High-Dose Intravenous Vitamin C in Anaesthesia: A Comprehensive Literature Review.

Preamble and opinion.

Ian Brighthope

The Exciting Benefits of High-Dose Intravenous Vitamin C in Anesthesia: A Bright Option for Surgical Patients

For patients preparing for surgery, high-dose intravenous (IV) vitamin C has emerged as a powerful and safe ally in enhancing recovery, comfort and reducing complications. This essential nutrient, celebrated for its antioxidant and healing properties, is showing remarkable results in peri-operative care, offering a range of benefits that can make your surgical experience smoother, safer and more comfortable. As a passionate advocate for patient well-being, I’m thrilled to share my experiences in how IV vitamin C can support you before, during, and after surgery, addressing pain, recovery, and overall health with a natural, cost-effective approach.

Pain Relief and Reduced Need for Opioids
High-dose IV vitamin C is a game-changer for managing postoperative pain. Studies, like those by Jeon et al. (2016) and Ayatollahi et al. (2017), show that a single (small) dose of 3 grams during surgery can significantly lower pain levels in the first 24 hours, whether you’re undergoing a colectomy or throat surgery. Patients report less discomfort and need fewer opioids, such as morphine, which means a reduced risk of side effects like nausea or sedation. Even in orthopedic procedures like hip replacements, vitamin C has been shown to ease pain at rest and during movement, helping you get back on your feet faster. For those with chronic pain conditions, such as complex regional pain syndrome (CRPS), post-herpetic neuralgia, or cancer-related pain, IV vitamin C offers powerful additional relief by calming inflammation and supporting nerve health, making it a versatile tool for long-term comfort. It all depends on the dose.

Faster Recovery and Cognitive Clarity
Surgery and anaesthesia can leave you feeling fatigued, but vitamin C is a vital supporter of your recovery. Its role in neurotransmitter synthesis helps maintain neurological stability, ensuring your brain stays sharp. Research highlights that maintaining adequate vitamin C levels prevents complications like delayed awakening, keeping your recovery on track. For older patients or those concerned about cognitive function, preclinical studies reveal that vitamin C protects brain cells from anaesthetic stress, promoting clearer thinking post-surgery. By supporting your body’s natural resilience, IV vitamin C helps you emerge from surgery feeling more energised and ready to heal.

Fewer Complications and Enhanced Healing
High-dose IV vitamin C (20 - 100gram) shines in reducing surgical complications. In cardiac surgery, studies like those by Hemilä and Suonsyrjä (2016) show it can cut the risk of postoperative atrial fibrillation by up to 50%, helping your heart stay strong and potentially shortening your time in the ICU or hospital. Patients also experience less postoperative nausea and vomiting, making the early recovery hours more comfortable. Beyond that, vitamin C’s critical role in collagen synthesis supercharges wound healing, ensuring your incisions and tissues repair quickly and beautifully, which may lower the risk of infections. Whether you’re having a minor procedure or a major operation, vitamin C supports your body’s ability to bounce back.

A Safe and Natural Boost for All Surgical Patients
One of the most exciting aspects of IV vitamin C is its safety and affordability. Administered in doses of 1–10 grams (or higher for specific cases), it’s well-tolerated by most patients and integrates seamlessly into surgical care. Its antioxidant powers combat the oxidative stress of surgery, protecting your organs and tissues while promoting overall wellness. From easing pain to supporting heart health, cognitive function, and wound healing, IV vitamin C is a holistic addition to your surgical journey.

My Recommendation
As someone dedicated to optimising your surgical experience, I wholeheartedly recommend that all patients undergoing surgery consider high-dose intravenous vitamin C before, during, and after their procedure. This simple, natural therapy can enhance your comfort, speed your recovery, and reduce complications, all while being gentle on your body. Discuss IV vitamin C with your anaesthetist and surgical team to ensure it’s tailored to your needs, and embrace this exciting option to make your surgery a smoother, more positive experience.

With vitamin C by your side and in your veins, you’re setting yourself up to reduce the risks of complications and death for a brighter, healthier recovery!

