April 2010 Issue

Debate on Antioxidants — Some Studies Suggest Efficacy While Others Question Safety
By Jasmin Ilkay, MPH, RD
Today’s Dietitian
Vol. 12 No. 4 P. 14

Are you among the estimated 30% of Americans taking antioxidant supplements? The myriad products available overflow market shelves and often confuse consumers and dietitians alike. While many people are aware of the potential disease-fighting ability of antioxidants, few may be aware of their potential for harm. Most scientists agree that antioxidants can likely help some people, but they also don’t appear to benefit many and are possibly detrimental to some.

Critical Concerns
A study published in The Journal of the American Medical Association (JAMA) in 2007 concluded that supplemental treatment with antioxidants beta-carotene, vitamin A, and vitamin E may actually increase mortality. The study authors also concluded that vitamin C does not reduce mortality rates. These findings sparked a critical debate among scientists that will likely continue for years.

Balz Frei, PhD, a professor and director of the Linus Pauling Institute, countered the JAMA study results, saying, “This is a flawed analysis of flawed data, and it does little to help us understand the real health effects of antioxidants, whether beneficial or otherwise.”1 Frei noted that the study reviewed 815 antioxidant trials but included only 68 of them in the analysis and claimed that two of the excluded studies, which were published in the Journal of the National Cancer Institute and The Lancet, may have countered the mortality results.

The JAMA study was not the first to question the safety of antioxidants. In the 1980s, findings from observational studies suggested that antioxidants vitamin A and beta-carotene could reduce the incidence of cancer.2  Researchers conducted two major studies to test this theory: the infamous Finnish ATBC (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) study and the CARET (Beta-Carotene and Retinol Efficacy Trial) study, both cancer prevention trials that began in 1985.

In the ATBC trial, researchers aimed to determine whether taking beta-carotene and/or vitamin E could prevent lung cancer and other cancers in 29,133 male Finnish smokers. According to The New England Journal of Medicine, the researchers reported that male subjects who took beta-carotene had an 18% increase in the incidence of lung cancer and an 8% increase in overall mortality after eight years. Vitamin E had no effect on lung cancer incidence or overall mortality. 

The CARET study evaluated the anticancer effects of daily beta-carotene and vitamin A supplements in more than 18,000 people who were smokers, former smokers, or workers exposed to asbestos. The National Cancer Institute reports that a four-year follow up with CARET participants showed a 28% increase in lung cancer incidence and a 17% increase in the rate of death.2 Compiling these preliminary results with those of the ATBC study, researchers decided to terminate the trial in January 1996, 21 months ahead of schedule.

Antioxidants in Review
To further understand the antioxidant conundrum, it’s useful to review the basics. Antioxidants block the negative effects of free radicals, which damage DNA, proteins, and lipids; augment the aging process; and play a role in weakening the immune system and in diseases such as cancer, diabetes, and cardiovascular disease. Conversely, naturally produced free radicals (by-products of metabolism) are essential for health. They destroy unhealthy cells, bacteria, and viruses and detoxify harmful chemicals.

The key to longevity is helping the body strike a delicate balance between allowing natural free radicals to work while preventing excess ones from causing damage. When the body can’t neutralize a surplus of free radicals, it is considered to be in oxidative stress. This proviso is what contributes to disease and aging. The philosophy behind taking antioxidant supplements is that a surplus (from supplements, not diet) can prevent harmful oxidative damage to cells. Despite the current debate on antioxidant supplements, many scientists still argue that these supplements have the potential to prevent and manage diseases in certain individuals.

Current scientific evidence is inconsistent as to whether supplemental forms of vitamins A (including beta-carotene), C, and E prevent or delay cancer or cardiovascular disease. Coenzyme Q10, another popular antioxidant supplement, most likely fails to reduce cancer risk but may improve the health of people with cardiovascular disease.3 To some extent, antioxidant vitamin supplements C, E, A, and beta-carotene are positively correlated to immune function.3 While these vitamins are frequently included in modern-day supplement regimens, consumers are beginning to favor more glamorous antioxidant sources.

Pining for a Cure
Pine bark extract comes from the bark of the French maritime pine (Pinus pinaster or Pinus maritima). The extract contains a group of compounds with proanthocyanidins, which are found in many plants (eg, cocoa, grape seed, grape skin, bilberry, cranberries). They are believed to act as one of the most powerful antioxidants.

