Vitamin C and cancer prevention: a controversial role
Among other pharmacological actions, vitamin C (ascorbic acid) is credited with having a beneficial role in the prevention of various diseases, including cancer (1).
The relationship between vitamin C and cancer has been a subject of controversy since the early 70’s (2). A high intake of fresh fruits and vegetables (main dietary source of vitamin C) has been associated with a lower risk of developing most types of cancer. A research carried out in the late 90’s showed a significant reduction of the risk in patients with a daily intake of a minimum of 80-110 mg of vitamin C, which led to the recommendation to consume at least five portions of fruit and vegetables a day (2).
A review of more than 90 epidemiological studies revealed that the majority of them support the existence of a protective effect of vitamin C in the incidence of cancer, the odds ratio being approximately twice as high amongst those who ingest small amounts compared to those with a high intake of vitamin C. Studies show a protective effect on various cancers (breast, oral, stomach, esophagus, pancreas, lung, cervix and rectum), although significant effects were only found in a third part of the these. (1-3). However, it should be noted that the evidence regarding the possible role of vitamin C in cancer prevention comes from observational studies since there are no large-scale primary prevention trials available (3).
Vitamin C acts as a potent antioxidant. Its in vitro cytotoxic properties seem to be due to its capacity to generate hydrogen peroxide (H2O2), which would preferentially damage cancer cells, not affecting healthy cells. The reason for this selectivity remains unknown. Intravenous (IV) administration of high doses of vitamin C would be needed in order to achieve the necessary plasma concentrations required to generate cytotoxicity (1).
Early studies pointed out that high-dose vitamin C by intravenously infusion for ten days, followed by oral administration, increased the average survival of terminal cancer patients. However, on the one hand, there are methodological deficiencies, and on the other, these results have not been subsequently corroborated by other studies in which same doses of vitamin C were administered exclusively orally (1,2).
Clinical trials with vitamin C, phase I and II, are currently being carried out in patients with solid tumours. The recently published results of one of these trials do not show an objective anti-cancer response (4), in line with the data available in animal trials in which a decline but no suppression of the tumour growth has been observed (5).
Furthermore, administration of high doses of vitamin C is not free of adverse reactions. Thus, some cases of hemolysis have been reported in individuals with glucose-6-phosphate dehydrogenase deficiency and other cases related to stone formation in the urinary tract due to acidification of the urine (1).
It is known that part of the effectiveness of cancer treatments (chemotherapy, radiotherapy) is based on the production of oxidative stress. Several studies are available (in vitro and in vivo) which show that the use of vitamin C may increase the effectiveness of some of the anti-cancer therapies studied. By contrast, a study carried out with cancer cells previously treated with vitamin C shows a significant decrease of the effectiveness of some anti-cancer drugs, as vitamin C appears to protect the mitochondria of cancer cells (6). This could pose a risk since many cancer patients take vitamin and mineral supplements. Nevertheless, it seems that doses of vitamin C included in vitamin preparations should not affect the efficacy of chemotherapy results (1).
In conclusion, the relationship between vitamin C and cancer remains a subject of controversy. While there is evidence from epidemiological studies that support the existence of a protective effect, it appears that oral administration does not provide sufficient plasma concentrations to exert anti-cancer action and therefore intravenous administration is necessary. In addition, its cytotoxic activity has only been observed in vitro.
In any case, the effect caused by the intake of vitamin C supplements on cancer cells needs clarification, especially when used together with anti-cancer treatments related to oxidative stress.