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The future looks encouraging for antioxidant research, despite some new articles that questioned the effectiveness of antioxidant supplements.

The future looks encouraging for antioxidant research, despite some new articles that questioned the effectiveness of antioxidant supplements. Research, manufacturing, and marketing efforts related to antioxidant ingredients are growing and consumer interest remains strong, according to manufacturers. In particular, antioxidants derived from plant-based sources, such as fruits and vegetables, are generating a lot of excitement and have been receiving a great deal of attention from researchers. While more studies need to be done on these antioxidant ingredients, early studies have been promising, leading many researchers to believe the time is ripe for more fruit-based products.

Photo courtesy of FutureCeuticals.



A science advisory issued by the American Heart Association’s (AHA; Dallas) nutrition committee in the August 3 issue of Circulation said that antioxidant supplements should no longer be recommended for the prevention of heart disease. According to AHA, while diets rich in antioxidants have been shown to be beneficial, studies with supplements of antioxidant nutrients, such as vitamins A, C, and E, have produced mixed results.

The Council for Responsible Nutrition (CRN; Washington, DC) immediately challenged the advisory, citing examples of four large cohort studies that showed positive results. Saying that AHA was “trying to prematurely close the door on supplement use,” CRN president Annette Dickinson, PhD, pointed out that some of the negative trials were secondary intervention trials on patients with heart disease, while some of the positive trials were primary prevention trials on healthy individuals. “Even if recent secondary intervention trials have been disappointing,” she said, “those results do not trump the epidemiological data on primary prevention.”

Some ingredient suppliers, such as Carotech Inc. (Edison, NJ), also suggested that flaws in the studies could have skewed the results. For instance, Carotech vice president W. H. Leong noted that in a recent review of studies on vitamin E published in the Archives of Internal Medicine, all of the studies used the same form of vitamin E. “Numerous objections were raised against these trials, most notably the doses used, but the real problem could have been that alpha-tocopherol does not itself provide the right vitamin E activity and protection for the heart,” Leong said. “These studies were carried out with regular commercial vitamin E supplements that did not contain the other forms of vitamin E such as tocotrienols, which could explain some of the inconsistent results in the studies.”

In addition, studies published a few weeks after the AHA advisory suggest that antioxidants may offer benefits unrelated to heart disease. A study in the August 18 issue of the Journal of the American Medical Association, for example, found that vitamin E appeared to improve respiratory tract health in the elderly. In the study, which was led by Simin Nikbin Meydani, PhD, of Tufts University (Medford, MA), more than 600 nursing-home residents were given a multivitamin that supplied 50% of the recommended daily allowance of several micronutrients. About half of the patients were also given an additional 200 IU of vitamin E, while the other half were given a placebo. CRN’s Dickinson said the study “further illuminates the importance of vitamin E supplementation for the elderly, who are generally at risk for nutrient inadequacy.”



Some of the most promising new research on antioxidants involves antioxidants derived from fruits and vegetables. Epidemiological studies have linked a plant-based diet to a lower incidence of disease, and in recent years, scientists have begun to more closely examine the role of phytochemicals in nutrition. One theory suggests that brightly colored fruits and vegetables are healthy because their pigments act as potent antioxidants. In nature, these pigments are thought to serve a variety of defensive functions for plants and may offer protection against ultraviolet light, oxidation, and other environmental factors.

Several ingredient suppliers have introduced antioxidant products that are based on extracts from berries, which often contain high amounts of antioxidant pigments, such as anthocyanins and proanthocyanidins. While some ingredients are derived from a single fruit extract, most new antioxidant ingredients are actually a combination of extracts from several fruit sources. According to Hartley Pond, sales manager at FutureCeuticals (Momence, IL), this is because research suggests it is best to consume a broad spectrum of fruits. “The phytonutrients found in cranberries differ from those found in strawberries, blueberries, and cherries,” Pond says. “By consuming fruit extracts and powders in combination, one can achieve a broader nutritional profile.”

Manashi Bagshi, PhD, research scientist at InterHealth Nutraceuticals (Benicia, CA), agrees. “The combination has a synergistic effect,” Bagshi says. “The more anthocyanins you have, the better the antioxidant is.”

