Before surgery, most patients undergo tests such as blood counts, clotting tests, and heart checks. Vitamin D levels are usually not checked. But a new clinical study suggests this test could be valuable, especially for women having breast cancer surgery.
A study in Regional Anesthesia & Pain Medicine found women with low vitamin D before breast cancer surgery had more pain and used more opioid painkillers in the first 24 hours after surgery than women with enough vitamin D. This link stayed strong even after adjusting for age, weight, fitness, and surgery length, making vitamin D status a clear predictor of pain after surgery.
Building on these findings, the authors note that this is the first study to directly examine the connection between vitamin D levels before surgery and pain right after breast cancer surgery, a group in which managing pain is especially important.
Why Vitamin D and Pain?
Vitamin D does more in the body than support bone health. Understanding this explains why it could influence post-surgical pain.
Vitamin D acts more like a hormone than just a vitamin. Every cell in the body has receptors for it. These include immune system cells, nerves, and cells that signal inflammation. New research suggests that vitamin D affects how the body processes pain in at least two ways.
First, vitamin D reduces the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6, and prostaglandin E2. These chemicals increase pain after tissue injury. Surgery triggers them, causing acute pain.
Second, low vitamin D has been linked to increased nerve sensitivity. The nervous system can also overreact to pain signals, which is called central sensitization. For people with low vitamin D levels, the same injury after surgery can feel more painful than it would for someone with normal vitamin D levels.
Scientists do not fully understand these processes or how vitamin D affects pain. Still, clinical evidence is growing, and this study adds key information.
The Study: How It Was Designed
Researchers at Fayoum University Hospital in Egypt ran a study from September 2024 to April 2025. They included 184 women, ages 20 to 65, all scheduled for breast cancer surgery called a modified radical mastectomy.
Before surgery, each participant had their serum 25-hydroxyvitamin D (25(OH)D) level measured. This is the circulating form of vitamin D and is considered the most reliable indicator of vitamin D status. Based on this measurement, participants were divided into two equal groups of 92. One group had vitamin D deficiency (levels below 30 nmol/L); the other had sufficient vitamin D (levels of 30 nmol/L or above).
Neither patients nor staff knew each woman’s group until after 24 hours. This reduced bias in pain measurement and treatment.
All patients got the same anesthesia and pain management plan. They received intravenous paracetamol every eight hours and had a device to give themselves tramadol as needed. Pain was measured on an 11-point scale right after surgery and again at 6, 12, 18, and 24 hours. Both groups were similar in age, weight, fitness, and surgery length.
The Results: A Stark and Consistent Difference
At 12 hours after surgery, 17.4% of vitamin D-deficient patients had moderate to severe pain (score above 3), compared to only 2.2% with enough vitamin D. This 15.2% difference was statistically significant.
The divergence appeared even earlier. By 6 hours after surgery, 32.6% of vitamin D-deficient patients reported moderate to severe pain. In the vitamin D-sufficient group, only 19.6% had this level of pain. Researchers calculated the overall pain burden over the 24-hour period using the area under the pain score curve. Vitamin D-deficient patients had a significantly heavier overall pain load.
After adjusting for other factors like age, BMI, fitness, surgery length, and opioid use, vitamin D deficiency was still linked to more moderate to severe pain in the first 24 hours. People with low vitamin D had 3.12 times higher odds of experiencing this pain than those with sufficient vitamin D.
More Pain, More Opioids
Vitamin D deficiency affected more than pain scores. It also increased opioid consumption, which is a clinically important outcome. Opioid use carries risks, including nausea, respiratory depression, and dependency.
During surgery, patients with low vitamin D received about 8 micrograms more fentanyl than those with enough vitamin D. This was a small but significant difference. The gap was much larger after surgery. Over 24 hours, vitamin D-deficient patients consumed an average of 380 mg of tramadol, while those with sufficient vitamin D consumed 268 mg. That is over 112 mg more, or about 42% higher opioid use.
This large difference in tramadol use had other effects. Nausea was more common among patients with low vitamin D levels, with a 13% higher risk. This is expected when opioid use increases. Hospital stays were also slightly longer for this group, though it is unclear how significant this difference is.
Importantly, no patients in either group experienced severe pain (score of 7 or higher) during the study period. No one developed respiratory depression. Researchers attributed this to the effectiveness of the standardized pain management protocol. The observed difference was driven entirely by moderate pain (scores of 4 to 6) being more common in the vitamin D-deficient group.
What This Means in Practice
Vitamin D deficiency is very common in breast cancer patients. Some studies estimate that 70 to 80% of these patients have low vitamin D, possibly due to the cancer itself, inflammation, and less sun exposure during illness. This makes the time before surgery an important chance to address the problem.
The researchers note that their findings suggest a plausible clinical pathway. Checking vitamin D levels as part of routine preoperative assessment in breast cancer patients, and supplementing those found to be deficient before surgery, could be valuable. Vitamin D supplementation is safe, inexpensive, and widely available. If it can meaningfully reduce postoperative pain and opioid use, the benefit-to-cost ratio would be highly favorable.
However, there are important limitations. This was an observational study, not a randomized trial. Even though the study was carefully designed and blinded, it cannot prove that low vitamin D levels cause more pain after surgery; it only shows that the two are linked. Other factors, like cancer stage, anxiety, depression, sleep, or chemotherapy, might also play a role. The study was conducted at a single hospital in Egypt with a single patient group. The results may not apply everywhere.
The authors clearly state these limitations. They recommend future randomized trials to test whether giving vitamin D supplements before surgery really reduces pain in breast cancer patients with low vitamin D.
The Bottom Line
This study supports that vitamin D affects pain and opioid use after surgery. For women having breast cancer surgery, having low vitamin D before surgery seems to triple the risk of significant pain and leads to higher opioid use.
A simple blood test before surgery, followed by vitamin D supplements if needed, could be an easy and low-risk way to help breast cancer patients recover better. While more research is needed, the results from this study are strong enough to be taken seriously.
Reference
Abdelhady, M. A., Boulos, M. L., Hamed, M. A., Masry, D. H., Ragab, S. G., & Ragab, M. H. (2026). Association between preoperative vitamin D level and postoperative pain in patients undergoing breast cancer surgery: a prospective observational study. Regional Anesthesia & Pain Medicine. https://doi.org/10.1136/rapm-2025-107495