One of the frequently made claims from the alternative medicine world is that vitamin C prevents cancer. Or cures cancer. Or does something with cancer. But what is the science behind vitamin C and cancer?
Of course, there are over 200-250 different cancers, each with a different etiology, pathophysiology and prognosis, so it’s rather incredible to believe that vitamin C has that much effect on any of those cancers. But the claims, and its adherents, persist despite the lack of robust evidence supporting these claims.
Frankly, there are just a handful of ways to prevent cancer. One of those ways, eat a balanced diet, implies consuming appropriate amounts of nutrients, like vitamin C I suppose. But does it mean that taking a handful of vitamin C tablets has some beneficial effect on cancer prevention or treatment? Well, let’s take a look.
Vitamin C and cancer – Linus Pauling
If there’s anyone responsible for the whole vitamin C and various diseases fad, it has got to be Linus Pauling, a two-time Nobel Prize winner (an extremely rare honor). By the 1960s, he had been convinced that massive doses of vitamins, a field now called orthomolecular medicine, considered an alternative medicine, could prevent a lot of diseases. He even pushed for orthomolecular psychiatry, advocating that “orthomolecular therapy, the provision for the individual person of the optimum concentrations of important normal constituents of the brain, may be the preferred treatment for many mentally ill patients.”
He also began making claims that mega-doses of vitamin C could be used to treat or prevent cardiovascular disease and the common cold. Despite the lack of robust evidence that it works, Pauling’s claims remain a standard of the alternative medicine world.
Pauling then moved into the world of vitamin C and cancer, claiming that it could treat or prevent cancer. He published two studies (here and here) that claimed that vitamin C increased survival by as much as four times (compared to untreated patients) in a group of 100 terminal patients.
The studies were roundly criticized by other researchers. An evaluation of Pauling’s researched found that the patient groups were actually different, which lead to a high amount of bias. The vitamin C group was actually less sick than the control group upon entering the study.
Furthermore, researchers at Mayo Clinic published a well controlled trial in 1979, along with another in 1985, which established that high-dose vitamin C was no better than placebo for treating cancer. Both studies concluded that there was no benefit to high-dose vitamin C for cancer.
Despite nearly total debunking of Pauling’s claims about vitamin C by legitimate scientific evidence, the legend persists. Part of this persistence is a result of boatloads of laboratory research out there that seems to hit the news every month.
Vitamin C and cancer – preclinical research
Preclinical research is that body of biomedical research that relies on animal or in vitro models. This type of primary research is generally of moderate quality on the hierarchy of biomedical research.
Only a small percentage of drugs (and let’s be clear, using megadoses of vitamin C is a drug) that show promise in preclinical research end up having any clinical utility. In fact, less than 13% of drugs that enter clinical trials ever receive FDA approval.
There is a tendency for the press to overstate the results from preclinical research, so we quickly translate a study that shows that vitamin C in a cell culture treats a particular study to the headline “Vitamin C cures cancer again.”
Recently, two studies (here and here) seem to indicate that vitamin C could prevent leukemia. To be fair, the NBC News article was careful in its presentation of the data, but it started the article with “Here’s another reason to make sure you’re eating plenty of vitamin C.”
First of all, these studies looked at a very specific type of leukemia where a mutation in the TET2 gene leads to certain cancers, including acute myeloid leukemia. Vitamin C mimics TET2 restoration, so it helps other cancer drugs attack the leukemia. And neither article suggested, or even hinted, that megadoses of vitamin C improved the effect of standard chemotherapy. All it said was that maintaining proper vitamin C levels through diet helped attack to the cancer.
The researchers did not say that the vitamin C treated the cancer directly. They did not say that it could prevent leukemia. They did not say mega doses of vitamin C would do anything.
The National Cancer Institute reviewed the most important preclinical studies, and I’m not sure there is any robust evidence that vitamin C, especially in megadoses, has any value.
Many studies showed that vitamin C enhances the effects of some chemotherapy drugs, again in animal and cell culture studies. However, and this is a critical however, there is a large amount of evidence that vitamin C has no effect. Or has a negative effect on many chemotherapy drugs.
But the only thing that matters regarding vitamin C and cancer are robust and well done clinical trials. All of these preclinical studies do not and cannot provide us with any clinical information that would tell an oncologist to suddenly use vitamin C in any therapy.
Vitamin C and cancer – clinical trials
As I mentioned before, clinical trials tell us whether a medical modality actually shows a benefit in human beings. And even better, systematic reviews, which compile the data from similar clinical trials, provide us the best quality evidence about the effectiveness of a potential medical treatment.
Below is a list of these clinical studies and reviews for various cancers that are of the highest quality:
- In a meta-review of 49 clinical trials involving nutrients and cancer, Schwingshackl et al. stated that “Vitamins D, C, and K; selenium; zinc; magnesium; and eicosapentaenoic acid showed no significant risk reduction for any of the outcomes.” In other words, these nutrients did not reduce the risk of cancer.
- In a meta-review of 51 studies, Fulan et al. found that there was no change in risk of breast cancer after consumption of vitamin C.
- In a systematic review and meta-analysis of 9 studies involving vitamin C, Papaioannou et al. concluded that vitamin C is “not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.” On the other hand, in a meta-review of observational studies, Yu et al. found a “limited association” between dietary vitamin C and colorectal cancer, but again, it is not robust data that would support an evidence based medicine decision about cancer therapy.
- In a systematic review of 14 studies of vitamin C and prostate cancer, Stratton and Godwin determined that, “there is no convincing evidence that the use of supplemental multivitamins or any specific vitamin affects the occurrence or severity of prostate cancer.”
- In a Cochrane Review of research on nutrients on lung cancer in healthy individuals, Cortés-Jofré et al. determined that “there is no evidence for recommending supplements of vitamins A, C, E, selenium, either alone or in different combinations, for the prevention of lung cancer and lung cancer mortality in healthy people.” However, another review stated that there may be a limited protective effect for vitamin C against lung cancer in smokers. But the authors clearly stated that the best protect effect was to stop smoking.
- Wilson et al. concluded that “the use of high-dose IV vitamin C (on any cancer) cannot be recommended outside of a clinical trial.”
Most individual clinical studies that examined the effect of vitamin C on a variety of cancers have been small in size and have had a very limited, if any, effect on the prognosis of the disease. The weakness of these types of studies contributes to an overall skepticism about any beneficial effect of vitamin C on cancer.
For example, in a 2014 Phase I clinical trial, Ma et al. evaluated the toxicities with combining IV vitamin C (ascorbate) with typical chemotherapy agents in ovarian cancer. Twenty-seven patients were randomly assigned to receive either chemotherapy alone or chemotherapy and IV vitamin C concurrently. They concluded that the addition of IV vitamin C was associated with reduced chemotherapy-related toxicities.
- Bad statistics that might lead to numerous false positives.
- The high amount of vitamin C delivered intravenously far exceeds the levels of chemotherapy used.
- The study was tiny and not randomized or blinded. According to Gorski, “there would have had to have been an enormous effect to produce a statistically significant effect on survival or progression in such a small study.”
- There was no difference in the two groups for the most severe forms of toxicity. In other words, their conclusion that vitamin C was associated with reduced chemotherapy-related toxicities was not really supported by the evidence.
Vitamin C and cancer is one of those alternative medicine icons that has never been shown to be supported by real scientific evidence.
Is there much evidence that vitamin C prevents cancer? Not much at all.
Is there much evidence that vitamin C can treat cancer? Again, there is mostly none.
To quote Dr. Gorski from the aforementioned article:
This latest highly unimpressive study being touted as evidence that high dose intravenous ascorbate/vitamin C therapy is anything other than a long run for a short slide is merely part of the campaign to insinuate quackademic medicine even more firmly into the mainstream than it has regrettably already succeeded in doing.
