The Body's Best Preservative:

The Body's Best Preservative:
Antioxidants and Health

By Kimberly J. Decker 
Contributing Editor

The assumption that antioxidants are good for you presupposes that oxidation is badgenerally, it is. Oxidation occurs when atoms lose electrons. It makes automobiles rust and oil go rancid and happens all the time in our bodies. Explains Dov Hartal, a Tel Aviv-based scientific advisor to LycoRed Corp., Fairfield, NJ: Our whole existence is based on oxidation. The cellular respiration that converts energy stored in food to adenosine triphosphate (ATP); communication channels between cells; and the inflammatory response to infection and tissue damage depend largely on helpful oxidation.

When oxidation recklessly targets the structure and substance of what we arecell membranes, enzyme complexesit not only damages those structures, but generates more of the agents that perpetuate oxidation. These agents, free radicals, are atoms or molecules whose unpaired electrons render them unstable and highly reactive. Seeking to restore their stereo-chemical stability, free radicalsthe peroxyl and hydroxyl radicals, hydrogen peroxide, super-oxide ion, peroxynitrite, and singlet oxygen being common examplesnab electrons from our cellular structures and components to top off their own unfilled shells. Having done so, they leave these newly oxidized victims electron-deficient themselves and as reactive as the original radicals. These new radicals then grab electrons from their nearest prey and spark a redox brushfire, fueling small-scale biological destruction and chemical chaos.

Evolution has ceded us enzymes, such as superoxide dismutase and glutathione peroxidase, as well as compounds like glutathione and thiols to defend against the natural oxidative damage we sustain. But, notes Hartal, In this modern society, we are attacked by a large number of free radicalsmuch more than a human being was originally exposed to from pollution, from chemicals, etc. And we live longer than we used to. Therefore, theres cumulative damage of those free radicals with time. 

Thus runs the idea behind the Free Radical Theory of Aging, which proposes that just as a lifetime of oxidation leaves an auto body caked in rust, a similar buildup of oxidative assault deteriorates the human body. As Bill Haddad, vice president, technical services, American Fruit Processors, Pacoima, CA, puts it: If you place a piece of steel in water, there is a lag time before the rusting process starts. Then there is an accelerated rate at which rusting occurs, and then there is a leveling off of that process where it somewhat slows down and just continues to rust over a long period of timeeventually deteriorating to a point of nonexistence.

The oxidative rusting of our DNA, mitochondria, enzymes and cell membranes also leads to chronic diseases such as atherosclerosis, Alzheimers disease and various cancers, particularly colon and lung. But by recognizing oxidations role in these degenerative processes, we hold the key, if not to their outright reversal, at least to their attenuation. After all, studies show that stimulating the expression of the antioxidant catalase in mice increases their average life span by 20%. As Haddad says, Unfortunately, you cannot stop time as you age. But you can slow down the physical aging process.

Antioxidants to the rescue 

And we dont need a time machine to do so. We just need dietary antioxidantsphytochemicals that evolved to protect plants from oxidation, but can bolster our inborn defenses, as well. They do so not so much by preventing oxidation, but by offering themselves up for oxidation so our bodys structures dont have to. By sparing our tissues from oxidative damage, antioxidants act as the bodys fall guys, sacrificing their electrons to neutralize a free radicals jittery unpaired ones. And because an oxidized antioxidant is often relatively stable, its resonance stability freezes the oxidative chain reaction before it starts.

Antioxidants do their job in several ways. Free radical quenchers, a category that includes tocopherols; rosemary, sage and other botanical extracts; and synthetics like BHA and BHT, function by donating a hydrogen to quench the free radical and convert it into a less-reactive radical, says Gary Hainrihar, vice president, sales and marketing, Kalsec Inc., Kalamazoo, MI. By contrast, metal chelators or sequestrants, such as vitamin C, dont intercept free radicals, but associate with the metal catalysts that initiate free-radical generation. And carotenoid pigments, such as betacarotene, lycopene, and the xanthophylls lutein and zeaxanthin, prevent oxidation by using their long chains of double-bonded carbons to absorb oxidizing wavelengths of UV light that would otherwise wreak havoc on cells and tissues.

