Researchers from the Quadram Institute contributed to a study led by the University of California San Francisco that looked at markers of cognitive decline in older, healthy volunteers with levels of vitamin B₁₂ considered normal by current standards.

They found that the volunteers with lower vitamin B₁₂ concentrations, but still above the threshold for being defined as deficient, tended to show more signs of neurological damage and cognitive decline.

The researchers are calling for the thresholds that define a deficiency in vitamin B₁₂ to be revisited, along with more research about how vitamin B₁₂ levels impact ageing of the brain.

Vitamin B₁₂ is needed by the body for a range of functions, including making DNA and blood cells. It also plays a vital role in the production of the sheath that surrounds nerves, like the insulation around an electrical wire.

Humans can’t make vitamin B₁₂. We rely on dietary sources, which are limited mainly to animal-based foods as vitamin B₁₂ is not found in plants. This can put vegan and vegetarian people at risk of being vitamin B₁₂ deficient, unless they take a supplement. But there aren’t reliable figures for how many people may be affected vitamin B₁₂ deficiency, leading to it being part of the problem of ‘hidden hunger’ where parts of the population lack vital micronutrients.

A deficiency in vitamin B₁₂ can produce a wide range of symptoms. Anaemia, caused by a lack of red blood cells, triggers tiredness and shortness of breath and can be picked up in blood tests.

Neurological symptoms, including confusion, memory loss, muscular coordination and visual impairments, can be harder to diagnose and link back to a vitamin B₁₂ deficiency. Previous studies have shown that vitamin B₁₂ deficiency plays a role in mild cognitive impairment and Alzheimer’s disease.

In the UK a level below 180 nanograms per litre of vitamin B₁₂ in the blood is considered to be deficient. In the US the level is 200 ng/L.

However, a significant number of older people reporting neurological symptoms but with vitamin B₁₂ levels above that threshold have seen their symptoms improve with vitamin B₁₂ supplementation.

This has prompted this new study into vitamin B₁₂ levels and markers of nervous system injury in older adults, which has been published in journal Annals of Neurology.

The team from the University of California, San Francisco (UCSF) Memory and Aging Center enrolled 231 healthy volunteers, with an average age of 71. Each had their blood samples analysed for the presence of variants of vitamin B₁₂ by the Quadram Institute’s research team.

The Quadram Institute has advanced facilities that can help analyse different biomolecules, with the ability to detect them at the tiniest concentrations. They developed methods for quantifying various versions of vitamin B₁₂ in the samples to get a full picture of the volunteers’ vitamin B₁₂ levels.

All participants in the study had levels above the threshold indicating deficiency.

The participants took part in a series of tests designed to assess their neurological status, as well as having blood tests for known signs of neural injury.

Analysing the data showed that participants with lower vitamin B₁₂ levels had impaired brain processing speed and a greater delay in responding to a visual stimulus. MRI scans also showed an association between lower vitamin B₁₂ status and areas of damaged brain tissue.

This indicates that they could be experiencing cognitive decline, even though their vitamin B₁₂ levels are above the current threshold that would indicate a damaging deficiency. These effects were amplified the older the participants were.

Professor Martin Warren from the Quadram Institute was involved in the study. He is an expert on the biochemistry of vitamin B₁₂, and co-founder of the CluB12 network of scientists and healthcare professionals.

“This study underscores the need to reassess what constitutes an optimal level of vitamin B₁₂” said Prof. Warren.

“The observed correlation with cognitive decline highlights the urgency of addressing vitamin B₁₂ deficiency, potentially through food fortification. Beyond increasing vitamin B₁₂ availability in foods, we must also enhance diagnostic methods to better identify those who require higher vitamin B₁₂ intake.”

“It’s imperative that we get a handle on the biology of vitamin B₁₂ deficiency and how it affects brain ageing, as it could be a relatively simple way of preventing cognitive decline in a significant proportion of the population.”

The implication of the threshold for deficiency being too low is that a much larger proportion of the population may be affected. The neurological effects and cognitive decline are subtle and may not be noticed until they have further progressed.

Providing vitamin B₁₂ supplements to older people could help ward off some of these effects.

Efforts to increase the levels of vitamin B₁₂ in the diet, for example through fortification, could also prove beneficial.

“At Quadram, in collaboration with our partners at the John Innes Centre, we are actively exploring innovative ways to incorporate vitamin B₁₂ into plant-based foods while also developing new gold-standard diagnostic approaches to improve detection and intervention,” said Prof. Warren.

Funding: The research was supported by the Westridge Foundation and the Canadian Institutes of Health and Research. Quadram Institute Bioscience receives strategic support from the Biotechnology and Biological Sciences Research Council, part of UK Research & Innovation.

Reference: Beaudry-Richard, A., et al, (2025), Vitamin B₁₂ Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults. Annals of Neurology DOI: https://doi.org/10.1002/ana.27200