Vitamin D deficiency linked to increased dementia risk, supplements may help

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In a recent study published in The American Journal of Clinical Nutrition, researchers investigated the associations between vitamin D (serum and supplementation status) and dementia (all-cause, vascular [VD], and Alzheimer's disease [AD]). They analyzed a plethora of covariates, including demographic, socioeconomic, biomarker, genetic, lifestyle, and health-care reports from a long-term (12-17 years) prospective cohort comprising 269,229 UK Biobank participants between the ages of 55 and 69.

Study findings revealed that despite 5-20% of participants reporting regular Vitamin D supplementation, 18.3%, and 34.0% were found to have vitamin D deficiency and insufficiency, respectively. Regression analyses highlight the association between vitamin D and dementia –vitamin D deficiency corresponded with a 19-25% increased risk of all three dementia types.

Study: The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer’s disease, and vascular dementia: a UK Biobank based prospective cohort study. Image Credit: Fototocam / ShutterstockStudy: The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer’s disease, and vascular dementia: a UK Biobank based prospective cohort study. Image Credit: Fototocam / Shutterstock

The global burden of dementia

Dementia is an umbrella term referring to a group of conditions negatively affecting memory, cognition, and everyday decision-making, causing severe disability and quality of life (QoL) reductions in patients suffering from the condition. Dementia is an age-related complication – despite occurring in young adults on occasion, dementia predominantly impacts older adults, with the risk of contracting the condition non-linearly increasing with age.

Dementia is a global concern, affecting between 55 and 60 million people and almost 10% of the human population above the age of 60 years. Unfortunately, no cure for the neurogenerative ailment exists, with clinical interventions focused on prevention, onset delay, and case-by-case symptomatic management. Despite an 'explosion' of research aimed at addressing this global burden, the diverse mechanisms underpinning dementia ensure that effective therapeutics aimed at reversing the condition remain elusive.

Therefore, a pressing need exists to arrest dementia before it occurs by improving diagnostic accuracy and prediction power and identifying modifiable risk factors early, thereby increasing the odds of preventing disease onsets. While hitherto not formally implicated in dementia initiation or progression, unrelated research has suggested that vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) levels of <30 nmol/L) and insufficiency (<50 nmol/L) may enhance dementia risk.

Previous clinical trials focused on vitamin D present conflicting results along the cognitive spectrum. While some have found benefits to vitamin D supplementation, others have not. These trials typically involve small sample sizes and limited study durations, poorly efficient at revealing long-term trends in cognitive ailments like dementia. A large-scale, long-term prospective study would help alleviate these challenges, informing medical practitioners and, most importantly, the general public with the tools they need to fight these terrifying conditions.

About the study

In the present study, researchers obtained long-term data from the United Kingdom (UK) Biobank to unravel the associations between vitamin D (supplementation and status) and dementia (risk and prevalence). The UK Biobank is a large-scale (n = 502,366) longitudinal study of English participants between the ages of 37 and 73 aimed at analyzing and improving QoL, public health, and healthy aging. For the present study, individuals between the ages of 55 and 69 with no prior history of dementia and complete baseline serum 25(OH)D concentration and vitamin D supplementation datasets were included. Age 55 marks a tipping point in dementia prevalence, as noted by its incidence rate (0.2% for individuals below 55; 2.6% for individuals above 55).

Data collection was extensive and included demographics, socioeconomics, medical histories, self-reported diet and supplementation questionaries, and ethnicity. Participant blood samples were collected, and the chemiluminescent immunoassay technique was used to quantify vitamin D concentrations in each sample. Questionnaire results (specifically self-reported supplementation information) were used to assign participants into vitamin D, multivitamin, or control cohorts.

From prior research with the same study population, authors identified 49 determinants of vitamin D supplementation and 49 determinants of vitamin D deficiency. The same determinants were used to characterize vitamin D status in this study. Data from UK Biobank records (hospital, medical, prescription) were used to assess and predict dementia risk using relevant mathematical models.

The association between vitamin D and dementia outcomes was achieved using four independent Cox proportional hazards regression models for insufficiency and five models for supplementation subcategories. Sex, skin color, body mass index (BMI), and APOE ε4 allele status were considered subgroups for subgroup and sensitivity analyses.

Study findings

After applying study inclusion criteria to the UK Biobank cohort, 269,229 participants were included in the present work. The mean participant age was found to be 62.1 years, with 52.3% (n = 140,857) female participants. Anthropometric data revealed that 44.1% of participants were overweight, 25.2% were obese, 8.8% were heavy smokers, and 12.0% reported heavy alcohol use.

"The prevalence for hypertension, diabetes mellitus, and coronary heart disease was 35.5%, 6.3%, and 8.3%, respectively. The median count of chronic diseases was 2, with an interquartile range spanning from 1 to 3."

The chemiluminescent immunoassay results revealed that 18.3% of the cohort displayed vitamin D deficiency, and 34.0% presented insufficiency. Only 5% and 19.8% of participants reported vitamin D or multivitamin supplementation, respectively.

"Of note, the 25(OH)D levels were higher among vitamin D users (59.3 nmol/L) and multivitamin users (56.0 nmol/L) compared to non-users (47.9 nmol/L). Consequently, the prevalence of vitamin D deficiency was much lower among subjects using vitamin D supplements (6.9%) or multivitamin supplements (9.5%) than among non-users (21.3%)."

Over the 13.6 (median) years of follow-up, 2.6% (n = 7,087) of participants developed all-cause dementia. Of these, 3,616 and 1,815 were diagnosed with Alzheimer's disease (AD) and vascular dementia (VD), respectively. Hazards analyses reveal that vitamin D deficiencies were associated with a 25% increased risk of developing all-cause dementia. Subgroup analyses validated these results, with all but one subgroup showing no additional trend in dementia-deficiency investigations.

"However, a particularly intriguing pattern emerged from our subgroup analysis based on skin color. It appeared that neither vitamin D deficiency nor vitamin D insufficiency were associated with the dementia outcomes in study participants with darker skin tones."

Surprisingly, the same skin color association was found during vitamin dementia-supplementation investigations. These investigations, however, highlight the benefits of supplementation, with multivitamin supplements associated with a 14% dementia risk reduction and 25% when taking medically prescribed high-dosage vitamin D supplements.

"While our results are encouraging and suggest a potential role for vitamin D supplementation in dementia prevention, particularly for those with vitamin D deficiency, we advocate caution due to the observational nature of this study. RCTs with long follow-up periods are indispensable to establish the efficacy in dementia prevention strategies."

Journal reference:
  • Chen, L., Sha, S., Stocker, H., Brenner, H., & Schöttker, B. (2024). The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer's disease, and vascular dementia: A UK Biobank based prospective cohort study. The American Journal of Clinical Nutrition. DOI – 10.1016/j.ajcnut.2024.01.020,
Hugo Francisco de Souza

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.


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