All About Antioxidants

By Marie Spano, M.S., R.D., Contributing Editor

Antioxidantsminerals, vitamins and phytochemicals, such as flavonoidsmay protect against the free radicals that are implicated in cell damage and aging, heart disease, cancer and other diseases. While antioxidants are easy to find in certain foods and specific ingredients, the science behind their measurement is more difficult.

Significance of antioxidants

Antioxidants are found in fruits and vegetables, nuts, grains, milk products, teas, legumes, spices, herbs, and some meats, poultry and fish. They are defined as substances that may protect human cells against the effects of highly unstable free radicals and, therefore, potentially disease-producing cell damage (U.S. National Library of Medicine). However, this simplistic regulatory definition of antioxidants does not capture the complex biological reactions of this broad category of nutrients. Most of them are multifunctional, and some are anti-inflammatory compounds, cell-signaling agents, and some up- or down-regulate gene expression (part of what cell-signaling agents do)," says Jeffrey Blumberg, Ph.D., director, Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston. "In addition, some antioxidants function weakly on reactive oxygen species, but they tell the cell to up-regulate antioxidant defense systemstechnically not acting as antioxidants in the way the FDA defines it."

Although the formal definition of antioxidants is based on their ability to protect against free-radical-induced cell damage, their impact on biomarkers of oxidative stress depends on many factors, including the baseline value of the biomarkers, initial status of the antioxidant defense network within the body, amount of antioxidants consumed, duration of consumption, absorption, metabolism, and mechanism of action of the specific antioxidants (Nutrients, 2010; 2:929-949). Additionally, the relevance of these biomarkers as predictors of disease risk is, in some cases, unclear (American Journal of Clinical Nutrition, 2005; 81:261S-267S). 

Despite the complexities that underlie the actions of antioxidants within the body, they are important for good health. Many studies show if you eat more of these compounds you decrease your risk of heart disease, diabetes, cancer and numerous other diseases,"  notes Blumberg. "But those foods contain many other healthy compounds, as well."

Importance of select antioxidants

We know the most about vitamins C and E, which, in addition to selenium, are essential. In fact, a deficiency of any of these nutrients will lead to a deficiency syndrome and death. In addition to acting as antioxidants, vitamins C and E, carotenoids and various polyphenols also have other mechanisms of action, including anti-inflammation, induction of phase 2 detoxification enzymes, and modulation of redox-sensitive signal transduction and gene expression (Nutrients, 2010; 2:929-949).

High intakes of vitamin C-rich fruits and vegetables may lower ones risk of some types of cancer, including lung, breast and colon cancers. Additionally, vitamins C and E, as part of a multinutrient combination that also includes beta carotene and zinc oxide, may significantly reduce risk of developing advanced stages of age-related macular degeneration (AMD) and vision loss in patients with AMD (Archives of Ophthalmology, 2001; 119:1,439-1,452). However, more isnt always better. In the Selenium and Vitamin E Cancer Prevention Trial, men who took a vitamin E supplement (400 IU dl-alpha-tocopheryl acetate) for an average of 5.5 years had a 17% increased risk of prostate cancer (JAMA, 2011; 306(14):1,549-1,556).

Observational studies show populations with higher blood levels or intake of selenium, a trace mineral that also functions as an antioxidant, have a lower death rate from cancer. Additionally, a multicenter double-blind, randomized, placebo-controlled study examining the impact of 200 mcg selenium supplementation over a mean 2.8 years on skin cancer incidence over a period 4.8 years found selenium did not protect against skin basal or squamous-cell carcinomas of the skin, but it did reduce the occurrence and death from total cancers and incidence of prostate, colorectal and lung cancer (JAMA, 1996; 276:1,957-1,963).

Though increased dietary intake of antioxidants may decrease risk of some diseases, supplementation studies are mixed, due, in part, to the fact that supplements do not contain the additional beneficial compounds found in antioxidant-rich foods. A review of 68 randomized trials examining the effects of antioxidant supplements and mortality found antioxidant supplements had a statistically significant beneficial effect in populations at risk of micronutrient deficiencies of vitamins C and E, selenium, beta-carotene and other nutrients such as zinc, all of which play roles in the human bodys antioxidant defense network. Supplementation may be beneficial in those with inadequate nutrient intake, even without clear signs and symptoms of inadequate intake, but may provide no benefit in those individuals who have an adequate intake. In addition, excess supplemental beta carotene, vitamin A and vitamin E may increase mortality in some populations (JAMA, 2007; 297:842-857; Nutrients, 2010; 2:929-949).