Ian Brighthope

High-Dose Intravenous Vitamin C in Anaesthesia: A Comprehensive Literature Review

Introduction
High-dose intravenous vitamin C (ascorbate) has garnered interest in perioperative medicine for its potential benefits in patients undergoing surgery and anesthesia. Vitamin C is a potent antioxidant and cofactor in pathways crucial for tissue healing, adrenal function, and neurotransmitter synthesis [1][2]. The surgical and anesthetic period is known to induce oxidative stress and inflammatory responses, contributing to organ injury, pain, and other postoperative complications [1][2]. It is hypothesized that vitamin C’s antioxidant effects could mitigate these issues and improve outcomes [1][2]. In surgical patients, stress can deplete plasma vitamin C levels, and some patients (especially those malnourished or critically ill) may have suboptimal vitamin C status preoperatively [3][4]. These factors have prompted investigations into whether supplementing high-dose intravenous vitamin C perioperatively can improve pain control, recovery, and overall outcomes in the context of anesthesia and surgery.

Analgesic Effects and Pain Management
One of the most studied applications of intravenous vitamin C in anesthesia is its role in acute postoperative pain management. Multiple randomized controlled trials (RCTs) have assessed vitamin C’s opioid-sparing and analgesic effects after surgery. In a landmark RCT, Jeon et al. (2016) evaluated 3 g of intravenous vitamin C given intraoperatively in patients undergoing laparoscopic colectomy [3][5]. The vitamin C group experienced significantly lower pain scores in the first 24 hours after surgery and a reduction in opioid (morphine) consumption compared to placebo controls [3][3]. Similarly, Ayatollahi et al. (2017) reported that 3 g IV vitamin C given during uvulopalatopharyngoplasty (with tonsillectomy) led to reduced postoperative pain intensity and delayed the time to first analgesic request, without increasing adverse effects [4][4]. These individual trials align with findings from a meta-analysis by Hung et al. (2020), which pooled data from randomized trials and found that perioperative vitamin C supplementation was associated with significantly lower postoperative pain scores and opioid requirements in the first 24 hours after various surgeries [2][3]. Notably, vitamin C’s analgesic benefit may be most pronounced in the immediate postoperative period, potentially aiding early recovery and mobilization. Vitamin C has also been explored as part of multimodal analgesia strategies. For example, combining IV vitamin C with other analgesic adjuncts like magnesium sulfate during surgery has shown additive effects in reducing postoperative pain and nausea in some studies [6][7]. In orthopedic surgery, a recent RCT by Han et al. (2024) investigated a single 3 g IV dose of vitamin C during total hip arthroplasty. The vitamin C group had reduced 24-hour morphine consumption and lower pain scores at rest and with movement on postoperative day 1 [5][5]. Although the differences in that trial did not exceed predefined minimal clinically important thresholds, the results still indicate a trend toward improved analgesia with vitamin C supplementation. Given the risks of opioids (respiratory depression, sedation, nausea, etc.), an adjunct that safely lowers opioid needs is valuable. Indeed, a systematic review in the British Journal of Anaesthesia by Suter et al. (2022) concluded that vitamin C was associated with reduced pain scores and cumulative morphine consumption up to 48 hours after surgery, although it did not conclusively shorten hospital length of stay in non-cardiac surgeries [1][5]. Beyond acute surgical pain, high-dose vitamin C has been studied in chronic and neuropathic pain conditions often managed by anesthesiologists or pain specialists. A 2024 comprehensive review by Likar et al. surveyed the use of high-dose IV ascorbate in various pain syndromes [6][6]. The evidence, albeit heterogeneous, suggests that vitamin C can be a useful adjunct for complex regional pain syndrome (CRPS), where it has been associated with reduced incidence and severity of CRPS after limb surgeries in earlier studies. It may also provide relief in post-herpetic neuralgia and other neuropathic pain states, as well as in certain tumor-related (cancer) pain [6]. For example, vitamin C’s antioxidant and anti-inflammatory properties are thought to reduce neurogenic inflammation and oxidative damage, which are contributors to chronic pain maintenance [6]. While these findings extend beyond the immediate perioperative period, they reinforce the notion that ascorbate has broad analgesic and neuroprotective actions that could be harnessed in perioperative care. High-dose IV vitamin C appears to be a safe and effective integrative therapy for various pain conditions when used appropriately, addressing underlying oxidative and inflammatory processes that standard analgesics do not [6][6].

