Vitamin D supplementation touted for dementia prevention in high-risk individuals

Vitamin D may offer brain boosting benefits, with a large study providing evidence that vitamin D supplementation exerts some effect in the prevention of dementia.

In a cohort of 12,388 older adults enrolled through the National Alzheimer's Coordinating Center in the US, vitamin D supplementation was associated with lower incidence of dementia over 10 years (hazard ratio [HR], 0.60, 95 percent confidence interval [CI], 0.55–0.65; p<0.001). [Alzheimers Dement 2023;doi:10.1002/dad2.12404]

Significantly more participants who were taking vitamin D supplements lived free of dementia for longer, with the 5-year dementia-free survival being 83.6 percent (95 percent CI. 82.3–84.9) as opposed to 68.4 percent (95 percent CI, 67.1–69.7) among those who were not taking any vitamin D supplements.

Of note, the findings on the beneficial effects of vitamin D supplementation on dementia incidence were consistent across each vitamin D formulation: calcium–vitamin D (HR, 0.56, 95 percent CI, 0.49–0.64; p<0.001), cholecalciferol (HR, 0.63, 95 percent CI, 0.53–0.75; p<0.001), ergocalciferol (HR, 0.61, 95 percent CI, 0.53–0.71; p<0.001), and their combinations (HR, 0.50, 95 percent CI, 0.40–0.64; p<0.001).

Another interesting finding is that while vitamin D supplementation had favourable effects across all strata of sex, cognitive diagnosis, and APOE ε4 status, there were significant differences within the subgroups, according to researchers led by Prof Zahinoor Ismail of the University of Calgary, Calgary, Alberta, Canada and University of Exeter, Exeter, UK.

Interaction analyses showed that the incidence rates of dementia among participants who were taking vitamin D supplements were much lower for women than men (HR, 0.51 vs 0.74; p<0.001), for those with normal cognitive function than their counterparts with mild cognitive impairment (HR, 0.44 vs 0.67; p<0.001), and APOE ε4 noncarriers than carriers (HR, 0.53 vs 0.67; p=0.005).

“We know that vitamin D has some effects in the brain that could have implications for reducing dementia; however, so far, research has yielded conflicting results,” according to lead investigator Prof Zahinoor Ismail of the University of Calgary, Alberta, Canada and University of Exeter, Exeter, UK. [Am J Ther 2021;28:e638-e648; CNS Drugs 2021;35:1249-1264; J Neurol Neurosurg Psychiatry 2019;90:1347-1352; J Alzheimers Dis 2013;37:147-171; J Gerontol A Biol Sci Med Sci 2012;67:1205-1211]

“Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, [that is] before the onset of cognitive decline,” Ismail said.

Next steps

Also known as the sunshine supplement, vitamin D helps flush out amyloid beta (Aβ) aggregates, one of the hallmarks of Alzheimer's disease, from the brain and prevent the build-up of Aβ-induced tau, which is another protein involved in the development of dementia. [Neuroscience 2016;322:28-38; J Alzheimers Dis 2012;29:51-62; Int J Mol Sci 2020;21:4215]

There is also evidence to suggest that low levels of serum vitamin D contribute to a greater risk of dementia and Alzheimer's disease. Yet, Ismail and colleagues acknowledged that the role of vitamin D supplementation as a potential intervention for prevention is still debated and remains uncertain. [Nutr J 2015;14:76; Am J Clin Nutr 2019;110:246-253; J Neurol Neurosurg Psychiatry 2019;90:1347-1352]

“Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected. The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case,” said co-investigator Dr Byron Creese of the University of Exeter.

“The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time,” Creese shared.

The VitaMIND study enrols people at least 40 years old, who are asked to complete annual questionnaires on detailed lifestyle factors and undergo cognitive testing to determine what keeps the brain sharp in later life.