Proponents claim that pine bark extract protects against arthritis, cancer, heart disease, retinopathy, varicose veins, and diabetes-related complications. Of these conditions, current research suggests that pine bark extract may be useful in decreasing blood pressure and LDL cholesterol levels while also improving circulation (decreased edema in the legs).4 Stanford University researchers are currently recruiting subjects for a randomized, double-blind prevention trial that aims to investigate the efficacy of Flavangenol, a brand of pine bark extract, in lowering blood pressure and improving glycemic control and plasma lipoprotein profiles. Lester Packer and colleagues at the University of California, Berkeley agree that pine bark extract, marketed as Pycnogenol, is one of the most potent antioxidants they have researched to date.5

Only time and more research will determine whether pine bark extract is as promising as it appears.

Beneficial When Bottled?
The supplement industry promotes exotic fruits bottled up as antioxidant supplements as a modern-day fountain of youth. Açaí berries, mangosteen, goji berries (wolfberries), and noni are all naturally high in antioxidants when consumed as whole fruits and fresh juices. Citing a handful of studies, some supplement companies claim that these “mysterious” fruits prevent cancer and other diseases and delay aging. Besides being leery of the quality of unregulated supplements in general, current scientific evidence does not justify the high cost of these exotic fruit-based supplements, especially in light of current economic conditions.

The More the Better
The meta-analysis study suggesting that certain antioxidants can actually increase the risk of mortality or have no effect at all correlates with a theory that multiple antioxidant supplements may be more effective.

A 1999 review article published in the Journal of the American College of Nutrition discussed the use of multiple antioxidant vitamins in cancer therapy. The study authors stated that at lower doses, certain individual antioxidants may be ineffective or actually stimulate cancer cell growth. This motivated researchers to conduct in vitro studies to reveal whether certain groups of antioxidants can prevent cancer cell growth. The researchers conclude that an in vitro study with a mixture of four antioxidants (in the form of 13-cis-retinoic acid, sodium ascorbate, d-a-tocopheryl succinate, and polar carotenoids without any beta-carotene) significantly inhibited the growth of human melanoma cells in culture doses where each component individually had no effect.6 This study suggests that increasing the diversity of antioxidants may actually enhance one’s protection against oxidative damage to cells.

Since the 1999 review article, the Journal of the American College of Nutrition published additional articles showing the positive effects of multiple antioxidant supplement therapies with managing Parkinson’s disease, Alzheimer’s disease, cancer, and other chronic conditions.

Power of Produce
The current debate over the value of antioxidant supplements will likely continue for years. The available research is contradictory. However, all scientists and dietitians can agree on this: Eating whole fruits, vegetables, and grains packed with natural antioxidants decreases the risk of cancer, heart disease, diabetes, and a multitude of other diseases. Tell your clients to take a shopping trip through the produce section for their antioxidants. In terms of antioxidant protection, fruits and veggies do matter.*


* Fruits & Veggies — More Matters is a national health initiative to promote increased fruit and vegetable consumption.

— Jasmin Ilkay, MPH, RD, is a lecturer for the human nutrition and food science department at the California State Polytechnic University in Pomona and a freelance writer specializing in dietary supplements, child and family nutrition, and eating disorders.


1. Oregon State University. Study citing antioxidant vitamin risks based on flawed methodology. February 27, 2007. Available at: http://oregonstate.edu/dept/ncs/newsarch/2007/Feb07/vitaminstudy.html

2. National Cancer Institute. Beta-carotene supplements confirmed as harmful to those at risk for lung cancer. Available at: http://www.cancer.gov/clinicaltrials/results/final-CARET1204. Accessed March 2010.

3. Sarubin-Fragakis AS, Thomson CA. The Health Professional’s Guide to Popular Dietary Supplements, 3rd edition. Chicago: American Dietetic Association; 2006.

4. Stafford RS, Stanford University UPBEAT research team. Understanding pine bark extract an as alternative treatment (UPBEAT): Orientation for antioxidant study. Available at: http://ppop.stanford.edu/documents/antioxidant-presentation.pdf

5. Sanders R. Pine bark extract is a potent antioxidant, and may help boost the effects of vitamin C and other antioxidants, UC Berkeley scientists report. February 5, 1998. Available at: http://berkeley.edu/news/media/releases/98legacy/02_05_98a.html. Accessed February 2010.

6. Prasad KN, Kumar A, Kochupillai V, Code WC. High doses of multiple antioxidant vitamins: Essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr. 1999;18(1):13-25.