Effects on Anesthesia Recovery and Cognitive Function
Another area of interest is whether vitamin C can influence recovery from anesthesia and protect against anesthesia-related cognitive disturbances. General anesthesia and surgical stress can lead to postoperative fatigue, delirium, or cognitive dysfunction in susceptible patients. Vitamin C, being vital for neurotransmitter synthesis and an antioxidant, has been hypothesized to improve emergence from anesthesia or reduce neurocognitive side effects. Clinical evidence so far is limited. A randomized trial by Talley et al. (2009) examined if ascorbic acid expedited the return of consciousness after general anesthesia but found no significant difference in recovery times or early cognitive function between vitamin C and placebo groups [7][6]. This suggests that a single dose of vitamin C does not notably speed immediate anesthesia emergence or awakening. However, vitamin C’s longer-term neuroprotective effects have been demonstrated in preclinical studies. Cheng et al. (2015) reported that vitamin C administration attenuated isoflurane-induced cognitive impairment in animal models [8][8]. In that study, mice exposed to the anesthetic isoflurane showed impaired learning and memory along with increased neuronal apoptosis; treatment with high-dose vitamin C mitigated these effects, reducing markers of oxidative stress and neuronal injury in the brain [8]. The vitamin C also inhibited isoflurane-triggered caspase-3 activation in neural cells, suggesting a mechanism by which it could protect against anesthesia-related neurotoxicity [8]. While these results are from laboratory settings, they indicate that vitamin C might help preserve cognitive function in the context of anesthetic exposure, an area that could be relevant to preventing postoperative delirium or longer-term cognitive decline (e.g., in older surgical patients). In human studies of postoperative delirium or cognitive dysfunction, direct evidence for vitamin C is sparse. However, it is noteworthy that vitamin deficiencies (including vitamin C) have been linked to a higher risk of neurological complications after anesthesia. A recent systematic review by Bagheri Moghaddam et al. (2025) found that patients with severe vitamin C deficiency can experience acute onset of cardiovascular instability or mental status changes during or immediately after anesthesia [11][11]. In two case reports included in that review, patients with unrecognized scurvy (vitamin C deficiency) developed refractory hypotension and delayed awakening under anesthesia, problems that resolved with vitamin C repletion [11]. This underscores the importance of adequate vitamin C levels for neurologic and hemodynamic stability in the perioperative period. While those are extreme examples, they support the concept that vitamin C contributes to neurologic recovery and stability, especially in deficient individuals. Overall, more clinical research is needed to determine if prophylactic vitamin C can reduce the incidence or severity of postoperative delirium or cognitive dysfunction in routine surgical populations.

Perioperative Outcomes and Organ Protection
Researchers have also explored intravenous vitamin C for various other anesthesia-related outcomes. One such outcome is postoperative nausea and vomiting (PONV). Although not a primary antiemetic, vitamin C may have ancillary benefits. In the meta-analysis by Hung et al., patients who received vitamin C had a slightly lower incidence of early postoperative nausea or vomiting within the first 2 hours post-op [6]. This trend did not always reach statistical significance and was not observed at later time points, but it hints at a potential role of antioxidants in PONV prophylaxis. Another trial combining magnesium and vitamin C noted reduced nausea scores, suggesting vitamin C could enhance antiemetic regimens when used together with other agents [7]. Cardiovascular outcomes have been another focus, particularly in cardiac surgery where oxidative stress is profound. Vitamin C supplementation has been studied for preventing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery under cardiopulmonary bypass. A meta-analysis by Hemilä and Suonsyrjä (2016) reviewed clinical trials and found that vitamin C (either oral or IV, often 2 g/day) significantly reduced the incidence of atrial fibrillation after cardiac surgery in several studies [10][8]. The benefit was more pronounced in certain subgroups (e.g., patients outside the US), reflecting variability in patient populations and protocols. Nonetheless, the pooled data suggested roughly a 50% reduction in odds of POAF with vitamin C prophylaxis [8][8]. Additionally, an RCT in Iran by Sadeghpour et al. (2015) reported that high-dose vitamin C (given as 1.5 g IV every 6 hours for the first day after surgery) not only tended to reduce arrhythmia incidence but also significantly shortened ICU and hospital lengths of stay after CABG surgery [9][9]. These findings imply that ascorbate’s stabilization of myocardial electrophysiology and reduction of oxidative injury could translate into tangible postoperative cardiac benefits. In critical care and septic shock scenarios (often managed by anesthesia/ICU physicians), vitamin C has been investigated as part of a therapy cocktail (with thiamine and hydrocortisone) to improve outcomes. Early studies suggested high-dose IV vitamin C might reduce organ failure and mortality in sepsis, although more recent rigorous trials have shown mixed or no significant benefits. While this is slightly outside the elective perioperative setting, it highlights vitamin C’s organ-protective potential under extreme oxidative stress conditions. Vitamin C’s fundamental role in collagen synthesis and wound healing also underscores its importance for surgical patients. Adequate vitamin C can support better wound healing and possibly lower the risk of wound infections. Patients with sufficient ascorbate levels are better equipped to heal surgical incisions and anastomoses, whereas deficient patients might have impaired wound healing and higher infection risk. Although no large trials specifically focus on vitamin C and surgical site infection rates, this principle is well established biochemically and often cited in perioperative nutrition optimization guidelines.

