March 1, 2023

expert reaction to observational study on vitamin D supplementation and dementia diagnoses

A study published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring looks at vitamin D supplementation and dementia.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, says:

“This study builds on previous research which suggests that taking certain types of vitamin D supplements might have an effect on a person’s chances of developing dementia. Its findings hint that the onset of dementia happens later among people with a history of taking common vitamin D supplements, and that the effect appears stronger among people without genetic risk factors or existing memory and thinking difficulties.

“But there is more work to do to properly understand this link – the study didn’t collect data on participants’ lifestyle and health history in the years before the research began. This is an important omission. Extensive research shows that habits and behaviours in midlife, such as keeping a healthy heart or not smoking, can reduce our dementia risk in later life. In their research paper, the researchers speculate as to how the vitamin D could be linked to dementia risk, but these claims need additional research to confirm. 

“To keep our brains healthy as we age, there’s clear evidence that things like not smoking, staying mentally and physically active, only drinking in moderation, and keeping our blood pressure and cholesterol in check, all have a positive effect.  At this stage, there’s not enough evidence to add vitamin D supplements to that list. We’ll need to wait for further to fill in the gaps, including research that measures dosage and the role of other factors such as diet and exercise.

“Find out more about how we as individuals can reduce our dementia risk, using our new Think Brain Health Check-in tool.”

Prof Martin Hewison, Interim Director of the Institute of Metabolism and Systems Research (IMSR) and Professor of Molecular Endocrinology, University of Birmingham, said:

“In common with many other human health issues, previous reports have linked Alzheimer’s disease with vitamin D deficiency. This does not necessarily mean that vitamin D deficiency is cause of dementia – for example, the onset of dementia may prevent people from outdoor activities that normally stimulate their vitamin D production (the action of UVB light on skin is a major driver of vitamin D levels even in northern countries such as the UK).

“The new report by Ghahremani et al attempts to address this issue of whether vitamin D deficiency is a cause or consequence of dementia by studying over 12,000 people in the National Alzheimer’s Coordinating Centre (NACC) database, based in the USA. Importantly, all of the subjects were dementia-free at the start and the study simply examined which of these people went on to develop dementia. The key message from this study was that those people who had received vitamin D supplements were 40% less likely to develop dementia.

“This is accurately reflected in the press release, which also highlights some of the important additional information from this study. For example, vitamin D supplementation was only effective before the onset of cognitive decline. This is consistent with many other aspects of vitamin D and human health, where vitamin D supplementation may be most beneficial in preventing a disease rather than treating it.

“The authors are realistic in their report. The study has several strength – notably the large number of people included in the analysis, and the fact that this was done prior to the onset of disease. However, as the author point out, the key weakness of the study is that the authors were unable to provide vitamin D levels for the study participants. What were these levels at the start? In particular, how many people were vitamin D deficient? And, of course, were vitamin D levels higher in those people who took vitamin D supplements? This is not properly detailed in the press release, which simply says “However, no blood levels were drawn to test this hypothesis”. Another key limitation is that the study participants did not take a single type or dose of vitamin D supplement so it is still unclear what dose might be most effective with respect to Alzheimer’s disease.

“Despite these limitations, the paper is important because it suggests that taking vitamin D supplements may have some overall benefits in preventing or delaying dementia. As such, the study provides a platform for future work that might provide more solid evidence for this benefit of vitamin D. As the press release states, the authors of the current study – in Calgary (Canada) and Exeter (UK) – are currently involved in the VitaMIND supplementation trial that will explore whether vitamin D supplementation affects cognition over time. However, a word of caution is needed here. Many previous vitamin D supplementation studies have been ineffective, often because of the difficulties in designing these trials. For example, supplementation may be needed over many years to be effective, and supplementation may only be effective in those people who are vitamin D deficient at the start. This is a major hurdle for vitamin D randomized control supplementation trials as, ethically, anyone who is known to be vitamin D deficient should receive a supplement and not the placebo.

“Despite all of these difficulties associated with vitamin D supplementation, it will be interesting to see what the VitaMIND trial shows. In the meantime, the current study provides further support for vitamin D supplementation in elderly people. This has musculoskeletal benefits for the elderly, but it is exciting to think that it may also have some benefits for increasingly common health problems such as Alzheimer’s disease.”

