Vitamin B12 and brain volume

“A diet rich in fish, meat and milk could help to protect against memory loss in old age”, is the headline in The Daily Telegraph . A study in 107 elderly people found that those with lower levels of vitamin B12 in their blood “were six times more likely to experience brain shrinkage than those with higher levels.” Vitamin B12 is found in milk, meat, fish and fortified cereals, and is known to play a role in keeping the nervous system healthy.

This relatively small study does show a link between lower levels of B12 in the blood and changes in brain volume, but it did not look at whether this was associated with noticeable cognitive decline or the effects of supplementing the diet with vitamin B12. Vitamins and minerals have an important role to play in maintaining a healthy mind and body, and ideally, people should aim to consume the recommended amounts by eating a healthy balanced diet. Vitamin B12 deficiency most frequently occurs in the elderly, and those who worry that they are not getting the required amounts may wish to discuss with their doctor whether taking supplements would be appropriate.

Where did the story come from?

Dr Anna Vogiatzoglou and colleagues from the University of Oxford and universities in Norway and Australia carried out this research. The study was funded by the Alzheimer’s Research Trust (UK), the Medical Research Council, the Charles Wolfson Charitable Trust, the Norwegian Foundation for Health and Rehabilitation through the Norwegian Health Association, Axis-Shield and the Johan Throne Holst Foundation for Nutrition Research. It was published in the peer-reviewed medical journal: Neurology .

What kind of scientific study was this?

This was a prospective cohort study that assessed the relationship between levels of vitamin B12 in the body and loss of brain volume in elderly people. Brain shrinkage is known to be associated with the onset of Alzheimer’s disease and is often used as a marker of disease progression. Although some studies have suggested that low vitamin B12 levels are associated with cognitive problems, others have found no such link.

The researchers enrolled elderly people aged over 60 who were looked after themselves and lived in the community. Volunteers had medical examinations and were assessed using standard measurement tests to see if they had cognitive impairment. Of these volunteers, those who did not have cognitive impairment (148 people) were included in the study. The researchers took blood from the volunteers and measured the levels of vitamin B12 and other related chemicals (metabolites) that indicate the levels of B12 in the blood. They also used MRI scanning to measure their brain volume. After enrolment, volunteers had annual clinical examinations, MRI scans of their brains and repeated cognitive testing. The researchers followed the participants for five years.

For their analyses, the researchers only included the 107 volunteers (aged 61 to 87 years old, average age 73 years), who had MRI scans at the start and end of the study. The other 42 volunteers had died or withdrawn from the study.

The researchers used statistical methods to look at whether levels of vitamin B12 and related chemicals in the blood were related to percentage changes in brain volume. They adjusted these analyses for factors that might affect brain volume (potential confounding factors), including age, gender, education, brain volume at the start of the study, scores on the cognitive tests, blood pressure, presence or absence of the ε4 form of the ApoE gene (as this is known to be linked to Alzheimer’s disease) and the levels of various chemicals in the blood.

The researchers split the volunteers into three groups (tertiles) based on the levels of B12 in the blood (low, medium and high). They also split them into three groups based on the percentage changes in brain volume seen. They then looked at whether those with lower levels of B12 in the blood were more likely to be in the highest group of percentage change in brain volume.

What were the results of the study?

Based on accepted standards, none of the volunteers was classified as having a vitamin B12 deficiency. The researchers found that people with lower B12 levels in the blood at the start of the study had greater percentage decreases in brain volume than those with higher levels. This relationship remained significant when the researchers adjusted for potential confounding factors such as age, gender and brain volume at the start of the study. People with vitamin B12 levels in the lowest third of measurements were about six times more likely to have brain volume loss in the highest third of measurements than those with the highest levels of vitamin B12.

What interpretations did the researchers draw from these results?

The researchers concluded that low vitamin B12 levels may be a potentially modifiable cause of brain volume reduction and therefore cognitive impairment in the elderly. They suggest that more research is needed to investigate this link, and whether increasing B12 levels could reduce the risk of cognitive impairment in the elderly.

What does the NHS Knowledge Service make of this study?

There are a number of points to consider when interpreting this study.

• This was a relatively small study and larger studies will be needed to confirm the findings. 
• This type of study can provide evidence of an association between two factors over time, but cannot prove that the vitamin B12 levels directly caused the loss in brain volume. Other factors may be responsible for both the low B12 levels and the brain volume changes. The researchers did adjust for known factors that might be having an effect, which does increase the confidence in the results, but other unknown factors may still be playing a role.
• This study did not look at whether the changes in brain volume were associated with cognitive impairment; therefore, it is not possible to say from this study whether low vitamin B12 levels are associated with greater reductions in cognitive ability over time in the elderly.
• The participants in this study had a relatively high level of education and were relatively healthy; results might not be the same in people with different characteristics.
• Although the study found an association between B12 levels and brain volume loss, this does not necessarily mean that taking vitamin B12 supplements would reduce cognitive impairment in the elderly. Randomised controlled trials looking at the effects of B12 supplementation will be needed to determine if this is the case, as well as to assess any potential risks.

Ideally, people should aim to consume the recommended amounts of vitamins and minerals by eating a healthy balanced diet. Vitamin B12 deficiency most frequently occurs in the elderly and those who are worried they may not be getting the required amounts may wish to discuss this with their doctor.

Sir Muir Gray adds...

And exercise helps too.