April 2013 Issue

Dietary Antioxidants — Do Foods and Supplements With High Antioxidant Values Guarantee Better Health?
By Sharon Palmer, RD
Today’s Dietitian
Vol. 15 No. 4 P. 42

For years, edible plants competed for the title of the highest ORAC, a measurement of foods’ total antioxidant capacity. Yet scientists suggest antioxidant metabolism and bioavailability are the keys to greater health benefits. Today’s Dietitian discusses this hot topic with some of the world’s leading dietary antioxidant researchers.

In today’s world of high-tech nutrition, plugged-in consumers use apps to help locate the “real” antioxidant value of hundreds of foods as they shop. This is the same world that’s home to too many high-antioxidant “superfruits” to count.

A plethora of plant foods keeps scratching their way to the top of the oxygen radical absorbance capacity (ORAC) list, a chemical laboratory analysis technique that measures the total antioxidant capacity of foods. One day goji berries are No. 1, and the next day it’s Moringa oleifera tea. Plus hundreds of antioxidant supplements boast of their high ORAC scores and are marketed to consumers interested in preventing diseases associated with aging.

Unfortunately, the message that ORAC is simply a laboratory analysis that measures antioxidant capacity in a test tube, not in a human, has gotten lost in all of this hype. 

“Because modern-day consumers are constantly bombarded with information, they may naturally look for product comparisons based on quantifiable levels and values,” says Navindra P. Seeram, PhD, an assistant professor at the Bioactive Botanical Research Laboratory at the University of Rhode Island. “Unfortunately, this has led to a misuse in the term ‘antioxidants’ in products, including whole foods, beverages, and supplements that are touted against each other based on ‘antioxidant levels’ derived from a vast array of laboratory-based assays, which has led to considerable consumer confusion.”

Subsequently, health organizations and nutrition researchers alike are trying to clean up the antioxidant business. Recently, the USDA removed the USDA ORAC Database for Selected Foods from its website, citing mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds on human health. The USDA reports that ORAC values routinely are misused by food and dietary supplement manufacturing companies to promote their products and by consumers to guide their food and dietary supplement choices.1 

“One of the reasons the USDA removed the ORAC database from its website was it felt that some companies were abusing this resource by suggesting that it supported the purported content and health claims about their products,” says Jeffrey B. Blumberg, PhD, a professor and the director of the Antioxidants Research Laboratory at Tufts University. “But the ORAC is an in vitro assay and one of several related methods that, by definition, does not account for bioavailability, distribution, and metabolism of a product’s ingredients. Further, correlations between ORAC results and clinical outcomes are lacking. However, the problem is not with the assay itself but rather how its results have been interpreted. A high ORAC value of a food, beverage, or supplement as an indicator of health benefits is misleading.”

The Antioxidant Message
A major problem regarding antioxidants has been an oversimplification of nutrition terms used in the media. Antioxidant seemed to be an easy term that consumers caught on to even though they didn’t understand the complicated science behind it. And food and supplement marketers were all too eager to jump onto the antioxidant bandwagon.

“Many people have been persuaded by the marketing of products that are ‘high’ or ‘rich’ in antioxidants; presumably, this approach is working because many companies have used this description and continue to do so,” Blumberg says. “Basic marketing principles include make it simple, make it understandable, and make it actionable. But we’ve gone too far down the road by suggesting the reason that fruits and vegetables are good for you is because they contain antioxidants, and those with the most of these nutrients are ‘superfoods.’”

So what’s the problem with delivering the antioxidant message? According to Blumberg, “Communicating clearly about antioxidants in this way is misleading because many of these compounds, including thousands of carotenoids and polyphenols in plant foods, act to quench free radicals effectively only in vitro, not in vivo. Nonetheless, they’re certainly bioactive, serving to inhibit inflammation, increase detoxification, and upregulate some antioxidant enzymes. But inaccurate statements today may lead to problems in the near future, as research more fully elucidates all these mechanisms of action to promote health and reduce the risk of chronic disease. Some consumers may then complain, ‘But you told me it was the antioxidants.’” 

“In the marketing area, everyone wanted to get the highest ORAC value, but it wasn’t the whole story,” says Ron Prior, PhD, a nutritionist and research chemist and an adjunct professor in the department of food science at the University of Arkansas. “You need to understand what’s in a particular food, how it’s absorbed and broken down, and the amount that gets into the tissues of the body,” Prior says.

An expert in plant antioxidant research, Prior recently authored the report “Antioxidant Food Databases? Valuable or Not?” which explored the recent action by the USDA to dismantle its ORAC database on the organization’s website.2

“Another problem is that we’re making people think it’s no longer the vitamins, minerals, or fiber but only the phytochemicals that promote health,” Blumberg says. “But the reason plant foods are good for you is because of everything they contain. There’s synergy for all of these ingredients—synergies between ingredients within one food and between multiple foods. That’s why the Dietary Guidelines for Americans recommends we consume a diversity of fruits, vegetables, and whole grains.”

