Why Both Low and High Vitamin B12 Levels Can Harm Brain Health

The Surprising Connection Between Vitamin B12 Levels and Cognitive Health in Older Adults

Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays a critical role in several essential bodily functions, particularly in the development and maintenance of the nervous system, red blood cells, and nucleic acids like DNA and RNA. For many, B12 is considered a crucial part of the diet, found naturally in foods like fish, meat, eggs, and dairy products. Additionally, it is often added to fortified cereals and nutritional yeast, and supplements are readily available for those who may not consume enough of these foods.

While vitamin B12 deficiency is considered relatively rare, low or marginal B12 levels are more common, affecting up to 40% of Western populations. A new study has found that in older adults, both lower and higher levels of vitamin B12—particularly within what are considered normal ranges—may be linked to cognitive issues. This has prompted experts to re-evaluate what constitutes a "normal" or "healthy" B12 level in the context of aging and cognitive function.

Why Vitamin B12 Matters

Vitamin B12 is critical for nerve tissue development, brain function, and red blood cell production. Without adequate B12, nerve damage can occur, and individuals may experience symptoms like fatigue, weakness, and difficulty concentrating. It also plays an essential role in the formation of myelin, the protective covering around nerve fibers, and aids in maintaining the health of the central nervous system.

While vitamin B12 deficiency is commonly associated with more severe symptoms, lower levels of B12 may still impact the brain, leading to cognitive decline, even in the absence of a full-blown deficiency. The new study adds an intriguing twist to this narrative by suggesting that both low and high levels of B12—within the "normal" range—may have adverse effects on cognitive health in older adults.

The Study: Exploring the Link Between B12 and Cognitive Decline

The research, published in Annals of Neurology, focused on healthy older adults, all recruited for the Brain Aging Network for Cognitive Health at the University of California, San Francisco. A total of 231 participants, with an average age of 71.2 years, were included in the study. Blood samples were collected to measure serum total B12 levels and levels of holo-transcobalamin (holo-TC), which represents "active" B12—meaning the fraction of B12 that is biologically available to cells.

The researchers divided the participants into two groups based on their B12 levels: those below the mean level of 408 pmol/L and those above it. They controlled for a variety of factors, such as age, sex, cardiovascular risk, body mass index (BMI), and the presence of the APOEε4 allele (a known genetic risk factor for Alzheimer’s disease).

The results revealed some surprising findings:

• Lower B12 Levels: Participants with lower levels of B12 (even within the normal range) showed a delay in multifocal visual evoked potential (mfVEP), indicating slower signal conduction in the brain. These individuals also exhibited slower processing speeds on cognitive tests and had larger volumes of white matter hyperintensities—a type of brain change linked to cognitive decline.
• Higher B12 Levels: On the other end of the spectrum, those with higher levels of B12 had increased levels of T-Tau protein, a biomarker of neurodegeneration and dementia. This correlation was most significant when high B12 levels coincided with low levels of active B12 and high levels of "inactive" B12.

Implications of Low B12 Levels on Cognitive Function

For many years, health guidelines have considered B12 deficiency to be a condition in which levels fall below a certain threshold. However, this new study suggests that lower B12 levels—even within the “normal” range—may still have significant impacts on brain function. Specifically, the study linked these lower levels to slower processing speeds, indicating a delay in how the brain processes information. In addition to slower processing, lower B12 levels were associated with structural brain changes, such as an increase in white matter hyperintensities, which can be indicative of cognitive decline or dementia.

Dr. Ari J. Green, the lead author of the study, explained that the results show multiple negative effects when B12 levels are in the lower end of what is considered normal. “Slowed transmission of signals in the brain, slowed processing speed on cognitive tests, and MRI evidence of white matter injury were observed in participants who had B12 levels that were technically adequate, but lower than the norm,” he said. Notably, the study emphasized the importance of measuring "active" B12 levels, which are often not routinely assessed, as these levels may provide a more accurate picture of the vitamin's effect on brain function.

The Impact of Higher B12 Levels

Interestingly, the study also found that higher levels of B12—again, within the “normal” range—were associated with neurodegeneration. Specifically, higher B12 levels were linked to increased levels of T-Tau protein, a marker of neurodegeneration. In addition, researchers observed a correlation between high levels of inactive B12 (holo-HC) and biomarkers of axon injury. Although the researchers were unable to directly measure inactive B12 levels in the study, these findings raise questions about the potential negative effects of excessively high B12 levels in the blood.

This paradoxical result suggests that there might be an optimal range for B12 levels, and that exceeding this range could contribute to cognitive decline, just as insufficient levels might. It also underscores the importance of considering the balance between active and inactive B12, not just total B12 levels, when assessing an individual's cognitive health.

Rethinking B12 Recommendations

Given the findings of this study, experts are questioning whether current recommendations for B12 levels need to be adjusted, particularly in older adults. Dr. Green suggested that B12 guidelines should take into account both active and inactive B12 levels and consider their relationship to neurological and cognitive health. “Measuring what is adequate by just looking at the average or distribution of levels in the population doesn’t necessarily mean these levels are optimal for cognitive function,” he said.

Study Reference: https://onlinelibrary.wiley.com/doi/10.1002/ana.27200

The Importance of B12 in the Diet

Vitamin B12 is naturally found in animal-based foods such as fish, meat, poultry, eggs, and dairy products. For those who follow a vegetarian or vegan diet, supplements or fortified foods may be necessary to maintain adequate B12 levels. In addition, individuals with certain medical conditions—such as gastrointestinal disorders or those who have undergone weight-loss surgery—may have difficulty absorbing B12 from food, making supplementation important for maintaining healthy B12 levels.

The National Institutes of Health (NIH) recommends that adults over the age of 14 consume 2.4 micrograms of vitamin B12 per day. Given that B12 is generally considered safe, even at high doses, the body will excrete any excess that it does not need. However, both low and high B12 levels could potentially lead to cognitive issues, as suggested by this study.

Conclusion: A Balanced Approach to Vitamin B12

This groundbreaking study highlights the complex relationship between vitamin B12 levels and cognitive function in older adults. While B12 deficiency remains a concern, the study suggests that both low and high levels of B12—within the normal range—could potentially impact brain health. As such, there may be a need to rethink the clinical guidelines for B12 levels and consider not only total blood levels but also the active form of B12, which plays a more direct role in neurological health.

For individuals, especially older adults, it is crucial to maintain adequate B12 levels, but the findings from this study suggest that both low and excessively high levels of B12 may contribute to cognitive issues. Monitoring B12 levels and adjusting intake appropriately could be key to maintaining optimal brain health as we age.