In addition to beta carotene, two other carotenoids are gaining ground. Lutein and zeaxanthin, found in the retina of the eye, protect the lens from oxidative damage and reduce ocular inflammation (Progress in Retinal Eye Research, 2012; 31:303-315; Molecular Vision, 2011; 17:3,180-3,190). Lutein and zeaxanthin supplementation (20 mg lutein or 10 mg of each) for 48 weeks improved retinal functioning in those with early AMD (American Journal of Ophthalmology, 2012; doi:10.1016/j.ajo.2012.04.014),  and supplementation has been shown to stabilize or improve visual acuity and contrast sensitivity in those with AMD (European Journal of Ophthalmology, 2012; 22:216-225).

Polyphenolsantioxidants found in plant-derived foods that may contribute to the bitterness, astringency, color, flavor, odor and oxidative stability of a foodare currently considered the most abundant antioxidants in the diet, with over 8,000 polphenolic compounds identified in plants. Flavonoids, stillbenes and lignans are all polyphenols, and flavonoids are further divided into six major subclasses: flavonols, flavanones, flavanols, flavones, anthocyanins and isoflavones (Oxidative Medicine and Cellular Longevity, 2009; 2:270278). Human cell research and animal studies suggest supplemental doses of polyphenols contribute to health and the prevention of cardiovascular diseases, cancers, neurodegenerative diseases, diabetes and osteoporosis (Critical Reviews in Food Science and Nutrition, 2005; 45:287-306). In addition, some polyphenols, either through food or dietary supplements, positively impact biomarkers of cardiovascular disease (American Journal of Clinical Nutrition, 2005; 81:215S-217S). However, results vary among individuals. Extensive metabolism of polyphenols occurs in the gut, and metabolism depends on your gut flora if you receive a benefit," according to Blumberg. Although commonly defined as dietary antioxidants, the physiological effects of flavonoids appear mediated largely by their metabolites acting to modulate cell cycling, cell proliferation, detoxification and inflammation mediated via cell-signal transduction pathways (Journal of Nutrition in Gerontology and Geriatrics, 2012; 31:114). For instance, anthocyanins, a category of flavonoids found in brightly colored red and purple produce, such as berries, have antioxidant and anti-inflammatory effects acting as COX 1 and 2 inhibitors, in addition to inhibiting lipid peroxidation (Journal of Agricultural and Food Chemistry, 2003; 51:1,9481,951). Also, cocoa flavonols, found in dark chocolate, can improve endothelial functioning, biomarkers of oxidative stress, inflammation, vascular reactivity and blood pressure (Journal of the American College of Nutrition, 2004; 23:197204). And, though naturally fermented cocoa bean is rich in flavonols, these compounds are bitter tasting, so many chocolate companies remove flavonols for a product that is sweeter yet not as rich in antioxidants.

Measuring antioxidant capacity

According to Blumberg, total antioxidant capacity (TAC) assays have a useful role in research studies. However, they do not directly correlate to action in vivo. What happens in a test tube may have little or no relation to what happens in the human body. All of the reactions that happen in the human body cant happen in the test tube, so we are not given a full picture of an ingredient or compound's action if we only zone in on a test-tube study. It is therefore misleading to use information about TAC on labels. In fact, USDA took their database about TAC values off their website as manufacturers were abusing this data for labeling and marketing."

Aside from using TAC, marketers can use an antioxidant nutrient-content claim for antioxidants that have an established RDI, such as vitamin C, (Title 21 of the Code of Federal Regulations (CFR), Part 101). Additionally, a claim can be made that describes antioxidant properties of a product for antioxidants that do not have an RDI but participate in antioxidant processes. Structure/function claims can also be made about antioxidants, as long as such claims are not false and misleading (21 CFR 101.549(g)(4); 62 FR 49868 at 49873). However, instead of simply calling compounds antioxidants on nutrition labels, Blumberg recommends companies differentiate your product by saying, contains anthyocyanins, and then tell consumers why that category of antioxidants or compounds is beneficial for them. Tell them their mechanism of action and what differentiates your product. Educate them about your messaging and why it is so special."

There are thousands of antioxidants in our food, and compelling science behind their various roles in human health. However, science is still too limited to formulate specific recommendations for the general population. And, one major challenge of conducting randomized controlled trials to examine the safety and efficacy of antioxidants is the need for long-duration studies and validated biomarkers (Nutrients, 2010; 2:929-949).  Getting enough, and enough of the right ones, is the question," Blumberg says. "With antioxidants we are where vitamins were 70 or 80 years ago. We have a long way to go, but science moves faster these days."

Marie Spano, M.S., R.D., CSCS, is a nutrition communications expert whose work has appeared in popular press magazines, e-zines and nutrition-industry trade publications. She has been an expert guest on NBC, ABC and CBS affiliates on the East Coast. For more information, visit mariespano.com.