Impact of vitamin D supplementation on all-cause mortality: randomized trials revisited
Background & aims - Vitamin D insufficiency and deficiency are common worldwide and linked to adverse health outcomes, including higher all-cause mortality. Two large randomized controlled trials (VITAL and D-Health), conducted in mostly vitamin D-sufficient populations, found no mortality benef...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2026
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| In: |
Clinical nutrition
Year: 2026, Volume: 58, Pages: 1-8 |
| ISSN: | 1532-1983 |
| DOI: | 10.1016/j.clnu.2026.106597 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.clnu.2026.106597 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0261561426000245 
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| Author Notes: | Youqing Wang, Sha Sha, Tafirenyika Gwenzi, Ben Schöttker, Hermann Brenner |
| Summary: | Background & aims - Vitamin D insufficiency and deficiency are common worldwide and linked to adverse health outcomes, including higher all-cause mortality. Two large randomized controlled trials (VITAL and D-Health), conducted in mostly vitamin D-sufficient populations, found no mortality benefits of vitamin D supplementation. This study aims to estimate the expected effects of vitamin D supplementation in target populations with vitamin D insufficiency or deficiency.. - Methods - We emulated the VITAL and D-Health trials using data from the UK Biobank cohort to estimate expected effects of the observed increases in serum 25-hydroxyvitamin-D (25(OH)D) concentrations by 30 nmol/L and 38 nmol/L. In alternative analyses, study populations meeting the trial inclusion criteria (n = 237,502 and 185,809) were either weighted to yield distributions of 25(OH)D as observed in the trials, or restricted to people with vitamin D insufficiency or deficiency. Expected effects on all-cause mortality over the mean trial follow up times (5.3 and 5.7 years) were estimated using Cox models. - Results - Emulated trials with study populations weighted to the 25(OH)D distributions of the original trials yielded null results similar to those reported (hazard ratios [HR] 0.97 [95 % CI: 0.92-1.02] and 1.02 [95%CI: 0.97-1.07]). In contrast, major mortality reduction was expected in emulated trials that were restricted to people with vitamin insufficiency (HR 0.85 [95%CI: 0.79-0.91] and 0.81 [95%CI: 0.76-0.86]) or deficiency (HR 0.79 [95%CI: 0.72-0.87] and 0.75 [95%CI: 0.69-0.81]).. - Conclusions - Null effects of vitamin D supplementation were to be expected in trials conducted in vitamin D sufficient populations. Emulated trials suggest a potential for major mortality reduction in vitamin D insufficient and deficient populations.. |
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| Item Description: | Online verfügbar: 10. Februar 2026, Artikelversion: 19. Februar 2026 Gesehen am 24.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1532-1983 |
| DOI: | 10.1016/j.clnu.2026.106597 |