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    Features

    Antioxidants: High Expectations for a High Quality of Life

    In a market filled with so many options for consumers, only the best will rise to the top—and stay there.

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    Mark Crawford, Contributing Editor03.01.11
    Almost everyone knows the basics—free radicals damage cell membranes and DNA through a process known as oxidative stress, which may lead to future health problems and the early onset of disease or aging. The good news, of course, is that antioxidants “fight” these dangerous compounds and help preserve health and longevity.

    Average consumers are far more interested in wellness and health than they used to be, especially Baby Boomers. Boomers, who will be living longer and staying more active than generations before them, are already refusing to accept the natural signs of aging.

    “Consumers continue to seek the proverbial ‘fountain of youth’ and are willing to spend their hard-earned dollars on natural anti-aging moisturizers and supplements that may erase those fine lines that crop up over time,” said Steve Holtby, president and CEO of Soft-Gel Technologies, Los Angeles, CA. “Generation-X/30-something consumers are also striving to maintain their youthful looks. They are spending thousands of dollars on cosmetic products and procedures to help reverse, or at least suspend, the aging process.” 

    As a result, antioxidants are in huge demand across a broad range of demographics. The market is already packed with a variety of ingredients considered to have antioxidant capabilities. Researchers and ingredient suppliers continue to scour the globe, including rainforests and other remote locations, hoping to discover the next new group of antioxidants more powerful than the last.

    Right now consumers are especially interested in superfruits, both long-time standards such as cranberries and blueberries and less familiar, more exotic entries. “Superfruits such as acai, mangosteen, goji and pomegranate are flying off both brick-and-mortar and Internet shelves,” indicated Sherry Torkos, a holistic pharmacist and nutritional and research consultant for Pharmachem Laboratories, Kearny, NJ.

    Also increasingly popular are green-food products, which are typically presented as high-dose, powdered beverage mixes that contain nutrient greens and fruits to supplement the vegetables and fruits that aren’t being consumed in most people’s diets. Some green-food and red-food manufacturers, such as Blauvelt, NY-based RFI Ingredients, are developing highly concentrated liquid antioxidant extracts from these foods, which can be labeled as “fresh brewed” if they are extracted with water.

    “These extracts contain much higher levels of polyphenols and antioxidants than single-strength products do, and can be added to beverages to boost the polyphenol and flavonoid content and enhance flavor,” explained Jeff Wuagneux, CEO and president of RFI Ingredients.

    Top-Shelf Reputations

    Famous, long-standing antioxidants—vitamin C, vitamin E, selenium, beta-carotene, blueberries, cranberries, alpha lipoic acid (ALA) and coenzyme Q10 (CoQ10), to mention a handful—continue to be in high demand. Even though they have been well-studied, researchers continue to find new ways to increase their efficacy.

    For example, both ALA and CoQ10 are supported by high-quality research demonstrating consistent health benefits, especially regarding heart health, diabetes/blood sugar management, gum/oral health and overall anti-aging. One way scientists are improving the function of these ingredients is by developing enhanced delivery systems, such as Pharmachem Laboratories’ patented pre-chelation technology, which boosts the digestion and absorption of CoQ10, selenium and other nutrients.

    Polyphenols—antioxidants found in tea and dark chocolate, among other dietary sources—have also long been known to benefit overall health. Now they are being studied for possible effects on vascular health (including blood pressure) and on the body’s ability to use insulin. “Laboratory studies suggest that EGCG, a polyphenol found in green tea, may protect against cardiovascular disease and have a beneficial effect on insulin activity and glucose control,” said Soft Gel’s Mr. Holtby.

    Blueberries have always been a consumer favorite—not just for their antioxidants but also because they are an easy-to-formulate, flavorful ingredient for a variety of products.

    Tom Payne, industry specialist for the U.S. Highbush Blueberry Council, cited animal studies by the USDA Human Nutrition Research Center (HNRC) that demonstrate the health benefits of blueberries, especially regarding motor skills and brain function.

    “Blueberry-fed mice performed better than their control group counterparts in motor behavioral learning and memory,” said Mr. Payne. “Researchers also found a marked decrease in oxidative stress in two regions of the brain and better retention of signal-transmitting neurons compared with the control mice. The compound that appears responsible for this neuron protection—anthocyanin—gives blueberries their color and may be the key to their antioxidant and anti-inflammatory properties.”

