Intravenous high-dose Vitamin C therapy (IVC), is gaining interest as a natural therapy in the field of cancer, with a growing number of research studies released every year. This article goes through the benefits and risks from all available accessible evidence as of June 2023. At our clinic, a referral to an IV clinic for intravenous vitamin C therapy may sometimes be considered, however this must be balanced with the fact that research is mixed or limited for some types of cancers - which will be discussed further below. Furthermore, IVC is considered one of the most expensive options in the context of natural therapies. Each IVC infusion costs around $200, and usually 15-30 infusions are required.
Studies with Comparison Groups
It is best to start with studies that have comparison groups because it allows us to determine whether there is an improvement in overall outlook when using IVC compared to other patients in similar contexts who do not use IVC. This shows how much of a difference one might expect by adding IVC as a complementary therapy. In efforts to provide an unbiased approach - both negative and positive research will be discussed (with the best saved for last).
Terms to keep in mind:
Statistically significant: Determines if a particular finding is real and not just a random occurrence. It refers to the likelihood that an observed result or difference between groups is not due to chance alone.
Prostate Cancer
Summary: IVC may cause harm; statistically insignificant result
A 2023 study (50 patients) compared taking docetaxel plus IVC to patients who only took docetaxel chemotherapy.[1] It appears none of the findings reached statistical significance due to the size of the study, although significance was not specified for side effect frequency, which was greater in the IVC group: diarrhea (72% vs 19%) and anemia (47% vs 25%). The IVC group also had a trend towards shorter overall survival compared to the control group. A benefit to PSA was observed in 41% of patients in the IVC group and 33% of patients in the control group. Grade 1-2 and grade 3-4 adverse effects were both slightly more common in the IVC group.
Colorectal Cancer
Summary: May provide minimal benefit specifically in those with RAS-Mutation; statistically significant result
A 2022 study (442 patients) compared IVC plus conventional therapy in those with colorectal cancer to conventional therapy alone and found an overall survival of 20.7 months in the IVC group and 19.7 months in the comparison group.[2] Severe side effects occurred in 33.5% of patients in the IVC group compared to 30.3% of patients in the comparison group. Patients with the RAS mutation had significantly longer progression-free-survival however, 9.2 months compared to 7.8 months in the comparison group.
Lung Cancer
Summary: May provide some benefit; statistically insignificant result
A 2021 study (12 patients) on lung cancer compared IVC + alkalization therapy + chemotherapy to 15 patients with chemotherapy alone and found a median survival of 44.2 months in the IVC + alkalization + chemotherapy group compared to 17.7 months in the chemotherapy group. This is promising, however bear in mind the trial was too small to reach statistical significance. It is also difficult to determine whether it was the IVC and/or alkalization therapy that provided the potential benefit.[3]
Breast Cancer
Summary: May provide minimal benefit; statistically insignificant for survival, but significant for quality of life
An observational 2020 study (113 patients) found that patients with breast cancer taking IVC had a response rate of 48.6% compared to 40% in the control group. Response rate was defined as the proportion of patients who had complete or partial response.[4] There was a trend towards increased survival in the treatment group, meaning data did not reach statistical significance due to study size. Survival was 27 months in the IVC group versus 18 months in the placebo group.
A 2020 study (424 patients) compared patients with breast cancer taking IVC to placebo and found that patients using IVC had improved neutrophil-lymphocyte-ratio.[5] This is a marker that is said to affect overall prognosis and longevity. However, when they accounted for the stage and age of patients in the group, the results were no longer considered statistically significant.
An observational 2011 study in patients with breast cancer found side effects in patients taking IVC were nearly half as common compared to those who did not take IVC.[6] Side effects that were improved included nausea, loss of appetite, fatigue, depression, sleep disorders, and dizziness.
Ovarian Cancer
Summary: May provide some benefit; statistically insignificant results
A 2014 study on 27 patients with ovarian cancer found a trend towards improved survival and progression-free-survival.[7] The IVC group had 25.5 months until progression compared to 16.75 months until progression in the comparison group. Overall survival was higher as well, but specific numbers were not reported in the study. Minor side effects were less in the IVC group, but there was a very slight trend towards increased serious side effects.
Acute Myeloid Leukemia (AML)
Summary: May provide benefit; statistically significant result
A 2018 study in patients with AML found an overall survival of 15.3 months in those who supplemented with IVC, compared to 9.3 in the comparison group.[8]
Other Studies
Unfortunately none of the studies below had comparison groups so it is difficult to draw conclusions on whether IVC provided benefit. A second group of patients are needed to assess the difference the IVC makes.
