Antioxidants: Free-Radical Antidote

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Wayne G. Geilman, Ph.D., senior research scientist, Pure Fruit Technologies, suggested the main draw is the fact that scientists have connected free radicals to so many degenerative biologic functions. "This knowledge, combined with the increase in the median age, has fueled interest in antioxidants," he said. "This population wants to enjoy life to the fullest and is willing to combat the effects of aging on all fronts. Antioxidants are becoming the weapon of choice to do this.

Although consumers may not be able to interpret all the scientific jargon concerning how antioxidants work, they have the feeling that they do work, that they are generally safe and that they can be part of a proper diet."

As retailers of natural products, it's a positive that there is a dawning awareness about the potential of antioxidants for consumers. However, to be able to market products effectively and steer consumers toward the right products for their needs, it helps to understand some of the physiological basics of antioxidants.

The bottom line is these powerful compounds stop a potential cascade of cellular-level damage caused by free radicals, highly reactive molecules featuring an unpaired electron in their outer shell. To stabilize themselves, they steal an electron from a nearby molecule. Losing an electron to a free radical can turn the victim into a radical, creating the potential for cascading damage to healthy cells.

"There are both internally and externally generated sources of free radicals," noted Beeta Little, director of product development and technical services, Bluebonnet Nutrition Corp. "Some of the internally generated sources are energy production, byproducts from energy metabolism, reactions involving transition metals such as iron, exercise and inflammation. Externally generated sources include cigarette smoke, environmental pollutants, radiation, ultraviolet light, certain drugs, ozone and alcohol."

Oxidants can damage cells by starting chemical chain reactions, or by damaging DNA at the cellular level. "Our DNA is the blueprint for life," said Cheryl Myers, director of product development, Enzymatic Therapy. "If the blueprint is damaged, you have problems when the cell goes to recreate itself. Either it's not as efficient or you have mutations in the cell. So preventing that DNA damage is critical to managing all aspects of the degeneration process in our bodies."

Fortunately, plants and animals have developed mechanisms to fight oxidative damage by manufacturing antioxidant compounds within the body (endogenous generation); unfortunately, levels of these fighters decline with age, making ingestion of exogenous antioxidants increasingly important to maintain the body's integrity.

"Young people generally make lots of antioxidants naturally, but middle age often signals a decline in antioxidants made by the body," said Brant Herman, Pomology. "Supplements can support the body's production and maintenance of maximum levels of these essential antioxidants."

One of the body's own protective mechanisms is the enzyme glutathione peroxidase (GPx), which targets lipid hydroperoxide and hydrogen peroxide. Increasing fruit and vegetable intake can improve production of GPx. Supplemental selenium can also bolster the activity of the selenium-containing GPx.2.

The body also creates superoxide dismutase (SOD), an enzyme that targets superoxide, breaking it down to hydrogen peroxide and oxygen. Superoxide is used in a positive way by the immune system to squash microscopic pathogens, but can also inactivate those enzymes that control free iron, which can lead to formation of hydroxyl free radicals. SOD supplementation (as GliSODin, from P.L. Thomas & Co.) may protect DNA from oxidative damage, and increase blood antioxidant activity and status.

Beyond the internal defenses, nature has provided thousands of powerful antioxidant compounds in the foods we eat; these antioxidants can be broadly classified as water-soluble (hydrophilic) and fat-soluble (lipophilic). In general, water-soluble antioxidants react with oxidants in the cell cytoplasm and plasma, while lipid-soluble antioxidants protect cell AO membranes from lipid peroxidation.

"Since our bodies contain both water-soluble and fat-soluble compartments, we need to have both kinds of antioxidants," said Angelica Vrablic, Ph.D., nutrition research manager, American Health. "Antioxidant formulations should cover both water-soluble and fat-soluble antioxidants along with other effective plant-based ingredients such as bioflavonoids or anthocyanins."

Several essential nutrients count antioxidant activity among their benefits. Vitamin C, one of the best known antioxidants, is a water-soluble compound with promising protective activity against oxidation in brain tissue and the eyes, 5,6 and acts as a foil for oxidative stress relative to cardiovascular disease (CVD). Marci Clow, senior director of product research, Rainbow Light Nutritional Systems, added: "Vitamin C protects our bodies from the effects of pollutants by joining with oxygen and enzymes to convert toxic substances into non-toxic derivatives excreted in the urine. It's a good idea to fake a vitamin C formula that includes bioflavonoids because they may increase vitamin C's activity, as well as providing antioxidant protection of their own."

