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Seasonally Normalized Vitamin D Status and Long-Term Mortality and Multisystem Disease Risk in the UK Biobank
Israel A, Weizman A, Ashkenazi S, Magen E, Merzon E, Vinker S, Rappoport N.. medRxiv, 2026-10-09
Topic: Air pollution and environmental exposures
Background Vitamin D deficiency has been associated with mortality and chronic disease. In a recent study of Israeli Leumit Health Services (LHS) and US TriNetX populations, severe deficiency was reproducibly associated with mortality and multisystem morbidity, while longitudinal supplementation reconstructed from pharmacy dispensing was associated with lower risk. Methods We sought to reproduce these associations and address a wide range of potential confounders in the deeply phenotyped UK Biobank. Baseline circulating 25-hydroxyvitamin D [25(OH)D] was standardized to a common late-winter nadir using an eight-harmonic model, and participants were categorized according to nadir-equivalent 25(OH)D as <5, 5-10, 10-15, 15-20, or ≥20 ng/mL. Primary survival analyses used one-year delayed entry and complete-case multivariable adjustment. Results Analyses included 412,020 participants and 31,197 deaths. Mortality hazard ratios were 2.03 (95% CI 1.90-2.18), 1.34 (1.29-1.39), 1.08 (1.04-1.11), respectively, for <5, 5-10 and 10-15, versus ≥20 ng/mL. Associations previously observed in LHS and TriNetX were reproduced, notably for diabetes, myocardial infarction, cerebrovascular disease, dementia, diabetic retinopathy, and end-stage renal disease, whereas skin malignancies showed the opposite gradient, consistent with greater ultraviolet exposure. DAG-informed causal analyses using generalized overlap weighting achieved acceptable balance across measured covariates; weighted 10-year mortality was 9.7% with very severe deficiency versus 4.8% with ≥20 ng/mL, supporting a causal interpretation. Estimates remained stable with landmark lags extending to 5 years after measurement. Conclusions Seasonally normalized 25(OH)D identifies a reproducible state of systemic vulnerability while reducing exposure misclassification caused by calendar timing of measurement. An interactive implementation of the normalization model is available: https://vitamind.medil.ai .
Key findings
- Background Vitamin D deficiency has been associated with mortality and chronic disease.
- In a recent study of Israeli Leumit Health Services (LHS) and US TriNetX populations, severe deficiency was reproducibly associated with mortality and multisystem morbidity, while longitudinal supplementation reconstructed from pharmacy dispensing was associated with lower risk.
- Results Analyses included 412,020 participants and 31,197 deaths.
- Mortality hazard ratios were 2.03 (95% CI 1.90-2.18), 1.34 (1.29-1.39), 1.08 (1.04-1.11), respectively, for <5, 5-10 and 10-15, versus ≥20 ng/mL.
- DAG-informed causal analyses using generalized overlap weighting achieved acceptable balance across measured covariates; weighted 10-year mortality was 9.7% with very severe deficiency versus 4.8% with ≥20 ng/mL, supporting a causal interpretation.
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Study details
- Study designlongitudinal study
- Participants412,020
- Effect size9.7%; 4.8%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 50 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 62 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 412,020 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 31 of the 62 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Israel, A., Weizman, A., Ashkenazi, S., Magen, E., Merzon, E., Vinker, S., et al. (2026). Seasonally Normalized Vitamin D Status and Long-Term Mortality and Multisystem Disease Risk in the UK Biobank. medRxiv. https://doi.org/10.64898/2026.10.07.26364983
Vancouver
Israel A, Weizman A, Ashkenazi S, Magen E, Merzon E, Vinker S, et al. Seasonally Normalized Vitamin D Status and Long-Term Mortality and Multisystem Disease Risk in the UK Biobank. medRxiv. 2026. doi:10.64898/2026.10.07.26364983.
BibTeX
@article{israel2026-11723cae,
author = {Israel, A. and Weizman, A. and Ashkenazi, S. and Magen, E. and Merzon, E. and Vinker, S. and Rappoport, N.},
title = {{Seasonally Normalized Vitamin D Status and Long-Term Mortality and Multisystem Disease Risk in the UK Biobank}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.07.26364983},
url = {https://doi.org/10.64898/2026.10.07.26364983}
}
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