Nutritional support for acute, chronic, surgical, and cancer-related pain
Part 1 in our three-part series on vitamin C, pain, and opioid addiction.
What do humans have in common with other primates, bats, and guinea pigs? (No, not a love of cheese!) We cannot make L-gulonolactone oxidase (GLO), the enzyme needed to biosynthesize ascorbate (vitamin C) in the body.1–3
While rats, cats, dogs, and most other mammals can make their own vitamin C, we humans have to consume the nutrient in our diet. And when we don’t? We get into trouble.
Thankfully, it’s easy enough to get vitamin C from food and nutritional supplements – and doing so can not only support our immune systems, but also support skin integrity, preserve bone density, maintain dental health, stave off allergic reactions, support a balanced mood, and even fight drug addiction.
Opioid tolerance and dependency often start with medication to help relieve pain.4 Fortunately, vitamin C has been shown to be a both safe and effective analgesic. Vitamin C may therefore help a person avoid opioid medications entirely, or allow them to use lower doses of them in order to manage their pain symptoms. This in turn may reduce an individual’s likelihood of getting addicted to opioids. By alleviating pain, vitamin C can reduce our need for “harder hitting” (and typically addictive) medications.
By alleviating pain, vitamin C can reduce our need for “harder hitting” (and typically addictive) medications.
This is Part One of our series on vitamin C and addiction, in which we take a closer look at the vitamin’s analgesic (pain relieving) potential. In Part Two, we consider the evidence for vitamin C’s anti-addictive properties in preventing and treating opioid use disorder (OUD, or opioid addiction). In Part Three, we dissect the biochemistry of the vitamin to understand the science behind its wide range of effects.
Vitamin C for pain associated with surgery
Studies have shown that vitamin C supplementation is associated with a decreased requirement for opioid analgesics in surgical settings.5 In a randomized double-blind trial,6 80 patients were assigned to receive either a single 2 gram dose of oral vitamin C or a placebo one hour before undergoing anesthesia for laparoscopic cholecystectomy. In the first 24 hours after surgery, those who received vitamin C required much less morphine to manage their pain than those who received placebo. Intravenous (IV) vitamin C was observed to yield similar outcomes on postoperative (post-op) pain.5,7 These clinical trials in humans echo the findings of a mouse study in which vitamin C was shown to yield additive anti-nociceptive (pain blocking) effects with the conventional pain medications tramadol and morphine.8
In the first 24 hours after surgery, those who received vitamin C required much less morphine to manage their pain than those who received placebo.
When we consider some of the risk factors for opioid use disorder (opioid addiction), the potential implications of these studies are immense. Those undergoing surgery — including low-pain, outpatient, and elective procedures — are at increased risk of persistent opioid use.9 According to a 2014 retrospective analysis, 75% of heroin users in treatment said that their opioid misuse began with legal prescription painkillers.10
Vitamin C is also helpful for healing post-surgery due to its positive effects on collagen synthesis and wound healing.11–13
The body’s demand for vitamin C increases during times of surgery, illness, and stress. According to a review on the topic, patients require more than the recommended daily allowance (RDA) of vitamin C post-op, and the administration of exogenous vitamin C is associated with better surgical outcomes.14 In fact, our vitamin C plasma levels drop after trauma and surgery.14
Our vitamin C plasma levels drop after trauma and surgery.
This is perhaps no surprise, when we consider the animals that can synthesize vitamin C within their bodies. When in pain, or ill, or otherwise stressed, these mammals increase their endogenous vitamin C production. They also curiously ramp up their vitamin C synthesis when they’re on a variety of drugs – including analgesics!15
Vitamin C for cancer-related pain
High doses of vitamin C have been shown in several studies to ease cancer-related pain and improve quality of life in those with the disease.16–20 Vitamin C has successfully helped those with fibrosarcoma related pain (in which 10 g/d oral vitamin C for 19 days yielded better pain control by opiates); severe pain from breast cancer with skeletal metastases (wherein 5 g/d IV vitamin C for seven days yielded no further need for opiates after the fourth day, and was followed by and sustained by 8 g/day oral vitamin C for 70 days); and pain from bladder cancer with skeletal metastases previously inadequately controlled by morphine (in which 10 g/day IV vitamin C for 10 days followed by 10 g/day oral vitamin C for 24 days resulted in no further need for opiates).21
High doses of vitamin C have been shown in several studies to ease cancer-related pain and improve quality of life in those with the disease.
