{"id":826,"date":"2018-01-03T08:23:12","date_gmt":"2018-01-03T08:23:12","guid":{"rendered":"http:\/\/seleniumfacts.com\/?p=826"},"modified":"2018-01-12T17:25:03","modified_gmt":"2018-01-12T17:25:03","slug":"selenium-antioxidants-combination-cancer","status":"publish","type":"post","link":"https:\/\/seleniumfacts.com\/index.php\/selenium-antioxidants-combination-cancer","title":{"rendered":"Selenium and antioxidants in combination against cancer"},"content":{"rendered":"<figure id=\"attachment_840\" aria-describedby=\"caption-attachment-840\" style=\"width: 300px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-840 size-medium\" src=\"http:\/\/seleniumfacts.com\/wp-content\/uploads\/2017\/12\/Antioxidants-300x202.png\" alt=\"\" width=\"300\" height=\"202\" srcset=\"https:\/\/seleniumfacts.com\/wp-content\/uploads\/2017\/12\/Antioxidants-300x202.png 300w, https:\/\/seleniumfacts.com\/wp-content\/uploads\/2017\/12\/Antioxidants.png 640w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption id=\"caption-attachment-840\" class=\"wp-caption-text\"><strong>Nothing is clear-cut, it seems.\u00a0 Yes, we want to eat fruits and berries for their antioxidant content.\u00a0 But, fruits and berries are full of the sugar called fructose.\u00a0 So, like everything else, we need to eat fruits and berries in moderation.\u00a0 In this report, I focus on studies of selenium and antioxidant combinations to prevent cancer.<\/strong><\/figcaption><\/figure>\n<p style=\"text-align: left;\"><strong>On the topic of cancer and selenium as a cancer chemo-preventive agent, we know some basic facts from published research:<\/strong><\/p>\n<ul>\n<li><strong>selenium prevents or delays tumor development in animals [Schrauzer]<\/strong><\/li>\n<li><strong>regions with low selenium intakes are regions with higher incidence of cancer [Schrauzer]<\/strong><\/li>\n<li><strong>greater exposure to selenium is associated with lower incidence of cancer [Cai]<\/strong><\/li>\n<li><strong>single interventions with <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15084104\" target=\"_blank\" rel=\"noopener noreferrer\"><em>high-selenium yeast<\/em><\/a> preparations reduce the incidence of cancer [Clark; Yu; Li]<\/strong><\/li>\n<\/ul>\n<p><strong>What do randomized controlled studies reveal about the efficacy of selenium and antioxidant combinations against the development of cancerous tumors, I wondered.<\/strong><\/p>\n<p><strong>The first studies to come to mind were the Linxian <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/8360931\" target=\"_blank\" rel=\"noopener noreferrer\">Nutritional Intervention Studies<\/a>, which are probably just as important in the history of selenium and cancer research as Professor Larry Clark&#8217;s <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/8971064\" target=\"_blank\" rel=\"noopener noreferrer\">Nutritional Prevention of Cancer <\/a>study is.<\/strong><\/p>\n<h3><strong>Professor Blot\u2019s Linxian Nutrition Intervention Studies in China<\/strong><\/h3>\n<p>The Linxian studies were a very big research undertaking.\u00a0 The researchers enrolled 29,584 study participants aged 40 to 69 years from four Linxian County municipalities.\u00a0 The study participants lived in a region of China characterized by constantly low intakes of selenium and by high cancer mortality rates.<\/p>\n<p>The researchers randomly placed the study participants into one of four research groups:<\/p>\n<ul>\n<li>Group A: the zinc and retinol (Vitamin A) group<\/li>\n<li>Group B: the riboflavin and niacin (B vitamins) group<\/li>\n<li>Group C: the Vitamin C and molybdenum group<\/li>\n<li>Group D: the <strong><em>high-selenium yeast<\/em><\/strong>, Vitamin E, and<em> beta<\/em>-carotene group<\/li>\n<\/ul>\n<p>The study data showed that there were no interesting outcomes of the first three supplementation regimens.\u00a0 However, the data from Group D, the group taking a high-selenium yeast supplement daily, did show exciting results.