25-hydroxyvitamin D
nmol/L or ng/mL
Circulating vitamin D status. Strongly confounded by time outdoors, latitude, adiposity, and wealth.
Observational catalogs link 25(OH)D to almost every chronic disease and to socioeconomic markers. Mendelian randomization and large RCTs (VITAL) have collapsed most of those claims. Correcting clinical deficiency is a medical act. Treating 25(OH)D as an economic or leadership lever is not supported.
Also called vitamin D, calcidiol.
Connected relationships
Randomized trial · High confidence
25-hydroxyvitamin D→Cognitive performance
A rise in 25-hydroxyvitamin D does not identify a change in Cognitive performance.
Kang 2022 found that 2000 IU a day of vitamin D3 versus placebo did not slow cognitive decline among 4218 adults aged 60 and older in VITAL (pooled annual global-score difference 0.01, 95% CI -0.01 to 0.02). Corbett 2025 and Pham 2023 then also found no cognitive gain.
Randomized trial · Moderate
25-hydroxyvitamin D→Depression
A rise in 25-hydroxyvitamin D does not identify a change in Depression.
Okereke 2020 found that 2000 IU a day of vitamin D3 versus placebo did not change the risk of depression or clinically relevant depressive symptoms among 18353 adults aged 50 and older in VITAL-DEP (hazard ratio 0.97, 95% CI 0.87 to 1.09). Rahman 2023 then found the same null on PHQ-9 in D-Health.
Mendelian randomization · High confidence
25-hydroxyvitamin D→Employment status
A rise in 25-hydroxyvitamin D does not identify a change in Employment status.
Genetic instruments for 25(OH)D do not buy you a job. The observational D–success link was a marker.
Observational · High confidence
25-hydroxyvitamin D↔Disposable income
A rise in 25-hydroxyvitamin D does not identify a change in Disposable income.
People with money and outdoor lives have higher 25(OH)D. That is not D causing the money.
Mendelian randomization · Contested
25-hydroxyvitamin D→All-cause mortality
Higher 25-hydroxyvitamin D moves All-cause mortality in a non-linear way. Dose or timing can flip the sign.
Sutherland 2022 found an L-shaped Mendelian randomization link between genetically predicted 25(OH)D and all-cause death in 307,601 white-European UK Biobank adults, with risk falling until about 50 nmol/L, while Trummer 2013 and Ong 2019 found no linear genetic effect.
Observational · High confidence
Time outdoors→25-hydroxyvitamin D
Higher Time outdoors increases 25-hydroxyvitamin D.
Skin makes 25(OH)D from UV-B; Samefors 2021 then showed that encouraging 40 Swedish nursing-home residents outdoors for two summer months raised median serum 25(OH)D from 42.5 to 53.5 nmol/L.
Cases
Sources
- JH Kang et al. (2022). Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial.
- A Corbett et al. (2025). Impact of Vitamin D Supplementation on Cognition in Adults With Mild to Moderate Vitamin D Deficiency: Outcomes From the VitaMIND Randomized Controlled Trial.
- H Pham et al. (2023). Vitamin D supplementation and cognition-Results from analyses of the D-Health trial.
- OI Okereke et al. (2020). Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.
- ST Rahman et al. (2023). Effect of vitamin D supplementation on depression in older Australian adults.
- NM Alavi et al. (2020). Effect of vitamin D supplementation on depression in elderly patients: A randomized clinical trial.
- X. Meng et al. (2019). Phenome-wide Mendelian-randomization study of genetically determined vitamin D on multiple health outcomes using the UK Biobank study
- X. Jiang et al. (2021). The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study
- P. Autier et al. (2014). Vitamin D status and ill health: a systematic review
- J. E. Manson et al. (2019). Vitamin D supplements and prevention of cancer and cardiovascular disease
- JP Sutherland et al. (2022). Vitamin D Deficiency Increases Mortality Risk in the UK Biobank : A Nonlinear Mendelian Randomization Study.
- O Trummer et al. (2013). Vitamin D and mortality: a Mendelian randomization study.
- JS Ong et al. (2019). Vitamin D and overall cancer risk and cancer mortality: a Mendelian randomization study.
- M Samefors et al. (2021). Sunlight Exposure and Vitamin D Levels in Older People- An Intervention Study in Swedish Nursing Homes.