The study: what was done and what was found
Researchers at the University of São Paulo prospectively enrolled 227 women scheduled for breast cancer surgery. Pre-operative serum 25-hydroxyvitamin D (25-OHD) levels were measured and patients were followed for post-operative pain scores at 24, 48 hours, and 30 days using validated numeric rating scales.
The key finding: patients with 25-OHD below 50 nmol/L had 3.2 times higher odds of experiencing moderate-to-severe pain (NRS ≥4/10) at 24 hours post-operatively, and 2.8 times higher odds at 48 hours, compared to vitamin D-sufficient patients (25-OHD ≥75 nmol/L).
Vitamin D-deficient patients also required significantly higher total opioid doses in the 48 hours following surgery — an important finding given ongoing concerns about opioid-related complications and dependency in oncology patients.
"These data suggest that vitamin D status should be considered as part of routine pre-operative assessment, at least in cancer surgery patients. Correcting deficiency is cheap, safe, and takes 8-12 weeks — well within typical surgical planning timelines." — Study co-author, 2026
Vitamin D and pain: the biological mechanism
The link between vitamin D deficiency and pain sensitivity is not new — it has been observed in fibromyalgia, chronic musculoskeletal pain, and neuropathic pain conditions for over a decade. Several mechanisms are proposed:
- Neuroinflammation: Vitamin D receptors (VDR) are expressed on immune cells and neurons. Deficiency promotes pro-inflammatory cytokine release (IL-6, TNF-α) that sensitises pain pathways.
- Central sensitisation: Vitamin D modulates descending pain inhibitory pathways. Deficiency may reduce endogenous pain suppression.
- Prostaglandin regulation: Vitamin D suppresses cyclooxygenase-2 (COX-2) expression, reducing prostaglandin-mediated pain sensitisation at surgical sites.
- Muscle function: Deficiency causes proximal myopathy and impairs muscle repair — both contributing to post-operative pain and functional recovery.
Vitamin D reference ranges: what the numbers mean
Note: Units vary internationally. The UK and most of Europe use nmol/L. The US commonly uses ng/mL. To convert: divide nmol/L by 2.496 to get ng/mL. Use our free Lab Values Converter for instant conversion.
Who is at highest risk of vitamin D deficiency?
| Risk factor | Mechanism | Estimated prevalence |
|---|---|---|
| Living above 50° latitude (UK, Northern Europe) | Insufficient UVB exposure Oct–Apr | ~40% deficient in winter |
| Dark skin pigmentation | Melanin reduces UVB absorption | Up to 75% in some UK studies |
| Obesity (BMI >30) | Sequestration in adipose tissue | ~35% higher deficiency risk |
| Age over 65 | Reduced skin synthesis, less outdoor time | ~30-50% insufficient |
| Malabsorption (IBD, coeliac, post-bariatric) | Reduced GI absorption | Highly variable, often severe |
| Exclusively breastfed infants | Breast milk low in vitamin D | Without supplementation: most |
Pre-operative implications: should we screen routinely?
Current pre-operative assessment guidelines in most countries do not mandate vitamin D testing. This study — and the growing body of literature linking vitamin D deficiency to pain, immune function, and surgical complications — suggests that may need to change, at least for elective cancer surgery.
The practical argument is compelling: a serum 25-OHD test costs approximately £20-30 in the UK. If deficiency is found, a loading regimen (50,000 IU weekly for 8 weeks) costs under £15 and achieves sufficiency in most patients within the pre-operative planning window. The potential to reduce post-operative opioid use and pain burden represents significant clinical and health economic value.
Treatment: correcting vitamin D deficiency
| Severity | 25-OHD level | Typical regimen | Duration to sufficiency |
|---|---|---|---|
| Severe deficiency | <25 nmol/L | 50,000 IU/week (D3) | 8-12 weeks |
| Deficiency | 25-50 nmol/L | 50,000 IU/week or 4,000 IU/day | 6-10 weeks |
| Insufficiency | 50-75 nmol/L | 1,000-2,000 IU/day | 4-8 weeks |
| Maintenance | ≥75 nmol/L | 800-1,000 IU/day | Ongoing |
Cholecalciferol (D3) is preferred over ergocalciferol (D2) for supplementation — D3 raises serum 25-OHD more reliably and sustains levels longer. Co-supplementation with calcium is not routinely required unless there is co-existing deficiency or osteoporosis.
What this means for clinical practice today
This study will not immediately change pre-operative guidelines. But for clinicians involved in cancer surgery planning — surgeons, anaesthetists, and oncology nurses — it provides evidence-based justification for adding a simple, cheap vitamin D check to the pre-operative workup, particularly for patients with known risk factors.
For patients awaiting elective surgery: discuss vitamin D status with your GP at your pre-assessment appointment. If you live in a northern latitude, are over 65, or have limited sun exposure, there is a reasonable chance you are deficient — and correction before surgery is safe, inexpensive, and potentially meaningful for your post-operative recovery.
Frequently Asked Questions
References
- Lima MADD, et al. "Vitamin D deficiency and acute postoperative pain in breast cancer surgery." Pain Medicine. 2026.
- Hicks GE, et al. "Associations between vitamin D status and pain in older adults." JAGS. 2008;56(5):785-791.
- NICE. Vitamin D: supplement use in specific population groups (PH56). NICE, 2014.
- Holick MF. "Vitamin D deficiency." NEJM. 2007;357(3):266-281.