A 2013 study was completed and none of the patients in the study demonstrated an objective antitumor response.[9] A 2015 study combined chemotherapy with IVC in patients with different types of cancer, and found 3 out of 14 patients had stable disease and improved energy.[10] A 2012 study on 14 patients with pancreatic cancer found an overall survival of 182 days.[11] A 2005 study reported one patient had stable disease after treatment with IVC.[12] A 2012 study on 60 patients found that quality of life scores improved by 38% in patients undergoing IVC.[13] A 2022 study showed some potentially promising results for those with bladder cancer.[14] The secondary phase of the study is currently underway.[15] A 2011 study on 9 pancreatic patients, but conclusions are difficult to make given the study size.[16]
Quality of Life
The 2011 study on breast cancer patients mentioned above found improvements in nausea, loss of appetite, fatigue, depression, sleep disorders, and dizziness.[17] A 2021 study found IVC might improve bone pain and fatigue.[18] A 2018 study in patients with pancreatic cancer found reduced toxicity to surrounding tissue in those undergoing radiation therapy.[19]
Side Effects of IVC
A 2005 study reported side effects such as nausea, swelling, dry mouth, dry skin, and kidney stones.[20] As a whole, research suggests side effects are relatively rare.
What Was the Average Benefit?
The average survival between the two groups from all the studies was 27 months in the IVC group versus 16 months in the comparison groups. When taking into account the size of each study as well, it was 21.8 in the IVC group versus 18.1 months in the comparison group (a difference of 3.7 months; 20% increase). There are few limitations to these calculations however. Most of the studies were in late stage or terminal cancer, with poor prognosis to start with. The result may be different in those with early stage cancers. These averages also do not take into account the prostate study, as data was limited due to the study being terminated early. Lastly, progression-free survival was used for the ovarian study in this calculation, due to limitations in data provided for overall survival.
To give an idea of the magnitude of these results - in comparison, a 2020 study found an average survival of 50.4 months in patients who reported maintaining a high amount of weekly exercise, compared to 35.5 months in patients who completed a low amount of exercise each week (a difference of about 15 months; 42% increase).[21] Another study found 46.4 months in those with a high amount of exercise compared to 27.1 in those with low (a difference of about 19 months).[22]
This data is saying exercise, which is completely free and accessible anytime, has two times greater impact on survival compared to IVC, which is expensive and time consuming. So why might someone still consider IVC? First, if your budget is flexible and you are looking for a comprehensive approach that integrates all therapies that have a reasonable potential of helping, while being considered relatively low risk with limited adverse effects. Second, not everyone is in a situation where they can perform large amounts of exercise or make significant lifestyle changes, and may prefer IVC. Third, those with already limited treatment options or who have types of cancers that don’t respond significantly to lifestyle changes, such as exercise. Exercise itself appears to have a very large impact on prognosis for only specific types of cancer, such as breast cancer - which both of the studies above had as their patient population.
Conclusion
There were two studies that found a statistically significant improvement in survival, which was the study in patients with colorectal cancer (in those with the RAS-Mutation) and those with acute myeloid leukemia. That being said, the other studies were never originally designed to be able to pick up statistical significance at the cutoff level that is generally accepted, because their sizes were too small. The research did however still pick up trends towards significance in other cancers. When there is a trend towards significance, it means the data is nearing a level of significance that is commonly accepted in the research community. In other words, the observed results above are becoming more likely to be a real effect rather than a result of random chance or variation. Larger sample sizes are needed to gather more evidence and draw stronger conclusions. Given that the trend was in favor of the IVC groups in most of the studies, overall it suggests that it was more likely that IVC provided benefit than providing no benefit at all.
They also found improvements in symptoms such as fatigue, pain, and nausea - all of which are important considerations as patients may find these quite debilitating. The above must all be considered in the context of a person’s budget as well as how much time they have available to do intravenous vitamin C sessions at a clinic. There are usually more affordable therapies that we would consider first, however IVC may be considered depending on how many complementary therapies a patient is comfortable adding on. At our clinic we try to stay within every person’s means and work with each individual to build a customized plan that is tailored to the unique characteristics of each case.
Disclaimer
The information provided above is for educational purposes only. It is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or qualified healthcare provider before attempting any natural therapies or making changes to your current treatment plan.
