Vitamin D in Oncology

Widespread deficiency in cancer patients with emerging evidence for survival benefit when optimized

Key Points

• Vitamin D deficiency (25-OH-D <20 ng/mL) is present in 40–80% of cancer patients at diagnosis across cancer types.
• The VITAL trial (n=25,871, 5 years): Vitamin D3 2,000 IU/day significantly reduced cancer mortality by 17% overall and 25% in patients with normal BMI.
• VDR (Vitamin D receptor) is expressed in most cancer cells; 1,25-(OH)2D3 (active form) induces differentiation, inhibits proliferation, and modulates immune function.
• Target 25-OH-D serum level for cancer patients: 40–60 ng/mL; testing and supplementation to goal is now part of most integrative oncology protocols.
• Vitamin D toxicity (hypercalcemia) is rare at maintenance doses ≤4,000 IU/day; recheck levels at 3 months after starting supplementation.
• Synergistic with calcium for bone protection in patients on aromatase inhibitors, androgen deprivation therapy, or long-term corticosteroids.

Biology and Cancer Risk

Vitamin D3 (cholecalciferol) is synthesized in skin from 7-dehydrocholesterol under UVB radiation (280–315 nm) and converted to 25-hydroxyvitamin D3 (25-OH-D, calcidiol) in the liver, then to the active hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3, calcitriol) by 1-α-hydroxylase in the kidneys and, critically for oncology, in many peripheral tissues including cancer cells themselves. The vitamin D receptor (VDR) — a nuclear hormone receptor — is expressed in over 30 tissue types, including most cancer cell types (breast, prostate, colorectal, lung, lymphoma, leukemia). Binding of…

VITAL Trial and Clinical Evidence

The VITAL trial (Manson et al., NEJM 2019 + 2022 update) is the definitive RCT for vitamin D supplementation in cancer prevention and outcomes. Findings: **Design:** 25,871 US adults (mean age 67), randomized to vitamin D3 2,000 IU/day + omega-3 fish oil, vitamin D alone, omega-3 alone, or double placebo. Median follow-up 5.3 years. **Primary Cancer Prevention:** Vitamin D3 did not significantly reduce total cancer incidence vs. placebo (HR 0.96, p=0.07 — near-significant trend). **Cancer Mortality (key finding):** Vitamin D3 significantly reduced cancer mortality by 17% (HR 0.83, 95% CI…

Clinical Protocols

**Testing and Target Levels:** All patients at cancer diagnosis should have 25-OH-D measured. The integrative oncology target range is 40–60 ng/mL (100–150 nmol/L), which is higher than the general population sufficiency threshold of 20 ng/mL, reflecting the biological evidence for anti-cancer effects at higher concentrations. **Repletion Dosing:** - Level 20–30 ng/mL: 2,000–3,000 IU/day vitamin D3 - Level 10–20 ng/mL: 4,000 IU/day or short-course weekly 50,000 IU × 8 weeks, then 2,000–3,000 IU/day maintenance - Level <10 ng/mL: 50,000 IU weekly × 12 weeks (prescription ergocalciferol D2 or…