Vitamin B12 is essential for the brain and nervous system. Even with normal tests, its active form may be low, affecting memory and increasing the risk of dementia. A study in elderly people showed that low levels of active B12 are linked to poorer cognitive function and brain damage, suggesting that the criteria for deficiency need to be revised.
Vitamin B12, also called cobalamin, is an essential nutrient for the proper functioning of our body. It is obtained mainly through food, especially in foods of animal origin, such as meat, eggs, milk and dairy products.
Since our body cannot produce B12 on its own, we need to consume it regularly.
Vitamin B12 deficiency can occur for two main reasons: lack of intake (such as in strict vegan diets, which do not include foods of animal origin) or problems with the absorption of the vitamin by the body.
Some health conditions, surgeries in the digestive system or even aging can make it difficult to absorb B12.
When vitamin B12 levels in the body drop drastically, serious symptoms can occur, mainly affecting the blood and nervous system. In the blood, deficiency can cause a specific type of anemia called megaloblastic anemia, which leads to intense fatigue and weakness.
In the nervous system, the effects are even more worrying: a problem called subacute combined degeneration of the spinal cord can occur, which affects motor coordination, causes numbness and tingling in the limbs, and muscle weakness.
Researchers analyzed brain and spinal cord tissue from people with B12 deficiency and noticed that there was damage to the myelin, a protective layer that surrounds the nerves and facilitates the transmission of nerve impulses.
This indicates that vitamin B12 plays a crucial role in maintaining the health of the nervous system. In addition to the physical impacts, a lack of B12 can affect the mind: memory difficulties, mental confusion, mood swings and even dementia and psychosis can occur.
A study called VITACOG showed that vitamin B12 supplementation, along with other B vitamins, helped slow brain atrophy (loss of brain mass) in older people with mild cognitive impairment, as well as improving performance on memory and reasoning tests.
In addition, B12 deficiency has been associated with an increase in brain lesions visible on MRI scans, which can be signs of circulatory problems or damage to the brain structure.
In some cases, B12 deficiency does not manifest itself in an obvious way, but can be detected by blood tests. This phenomenon is called subclinical cobalamin deficiency (SCCD) and occurs mainly in older people. Even without apparent symptoms, this deficiency can increase the risk of cognitive decline over time.
Currently, blood tests measure different forms of vitamin B12 in the body. After the vitamin is ingested, it needs to be transported through the blood to reach the cells, and this is done through proteins called haptocorrin (HC) and transcobalamin (TC).
Only transcobalamin can deliver B12 directly to the body's cells, through a specific receptor. Therefore, the active fraction of vitamin B12 is called Holo-TC (holo-transcobalamin), while the fraction transported by haptocorrin (Holo-HC) is not immediately usable by the body and may end up being eliminated.
Given this, scientists have come up with an important hypothesis: even when overall blood B12 levels appear normal, if the active fraction (Holo-TC) is low, there may be negative impacts on brain and nervous system health. To investigate this relationship, a study looked at several factors in a group of healthy older adults, including:
Neurological tests, to assess nerve function and brain processing speed.
MRI scans, to detect possible brain damage.
Blood tests, to measure markers of neuronal and myelin health.
The results showed that people with lower Holo-TC levels performed worse on cognitive tests, had delays in nerve impulse transmission, and were more likely to have brain damage on MRI scans.
Furthermore, high levels of Holo-HC (the inactive fraction of the vitamin) have been associated with increased levels of Tau, a protein linked to neurodegenerative diseases such as Alzheimer's.
Currently, in the United States, a B12 level below 148 pmol/L is considered deficient. However, this value was defined solely based on population statistics, without taking into account the clinical manifestations of the deficiency.
Studies have shown that many people with clear symptoms of B12 deficiency still have levels above this limit and that B12 supplementation can be beneficial even when tests do not indicate severe deficiency. Therefore, experts suggest that the criteria for diagnosing and treating B12 deficiency need to be revised.
Overall, this study raises an important question: do levels considered "normal" of B12 really ensure optimal functioning of the nervous system? The results suggest that even within the range considered adequate, some people may experience subtle neurological impacts that can be prevented or minimized with adequate intake of the vitamin.
This reinforces the need to pay closer attention to B12 levels, especially in the elderly, to prevent long-term cognitive and neurological problems.
READ MORE:
Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults
Alexandra Beaudry-Richard, Ahmed Abdelhak, Rowan Saloner, Simone Sacco, Shivany C. Montes, Frederike C. Oertel, Christian Cordano, Nour Jabassini, Kirtana Ananth, Apraham Gomez, Azeen Keihani, Makenna Chapman, Sree Javvadi, Shikha Saha, Adam Staffaroni, Christopher Songster, Martin Warren, John W. Boscardin, Joel Kramer, Bruce Miller, Joshua W. Miller, Ralph Green and Ari J. Green
Annals of Neurology. 10 February 2025
Abstract:
Vitamin B12 (B12) plays a critical role in fatty- and amino-acid metabolism and nucleotide synthesis. While the association between B12 deficiency and neurological dysfunction is well-known, the exact threshold for adequacy remains undefined in terms of functional impairment and evidence of injury. The objective was to assess whether B12 levels within the current normal range in a cohort of healthy older adults may be associated with measurable evidence of neurological injury or dysfunction. We 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). We performed multifocal visual evoked potential testing, processing speed testing, and magnetic resonance imaging to assess neurological status. Moreover, we measured serum biomarkers of neuroaxonal injury, astrocyte involvement, and amyloid pathology. Low (log-transformed) B12, especially decreased holo-transcobalamin, was associated with visual evoked potential latency delay (estimate = −0.04; p = 0.023), processing speed impairment (in an age-dependent manner; standardized β = −2.39; p = 0.006), and larger volumes of white matter hyperintensities on MRI (β = −0.21; p = 0.039). Remarkably, high levels of holo-haptocorrin (biologically inactive fraction of B12) correlated with serum levels of Tau, a biomarker of neurodegeneration (β = 0.22, p = 0.015). Healthy older subjects exhibit neurological changes at both ends of the measurable “normal” B12 spectrum. These findings challenge our current understanding of optimal serum B12 levels and suggest revisiting how we establish appropriate nutritional recommendations. ANN NEUROL 2025
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