Dosage, Safety, and Pharmacokinetics
Dosage: In the context of anesthesia, “high-dose” intravenous vitamin C generally refers to doses well above the daily dietary requirement, often in the gram range. Common regimens in studies have included single doses such as 1 g, 2 g, or 3 g IV given preoperatively or intraoperatively. For instance, beneficial effects on pain were observed with 1 g IV in a cholecystectomy trial and with 3 g IV in orthopedic and ENT surgery trials [2][4]. Some protocols in cardiac surgery or critical care have used repeated dosing (e.g., 6 g/day divided into multiple infusions) over 1–4 days. In chronic pain management (e.g., CRPS or cancer pain), even higher doses (7.5 g to 25 g IV infusions) have been used intermittently under medical supervision [6]. It is important to note that vitamin C has nonlinear pharmacokinetics; oral dosing is limited by intestinal absorption, whereas IV administration can achieve blood levels far higher, potentially needed for its acute pharmacological effects.
Safety: High-dose IV ascorbate is generally well tolerated in perioperative patients, but certain precautions are necessary. The most significant safety concern is in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. High-dose vitamin C can act as a pro-oxidant in G6PD-deficient patients, leading to hemolysis. Therefore, screening for G6PD deficiency is recommended before administering very large doses (e.g., >10 g) of vitamin C, especially in populations where this enzyme deficiency is prevalent. Another consideration is renal function: vitamin C is cleared renally, and at high doses it is metabolized to oxalate. Patients with renal impairment or dehydration are at risk for oxalate crystal deposition and kidney stone formation when given high doses. Ensuring adequate hydration and renal function is prudent before infusion. In practice, doses up to 2–3 g IV are considered safe in individuals with normal renal function, and even doses up to 10–15 g have been given without issue, but caution is advised beyond that range. Vitamin C can occasionally cause mild side effects such as flushing, headache, or nausea during infusion, but these are infrequent. Intravenous administration should be done slowly (typically over 30–60 minutes for multi-gram doses) to avoid any transient hypotension or dizziness that can occur with rapid infusion. Another interesting safety note is that high-dose vitamin C can interfere with certain point-of-care glucometers, falsely elevating blood glucose readings due to the chemical interaction. Anesthesiologists should be aware of this to avoid inappropriate insulin administration during perioperative glucose management if the patient is receiving high-dose ascorbate. Overall, the safety profile of IV vitamin C is favorable, especially when compared to many drugs used in the perioperative period. There have been no reports of serious allergic reactions to pure ascorbic acid injections (it is not immunogenic). Its use is contraindicated only in a few scenarios (severe renal failure, known oxalate kidney stones, G6PD deficiency, or iron overload states where vitamin C could theoretically enhance iron absorption). In sum, when used judiciously, high-dose IV vitamin C is a safe adjunct in anesthesia practice.

