Vitamin D’s Impact on Cancer Incidence and Mortality: A Systematic Review
Nutrients 2025, 17(14), 2333; https://doi.org/10.3390/nu17142333
by Sunil J. Wimalawansa ORCID
CardioMetabolic & Endocrine Institute, North Brunswick, NJ, USA
Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure.
Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies.
Results: Beyond genomic actions via calcitriol [1,25(OH)2D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin’s and non-Hodgkin’s lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40–80 ng/mL) significantly lowers cancer risks and mortality.
Conclusions: While many observational studies support vitamin D’s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D3 doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality.
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Review of study by Perplexity AI
Table of Vitamin D and Cancer
| Cancer Type | Prevention Evidence | Treatment/Survival Evidence | Optimal 25(OH)D Level |
| Colorectal Cancer | Strong: 50% ↓ risk per 1000 IU increase | Strong: ↓ mortality with higher 25(OH)D | >40 ng/mL, preferably >50 ng/mL |
| Breast Cancer | Strong: 60-77% ↓ risk with higher intake | Strong: Improved survival (meta-analyses) | >40 ng/mL, optimal ≥60 ng/mL |
| Gastric Cancer | Moderate: Inverse association with UVB/25(OH)D | Moderate: Better clinical outcomes | >40 ng/mL |
| Ovarian Cancer | Strong: Inverse correlation with UVB exposure | Limited data available | >40 ng/mL |
| Non-Hodgkin's Lymphoma | Strong: ↓ risk with higher vitamin D levels | Strong: ↓ mortality with adequate levels | >40 ng/mL |
| Bladder Cancer | Moderate: Higher 25(OH)D → ↓ risk | Limited data available | >40 ng/mL |
| Esophageal Cancer | Moderate: Strong inverse association with UVB | Limited data available | >40 ng/mL |
| Pancreatic Cancer | Limited: Some benefit with 400 IU daily* | Conflicting: Very high levels may worsen outcomes | Unclear - very high levels problematic |
| Lung Cancer | Moderate: Meta-analysis shows ↓ incidence | Strong: Survival benefits in stage IV patients | >40 ng/mL |
| Thyroid Cancer | Moderate: Lower 25(OH)D in cancer patients | Strong: Low 25(OH)D → poor prognosis | >40 ng/mL |
| Oral/Nasopharyngeal Cancer | Moderate: Hypovitaminosis D ↑ risk | Moderate: Better outcomes with adequate levels | >40 ng/mL |
| Melanoma | Moderate: Higher 25(OH)D → thinner tumors | Strong: Independent prognostic factor | >40 ng/mL |
| Prostate Cancer | Conflicting: Some ↑ risk with very high levels | Strong: Higher mortality in lowest tertile | Complex - moderate levels may be optimal |
| Hematologic Malignancies | Strong: Low 25(OH)D predicts poor outcomes | Strong: Poor outcomes with deficiency | >40 ng/mL |
Key: ↓ = reduced/lower, ↑ = increased/higher, * = conflicting evidence
Most Compelling Evidence for Prevention:
- Colorectal Cancer: 50% risk reduction with 1000 IU vitamin D increase1
- Breast Cancer: 60-77% risk reduction with higher vitamin D intake1
- Non-Hodgkin's Lymphoma: Strong inverse relationship with vitamin D levels1
Strongest Evidence for Treatment/Survival:
- Multiple Cancer Types: Improved survival across colorectal, breast, lung, thyroid, melanoma, and hematologic malignancies1
- Mortality Reduction: Consistent pattern of lower cancer mortality with higher 25(OH)D levels1
Important Caveats: Pancreatic and Prostate
- Pancreatic Cancer: Complex relationship - some benefit at moderate doses, but very high levels may increase risk1
- Prostate Cancer: J-shaped curve - both very low and very high levels associated with increased risk1
Optimal Dosing:
- Minimum effective serum 25(OH)D level: 40 ng/mL (100 nmol/L)1
- Optimal range for most cancers: 50-80 ng/mL1
- Daily vitamin D3 requirements: 70-90 IU/kg body weight (non-obese)1
- Obese individuals: Require 3-4 times higher doses1
Mechanisms of Action:
Vitamin D reduces cancer risk and improves outcomes through multiple mechanisms including decreased cell proliferation, increased apoptosis, reduced angiogenesis, and decreased metastasis1.
The study emphasizes that current government recommendations (20-30 ng/mL) are insufficient for cancer prevention, and maintaining levels above 40 ng/mL, preferably 50-80 ng/mL, provides optimal protection against most cancers1.
1 Reference
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Related items in Vitamin D Life
- Cancer, Vitamin D - many studies
- Vitamins fight cancer: 9 of the 10 most cited studies were for Vitamin D - Dec 2024
- Incidence of many cancers increased 1.5 X in a generation – June 2024
- 23 Cancers in the US are associated with low UVB - Grant April 2024
- 18 Cancers might be fought by Vitamin D – March 2025
- 13 Cancers are helped by Vitamin D – Biobank July 2023
- Magnesium and Cancer - many studies
- Childhood Cancers - Vitamin D can help - many studies
- 79% increase in cancer under age 50 in 3 decades - Sept 2023
- Response to Vitamin D - many studies
Those with poor response can:- 1) Take a better form of vitamin D
- 2) Take additional supplements that get past gene barriers
- 3) Take a gut-friendy form of Vitamin D
- 4) Take topical Vitamin D
Takes >10,000 IU daily to get 98.5% of levels > 40 ng
Doce/Response data from 36 studies
solid line = mean response (50% above, 50% below)
Lower dashed line = 97.5% will have achieved the level
15+ Vitamin D Life pages have SUNIL in the title
The list is automatically updated