When researchers follow populations with diets rich in these and any of the thousands of other antioxidants, a striking pattern surfaces. Such populations almost always live longer and are more healthy. We first observed and described this correlation mid-20th century in studies such as those that established the diet-health relationship of the Mediterranean diet. Ever since, the weight of epidemiological evidence has only confirmed the link between high intakes of fruits, vegetables and whole grains and positive health outcomes ranging from lower rates of cancer and heart disease to outstanding life expectancies free from the degenerative disorders that plague more post-industrial cultures.

The devil is in the details 

Examined in light of the free-radical theory of aging, then, the good health that researchers observed in largely vegetarian populations led them to ask if the antioxidants in their diets were responsible. If oxidative stress is the cause, the pathology, or both of any chronic disease, this is the reason, why the epidemiology says you should consume more fruits and vegetables, says Joe A. Vinson, Ph.D., professor, department of chemistry, University of Scranton, Scranton, PA.

Ginny Bank, vice president, research and development, RFI Ingredients, Blauvelt, NY, agrees: There are plenty of studies out there that talk about antioxidants from fruits and vegetables in general, and how, over the long-term, they can help prevent heart problems and cancer.

But conclusions drawn from epidemiology take us only so far. Its not enough to know that antioxidants, in aggregate, make us healthy. Science seeks details: mechanisms, locations of action, which antioxidants alter the progression or repression of which diseases. Massive population effects obscure these particulars. And rather than reveal a causal relationship between an antioxidant and a condition, they deal only in correlations.

So scientists tighten their focus and study individual antioxidants in a clinical or laboratory setting, isolating and extracting the compounds from food sources and testing them against controls in vitro or in human subjects. Martin Starr, Ph.D., science advisor to the Cranberry Institute, East Wareham, MA, notes, Its so simple to look in the test tube, relatively speaking, compared to looking in the body, which is like a trillion test tubes doing different things at different rates with different reactants. The approach affords researchers control and rewards them with specificity.

But while such inquiries allow us to isolate an antioxidants effects, that doesnt mean that antioxidants operate in isolation. Once we go from the test tube to the body, all of a sudden, things behave differently, Starr says. Whether youre looking into health maintenance or cures, once you start fooling around with the body, nothing is absolute except that whatever happens probably isnt going to turn out like you thought it would as a researcher.

Thus, observes Mary Jo Feeney, MS, RD, FADA, a Bay Areabased nutrition advisor to the California Dried Plum Board, the effort to study the effects of individual antioxidants presents a paradox of its own. From a researchers standpoint, she says, they isolate the compounds to see if they have any effect. But its a catch- 22: Somebody wants to determine that antioxidant X has an effect, but when they isolate X to do the study, it doesnt turn out to have the same effect as it does in the food.

Not surprisingly, then, the results of many studies on the health effects of isolated antioxidant supplements run from ambivalent to downright discouraging. For example, the Cambridge Heart Antioxidant Study followed 2,000 patients with ischemic heart disease and found that, although those who received 400 or 800 IU of vitamin E daily reduced their incidence of non-fatal myocardial infarction by 77%, researchers dont know if that was because of Es antioxidant or anticoagulant activity.

As for a study conducted at the National Cancer Institute, Bethesda, MD, and reported in the February 2006 Journal of the National Cancer Institute, among 29,361 men enrolled in a prostate-cancer screening trial, supplementation with vitamins E and C and betacarotene had no association with prostate cancer incidence. And more alarmingly, the 1994 Alpha- Tocopherol/Beta-Carotene Cancer Prevention (ATBC) Study found that lung cancer rates in Finnish male smokers rose significantly with beta-carotene supplementationso much so that researchers halted that portion of the study.

Measure for measure 

As if determining the behavior of an individual antioxidant werent challenging enough, drawing a bead on the doings of the full complement of antioxidants in a food adds several more layers of complexity, beginning with the quantification of antioxidant content and the qualification of antioxidant efficacy. Were just in the beginnings of being able to measure these things, Vinson says. All our studies are based on a pure compound, like a drug. And those are easy things to dochange one variable and thats it. But when youre talking about foods and beverages, there are variables all over the place that you cannot control.

