Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects
Open accessAbstract
BACKGROUND: Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown. METHODS AND FINDINGS: We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25 g/50 ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study. CONCLUSIONS: High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.
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Even very high doses of i.v. vitamin C (ranging from 1 to 200 g and given repeatedly) are apparently well tolerated in most patients.
“Interestingly, even very high doses of i.v. vitamin C (ranging from 1 to 200 g and given repeatedly) are apparently well tolerated in most patients [206].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [206]
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Cites
Complementary and alternative medicine use among adults: United States, 2002
Barnes, P. M., Powell‐Griner, E., McFann, K., & Nahin, R. L. (2004) · Seminars in Integrative Medicine · doi:10.1016/j.sigm.2004.07.003 · Cited by 2,176 · see citing works
Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance
Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3704 · Cited by 1,325 · see citing works
Self-citationChen, Q., Espey, M. G., Krishna, M. C., Mitchell, J. B., Corpe, C. P., Buettner, G. R., Shacter, E., & Levine, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506390102 · Cited by 1,075 · see citing works
Self-citationVitamin C pharmacokinetics: Implications for oral and intravenous use
Padayatty, S. J., Sun, H., Wang, Y., Riordan, H. D., Hewitt, S. M., Katz, A., Wesley, R. A., & Levine, M. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-7-200404060-00010 · Cited by 992 · see citing works
Self-citationKennedy, C. O. (1971) · British Homeopathic journal · doi:10.1016/s0007-0785(71)80027-3 · Cited by 976 · see citing works
Chen, Q., Espey, M. G., Sun, A. Y., Pooput, C., Kirk, K. L., Krishna, M. C., Khosh, D. B., Drisko, J., & Levine, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804226105 · Cited by 854 · see citing works
Self-citationCameron, E., & Pauling, L. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.10.3685 · Cited by 710 · see citing works
Chen, Q., Espey, M. G., Sun, A. Y., Lee, J.-H., Krishna, M. C., Shacter, E., Choyke, P. L., Pooput, C., Kirk, K. L., Buettner, G. R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702854104 · Cited by 676 · see citing works
Self-citationMoertel, C. G., Fleming, T. R., Creagan, E. T., Rubin, J., O'Connell, M. J., & Ames, M. M. (1985) · New England Journal of Medicine · doi:10.1056/nejm198501173120301 · Cited by 637 · see citing works
Creagan, E. T., Moertel, C. G., O'Fallon, J. R., Schutt, A. J., O'Connell, M. J., Rubin, J., & Frytak, S. (1979) · New England Journal of Medicine · doi:10.1056/nejm197909273011303 · Cited by 584 · see citing works
Criteria and recommendations for vitamin C intake
Levine, M. (1999) · JAMA · doi:10.1001/jama.281.15.1415 · Cited by 559 · see citing works
Self-citationA new recommended dietary allowance of vitamin C for healthy young women
Levine, M., Wang, Y., Padayatty, S. J., & Morrow, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171318198 · Cited by 496 · see citing works
Self-citationCameron, E., & Pauling, L. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.9.4538 · Cited by 476 · see citing works
Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
Hoffer, L. J., Levine, M., Assouline, S., Melnychuk, D., Padayatty, S. J., Rosadiuk, K., Rousseau, C., Robitaille, L., & Miller, W. H. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn377 · Cited by 375 · see citing works
Self-citationVerrax, J., & Calderón, P. B. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.016 · Cited by 232 · see citing works
Vitamin C Antagonizes the Cytotoxic Effects of Antineoplastic Drugs
Heaney, M. L., Gardner, J. R., Karasavvas, N., Golde, D. W., Scheinberg, D. A., Smith, E. A., & O’Connor, O. A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1490 · Cited by 229 · see citing works
Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency.