Vitamin E, the collective name for a set of eight related tocopherols and tocotrienols, are fat-soluble antioxidants. Alpha-tocopherol has been the most studied form, although all the isomers are considered critical in the body. "Vitamin E complex is helpful for healthy immune and cardiovascular function, as well as preventing cholesterol fractions from oxidizing into more harmful forms," noted Neil Levin, CCN, nutrition education manager, NOW Foods.

While vitamins C and E may be essential and well-studied, the hottest antioxidant on the scene would probably be coenzyme Q10 (CoQ10). "This is the spark plug that ignites the energy production within the cell, keeping it alive and healthy," Myers said. "CoQ10 facilitates the energy process, but also works as an antioxidant by picking up free molecules and taking them elsewhere during the chain reaction that creates energy. CoQ10 is so important that the body makes the majority of what you need; however, the older you get, the less CoQ10 the body can produce."

Geilman also called out CoQ10 as the most important single antioxidant. "CoQ10 is designed to be an electron sink and is necessary for the mitochondria to produce ATP, which is the currency of energy in the cell," he said. "Controlled free radical production is the key to respiration, and CoQ10 is the controlling factor."

Controlling free radical production and quenching ROS before the chain reaction of damage can occur is particularly important, as oxidative stress has also been associated with the pathogenesis of many human diseases. However, it is still unknown whether the oxidative stress is the cause or a consequence of such diseases. This hasn't prevented great interest among scientists to elucidate the interaction between antioxidants and disease pathogenesis. As of mid-October 2007, for example, there were more than 280 U.S. government-funded studies recruiting or in planning stages examining different antioxidants and disease conditions.

What does this mean for supplementation? Most marketers encourage consumers to take a comprehensive multivitamin/mineral product as a foundation, and then look at the science to see whether other compounds might provide extra support. "People should consider using a multivitamin as a nutritional base, and taking additional antioxidants to meet their individual needs," Levin said. "Family history and other risk factors will frequently identify areas where specific nutrients can be helpful in maintaining optimal health against known challenges. This provides both a framework and motivation to optimize protective nutrition."

Herman added: "Specialized antioxidant formulations are an important addition to the supplement landscape, as important research has found a link between the benefits of fruit-based antioxidants and specific health issues, such as joint support, menopause, cardiovascular support and many other conditions."

While free radicals and antioxidants play a role in every cell in the body, there are a few areas that are generating more investigation than others.

Protecting the Brain

The brain's high levels of lipids make it especially susceptible to oxidation. As is the case in the rest of the body, oxidation can damage cells, tissues and genetic material in the brain. Cellular generation of ROS causes oxidative damage to nucleic acid, carbohydrate, protein and lipid components of the brain, where damaged neuronal cells cannot be readily regenerated. Unchecked oxidation can contribute to degenerative illnesses such as Alzheimer's disease (AD), Parkinson's disease (PD) and dementia.

Studies have found positive results from interventions with antioxidant compounds. Italian researchers drew a connection between AD and mild cognitive impairment, and depressed peripheral levels of antioxidants, including vitamins A, C and E, carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene and beta-carotene) and SOD. French scientists reported older adults with low cognitive function appear to have lower levels of lycopene and zeaxanthin.

Tocotrienol, a specific form of vitamin E, may be able to protect against neurological maladies marked by oxidative stress." Researchers have linked higher intake of vitamin E, from both food and supplements, to a reduction in cognitive decline seen in aging.

CoQ10 plays a particularly critical role in the brain. Scientists have found CoQ10 supplementation may help stave off AD, PD and other neurodegenerative disorders. COQ10 supplementation appears to protect neuronal cells from amyloid peptide toxicity by reducing the concentration of superoxide anion. Combined supplementation with CoQ10 and alpha-tocopherol in aged mice improved brain function, as measured by cognitive tests, according to research from the University of North Texas, Fort Worth.

Another powerful antioxidant for brain function, alpha lipoic acid (ALA), is water- and fat-soluble and is capable of crossing the blood-brain barrier. Clinical studies have shown ALA may help maintain healthy memory and mental focus, and improve memory, especially in older adults.

The endogenous antioxidant hormone melatonin scavenges free radicals quite well, especially in brain tissue. Not only does it combat oxidative stress in the hippocampus by increasing tissue levels of GPx, SOD and other antioxidant enzymes, it also protects the brain from oxidative stress common in PD by scavenging hydroxyl radicals in the mitochondria.

From the botanical realm, grape seed extract may protect the nervous system from ROS, and shield the brain from oxidative damage by inhibiting free radical-induced lipid peroxidation. Pomegranate antioxidant phenols are also neuroprotective, although the exact mechanism behind its ability to reduce the amyloid load in AD has not been determined.

Visualizing The Benefit

While the eyes serve as windows to the soul, they're also windows that let in UV light, a key contributor to oxidation. The retina is an ideal environment for the generation of free radicals since it has both high levels of blood (and thus oxygen) supply and high light exposure. Further, the eye's photoreceptor membranes are rich in polyunsaturated fatty acids, making them particularly susceptible to oxidative damage.

Antioxidants, therefore, serve a vital role. In fact, the research is strong enough that the U.S. National Eye Institute (NEI) has urged adults who have or are at risk of age-related macular degeneration (AMD)—a leading cause of blindness—to consider taking supplements based off the formulation used in the long-term Age-Related Eye Disease Study (AREDS)—vitamins C, E, beta-carotene and zinc. The AREDS study found high-dose antioxidant supplementation reduced the risk of progression to advanced AMD by 25% percent, and the risk of moderate vision loss by 19 percent.

Carotenoids are particularly important antioxidants in the eyes. The connection between retinal protection and lutein and zeaxanthin is based in the macular pigment, which contains healthy amounts of each carotenoid. Supplementation with lutein and zeaxanthin may prevent retinal degeneration via protection from damaging sunlight.

In one trial, 90 AMD patients who supplemented for 12 months with 10 mg/d lutein (as FloraGLO Lutein, from Kemin Health) alone, or in conjunction with a broad spectrum antioxidant formula including vitamins and minerals, showed improved visual function, Additional research out of England found administration of 20 mg/d lutein ester (as Xangold, from Cognis), equivalent to 10 mg/d free lutein, benefited patients with early AMD by increasing macular pigment optical density (MPOD) and plasma lutein concentrations.

The carotenoid astaxanthin may also protect the eyes from lipid peroxidation, as studies have shown combining astaxanthin with lutein and zeaxanthin can decrease lipid peroxidation and oxidative stress markers in human lens epithelial cells exposed to UV radiation.

Fat-soluble carotenoids are joined in their quest to protect the eyes from oxidative stress by a host of water-soluble flavonoid compounds. Specific flavonoids that may protect the eyes against antioxidant damage include quercetin and the green tea polyphenol epigallocatechin gallate (EGCG). Anthocyanins, another class of flavonoids, are found.

In a wide range of fruits, particularly berries, and may help improve vision and preserve capillary integrity, In particular, anthocyanins from bilberry, lignonberry (Vaccinium vitis-ideae) and black currant (gibes nigrum) may protect against lipid and protein oxidation in the eye. Flavonoids from French maritime pine bark extract (as Pycnogenol, from Natural Health Science) may also inhibit oxidative damage and increase activity of GPx and glutathione reductase in the retina, inhibiting diabetic retinopathy and cataract formation.

The Heart Of The Matter

The role of oxidation in disease pathology has been most elucidated in cardiovascular disease (CVD). Specifically, oxidation of low-density lipoprotein (LDL), the "bad" cholesterol, appears to trigger the process of atherogenesis, the development of fatty buildups in the arteries. This can progress into atherosclerosis and CVD.

The American Heart Association (AHA) recommends people consume a diet high in food sources of antioxidants and other heart-protecting nutrients, such as fruits, vegetables, whole grains and nuts; it doesn't recommend the use of antioxidant supplements to prevent CVD “until more complete data are available.”

However, there has been a good deal of research into the use of specific antioxidants to promote heart health. Vitamin E is possibly best known for its activity in this area. Vitamin E has been shown to inhibit lipid peroxidation of low-density lipoprotein (LDL) cholesterol and/or atherosclerosis. It also has limited oxidative stress in hypertensive animals.

CoQ10 also plays a key role in heart health, as it can protect heart cell mitochondria from oxidative stress and damage, "The heart is so dependent on a constant, uninterrupted stream of energy, that each cell in the heart could have up to 4,000 mitochondria, compared to just a few in most cells" Myers noted. "In conditions that affect the heart muscle, like heart attack or cardiomyopathy, adding CoQ10 helps improve the muscular function of the heart.

In animal research, CoQ10 supplementation (as Q-Gel from Tishcon) has reduced markers of oxidative damage and inhibited development of atherosclerosis, Similar findings have been reported in human trials, in which CoQ10 supplementation can modify oxidative stress and the atherogenic ratio, while increasing the activity of endogenous antioxidant enzymes.

Researchers have also turned to carotenoids and flavonoids to help the heart. In a study in hypertensive patients, 250 mg/d of lycopene-rich tomato extract (as Lyc-O-Mato, from LycoRed) reduced lipid peroxidation markers, and both systolic and diastolic blood pressure readings.

Similarly, a study out of California showed one month of supplementation with grape seed extract (as MegaNatural BR from Polyphenolics) could significantly reduce blood pressure and the concentration of oxidized LDL in plasma. Green tea's EGCG may also prevent oxidative modifications of LDL, reduce surrogate markers of atherosclerosis and lipid peroxidatlon, and reduce postprandial lipidemia in hypercholesterolemic subjects.

Berries are also rich in antioxidant polyphenols. Cranberry flavonoids have been shown to reduce lipid peroxidation in atherosclerosis and CVD, while blueberry's polyphenols may inhibit ROS formation in red blood cells. Pomegranate, meanwhile, can reduce oxidative stress in macrophage and endothelial cells.

One specialty product—Radical Fruits, from Garden of Life—combines raspberry, prune, pomegranate, blueberry, grape and strawberry extracts, and was the subject of a randomized, double blind, placebo-controlled trial.

Hypercholesterolemic subjects taking 900 mg Radical Fruits three times daily for four weeks had reduced plasma total cholesterol, increased high-density lipoprotein (HDL) cholesterol and decreased urinary oxidative markers. "Conducting primary research on our Radical Fruits formula was important," said Garden of Life's Leonid Ber, M.D. "Rather than just a combination of other research studies, we really showed that this specific formula has biological activity in the body."

They’ve Got Muscles

It's not just the organs looking for support from antioxidants; muscles are also subjected to free radical damage. During exercise, oxygen consumption increases significantly, which leads to a large increase in production of oxidants, resulting in damage that contributes to muscle fatigue during and after exercise. The inflammatory response that occurs after exercise is also associated with oxidative stress, as free radicals are produced by neutrophils to remove tissue damaged by exercise; therefore, antioxidants can promote recovery and muscle adaptation.

Vitamin C has been extensively studied in cases of exercise-induced oxidative stress. In one study, insufficient vitamin C status correlated to low serum concentrations of lipid peroxides and increased muscle damage in female weightlifters. A Spanish study found vitamin C supplementation in volunteer endurance athletes increased antioxidant enzymes and plasma antioxidant levels during athletic competition and short-term recovery. Vitamin C taken on a regular basis before rigorous exercise may even reduce muscle soreness, delay creatine kinase increases and prevent blood glutathione oxidation.

Combining vitamin C with vitamin E and beta-carotene may have further benefits, according to a stuffy from Universitat de les llles Balears, Spain. Male athletes who received 500 mg/d vitamin E, 30 mg/d beta-carotene and 1 g/d vitamin C for three months during training had a higher maximal oxygen uptake and lower increases in blood lactate concentration, improving the efficiency of obtaining aerobic energy.

Antioxidant Synergy

While antioxidants have been studied for their specific attributes and activities, it is the greater synergy that benefits the body. In addition, the action of one antioxidant often is dependent on the actions of others throughout the system. "Supplementing with a variety of antioxidants is important for maximizing their individual effects, since research has shown certain antioxidants act synergistically with one another, and because different types of antioxidants act in different parts of the cellular milieu," said Bob Terry, Ph.D., technical services director, Green Foods Corp.

