Scientists discover strange link between low vitamin D and pain

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) could potentially benefit from supplementation before undergoing a radical mastectomy, a major operation in which an entire breast is surgically removed.

Vitamin D May Play a Role in Pain

Vitamin D is best known for its role in bone health, but growing evidence suggests it may also influence how the body senses and processes pain. Researchers believe this could be related to vitamin D's effects on inflammation and the immune system, both of which can influence pain responses.

Vitamin D deficiency is also frequently reported among people with breast cancer, prompting researchers to investigate whether low levels might affect pain following surgery.

To explore that possibility, researchers conducted a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025. A prospective study follows patients forward in time, while an observational study tracks what happens without assigning participants to different treatments.

The study included 184 breast cancer patients scheduled to have one entire breast surgically removed.

Comparing Patients With High and Low Vitamin D

Half of the participants were classified as vitamin D deficient (below 30 nmol/L), while the other half had vitamin D levels considered sufficient (above 30 nmol/L).

The two groups were broadly similar. Patients in the vitamin D deficient group had an average age of 44, compared with 42 in the vitamin D sufficient group.

Everyone received the hospital's standard treatment during and after surgery. Importantly, the doctors and other clinical staff caring for the patients did not know their vitamin D status, reducing the chance that this information could influence pain treatment.

During surgery, patients received fentanyl, a powerful opioid used to control acute pain. After surgery, every patient received paracetamol through an intravenous drip every 8 hours.

Patients could also give themselves tramadol (another opioid analgesic) by pressing a button connected to a patient-controlled pain relief system. This allowed researchers to track how much additional opioid medication each person needed.

Low Vitamin D Linked to More Pain

Patients rated their pain immediately after surgery and again at 6 hours, 12 hours, 18 hours and 24 hours. Researchers also recorded nausea, vomiting, sedation levels, and how long patients remained in the hospital.

A clear difference emerged during the first day of recovery.

Patients with vitamin D deficiency were three times more likely to report moderate to severe postoperative pain at any point during the first 24 hours compared with patients who had sufficient vitamin D levels.

However, none of the patients in either group experienced what researchers classified as severe pain (7 or over on a scale of 0 to 10). The difference between the groups came entirely from moderate pain (4-6 on the pain scale).

Patients With Low Vitamin D Used More Opioids

The difference also appeared in the amount of pain medication patients required.

Those with vitamin D deficiency received an average of 8 μg more fentanyl during surgery. Researchers described that difference as modest.

The gap was much larger after surgery.

Patients in the vitamin D-deficient group used substantially more tramadol (112mg) than patients with sufficient vitamin D. Patients controlled the medication themselves, up to a maximum dose of 50mg per hour.

Greater opioid use matters because these drugs can cause side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependency and addiction.

Postoperative nausea was more common among patients with vitamin D deficiency. Vomiting occurred only in the deficient group, although the difference was small and was not statistically significant, meaning researchers could not confidently rule out chance as the explanation.

The Study Cannot Prove Cause and Effect

The findings point to a potentially important connection between vitamin D and surgical pain, but the researchers emphasized several limitations.

Because the study was observational and conducted at a single center, it cannot show that vitamin D deficiency directly caused patients to experience more pain or use more opioids.

Researchers also did not measure inflammatory markers, so they could not investigate the biological mechanisms that might explain the relationship between vitamin D and pain.

The study also lacked information on several factors that could potentially influence postoperative pain, including anxiety, depression, cancer stage, cancer treatment, and sleep disturbance before surgery.

Despite those limitations, the researchers conclude, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They suggest, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain."