One of the most common questions I get from patients with cancer is whether or not IV vitamin C is helpful during cancer treatment. I think the answer is usually yes. I think it’s also worthwhile to clarify why it can be helpful and address some common misconceptions about how it does (and doesn’t) work.

 

IV vitamin C has been a topic of interest in the world of health for decades. Vitamin C was originally isolated in the 1920s, by the Hungarian biochemist Albert Szent-Gyorgy (who went on to win the Nobel prize for the discovery in 1937). He described its importance in preventing scurvy (hence all the sailors eating lemons, limes, and other citrus), as well as its broader role in metabolism.

 

Later, in the 1970s, vitamin C was popularized in large part by Linus Pauling, another giant in the field of medicine (he won the Nobel Prize in Chemistry in 1954 for work related to chemical bonding and molecular structure). He was an early advocate for using vitamin C to treatment a number of health conditions, including cancer, and wrote a book about its role in the common cold (“Vitamin C and the Common Cold”).

 

Vitamin C has several potential health benefits.

 

It’s an antioxidant. An antioxidant is a compound that protects cells in the body from damage by free radicals. Free radicals are unstable molecules that can cause damage to DNA, proteins, and lipids. This damage—called oxidative stress—is implicated in a variety of diseases, including cancer, cardiovascular disease, neurological diseases, and other aging-related health concerns. As an antioxidant, vitamin C is a scavenger of free radicals, helping clean up the inner environment of the body. It can also help in the regeneration of other antioxidants in the body, like Vitamin E.

 

It promotes collagen formation. In addition to its role as an antioxidant, it is essential for the synthesis of collagen, which is a protein that is a fundamental component of skin, tendons, ligaments, and blood vessels. Collagen is responsible for strength and elasticity in these tissues.

 

It enhances immune function. It does this in several ways. First, by promoting collagen formation, it ensures the integrity of skin and mucous membranes (the first lines of defense against pathogens). Second, it augments the effect of various immune cells (including neutrophils, macrophages, and lymphocytes).1  This effect also helps regulate the body’s inflammatory response (and is the reason vitamin C has become so popular for managing colds and other common infections).

 

It improves iron use – Vitamin C not only increases absorption of iron in the gut, it also increases the production of iron carriers (ferritin) in the body and reduces iron losses.2 This is why we often recommend patients take vitamin C with their iron supplement if they are iron deficient.

 

The dose of vitamin C needed depends on the goal. To prevent scurvy, for example, relatively low doses are needed—generally about 10 mg per day.3 To optimize immune function, higher doses (but not very high doses—100-200 mg per day) usually do the job.

 

This is where the vitamin C story gets really interesting. Once you’re taking in about 100-200 mg per day of vitamin C, your system gets saturated—any extra just gets excreted in the urine. This assumes, of course, that your body is actually absorbing all of the vitamin C you take in, which is not always the case if your gut function is impaired, if you have a chronic illness, or if a major oxidative stressor (like smoking) is present.4 This is why we often check vitamin C levels, and why some people do need higher doses—sometimes significantly higher.5 For many people, though, more is not better—taking more than 2 or 3 grams orally doesn’t increase the concentration in the body (and may have some mild side effects, like diarrhea).       

 

This brings us back to the question of vitamin C during cancer treatment. Early studies found that high doses of vitamin C could kill cancer cells. This research stalled for a number of years after several studies found that high doses of vitamin C (up to 10 grams per day) were not effective in treating cancer.6 Research has since found that how the vitamin C is given matters. When taken orally, vitamin C concentrations in the body are very closely controlled, with a maximum concentration in the blood of about 250 micromoles per liter. Concentrations needed to kill cancer are much, much higher than this— 5 millimole per liter or more, which is over twenty times higher than the concentration than can be achieved through oral doses.7 To reach these levels, vitamin C must be given intravenously. When given in this form, vitamin C has been found to be lethal to many types of cancer cells. There are several explanations for this, but what’s especially fascinating is that at much higher doses, vitamin C becomes a pro-oxidant, in addition to an antioxidant, and creates ROS within cancer cells. Specifically, very high doses of vitamin C appear to exploit three vulnerabilities in cancer cells. It’s worth noting that the following explanation is a bit of an oversimplification, and this mechanism is still a bit theoretical—for more in depth explanation, you can read the original paper in Nature Reviews here (or if it’s too much detail, feel free to skip it):8

 

1. Cancer cells are more sensitive to oxidative stress.9 Cancer cells have a higher metabolic rate than normal cells. While ROS can cause damage to a normal cell that may lead to the development of cancer, once the cell becomes cancerous, it becomes more sensitive to further damage, and actually increases biochemical pathways in itself that reduce the effects of ROS.10  Many cancer treatment approaches (like chemotherapy and radiation) exploit this increased sensitivity to oxidative stress, and vitamin C can as well. While there might theoretically be a risk for collateral damage by causing oxidative stress (which can certainly happen with chemotherapy), intravenous vitamin C appears to be selectively toxic to cancer cells because of the next two vulnerabilities.

2. Cancer cells have increased iron levels.11 Iron can interact with vitamin C to produce hydrogen peroxide and a hydroxide anion, both ROSs which are lethal to cancer cells. Vitamin C can also break down into hydrogen peroxide outside the cells, which can then diffuse into the cancer cells and react with the iron in these cells. Because cancer cells have more iron than normal cells, the hydrogen peroxide disproportionately affects the cancer cells. This hydrogen peroxide also increases the concentration of dehydroascorbic acid (DHA) in the cancer cell, which is important for the final vulnerability.