    In other developments, research continues to demonstrate the health benefits of glutathione, which is found in every cell of the body and is another major player in the antioxidant market. “According to researchers at Emory University, levels of glutathione vary during a 24-hour period, spiking about six hours after each meal and hitting their lowest point in the morning hours,” said Karen Todd, director of marketing for Kyowa Hakko New York, NY. “Because glutathione levels can only be increased through food intake or dietary supplementation, unless people get up during the night and eat their glutathione levels will be lowest in the morning.”

    Antioxidants can also work together synergistically to create enhanced health benefits. Some of these antioxidants may not have relevant biological activity individually, or work through the same biochemical mechanisms; yet together they can create an interlinked defense system that protects against disease associated with oxidative stress.

    Most antioxidants lose their protective power once they have quenched a single free radical. “Five antioxidants—alpha lipoic acid, the complete vitamin E complex (tocopherols and tocotrienols), vitamin C (in both fat-soluble and water-soluble forms), glutathione and CoQ10—are unique in their synergistic ability to ‘recycle’ one another into their active antioxidant forms,” explained Mr. Holtby. “Selenium (an essential cofactor of the enzyme thioredoxin reductase) and flavonoids are also proven antioxidants in the body’s defense system against oxidation.”

    Up-and-Comers

    More “exotic” high-antioxidant ingredients are being heavily marketed to consumers in the form of functional foods and beverages. “Some of these include the maqui berry (highest ORAC value of the known superfruits), acai, goji and other berries,” said Steve Siegel, vice president of Ecuadorian Rainforest, LLC, Belleville, NJ.

    Other superfruits include dragonfruit, cupuaçu, rambutan, camu camu and yuzu. European black currant and lingonberry, as well as various types of teas beyond the usual green and black varieties, such as Tulsi tea, are also rising in popularity.

    Super C-3-G has significant potential and antioxidant content. The extract is obtained from black rice (Oryza sativa L. indica) grown in Korea and has the same dark pigment found in other types of antioxidant-rich foods, such as berries.

    “However, unlike berries, black rice extract has greater than 25% anthocyanin content,” said Matt Phillips, president and CEO of Cyvex Nutrition, Irvine, CA. “The anthocyanins are composed of 90% cyanidin-3-glucoside (C-3-G). This is important because the amount of C-3-G appears to be directly proportional to the amount of antioxidant activity. Not only does black rice extract have the highest ORAC compared to other berry anthocyanin extracts, it also contains other valuable antioxidants such as vitamin E, tocotrienol and carotene. With such high ORAC levels there are quite a few studies being conducted on its benefits for eye health and other conditions.”

    Natural lutein esters, another rising star in the antioxidant market, are becoming popular for eye health and maintaining a youthful appearance. “These compounds play crucial roles in the macula, the part of the eye responsible for detailed vision,” noted Laura Troha, marketing manager for La Grange, IL-based Cognis Nutrition & Health, now part of BASF. “Compelling evidence shows natural lutein esters can increase macular pigment density, which has been associated with a lower risk of age-related macular degeneration. As for skin health, natural lutein esters improve skin hydration and elasticity. Research shows it also protects against damage from UV light.” 

    Emerging Contenders

    In vitro studies have demonstrated that cinnamon has antioxidant, anti-inflammatory, immunomodulatory and antimicrobial properties. This common spice contains some of the most varied and potent antioxidants of all plants, making it an important food in the control of oxidative stress and thereby the wide range of chronic diseases that are associated with oxidative damage. “In a comprehensive global analysis of more than 3100 different foods published in the January 2010 edition of the Nutrition Journal, cinnamon was found to have one of the highest antioxidant contents of all the foods studied,” Soft Gel’s Mr. Holtby pointed out.

    Turmeric’s principle constituent, curcumin, has been extensively studied by western researchers and scientists for its potent antioxidant activity. Turmeric is thought to reduce inflammation by lowering histamine levels and may also stimulate the adrenal glands to increase production of a hormone that reduces inflammation. It is often used to ease joint pain and inflammation associated with arthritis and other disorders.

