most cases of B12-related anaemia. However, a significant amount of people with B12 levels above that threshold have complained of neurological symptoms which improved when getting B12 supplementation. We show that in an older population, lower B12 levels (but above the current threshold of 148 pmol/L) are associated with impaired myelination (slower mfVEPs), neurological function (slower processing speed) and structure (higher WMH lesions on MRI). However, serum biomarkers for neurodegeneration (Tau and UCHL-1) were elevated in people with higher inactive B12 levels." Remember, dear readers, inactive B12 can not be taken up into the brain. It may be a mere marker, and not a cause of higher Tau levels.
 
The authors have drawn a number of important conclusions:
• The current threshold that defines B12 deficiency must be revisited.
• Clinicians should consider B12 supplementation in older patients with neurological complaints even if B12 levels are higher than 148 pmol/L. But, how do we select these individual;s, and what follow-up do we provide for them?
• Both low active B12 levels and high inactive B12 levels should be considered in future studies about the impact of B12 on neurological function;
• We must invest in more research about the underlying biology of B12 insufficiency since it may impact brain ageing and can be a preventable cause of cognitive decline.
 
Research grant providers should prioritize research in the aforementioned areas.