Supplementing With Antioxidants to Reduce the Risk of Cancer

According to an important study appearing in a recent issue of the European Journal of Nutrition, individuals who were taking antioxidant supplements at the start of the 11-year study period had a 48 percent reduction in the risk of cancer mortality. In addition, the risk of dying from all causes (all-cause mortality) was 42 percent lower among antioxidant supplement users. Of interest is the fact that taking only a basic multiple vitamin and mineral supplement (i.e., one not enriched with meaningful doses of antioxidants) did not confer any protection against cancer or all-cause mortality. These findings suggest that antioxidant supplements provide an important defense against cancer and death from other causes.¹

Most enlightened health care professionals are familiar with the experimental and preclinical studies showing that antioxidants quench and neutralize free radicals. Free radicals are unstable compounds that have been shown to damage DNA and increase risk of genetic mutations that can lead to cancer.² Human clinical trials have also shown that antioxidant supplements can improve immune function in older individuals.

Immune function is an important part of cancer prevention, as various immune cells either directly kill emerging cancer cells or modulate other immune cells that destroy cancer cells or prompt cancer cells to undergo apoptosis (programmed cell death).³ In addition, certain antioxidant vitamins exhibit other important anti-cancer properties, such as preserving gap junctions; inhibiting peptides (Bcl-2) that block apoptosis in cancer cells; sensitizing cytokine and cell membrane death receptors; inhibiting nuclear factor-kappa beta; down-regulating epidermal growth factor receptors, IGF-1 receptors, tyrosine kinase and phosphatidylinositol-3 kinase within cancer cells; as well as other anticancer mechanisms.^4-10

Diet, Lifestyle and Cancer

There is a marked overall difference in total cancer incidence between developed and developing countries. Cancers of the cervix, liver, stomach and mouth are the most common cancers in developing countries. In Iran, esophageal cancer is a major concern and in Southeast Asia, naspharyngeal cancer is disproportionately high. In developed countries, lung cancer, colon cancer, breast cancer, prostate cancer and bladder cancer are the leading cancers of clinical significance. (Skin cancer has the highest incidence of all cancers, but only melanomas present significant mortality risk.) Worldwide, the incidence of colon cancer varies 20-fold (highest in the U.S.; lowest in India), and breast cancer varies seven-fold (highest in U.S. Hawaiians; lowest in Israeli non-Jews). In Europe, total cancer rates are approximately 50 percent lower in Greece compared to Germany.¹¹

Evidence that this variation in cancer incidence is primarily a result of environmental and lifestyle factors, rather than genetic factors, is derived from several lines of investigation. First, studies of migrants moving from low- to high-risk areas have shown that migrants acquire the cancer incidence rate of their new country within a relatively short period of time. For example, colon cancer incidence can increase up to 20-fold within a single generation. Rising and declining incidence of tobacco-associated lung cancer has also been shown.

Forty years ago, the incidence of colon cancer in Japan was extremely low and rare. Today, Japanese men living in Japan have colon cancer rates twice as high as seen in the United Kingdom. Clearly, there has been too little time for the Japanese gene pool to change sufficiently to account for this sudden rise in colon cancer incidence. However, the affluence witnessed in Japan after World War II brought with it significant changes in terms of dietary patterns (e.g., more meat consumption, less fiber consumption) that mirrors the dietary patterns of much of the Western world, where colon cancer is the second-leading cause of cancer death (after lung cancer). A similar transformation has occurred in Hong Kong, where rates of colon, breast, prostate, endometrium and lung cancer have gone from being among the lowest in the world to incidence rates similar to that of the United States. Again, recently acquired affluence has brought about a Westernized shift in dietary and lifestyle practices in this region.¹¹

In regard to colon cancer in Japan, experts suggest the Japanese likely had a susceptibility to colon cancer that has been unmasked in recent years by their rapidly changing dietary patterns. Additional evidence to validate the contention that diet and lifestyle factors influence cancer risk more than genetic inheritance is highlighted by the finding that there is only a 10 percent cancer correlation among identical twins, even though both twin pairs stem from the same sperm and egg cell at conception. As such, in 90 percent of cases in which one of the twin pairs develops a particular cancer, the other twin pair does not, even though they share the same genetic blueprint.

