Vitamin C may be useful as an adjunctive therapy for pain relief in specific patient groups

Vitamin C photographed using cross polarization

A new review (1) has demonstrated that ascorbic acid (vitamin C) can play a beneficial role as an adjunctive therapy to traditional pain relief treatments for many hospital patients. In addition, the review explores the mechanisms for these effects. Vitamin C has the benefit of being both safe and cost effective. 

The review reveals that many hospital patients have a plasma vitamin status that is less than adequate (i.e. <50 µmol/L). A particular benefit of vitamin C supplementation to this patient group is lowering the need for opioid analgesics – for example, morphine. This becomes particularly important for patients suffering acute pain following surgery or from cancer metastasis. 

Scurvy, the best-known result of vitamin C deficiency produces symptoms of musculoskeletal pain primarily due to bleeding into tissues (2). In most cases, the pain is resolved within two weeks of treatment with sufficient vitamin C. 

Hospital patients often have low plasma vitamin C levels (hypovitaminosis C) i.e.  < 23µmol/L (3). Once hospitalized, trauma, surgery and sepsis have been shown to accelerate depletion of plasma vitamin C levels (4). Cancer patients often have a lower vitamin status than their healthy equivalents. The majority of them have hypervitaminosis (abnormally high storage levels of vitamins), while many have vitamin deficiencies (5). 

For healthy individuals, vitamin C intakes of between 100 to 200mg/day are required to provide a saturated blood plasma status, as these levels are required to stabilize the plasma levels of surgical and critically ill patients (4). Conventional cancer chemotherapy is known to seriously deplete vitamin C levels. Pharmaceutical substances, such as aspirin, can also have an adverse effect (6). 

A recent meta-analysis showed that the daily administration of vitamin C can decrease the incidence of complex regional pain syndrome (CRPS) following distal fracture surgery (7). Patients with osteoarthritis that undergo joint replacement surgery have been shown to benefit from reduced pain if administered 500mg per day of vitamin C prophylactically for 50 days following the operation (8). It is worth noting that typically rheumatoid arthritis patients have plasma vitamin C levels that are only one third of their healthy equivalents. 

Viral infections can attack nerve tissue and cause intense pain e.g. shingles (Herpes zoster). An randomized controlled trial (RCT) of 87 patients treated with 5g vitamin C administered intravenously for five days showed significantly decreased pain scores after eight and 16 weeks following the treatment (9). 

Sadly, many studies that have examined the effects of vitamin C therapy on pain have failed to take into account the pharmokinetics, specifically that saturation of blood plasma occurs at an oral dose of just 200mg per day, but that steady state levels in the plasma rarely exceed 80 µmol/L because it is very effectively excreted by the kidneys! In practice, vitamin C has a half-life of only about two hours in the plasma, hence high dose administration is best done in several smaller doses over the day (10). 

It is often assumed that any benefit of vitamin C in the context of pain relief must be due to its ability to combat oxidative stress, but in fact it is mechanistically much more complicated than that.  For example, vitamin C has anti-inflammatory properties though the precise mechanism is unknown. It is also a co-factor in the synthesis of catecholamine neurotransmitters and also for dopamine β-hydroxylase (which converts dopamine to norepinephrine) (11). 

This is clearly a topic worthy of further research. 

1. Carr AC & McCall C; “The role of Vitamin C in the treatment of pain: new insights”: J Transl Med 2017; 15:77. DOI 10.1186/s12967-017-1179-7 . 
2. Fain O: “Musculoskeletal manifestations of scurvy”; Joint Bone Spine 2005; 72(2): 124-8.
3. Gan R, Eintracht S & Hoffer LJ; “Vitamin C deficiency in a university teaching hospital”; J Am Coll Nutr 2008; 27(3): 428-33.
4. Fukushima R & Yamazaki E; “Vitamin C requirement in surgical patients”; Curr Opin Clin Nutr Metab Care 2010; 13(6): 669-76.
5. Mayland CR, Bennett MI & Allan K; “Vitamin C deficiency in cancer patients”; Palliat Med 2005; 19(1): 17-20.
6. Marcus SL, Dutcher JP, Paletta E et al.; “Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin-2 and lymphokine-activated killer cells”; Cancer Res 1987; 47(15): 4208-12.
7. Shibuya N, Humphers JM, Agarwal MR et al.; “Efficacy and safety of high-dose Vitamin C on complex regional pain syndrome in extremity trauma and surgery-systematic review and meta-analysis”; J Foot Ankle Surg 2013: 52(1): 62-6.
8. Zollinger PE, Ellis ML, Unal H et al.; “Clinical outcome of cementless semi-constrained trapeziometacarpal arthroplasty and possible effect of vitamin C on the occurrence of complex regional pain syndrome”; Acta Orthop Belg 2008; 74(3); 317-22.
9. Kim MS, Kim DJ, Na CH et al,; “A study of intravenous administration of vitamin C in the treatment of acute herpetic pain in postherpetic neuralgia”; Ann Dermatol 2016; 28(6): 677-83.
10. Paddayatty SJ, Sun H, Wang Y et al.; “Vitamin C pharmacokinetics: implications for oral and intravenous use”; Ann Intern Med 2004; 140(7); 533-7.
11. Levine M; “Ascorbic acid specifically enhances dopamine beta mono oxygenase activity in resting and stimulated chromoffin cells”; J Biol Chem 1986; 261(16); 7347-56.