Prof Susan Fairweather-Tait, Professor of Mineral Metabolism, University of East Anglia (UEA), said:

“There have been numerous claims on the health benefits of vitamin D based on association studies using epidemiological data, but most of these have yet to be confirmed. The findings described in this paper are intriguing and warrant further investigation. Examining an association between two variables requires robust and accurate measures of both, and using the intake of supplements as a proxy for vitamin D exposure means the study has a high risk of bias. I fully support the authors’ suggestion on future directions, namely that measurements of serum 25(OH)D are required. The evidence presented in this paper is not sufficient to draw firm conclusions on the link between vitamin D and dementia and a high level of caution is needed when interpreting the findings.”

Prof Gill Livingston, Professor in Psychiatry of older people, UCL, said:

“This study is well done but relies on data which has limitations which it cannot overcome. comparing 12388 volunteers with an average age of 71 and following them up for up to 10 years to see if they developed dementia The two groups are strikingly different. The press release ignores the difference in Mild Cognitive Impairments rates – this is very important. Around 40% of people diagnosed with MCI develop dementia over subsequent approximately 5 to 6 years so we would expect knowing nothing else rates of dementia to be in the Vit D group with MCI  11.2% versus 15.6%; a 44% difference.  However, those who took it were more likely to be white and less likely to be depressed than those who did not. There are other differences between groups. As dementia takes a long time to develop,  researchers are always concerned that when follow up is less than 10 years that what we are seeing is a difference between people already developing dementia and those not.  The rates of diagnosis begin to separate immediately and this suggests that many people were already developing dementia. The authors hypothesise that Vitamin D reduces amyloid and possibly tau deposition which are thought to contribute to Alzheimer’s disease but the higher rates of dementia are not only or mainly in Alzheimer’s.

“I agree with the authors that this is interesting but shows us little and am pleased they are doing a trial. As recommendations in the UK (study is in Exeter) are that all older people take Vitamin D at least in winter I am not sure how they are going to manage the placebo group.”

Prof Tara Spires-Jones, President-elect of the British Neuroscience Association; and Centre for Discovery Brain Sciences and UK Dementia Research Institute at The University of Edinburgh, said:

“This paper by Ghahremani and colleagues at the University of Calgary examined data from over 12,000 people to investigate there were associations between taking vitamin D supplements and dementia risk.  They observed that people who had taken vitamin D had lower rates of dementia and longer dementia-free survival than people who did not take the supplements. While this is a large, well-conducted study, it is important to note that this kind of association study cannot prove a causative link between vitamin D and lower dementia risk. For example, people who took the supplements could have healthier lifestyles in general and something else could be causing the lower dementia risk.” 

Dr Tom Russ, Director of the Alzheimer Scotland Dementia Research Centre; Consultant Psychiatrist & Honorary Clinical Reader, University of Edinburgh, said:

“This interesting study adds to the evidence that low levels of vitamin D could increase the risk of dementia. Like all observational studies, this research is limited in its conclusions. It used a large, high quality database to conduct the research, but the vitamin D supplementation was based on self-report and participants may or may not have been taking these consistently. It was also not possible for them to know which participants were vitamin D deficient and which had enough, which is likely the most important thing. They included some important risk factors which could potentially confound the association, but not all known risk factors for dementia which could be relevant. Previous evidence – particularly from Mendelian randomization studies – strongly implicates low levels of vitamin D as a risk factor for dementia, but we really need high quality studies which identify vitamin D deficient individuals and replace this to see if this affects their risk of dementia.”

‘Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status’ by Maryam Ghahremani et al. was published Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring at 12:00 noon UK time on Wednesday 1 March.

DOI: 10.1002/dad2.12404

Declared interests:

Prof Susan Fairweather-Tait: “I chair the FAO/WHO expert group on nutrient requirements for children aged 0-36 months (calcium, zinc and vitamin D)

I am a member of the EFSA Working Group on upper levels for vitamins and minerals

I am a member of the UK Scientific Advisory Committee for Nutrition and the Vitamin D fortification working group.”

Prof Gill Livingston: “I have no conflict of interest.”

Prof Tara Spires-Jones: “I have no conflicts with this study.”

Dr Tom Russ researches environmental risk factors for dementia, but is not actively working on research on vitamin D

For all other experts, no reply to our request for DOIs was received.