Rees, D. C., Kelsey, H., & Richards, J. D. (1993) · BMJ · doi:10.1136/bmj.306.6881.841 · Cited by 191 · see citing works
Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later
González, M. J., Miranda-Massari, J. R., Mora, E., Guzmán, A., Riordan, N. H., Riordan, H. D., Casciari, J. J., Jackson, J. A., & Román‐Franco, A. A. (2005) · Integrative Cancer Therapies · doi:10.1177/1534735404273861 · Cited by 136 · see citing works
Ascorbic Acid-Induced Hemolysis in G-6-PD Deficiency
CAMPBELL, G. D., STEINBERG, M. H., & BOWER, J. D. (1975) · Annals of Internal Medicine · doi:10.7326/0003-4819-82-6-810_1 · Cited by 134 · see citing works
Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent
Riordan, N. H., Riordan, H. D., Meng, X., Li, Y., & Jackson, J. A. (1995) · Medical Hypotheses · doi:10.1016/0306-9877(95)90137-x · Cited by 116 · see citing works
THE DIABETOGENIC EFFECT OF DEHYDROASCORBIC AND DEHYDROISOASCORBIC ACIDS
Patterson, J. (1950) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)56445-0 · Cited by 112 · see citing works
Bromley, J., Hughes, B. G. M., Leong, D. C., & Buckley, N. A. (2005) · Annals of Pharmacotherapy · doi:10.1345/aph.1e634 · Cited by 100 · see citing works
Acute Oxalate Nephropathy After Massive Ascorbic Acid Administration
Lawton, J. M. (1985) · Archives of Internal Medicine · doi:10.1001/archinte.1985.00360050220044 · Cited by 96 · see citing works
Reevaluation of Ascorbate in Cancer Treatment: Emerging Evidence, Open Minds and Serendipity
Padayatty, S. J., & Levine, M. (2000) · Journal of the American College of Nutrition · doi:10.1080/07315724.2000.10718941 · Cited by 94 · see citing works
Self-citationCanavese, C., Petrarulo, M., Massarenti, P., Berutti, S., Fenoglio, R., Pauletto, D., Lanfranco, G., Bergamo, D., Sandri, L., & Marangella, M. (2005) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2004.10.025 · Cited by 89 · see citing works
Wittes, R. E. (1985) · New England Journal of Medicine · doi:10.1056/nejm198501173120310 · Cited by 85 · see citing works
Acute oxalate nephropathy after a massive intravenous dose of vitamin C
WONG, K., Thomson, C. D., Bailey, R. R., McDIARMID, S., & Gardner, J. (1994) · Australian and New Zealand Journal of Medicine · doi:10.1111/j.1445-5994.1994.tb01477.x · Cited by 82 · see citing works
Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy
Cathcart, R. F. (1981) · Medical Hypotheses · doi:10.1016/0306-9877(81)90126-2 · Cited by 79 · see citing works
ASCORBIC ACID, CELL PROLIFERATION, AND CANCER
Cameron, E., & Rotman, D. (1972) · The Lancet · doi:10.1016/s0140-6736(72)90215-2 · Cited by 62 · see citing works
Losing and finding a way at C: New promise for pharmacologic ascorbate in cancer treatment
Levine, M., Espey, M. G., & Chen, Q. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.04.001 · Cited by 61 · see citing works
Self-citationVitamin C, the Common Cold and the Flu
Pauling, L. C. (1976) · Cited by 58 · see citing works
Vitamin C the Common Cold and the Flu
Whelan, E. (1977) · Nutrition Today · doi:10.1097/00017285-197701000-00008 · Cited by 50 · see citing works
Clinical and Experimental Experiences with Intravenous Vitamin C
Riordan, N. H., Riordan, H. D., Casciari, P., & Casciari, J. J. (2000) · Cited by 46 · see citing works
KLENNER, F. R. (2014) · Cited by 44 · see citing works
Cancer: the preconditioning factor in pathogenesis; a new etiologic approach.
Wj, M. (1954) · PubMed · Cited by 43 · see citing works
Ali, A., Njike, V. Y., Northrup, V. S., Sabina, A. B., Williams, A.-L., Liberti, L. S., Perlman, A. I., Adelson, H., & Katz, D. L. (2009) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2008.0410 · Cited by 41 · see citing works
Renal Failure Secondary to Massive Infusion of Vitamin C
McAllister, C. J. (1984) · JAMA · doi:10.1001/jama.1984.03350130016019 · Cited by 39 · see citing works
Renal failure secondary to massive infusion of vitamin C.
McAllister, C. J., Scowden, E. B., Dewberry, F. L., & Richman, A. (1984) · PubMed · Cited by 38 · see citing works
INACTIVATION OF POLIOMYELITIS VIRUS IN VITRO BY CRYSTALLINE VITAMIN C (ASCORBIC ACID)
Jungeblut, C. W. (1935) · The Journal of Experimental Medicine · doi:10.1084/jem.62.4.517 · Cited by 37 · see citing works
Patterson, J. (1951) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1951.165.1.61 · Cited by 37 · see citing works
The treatment of poliomyelitis and other virus diseases with vitamin C.