Quantifying antioxidants in foods is relatively straightforward. However, such quantities are at best benchmarks, given how much they vary with plant source, the conditions and treatment during cultivation, and post-harvest processing. For example, while a Brazil nut grown in the selenium-rich soil of Brazil may incorporate more than 100 mcg of selenium into its single kernel, consumers might need to eat 10 times as many nuts grown in a relatively selenium- poor American orchard to get the same amount of the mineral, according to a 1995 study published in the journal Chemosphere.

In addition, measuring total antioxidants in the body poses a significant challenge, Vinson says, because of the low levels of antioxidants, particularly non-nutrient antioxidants, in physiological fluids. And, asks Feeney, If youre trying to trace a particular compound in the body, what if that compound changes as it gets involved in whatever processes its involved in? It may lose a hydroxyl somewhere; it may lose a double bond. But it gets changed. And if youre still measuring it, you dont see it.

And the fact is, as Vinson says, that antioxidants do get extensively changed in the body into metabolites. These also could be, and probably are, the active components, rather than the original compounds in the food. Case in point: Several studies have found that only traces of unchanged resveratrol remain in the plasma after feeding with 25 mg of the phenolic in its trans isomer; meanwhile, concentrations of resveratrol metabolites peak at 2 mmol per liter 30 to 60 minutes following such feedings.

So in addition to measuring a bodysor a foodsantioxidant quantity, we measure its antioxidant efficacy. In the 1990s, researchers at the National Institute on Aging, Baltimore, developed an assay that compares an antioxidant samples ability to quench free radicals with that of a standardeither the watersoluble tocopherol derivative called Trolox when the radical being quenched is peroxyl, or gallic acid, when the radical is hydroxyl. Known as the ORAC, or oxygen radical absorption capacity, test, the assay has quantified the antioxidative capacity of everything from whole, fresh foods to plasma to pure chemicals to the antioxidant capacity of urine in nutritional testing. The values, usually expressed as micromoles of Trolox equivalents (TE) per gram of sample, range from around 3 mmol TE per gram for mangos and green peppers to red cabbages 40 mmol TE per gram to more than 100 mmol TE per gram for pomegranates and black raspberries.

Whats the matter with ORAC?

Although other tests exist, such as the Trolox-equivalent antioxidant capacity (TEAC), total oxyradical scavenging capacity (TOSC), and ferric-reducing antioxidant power (FRAP) tests, ORAC became the lingua franca for quantifying antioxidant activity, and with quantifiable results in hand, food and supplement marketers held up their products ORAC values as the final word in antioxidant effectiveness. Says Bank, ORAC took hold in the industry and the momentum just carried it forward.

But, notes Betty Burri, Ph.D., associate adjunct professor of nutrition at the University of California, Davis, ORAC values are more limited than the ORAC proponents would like you to believe. And indeed, since the tests widespread adoption, scientists have raised issues with some of its methodological shortcomings The tests marketer, Brunswick Laboratories LLC, Wareham, MA, has addressed the most common of these: replacing an unstable fluorescent probe used in the test with the less reactive fluorescein, and adjusting the method to accommodate fat-soluble antioxidants.

Nevertheless, as Bank points out, variables in the extraction of the antioxidant samples themselves can skew results, tempting some to deviate from standard procedures or solvents to post higher numbers. She also believes some of the science is getting lost as ORAC has become entangled in marketing.

Starr would agree. While the cranberrys antioxidants often rank as the most potent of all fruits, hes reluctant to build his brand around those findings, asking, Who ran the assay? Was it ORAC? Was it TEAC? Was it looking at total polyphenols? Because, depending on how and what method you run, you will get different results. So companies that build their whole message around being number one risk being toppled by the next hot thing. Rather than claim top status, therefore, cranberries bill themselves as a leading source or one of the top sources.

In the end, Bank views the misuse of the assay as a tragedy, because she thinks that ORAC is a really good, basic method for looking at this information. And her company relies on it as one of its most dependable quality-control checks. So, besides the fact that we say that one of our products has so-many ORAC units, for us it ensures that every lot of material we make is the same, she says. And well guarantee that every time you buy our product, it will meet those levels.

