Selenium and Prostate Cancer. Antioxidant Use During Chemotherapy

Research Review & Commentary
By Shari Lieberman, Ph.D., CNS, FACN

Selenium Supplementation, Baseline Plasma Selenium Status and Incidence of Prostate Cancer: An Analysis of the Complete Treatment Period of the Nutritional Prevention of Cancer Trial.
Duffield-Lillico AJ, Dalkin BL, Reid ME, Turnbull BW, Slate EH, Jacobs ET, Marshall JR, Clark LC. BJU Int. 2003 May; 91(7):608-12.

Research Abstract
The Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 micrograms daily) was designed to test the hypothesis that selenium supplementation could reduce the risk of recurrent nonmelanoma skin cancer among 1,312 residents of the Eastern USA. However, secondary analyses of the study showed a striking inverse association between selenium supplementation and prostate cancer incidence.

A subsequent report revealed that this effect was accentuated among men with the lowest baseline plasma selenium concentrations. Selenium supplementation significantly reduced the overall incidence of prostate cancer.

The protective effect of selenium supplementation appeared to be confined to those with a baseline PSA level of less than 4 ng/ml. The NPC trial demonstrated a significant protective effect of selenium supplementation on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline PSA and plasma selenium concentrations.

Dr. Shari's Commentary
I wish this study received as much press as ephedrine. This is an important study in that it demonstrates a clear protective effect of selenium on prostate cancer risk.

High selenium intakes have been shown to be protective against a wide variety of cancers and countries with high selenium soil (the United States not being one of them) have a lower risk of many cancers.

In countries with high selenium soil, inhabitants may consume as much as 500-750 mcg of selenium each day. Selenium is essential for the production of glutathione peroxidase—a very powerful free-radical scavenger.

What the study suggests is that 200 mcg of selenium is more protective in men with the lowest levels of selenium and lower baseline PSA levels. If they had lower PSA levels, this also suggests either no cancer at that time or extremely early stage prostate cancer. Americans ingest very low levels of selenium through their food. It is removed during milling of whole grains to white flour and most soil is deficient in selenium.

Also, glaciated areas are notoriously low in selenium. My personal opinion is that higher levels of selenium yield a higher protective and therapeutic effect for prostate, breast and other cancers.

Selenium is safe in higher levels (like chromium) up to about 1 mg. Given the present cancer epidemic, I routinely recommend at least 400 mcg per day for those at risk of cancer and perhaps 400-1,000 mcg per day to those with active cancer.

Even the Food and Nutrition Board acknowledges that selenium toxicity would only occur if 2,400-3,000 mcg per day were ingested. So, less than one milligram or 1,000 micrograms is certainly within this limit. There is a ton of animal and human data demonstrating the anticancer effects of selenium yet it is so rarely used in clinical oncology-go figure.

The Use of Antioxidant Therapies During Chemotherapy
Drisko JA, Chapman J, Hunter VJ,
Gynecol Oncol. 2003;88:434-439

Research Abstract
It is accepted that antioxidants are useful in the reduction of adverse side effects of chemotherapy, although most oncologists believe that antioxidants reduce the effectiveness of chemotherapy and radiation therapy.

There is evidence that antioxidants used alongside chemotherapy may help reduce tumor size and increase longevity. The concern regarding antioxidant therapies interfering with chemotherapy and radiation is the lowering of oxidative damage of chemotherapy by antioxidants, thereby reducing its effectiveness. Evidence supporting this mechanism is not present.

Antioxidants act as biological response modifiers and can directly induce apoptosis in cancer cells. There is scientific evidence that antioxidants enhance the antitumor effects of chemotherapy in vitro and in vivo. Chemotherapy does not kill tumor cells by damaging essential biological functions but by initiating programmed cellular responses.

The common antioxidants used during cancer treatment include mixed tocopherols and tocotrienols, beta-carotene, which includes natural mixed carotenoids, vitamin C and vitamin A.

Antioxidants work in conjunction with each other to quench reactive oxidant species. Vitamin C, at many times the Recommended Daily Allowance, is a potent immunomodulator and has been found to be preferentially cytotoxic to cancer cells. Vitamin C enhances the activity of natural-killer cells in vivo and also enhances B- and T-cell activity.

At doses in the gram range, it has been shown to increase survival time of patients with malignancies. Vitamin C may be killing cancer cells through the mechanism of intracellular generation of toxic hydrogen peroxide produced by the oxidized form of ascorbic acid, dehydroascorbate. Plasma saturation has been found to reach 80 percent at a 200-mg oral dose, and saturation has been observed at 1,000 mg/day.

