25-hydroxyvitamin D → Cognitive performance

Mechanism

Observational papers have tied low 25(OH)D to cognitive decline. The vitamin D receptor is expressed in cortex and hippocampus. Reverse causation can produce the same correlation: people who are starting to slip go indoors, and the number falls. Kang, Vyas, Okereke, and colleagues tested 2000 IU a day of cholecalciferol inside VITAL. VITAL-Cog assessed 3424 people aged 60 and older by phone on eight tests, then again 2.8 years later. CTSC-Cog assessed 794 people in person on nine tests, then again 2.0 years later. The primary was annual change in a global composite. The pooled difference versus placebo was 0.01 standard units per year (95% CI -0.01 to 0.02, p=0.39). Baseline 25(OH)D did not modify the result (p=0.84). A year of the same dose in the parent trial raised mean 25(OH)D from 29.8 to 41.8 ng/mL. The blood number moved. The tests did not. A pre-specified analysis found slower decline among Black participants (difference 0.04, 95% CI 0.01 to 0.08). The authors call that modest and ask for confirmation. It does not rewrite the primary. Corbett and colleagues (VitaMIND, 2025) tested 4000 IU a day against placebo for 24 months in 620 UK adults aged 50 and older, enrolled for predicted mild to moderate deficiency and early cognitive impairment. The primary was a computerized Trail Making B score. The between-group difference was 5770 (95% CI -2189 to 13,730). The abstract does not name the unit. Cohen d was 0.11 (P=0.16). Secondary cognition was also null. Pham and colleagues analyzed cognition inside D-Health, a five-year Australian trial of monthly 60,000 IU versus placebo. A random sample aged 70 and older sat the Telephone Interview for Cognitive Status at year 2 (3887 people) and year 5 (3614). The mean difference was 0.04 (95% CI -0.14 to 0.23). Cognitive impairment (TICS 25 or below) had an odds ratio of 1.00 (95% CI 0.75 to 1.33). It is the D-Health cognition read, not a new assigned design.

Caveats

The VITAL sample was generally healthy and well educated. More than half had some postgraduate study. Few people were vitamin D deficient. Placebo-arm decline was modest. Two assessments over two to three years can miss a slow effect. The larger arm used telephone tests. Participants could take up to 800 IU a day of vitamin D outside the trial. The Black-participant finding was pre-specified but not the primary. VitaMIND is smaller than Kang. The abstract names 620 adults. Deficiency was a questionnaire prediction, not a blood number for most people. The published table uses 163 people on placebo and 174 on vitamin D for the 24-month Trail Making B contrast. The trial was remote, 75 percent women, 98 percent White, and already online. The authors say they did not enroll enough people with 25(OH)D below 25 nmol/L to answer severe deficiency. The confidence interval crosses zero. This page does not treat VitaMIND as a flip of Kang. D-Health used a monthly bolus, not a daily pill. There was no baseline TICS. The sample was largely replete Australians. That add-on paper does not change the trial stamp. This is not a trial of treating rickets, institutionalized deficiency, or dementia. It does not speak to employment or income. This page is not an argument against treating a true deficiency.

Effect

qualitative. Kang 2022 VITAL: pooled annual global MD 0.01 (95% CI -0.01, 0.02), N=4218. Corbett 2025 VitaMIND: TMT-B MD 5770 (CI -2189 to 13730), N=620. Pham 2023 D-Health: TICS MD 0.04 (CI -0.14 to 0.23).

Nodes

Named confounders

• Time outdoors
• Educational attainment
• Disposable income

Papers

• Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial.

  JH Kang, CM Vyas, OI Okereke, S Ogata, M Albert, IM Lee, D D'Agostino, JE Buring · 2022 · Scientific reports

• Impact of Vitamin D Supplementation on Cognition in Adults With Mild to Moderate Vitamin D Deficiency: Outcomes From the VitaMIND Randomized Controlled Trial.

  A Corbett, R Taylor, D Llewellyn, JM Ranson, A Hampshire, E Pickering, A Palmer, D Aarsland · 2025 · Journal of the American Medical Directors Association

• Vitamin D supplementation and cognition-Results from analyses of the D-Health trial.

  H Pham, M Waterhouse, S Rahman, C Baxter, BD Romero, DSA McLeod, BK Armstrong, PR Ebeling · 2023 · Journal of the American Geriatrics Society