Fr, K. (1949) · PubMed · Cited by 37 · see citing works
Massive doses of vitamin C and the virus diseases
KLENNER, F. R. (1951) · PubMed · doi:10.5281/zenodo.10932887 · Cited by 37 · see citing works
de la Vega, L. P., Lieske, J. C., Milliner, D. S., Gonyea, J., & Kelly, D. G. (2004) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607104028006435 · Cited by 31 · see citing works
VITAMIN C IN RELATION TO EXPERIMENTAL POLIOMYELITIS
Sabin, A. B. (1939) · The Journal of Experimental Medicine · doi:10.1084/jem.69.4.507 · Cited by 30 · see citing works
Haemolysis induced by ascorbic acid in paroxysmal nocturnal haemoglobinuria
Iwamoto, N., Kawaguchi, T., Horikawa, K., Nagakura, S., Hidaka, M., Kagimoto, T., Takatsuki, K., & Nakakuma, H. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91195-9 · Cited by 30 · see citing works
Intravenous nutrient therapy: the "Myers' cocktail".
Gaby, A. R. (2002) · PubMed · Cited by 30 · see citing works
A FURTHER CONTRIBUTION TO VITAMIN C THERAPY IN EXPERIMENTAL POLIOMYELITIS
Jungeblut, C. W. (1939) · The Journal of Experimental Medicine · doi:10.1084/jem.70.3.315 · Cited by 27 · see citing works
FURTHER OBSERVATIONS ON VITAMIN C THERAPY IN EXPERIMENTAL POLIOMYELITIS
Jungeblut, C. W. (1937) · The Journal of Experimental Medicine · doi:10.1084/jem.66.4.459 · Cited by 21 · see citing works
Vitamins C and E and the Prevention of Preeclampsia
Briley, A. L., Poston, L., & Shennan, A. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmc061414 · Cited by 21 · see citing works
Massive doses of vitamin C and the virus diseases
Klenner, F. R. (1951) · doi:10.5281/zenodo.14495005 · Cited by 20 · see citing works
Acute hepatitis treated with high doses of vitamin C. Report of a case.
Calleja, H. B., & Brooks, R. H. (1960) · PubMed · Cited by 7 · see citing works
Ascorbic acid‐induced hemolysis of paroxysmal nocturnal hemoglobinuria erythrocytes
Iwamoto, N., Nakakuma, H., Ota, N., Shimokado, H., & Takatsuki, K. (1994) · American Journal of Hematology · doi:10.1002/ajh.2830470426 · Cited by 4 · see citing works
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [1]Nutrition Business Journal 2008 NBJ's Supplement Business Report 2008: An Analysis of Markets, Trends, Competition and Strategy in the U.S. Dietary Supplement Industry. Figure 3–33(Table 1); Figure 4–18 Boulder, CO Penton Media INC. Lifestyle Division. New Hope Natural Media
Cited by
Sorted by citations
Vitamins C and E: Beneficial effects from a mechanistic perspective
Traber, M. G., & Stevens, J. F. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.017 · Cited by 1,076 · see citing works
Ascorbic acid: Chemistry, biology and the treatment of cancer
Du, J., Cullen, J. J., & Buettner, G. R. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.06.003 · Cited by 1,071 · see citing works
Vitamin C: The known and the unknown and Goldilocks
Padayatty, S., & Levine, M. (2016) · Oral Diseases · doi:10.1111/odi.12446 · Cited by 753 · see citing works
Self-citationOxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities.