Additionally, since the 1940s, many population studies have examined the association between diet and cancer. Taken together, the evidence suggests that 32-35 percent of cancers are attributed to nutrition, although the contribution of diet to specific types of cancer varies from as little as 10 percent for lung cancer to 80-90 percent for colorectal cancers. These studies suggest that nutrition appears to account for approximately 50 percent of breast cancers and 75 percent of prostate cancers.^11-12

What is under intense investigation at this time are studies examining individual dietary nutrients to help discern which dietary factors promote cancer and which may prevent cancer. There is broad consensus at this time that factors such as obesity and alcohol consumption increase cancer risk, while consumption of fruits and vegetables reduces cancer risk. Experts also agree that cancer arises from a complex interaction of genetic factors, individual metabolic characteristics and diet.

By themselves, common gene polymorphisms (variation in gene coding from one individual to another) that regulate metabolism of food constituents and/or frequently encountered environment agents (tobacco smoke, air pollution, asbestos exposure, etc.) are unlikely to confer large cancer risks, but they might do so in individuals who smoke, drink alcohol regularly, have a particular dietary pattern or are exposed to environmental agents to which they are susceptible.¹¹

The EPIC Study

To help decipher the complex relationship between diet and cancer, the European Prospective Investigation into Cancer and Nutrition (EPIC) Study was initiated in 1992. The EPIC Study has been following over 500,000 people living in 10 European countries (Denmark, France, Germany, Greece, Italy, The Netherlands, Norway, Spain, Sweden and the United Kingdom). A great deal of data including weight, height, lifestyle factors (including dietary behaviors) personal history and blood samples were collected at the beginning of the study, with periodic follow-up of these parameters collected on an ongoing basis.¹¹

In the 2011 EPIC Study update, published by Li, et al., in the European Journal of Nutrition,1 researchers showed impressive evidence for the use of antioxidant supplements in the prevention of cancer and all-cause mortality, as mentioned above. In the 2011 report, scientists based these findings on the analysis of 23,943 subjects, all free of cancer and heart disease at the start of the study.

After 11 years of monitoring, there were 1,101 deaths, of which 513 were from cancer and 264 from cardiovascular conditions. After controlling for other confounding variables, researchers noted that individuals who voluntarily started taking antioxidant supplements prior to the beginning of the study showed a significantly reduced risk of both cancer and all-cause mortality.¹ Researchers affiliated with the EPIC Study indicate that research such as this, which involves following a large number of subjects for many years, is the only valid method to evaluate the influence of diet, lifestyle and environmental factors on cancer risk.¹¹

Application for You and Your Patients

The EPIC Study suggests that antioxidant supplements have the potential to help reduce the risk of cancer, heart disease and all-cause mortality. Many experimental and preclinical studies have shown impressive anti-cancer and anti-heart-disease mechanisms through which antioxidants may reduce the risk of these and other diseases.

In my teaching capacity as a faculty member of the Integrative Cancer Therapy Fellowship Program (a one-year program offered to medical doctors through the American Academy of Anti-Aging Medicine, I have met many integrative cancer doctors who routinely incorporate the use of high doses of certain antioxidants into the treatment regimens of their cancer patients. They do so in accordance with experimental evidence, which has demonstrated the multimodal ways various antioxidants combat cancer (apoptosis, decreased proliferation, immune modulation, gap junction preservation, etc.). According to their experience, certain antioxidant supplements, along with other types of supplements and dietary practices, are an important aspect of cancer treatment for many patients.

The first landmark clinical study of its kind to show the importance of supplementation with cancer patients was published in Molecular Aspects of Medicine in 1994. Researchers showed that antioxidant supplements could play a key role in preventing the recurrence of breast cancer.¹³ Over the years, other studies have shown important anti-cancer benefits of antioxidant supplements when administered to patients with prostate cancer, cervical dysplasia, oral leukoplakia, atrophic gastritis, and other cancerous and precancerous conditions.^{7, 14-18}

In clinical practice, it is common to encounter patients who take a standard multiple vitamin and mineral each day for the purposes of increasing well-being and energy, and decreasing the risk of degenerative diseases. The EPIC Study suggests that unless a multiple vitamin / mineral supplement is enriched with meaningful doses of antioxidants, then it is unlikely to provide significant anti-cancer and anti-heart disease properties.¹ Accordingly, health practitioners should review the antioxidant dosages contained in the supplements their patients are taking and, when appropriate, direct them to supplements that contain meaningful concentrations of antioxidants (e.g., vitamin E succinate: 400 IU; vitamin C: 500-1,000 mg; selenium: 100-200 mcg; etc.). This one simple intervention may help reduce the patient`s risk of cancer by almost 50 percent and all-cause mortality by 42 percent over the ensuing decades, according to the finding of Li, et al.

References

1. Li K, Kaaks R, Linseisen J, Rohrmann S. Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg). European Journal of Nutrition. Published online July 22, 2011.
2. Lee KW, Lee HJ, Surh YJ, Lee CY. Vitamin C and cancer chemoprevention: reappraisal. Am J Clin Nutr, 2003;78(6):1074-1078
3. Thomas WR, Holt PG. Vitamin C and immunity: an assessment of the evidence. Clin Exp Immunol, 1978;32(2):370–379.
4. Shiau C, Huang J, Wang D, et al. Alpha tocopheryl succinate induces apoptosis in prostate cancer cells in part through inhibition of Bcl-xl/Bcl-2 function. J Biol Chem, 2006;281(17):11819-11825.
5. Israel K, Yu W, Sanders BG, Kline K. Vitamin E succinate induces apoptosis in human prostate cancer cells: role of Fas in vitamin E succinate-triggered apoptosis. Nutr Cancer, 2000;36(1):90-100.
6. Schindler R, Mentlin R. Flavonoids and vitamin E reduce the release of angiogenic peptide vascular endothelial growth factor from human tumor cells. Amer Soc for Nutr Jrnl, 2006;136:1477-1482.
7. Vaishampayan U, Hussain M, Seren S, et al. Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr & Cancer, 2007;59(1):1-7.
8. "Vitamin E Makes Prostate Cancer Cells Vulnerable." University of Rochester Medical Center news archives, March 28, 2002.
9. Wu K, Zhao Y, Li G, Yu W. c-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells. World J Gastroenterol, 2004;10(8):1110-1114.
10. Zhang Y, Ni J, Messing EM, et al. Vitamin E succinate inhibits function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. Proceedings of the National Academy of Sciences, 2002;99(11):7408-7413.
11. Bingham S, Riboli E. Diet and cancer – The European Prospective Investigation Into Cancer and Nutrition. Nature Reviews – Cancer, March 2004;4:206-215.
12. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Instit, 1981;66:1191-1308.
13. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in high risk patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med, 1994;15(Suppl):231S-40S.
14. Van Eenwyk J, Davis FG, Bowne PE. Dietary and serum carotenoids and cervical intraepithelial neoplasia. Int J Cancer, 1991;48:34-8.
15. Liu T, Soong SJ, Wilson NP, et al. A case control study of nutritional factors and cervical dysplasia. Cancer Epidemiol Biomark Prev, 1993;2(6):525-30.
16. Rembiasz K, budzynski A, Karcz D, et al. Multifocal atrophic gastritis: pathogenesis and therapeutic implications. Eur J Gastrenerol Hepatol, 2005;17(8):857-63.
17. Stich HF, Rosin MP, Vallejera MO. Reduction with vitamin A and beta-carotene administration of proportion of micronucleated buccal mucosal cells in Asian betel nut and tobacco chewers. Lancet, 1984;1:1204-6.
18. Garewal HS. Emerging role of beta-carotene and antioxidant nutrients in prevention of oral cancer. Arch Otolaryn, Head Neck Surg, 1995;121(2):141-4.