The goal of therapy is to attain vitamin C levels of greater than 200 mg/dl given intravenously. In patients with malignancies, much higher doses are needed to kill cancer cells. Intravenous therapy can get the dose above 200 mg/dl, resulting in tumor cell cytotoxicity and with virtually no effect on normal tissue. The longer the plasma level is maintained above 200 mg/dl, the more effective the cytotoxic effect will be. Ascorbate plasma levels above 200 mg/dl, which would be cytotoxic to cancer cells, are not likely to be attained with oral regimens alone.

Vitamin C has been shown to increase the activity of doxorubicin, cisplatin and paclitaxel. Natural mixed carotenoids in doses up to 20-40 mg/day have been shown to act synergistically with cisplatin. These amounts have been shown to increase cell differentiation in vivo, which promotes apoptosis of cancer cells. Human evidence suggests an inverse relationship between vitamin E levels and tumor incidence.

Vitamin E has been shown to decrease the toxicity of chemotherapy without reducing its effectiveness. Retinoic acid and its derivatives can induce cell differentiation and growth inhibition in some cancer cell lines. High doses of retinoic acid may be taken for a specific period orally without fear of normal tissue toxicity.

Retinoic acid shows benefit in combination with chemotherapy, and there is no evidence of reduced effectiveness of chemotherapy. Evidence is growing that antioxidants may be used with certain chemotherapeutic agents to enhance their effectiveness.

Dr. Shari's Commentary
I applaud Dr. Drisko's work. This is the second paper she and her colleagues have written confirming that antioxidants should be given along with chemotherapy. I will also add that they should also be given along with radiation (as she also suggests in this paper). Another important fact is that cancer cells have abnormal membranes.

When you take high levels of antioxidants orally or intravenously they will flood into cancer cells and cause their death. Since normal cells do not have these extremely abnormal permeable membranes, they are protected by these antioxidants since the antioxidants don't "flood" into the cell but are absorbed only to a certain degree.

Dr. Drisko has also made the important distinction between natural and synthetic beta carotene and vitamin E, in short, that only the natural forms should be used.

Another form of vitamin E known as d-alpha-tocopheryl succinate was developed specifically to target cancer cells and the research has shown it to be very effective against many different types of cancer and synergistic with chemotherapy and radiation.

It is important that oncologists get with the program and educate themselves in the science of antioxidants and their role in oncology, rather than perpetuating the belief that antioxidants reduce the effectiveness of chemotherapy and radiation therapy. Nutrition is a science, not a religion based on belief.

Dr. Shari Lieberman
Dr. Lieberman earned her Ph.D. in Clinical Nutrition and Exercise Physiology from The Union Institute, Cincinnati, Ohio, and her M.S. degree in Nutrition, Food Science and Dietetics from New York University. She is a Certified Nutrition Specialist (C.N.S.); a Fellow of the American College of Nutrition (FACN); a member of the New York Academy of Science; a member of the American Academy of Anti-Aging Medicine (A4M); a board member of the Certification Board for Nutrition Specialists; President of the American Association for Health Freedom and the recipient of the National Nutritional Foods Association 2003 Clinician of the Year Award. She has been in private practice as a clinical nutritionist for more than 20 years in New York City.

Dr. Lieberman is a frequent guest on many television and radio shows and her name is often seen in magazines as an authority on nutrition. Dr. Lieberman has authored several books on nutrition and integrative medicine. Her best-selling The Real Vitamin & Mineral Book (Avery/Penguin Putnam 2003) was recently released in its third edition. Dr. Lieberman serves as a faculty member of the University of Bridgeport, School of Human Nutrition graduate program, and as an industry consultant. She is a contributing editor to the American Medical Association's Fifth Edition of Drug Evaluations; a peer reviewer for scientific publications; a published scientific researcher and a presenter at numerous scientific conferences.

The information in this article is not intended to provide personal medical advice, which should be obtained from a medical professional, and has not been approved by the U.S. FDA.

Copyright 2004 by Vitamin Research Products, Inc. The Vitamin Research News is intended solely for individual, non-commercial use. All other uses are prohibited without written permission from VRP. The Vitamin Research News is protected by U.S. and international copyright laws and may not be reproduced, distributed, transmitted, displayed, published or broadcast in any form, or by any means whether now known or hereinafter devised, without prior written permission from VRP.

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