Rodrigo, R., Fernández-Gajardo, R., Gutiérrez, R., Matamala, J. M., Carrasco, R., Miranda-Merchak, A., & Feuerhake, W. (2013) · CNS and Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050015 · Cited by 621 · see citing works
Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination
Doseděl, M., Jirkovský, E., Macáková, K., Krčmová, L., Javorská, L., Pourová, J., Mercolini, L., Remião, F., Nováková, L., Mladěnka, P., et al. (2021) · Nutrients · doi:10.3390/nu13020615 · Cited by 553 · see citing works
Ma, Y., Chapman, J., Levine, M., Polireddy, K., Drisko, J., & Chen, Q. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007154 · Cited by 501 · see citing works
Self-citationVitamin C: A concentration-function approach yields pharmacology and therapeutic discoveries
Levine, M., Padayatty, S. J., & Espey, M. G. (2011) · Advances in Nutrition · doi:10.3945/an.110.000109 · Cited by 357 · see citing works
Self-citationMonti, D., Mitchell, E. P., Bazzan, A. J., Littman, S. J., Zabrecky, G. P., Yeo, C. J., Pillai, M. V., Newberg, A. B., Deshmukh, S., & Levine, M. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029794 · Cited by 270 · see citing works
Self-citationVitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis
Hemilä, H., & Chalker, E. (2019) · Nutrients · doi:10.3390/nu11040708 · Cited by 263 · see citing works
Wagner, A. E., Boesch, C., Breckwoldt, D., Schrader, C., Schmelzer, C., Döring, F., Hashida, K., Hori, O., Matsugo, S., & Rimbach, G. H. (2011) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-11-1 · Cited by 221 · see citing works
Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly
Shenoy, N. K., Creagan, E. T., Witzig, T. E., & Levine, M. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.07.014 · Cited by 207 · see citing works
Self-citationVitamin C for preventing and treating pneumonia
Hemilä, H., & Louhiala, P. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005532.pub3 · Cited by 203 · see citing works
Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19
Holford, P., Carr, A. C., Jovic, T. H., Ali, S. R., Whitaker, I. S., Marik, P. E., & Smith, A. D. (2020) · Nutrients · doi:10.3390/nu12123760 · Cited by 201 · see citing works
Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer
Espey, M. G., Chen, P., Chalmers, B. P., Drisko, J., Sun, A. Y., Levine, M., & Chen, Q. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.03.007 · Cited by 190 · see citing works
Self-citationPotential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence
Vissers, M. C. M., & Das, A. B. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00809 · Cited by 188 · see citing works
Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome
Boretti, A. A., & Banik, B. K. (2020) · PharmaNutrition · doi:10.1016/j.phanu.2020.100190 · Cited by 168 · see citing works
Kuiper, C., & Vissers, M. C. M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00359 · Cited by 163 · see citing works
The role of vitamin C in the treatment of pain: new insights
Carr, A. C., & McCall, C. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1179-7 · Cited by 160 · see citing works
Role of Vitamin C in Skin Diseases
Wang, K., Jiang, H., Li, W., Qiang, M., Dong, T., & Li, H. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00819 · Cited by 158 · see citing works
Oncometabolites‐driven tumorigenesis: From genetics to targeted therapy
Morin, A., Letouzé, É., Gimenez‐Roqueplo, A., & Favier, J. (2014) · International Journal of Cancer · doi:10.1002/ijc.29080 · Cited by 150 · see citing works
Liu, F., Zhu, Y., Zhang, J., Li, Y., & Peng, Z. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-039519 · Cited by 148 · see citing works
Vollbracht, C., & Kraft, K. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.899198 · Cited by 146 · see citing works
The Influence of Micronutrients in Cell Culture: A Reflection on Viability and Genomic Stability
Arigony, A. L. V., de Oliveira, I. M., Machado, M. S., Bordin, D. L., Bergter, L., Prá, D., & Henriques, J. A. P. (2013) · BioMed Research International · doi:10.1155/2013/597282 · Cited by 136 · see citing works
Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge
Carr, A. C., & Cook, J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01182 · Cited by 133 · see citing works
Intravenous Vitamin C and Cancer: A Systematic Review
Fritz, H., Flower, G., Weeks, L., Cooley, K., Callachan, M., McGowan, J., Skidmore, B., Kirchner, L., & Seely, D. (2014) · Integrative Cancer Therapies · doi:10.1177/1534735414534463 · Cited by 124 · see citing works
Hoffer, L. J., Robitaille, L., ZAKARIAN, R. J., Melnychuk, D., Kavan, P., Agulnik, J. S., Cohen, V., Small, D. I., & Miller, W. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120228 · Cited by 123 · see citing works
Ascorbic acid intake and oxalate synthesis
Knight, J. L., Madduma-Liyanage, K., Mobley, J. A., Assimos, D. G., & Holmes, R. P. (2016) · Urolithiasis · doi:10.1007/s00240-016-0868-7 · Cited by 119 · see citing works
Jacobs, C. M., Hutton, B., Ng, T. L., Shorr, R., & Clemons, M. J. (2015) · The Oncologist · doi:10.1634/theoncologist.2014-0381 · Cited by 114 · see citing works
Rodrigo, R., Prieto, J. C., & Castillo, R. L. (2012) · Clinical Science · doi:10.1042/cs20110663 · Cited by 111 · see citing works
Vitamin C: Overview and Update
Schlueter, A. K., & Johnston, C. S. (2011) · Journal of Evidence-Based Complementary & Alternative Medicine · doi:10.1177/1533210110392951 · Cited by 112 · see citing works
Shibuya, N., Humphers, J. M., Agarwal, M. R., & Jupiter, D. C. (2012) · The Journal of Foot & Ankle Surgery · doi:10.1053/j.jfas.2012.08.003 · Cited by 107 · see citing works
The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life
Carr, A. C., Vissers, M. C. M., & Cook, J. S. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00283 · Cited by 104 · see citing works
Nutritional perspectives for the prevention and mitigation of COVID-19
Akhtar, S., Das, J. K., Ismail, T., Wahid, M., Saeed, W., & Bhutta, Z. A. (2020) · Nutrition Reviews · doi:10.1093/nutrit/nuaa063 · Cited by 102 · see citing works
Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics
Parrow, N. L., Leshin, J. A., & Levine, M. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5372 · Cited by 101 · see citing works
Self-citationEvaluation of Vitamin C for Adjuvant Sepsis Therapy
Wilson, J. X. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5401 · Cited by 101 · see citing works
Intravenous vitamin C in the supportive care of cancer patients: A review and rational approach
Klimant, E., Wright, H., Rubin, D., Seely, D., & Markman, M. (2018) · Current Oncology · doi:10.3747/co.25.3790 · Cited by 99 · see citing works
Vitamin C and common cold-induced asthma: a systematic review and statistical analysis
Hemilä, H. (2013) · Allergy Asthma and Clinical Immunology · doi:10.1186/1710-1492-9-46 · Cited by 96 · see citing works
Vitamin C supplementation for the primary prevention of cardiovascular disease
Al-Khudairy, L., Flowers, N., Wheelhouse, R., Ghannam, O., Hartley, L., Stranges, S., & Rees, K. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011114.pub2 · Cited by 94 · see citing works
Aïm, F., Klouche, S., Frison, A., Bauer, T. W., & Hardy, P. P. (2017) · Orthopaedics & Traumatology Surgery & Research · doi:10.1016/j.otsr.2016.12.021 · Cited by 94 · see citing works
Chen, P., Yu, J., Chalmers, B., Drisko, J., Yang, J., Li, B., & Chen, Q. (2011) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e32834fd01f · Cited by 92 · see citing works
Self-citationPossible application of high-dose vitamin C in the prevention and therapy of coronavirus infection
Hoang, B. X., Shaw, G., Fang, W., & Han, B. (2020) · Journal of Global Antimicrobial Resistance · doi:10.1016/j.jgar.2020.09.025 · Cited by 90 · see citing works
Barakat, H., Aljutaily, T., Almujaydil, M. S., Algheshairy, R. M., Alhomaid, R. M., Almutairi, A. S., Alshimali, S. I., & Abdellatif, A. A. H. (2022) · Biomolecules · doi:10.3390/biom12101514 · Cited by 89 · see citing works
Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells
Lee, S. J., Jeong, J., Lee, I. H., Lee, J., Jung, J. H., Park, H. Y., Lee, D. H., & Chae, Y. S. (2019) · Anticancer Research · doi:10.21873/anticanres.13172 · Cited by 85 · see citing works
Herst, P. M., Broadley, K. W. R., Harper, J. L., & McConnell, M. J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.01.021 · Cited by 85 · see citing works
Kuhn, S.-O., Meissner, K., Mayes, L. M., & Bartels, K. (2018) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000000549 · Cited by 82 · see citing works
The Effects of High Concentrations of Vitamin C on Cancer Cells
Park, S. (2013) · Nutrients · doi:10.3390/nu5093496 · Cited by 80 · see citing works
Mikirova, N. A., Casciari, J. J., Riordan, N. H., & Hunninghake, R. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-191 · Cited by 80 · see citing works
The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome
Traber, M. G., Buettner, G. R., & Bruno, R. S. (2018) · Redox Biology · doi:10.1016/j.redox.2018.101091 · Cited by 79 · see citing works
Jaswal, V., Palanivelu, J., & Chidambaram, R. (2018) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2018.04.008 · Cited by 79 · see citing works
Vitamin C supplementation in the critically ill: A systematic review and meta-analysis
Zhang, M., & Jativa, D. F. (2018) · SAGE Open Medicine · doi:10.1177/2050312118807615 · Cited by 76 · see citing works
The potential role of vitamin C in empowering cancer immunotherapy
Bedhiafi, T., Inchakalody, V. P., Fernandes, Q., Mestiri, S., Billa, N., Shahab Uddin, M. S., Merhi, M., & Dermime, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112553 · Cited by 77 · see citing works
Treatment of Irradiated Mice with High-Dose Ascorbic Acid Reduced Lethality
Sato, T., Kinoshita, M., Yamamoto, T., Ito, M., Nishida, T., Takeuchi, M., Saitoh, D., Seki, S., & Mukai, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117020 · Cited by 74 · see citing works
Nielsen, T. K., Højgaard, M., Andersen, J. T., Poulsen, H. E., Lykkesfeldt, J., & Mikines, K. J. (2014) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12323 · Cited by 71 · see citing works
High-Dose Vitamin C in Advanced-Stage Cancer Patients
Zasowska‐Nowak, A., Nowak, P. J., & Ciałkowska-Rysz, A. D. (2021) · Nutrients · doi:10.3390/nu13030735 · Cited by 69 · see citing works
Kuiper, C., Dachs, G. U., Munn, D., Currie, M. J., Robinson, B. A., Pearson, J. F., & Vissers, M. C. M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00010 · Cited by 69 · see citing works
Novel Therapeutic Strategies for Traumatic Brain Injury: Acute Antioxidant Reinforcement
Fernández-Gajardo, R., Matamala, J. M., Carrasco, R. A., Gutiérrez, R., Melo, R., & Rodrigo, R. (2014) · CNS Drugs · doi:10.1007/s40263-013-0138-y · Cited by 68 · see citing works
Majidi, N., Rabbani, F., Gholami, S., Gholamalizadeh, M., Bourbour, F., Rastgoo, S., Hajipour, A., Shadnoosh, M., Akbari, M. E., Bahar, B., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.717816 · Cited by 68 · see citing works
High-dose intravenous vitamin C improves quality of life in cancer patients
Takahashi, H., Mizuno, H., & Yanagisawa, A. (2012) · Personalized Medicine Universe · doi:10.1016/j.pmu.2012.05.008 · Cited by 68 · see citing works
Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction
Rodrigo, R., Libuy, M., Feliú, F., & Hasson, D. (2013) · BioMed Research International · doi:10.1155/2013/437613 · Cited by 68 · see citing works
Campbell, E. J., Vissers, M. C. M., Wohlrab, C., Hicks, K. O., Strother, R. M., Bozonet, S. M., Robinson, B. A., & Dachs, G. U. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.08.027 · Cited by 67 · see citing works
Nephrotoxicity of Alternative Medicine Practice
Luyckx, V. A. (2012) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2012.04.005 · Cited by 67 · see citing works
Chen, S., Roffey, D. M., Dion, C.-A. B., Arab, A., & Wai, E. K. (2015) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000218 · Cited by 66 · see citing works
Oxalate Nephropathy and Intravenous Vitamin C
Cossey, L. N., Rahim, F., & Larsen, C. P. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2013.01.025 · Cited by 63 · see citing works
Plant-Based Diets Reduce Blood Pressure: A Systematic Review of Recent Evidence
Tomé‐Carneiro, J., & Visioli, F. (2023) · Current Hypertension Reports · doi:10.1007/s11906-023-01243-7 · Cited by 69 · see citing works
Ghalibaf, M. H. E., Kianian, F., Beigoli, S., Behrouz, S., Marefati, N., Boskabady, M., & Boskabady, M. H. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01169-1 · Cited by 60 · see citing works