<\/p>\n<ul>\n<li>9% reduction in deaths from all causes<\/li>\n<li>13% reduction in deaths from all forms of cancer<\/li>\n<li>21% reduction in deaths from gastric cancer<\/li>\n<li>20% reduction in deaths from various other cancers<\/li>\n<\/ul>\n<p>The results from the <a href=\"http:\/\/seleniumfacts.com\/linxian-study-selenium-cancer-prevention\/\" target=\"_blank\" rel=\"noopener noreferrer\">Linxian Nutrition Intervention Studies<\/a> confirmed what researchers had seen in animal studies: selenium prevented or delayed the development of cancer tumors [Blot].<\/p>\n<h3><strong>Professor Hercberg\u2019s Su.Vi.Max. Study in France<\/strong><\/h3>\n<p>Next came reports from the big French study \u2013 the <em>Suppl\u00e9mentation en Vitamines et Min\u00e9raux Antioxydants<\/em> (Su.Vi.Max.) study \u2013 also a randomized, double-blind, placebo-controlled study.\u00a0 The<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15557412\" target=\"_blank\" rel=\"noopener noreferrer\"> Su.Vi.Max. study<\/a> enrolled 13,017 adults aged 35 \u2013 60 years of whom roughly 60% were women [Hercberg].<\/p>\n<p>The treatment regimen consisted of the following micronutrients:<\/p>\n<ul>\n<li>100 micrograms <strong><em>high-selenium yeast<\/em><\/strong><\/li>\n<li>6 milligrams <em>beta-carotene<\/em><\/li>\n<li>120 milligrams Vitamin C<\/li>\n<li>30 milligrams Vitamin E<\/li>\n<li>20 milligrams zinc<\/li>\n<\/ul>\n<p>Study participants assigned to the control group took matching placebos daily.<\/p>\n<p>The researchers followed the study participants were for a median period of 7.5 years.\u00a0 The study data revealed a surprising finding.\u00a0 The supplementation with micronutrients headed by 100 micrograms of high-selenium yeast produced significant health benefits in the French men but not in the French women:<\/p>\n<ul>\n<li>lower total cancer incidence<\/li>\n<li>lower all-cause mortality<\/li>\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26374140\" target=\"_blank\" rel=\"noopener noreferrer\">healthier aging<\/a> [Assman 2015]<\/li>\n<\/ul>\n<p>How to explain these unexpected sex differences in the effects of the Su.Vi.Max. study?\u00a0 The researchers suggested various hypotheses:<\/p>\n<ul>\n<li>The women in the study had higher baseline vitamin C and <em>beta<\/em>-carotene status than the men did &#8212; this could have made a difference.<\/li>\n<li>Hormonal differences could have resulted in a difference.<\/li>\n<li>There were differences in <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16115341\" target=\"_blank\" rel=\"noopener noreferrer\">baseline antioxidant status <\/a>between the men and the women.\u00a0 These baseline antioxidant status differences were associated with differences in cancer risk in men but not in women [Galan 2005].<\/li>\n<\/ul>\n<h3><strong>Dr. Prasad\u2019s Oral Cancer Study in India<\/strong><\/h3>\n<p>Researchers in Hyderabad, India, reported the results of a smaller cancer chemoprevention study using<em><strong> high-selenium yeast<\/strong><\/em> in combination with antioxidants [Prasad].\u00a0 The researchers enrolled 298 patients diagnosed with precancerous lesions in their mouths in either an active treatment group or a placebo group.<\/p>\n<p>The patients in the active treatment group took the following <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/7549753\" target=\"_blank\" rel=\"noopener noreferrer\">selenium and antioxidant combination<\/a> for a year:<\/p>\n<ul>\n<li><strong><em>High-selenium yeast<\/em><\/strong><\/li>\n<li>Vitamin A<\/li>\n<li>Riboflavin<\/li>\n<li>Zinc<\/li>\n<\/ul>\n<p>The selenium and antioxidants combination supplement reduced the incidence of micronuclei and DNA adducts significantly.\u00a0 The placebo did not produce a reduction.<\/p>\n<p><em>Note: The extent of micronucleated cells and carcinogen DNA adducts is an indicator of the extent of DNA damage.\u00a0 Reduction in the frequency of micronuclei and DNA adducts is an indication of reduced risk of cancer [Prasad].