Steven Bratman, MD
In the 1990s, antioxidants became famous as the nutritional equivalent of the fountain of youth. Increasing your intake of
vitamin E, beta-carotene, and
was promoted as an easy and painless way to prevent
heart disease, vision problems,
arthritis, and many other illnesses.
Unfortunately, recent research has put a damper on this excitement. It now appears that antioxidant proponents had jumped the gun. In fact, these supplements may have little benefit for these purposes. Worse still, some may even
risk of cancer and heart disease.
Antioxidants are chemical substances naturally found in foods. They function as a protective shield against harmful, unstable molecules known as free radicals. Free radicals are produced throughout the body as a result of normal body functions. They have some important uses, such as fighting infection. However, free radicals can also cause harm to healthy tissues and are believed to play a role in many diseases.
The potential harmful effects of excessive free radicals range from cosmetic to life-threatening. They may break down skin tissue, making it look older than it is. They may injure the lens of the eye, leading to the early development of
cataracts. And they may make it harder for cells to repair themselves, which can increase the risk of cancer, heart disease, and other diseases of age.
The body itself has a well-developed system to contain free radicals. High consumption of certain nutrients might boost this system, and thereby improve health.
There are a variety of antioxidants present in many different foods. The following is a list of the most well known antioxidants and the foods in which they are found. Also listed are selenium and manganese, which are not antioxidants themselves, but are necessary for the body to create its own natural antioxidants.
Scientists became interested in antioxidants several decades ago when they noticed that people who regularly consumed fruits, vegetables, and other foods high in antioxidants had a lower incidence of diseases such as
cancer, heart disease,
arthritis, age-related vision problems,
Parkinson’s disease, and many other conditions. Speculation began to grow that perhaps antioxidants might be key to preventing degenerative diseases and slowing the aging process.
However, in such observational studies it is difficult to rule out other factors that may play a role. For example, people who take vitamins may also exercise more or take better care of themselves in other ways. Such factors make the results of these studies less reliable.
Scientists in the early 1990s raised the possibility that other factors in fruits and vegetables besides the major antioxidants were responsible for their beneficial health effects. Or, alternatively, that antioxidant ingredients had to be present in certain combinations, or in the context of a whole food. Nonetheless, based on studies that showed positive physiologic changes when these antioxidants were taken, many scientists remained convinced that isolated antioxidant supplements should be helpful. So, they tested this theory in a large study, enrolling tens of thousands of people who took antioxidant supplements for several years.
Much to everyone’s surprise, the majority of these studies did not support a beneficial effect for antioxidant supplementation. Not only did antioxidant supplements fail to prevent illness, they appeared to increase it under certain circumstances. This was true, not only when isolated antioxidants were used, but with combined antioxidant therapies as well.
An analysis of randomized trials investigating the effects of antioxidant supplements on longevity found no decrease in mortality—with the possible exception of selenium. Moreover, vitamins A and E and beta-carotene appeared to modestly, but significantly, increase mortality. This was true whether the supplements were used alone or in combination.
The history of the supplement beta-carotene and its potential cancer-preventing benefits provides an example of antioxidants’ disappointing record. The story began in the early 1980s when the cumulative results of many studies suggested that people who eat a lot of fruits and vegetables are significantly less likely to get cancer. A close look at the data pointed to carotenes as the active ingredients in fruits and vegetables. It appeared that a high intake of dietary carotene might significantly reduce the risk of cancers of the
stomach. In addition to these observational studies, evidence from laboratory evaluations showed that beta-carotene helped prevent healthy cells from becoming cancerous.
The possibility that a simple, cheap supplement could reduce cancer rates excited researchers. In a relatively short time, funds were gathered to conduct several large trials. Most of these studies enrolled people in high-risk groups such as smokers, because it is easier to see results in a study when you look at people who are more likely to develop the disease you are studying.
In 1994, the results of the Alpha-Tocopherol, Beta-Carotene (ATBC) study dashed researchers hopes. The results of this 29,133-person study showed that beta-carotene supplements did not prevent lung cancer, but actually increased the risk of getting it by 18%.
In January 1996, researchers monitoring the Beta-Carotene and Retinol Efficacy Trial (CARET) confirmed the prior bad news with more of their own: the beta-carotene group had 46% more cases of lung cancer deaths. This study involved smokers, former smokers, and workers exposed to asbestos. Alarmed, the National Cancer Institute ended the $42 million CARET trial 21 months sooner than planned.
Similar results were seen in another large study that did not focus on smokers. In the 12-year Physicians' Health Study of 22,000 male doctors, 50 mg of beta-carotene taken every other day had no effect on the risk of cancer or heart disease. Another large study of beta-carotene supplements failed to find any effect on the risk of cancer in women.
Undaunted, proponents of antioxidants argued that while beta-carotene alone may have no measurable effect, combining it with other antioxidants may still produce beneficial results. To date, however, studies evaluating mixtures of antioxidant supplements have failed to yield conclusive results.
The news is slightly better for two other antioxidant supplements: vitamin E and selenium. Each of these supplements has some evidence from trials indicating that they may reduce risk of certain forms of cancer. However, this evidence is far from definitive, and subsequent research has yet to confirm these findings. Worse, in some studies, doses of vitamin E above 150 IU per day were associated with increased risk of death. Selenium remains under trial as a possible agent for preventing colon cancer, but it will likely take several additional years to know whether supplementation is of health value.