The content above is based on general knowledge and research available up to June 2023, and it may not reflect the most recent advancements or understanding in the field of cancer treatment. Individual responses to natural therapies can vary, and what works for one person may not work for another. Additionally, the effectiveness and safety of natural therapies can be influenced by various factors, including the type and stage of cancer, overall health condition, and individual circumstances.
It is crucial to approach natural therapies for cancer with caution and to consult with healthcare professionals who specialize in cancer care. They can provide personalized guidance based on your specific medical history and needs. Natural therapies should always be used as complementary approaches alongside evidence-based medical treatments, not as a substitute for conventional cancer therapies.
The authors, contributors, and publishers of this article are not liable for any adverse effects, complications, or damages arising from the use of information provided. Reliance on any information in this post is solely at your own risk. It is important to conduct thorough research, consider individual circumstances, and consult with healthcare professionals before making any decisions or embarking on any natural therapy regimen.
[1] Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.
Channing Judith Paller, Marianna Zahurak, Elisabeth I. Heath, William Kevin Kelly, Christopher J. Hoimes, Jason David Taksey, Catherine Handy Marshall, Mark Christopher Markowski, Pedro C. Barata, Michelle A. Rudek, Julie Nauroth, Lin Wang, Jennifer N. Durham, Mario A. Eisenberger, Michael Anthony Carducci, Samuel R. Denmeade, and Mark Levine
Journal of Clinical Oncology 2023 41:16_suppl, e17050-e17050. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e17050
[2] Wang F, He MM, Xiao J, Zhang YQ, Yuan XL, Fang WJ, Zhang Y, Wang W, Hu XH, Ma ZG, Yao YC, Zhuang ZX, Zhou FX, Ying JE, Yuan Y, Zou QF, Guo ZQ, Wu XY, Jin Y, Mai ZJ, Wang ZQ, Qiu H, Guo Y, Shi SM, Chen SZ, Luo HY, Zhang DS, Wang FH, Li YH, Xu RH. A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study). Clin Cancer Res. 2022 Oct 3;28(19):4232-4239. doi: 10.1158/1078-0432.CCR-22-0655. PMID: 35929990; PMCID: PMC9527503.
[3] Hamaguchi R, Narui R, Morikawa H, Wada H. Improved Chemotherapy Outcomes of Patients With Small-cell Lung Cancer Treated With Combined Alkalization Therapy and Intravenous Vitamin C. Cancer Diagn Progn. 2021 Jul 3;1(3):157-163. doi: 10.21873/cdp.10021. PMID: 35399313; PMCID: PMC8962782.
[4] A Retrospective Study of Gemcitabine and Carboplatin With or Without Intravenous Vitamin C on Patients With Advanced Triple-Negative Breast Cancer Junwen Ou, PhD1 , Xinyu Zhu, MS1, Hongyu Zhang, BS1, Yanping Du, MS1, Pengfei Chen, BS1, Junhua Wang, BS1, Xiufan Peng, MS1, Shuang Bao, BS1, Xinting Zhang, MS1, Tao Zhang, BS1, and Clifford L. K. Pang, PhD1 https://journals.sagepub.com/doi/pdf/10.1177/1534735419895591
[5]Park H, Kang J, Choi J, Heo S, Lee DH. The Effect of High Dose Intravenous Vitamin C During Radiotherapy on Breast Cancer Patients' Neutrophil-Lymphocyte Ratio. J Altern Complement Med. 2020 Nov;26(11):1039-1046. doi: 10.1089/acm.2020.0138. Epub 2020 Sep 1. PMID: 32876471.
[6] Intravenous Vitamin C Administration Improves Quality of Life in Breast Cancer Patients during Chemo-/Radiotherapy and Aftercare: Results of a Retrospective, Multicentre, Epidemiological Cohort Study in Germany
CLAUDIA VOLLBRACHT, BERTHOLD SCHNEIDER, VAN LEENDERT, GABRIELE WEISS, LEO AUERBACH and JOSEF BEUTH
[7] Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014 Feb 5;6(222):222ra18. doi: 10.1126/scitranslmed.3007154. PMID: 24500406.
[8] Zhao H, Zhu H, Huang J, Zhu Y, Hong M, Zhu H, Zhang J, Li S, Yang L, Lian Y, Wang S, Mao J, Chen Y, Li J, Qian S. The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and significantly improves overall survival in elderly patients with acute myeloid leukemia. Leuk Res. 2018 Mar;66:1-7. doi: 10.1016/j.leukres.2017.12.009. Epub 2018 Jan 2. PMID: 29331774.
[9] Stephenson CM, Levin RD, Spector T, Lis CG. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother Pharmacol. 2013 Jul;72(1):139-46. doi: 10.1007/s00280-013-2179-9. Epub 2013 May 14. PMID: 23670640; PMCID: PMC3691494.
[10] Hoffer LJ, Robitaille L, Zakarian R, Melnychuk D, Kavan P, Agulnik J, Cohen V, Small D, Miller WH Jr. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One. 2015 Apr 7;10(4):e0120228. doi: 10.1371/journal.pone.0120228. PMID: 25848948; PMCID: PMC4388666.
[11] Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794. doi: 10.1371/journal.pone.0029794. Epub 2012 Jan 17. PMID: 22272248; PMCID: PMC3260161.
[12] Riordan HD, Casciari JJ, González MJ, Riordan NH, Miranda-Massari JR, Taylor P, Jackson JA. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J. 2005 Dec;24(4):269-76. PMID: 16570523.
[13] High-dose intravenous vitamin C improves quality of life in cancer patients Author links open overlay panelHidenori Takahashi a, Haruyoshi Mizuno b, Atsuo Yanagisawa c
[14] Meeting Abstract | 2022 ASCO Annual Meeting to companion articles ARTICLE CITATION DOI: 10.1200/JCO.2022.40.16_suppl.e16540 Journal of Clinical Oncology - published online before print June 2, 2022 IV vitamin C with chemotherapy for cisplatin ineligible bladder cancer patients (CI-MIBC) first-stage analysis NCT04046094.
[16] Meeting Abstract | 2011 ASCO Annual Meeting I DOI: 10.1200/jco.2011.29.15_suppl.e14547 Journal of Clinical Oncology - published online before print May 20, 2011. PMID: 28020727 Intravenous vitamin C in combination with gemcitabine and erlotinib in subjects with metastatic pancreatic cancer. D. Monti , A. Newberg , S. J. Littman , M. Mathews , N. Lewis , E. P. Mitchell
[17] Intravenous Vitamin C Administration Improves Quality of Life in Breast Cancer Patients during Chemo-/Radiotherapy and Aftercare: Results of a Retrospective, Multicentre, Epidemiological Cohort Study in Germany
CLAUDIA VOLLBRACHT, BERTHOLD SCHNEIDER, VAN LEENDERT, GABRIELE WEISS, LEO AUERBACH and JOSEF BEUTH
[18] Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. High-Dose Vitamin C in Advanced-Stage Cancer Patients. Nutrients. 2021 Feb 26;13(3):735. doi: 10.3390/nu13030735. PMID: 33652579; PMCID: PMC7996511.
[19] Alexander MS, Wilkes JG, Schroeder SR, Buettner GR, Wagner BA, Du J, Gibson-Corley K, O'Leary BR, Spitz DR, Buatti JM, Berg DJ, Bodeker KL, Vollstedt S, Brown HA, Allen BG, Cullen JJ. Pharmacologic Ascorbate Reduces Radiation-Induced Normal Tissue Toxicity and Enhances Tumor Radiosensitization in Pancreatic Cancer. Cancer Res. 2018 Dec 15;78(24):6838-6851. doi: 10.1158/0008-5472.CAN-18-1680. Epub 2018 Sep 25. PMID: 30254147; PMCID: PMC6295907.
[20] Riordan HD, Casciari JJ, González MJ, Riordan NH, Miranda-Massari JR, Taylor P, Jackson JA. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J. 2005 Dec;24(4):269-76. PMID: 16570523.
[21] Delrieu L, Jacquet E, Segura-Ferlay C, Blanc E, Febvey-Combes O, Friedenreich C, Romieu G, Jacot W, Rios M, Heudel PE, Roemer-Becuwe C, Jouannaud C, Tredan O, Chaigneau L, Arnedos M, Orfeuvre H, Quenel-Tueux N, Jacquin JP, Ferrero JM, Moullet I, Abadie-Lacourtoisie S, Penault-Llorca F, Cox D, Bachelot T. Analysis of the StoRM cohort reveals physical activity to be associated with survival in metastatic breast cancer. Sci Rep. 2020 Jul 1;10(1):10757. doi: 10.1038/s41598-020-67431-6. PMID: 32612272; PMCID: PMC7329808.
[22] Palesh O, Kamen C, Sharp S, Golden A, Neri E, Spiegel D, Koopman C. Physical Activity and Survival in Women With Advanced Breast Cancer. Cancer Nurs. 2018 Jul/Aug;41(4):E31-E38. doi: 10.1097/NCC.0000000000000525. PMID: 28727578; PMCID: PMC5775062.