    A big surprise for many consumers is that chia seed provides a significant amount of antioxidants (caffeic acid, chlorogenic acid, quercetin, kaemferol and myrecetin). “In fact, the ORAC value of chia seed is comparable to that of fresh blueberries,” said Pharmachem’s Ms. Torkos. “It is very unique for a seed to have this level of antioxidants.

    A wealth of new research findings continue to support the potential of resveratrol, a powerful antioxidant that has been shown to significantly impact the aging process, regulate cardiovascular function and fight cancer. It achieved “superstar” status, partly due to promotion by Dr. Mehmet Oz on Oprah.

    “Preliminary evidence suggests that trans-resveratrol has antioxidant activity and also causes blood vessel dilation,” said Mr. Holtby. “It scavenges free radicals and other oxidants and inhibits low density lipoprotein (LDL) oxidation. Resveratrol has been found to exert a number of potentially cardioprotective effects in vitro, including the inhibition of platelet aggregation, promotion of vasodilation by enhancing the production of nitric oxide and inhibition of inflammatory enzymes.”

    “Some fundamental aspects of resveratrol’s action need to be understood before it can be developed into a clinically viable anti-cancer drug,” added Lakshmi Prakash, vice president of innovation and business development for Sabinsa Corporation in East Windsor, NJ. “These pertain to the key mechanism(s) by which resveratrol potentiates its effects. Current research suggests these might be through novel pathways requiring an understanding of cellular uptake, sentinel targets and in vivo biological networks. The metabolism of resveratrol and its bioavailability also warrant further consideration in light of recent in vitro and in vivo studies.”

    Key Challenges

    Antioxidants have broad appeal because they have been linked to good health and disease prevention. Educating consumers about antioxidants with solid, easy-to-understand science can be a challenge—many marketers simply tout that antioxidants help protect the body against oxidative damage caused by free radicals. “Properly promoting these key nutrients, however, requires taking scientific evidence and presenting it to the consumer in a simple, understandable manner,” stressed Soft Gel’s Mr. Holtby.

    With the recent upsurge in FDA/FTC warning letters pertaining to inaccurate or excessive antioxidant claims in food products (Lipton, POM Wonderful are some recent examples), companies are likely to be more careful with their messaging in 2011. 

    “This fear of antioxidant claims may cause a slowdown in the market trend for antioxidants in foods as companies choose to be more careful about what they say,” RFI’s Mr. Wuagneux stated.

    But doing scientific studies won’t necessarily allow companies to make claims Mr. Wuagneux said.  “POM Wonderful had studies and they were called on it by FTC; in fact POM is filing suit against them. Instead of using the word ‘antioxidant’ companies can make content claims with words like ‘polyphenols’ or ‘flavonoids.’ These words are almost mainstream and are fairly well-known to be antioxidant compounds. It may also be possible to discuss ‘free radical scavenging’ instead of ‘antioxidants.’”

    Mr. Wuagneux further noted that the way manufacturers respond to this issue would depend considerably on the resolution of the dispute between POM and FTC.

    The ORAC (oxygen radical absorbance capacity) assay continues to be a challenge. This testing method places an antioxidant “value” on both foods and supplements by measuring the degree to which a sample inhibits the action of an oxidizing agent and how long it takes. ORAC testing has made a significant impact on the industry’s ability to quantify antioxidant performance.

    “The ORAC assay measures the fluorescence of a target attacked by free radicals, Sabinsa’s Dr. Prakash explained. “It typically uses a single concentration of antioxidant or extract, should be conducted at a range of concentrations and the reaction conditions should be carefully controlled.”

    For example, she said some test substances are sensitive to light and temperature, so samples stored in brown bottles under refrigeration give different results than those left on the bench top in clear glass.

    Another problem with ORAC is the interaction of the sample with the fluorescein reagent used in the test. Some phenols bind to it, probably through hydrogen bonding or pi interactions, preventing decay of fluorescein fluorescence. “When this happens,” Dr. Prakash said, “the test overestimates antioxidant activity, giving extraordinarily high ORAC values that are unrelated to actual radical scavenging activity.”

    Test tube ORAC values also don’t tell the full tale of the “power” of an antioxidant.