That’s about as clear as we can get regarding vitamin C and cancer. There’s not much there.
- Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z, Crane GM, Cowin BL, Bruner E, Murphy MM, Chen W, Spangrude GJ, Hu Z, DeBerardinis RJ, Morrison SJ. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017 Aug 21. doi: 10.1038/nature23876. [Epub ahead of print] PubMed PMID: 28825709.
- Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3685-9. PubMed PMID: 1068480; PubMed Central PMCID: PMC431183.
- Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4538-42. PubMed PMID: 279931; PubMed Central PMCID: PMC336151.
- Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski MT, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Martín MT, Guillamot M, Banh RS, Xu M, Figueroa ME, Dickins RA, Abdel-Wahab O, Park CY, Tsirigos A, Neel BG, Aifantis I. Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression. Cell. 2017 Aug 16. pii: S0092-8674(17)30868-1. doi: 10.1016/j.cell.2017.07.032. [Epub ahead of print] PubMed PMID: 28823558.
- Cortés-Jofré M, Rueda JR, Corsini-Muñoz G, Fonseca-Cortés C, Caraballoso M, Bonfill Cosp X. Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev. 2012 Oct 17;10:CD002141. doi: 10.1002/14651858.CD002141.pub2. Review. PubMed PMID: 23076895.
- Creagan ET, Moertel CG, O’Fallon JR, Schutt AJ, O’Connell MJ, Rubin J, Frytak S. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med. 1979 Sep 27;301(13):687-90. PubMed PMID: 384241.
- Fulan H, Changxing J, Baina WY, Wencui Z, Chunqing L, Fan W, Dandan L, Dianjun S, Tong W, Da P, Yashuang Z. Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression. Cancer Causes Control. 2011 Oct;22(10):1383-96. doi: 10.1007/s10552-011-9811-y. Epub 2011 Jul 15. PubMed PMID: 21761132.
- 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. PubMed PMID: 24500406.
- Moertel CG, Fleming TR, Creagan ET, Rubin J, O’Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med. 1985 Jan 17;312(3):137-41. PubMed PMID: 3880867.
- Papaioannou D, Cooper KL, Carroll C, Hind D, Squires H, Tappenden P, Logan RF. Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis. Colorectal Dis. 2011 Oct;13(10):1085-99. doi: 10.1111/j.1463-1318.2010.02289.x. Epub 2010 Apr 19. Review. PubMed PMID: 20412095.
- Ruano-Ravina A, Figueiras A, Freire-Garabal M, Barros-Dios JM. Antioxidant vitamins and risk of lung cancer. Curr Pharm Des. 2006;12(5):599-613. Review. PubMed PMID: 16472151.
- Schwingshackl L, Boeing H, Stelmach-Mardas M, Gottschald M, Dietrich S, Hoffmann G, Chaimani A. Dietary Supplements and Risk of Cause-Specific Death, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis of Primary Prevention Trials. Adv Nutr. 2017 Jan 17;8(1):27-39. doi: 10.3945/an.116.013516. Print 2017 Jan. Review. PubMed PMID: 28096125; PubMed Central PMCID: PMC5227980.
- Stratton J, Godwin M. The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis. Fam Pract. 2011 Jun;28(3):243-52. doi: 10.1093/fampra/cmq115. Epub 2011 Jan 27. Review. PubMed PMID: 21273283.
- Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP. Review of high-dose intravenous vitamin C as an anticancer agent.Asia Pac J Clin Oncol. 2014 Mar;10(1):22-37. doi: 10.1111/ajco.12173. Review. PubMed PMID: 24571058.
- Xu X, Yu E, Liu L, Zhang W, Wei X, Gao X, Song N, Fu C. Dietary intake of vitamins A, C, and E and the risk of colorectal adenoma: a meta-analysis of observational studies. Eur J Cancer Prev. 2013 Nov;22(6):529-39. doi: 10.1097/CEJ.0b013e328364f1eb. PubMed PMID: 24064545.
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