Myers agreed with the assessment. "We pay lip service to how important diversity is in many parts of society, but this is an area where it's critical," she said. "We want to take in thousands of phytonutrients through our diet by consuming the broadest range of locally grown, fresh fruits and vegetables. The wider variety of antioxidants you get, the more likely you'll have improved health. There is no one size fits all."

Lizanne Falsetto, CEO, thinkproducts, affirmed the importance of a diet rich in fruits and vegetables, which are themselves loaded with interconnected antioxidant compounds. "A recent study stated fruits and vegetables in combination have synergistic effects on antioxidant activities, leading to greater reduction in risk of heart disease and cancers," she said. "Consumers are best off taking a synergistic complex of naturally occurring antioxidants."

Part of this search for synergy is driving interest in whole foods and super-foods. "There is ample nutrition available in real, whole, organic foods," said Mic LeBel, a public relations professional who works with companies including Guayaki Yerba Mate and Amazing Grass. "Many companies are offering functional foods and beverages that offer antioxidants and a wealth of other key nutrients via whole foods as opposed to supplements or nutrient fortification."

Jeremy Black, vice president of marketing, Sambazon, added: "Whole food nutrition is a concept that seems to be resonating with more people and is something we've always based our products on." His assessment was shared by Zach Adelman, president and founder of Navitas Naturals, which supplies functional foods and supplements. "There are these nutritious foods that are being discovered and brought to America from around the world," he said, specifically mentioning goji berries, cacao seeds, camu camu, pomegranate, acai and maca root. "These foods are different and unusual for consumers, so retailers can demo them and help shoppers taste the foods and learn how to integrate them into their daily diet."

Terry said the launch of more exotic offerings is complemented by long-standing product SKUs like green foods. "Whole food sources of antioxidants may be obtained from whole food supplements processed in a manner that protects and stabilizes their constituent antioxidants," he said. 'Fortunately, fruit, vegetable and green cereal grass and whole food powders are made specifically to provide an excellent array of antioxidants and other supportive nutrients that can help us obtain the full spectrum 'rainbow diet' every day."

Mike Pugh, senior manager of research and development, XanGo, also advocated consumers seek whole food nutrition. "Historically, whole foods have been consumed by people for hundreds of years as part of a regular diet, and science is now identifying specific properties within these foods that benefit human health and wellness," he said "we believe whole foods are the best option for obtaining those nutrients, and that is why we use a whole fruit puree of the mangosteen fruit in our product."

While the functional foods and beverage space is seeing a number of product launches to maximize on this interest, retailers need to ensure the products are delivering quality nutrition. "Just adding an active substance to a food or liquid without extensive testing may create a marketable product, but one that risks being spoiled or poorly utilized by the body," Levin said. "Interactions that lead to degradation of potency or proliferation of undesirable microbes are some potential problems affecting the stability and potency of functional food ingredients, because long-term stability of ingredients added to foods is still largely unknown. Proper testing of products and packaging is a must."

The quest for quality also means staying up to date with current research and asking for product substantiation,-Clow said. "To make intelligent recommendations to consumers, it's important to understand the features and benefits of the products you're offering," she said. In addition, she suggested asking questions of consumers to establish the best product to suit their needs: What kind of support are they looking for?

Do they have any special dietary restrictions, nutritional needs or health concerns? Are they willing to take three to six multivitamin tablets a day, or would they prefer a one-a-day? This can also help broach the topic of specific health concerns, which make the goal of supplementation more tangible.

Ultimately, Vrablic said, "antioxidant protection is hard to see'. Retailers need to address consumer concerns such as anti-aging, skin health, eye health and immune health, which are all a function of overall antioxidant health. Education plays a key role in understanding antioxidants and the role they play in everyday wellness, and retailers should partner with manufacturers to help customers make wise and confident supplement choices."

And while the science continues to evolve, retailers are on the front lines helping consumers fight the degeneration induced by free radical damage. "Follow the clinical science to guide you to antioxidant substances that are best supported for the customer's needs, [but] don't worry if the science is preliminary or not yet definitive, as long as it is promising," Levin said. "By the time it is officially accepted, it will probably be 20 or 30 years from now. We simply can't waif that long to stave off the ravages of aging by using safe, natural antioxidants."

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