A recent study has sparked important discussions regarding vitamin B12 levels and their potential impact on cognitive health, particularly among older adults. Conducted with 231 healthy participants who had a mean age of 71.2 years, the research highlights the complexities surrounding B12 levels that, while within the normal range, may still contribute to cognitive decline.
The National Institutes of Health (NIH) recommends that individuals over the age of 14 should consume 2.4 micrograms of vitamin B12 daily. This vitamin, primarily found in animal products such as dairy, fish, meat, poultry, and eggs, plays a crucial role in maintaining neurological function. However, the study's findings suggest that both lower and higher levels of B12 may be linked to cognitive issues, prompting a reevaluation of what constitutes adequate B12 levels.
Researchers categorized participants based on their serum B12 levels—those below and above the mean of 408 pmol/L. They adjusted their analyses for various factors including age, sex at birth, cardiovascular risk factors, body mass index (BMI), the presence of the APOEε4 allele, HbA1C levels, and educational attainment. The results revealed concerning trends associated with lower ranges of B12 that had previously been considered acceptable.
“Our work shows what appear to be multiple negative effects for some people when their B12 levels are in the lower range of what has long been considered adequate or normal (and would not qualify as deficient). This includes slowed transmission of signals in the brain, slowed processing speed on cognitive tests and MRI evidence of white matter injury. Most importantly, these effects are strongest when looking at the ‘active’ fraction of B12 (which is not routinely checked) rather than just total blood B12 levels.”
— Ari J. Green, MD, lead author of the study
Dr. Green's comments underscore the need to differentiate between total B12 levels and active B12, or holo-transcobalamin (holo-TC), which is the biologically available form of the vitamin. While vitamin B12 deficiency is rare, affecting only about 3% of adults, low or marginal levels are a widespread concern, impacting up to 40% of Western populations.
Clifford Segil, DO, a neurologist not involved in the study, emphasized that it is reasonable to consider treatment for patients who exhibit memory loss, even if their B12 levels are technically classified as normal. He noted that elderly patients with low B12 levels showed significant slowing in the electrical impulses from their eyes to their occipital lobes, suggesting that inadequate B12 could affect the insulation of brain nerves.
“This study noted elderly patients with low B12 levels had slowing of an electrical impulse from their eye to their occipital lobe and proposed this could be due to B12 affecting the insulation of brain nerves. It concluded rethinking what a low B12 level should be in clinical practice. This is very reasonable as I routinely treat patients with B12 levels that are technically within normal though have memory loss.”
— Clifford Segil, DO
Aside from dietary sources, such as fortified breakfast cereals and nutritional yeast, many individuals may require supplements to maintain healthy B12 levels. Particularly for vegetarians and vegans who do not consume animal products—where B12 is predominantly found—supplements can be beneficial. Dr. Segil advised the general public to consider multivitamins containing B12 instead of standalone supplements.
The study also opened the door to further investigation into how both low and high levels of B12 might relate to neurological health. Dr. Green pointed out that high levels of inactive B12 could be associated with markers indicating axon injury, although this aspect requires more research for a comprehensive understanding.
“We also saw that high levels of ‘inactive’ B12 in the blood may be associated with a blood marker of axon injury. It should be noted that we did not have a means of directly measuring inactive B12 levels in the paper but had to calculate the level from other measurements. The full meaning of this result needs further study but it suggests that measuring total blood B12 may mislead doctors and patients in some situations to think that active B12 levels are adequate.”
— Ari J. Green, MD
Dr. Green further stated that current recommendations for vitamin B12 intake should undergo significant reconsideration—not merely based on blood levels but also by evaluating active versus inactive forms and assessing neurological function.
“We believe that recommendations for B12 should be very likely reconsidered — and not just based on B12 blood levels but considering measures of active vs inactive B12 and looking at measures of neurological and cognitive function. Measuring what is adequate by just measuring what is average (and the distribution) in the population does not prove that the levels are adequate for any nutrients,”
— Ari J. Green, MD
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