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

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In a recently published study, Dr American Journal of Clinical Nutrition, Researchers investigated associations between vitamin D (serum and supplementation status) and dementia (all-cause, vascular). [VD]and Alzheimer’s disease [AD]) analyzed a range of covariates, including demographic, socio-economic, 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 years.

The study found 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 analyzes highlight the association between vitamin D and dementia – vitamin D deficiency corresponds to a 19–25% increased risk of all three types of dementia.

Study: Associations of serum vitamin D status and vitamin D supplement use with all-cause dementia, Alzheimer's disease and vascular dementia: a UK Biobank-based prospective cohort study.  Image credit: PhotoCam/ShutterstockStudy: Associations of serum vitamin D status and vitamin D supplement use with all-cause dementia, Alzheimer’s disease and vascular dementia: a UK Biobank-based prospective cohort study. Image credit: PhotoCam/Shutterstock

The global burden of dementia

Dementia is an umbrella term that refers to a group of conditions that negatively affect memory, cognition, and daily decision-making, resulting in severe disability and reduced quality of life (QoL) in patients. Dementia is an age-related complication – although it occasionally occurs in young adults, dementia predominantly affects older adults, with the risk of developing the disease increasing non-linearly with age.

Dementia is a worldwide concern, affecting 55 to 60 million people and approximately 10% of the population over the age of 60. Unfortunately, there is no cure for neurodegenerative diseases, clinical interventions focus on prevention, delaying onset and case-by-case symptomatic management. Despite an ‘explosion’ of research aimed at addressing this global burden, the various mechanisms underlying dementia that lead to effective therapeutics aimed at reversing the condition remain elusive.

Therefore, a critical need exists to prevent dementia before it occurs by improving diagnostic accuracy and predictive power and early identification of modifiable risk factors, thereby increasing the likelihood of preventing the onset of the disease. Although not formally associated with dementia onset or progression, unrelated studies have suggested that vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) levels <30 nmol/L) and insufficiency (<50 nmol/L) may Increases risk of dementia.

Previous clinical trials focusing on vitamin D presented conflicting results along the cognitive spectrum. While some have found vitamin D supplements beneficial, others have not. These trials typically involve small sample sizes and limited study durations, and are poorly powered to reveal long-term trends in cognitive illnesses such as dementia. A large-scale, long-term prospective study would help alleviate these challenges, equipping medical practitioners and, most importantly, the general public with the tools needed to combat this dire condition.

About the study

In the current study, researchers obtained long-term data from the United Kingdom (UK) Biobank to uncover the relationship between vitamin D (supplementation and status) and dementia (risk and prevalence). UK Biobank is a large-scale (n = 502,366) longitudinal study of English participants aged 37 to 73 years which aims to analyze and improve QoL, public health and healthy ageing. For the current study, individuals aged 55 to 69 years with no prior history of dementia and complete baseline serum 25(OH)D concentrations and vitamin D supplementation datasets were included. Age 55 marks a tipping point in dementia prevalence, as indicated by its prevalence rates (0.2% for persons under 55; 2.6% for persons over 55).

Data collection was comprehensive and included demographic, socioeconomic, medical history, self-reported diet and supplement questions, and ethnicity. Blood samples were collected from the participants and a chemiluminescent immunoassay technique was used to quantify the vitamin D concentration in each sample. Questionnaire results (specifically self-reported supplement information) were used to allocate participants to vitamin D, multivitamin, or control groups.

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

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

Study results

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) of female participants. Demographic 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 of hypertension, diabetes mellitus, and coronary heart disease was 35.5%, 6.3%, and 8.3%, respectively. The median number of chronic diseases was 2, with an interquartile range of 1 to 3.”

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

“Of note, 25(OH)D levels were higher in vitamin D users (59.3 nmol/L) and multivitamin users (56.0 nmol/L) than in non-users (47.9 nmol/L). Consequently, the prevalence of vitamin D “vitamin D supplements (6.9%) or non-users of multivitamin supplements (9.5%) were significantly less likely to have D deficiency than non-users (21.3%).

During 13.6 (median) years of follow-up, 2.6% (n = 7,087) of participants developed generalized dementia. Of these, 3,616 and 1,815 were diagnosed with Alzheimer’s disease (AD) and vascular dementia (VD), respectively. Risk analyzes revealed that vitamin D deficiency was associated with a 25% increased risk of all-cause dementia. Subgroup analyzes confirmed these findings, with all but one subgroup showing no additional trend in the dementia-deficit probe.

“However, a particularly striking pattern emerged from our subgroup analysis based on skin color. It appears that vitamin D deficiency or vitamin D insufficiency was not associated with dementia outcomes in study participants with darker skin tones.”

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

“While our results are encouraging and suggest a potential role for vitamin D supplementation in the prevention of dementia, particularly in those with vitamin D deficiency, we advise caution due to the observational nature of this study. RCTs with long follow-up periods are essential to establish. Ethics in Dementia Prevention Strategies.”

Journal Reference:

  • Chen, L., Sha, S., Stocker, H., Brenner, H., & Schöttker, B. (2024). Associations of serum vitamin D status and vitamin D supplement use with all-cause dementia, Alzheimer’s disease and vascular dementia: a UK Biobank-based prospective cohort study. American Journal of Clinical Nutrition. DOI – 10.1016/j.ajcnut.2024.01.020,

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