The ORAC Story
ORAC, which measures the degree of inhibition of peroxy-radical-induced oxidation by compounds, is fairly well known as a method for measuring antioxidant capacity in foods, but it’s just one of several chemical techniques that have been developed. Other measures of antioxidant capacity include ferric ion reducing antioxidant power and trolox equivalence antioxidant capacity assays, which use different radical or oxidant sources and generate distinct values that can’t be compared directly.1

“ORAC doesn’t distinguish between different categories; it’s responsive to some antioxidants and not others,” Blumberg says. “For some compounds, the results are very high, and for some, they are low. It’s not a very good assay for certain lipid-soluble compounds, such as carotenoids. Few of the assays correlate very well with one another.”

Linking Antioxidant Levels to Human Health
The debate over antioxidants extends to whether they can, indeed, be linked to human health benefits. Phytochemicals are defined as nonessential nutrients found in plant foods, many of which have been established as bioactive and may affect human health. The largest group of phytochemicals is the polyphenols, comprised mainly of flavonoids, which are commonly defined as dietary antioxidants. 

According to a review by Tufts University researchers, evidence from observational studies indicates that regular consumption of foods containing flavonoids may reduce the risk of several chronic conditions, including neurodegenerative diseases, atherosclerosis, and certain forms of cancer. But much basic information about their nutrient characteristics in humans remains limited, including their bioavailability and metabolism, interactions with other dietary factors, mechanisms of action, and intakes associated with specific health outcomes.3

So should we stop talking about antioxidant levels altogether? “That’s a huge hot button in our group. I do feel that it’s throwing the baby out with the bath water,” says Mary Ann Lila, director of the Plants for Human Health Institute and a David H. Murdock distinguished professor at North Carolina State University.

“ORAC is a good marker; it’s a good way to gauge antioxidant capacity. But antioxidants are only the tip of the iceberg as far as the benefits of phytoactives,” Lila says. “There are anti-inflammatory effects and upregulation of enzymes that catalyze disease-suppressing reactions. Antioxidants will tell you something—people know that now. A vitamin C pill will give you a lot of antioxidants, but it’s not the same thing as a blueberry, which is complex. You have to dig deeper, into in vivo studies.”

Interestingly, some recent evidence links ORAC levels to health outcomes. “There’s a good relationship with the ORAC levels in food to intake of dietary antioxidants and effects on health, such as cancer and metabolic syndrome,” Prior says. “I think it’s a valuable tool, but people need to understand, like any lab analysis, it has limitations.” He reports that in the last three years, there have been more than 25 publications dealing with dietary antioxidants and in vivo antioxidant status or disease.2

For example, a 2012 Swedish study, which included more than 31,000 women, assessed the impact of dietary total antioxidant capacity on stroke incidence. They found that the highest intake of total antioxidant capacity was linked with a lower risk of stroke in both cardiovascular disease-free women and those women with a history of the condition.4 And the ORAC database was linked with decreased risks of endometrial cancer, comparing the highest tertile of total phenolic intake with the lowest.5

Moving Beyond In Vitro
To better understand antioxidants and health—as is the case with most nutrition research—studies begin in the lab and then move on to animals and humans. “Researchers are getting more and more on the same page about antioxidants. People are [understanding] that antioxidants are only one biomarker—not the one that gives us the most information,” Lila says. “More and more research can no longer be accepted when you give simply the polyphenolic profile of a plant; you must have more. These things cost money; ORAC was so cheap to do. To do an animal study costs 10 times more, so it’s difficult to get this data under our belts. I’ve been involved with researching blueberries in diabetes and tomatoes in prostate cancer, and in these cases, the research started off at one level, but in the past 15 years, everything has moved to clinical trials with humans.”

For example, blueberry research debuted with the ORAC data, followed by the work of the late James Joseph, PhD, director of the neuroscience laboratory at the USDA-ARS Human Nutrition Research Center on Aging at Tufts University, who conducted his legendary animal studies on the effects of blueberry antioxidants.

Lila says the whole focus of blueberry research now is on clinical trials, like the one she just completed, which investigated the effects of blueberries on high-performance athletes. Other blueberry studies have linked blueberry bioactives with enhanced insulin sensitivity in obese, nondiabetic, and insulin-resistant subjects6 and decreased cardiovascular risk factors in obese men and women with metabolic syndrome.7

While scientists are exploring new frontiers, there’s still a long way to go. “Today, antioxidant research is where most vitamins were about 60 years ago. We’re still trying to characterize what these compounds are, their bioavailability, and active principles,” Blumberg says. 

What Happens in the Human Body?
Antioxidant researchers are playing detective, trying to uncover what happens to bioactives once they’re consumed. “We’re beginning to explore how lycopene works in the prostate and anthocyanins in the brain, and what tissues they end up in,” Prior says. “In the whole research area, anticancer activity and cell death in tissue cultures may mean nothing in vivo if it doesn’t make it into the tissue. We don’t have much information about how these compounds get into the body tissues. We were surprised to find that anthocyanins get into the brain tissue. Anthocyanins contribute to the antioxidant capacity of berries, but they’re very unstable and the amount that actually gets absorbed may be as low as one-tenth of 1% from the amount consumed in the diet.”

