VITAMIN E, VITAMIN C & SELENIUM DO NOT PREVENT CANCER
These past 5 years have seen the dashing of the hopes of many cancer physicians and researchers who, like me, had hoped that antioxidant vitamin supplements would prove to be potent cancer prevention agents. These hopes were built up over the previous decade as multiple clinical and laboratory studies reported encouraging results with Vitamin E, Vitamin C and selenium in the prevention of breast cancer, prostate cancer, and other types of cancer. However, most of these studies were performed using research methods that are far less rigorous than the “gold standard” prospective, randomized, placebo-controlled clinical trial.
Most of the previous research studies performed in this area have relied upon dietary questionnaires, tests of human cancer cells growing in laboratory Petri dishes, and the injection of human tumor cells into mice that have been genetically altered to have a faulty immune system. While research studies such as these occasionally yield results that are subsequently reproduced and confirmed in humans, the results of the vast majority of such “low-powered” research studies are, unfortunately, not validated by “Level 1” prospective, randomized clinical research trials in humans. However, for most of the past decade, all that has been available in terms of cancer prevention research studies have been these relatively weak research studies. Over the last 5 years, however, several very large placebo-controlled prospective clinical cancer prevention trials have reported their results, and the news from these trials has been uniformly disappointing.
This week, two more long-awaited large prospective placebo-controlled cancer prevention trials have reported their preliminary results in the Journal of the American Medical Association.
The first of these two studies is the SELECT Trial (Selenium and Vitamin E Cancer Prevention Trial), which was a huge prostate cancer prevention study that enrolled more than 35,000 middle-aged men. In the SELECT Trial, study volunteers were secretly randomized to one of 4 different groups. One group received placebo (sugar) pills, only, while the remaining groups were assigned to receive selenium alone, Vitamin E alone, or both selenium and Vitamin E. All men were clinically free of prostate cancer when they joined this enormous multi-center research study.
The SELECT Trial, the largest prospective cancer prevention research study ever conducted, was originally planned to continue for as long as 12 years, but was prematurely ended after an interim review of the research data raised significant concerns. Half of the 35,533 men participating in this study had been observed for just over 5 years, while the remaining half had been observed less than 5 years, when the study was shut down.
Among the men randomized to secretly receive Vitamin E alone, the risk of developing prostate cancer was actually 13 percent higher than what was observed in the group of men who received only placebo tablets. The men who received only selenium supplements experienced a 5 percent greater risk of prostate cancer when compared to the men in the placebo group. Finally, the men who were secretly randomized to receive both Vitamin E and selenium supplements experienced an identical risk of prostate cancer when compared to the men in the placebo group. (The slight increase in prostate cancer risk that was observed in the groups receiving only selenium and only Vitamin E did not, however.) Not only was there no apparent reduction in prostate cancer risk among the men who received Vitamin E and/or selenium in this study but, importantly, there was also no difference in the risk of other types of cancer observed among the 4 groups of study volunteers.
Although additional years of observing the more than 35,000 men who participated in this clinical trial may reveal additional findings, the interim results of this huge and extremely well conducted prospective cancer prevention trial are disappointing, to say the least. However, the preliminary findings of the SELECT trial join a growing number of other large-scale prospective, randomized, placebo-controlled cancer prevention and cardiovascular disease prevention research trials that have recently revealed absolutely no disease prevention effects associated with the most commonly used antioxidant vitamin supplements.
The SELECT Trial, like other recent large and very expensive “gold standard” disease prevention research trials, raises serious questions about the clinical utility of individual antioxidant vitamin supplements, and takes us back to our much earlier view that there is likely to be little, if any, benefit associated with taking extra doses of dietary antioxidants outside of a well-balanced diet. I have previously included these same antioxidant vitamins, and other antioxidant dietary supplements, in my own little plastic tray of vitamins and supplements. However, with the advent of several recent very large prospective, randomized clinical trials showing no health benefits associated with most of these supplements, and with several of these clinical trials actually showing an increase in serious illnesses, and even death, associated with some of these same dietary supplements, I have recently updated my secret little tray of supplements. To my wife’s relief, the number of plastic vitamin and supplement bottles crammed into her kitchen cabinets has been on the decline, recently. Now, let me discuss the second cancer prevention trial also published in the current issue of the Journal of the American Medical Association.
The results of the second large prospective cancer prevention study, The Physicians’ Health Study II, have also been much anticipated. In this study, 14,641 clinically healthy male physicians, aged 50 years and older, were secretly randomized to receive Vitamin E supplements every other day, Vitamin C supplements every day, or identical placebo (sugar) tablets. The average duration of follow-up for this large number of healthy middle-aged men was 8 years. During this nearly decade-long period of follow-up, 1,943 cases of cancer were diagnosed, including 1,008 cases of prostate cancer.
Compared with the men who were secretly randomized to receive the placebo pills, there was absolutely no difference in the incidence of prostate cancer, or of any other type of cancer, observed among the men who secretly received either the Vitamin E or the Vitamin C supplements.