    “The more aggressively the test tube ORAC value is used for marketing a product, the more obvious it becomes that nothing else was ever tested on the product,” commented Frank Schonlau, director of scientific communications for Natural Health Science in Chicago, IL. “Key issues that come into play are ingredient specifications, safety data, bioavailability, stability testing and clinical research. Test tube ORAC values can mislead consumers to believe a product is validated.”

    In fact, the ORAC value of the blood of human subjects can be investigated before and after consumption of antioxidants to evaluate their efficacy. Such experiments have been repeatedly carried out with Pycnogenol and are published in peer-reviewed medical journals (i.e., Devaraj et al., Lipids, 2002). “Such ORAC investigations in humans in controlled clinical trials will require a budget of $100,000 compared to $100 for a test tube ORAC assay, ” Mr. Schonlau added. “Yet such clinical studies are much more compelling because they prove the antioxidant is bioavailable and indicate the dosage required to exert an effect in the body.”

    Condition-Specific Antioxidants

    Consumers are increasingly looking for antioxidants that can help them manage specific health conditions. An antioxidant such as lutein is fairly well known for its benefits for eye health, just as cranberries are generally recognized for their ability to treat urinary tract infections. As antioxidants continue to grow in popularity and the list of antioxidants gets longer, consumers are eager to find condition-specific antioxidant products.

    “A lot of the trends in the industry right now are specifically related to aging and disease conditions,” said Kyowa Hakko’s Ms. Todd. “Therefore companies are looking at solutions to increase mobility and improve digestion because these are key issues for people as they age. Although glutathione has several health benefits, at Kyowa Hakko we are keeping our message simple right now and focusing on its antioxidant/anti-aging applications. “

    “Beauty from within” is a relatively new product category of ingestibles, sometimes referred to as cosmeceuticals and nutricosmetics. These antioxidants are being positioned as “beauty enhancing” ingredients. “New niche opportunities exist for pairing shelf-stable beauty food concepts with cosmetic brands in department stores where food is not traditionally sold,” said the U.S. Highbush Blueberry Council’s Mr. Payne.

    Antioxidant research is also shifting its focus from oxidative stress to inflammation. Oxidative stress and inflammation are interrelated—inflammatory cells generate reactive oxygen species, while oxidative stress may participate in the initiation of inflammation, a process often associated with aging. A consumer suffering from arthritis would rather turn to a product with proven efficacy for reducing joint problems than, say, an antioxidant only boasting high ORAC values.

    “High sensitivity C-reactive protein is a major marker in the bloodstream indicative of inflammatory processes in the body,” said Natural Health Science’s Mr. Schonlau. “Taking an antioxidant may help to lower these inflammatory processes and consequently this marker will decrease in the blood.”

    Standing Out in the Crowd

    Key factors making a product successful in today’s crowded antioxidant market include a sound, scientific understanding of its health benefits, delivery systems that are favored by consumers, acceptable price points and science-based marketing/outreach that strives to educate consumers, allowing them to make informed decisions. Consumers are more informed than ever before and have a myriad of choices at their fingertips—a company can have the best science in the world, but if consumers don’t know about the benefits of the product, or understand them, they will move on to the next one.

    For today’s consumer, antioxidant products must meet both the nutritional/health standards and lifestyle demands for every key demographic—especially teen, parent, adult and senior. They will buy items that best fit their activity levels and interest patterns. The products must be easy to consume and be available in a preferred delivery form (i.e., food, supplement, energy bar, gummies, beverages).

    The source and quality of the ingredients and manufacturing processes are also being considered more seriously by customers. “Product quality is center stage with more focus on the supply chain and a specific brand’s reputation,” said Cognis’ Ms. Troha. “Consumers are looking more closely at where a product is derived, how it’s produced and whether it’s sustainable.”

    At RFI, researchers are also conducting more clinical studies with selected antioxidants. “These types of studies, which actually show some quantitative effect of antioxidant supplementation over time, will ultimately make products stand out, both on the ingredient and finished product level,” Mr. Wuagneux said. “This is the future of the industry.”   

    About the author: Mark Crawford is a freelance writer based in Madison, WI. Armed with a science background, he writes about a variety of subjects, from manufacturing to discovery to commercialization to testing/verification to market performance. Personally, natural health is one of his favorite fields. He can be reached at mark.crawford@charter.net.
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