Lila has worked with tracking radiolabeled blueberry polyphenols, as well as lycopene and carotenoids in animal models, to understand where these compounds accumulate in the body. “We were the first to demonstrate anthocyanins from blueberries cross the blood-brain barrier and get to the brain,” says Lila, whose blueberry research was published in the Journal of Agricultural and Food Chemistry.8

“Indeed, we’ve learned that for many phytochemicals, it’s not the parent plant compound that’s bioactive; it’s the metabolites created by the gut flora, liver, lung, retina, or other tissues in the body,” says Blumberg, who reports that conversion of these metabolites also may be related to nutrigenomics. For example, some day health practitioners may be able to determine whether a particular patient has the ability to convert isothiocyanates from broccoli into cancer-preventing compounds. 

“In many cases, these compounds actually stimulate the body’s natural defense system of endogenous antioxidants. It may even be something different, such as [the] effects [of bioactive compounds] on inflammation, cell division, or apoptosis,” Prior adds. “Bioactives also may be modified and conjugated with glucuronide or sulfate, which the body usually does to detoxify compounds.” 

Scientists are just starting to scratch the surface when it comes to these bioactives. “We need the same sort of understanding for phytochemicals that we have today for the basic aspects of vitamins, such as needs of toddlers, adults, and the elderly and how they’re absorbed and metabolized, which is how we developed the RDAs [Recommended Dietary Allowance]. We lack a great deal of that information, and it’s going to be a critical part of growing our knowledge base and applying it in a thoughtful manner,” Blumberg says.

Supplements vs. Real Food
Science supports the benefits of bioactive compounds in plants vs. isolated in supplement form. “People think that antioxidants are good for them, and more is better. One of the problems is that when you start isolating some of these compounds, such as antioxidants, and take them singly [in pill form], they may have an opposite effect—they may act as pro-oxidants [substances that promote oxidative stress],” says Prior, who adds that to get a high ORAC value, some companies add cheap compounds to supplements.

“The strength of evidence is really quite limited for antioxidant supplements,” Blumberg says. To go from red wine to thinking the benefits are only about resveratrol and then from the miniscule doses of resveratrol in red wine to taking gram quantities of resveratrol in supplements is jumping the gun, he adds. 

Bottom Line
So what’s the best advice dietitians can give the public on antioxidants? 

“In my opinion, the smartest recommendation is to continue to eat a wide variety of whole plant foods. How else will you get the triple whammy of macronutrients, micronutrients, and phytonutrients?” Seeram says.

“I advise combining different foods—don’t use just one food—for a combination of different foods predominant in compounds that are going to have high antioxidant capacity,” Prior says. He notes that the average American diet has a total antioxidant capacity of about 3,000 to 5,000 ORAC units (expressed as micromoles of trolox equivalents), but it needs to increase to roughly 12,000, which would be equivalent to eight to nine servings of fruits and vegetables per day. “There’s no question that we need to consume a higher quantity and variety of foods that are high in antioxidants,” Prior says.

“The phytochemical story is a useful one, and people are using it to choose more colorful fruits and vegetables with deeper hues because these are indicators of different phytochemical profiles,” Blumberg says. “The story is about underscoring the advice that we’re already trying to give, but it makes a more persuasive argument that all fruit isn’t the same. They all contain different things, and they all contribute to your health.”

— Sharon Palmer, RD, is a Los Angeles-based food and nutrition writer. She’s also the author of The Plant-Powered Diet, the editor of Environmental Nutrition, and a contributing editor to Today’s Dietitian.

 

References
1. Oxygen radical absorbance capacity (ORAC) of selected foods, Release 2 (2010). US Department of Agriculture website. http://www.ars.usda.gov/services/docs.htm?docid=15866. Accessed December 1, 2012.

2. Prior R. Antioxidant food databases? Valuable or not? Brunswick Laboratories website. http://www.brunswicklabs.com/Portals/153979/docs/A Response to the USDA ORAC Statement.pdf. Accessed December 1, 2012.

3. Corcoran MP, McKay DL, Blumberg JB. Flavonoid basics: chemistry, sources, mechanisms of action, and safety. J Nutr Gerontol Geriatr. 2012;31(3):176-189.

4. Rautiainen S, Larsson S, Virtamo J, Wolk A. Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women. Stroke. 2012;43(2):335-340.

5. Gifkins D, Olson SH, Demissie K, Lu SE, Kong AN, Bandera EV. Total and individual antioxidant intake and endometrial cancer risk: results from a population-based case-control study in New Jersey. Cancer Causes Control. 2012;239(6):887-895.

6. Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr. 2010;140(10):1764-1768.

7. Basu A, Du M, Leyva MJ, et al. Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome. J Nutr. 2010;140(9):1582-1587.

8. Lila MA, Ribnicky DM, Rojo LE, et al. Complementary approaches to gauge the bioavailability and distribution of ingested berry polyphenolics. J Agricul Food Chem. 2012;60(23):5763-5771.

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