<\/em><\/p>\n<h3><strong>Dr. Bonelli\u2019s Recurrent Adenomas Study in Italy<\/strong><\/h3>\n<p>Italian researchers tested the effects of selenium and antioxidant supplementation <em>vis-\u00e0-vis<\/em> the rate of the recurrence of adenomas in the large bowel.<\/p>\n<p>The researchers enrolled 411 patients who had had polyps removed from their colons.\u00a0 Patients in the active treatment group took the <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23065023\" target=\"_blank\" rel=\"noopener noreferrer\">following antioxidants in combination with 200 micrograms of selenium<\/a> daily:<\/p>\n<ul>\n<li>2 milligrams Vitamin A<\/li>\n<li>4.4 milligrams of Vitamin B6<\/li>\n<li>180 milligrams Vitamin C<\/li>\n<li>30 milligrams Vitamin E<\/li>\n<li>30 milligrams zinc gluconate<\/li>\n<\/ul>\n<p>Patients assigned to the control group took matching placebos daily.<\/p>\n<p>The researchers did colonoscopies on these patients at the 1-year, 3-year, and 5-year points of the study.<\/p>\n<p>They found that the <a href=\"http:\/\/seleniumfacts.com\/selenium-and-colorectal-cancer-bonelli-study\/\" target=\"_blank\" rel=\"noopener noreferrer\">selenium and antioxidant treatment<\/a> gave a 39% reduction in adenoma recurrence, both in the case of small tubular adenomas and of advanced adenomas.\u00a0 This is an exciting result because adenoma recurrence foretells increased risk of colorectal cancer [Bonelli 2013].<\/p>\n<h3><strong>Selenium in combination with antioxidants and cancer prevention<\/strong><\/h3>\n<p>Blot and Linxian, Hercberg and Su.Vi.Max., Prasad and micronuclei and DNA adducts, Bonelli and recurrent adenomas \u2013 all good solid research results confirming the role of\u00a0selenium and antioxidants in the prevention of cancer.<\/p>\n<p>There remains to be described the 800-pound gorilla in the room: The Selenium and Vitamin E Cancer Prevention Trial (the SELECT study) in the United States.<\/p>\n<h3><strong>The SELECT study of selenium and vitamin E and prostate cancer <\/strong><\/h3>\n<p>The basic premise of the <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19066370\" target=\"_blank\" rel=\"noopener noreferrer\">SELECT study<\/a> \u2013 enrolling 35,533 men at hundreds of medical treatment sites in the U.S., Canada, and Puerto Rico \u2013 was that there was good reason to think that supplementation with selenium and vitamin E could prevent the development of prostate cancer [Lippman].<\/p>\n<p>The SELECT study was <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21990298\" target=\"_blank\" rel=\"noopener noreferrer\">stopped ahead of schedule<\/a> because none of the supplementation regimens was showing the anticipated benefits [Klein].<\/p>\n<p>Numerous selenium researchers have raised questions about the formulation of the selenium supplement (a synthetic l-selenomethionine supplement instead of a high-selenium yeast supplement) and about the high baseline selenium status of the study participants.<\/p>\n<p>Why, given the good results of Professor Clark&#8217;s Nutritional Prevention of Cancer study, Professor Blot&#8217;s Linxian Nutrition Intervention study, Dr. Yu&#8217;s Qidong Selenium Treatment study, and Dr. Prasad&#8217;s Nutrition Intervention study, all with <em><strong>high-selenium yeast preparations<\/strong><\/em>, did the SELECT researchers choose to use a synthetic l-selenomethionine preparation?<\/p>\n<p>I will want to address the issues raised by the misconceived SELECT study in a future article on this Web-site.<\/p>\n<h3><strong>Conclusion<\/strong><\/h3>\n<p>Selenium supplementation, alone and in combination with other antioxidants, has shown significant results in terms of the reduction of cancer incidence and cancer mortality.\u00a0 The exact mechanisms of selenium\u2019s chemoprevention of cancer are not yet known.<\/p>\n<p>Possible explanations for the efficacy of selenium in the prevention of cancer include but are not limited to the following effects of selenium:<\/p>\n<ul>\n<li>on the process of apoptosis<\/li>\n<li>on the activity of the selenium-dependent selenoenzymes<\/li>\n<li>on the functioning of the immune system<\/li>\n<li>on the metabolism of carcinogens<\/li>\n<li>on tumor cell growth [L\u00fc 2016]<\/li>\n<\/ul>\n<p><strong><em>High-selenium yeast supplements<\/em><\/strong> are the most effective <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2596749\/\" target=\"_blank\" rel=\"noopener noreferrer\">selenium supplements<\/a>.<\/p>\n<h3>Sources<\/h3>\n<p>Assmann, K. E., Andreeva, V. A., Jeandel, C., Hercberg, S., Galan, P., &amp; Kesse-Guyot, E. (2015). Healthy Aging 5 Years After a Period of Daily Supplementation With Antioxidant Nutrients: A Post Hoc Analysis of the French Randomized Trial SU.VI.MAX. American Journal of Epidemiology, 182(8), 694-704.<\/p>\n<p>Blot, W. J., Li, J. Y., Taylor, P. R., Guo, W., Dawsey, S., Wang, G. Q., &amp; Li, B. (1993). Nutrition intervention trials in Linxian, China: supplementation with specific vitamin\/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Journal of The National Cancer Institute, 85(18), 1483- 1492.<\/p>\n<p>Bonelli, L., Puntoni, M., Gatteschi, B., Massa, P., Missale, G., Munizzi, F., &amp; Bruzzi, P. (2013). Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. Journal of Gastroenterology, 48(6), 698-705.<\/p>\n<p>Cai, X., Wang, C., Yu, W., Fan, W., Wang, S., Shen, N., &amp; Wang, F. (2016). Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression. Scientific Reports, 619213.<\/p>\n<p>Galan, P., Brian\u00e7on, S., Favier, A., Bertrais, S., Preziosi, P., Faure, H., &amp; Hercberg, S. (2005). Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels? The British Journal of Nutrition, 94(1), 125-132.<\/p>\n<p>Hercberg, S., Galan, P., Preziosi, P., Bertrais, S., Mennen, L., Malvy, D., &amp; Brian\u00e7on, S. (2004). The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Archives of Internal Medicine, 164(21), 2335-2342.<\/p>\n<p>Klein, E. A., Thompson, I. J., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., &amp; Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA, 306(14), 1549-1556.<\/p>\n<p>Li, W., Zhu, Y., Yan, X., Zhang, Q., Li, X., Ni, Z., &amp; \u2026 Zhu, J. (2000). [The prevention of primary liver cancer by selenium in high risk populations]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine], 34(6), 336-338.<\/p>\n<p>Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G., &amp; &#8230; Coltman, C. J. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama, 301(1), 39-51.<\/p>\n<p>Prasad, M. P., Mukundan, M. A., &amp; Krishnaswamy, K. (1995). Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity. European Journal of Cancer. Part B, Oral Oncology, 31B(3), 155159.<\/p>\n<p>Schrauzer, G.N., White, D.A., &amp; Schneider, C.J.\u00a0 (1977).\u00a0 Cancer mortality correlation studies&#8211;III: statistical associations with dietary selenium intakes. Bioinorganic Chemistry, 7(1):23-31.<\/p>\n<p>Yu, S. Y., Zhu, Y. J., &amp; Li, W. G. (1997). Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological Trace Element Research, 56(1), 117-124.<\/p>\n<p>The information contained in this review article is not intended as medical advice and should not be construed as such.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>On the topic of cancer and selenium as a cancer chemo-preventive agent, we know some basic facts from published research: selenium prevents or delays tumor development in animals [Schrauzer] regions with low selenium intakes are regions with higher incidence of cancer [Schrauzer] greater exposure to selenium is associated with lower incidence of cancer [Cai] single &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/seleniumfacts.com\/index.php\/selenium-antioxidants-combination-cancer\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Selenium and antioxidants in combination against cancer&#8221;<\/span><\/a><\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[],"class_list":["post-826","post","type-post","status-publish","format-standard","hentry","category-cancer"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - 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