However, Pinkerton et al.’s open-label pilot study of patients with chronic pain secondary to cancer and/or cancer treatment did not find any clinically significant benefit from vitamin C.22 This may be because the study’s dosing protocol wasn’t assertive enough: patients already suffering from pain and already taking opioid medications received a mere 1 g of vitamin C twice daily over a brief three-day study period. While a short burst of treatment may help in acute settings, higher doses of vitamin C for longer periods of time may be necessary when it comes to managing chronic pain in those already on opioids.
Vitamin C for chronic pain
People living with chronic pain are also at risk of developing opioid use disorder:23 It has been estimated that up to half of all people who take opioids for chronic, non-cancer pain will become addicted.24 Considering that 40% of older adults live with chronic pain,25 that’s a pretty high number of people at risk.
Fortunately, several recent clinical trials have demonstrated high dose vitamin C’s analgesic properties in a variety of chronic pain conditions. For example, vitamin C (primarily in IV form) has been shown in numerous trials to ease the pain of both acute and post herpetic neuralgia (a complication of shingles).26–30 Vitamin C has also demonstrated considerable benefit in complex regional pain syndrome (CRPS).31–33 It may also help prevent the development of CRPS after acute fracture:34 In a trial of over 400 patients with recent wrist fracture, vitamin C (500mg daily) was observed to reduce the risk of developing subsequent CRPS.31
In a trial of over 400 patients with recent wrist fracture, vitamin C (500mg daily) was observed to reduce the risk of developing subsequent complex regional pain syndrome (CRPS).
Vitamin C may also fight pain by preventing osteoarthritis and slowing its progression.
Vitamin C has been shown to reduce patients’ need for painkillers after surgery and reduce the risk of chronic pain conditions arising after acute injury.6,34 The pain-relieving benefits of vitamin C have also been observed in the contexts of cancer-related pain and chronic pain.5,17,31–33
Low to moderate doses of vitamin C may ease pain and thus reduce the need for opioid and other pharmaceutical medications in the first place. This will invariably spare an individual the undesirable side effects of pharmaceutical painkillers and reduce the risk of addiction.
Check out Part Two of our series on vitamin C, in which we consider and critique the evidence for using vitamin C to treat opioid withdrawal.
In Part Three, we will tackle the biochemistry of this versatile vitamin to better understand its mechanisms of action in preventing opioid use disorder.
…And learn more about other natural remedies for pain relief!
ReferencesClick here to see References
- Yang H. Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis. Biochem Genet. 2013;51(5-6):413-25.
- Stone I. Hypoascorbemia, the genetic disease causing the human requirement for exogenous ascorbic acid. Perspect Biol Med. 1966;10(1):133-4.
- Stone I. The natural history of ascorbic acid in the evolution of the mammals and primates and its significance for present-day man. J Orthomol Psychiatry. 1972;1(2):82-9.
- Vadivelu N, et al. The opioid crisis: a comprehensive overview. Curr Pain Headache Rep. 2018;22(3):1-7.
- Jeon Y, et al. Effect of intravenous high dose vitamin C on postoperative pain and morphine use after laparoscopic colectomy: a randomized controlled trial. Pain Res Manag. 2016;2016.
- Kanazi GE, et al. Effect of vitamin C on morphine use after laparoscopic cholecystectomy: a randomized controlled trial. Can J Anesth. 2012;59(6):538-43.