The evidence for a generalized anticancer effect with other antioxidant supplements, such as vitamin C,
green tea, is not persuasive either, since it is limited almost entirely to observational and test tube studies. Vitamin E or selenium may even increase the risk of
There is an ongoing debate that focuses on antioxidants and their effects on
radiation therapy. It is unclear whether antioxidants interfere with the effects of these therapies by reducing their effectiveness or by enhancing it. There have been studies published that support each of the opposing ideas. This is a controversial area that requires additional research.
There is no harm in eating foods rich in antioxidants.
As with cancer prevention, the results of many large observational studies suggest that higher consumption of antioxidant supplements may decrease heart disease risk. However, other trials have failed to find benefit with vitamin E, beta-carotene, vitamin C, or mixed antioxidants—some even suggest that such supplements may increase risk.
Similarly, intervention trials have not consistently found that antioxidants are helpful for macular degeneration. Mixed antioxidants have also failed to be helpful for preventing cataracts, but the antioxidant lutein has shown promise for this condition.
Researchers have discovered, though, that antioxidant supplements may help to improve fertility in men who have unexplained infertility. It is believed that antioxidants may help to fight against damage to sperm cells.
There are two possible interpretations of these results. One, the more hopeful possibility, is that antioxidants really are helpful, but only when they are taken in the form of naturally occurring food. If this is correct, consuming more fruits and vegetables may be health promoting, while the benefits of taking vitamin supplements still needs to be proven.
However, another possibility is that the apparent correlation between antioxidant intake and reduced rate of disease does not indicate cause and effect, and that consuming extra antioxidants in any form will fail to prevent disease.
So what should an educated consumer do? The best option is probably to eat plenty of fruits and vegetables. If your vegetable or fruit has color to it, it almost certainly contains an antioxidant that might provide a health benefit. Some people may also want to “hedge their bets” and take a multivitamin/multimineral tablet that supplies nutrients at basic nutritional doses. Because of studies showing risk at high doses, vitamin E dosage should probably remain below 150 IU daily, and even this dose does not guarantee safety, as rare adverse effects are difficult to measure. Similarly, we do not know if low doses of beta carotene increase cancer risk.
American Dietetic Association
Canada's Food Guide
Dietitians of Canada
Antioxidant food table. Cleveland Clinic website. Available at: http://my.clevelandclinic.org/heart/prevention/nutrition/antioxidants.aspx. Accessed August 19, 2013.
Antioxidants. Academy of Nutrition and Dietetics website. Available at: http://www.eatright.org/public/content.aspx?id=6792. Accessed August 19, 2013.
Antioxidants and cancer prevention: fact sheet. National Cancer Institute website. Available at: http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants. Updated July 28, 2004. Accessed August 19, 2013.
Albanes D. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-tocopheral Beta-carotene Cancer Prevention Study.
Am J Clin Nutr.
Brown BG, Crowley J. Is there any hope for vitamin E?
Gill S, Sinicrope FA. Colorectal cancer prevention: is an ounce of prevention worth a pound of cure?
Greenberg ER. A clinical trial of antioxidant vitamins to prevent colorectal adenoma: Polyp Prevention Study Group.
New Engl J Med.
Hennekens CH. Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasm and cardiovascular disease.
New Engl J Med.
Klein EA. Chemoprevention of prostate cancer.
Crit Rev Oncol Hematol.
Manganese. Oregon State University Linus Pauling Institute website. Available at: http://lpi.oregonstate.edu/infocenter/minerals/manganese/. Accessed August 19, 2013.
Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar
E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause
Ann Intern Med.
2005;142:37-46. Summary for patients
Ann Intern Med.
Olmedilla B, Granado F, Blanco I, et al. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-year double blind, placebo-controlled pilot study.
Peralta EA, Viegas ML, Louis S, Engle DL, Dunnington GL. Effect of vitamin E on tamoxifen-treated breast cancer cells.
2006;140:607-614 [discussion 614-615]. [Epub ahead of print]
Prasad KN. Antioxidants in cancer care: when and how to use them as an adjunct to standard and experimental therapies [review].
Expert Rev Anticancer Ther.
Prasad KN, Cole WC, Kumar B, Che Prasad K. Pros and cons of antioxidant use during radiation therapy [review].
Cancer Treat Rev.
Simone CB II, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1 [review].
Altern Ther Health Med.
Simone CB II, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 2 [review].
Altern Ther Health Med.
Special report: the trials of beta-carotene: is the verdict in?
Tufts Diet and Nutrition Letter.
Steinberg D. Clinical trials of antioxidants in atherosclerosis. Are we doing the right thing?
Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial.
Zhang YH. Possible immunologic involvement of antioxidants in cancer prevention.
Am J Clin Nutr.
3/16/2007 DynaMed's Systematic Literature Surveillance
http://www.ebscohost.com/dynamed: Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.
2/14/2011 DynaMed's Systematic Literature Surveillance
http://www.ebscohost.com/dynamed: Showell M, Brown J, Yazdani A, Stankiewicz M, Hart R. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2011;(1):CD007411.
6/7/2012 DynaMed's Systematic Literature Surveillance
http://www.ebscohost.com/dynamed: Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2012;3:CD007176.
2/24/2014 DynaMed's Systematic Literature Surveillance
http://www.ebscohost.com/dynamed: Kristal A, Darke A, et al. Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst. Available at: http://jnci.oxfordjournals.org/content/early/2014/02/21/jnci.djt456.abstract?sid=b07c002f-580d-43be-b88d-7af6a06f5a10 Published February 22, 2014. Accessed February 24, 2014.
Last reviewed August 2013 by Michael Woods, MD
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
Copyright © EBSCO Publishing. All rights reserved.