3. Cancer cells have increased expression of GLUT1. Cancer cells break down and use glucose at rates much higher than in regular cells. This happens through a metabolic reprogramming called the Warburg effect (which was initially described in the 1920s), a process crucial for tumor survival and growth.12 One of the ways this happens is through increases in GLUT1, a protein that transports glucose into cells. Vitamin C is oxidized to DHA. DHA is structurally very similar to glucose and is efficiently taken up by GLUT1. Once inside the cancer cell, DHA is converted back into vitamin C (ascorbate), using up important energy molecules (glutathione and NADPH), slowing growth. This process also uses antioxidants in the cell, producing ROSs that lead to further damage to the cancer cell.

 

This is a complex explanation, but the research is bearing it out. A number of recent studies have shown benefit in a variety of malignancies, 13,14, and many larger studies are being conducted.

 

IV vitamin C tends to be safe and well tolerated. In fact, it usually reduces symptoms associated with cancer and chemotherapy. A number of studies have shown significant reduction in concerns related to pain, nausea, appetite, fatigue, depression, sleep, dizziness, and bleeding when patients received IV vitamin C.15,16 Part of the symptom improvement may be due to correction of low vitamin C levels (which is much more common in patients with cancer) and antioxidant replenishment.  While generally safe, there are rare case reports of kidney injury (usually from oxalate, which is a product of vitamin C metabolism).17 In patients with G6PD deficiency (a condition that can cause fragile red blood cells), IV vitamin C can cause hemolytic anemia, so we screen for the condition before using IV vitamin C.

 

Some have argued that using vitamin C during cancer treatment might reduce the effectiveness of chemotherapy. The rationale for this is that many chemotherapy drugs are pro-oxidants that work creating oxidative stress (causing damage to DNA, proteins, and lipids). Giving an antioxidant could theoretically reduce the effectiveness of a pro-oxidant. While that may be true with a generic antioxidant, when given intravenously, we now know that vitamin C has a pro-oxidant effect against cancer cells, not an antioxidant effect. Vitamin C more likely enhances the effectiveness of chemotherapy rather than decrease it.

 

The take home point here is that I find the rationale for giving IV vitamin C as part of cancer treatment to be quite compelling. At low doses, there may be some benefit to cellular function, but the real excitement happens at high doses, which can only be achieved intravenously.

 

References

1.         Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. doi:10.3390/nu9111211

2.         Lane DJR, Richardson DR. The active role of vitamin C in mammalian iron metabolism: much more than just enhanced iron absorption! Free Radic Biol Med. 2014;75:69-83. doi:10.1016/j.freeradbiomed.2014.07.007

3.         Krebs HA. The Sheffield Experiment on the Vitamin C Requirement of Human Adults. Proc Nutr Soc. 1953;12(3):237-246. doi:10.1079/PNS19530054

4.         Jacob RA, Sotoudeh G. Vitamin C Function and Status in Chronic Disease. Nutr Clin Care. 2002;5(2):66-74. doi:10.1046/j.1523-5408.2002.00005.x

5.         Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care. 2010;13(6):669-676. doi:10.1097/MCO.0b013e32833e05bc

6.         Creagan ET, Moertel CG, O’fallon JR, et al. Failure of High-Dose Vitamin C (Ascorbic Acid) Therapy to Benefit Patients with Advanced Cancer: A Controlled Trial. N Engl J Med. 1979;301(13):687-690. doi:10.1056/NEJM197909273011303

7.         Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016;22(6):463-493. doi:10.1111/odi.12446

8.         Ngo B, Van Riper JM, Cantley LC, Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer. 2019;19(5):271-282. doi:10.1038/s41568-019-0135-7

9.         Schieber M, Chandel NS. ROS Function in Redox Signaling and Oxidative Stress. Curr Biol CB. 2014;24(10):R453-R462. doi:10.1016/j.cub.2014.03.034

10.       Chio IIC, Tuveson DA. ROS in Cancer: The Burning Question. Trends Mol Med. 2017;23(5):411-429. doi:10.1016/j.molmed.2017.03.004

11.       Guo Q, Li L, Hou S, et al. The Role of Iron in Cancer Progression. Front Oncol. 2021;11. Accessed August 16, 2023. https://www.frontiersin.org/articles/10.3389/fonc.2021.778492

12.       Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016;41(3):211-218. doi:10.1016/j.tibs.2015.12.001

13.       Monti DA, Mitchell E, Bazzan AJ, et al. 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

14.       Böttger F, Vallés-Martí A, Cahn L, Jimenez CR. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. J Exp Clin Cancer Res. 2021;40(1):343. doi:10.1186/s13046-021-02134-y

15.       Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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. Vivo Athens Greece. 2011;25(6):983-990.

16.       Carr AC, McCall C. The role of vitamin C in the treatment of pain: new insights. J Transl Med. 2017;15(1):77. doi:10.1186/s12967-017-1179-7

17.       Cossey LN, Rahim F, Larsen CP. Oxalate Nephropathy and Intravenous Vitamin C. Am J Kidney Dis. 2013;61(6):1032-1035. doi:10.1053/j.ajkd.2013.01.025