Both FutureCeuticals and InterHealth offer multiple-berry ingredients. FutureCeuticals’ VitaBerry, for instance, contains extracts from a number of fruit sources, including wild blueberry, grape, grapeseed, cranberry, prune, cherry, bilberry, and strawberry. “VitaBerry combines the high-antioxidant capacity of fruit extracts with fully intact freeze-dried whole powders that are standardized for specific phytonutrients,” Pond says. Similarly, InterHealth’s OptiBerry is a blend of six different berry extracts: wild blueberry, strawberry, cranberry, wild bilberry, elderberry, and raspberry seed.

The antioxidant properties of berries can be measured using a variety of standards, such as oxygen radical absorbance capacity (ORAC). According to Bagshi, InterHealth evaluated 20 different combinations of berry extracts before settling on the formula for OptiBerry. “It was found to be the most effective, producing significantly higher ORAC values than other berry blends,” Bagshi says. The formula also had the lowest cytotoxicity of all of the compounds tested. “We did a lactate dehydrogenase (LDH) test in vitro, and significantly less LDH leakage was detected when relatively high levels of OptiBerry were added to the cells.”

Another antioxidant ingredient derived from berries that combines multiple extracts is NutriCran GI, a powdered cranberry extract from Decas Botanical Synergies (Wareham, MA). According to Doug Klaiber, general manager at Decas Botanical Synergies, cranberries contain high amounts of proanthocyanidins and other antioxidants. “The cranberry is one of the better fruits for antioxidants,” Klaiber says. “I actually like to call it the MVP of fruits because it ranks so high.”

Cranberry powders are also very low in calories when compared with cranberry juice, Klaiber adds. “Cranberry juice and juice cocktails are very high in calories because of the sugar,” Klaiber says. “Even 100% juices have a lot of sugar. So for those people who are interested in getting all of the benefits of cranberries without all of the sugar, supplements can be a good alternative.” Klaiber says that Decas, which introduced a line of powdered cranberry extracts in 2004, has been collaborating with researchers at the University of Massachusetts (Amherst, MA) who have been studying the antimicrobial properties of cranberry extracts. Cranberry juice is often taken to support urinary tract health, and one reason why could be that proanthocyanidins make it more difficult for bacteria to attach themselves to cell walls.

Decas launched NutriCran GI at this year’s SupplySide West show held in Las Vegas in October. “It’s really targeted toward gastrointestinal health, but it’s also very high in antioxidants,” Klaiber says. “It’s a blend of cranberry powder, grapeseed extract, and wild blueberry powder.” According to Klaiber, cranberry extracts were found in one study by University of Massachusetts researchers to inhibit H. pylori bacteria in vitro; the study will soon be published in Process Biochemistry.



Palm fruit provides a rich source of tocotrienols, members of the vitamin E family that help fight oxidation. Vitamin E actually consists of tocopherols and tocotrienols, which have different chemical structures; tocopherols possess a saturated phytyl tail, while tocotrienols have an unsaturated isoprenoid side chain.

According to Carotech’s Leong, tocopherols and tocotrienols both scavenge free radicals. However, Leong adds that scientists’ views about the antioxidant effects of both kinds of molecules have been evolving.

“For many years, alpha-tocopherol was generally considered the most potent antioxidant against lipid peroxidation in the vitamin E group,” Leong says. “Recently, however, there has been a considerable discrepancy in its relative antioxidant effectiveness when compared with other isomers. On one hand, gamma-tocopherol was found to be more potent than alpha-tocopherol, particularly in its interaction with reactive nitrogen oxide species. On the other hand, alpha-tocotrienol was found to be a better antioxidant than alpha-tocopherol.”

One key to the antioxidant activity of tocotrienols is their ability to move through cell membranes. “Their greater mobility through the cell membranes also allows them to get ‘recharged’ or regenerated more quickly by vitamin C, glutathione, or CoQ10,” Leong says. Carotech recently earned a patent for one of its ingredients, Tocomin Suprabio System, which was designed to be more bioavailable in the gastrointestinal tract than other forms of tocotrienols. “In a two-period, two-sequence crossover study, the results showed that it was 200–300% more bioavailable, compared with the conventional tocotrienol oil extract,” Leong says.

Leong adds that the company also recently began promoting a new vitamin E ingredient, E Complex, which consists of all eight forms of vitamin E: alpha, beta, gamma, and delta tocopherols, and alpha, beta, gamma, and delta tocotrienols. “All of these different forms of vitamin E work synergistically to confer the maximum antioxidant protection,” Leong says.