The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity
Tian, W., Wang, Y., Xu, Y., Guo, X., Wang, B., Sun, L., Liu, L., Cui, F., Zhuang, Q., Bao, X., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.538157 · Cited by 59 · see citing works
Vuyyuri, S. B., Rinkinen, J., Worden, E., Shim, H.-K., Lee, S., & Davis, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067081 · Cited by 59 · see citing works
Rodrigo, R. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00093 · Cited by 59 · see citing works
Talib, W. H., Jum'Ah, D., Attallah, Z. S., Jallad, M. S., Kury, L. T. A., Hadi, R. W., & Mahmod, A. I. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1281879 · Cited by 57 · see citing works
Kawada, H., Kaneko, M., Sawanobori, M., Uno, T., Matsuzawa, H., Nakamura, Y., Matsushita, H., & Ando, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062717 · Cited by 55 · see citing works
Meena, S., Sharma, P., Gangary, S. K., & Chowdhury, B. (2014) · European Journal of Orthopaedic Surgery & Traumatology · doi:10.1007/s00590-014-1573-2 · Cited by 55 · see citing works
Chen, P., Stone, J., Sullivan, G., Drisko, J., & Chen, Q. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.031 · Cited by 55 · see citing works
Self-citationNielsen, T. K., Højgaard, M., Andersen, J. T., Jørgensen, N. R., Zerahn, B., Kristensen, B., & Henriksen, T. (2017) · Translational Andrology and Urology · doi:10.21037/tau.2017.04.42 · Cited by 55 · see citing works
Restoration of 5‐hydroxymethylcytosine by ascorbate blocks kidney tumour growth
Ge, G., Ding, P., Xu, Z., Guan, B., Xin, Z., He, Q., Zhou, Y., Li, X., Zhou, L., & Ci, W. (2018) · EMBO Reports · doi:10.15252/embr.201745401 · Cited by 55 · see citing works
Kim, M. S., Kim, D. J., Na, C. H., & Shin, B. S. (2016) · Annals of Dermatology · doi:10.5021/ad.2016.28.6.677 · Cited by 51 · see citing works
The Bioavailability of Vitamin C from Kiwifruit
Vissers, M. C. M., Carr, A. C., Pullar, J. M., & Bozonet, S. M. (2013) · Advances in food and nutrition research · doi:10.1016/b978-0-12-394294-4.00007-9 · Cited by 49 · see citing works
High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients
Giansanti, M., Karimi, T., Faraoni, I., & Graziani, G. (2021) · Cancers · doi:10.3390/cancers13061428 · Cited by 50 · see citing works
Vitamin C: From nutrition to oxygen sensing and epigenetics
Kietzmann, T. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102753 · Cited by 51 · see citing works
High-dose vitamin C management in dapsone-induced methemoglobinemia
Park, S.-Y., Lee, K.-W., & Kang, T.-S. (2013) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2013.11.036 · Cited by 47 · see citing works
Rodrigo, R., Prieto, J. C., Aguayo, R., Ramos, C., Puentes, Á., Gajardo, A. I. J., Panieri, E., Rojas-Solé, C., Lillo‐Moya, J., & Saso, L. (2021) · Molecules · doi:10.3390/molecules26185702 · Cited by 46 · see citing works
Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model
Kim, J., Cho, H.-S., Yang, H.-S., Jung, D.-J., Hong, S.-W., Hung, C., Lee, W. J., & Kim, D. (2012) · Immunobiology · doi:10.1016/j.imbio.2011.12.010 · Cited by 46 · see citing works
Pharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue
Kuiper, C., Vissers, M. C. M., & Hicks, K. O. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.09.023 · Cited by 45 · see citing works
Liu, Y., Pang, Y. K., Zhu, B., Uher, O., Caisová, V., Huynh, T., Taïeb, D., Vanova, K. H., Ghayee, H. K., Neužil, J., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2335 · Cited by 46 · see citing works
Self-citationEpigenetic Impacts of Ascorbate on Human Metastatic Melanoma Cells
Venturelli, S., Sinnberg, T. W., Berger, A., Noor, S., Levesque, M. P., Böcker, A., Niessner, H., Lauer, U. M., Bitzer, M., Garbe, C., et al. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00227 · Cited by 43 · see citing works
Vollbracht, C., Raithel, M., Krick, B., Kraft, K., & Hagel, A. (2018) · Journal of International Medical Research · doi:10.1177/0300060518777044 · Cited by 44 · see citing works