Staking a claim 

Beyond providing ORAC numbers to illustrate a products antioxidant ranking, what can a manufacturer tell consumers about the value of its antioxidant-rich items? Not much. Aside from repeating the advice to eat five to nine servings of fruits and vegetables a day, even providing benchmarks for antioxidant consumption remains a matter of speculation. Admits Vinson, People always ask me, How much chocolate do I need? How much tea do I need? And I just say, As much as possible.

Indeed, Burri says, It would be nice if we knew how much antioxidants you need, but that will depend on the person, the tissue to protect, and all sorts of things.

Also accounting for the uncertainty is a crucial difference between traditional vitamins and minerals and the wider class of antioxidant phytonutrients. Namely, the body needs vitamins and minerals; we established their recommended dietary allowances (RDAs), because eradicating deficiency diseasesrickets from insufficient vitamin D, for exampleboth warranted them and suggested an endpoint we could objectively meet. Antioxidants, by contrast, are not biologically essential. As Hartal says, You can live very well without lycopene at all.

Rather, because their greatest promise lies in their potential to optimize the health we already enjoy, I always look at antioxidants as cheap long-term insurance, Bank says.

When youre dealing in optimization, therefore, answering the question How much is enough? requires asking Enough for what? Says Burri: Usually, when were talking about antioxidants, were talking about people who want to live to be 90 instead of 85. And the irony there is that the consumer savvy enough to pursue antioxidants as a hedge against the likes of heart disease or macular degeneration probably eats a pretty good diet already, she says.

In any case, manufacturers mustnt set their goalsor the publics expectationstoo high when it comes to antioxidants. That means abstaining from claims about their anti-cancer, anti-heart disease, or even anti-wrinkle rolesnone of which the FDA has vetted. And, while informing the consumer on the latest antioxidant science via the label is acceptable, you have to remember that youre designing a product label with strict regulatory guidelines, not a public-service pamphlet.

Nevertheless, an embargo on antioxidant health claims may not be such a liability after all, considering that antioxidants health benefits accrue so slowly that consumers wouldnt notice them anyway. Says Haddad, In todays world, everyone wants an immediate reactionone they can see, feel, touch, etc. But antioxidants work very slowly over a long period of time. Because people do not see the effects immediately, many do not take them seriously.

Staying balanced 

People may know that they need more antioxidants, but they havent flocked to the fruits and vegetables that are their most obvious source. Says Jeannette Quinn, key account manager, GNT USA, Inc., Tarrytown, NY: People arent getting enough fruits and vegetables either, because they dont like them or they dont have enough time to eat them. What better reason, then, to help consumers get their fruits and vegetables via healthier products? The key ingredient: fruit and vegetable extracts for antioxidant fortification.

Granted, fortifying with antioxidants might be an imperfect solution. Karen Lapsley, Ph.D., director of scientific affairs, Almond Board of California, Modesto, CA, believes, Food sources of antioxidants are better than supplements because foods contain a mix of nutrients and compounds that tend to work synergistically to maximize the antioxidant potential. And indeed, synergy is the watchword of antioxidant effectiveness.

For example, a recent Tufts University study, conducted by Jeffrey Blumberg, Ph.D., senior scientist and director of the universitys Antioxidants Research Laboratory, showed that the vitamin E and antioxidants in almond skins worked together to reduce LDL oxidation more than would be expected if you merely summed the effects of vitamin E and almond skin antioxidants separately, Lapsley says. Specifically, the skins flavonoids increased LDL oxidation resistance by 18% on their own, while the addition of tocopherol-rich meat increased that resistance to 52.2%.

Echoing the total-is-more-thanthe- sum-of-its-parts theme is the case of lycopene, Hartal says. If you take lycopene alone, it has a certain effect in the prevention of LDL oxidation. But if you add tocopherols to it, the effect is greatly enhanced. The fact that the combination of nutrients may be more effective than an isolated compound might explain why tomato extractrich in all these antioxidants and morelowers LDL oxidation the most, and why diets plentiful in whole tomato show such strong correlations with heart-disease management.

