Antioxidants and Cancer
The use of antioxidants in cancer research and treatment has been debated over the years. In humans, there is general agreement that a diet rich in large quantities of plants with high levels of antioxidants is associated with a lower incidence of cancer. Research in the past, especially from Japan and Eastern Europe, involving the use of multiple antioxidants in the treatment of cancer generally, showed improved quality of life and longer survival times.
A CLOSER LOOK AT SPECIFIC ANTIOXIDANTS
Lycopene and resveratrol are two plant-derived antioxidants that can play a large part in cancer therapy.
RESVERATROL inhibits telomerase in cancer cells, but not in normal cells. Normally, telomeres (at the ends of chromosomes) shorten with each cell division. Eventually, a limit is reached and the cell will die. Telomerase in cancer cells replaces the shortened part of the telomere, and allows cancer cells to avoid this method of cell death. With telomerase inhibited, cancer cell telomeres shorten with each division and cannot avoid this means of cell death.1
LYCOPENE induces apoptosis. It regulates and normalizes the effect of IGF-1R (which is anti-apoptotic, allowing cancer cells to live indefinitely). With insulin, lycopene also processes glucose; cancer cells process far more glucose than normal cells. Blocking the activity of IGF-1R can help slow down the metabolism of cancer cells.
Resveratrol also blocks anti-apoptotic IGF-1R and, with proanthocyanidin (grape seed extract – another antioxidant) is also anti-angiogenic. This helps decrease the blood supply available to cancer cells.2
Antioxidants have also been connected with increased mortality of GI cancers.3 However, while another review showed they can help with chemotherapy toxicity, in other cases they were found have either no effect, or to interfere with the chemotherapy given for some kinds of cancers, especially in smokers.4
There can also be downsides to using antioxidants in treating cancer.
- Negative reviews began with a study of the use of beta carotene for the prevention and treatment of lung cancer. This was a gold standard, double blind, placebo controlled study enrolling large numbers of subjects; but it was stopped early because it became obvious that survival time was shorter in patients using beta carotene, than in those who did not use it.5 Part of the post-mortem procedure analyzed the lungs of deceased patients for beta carotene content. They were found to contain very high levels of the pro-oxidant form of beta carotene.
When antioxidants perform their function, they change to their pro-oxidant form. Those forms are not eliminated from the body as waste products. Instead, they are recycled back to their antioxidant form. Cycling back to the antioxidant form requires co-factors, and if those cofactors are not in place, the pro-oxidant forms increase. Pro-oxidants are pro-inflammatory, and inflammation increases the severity of cancer.
- More recently, the same problem occurred with a study of the use of vitamin E as the sole antioxidant as a potential aid in treating cancer. High doses of vitamin E were given to prostate cancer patients, without any co-factors, and the pro-oxidant form of E accumulated, shortening survival times for patients whose treatment included it. However, when vitamin E and selenium were given together, there was no such effect.6 Vitamin C is a primary co-factor in recycling vitamin E back to its antioxidant form. One wonders whether adding vitamin C to vitamin E plus selenium therapy would have shown an increase in survival time.
One study that used a combination of vitamins E and C did so by using both of them only every other day, which is not the way generally recommended by practitioners who use antioxidant therapy for cancer. As one would expect, this study showed no difference in the incidence of nine types of cancer.7
On the other hand, vitamin E has been shown to enhance the action of gemcitabine, a chemotherapeutic drug.8 When used with glutathione, it can decrease the severity of inflammation in oral mucosa occurring with chemotherapy and radiation.9 So the use of vitamin E in combination with other drugs or supplements has been shown to be beneficial.
- In contrast, increased selenium in the diet of elderly beagles resulted in less DNA damage in prostate cells and peripheral lymphocytes,10 and had a favorable effect on six markers associated with decreased cancer risk.11 One wonders whether the benefit comes from the fact that recommended dietary levels of selenium are too low (because of toxicity fears).
Users of nutritional supplements for various types of therapy have long advocated using natural sources of antioxidants, which contain a spectrum of each type. For example, using carrot powder as a source of carotenoids gives a full spectrum rather than just beta carotene alone. These practitioners would recommend this as the best use of antioxidants in cancer therapy – i.e. a broad spectrum of natural antioxidants would be better than one or two single antioxidants. This is an area that needs more research, but from some initial findings such as the vitamin E studies, one expects this to be true.
ANTIOXIDANTS AND CHEMOTHERAPY
The other thing to be aware of is the way in which antioxidants interact with chemotherapy and radiation therapy. If antioxidants are given on a daily basis along with chemotherapy, the result can be worse than when using chemotherapy alone.4
One of the ways that chemotherapy works is with the production of high levels of free radicals, which have a pro-oxidant effect. But chemotherapy is often given on a weekly, not a daily basis, and the level of free radicals rapidly diminishes, allowing non-cancerous cells a time to recover before the next dose.
If antioxidants are pulsed in between chemotherapy doses, they can help normal cells recover faster without decreasing the levels of free radicals produced by chemotherapy.
Antioxidants can be useful in cancer therapy, when used correctly. They are best used in combination rather than singly. When using them with chemotherapy, proper timing is important to get the best results.
1Shay JW, Bacchetti S. “A survey of telomerase activity in human cancer”. Eur J Cancer, 1997 Apr;33(5):787-91.
2S.M. Sagar, MD, D. Yance, MH, and R.K. Wong, MD. “Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer – Part 2”. Curr Oncol., 2006 June; 13(3): 99–107.
3Bjelakovic G, Nikolova D, Simonetti RG, et al. “Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements”. Aliment Pharmacol Ther, 2008; 28:689–703.
4Lawenda BD, Kelly KM, Ladas EJ, et al. “Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?” Journal of the National Cancer Institute, 2008; 100(11):773-783
5Cortes-Jofre M, Rueda JR, Corsini-Mun˜oz G, et al. “Drugs for preventing lung cancer in healthy people”. Cochrane Database Syst Rev, 2012, (10) CD002141.
6Klein EA, Thompson IM Jr, Tangen CM, et al. “Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)”. Journal of the American Medical Association, 2011; 306(14):1549–1556.
7Gaziano JM, Glynn RJ, Christen WG, et al. “Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial”. JAMA, 2009;301(1):52-62.
8Husain K, Francois RA, Yamauchi T, et al. “Vitamin E delta-tocotrienol augments the antitumor activity of gemcitabine and suppresses constitutive NF-kappaB activation in pancreatic cancer”. Mol Cancer Ther, 2011, 10:2363–72.
9Block KI, Koch AC, Mead MN, et al. “Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials”. Int J Cancer, 2008; 123:1227–39.
10Waters DJ, Shen S, Cooley DM, et al. “Eﬀects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate”. J Natl Cancer Inst, 2003; 95:237–41.
11Waters DJ, Shen S, Kengeri SS, et al. “Prostatic response to supranutritional selenium supplementation: comparison of the target tissue potency of selenomethionine vs. selenium-yeast on markers of prostatic homeostasis”. Nutrients, 2012; 4:1650–63.