Bodeker, K. L., Smith, B. J., Berg, D., Chandrasekharan, C., Sharif, S., Fei, N. H., Vollstedt, S., Brown, H., Chandler, M. L., Lorack, A. C., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103375 · Cited by 47 · see citing works
O’Leary, B. R., Houwen, F. K., Johnson, C. L., Allen, B. G., Mezhir, J. J., Berg, D., Cullen, J. J., & Spitz, D. R. (2018) · Radiation Research · doi:10.1667/rr14978.1 · Cited by 40 · see citing works
Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study
Chen, P., Reed, G. A., Jiang, J., Wang, Y., Sunega, J. M., Dong, R., Ma, Y., Esparham, A. E., Ferrell, R., Levine, M. N., et al. (2022) · Clinical Pharmacokinetics · doi:10.1007/s40262-022-01142-1 · Cited by 40 · see citing works
Self-citationThe unpaved journey of vitamin C in cancer treatment
Chen, Q., Polireddy, K., Chen, P., & Dong, R. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0509 · Cited by 40 · see citing works
Self-citationVitamin C induces apoptosis in AGS cells via production of ROS of mitochondria
Lim, J. Y., Kim, D.-H., Kim, B. R., Jun, J., Yeom, J. S., Park, J. S., Seo, J., Park, C. H., Woo, H. O., Youn, H., et al. (2016) · Oncology Letters · doi:10.3892/ol.2016.5212 · Cited by 39 · see citing works
Bayır, A. G., & Kızıltan, H. Ş. (2015) · Nutrition and Cancer · doi:10.1080/01635581.2015.1055366 · Cited by 38 · see citing works
Systems biology of antioxidants
Andriantsitohaina, R., Duluc, L., Rodríguez, J., del Valle, L. G., Guevara-García, M., Simard, G., Soleti, R., Su, D., Velázquez‐Pérez, L., Wilson, J. X., et al. (2012) · Clinical Science · doi:10.1042/cs20110643 · Cited by 39 · see citing works
Rodrigo, R., Hasson, D., Prieto, J. C., Dussaillant, G., Ramos, C., León, L., Gárate, J., Valls, N., & Gormaz, J. G. (2014) · Trials · doi:10.1186/1745-6215-15-192 · Cited by 38 · see citing works
Vitamin C-induced oxalate nephropathy: a case report
Gurm, H., Sheta, M. A., Nivera, N., & Tunkel, A. R. (2012) · Journal of Community Hospital Internal Medicine Perspectives · doi:10.3402/jchimp.v2i2.17718 · Cited by 37 · see citing works
Massive doses of vitamin C and the virus diseases
KLENNER, F. R. (1951) · PubMed · doi:10.5281/zenodo.10932887 · Cited by 37 · see citing works
Vitamin C for preventing and treating tetanus
Hemilä, H., & Koivula, T. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006665.pub3 · Cited by 38 · see citing works
Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications
Halabi, I. E., Bejjany, R., Nasr, R., Mukherji, D., Temraz, S. N., Nassar, F. J., Darsa, H. E., & Shamseddine, A. I. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092752 · Cited by 36 · see citing works
Kim, K., Bae, O., Koh, S. H., Kang, S., Lim, K., Noh, J.-Y., Shin, S., Kim, I., & Chung, J. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv133 · Cited by 36 · see citing works
Wohlrab, C., Vissers, M. C. M., Phillips, E., Morrin, H., Robinson, B. A., & Dachs, G. U. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00574 · Cited by 35 · see citing works
Wald, E., Badke, C. M., Hintz, L. K., Spewak, M. B., & Sanchez-Pinto, L. N. (2021) · Pediatric Research · doi:10.1038/s41390-021-01673-6 · Cited by 34 · see citing works
- Authors
- Padayatty, S. J., Sun, A. Y., Chen, Q., Espey, M. G., Drisko, J., & Levine, M.
- Affiliations
- National Institutes of Health (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Levine, Mark
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-07-07
- Volume
- 5
- Issue
- 7
- Pages
- e11414
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2898816
- OpenAlex
- W2108045872
- Cited by
- 304
- References
- 53
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 17 · 2023: 15 · 2022: 25 · 2021: 25 · 2020: 27 · 2019: 15 · 2018: 23 · 2017: 13 · 2016: 21 · 2015: 20 · 2014: 24 · 2013: 29 · 2012: 16
- FWCI
- 49.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
- Keywords
- intravenous vitamin C, high-dose vitamin C, adverse effects, phlebitis, lethargy, cancer therapy, drug interactions, renal dysfunction, glucose-6-phosphate dehydrogenase deficiency
- MeSH terms
- Complementary Therapies, Ascorbic Acid, Data Collection, Humans, Injections, Intravenous, United States, United States Food and Drug Administration
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