- Ayatollahi V, et al. Effect of intravenous vitamin C on postoperative pain in uvulopalatopharyngoplasty with tonsillectomy. Clin Otolaryngol. 2017;42(1):139-43.
- Zeraati F, et al. Ascorbic acid interaction with analgesic effect of morphine and tramadol in mice. Anesthesiol Pain Med. 2014;4(3):e19529.
- Brummett CM, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6):e170504.
- Cicero TJ, et al. The changing face of heroin use in the United States a retrospective analysis of the past 50 years. JAMA Psychiatry. 2014;71(7):821-6.
- Ringsdorf WM, Cheraskin E. Vitamin C and human wound healing. Oral Surgery, Oral Med Oral Pathol. 1982;53(3):231-6.
- Danielski LG, et al. Preoperative vitamin C supplementation improves colorectal anastomotic healing and biochemical parameters in malnourished rats. Int J Colorectal Dis. 2016;31(11):1759-66.
- MacKay D, Miller AL. Nutritional support for wound healing. Altern Med Rev. 2003;8(4):359-77.
- Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care. 2010;13(6):669-76.
- Nakano K, Suzuki N. Stress-induced change in tissue levels of ascorbic acid and histamine in tats. J Nutr. 1984;114(9):1602-8.
- Carr AC, et al. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Front Oncol. 2014;4(OCT):283.
- Murata A, et al. Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate. Int J Vitam Nutr Res Suppl. 1982;23:103-13.
- Yeom CH, et al. Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci. 2007;22(1):7.
- Takahashi H, et al. High-dose intravenous vitamin C improves quality of life in cancer patients. Pers Med Universe. 2012;1(1):49-53.
- Mercadante S, Fulfaro F. World Health Organization guidelines for cancer pain: a reappraisal. Ann Oncol. 2005;16:132-5.
- Cameron E, Campbell A. The orthomolecular treatment of cancer II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact. 1974;9(4):285-315.
- Pinkerton E, et al. An open-label pilot study of oral vitamin C as an opioid-sparing agent in patients with chronic pain secondary to cancer. Support Care Cancer. 2017;25(2):341-3.
- Volkow ND, McLellan AT. Opioid abuse in chronic pain — misconceptions and mitigation strategies. N Engl J Med. 2016;374(13):1253-63.
- Højsted J, Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain. 2007;11(5):490-518.
- Johannes CB, et al. The prevalence of chronic pain in United States adults: results of an internet-based survey. J Pain. 2010;11(11):1230-9.
- Schencking M, et al. Intravenous vitamin C in the treatment of shingles: results of a multicenter prospective cohort study. Med Sci Monit. 2012;18(4).
- Chen JY, et al. Plasma vitamin C is lower in postherpetic neuralgia patients and administration of vitamin C reduces spontaneous pain but not brush-evoked pain. Clin J Pain. 2009;25(7):562-9.
- Kim MS, et al. A study of intravenous administration of Vitamin C in the treatment of acute herpetic pain and postherpetic neuralgia. Ann Dermatol. 2016;28(6):677-83.
- Schencking M, et al. Intravenous administration of vitamin C in the treatment of herpetic neuralgia: two case reports. Med Schi Monit. 2010:CS58-61.
- Chen JY, et al. Treatment of postherpetic neuralgia with intravenous administration of vitamin C. Anesth Analg. 2006;103(6):1616-7.
- Zollinger PE, et al. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Jt Surg – Ser A. 2007;89(7):1424-31.
- Besse JL, et al. Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg. 2009;15(4):179-82.
- Cazeneuve JF, et al. Vitamin C and prevention of reflex sympathetic dystrophy following surgical management of distal radius fractures. Acta Orthop Belg. 2002;68(5):481-4.
- Stevermer JJ, Ewigman B. Give vitamin C to avert lingering pain after fracture. J Fam Pract. 2008;57(2):86-9.