So, if we can capture a fruit or vegetables broad spectrum of antioxidants in a balanced extract, weve brought that extract one step closer to replicating the merits of its source. Notes Bank, Theres a green tea product out there thats just EGCG. Now, everybody in the industry knows that EGCG is responsible for the majority of green teas antioxidant capacity. But does it make sense to isolate it? Shouldnt you still have it surrounded by its other natural components to keep the synergy? And, even if EGCG were as effective as a more diversified portfolio of flavanols, youd still have to petition FDA to grant it GRAS status before adding it to a food or beverage formula.

Thats why Quinns company developed a whole fruit-and-vegetable extract to capture the synergistic effects of the phytonutrients. In processing the extract, called Nutrifood, the company not only eschews chemical solvents but does not selectively extract for any one compound, Quinn says. Rather than teasing out just the beta-carotene from a carrot, he says, What we would come up with is the whole carrot concentrate containing a variety of carotenoids. A 3-gram serving of Earths Harvest, one such concentrate, provides 3.4 mg of total carotenoids, or the phytochemical equivalent of about 12 cup (42 grams) of fresh carrot, according to company literature. And, because youre left with a whole extract, there are some minerals left, some vitamins and other nutrients as well, and we feel that they all work together synergistically in an almost unknown fashion, he adds.

Hartals company follows a similar path in producing Lyc-O-Mato, a tomato lycopene complex available in lycopene concentrations running from 6% to 15%. One of the advantages of our product is that it contains all those phytonutrients that you have in the tomato, he says. First, we take the synergistic mixture of nutrients, which, in addition to lycopene, includes phytoene, phytofluene, tocopherols, betacarotene, phospholipids and phytosterols. Second, he adds, we release it from the structure of the tomato, so it is much more bioavailable. And third, we present it in the presence of oil, which enhances its bioavailability still further.

Making themselves useful 

The matter of bioavailability deserves further comment, as it can profoundly affect an antioxidants efficacy in our tissues. As Blumberg says, It is not appropriate to describe one antioxidant as better than another. Despite our labeling these thousands of nutrients as antioxidants, each acts slightly differently than the other in how it is absorbed and distributed throughout the body and into cells.

And, as Vinson says, The matrix affects the absorption, too. He cites the relationship between chocolates antioxidants and the effects of milk. You dont want to take milk chocolate, he says, at least not if antioxidant loading is your goal. And its not just a matter of dark chocolate containing more phenolics than milkalthough it does, by about a factor of two. Rather, the milk itself inhibits our absorption of the phenolics, he says, so you get a double-whammy negative on the milk chocolate. To wit, in a 2003 study published in Nature, researchers found absorption of chocolate flavonoids into the bloodstream was 46% less in the case of dark chocolate consumed with milk and 69% less with milk chocolate, compared to absorption seen from dark chocolate alone.

Lycopene and its carotenoid siblings display similar matrix dependencies. Being fat-soluble, they enter our tissues more readily when accompanied by lipids. This, notes Hartal, is a matter of solubility. If carotenoids are simply dissolved in the presence of oil, he says, then theyre much better-absorbed than in their crystallized form. Heat also helps because, Hartal continues, In the tomato, lycopene is located in tiny cells called chromoplasts, where it resides in the crystalline form. So youve got to release it, whether via heat, concentration or even physical means, anything that breaks down those chromoplasts and releases the lycopene.

Bioavailability becomes even more complicated in the case of lutein and zeaxanthin, and whether they enter our systems more effectively as mono- and di-esters, their naturally occurring form in plant material, or as free carotenoids. Saponification of the mono- and diesters, either through enzymes or hydrolysis by pH adjustment, cleaves the fatty-acid bond and releases the free xanthophylls, whose smaller molecular structure facilitates absorption in the digestive tract. But heres the catch, says Hainrihar. Free xanthophylls pigments are much less stable than when theyre in the ester form. nd that raises the question of how many actually survive passage through the gut. Then again, maybe the enzyme that cleaves the pigment knows to act at a point in the small intestine that allows it to slip through the cell membranes safely. At this point, its still just conjecture, as is so much of the antioxidant story.

