Vitamin D
Vitamin D Blood Levels
Higher vitamin D blood levels are consistently associated with lower all-cause mortality, but evidence for a direct causal effect or general-population benefit from supplementation remains inconclusive.
1. Introduction
The link between vitamin D and all-cause mortality has been studied across diverse populations and research designs.
Large-scale cohorts, meta-analyses, and Mendelian randomization studies consistently report that low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with higher all-cause and cause-specific mortality, particularly from cardiovascular disease (CVD) and cancer
(Song et al., 2024; Fan et al., 2020; Gaksch et al., 2017).
The association is non-linear: mortality risk decreases as vitamin D rises up to roughly 50–75 nmol/L, then plateaus or reverses at very high concentrations
(Durup et al., 2012; Michaëlsson et al., 2010).
Randomized controlled trials and Mendelian studies, however, have not consistently shown reduced mortality from supplementation
(Zhang et al., 2019; Neale et al., 2022).
Confounding factors such as lifestyle and underlying health remain likely contributors.
People with severe deficiency or limited sunlight exposure may benefit more from maintaining adequate vitamin D levels.
2. Methods
A search of more than 170 million research papers (Semantic Scholar, PubMed) identified 1,029 papers.
After screening and ranking, 50 high-quality studies were included.
Eight search strategies covered observational, interventional, and genetic evidence on vitamin D and mortality.
3. Results
3.1 Observational evidence
Large cohort and meta-analytic data show a robust inverse association between serum 25(OH)D and mortality.
Individuals with <30–50 nmol/L had a 1.2–2.1-fold higher risk of death compared with sufficient levels.
The curve is typically L- or reverse-J-shaped, with the lowest risk at 50–75 nmol/L
(Song et al., 2024; Fan et al., 2020).
3.2 Subgroup and cause-specific findings
Inverse associations are reported in postmenopausal women and in patients with diabetes, hypertension, osteoarthritis, kidney disease, or depression
(Liu et al., 2023; Wan et al., 2020).
Links are strongest for cardiovascular and, to a lesser extent, cancer mortality.
3.3 Supplementation and trials
Most randomized trials and meta-analyses show no significant reduction in all-cause mortality in the general population
(Barbarawi et al., 2019; Ruiz-García et al., 2023).
Small benefits may exist for cancer mortality or among people with baseline deficiency.
3.4 Genetic evidence
Mendelian randomization studies are mixed: some support a causal role for vitamin D at very low concentrations, while others suggest confounding by health status
(Sofianopoulou et al., 2023; Huang et al., 2019).
4. Discussion
Observational research supports a strong, non-linear inverse relationship between vitamin D and mortality, with the greatest benefit when moving from deficiency (<30–50 nmol/L) to sufficiency (50–75 nmol/L).
Yet supplementation trials and genetic analyses suggest that low vitamin D might often indicate poor health rather than cause it.
Targeted supplementation may help those who are severely deficient or have chronic diseases, but routine supplementation for everyone is not supported by high-certainty evidence.
At very high levels (>100 nmol/L), some studies even suggest increased risk.
5. Evidence summary
| Claim | Strength | Reasoning / Main sources |
|---|---|---|
| Low vitamin D (<30–50 nmol/L) linked to higher mortality | Strong | Consistent findings across cohorts and meta-analyses (Song 2024; Schöttker 2014) |
| Relationship is non-linear | Strong | L- or reverse-J-shaped curves, plateau at 50–75 nmol/L (Durup 2012) |
| Supplementation doesn’t lower mortality in general population | Moderate | Large RCTs show null or minimal effect (Neale 2022) |
| Deficiency may be a marker of poor health | Moderate | Genetic and RCT data imply confounding (Sofianopoulou 2023) |
| Benefit likely in deficient or high-risk groups | Moderate | Subgroup trials show improvement (Brenner 2017) |
| Very high levels (>100 nmol/L) might increase risk | Weak | Limited evidence (Michaëlsson 2010) |
6. Research gaps
| Population / Outcome | All-cause | CVD | Cancer | Supplementation | Mendelian |
|---|---|---|---|---|---|
| General population | 20 | 15 | 12 | 8 | 4 |
| High-risk or deficient | 10 | 8 | 7 | 6 | 2 |
| With comorbidities | 8 | 9 | 9 | 4 | 1 |
7. Open questions
| Research question | Why it matters |
|---|---|
| Does supplementation reduce mortality in severely deficient people? | Most RCTs excluded the deficient; targeted trials needed. |
| What is the optimal 25(OH)D threshold for mortality reduction? | Evidence of a threshold exists, but value and generalizability unclear. |
| Are high vitamin D levels harmful long-term? | Several studies suggest a U-shaped risk curve; safety data remain limited. |
8. Key references
- Song S et al. (2024) Clinical Nutrition, 43(9), 2156–2163. DOI
- Fan X et al. (2020) J Clin Endocrinol Metab. DOI
- Schöttker B et al. (2014) BMJ, 348 g3656. DOI
- Barbarawi M et al. (2019) JAMA Cardiology. DOI
- Neale R et al. (2022) Lancet Diabetes Endocrinol. DOI
- Sofianopoulou E et al. (2023) Lancet Diabetes Endocrinol. DOI
- Brenner H et al. (2017) J Nutrition, 147(7), 1325–1333. DOI
- Durup D et al. (2012) J Clin Endocrinol Metab, 97(8), 2644–52. DOI
- Michaëlsson K et al. (2010) Am J Clin Nutr, 92(4), 841–848. DOI
- Ruiz-García A et al. (2023) Nutrients, 15 (8), 1810. DOI
(Full list available via individual journal sources.)
Summary
Maintaining adequate vitamin D levels (around 50–75 nmol/L) is consistently linked with lower mortality in observational studies.
However, causal evidence is limited, and supplementation in already sufficient individuals shows little benefit.
Future research should clarify optimal thresholds and evaluate the safety of high concentrations.
Disclaimer: This summary was compiled using the Consensus App to aggregate and synthesize peer-reviewed research findings. It is provided for informational purposes only and should not replace professional medical advice.