Vitamin C Supplementation in Rheumatological Diseases: A Systematic Review

Aaron Lerner^{1, 2,} , Jozélio Freire de Carvalho^3, , Motti Haimi^{4, 5} and Carina Benzvi¹

¹Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Israel

²Ariel University, Ariel, Israel

³Núcleo de Pesquisa em Doenças Crônicas não Transmissíveis (NUPEN), School of Nutrition from the Federal University of Bahia, Salvador, Bahia, Brazil

⁴Health Systems Management Department, The Max Stern Yezreel Valley College, Emek Yezreel, Israel

⁵Meuhedet Healthcare Services - North District, Tel Aviv, Israel

Cite this paper:
Aaron Lerner, Jozélio Freire de Carvalho, Motti Haimi and Carina Benzvi. Vitamin C Supplementation in Rheumatological Diseases: A Systematic Review. International Journal of Celiac Disease. 2024; 12(1):22-27. doi: 10.12691/ijcd-12-1-5

Abstract

Vitamin C (VC) is a potent antioxidant that was tested in a few rheumatic diseases. However, no updated systematic review is available in the literature. PubMed/MEDLINE, EMBASE, and Scielo were searched for articles on VC and rheumatologic diseases between 1966 and March 2023. Eight articles were found, including 227 patients. The investigated diseases were fibromyalgia (n=2), rheumatoid arthritis (n=2), systemic lupus erythematosus (n=1), antiphospholipid syndrome (n=1), Kawasaki disease (n=1) and vasculitis (Wegener’s granulomatosis and microscopic polyangiitis) (n=1). Age varied from 7.1 to 53.5±2.7 years old, and female gender ranged from 50% to 100% in the included articles. Disease duration ranged from 10.2 to 14 ± 8 years. VC dosage ranged from 133 mg to 3,000 mg/day. Concerning outcomes, the fibromyalgia studies showed an improvement in clinical and laboratory parameters. Interestingly, one study in RA showed a significant decrease in disease activity after VC. The other studies showed an improvement in these oxidant levels. Specifically, the Kawasaki disease article showed an improvement in vasodilation after intravenous VC injection; while the lupus study did not observe this benefit. Vitamin C is a safe therapy for various rheumatologic diseases. The improved subjective complaints, objective signs and laboratory parameters are promising. However, reconfirmation in more well-controlled, double-blind, cross-over studies, is highly needed.

Keywords:
Vitamin C anti-oxidants anti-inflammatory rheumatoid arthritis fibromyalgia