As Lapsley says, The human body is not as efficient as lab equipment at extracting and absorbing nutrients, so it is essential to conduct research to look at the change in blood levels of antioxidants after eating a food. But even if we have to wait until our golden years before we can take inventory of any genuine health benefits that result from antioxidant intake, were sure to live better in the long run.

Kimberly J. Decker, a California-based technical writer, has a B.S. in Consumer Food Science with a minor in English from the University of California, Davis. She lives in the San Francisco Bay area, where she enjoys eating and writing about food. Contact her at

[email protected].

An Antioxidant Primer

You can't top Mother Nature for sheer creative ingenuity, and the staggering number and range of antioxidants she's given the plant world remind us that no matter how hard we try to suss out her doings, we'll always be playing catch-up. So, in the absence of an exhaustive accounting of all the antioxidants out there, consider the following a primer to the ones making the most news.

Alpha-tocopherol

Alpha-tocopherol is one of eight fat-soluble antioxidant vitamins--four tocopherols and four tocotrienols--that are collectively and individually known as vitamin E. However, alpha-tocopherol is apparently the only form that shows considerable biological activity, whereby, in association with membrane lipids, it donates electrons to roving free radicals, preventing a chain reaction of lipid oxidation. Recommended dietary allowances for adults are 15 mg (22.5 IU) per day.

The relationship between cancer and oxidative damage led some researchers to postulate a role for alpha-tocopherol in cancer prevention. However, several large prospective and placebo-controlled studies haven't found a conclusive link, whether the alpha-tocopherol came in supplement form or as a part of the diet. On the other hand, associations between alpha-tocopherol and reduced cardiovascular-disease risk are on firmer footing, although supplementation still doesn't seem as effective as food sources.

As for food sources, the best to tap for vitamin E include vegetable oils, nuts, whole grains and, to a lesser extent, green, leafy vegetables. For example, 1 oz. of almonds delivers a whopping 7.3 mg of vitamin E.

Vitamin C

As an antioxidant, water-soluble vitamin C, or ascorbic acid, is perhaps most celebrated for sequestering the metals that help catalyze oxidative reactions. Yet it also works in association with alpha-tocopherol to help regenerate that antioxidant after it's been oxidized. Adult males should shoot for getting 90 mg per day, females, 75 mg. If you smoke, the target rises to 125 mg and 110 mg for males and females, respectively.

The evidence for vitamin C as a heart protector is encouraging. The First National Health and Nutrition Examination Study (NHANES I) Epidemiologic Follow-up Study found a 42%-reduced risk of death from cardiovascular disease in men and a 25% lower risk in women who consumed more than 50 mg of vitamin C per day, even from supplements. A 20-year-long prospective study of more than 2,000 Japanese subjects also showed that stroke risk among those with the highest serum vitamin C levels were 29% lower than in those with the lowest levels. Case control studies also link higher vitamin C intakes with reduced rates of oral, esophageal, throat, stomach, colorectal, laryngeal and lung cancers.

It's hard not to get enough vitamin C. Five servings of fruits and vegetables--citrus, berries, kiwis, sweet potatoes, peppers, greens, squash you name it--will put you well over the top.

Coenzyme Q10

Ubiquinones--which, as their name suggests, are ubiquitous in animals--are not vitamins, per se, because our bodies generate them autogenously. They are, however, integral to cellular function. Fat-soluble and sporting a functional group known as a benzoquinone, ubiquinones appear most often in humans as ubidecaquinone, or coenzyme Q10 (CoQ10), which exists in nearly all cell membranes and lipoproteins. Its benzoquinone head is a consummate electron acceptor and donor. At this time, however, regulatory agencies haven't issued an intake requirement for it.