Although lutein is not derived from fruit, it is found in brightly colored plants and some vegetables, like marigolds and spinach. Kemin Foods (Des Moines, IA) recently secured a Canadian patent for its FloraGlo lutein that covers the process of forming, isolating, and purifying lutein from marigold flower petals. The patent is part of an international portfolio of patents owned by Kemin in countries such as the United States, Japan, Germany, and Australia.

“Our purified lutein is identical to the lutein found in spinach and other dark leafy vegetables, as well as in eggs,” says Zoraida DeFreitas, PhD, director of research and development for Kemin Foods. “Consumers of supplements, foods, and beverages enhanced with Kemin Foods’ FloraGlo lutein can be confident it is a quality ingredient made according to a proven and patented process.”

The Canadian patent comes on the heels of a recent decision by the Joint Expert Committee on Food Additives (JECFA), the scientific body of the Codex Alimentarius Commission, setting an acceptable daily intake for lutein and zeaxanthin alone or in combination at up to 2 mg per kg of body weight.

JECFA, which is administered by the Food and Agriculture Organization of the United Nations (New York City) and the World Health Organization (Geneva), included the new acceptable daily intake level in the report from its 63rd meeting held in Geneva June 8–17, 2004.

“The JECFA lutein intake recommendation is a global-scale acknowledgment of the safety of free lutein and zeaxanthin,” says Rodney Ausich, PhD, president of Kemin Foods. “While many health and nutrition researchers have suggested taking 6–20 mg of lutein based on their studies, the acceptable level stated in the JECFA report further supports past findings that supplemental free lutein is generally accepted as a safe compound for the human diet.”

Ausich adds that the company also received a letter of nonobjection from FDA regarding lutein’s GRAS status for several categories of foods and beverages. “Our GRAS attainment was completed through a number of self-determination reviews, in which outside expert panels examine safety data. The FDA letter is yet more evidence of FloraGlo lutein’s safety as a food ingredient.”



Another antioxidant ingredient that recently got a boost is vitamin E. Zila Nutraceuticals (Prescott, AZ) introduced its new Ester-E ingredient earlier this year.

“The response from our manufacturing partners in regard to Ester-E has been incredible,” says Steve Lefkowitz, director of sales and marketing at Zila. “Based upon their success with Ester-C and their knowledge of our commitment to the Ester brands through consumer advertising, almost all of our customers are folding Ester-E into their line offerings. In fact we achieved our first wave of national retail distribution in late July, which included Wal-Mart. Our advertising commitment to Ester-E began with national radio advertising in August.”

According to Larry Robinson, PhD, Zila’s director of research and development, in vitro and animal studies on Ester-E have already been conducted. “We are currently working to develop analytical testing methods for human clinical trials,” Robinson adds. “We are planning to begin trials at the University of Michigan later this year.”

And in other vitamin E news, DSM (Basel, Switzerland) announced on September 9 that it has opened the world’s largest vitamin E plant in Sissein, Switzerland. “Through this investment, DSM demonstrates its strong commitment to the industry and our customers, and once again confirms our position as the global leader in nutrition ingredients,” says Bob Hartmayer, COO of DSM Nutritional Products.

The new factory, which will produce about 25,000 tons of vitamin E per year, is equipped with integrated process controls and an on-site analytical laboratory to monitor quality and provide analytical services. “This new facility will meet the stringent industry demands for quality by ISO certification and includes systems to monitor full product traceability,” says Paul Gilgen, head of DSM’s global technical department.



Although some of the negative articles may have cast doubts about the efficacy of antioxidant supplements, industry stakeholders have also put forward a strong defense of antioxidants and offered rebuttals of critical articles. Moreover, ingredient suppliers and manufacturers have been ratcheting up their marketing and R&D efforts.

“We believe consumer interest in antioxidants remains strong,” says FutureCeuticals’ Pond. “While there have been recent inconclusive studies on certain vitamins, there is an overall consumer acceptance that a diet high in key vitamins is important to good health, and that supplementation, in addition to a quality diet, is a sound way to ensure good nutrition.”

As for antioxidants from fruits and berries, Pond adds that there has been quite a bit of positive news coming from the United States Department of Agriculture (USDA; Washington, DC) and university studies over the last few years. “The fact that major health organizations such as USDA, Harvard School of Public Heath, the 5-A-Day program, and many others are touting the importance of consuming multiple servings of fruits and vegetables for good health has helped raise public awareness of the importance of fruit-based antioxidants, as well as the important fibers and carbohydrates found in fruits and vegetables. We believe that consumer awareness and interest in fruit-based antioxidants will continue to grow.”

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