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Öztürk, H.S., Çimen, M.Y.B., Çimen, Ö.B., Kaçmaz, M. and Durak, I., "Oxidant/antioxidant status of plasma samples from patients with rheumatoid arthritis", Rheumatology international, 19(1–2),35–7,1999. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/10651080/.
[2]	Mason, S.A., Trewin, A.J., Parker, L. and Wadley, G.D., "Antioxidant supplements and endurance exercise: Current evidence and mechanistic insights", Redox biology, 352020 Aug. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/32127289/.
[3]	Kaźmierczak-Barańska, J., Boguszewska, K., Adamus-Grabicka, A. and Karwowski, B.T., "Two Faces of Vitamin C-Antioxidative and Pro-Oxidative Agent", Nutrients, 12(5) 2020 May. cited 2023 Jul 18; Available from: https:// pubmed.ncbi.nlm.nih.gov/ 32455696/.
[4]	Brzezińska, O., Styrzyński, F., Makowska, J. and Walczak, K., "Role of Vitamin C in Prophylaxis and Treatment of Gout-A Literature Review", Nutrients, 13(2),1–20,2021 Feb. cited 2023 Jul 18; Available from: https:// pubmed.ncbi. nlm.nih.gov/33671646/.
[5]	Colletti, A. and Cicero, A.F.G., "Nutracveutical Approach to Chronic Osteoarthritis: From Molecular Research to Clinical Evidence", International journal of molecular sciences, 22(23) 2021 Dec. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/34884724/.
[6]	Juraschek, S.P., Miller, E.R. and Gelber, A.C., "Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials", Arthritis care & research, 63(9),1295–306,2011 Sep. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/21671418/.
[7]	Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., et al., "The PRISMA 2020 statement: an updated guideline for reporting systematic reviews", BMJ (Clinical research ed), 3722021 Mar. cited 2023 Jul 9; Available from: https://pubmed.ncbi.nlm.nih.gov/33782057/.
[8]	Naziroǧlu, M., Akkuş, S., Soyupek, F., Yalman, K., Çelik, Ö., Eriş, S., et al., "Vitamins C and E treatment combined with exercise modulates oxidative stress markers in blood of patients with fibromyalgia: a controlled clinical pilot study", Stress (Amsterdam, Netherlands), 13(6),498–505,2010 Nov. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/20666654/.
[9]	Ali, A., Njike, V.Y., Northrup, V., Sabina, A.B., Williams, A.L., Liberti, L.S., et al., "Intravenous micronutrient therapy (Myers’ Cocktail) for fibromyalgia: a placebo-controlled pilot study", Journal of alternative and complementary medicine (New York, NY), 15(3),247–57,2009 Mar. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/19250003/.
[10]	Bae, S.C., Jung, W.J., Lee, E.J., Yu, R. and Sung, M.K., "Effects of antioxidant supplements intervention on the level of plasma inflammatory molecules and disease severity of rheumatoid arthritis patients", Journal of the American College of Nutrition, 28(1), 56–62,2009 Feb. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/19571161/.
[11]	Jaswal, S., Mehta, H.C., Sood, A.K. and Kaur, J., "Antioxidant status in rheumatoid arthritis and role of antioxidant therapy", Clinica Chimica Acta, 338(1–2),123–9,2003. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/14637276/.
[12]	Tam, L.S., Li, E.K., Leung, V.Y.F., Griffith, J.F., Benzie, I.F.F., Lim, P.L., et al., "Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: A double blind, placebo controlled pilot study", Journal of Rheumatology, 32(2),275–82,2005.
[13]	Ferro, D., Saliola, M., Meroni, P.L., Valesini, G., Caroselli, C., Praticó, D., et al., "Enhanced monocyte expression of tissue factor by oxidative stress in patients with antiphospholipid antibodies: effect of antioxidant treatment", Journal of thrombosis and haemostasis : JTH, 1(3),523–31,2003 Mar. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/12871461/.
[14]	Deng, Y.-B., Xiang, H.-J., Chang, Q. and Li, C.-L., "Evaluation by high-resolution ultrasonography of endothelial function in brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C", Circulation journal : official journal of the Japanese Circulation Society, 66(10),908–12,2002 Oct. cited 2023 Jul 18; Available from: https:// pubmed.ncbi. nlm.nih.gov/12381083/.
[15]	Harper, L., Nuttall, S.L., Martin, U. and Savage, C.O.S., "Adjuvant treatment of patients with antineutrophil cytoplasmic antibody-associated vasculitis with vitamins E and C reduces superoxide production by neutrophils", Rheumatology (Oxford, England), 41(3),274–8,2002. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/11934963/.
[16]	Sarban, S., Kocyigit, A., Yazar, M. and Isikan, U.E., "Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis", Clinical biochemistry, 38(11),981–6,2005 Nov. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/16150434/.
[17]	Blake, D.R., Unsworth, J., Outhwaite, J.M., Morris, C.J., Merry, P., Kidd, B.L., et al., "Hypoxic-reperfusion injury in the inflamed human joint", Lancet (London, England), 1(8633),289–93,1989 Feb. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/2563454/.
[18]	Surh, Y.J., Kundu, J.K., Na, H.K. and Lee, J.S., "Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals", The Journal of nutrition, 135(12 Suppl)2005. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/16317160/.
[19]	Kirby, B.S., Voyles, W.F., Simpson, C.B., Carlson, R.E., Schrage, W.G. and Dinenno, F.A., "Endothelium-dependent vasodilatation and exercise hyperaemia in ageing humans: Impact of acute ascorbic acid administration", Journal of Physiology, 587(9),1989–2003,2009.
[20]	Crecelius, A.R., Kirby, B.S., Voyles, W.F. and Dinenno, F.A., "Nitric oxide, but not vasodilating prostaglandins, contributes to the improvement of exercise hyperemia via ascorbic acid in healthy older adults", American journal of physiology Heart and circulatory physiology, 299(5)2010 Nov. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/20817831/.
[21]	Deng, Y. Bin, Li, T.L., Xiang, H.J., Chang, Q. and Li, C.L., "Impaired endothelial function in the brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C", The Pediatric infectious disease journal, 22(1),34–9,2003 Jan. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/12544406/.
[22]	Sabri, M.R., Tavana, E.N., Ahmadi, A. and Mostafavy, N., "Does Vitamin C improve endothelial function in patients with Kawasaki disease?", Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 20(1),32,2015 Jan.; Available from: /pmc/articles/PMC4354062/.
[23]	Khojah, H.M., Ahmed, S., Abdel-Rahman, M.S. and Hamza, A.B., "Reactive oxygen and nitrogen species in patients with rheumatoid arthritis as potential biomarkers for disease activity and the role of antioxidants", Free radical biology & medicine, 97,285–91,2016 Aug. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/27344969/.
[24]	Vollbracht, C. and Kraft, K., "Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C", Frontiers in pharmacology, 132022 Apr. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/35571085/.
[25]	Spoelstra-De Man, A.M.E., Elbers, P.W.G. and Oudemans-Van Straaten, H.M., "Vitamin C: should we supplement?", Current opinion in critical care, 24(4),248–55,2018 Aug. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/29864039/.
[26]	Berger, M.M. and Oudemans-Van Straaten, H.M., "Vitamin C supplementation in the critically ill patient", Current opinion in clinical nutrition and metabolic care, 18(2),193–201,2015 Mar. cited 2023 Jul 18; Available from: https:// pubmed.ncbi. nlm.nih.gov/25635594/.
[27]	Aisa-Álvarez, A., Pérez-Torres, I., Guarner-Lans, V., Manzano-Pech, L., Cruz-Soto, R., Márquez-Velasco, R., et al., "Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System", Cells, 12(9)2023 May. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/37174730/.
[28]	Navidhamidi, M., Nazari, A., Dehghan, S., Ebrahimpour, A., Nasrnezhad, R. and Pourabdolhossein, F., "Therapeutic Potential of Combined Therapy of Vitamin A and Vitamin C in the Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats", Molecular neurobiology, 59(4),2328–47,2022 Apr. cited 2023 Jul 18; Available from: https:// pubmed.ncbi. nlm.nih.gov/35072933/.
[29]	Ghalibaf, M.H.E., Kianian, F., Beigoli, S., Behrouz, S., Marefati, N., Boskabady, M., et al., "The effects of vitamin C on respiratory, allergic and immunological diseases: an experimental and clinical-based review", Inflammopharmacology, 31(2),653–72,2023 Apr. cited 2023 Jul 18; Available from: https:// pubmed.ncbi.nlm. nih.gov/36849854/.
[30]	Bernardo, D., Martínez-Abad, B., Vallejo-Diez, S., Montalvillo, E., Benito, V., Anta, B., et al., "Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in coeliac disease patients", Allergologia et immunopathologia, 40(1),3–8,2012 Jan. cited 2023 Jul 18; Available from: https://pubmed.ncbi.nlm.nih.gov/21420224/.