In its reduced form--denoted CoQH2--CoQ10 helps prevent lipid peroxidation in membranes and in low-density lipoproteins (LDLs). When teamed with alpha-tocopherol, it also preferentially spares the latter from oxidative damage. CoQ10 also appears to protect membrane proteins and DNA from oxidative damage in isolated mitochondria. While all this suggests its role in the prevention of cardiovascular disease and cancer, it's the compound's association with mitochondrial membrane proteins--the site of ATP synthesis--that has earned it the most attention as an age-defying antioxidant. Because free radicals are an inevitable consequence of ATP synthesis, and because their cumulative effects destroy mitochondria--and, ultimately, our organs--over time, some hope that by stanching mitochondrial oxidation and its attendant damage, CoQ10 can stanch aging, too. In fact, a famous study conducted in the 1970s did reveal an increased lifespan in mice injected with weekly doses of CoQ10.

Although our bodies make what CoQ10 they need on their own, rich food sources include meat, poultry and fish, and, for the vegetarians out there, canola oil and nuts.

Flavonoids

The flavonoids constitute the "big tent" class of antioxidants: A whole lot of compounds fit into it. What these diverse polyphenols share is a common three-ring chemical structure, a widespread presence in nearly every fruit and vegetable, and the potential to help explain why diets rich in said produce are conducive to good health.

Flavonoids are potent free-radical scavengers, and some also chelate metal ions that catalyze oxidative reactions. Studies show that by preventing the cyclooxygenase enzyme from breaking down prostaglandins, they reduce platelet stickiness and aggregation. However, they display these behaviors most convincingly in vitro, whereas their ability to do so in human tissues is less well understood. In fact, much of their health-promoting effect may be due less to flavonoids' antioxidative actions than to their other bioactive capacities.

Just tracing flavonoid levels in vivo is tricky, because their limited bioavailability and quick metabolism to a host of unfamiliar metabolites keep plasma and cellular concentrations as much as 1,000 times lower than those of other antioxidants.

Three of the more-frequently-studied flavonoids include the following:

Resveratrol

Whether they know it or not, when people speak of the French Paradox, they may be speaking of resveratrol. Plants produce this fat-soluble polyphenolic as a defense against environmental stress: ultraviolet radiation, infection, tissue damage, etc. There's hope that if we can get enough of it in our own bodies, it can similarly protect us.

In vitro, resveratrol acts as an antioxidant, scavenging free radicals and inhibiting oxidation of LDL cholesterol. In so doing, it prevents that "bad" cholesterol, as it's sometimes known, from forming artery-clogging plaques. Red wine's high levels of resveratrol (and flavonoids) led some to believe that resveratrol may help account for the French Paradox. To date, however, studies have yielded limited support for that theory and provide little evidence that resveratrol is as antioxidatively potent in our bodies as it is in a test tube. While resveratrol in the lab can inhibit platelet aggregation, improve vasodilation and attenuate the inflammatory response--all boons to heart health--resveratrol concentrations used in such experiments are generally higher than those measured in human plasma after resveratrol consumption.

Nevertheless, if you need an excuse to drink red wine, perhaps with a few grapes and peanuts on the side, the presence in each of resveratrol is as good a reason as any to sip and snack. Because resveratrol clusters in grape skins, the longer a wine maintains skin contact during fermentation, the greater its resveratrol extraction. Resveratrol content across red wines and wine-growing regions varies widely, ranging from around 0.30 mg to 1.07 mg per 5-oz. glass.

Beta carotene

A member of the provitamin-A class of carotenoids, beta carotene is a fat-soluble pigment that contributes to the orange color of fruits and vegetables. Our bodies convert dietary beta carotene to vitamin A, also called retinol, and this conversion is apparently beta carotene's only biologically required function. However, beta carotene's action as an antioxidant also interests scientists.

Research into the role of beta carotene in preventing oxidation-related disease has produced ambiguous results. Inarguably, diets abundant in foods rich with beta carotene correlate to reduced risk for cardiovascular disease and some cancers. But when studied in supplement form, beta carotene doesn't always yield the same positive outcomes. Several large, randomized, controlled trials have yet to show that high-dose supplementation lowers cardiovascular disease or cancer risk, and two such trials--the Alpha-Tocopherol Beta-Carotene (ATBC) trial in Finland and the Beta Carotene and Retinol Efficacy Trial (CARET) in the United States--even demonstrated an increased lung-cancer risk among smokers and former asbestos workers who took high-dose beta carotene supplements. Similarly, four randomized, controlled trials that looked at the relationship between beta carotene supplements and heart disease found no evidence that the supplements proved preventive.

