New research in both mice and humans investigated the link between vitamin A deficiency, brain development and Alzheimer’s risk. Researchers assessed mice who were genetically engineered to develop an Alzheimer’s-like condition.
Vitamin A, the name of a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters, helps boost the immune system and is mainly found in animal sources, including dairy, eggs, meat and oily fish, and some fruits and leafy vegetables.
Researchers found feeding mice vitamin A-deficient diets increased the development of abnormal clumps of protein associated with the condition. They further found the offspring of these mice performed poorly on a maze test designed to assess memory and situational awareness.
Causation Not Proven
Researchers also took blood samples from around 300 older adults in Chinese care homes and found vitamin A levels were linked with cognitive impairment.
But this one-off cross-assessment of a specific population sample doesn’t prove cause and effect. It could be the case that whatever factors lead to cognitive impairment in adults could also lower vitamin A levels.
And, as vitamin A deficiency is more of a recognised problem in non-Western countries, levels in this Chinese population may not be the same as the UK.
All people should be able to get enough vitamin A by eating a healthy diet. Pregnant women in particular should not take vitamin A supplements or eat foods known to have a very high vitamin A content, like liver, as excessive vitamin A can cause birth defects.
Similarly, older adults should not routinely take vitamin A supplements as they can increase the risk of osteoporosis and fractures.
Vitamin A Deficiency: Developing World Issue
The study was carried out by researchers from the Children’s Hospital of Chongqing Medical University in China and the University of British Columbia in Canada. Funding was provided by the National Natural Science Foundation of China and the Canadian Institutes of Health Research.
This study in both humans and mice aimed to see whether vitamin A deficiency may have a role in the development of Alzheimer’s disease.
The causes of Alzheimer’s, aside from known risk factors like older age and possibly genetics, remain largely unknown.
As the researchers say, vitamin A deficiency is a problem in the developing world, particularly among pregnant women, the elderly and young children.
Some studies have observed decreased vitamin A levels in people with Alzheimer’s, and there has been speculation that this could lead to increased amyloid protein plaque deposits characteristic of the disease.
This study aimed to look at the correlation between vitamin A deficiency and cognitive decline in elderly adults. The researchers also used a mouse model of Alzheimer’s to see whether vitamin A deficiency is linked with accumulation of protein plaques and memory deficits, and whether this could be reversed by taking supplements.
The human study involved a sample of older adults (average age 77) from 15 care homes in China.
They were assessed on how they performed everyday activities, and their cognitive function was measured using several well-validated assessments:
the Mini-Mental State Examination (MMSE)
the Clinical Dementia Rating Scale (CDR)
The participants also provided blood samples for analysis of vitamin A.
Researchers excluded people with anxiety, depression, severe dementia, Parkinson’s, diabetes or who were receiving vitamin A supplements. Of 650 potential adults, full data was available for 330 people.
The animal study involved mice genetically engineered to produce an enzyme involved in the production of amyloid beta protein plaques who then developed an Alzheimer’s-like condition.
The mice were split into two groups and fed for four weeks with either normal diets or a diet deficient in vitamin A.
At the same time, breeding was allowed. Six months after birth, the researchers tested the behavior of the mouse pups using the water maze test. They then analysed their blood samples.
They also carried out subsequent tests looking at the effect of switching between diets – for example, switching the vitamin A-deficient mums and their pups to a diet with normal vitamin A content immediately after birth, and vice versa.
After death, the researchers also analysed the mice brain tissue samples.
Human Study Results
The majority of older adults (61%) had normal blood vitamin A levels (defined as a level of 1.05 micromols or greater).
A quarter (26%) had marginal deficiency (0.70 to 1.05) and 13% were vitamin A deficient (less than 0.70).
Researchers found CDR and ADAS-Cog scores were significantly higher (worse) in those with deficiency or marginal deficiency compared with those with normal vitamin A levels. There was no difference in MMSE scores or how they performed daily activities.
However, when researchers pooled the deficient and marginally deficient groups, these people also had lower MMSE scores than the normal group.
About three-quarters of these combined deficient groups were said to have cognitive impairment. There was greater decline in these groups than the normal vitamin A group.
Mouse Study Results
In the mouse model of Alzheimer’s disease, mice were fed a diet marginally deficient in vitamin A, as this was more common in humans than complete vitamin A deficiency.
The researchers found these mice had brain tissue with increased levels of the enzyme involved in producing amyloid protein plaques.
Looking at the behavior of the mouse pups (the offspring of engineered mice), they found those whose mums were fed the deficient diet had no differences in mobility, escape time and vision from the normal-diet pups. However, these mice did display some spatial memory deficits when finding a hidden platform compared with the normal-diet pups.
When they looked at switching the diets after birth, the researchers found mice whose mums had been fed a deficient diet, but were then fed normal vitamin A after they were born, still showed spatial memory deficits compared with those who’d always had the normal diet.
However, there wasn’t a difference between those who’d always had the normal diet and those switched to a deficient diet after birth. This seems to suggest the deficits were set before birth.
They further found vitamin A supplementation improved the cognitive deficits in the mice.
The researchers say their study shows vitamin A deficiency is correlated with increased cognitive decline in elderly adults.
They also found marginal vitamin A deficiency promotes amyloid plaque deposition in Alzheimer’s model mice and leads to memory deficits. Meanwhile, vitamin A supplementation was found to improve deficiency.
“These results suggest that vitamin A supplementation might be a potential approach for Alzheimer’s disease prevention and treatment."
Overall, this study finds a link between vitamin A deficiency, or marginal deficiency, and poorer cognitive performance in older adults. Alzheimer’s mice fed a marginally deficient diet showed greater production of the amyloid protein plaques – and the researchers showed that the offspring of mice fed this diet had poorer spatial learning.
However, caution must be taking when drawing any conclusions from this study, and the results certainly should not be taken as a reason to start taking vitamin A supplements.
The human study was a one-off assessment of blood vitamin A levels and cognitive function that doesn’t prove cause and effect. We don’t know the temporal relationship and can’t say that low vitamin A preceded any cognitive decline.
This was also a fairly small sample of 330 people with variable levels of cognitive impairment – not all with dementia.
Another sample may not have found the same results, and the results may have been different in a sample of people from a different culture or society.
These people all came from China. As the researchers say, vitamin A deficiency is particularly a problem in developing countries. Some level of deficiency was quite prevalent in these people, but we can’t assume the same would be seen if sampling older adults from the UK, for example.
We don’t know how common vitamin A deficiency is among pregnant women in this country.
And pregnant women are not mice genetically engineered to develop Alzheimer’s. The mouse offspring were bred to develop cognitive impairment in any case, regardless of their exposure to vitamin A.
The findings are of interest and worthy of further study, but provide no evidence that vitamin A deficiency causes Alzheimer’s.
Always seek medical advice before taking vitamin A supplements. Most people in the developed world don’t need them, and they can be harmful in pregnancy as well as for older adults.
Zeng, J., Chen, L., Wang, Z. et al. Marginal vitamin A deficiency facilitates Alzheimer’s pathogenesis Acta Neuropathol (2017). doi:10.1007/s00401-017-1669-y
Image: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health