Conclusion
In summary, the current literature suggests that high-dose intravenous vitamin C can play a beneficial role in the perioperative setting as an adjunct therapy. Its most robustly demonstrated effect is in reducing postoperative pain and opioid requirements in the first 1–2 days after surgery, thereby potentially enhancing patient comfort and facilitating recovery [1][2][3]. Vitamin C’s antioxidant and anti-inflammatory properties appear to underlie these analgesic benefits, as well as its potential protective effects on organs and tissues exposed to surgical stress and anesthetic drugs. There is promising evidence that vitamin C supplementation may reduce the incidence of certain complications – for example, atrial fibrillation after cardiac surgery and perhaps early postoperative nausea – though findings are not yet uniform across all studies [9][10]. The vitamin’s impact on immediate anesthetic recovery is less clear; while it may not speed wake-up times, maintaining adequate vitamin C levels is important for neurological function and hemodynamic stability, especially in patients at risk of deficiency [7][11]. From a safety standpoint, high-dose IV ascorbate is inexpensive and has a wide margin of safety in most patients, making it an attractive option to explore further. Given the variability in study results, more high-quality RCTs are warranted to confirm optimal dosing strategies and specific patient populations that benefit the most. Future research may clarify whether routine perioperative vitamin C can improve outcomes like surgical site healing, decrease delirium, or shorten hospitalization in a cost-effective manner. Until then, anesthesiologists and surgical teams may consider the judicious use of vitamin C on a case-by-case basis – for instance, as part of multimodal analgesia in patients where opioid-sparing is crucial (opioid-tolerant patients, obstructive sleep apnea patients, etc.) or in those with known low vitamin C status. This comprehensive review highlights that vitamin C, a long-known essential nutrient, is re-emerging as a valuable adjunct in anesthetic and perioperative care. Its role in enhancing recovery and reducing complications aligns with the ongoing shift toward improving quality of recovery and patient outcomes after surgery. With a growing body of evidence supporting its benefits, high-dose intravenous vitamin C represents a promising, if still underutilized, tool in the anesthesia provider’s armamentarium.

References

1. Suter, M., Bollen Pinto, B., Belletti, A., & Putzu, A. (2022). Efficacy and safety of perioperative vitamin C in patients undergoing noncardiac surgery: A systematic review and meta-analysis of randomised trials. British Journal of Anaesthesia, 128(4), 664–678. https://doi.org/10.1016/j.bja.2021.11.039

2. Hung, K. C., Lin, Y. T., Chen, K. H., et al. (2020). The effect of perioperative vitamin C on postoperative analgesic consumption: A meta-analysis of randomized controlled trials. Nutrients, 12(10), 3109. https://doi.org/10.3390/nu12103109

3. Jeon, Y., Park, J. S., Moon, S., & Yeo, J. (2016). Effect of intravenous high-dose vitamin C on postoperative pain and morphine use after laparoscopic colectomy: A randomized controlled trial. Pain Research and Management, 2016, 9147279. https://doi.org/10.1155/2016/9147279

4. Ayatollahi, V., Dehghanpoor-Farashah, S., Behdad, S., Vaziribozorg, S., & Rabbani-Anari, M. (2017). Effect of intravenous vitamin C on postoperative pain in uvulopalatopharyngoplasty with tonsillectomy. Clinical Otolaryngology, 42(1), 139–143. https://doi.org/10.1111/coa.12684

5. Han, G., Gan, Y., Wang, Q., Sun, S., & Kang, P. (2024). Effect of perioperative single dose intravenous vitamin C on pain after total hip arthroplasty. Journal of Orthopaedic Surgery and Research, 19(1), 712. https://doi.org/10.1186/s13018-024-05193-x

6. Likar, R., Poglitsch, R., Bejvančický, Š., et al. (2024). The use of high-dose intravenous L-ascorbate in pain therapy: Current evidence from the literature. Pain and Therapy, 13(4), 767–790. https://doi.org/10.1007/s40122-024-00622-5

7. Talley, H. C., Wicks, M. N., Carter, M., & Roper, B. (2009). Ascorbic acid does not influence consciousness recovery after anesthesia. Biological Research for Nursing, 10(3), 292–298. https://doi.org/10.1177/1099800408323222

8. Cheng, B., Zhang, Y., Wang, A., Dong, Y., & Xie, Z. (2015). Vitamin C attenuates isoflurane-induced caspase-3 activation and cognitive impairment. Molecular Neurobiology, 52(3), 1580–1589. https://doi.org/10.1007/s12035-014-8959-3

9. Sadeghpour, A., Alizadehasl, A., Kyavar, M., et al. (2015). Impact of vitamin C supplementation on post-cardiac surgery ICU and hospital length of stay. Anesthesiology and Pain Medicine, 5(1), e25337. https://doi.org/10.5812/aapm.25337

10. Hemilä, H., & Suonsyrjä, T. (2016). Vitamin C for the prevention of postoperative atrial fibrillation after cardiac surgery: A meta-analysis. Advanced Pharmaceutical Bulletin, 6(2), 243–250. https://doi.org/10.15171/apb.2016.033

11. Bagheri Moghaddam, A., Raouf-Rahmati, A., Nemati, A., et al. (2025). Vitamin deficiency, a neglected risk factor for post-anesthesia complications: A systematic review. European Journal of Medical Research, 30(1), 97. https://doi.org/10.1186/s40001-025-02288-x

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