The lesson thus appears that foods may trump supplements in providing beta carotene's benefits. Pumpkins, sweet potatoes, carrot juice and all manner of green, leafy vegetables have beta carotene levels in the tens of thousands of µg per typical serving.

Lycopene

Like all 600-odd carotenoids, lycopene is a fat-soluble pigment. Unlike its cousin beta carotene, it's responsible for plants' bright-red tones, and it does not undergo conversion to vitamin A. Even so, it's the most-common carotenoid in the human body, and is among the most-potent carotenoid free-radical quenchers. Although it doesn't qualify for a recommended dietary allowance, an intake of 5 to 10 mg per day, researchers say, can benefit the average, healthy person.

Not surprisingly, given their red color, tomatoes and tomato products seem to hoard lycopene, and epidemiological data show a positive association between tomato consumption and reduced rates of prostate cancer. Several prospective cohort studies suggest the same, including one that, after following 47,000 men for eight years, found a 21%-lower prostate cancer risk in the subjects with the highest lycopene consumption relative to those with the lowest, while a 35%-lower relative risk emerged among those with the highest actual tomato intake.

Tomatoes account for 82% of our lycopene consumption, and research indicates that processing by cooking, concentrating or canning increases their lycopene bioavailability (as does consuming the tomatoes in a fatty medium--say, sautéed in olive oil). For example, 1 cup of canned tomato paste contains more than 75,000 mcg of lycopene, compared to about 4,600 mcg from an equal amount of raw tomato.

But don't forget: Tomatoes aren't the only sources of lycopene. Watermelon, pink grapefruit, guavas, red peppers and even baked beans have respectable levels, too.

Lutein and zeaxanthin

These two orange-yellow carotenoids--part of the xanthophylls class--form something of an antioxidant tag team in the eye. In fact, they're the only carotenoids found in ocular tissue, where they are prevalent in the lens and in the macula, located in the center of the retina. The arrangement of alternating double and single bonds in lutein and zeaxanthin allows it to absorb visible light--particularly in the blue portion of the spectrum--and thus protect the delicate assemblies of the eye from light-catalyzed oxidation.

This light-absorbing capacity implicates lutein and zeaxanthin in preventing cataracts and age-related macular degeneration (AMD); the latter is the leading cause of blindness in older adults in the United States. Three prospective studies of lutein and zeaxanthin's effects on cataracts showed that subjects with the highest dietary intakes were 20% to 50% less likely to need cataract surgery. Epidemiological studies also associate diets rich in lutein and zeaxanthin with reduced AMD rates, a theory that cross-sectional and case-controlled studies support. Even supplementation at 10 mg per day has produced small improvements in vision over a placebo. And while the jury's still out on whether definitive causal links exist, daily consumption of at least 6 mg of lutein and zeaxanthin from fruit and vegetable sources may lower AMD risk.

The best fruit and vegetable sources include leafy greens, particularly spinach and kale; green and yellow summer squashes; and even frozen peas. The xanthophyll-rich feeds traditionally used in poultry farming make chicken eggs a solid source of lutein and zeaxanthin, as well.

Selenium

A trace element that male and female adults require in amounts of 55 mcg per day, selenium serves as an integral component in enzymes known as selenoproteins. Among these are the antioxidant enzymes glutathione peroxidase and thioredoxin reductase. As part of the former, selenium enhances alpha-tocopherol activity, while as part of the latter, it helps regenerate vitamin C.

Animal studies link high levels of selenium supplementation with reduced cancer risk, and human epidemiological, case-control and prospective cohort studies support that correlation, particularly with respect to colon and prostate cancers.

In contrast to most of the other antioxidants discussed, selenium's best sources are animal-based, especially organ meats and seafood. Quantities in plants vary widely and reflect soil selenium contents, but Brazil nuts, with more than 800 mcg per oz., are a notoriously rich vegetarian source.