The results of this large prospective clinical trial, as with the SELECT Trial and other recently published large cancer prevention studies, shows that Vitamin E or Vitamin C supplementation has no apparent impact on the incidence of any type of cancer in otherwise healthy adults.
These two powerful prospective clinical research trials, which provide the highest available level of clinical research data among all types of clinical or laboratory research studies, are showing us, over and over again, that Vitamin C and alpha-tocopherol (the most common form of Vitamin E) supplements, when given in typical doses, appear to have absolutely no impact on cancer and cardiovascular disease risks in adults who eat a balanced diet. Moreover, recently published prospective clinical trials have actually found an increased risk of lung cancer among smokers taking beta-carotene (a member of the Vitamin A family), and an overall 4 to 5 percent increase in the risk of death among healthy research volunteers who were randomized to receive 400 International Units per day of Vitamin E.
The newly published results of these two very large cancer prevention trials, along with similarly negative results from other large prospective cancer prevention trials, should prompt all of us to reconsider the notion, based upon earlier and much less rigorous research, that taking supra-normal doses of vitamins and other dietary supplements are going to significantly decrease our risk of cancer, and other serious diseases, beyond the disease reduction benefits that have long been associated with eating a healthful and balanced diet. There is no question, based upon decades of epidemiological studies, that a diet low in fat (and very low in red meat and processed meats, in particular), and rich in fresh vegetables and fruits, can lower not only our risk of many of the most common cancer killers, but as an added bonus, can also lower our risk of cardiovascular diseases as well.
As the disappointing results related to Vitamins A, C and E continue to pile up, I often receive messages from readers more or less condemning these studies and their negative results. I generally remind these readers that I have sat in their midst for a couple of decades now, popping a rainbow-colored assortment of nearly every dietary antioxidant known to mankind. However, when the Level 1 clinical data starts coming in, and all of it is bad news, sometimes you just have to accept these findings, make an adjustment, and move on….
The good news is that, despite the accumulating disappointing news about dietary antioxidants as cancer prevention agents, between 60 and 80 percent of all cases of cancer can be prevented with judicious and fairly moderate lifestyle, diet and other behavioral strategies. My forthcoming book, “A Cancer Prevention Guide for the Human Race,” is based upon an exhaustive, global review of, literally, thousands of cancer prevention and cancer screening research studies. Despite all of the bad news about antioxidants, you can still tremendously reduce your lifetime risk of developing cancer by using an evidence-based approach that will also significantly reduce your risk of cardiovascular diseases at the same time. Look for this new cancer prevention book to arrive in the fall of 2009!
A POSSIBLE CURE FOR DOWN’S SYNDROME
I have received numerous inquiries regarding last week’s column on Down’s syndrome, also known as trisomy 21. In that column, I described the rather miraculous improvements in learning abilities observed in newborn mice born with a trisomy disorder that mimics Down’s syndrome. Prior to their birth, the pregnant mothers of these young trisomy mice were treated with two neuroprotective proteins. Following their birth, these young trisomy mice were found to do as well with several types of learning as young mice without trisomy.
I wrote to the authors of this study at the National Institutes of Health to inquire about their plans for possible early-phase human clinical trials with these two proteins. Unfortunately, I learned that, at the present time, no human clinical trials are in the works. I also contacted Dr. Steve Whitaker, who is the Chief Medical Officer for Allon Therapeutics, the Canadian biotechnology company that has developed these two experimental proteins. Dr. Whitaker very graciously responded after I mentioned to him that many parents of children with trisomy 21 have expressed a tremendous interest in participating in a clinical trial using these experimental proteins, after reading last week’s column. Unfortunately for families and patients with Down’s syndrome, Allon Therapeutics’ research focus, at this time, is pretty much limited to Alzheimer's disease, and cognitive impairments secondary to stroke and schizophrenia-related cognitive impairment.
My recommendation to parents who would like to see the National Institutes of Health develop an early-phase clinical trisomy 21 trial using these peptides is that you contact your Congressional Representative or Senator, and ask them to propose funding to carry out at least a small preliminary clinical trial with these neuroprotective proteins. It is time to assess the toxicity of these proteins in very carefully controlled prospective clinical trials and, if there is no significant toxicity associated with these drugs, to then proceed with actual testing of these compounds in humans within a placebo-controlled, randomized prospective clinical trial setting.
Copyright 2008. Robert A. Wascher, MD, FACS.
All rights reserved.
Dr. Wascher's Archives:
10-26-2008: Smoking & Quality of Life
10-19-2008: Agent Orange & Prostate Cancer
10-12-2008: Pomegranate Juice & Prostate Cancer
9-21-2008: Does TylenolŪ (Acetaminophen) Cause Asthma?
4-27-2008: Stents vs. Bypass Surgery for Coronary Artery Disease; The “DASH” Hypertension Diet & Cardiovascular Disease Prevention; Testosterone Therapy for Women with Decreased Sexual Desire & Function
4-6-2008: Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer; Human Papilloma Virus (HPV) Infection & Oral Cancer; Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)
12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality