It has long been a debate on whether vitamin B12 and memory performances are linked, and if vitamin B12, also known as cobalamin, can actually enhance cognitive presentation. Conflicting opinions and efforts in the form of different studies being carried out can be found in the medical community. Finally, there might be an answer to the debate, according to a new research.

A study published in The American Journal of Clinical Nutrition, in February 2016, concluded that there is an association of low vitamin B12 concentrations (within normal range) with poorer memory performance that can be due to reduced microstructural integrity of the hippocampus, a part of the brain that controls emotion, memory, and the autonomic nervous system.

The study used a cross sectional study design, and had a cohort of 100 patients, 52 of which were women, with amnestic mild cognitive impairment (MCI).

Mild cognitive impairment (MCI) can induce a small but noticeable decline in the cognitive abilities of a person. This can put a person at an increased risk for Alzheimer’s or other dementias. Long term surveillance tells us that 10 to 20 percent of the people above 65 years of age may have MCI. Amnestic MCI is a form of the disease where a person may start forgetting important information which he or she could have recalled easily at previous occasions.

The study used an Auditory Verbal Learning Test to access the performances of the patients. Using a median analysis, the study concluded that volume or microstructure of the brain partially explains the relationship between the vitamin B12 and memory performance.

Median analysis in statistics is based on regression analysis which hypothesizes that one variable A is affected by another variable B, through the manipulation of a variable C.

In the study, people with poorer-normal B12 levels showed lesser learning ability and recognition performance than people with high-normal B12. Also the integrity of microstructure of the hippocampus was lower in the patient with low-normal B12 levels, which partially mediated the effects of vitamin B 12 on the memory performance by 32-48 percent.

The study suggests future trials to access whether vitamin B12 intake may improve cognition in MCI patients.

Association Of Vitamin B12 Levels With Cognitive Function

Another paper published in The American Journal of Clinical Nutrition discusses the potential role of hippocampus as a mediator for vitamin B12 in memory. The article takes a deep dive in associations of these two with each other and potential functioning mechanism for this effect.

It is hypothesized that the association of vitamin B12 with cognition is context-dependent. Only some individuals will show cognitive impairment in low-normal B12 levels. Such subgroups can be of people carrying the ε4 allele of APOE, people who are depressed and have a very high folate status. However, it can be possible that the omega-3 fatty acid status can also influence the cognitive response to B12.

The mechanism of association of vitamin B12 with cognitive loss can be explained by a theory that the low levels of B12 can cause white matter damage in the brain, particularly the area mediating the cognitive function. This theory was given due to the characteristic white matter damage of the spinal cord in B12 deficiency. Another theory is that atrophy of the brain or of specific regions can be associated with the effects of low-normal levels of vitamin B12. Two separate longitudinal studies found that the whole brain atrophy rose as the concentrations of B12 declined. The subjects in the lowest 1/3 of the study population (lowest levels of B12) showed twice the atrophy status than in other 2/3 of the study population.

The most novel mechanism of action is the one discussed in the first study that we mentioned. It is a landmark study that ties the microscopic damage of hippocampus (specifically CA4-DG region) with memory impairment and changes in the vitamin B12 status.

The New Questions

The researcher asks many interesting questions and hypothesizes answers that are fundamental in ending this debate, such as why the damage due to low-normal status of B12 is limited to CA4-DG subfield. The author theorizes that it can be due to the damage of the perforant path that is shown to be damaged in the MRIs of several MCI patients.

Another question is how can the vitamin B12 status lead to damage in the perforant path or its target zone in dentate Gyrus? Three theories can answer this question.

  • Firstly, and unlikely, the original study adjusted for homocysteine levels and found the same results that there is an elevation in the hormone homocysteine which is a risk factor for Alzheimer’s disease.
  • Secondly, B12 is needed for DNA replication and its low levels can impair neurogensis, for which one of the key sites is dentate gyrus in the hippocampus of the brain.
  • Thirdly, insufficient B12 levels in the body can cause impaired methylation, leading to loss of myelin from axons in the cells of perforant pathway in the brain.

This leads the author to another question whether microstructural brain damage can be prevented or reversed by supplementing a person with B12. Several studies have shown that the damage can be partially reversed and slowed down after supplementation with vitamin B12. These results are consistent with the main study we discussed, and gives ‘hope that the prevention of cognitive decline due to low-normal vitamin B-12 status can be achieved by the simple step of supplementation with the vitamin’, according to the author.

This study has made several aspects of the debate clearer and the researcher urges the scientific community to no longer ignore the low-normal B12 level, which can cause long term brain damage if kept consistent. It is also recommended to adjust the additional B12 for people with serum concentrations lower than 300 pmol/L.

Vitamin B12

Vitamin B12 exits in several forms, and contains the mineral cobalt. Methylcobalamin and 5-deoxyadenosylcobalamin are the active forms that play an active role in human metabolism. It is a water-soluble vitamin, and is present in foods like fish, shellfish, meat, poultry, eggs, milk, and milk products. Foods are often fortified with vitamin B12 such as breakfast cereals, energy bars, and soy products. Fungi, plants, or animals and humans are not capable of producing vitamin B12. Only bacteria and archea have the ability and enzymes for its synthesis.

Cobalamin plays an important role in the synthesis of DNA. It also keeps the nerve cells and red blood cells healthy.

Recently, it was found that vitamin B12 used with vitamin B6 and folic acid reduces the risk of heart disease and age related macular degeneration in women. Low levels of vitamin B12 can cause weakness, memory loss, fatigue, and problems with the nervous system.

Vitamin B12 levels are typically accessed via serum or plasma levels. Values below 12-180 picomol/L (170-250 pg/mL) indicate a deficiency in adults. Recommended dietary allowance (RDA) is at 2.4 mcg/day for 14 years of age and above. No upper limit has been set due to the fact that at higher doses cobalamin has not been found to be dangerous in any study.

Vitamin B12 has been looked upon as a treatment for diseases like Alzheimer’s, breast cancer, heart disease, high cholesterol, sickle cell disease, and fatigue. The results have been inconclusive as of yet.