Vitamin D deficiency is becoming more prevalent in the general population and is associated with suboptimal health (all-cause mortality, cardiovascular disease, pulmonary ailments, diabetes mellitus, and cancer).1 It has also been proposed that vitamin D at physiological concentration may have preventive effects on many viral infections, including COVID-19.2 During acute stress and critical illness, such as the period after surgery, there is an increased tissue demand for vitamin D that is combined with a lower pool of available vitamin D.3 Therefore, insufficient vitamin D levels can have adverse effects on many outcomes following surgery.



In a study of approximately 2000 patients, low vitamin D levels were associated with a greater risk of acquiring bloodstream infections in the hospital, with the greatest risk in those patients with the lowest levels.4 In a smaller study, higher vitamin D levels protected against surgical site infections.5 Cells of the immune system express the vitamin D receptor, and it is likely that in low vitamin D states, the immune system becomes dysfunctional.


Delirium and Cognition

Delirium, a state characterized by acute confusion, inattention and disturbances in mental state, is very common after surgery. It increases hospital stay by 2–3 days and is associated with a 30-day mortality of 7–10%.6 In a study of over 4500 patients, low pre-hospital vitamin D levels increased the risk of delirium during hospitalization.7 In a smaller study of elderly patients undergoing cancer surgery, vitamin D deficiency was very common (72%) and higher vitamin D levels lowered the risk of cognitive deficits immediately after surgery.8 Vitamin D appears to be important for regulating the maintenance and survival of nerve cells and low vitamin D levels may increase the risk of brain dysfunction after surgery.



In a study of 226 women undergoing knee replacement surgery, vitamin D deficiency was a risk factor for moderate-to-severe knee pain early after surgery in postmenopausal women.9 Similarly, preoperative supplementation of Vitamin D in spine surgery patients decreased inflammation and the intensity of pain after surgery.10 Research has shown that vitamin D has anatomic, hormonal, neurological, and immunological influences on pain symptoms.11


Functional Recovery

Functional status at discharge has been shown to be a strong predictor of short-term and long-term morbidity as well as mortality in hospitalized patients. Recently, higher vitamin D levels were associated with better functional status in 300 patients discharged from an ICU.12 Similarly, in 1,029 elderly patients with hip fracture, low vitamin D levels were associated with lower walking ability after surgery.13 Even before surgery for knee or hip joint replacement, patients with low vitamin D levels had lower pre-operative physical activity.14 Since vitamin D is needed for optimal musculoskeletal health, potential muscle weakness from vitamin D deficiency is likely the reason for the worse functional status and recovery.



A number of studies have shown that individuals at the lower end of vitamin D levels are at significantly increased risk of mortality. For example, in a very large study that included 849,412 study participants from a broad medical population, subjects with the lowest levels of vitamin D had a 35% greater risk of dying.15 Even in critically ill surgical patients, lower vitamin D levels at admission was predictive of increased mortality at 90 days after surgery.3 From an analysis of a large number of randomized trials, vitamin D3 supplementation has been reported to decrease mortality.16


  1. Ginde AA, Liu MC, Camargo CA, Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. Mar 23 2009;169(6):626-32. doi:10.1001/archinternmed.2008.604
  2. Abdrabbo M, Birch CM, Brandt M, et al. Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection. Protein Sci. Nov 2021;30(11):2206-2220. doi:10.1002/pro.4190
  3. Quraishi SA, Bittner EA, Blum L, McCarthy CM, Bhan I, Camargo CA, Jr. Prospective study of vitamin D status at initiation of care in critically ill surgical patients and risk of 90-day mortality. Crit Care Med. Jun 2014;42(6):1365-71. doi:10.1097/CCM.0000000000000210
  4. Quraishi SA, Litonjua AA, Moromizato T, et al. Association between prehospital vitamin D status and hospital-acquired bloodstream infections. Am J Clin Nutr. Oct 2013;98(4):952-9. doi:10.3945/ajcn.113.058909
  5. Laviano E, Sanchez M, Gonzalez-Nicolas MT, et al. Surgical site infection in hepatobiliary surgery patients and its relationship with serum vitamin D concentration. Cir Esp (Engl Ed). Oct 2020;98(8):456-464. Infeccion del sitio quirurgico en cirugia hepatobiliopancreatica y su relacion con la concentracion serica de vitamina D. doi:10.1016/j.ciresp.2020.03.004
  6. Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth. Oct 2020;125(4):492-504. doi:10.1016/j.bja.2020.06.063
  7. Quraishi SA, Litonjua AA, Elias KM, et al. Association between pre-hospital vitamin D status and hospital-acquired new-onset delirium. Br J Nutr. Jun 14 2015;113(11):1753-60. doi:10.1017/S0007114515001245
  8. Zhang Y, Shan GJ, Zhang YX, et al. Preoperative vitamin D deficiency increases the risk of postoperative cognitive dysfunction: a predefined exploratory sub-analysis. Acta Anaesthesiol Scand. Aug 2018;62(7):924-935. doi:10.1111/aas.13116
  9. Song Y, Liu SF, Wu Z, Wang M, Cong RJ, Tao K. Effects of preoperative serum vitamin D levels on early clinical function outcomes and the moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty. Menopause. May 3 2021;28(8):893-898. doi:10.1097/GME.0000000000001789
  10. Krasowska K, Skrobot W, Liedtke E, et al. The Preoperative Supplementation With Vitamin D Attenuated Pain Intensity and Reduced the Level of Pro-inflammatory Markers in Patients After Posterior Lumbar Interbody Fusion. Front Pharmacol. 2019;10:527. doi:10.3389/fphar.2019.00527
  11. Shipton EA, Shipton EE. Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities. Pain Res Treat. 2015;2015:904967. doi:10.1155/2015/904967
  12. Brook K, Otero TMN, Yeh DD, Canales C, Belcher D, Quraishi SA. Admission 25-Hydroxyvitamin D Levels Are Associated With Functional Status at Time of Discharge from Intensive Care Unit in Critically Ill Surgical Patients. Nutr Clin Pract. Aug 2019;34(4):572-580. doi:10.1002/ncp.10196
  13. Lim C, Roh YH, Kim S, Nam KW. Preoperative Vitamin D Deficiency is Associated with Postoperative Functional Recovery and Complications after Hip Fracture Surgery. J Bone Metab. Nov 2021;28(4):333-338. doi:10.11005/jbm.2021.28.4.333
  14. Jacob EA, Blum L, Bedair HS, Freiberg AA, Quraishi SA. The Association of Vitamin D Status and Pre-operative Physical Activity in Patients with Hip or Knee Osteoarthritis. J Restor Med. Dec 2015;4(1):3-10. doi:10.14200/jrm.2015.4.0101
  15. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. Apr 1 2014;348:g1903. doi:10.1136/bmj.g1903
  16. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. Jan 10 2014;(1):CD007470. doi:10.1002/14651858.CD007470.pub3