The Antioxidant Appeal of Flavonoids

Who knew that beer and chocolate could be the 21st century's answer to multivitamins? Well, maybe they arent exactly the same thing. Then again, extracts from beer and chocolatenamely the flavonoids xanthohumol from beer and procyanidins from chocolate may be exactly what the naturopath ordered.

Flavonoids such as thesefound in hops and cocoa beansoccur naturally in plants but not in mammals. This means the only way humans receive flavonoids is by ingesting plants or their extracts. The Agricultural Research Service (ARS) under the U.S. Department of Agriculture (USDA) estimates U.S. flavonoid consumption is between 23 mg/d and 1,000 mg/d.

The health benefits of flavonoids were first discovered in 1930s Hungary by the Nobel Prize-winning biochemist Alber Szent-Gyorgi. He came across a class of plant compounds he named Vitamin P because they were found in plants and acted similarly to vitamin C in protecting blood vessels and capillaries. Years later, this antioxidant class was renamed polyphenols.

Under the umbrella of polyphenols are more than 4,000 chemically unique flavonoids, also known as bioflavonoids, that can be categorized according to their chemical structure. Subcategories include flavonols (such as quercetin from onions and Ginkgo biloba), flavanones (such as narigenin from oranges), isoflavones (such as daidzein from soy and red clover), catechins (such as EGCG from green tea) and anthocyanidins (such as cyanidin from bilberry and grapes). And all have been associated with health benefits. For instance, one study found quercetin, narigenin and a handful of other flavonoids reduced the risk of chronic diseasewhich covers a lot of ground.¹

For the manufacturer looking to invest in flavonoids for a food, beverage or supplement, this may be a good time to do so. In a recent Frost & Sullivan market report, the market analyst firm reported U.S. isoflavone and flavonoid producers should be looking for an early positioning in breakfast cereals, beverages, bakery and dairy products to get a toe-hold in a market where flavonoids are used marginally.

Flavonoids, as natural ingredients in fruit and vegetables, are ideal for the natural food products category as well as in the mainstream area, said Frank Schonlau, Ph.D., director of scientific communications at Horphag Research, the original developers of Pycnogenol, which is distributed by Hillside, N.J.-based Natural Health Science. They are currently gaining momentum in the food and beverage category.

The Science

Flavonoids go beyond the yeoman work of your average antioxidant, wrote Willow Lawson in the July 8, 2003, edition of Psychology Today. Scientists have found that certain flavonoids have antihistamine, antimicrobial, memory- and even mood-enhancing properties.

There is a wide range of botanically derived flavonoids with inherent health benefits, and cocoa and hops are no exception. In particular, cocoa has been found to have higher antioxidant content than tea or wine, thanks to high amounts of gallic acid equivalents (GAE) and epicatechin equivalents (ECE) per serving.² In terms of condition-specific benefits, researchers out of Japan reported cocoas flavonoids inhibited diabetes-induced cataract formation in a rat model³ and stopped the spread of tumors.⁴

And the worlds knowledge about beers health benefits is based in part from research out of Oregon State University, Corvallis, which indicated the hops used in most beers are a better source of antioxidants than red wine, green tea and soy. Hops contain xanthohumol, a prenylated flavonoid that has been seen to prevent carcinogenic activity in a mouse model⁵ and has been seen to be a potent antiviral agent against herpes simplex virus Type I and Type II.⁶

Another alcoholic drink with health potential is wine. Danish researchers reported that people who occasionally drink red wine had lower dementia rates.⁷ The scientists hypothesized the wines high flavonoid content was responsible for the beneficial effect.

Those flavonoids are thanks to the grapes that are crushed to make the wine. In a study of red grape seed proanthocyanidins, researchers reported 100 mg/kg in a rat model reduced free radical activity by 75 percent, lending itself to cardioprotection.⁸ (The grape seed extract used in the study was ActiVin, from San Joaquin Valley Concentrates in Fresno, Calif.) And a research review of grape seed extract (as MegaNatural Gold, manufactured by Madera, Calif.-based Polyphenolics) indicated oral intake decreased plasma total and LDL cholesterol in subjects with high cholesterol.⁹ And thats just the tip of the proverbial iceberg: A clinical trial out of London is currently investigating whether grape seeds flavonoids reduce radiation fibrosis, a side effect from radiotherapy.

Another grape by-product, resveratrol, accounts for 5 percent to 10 percent of grape skin biomass. The extract has been found to inhibit each stage of multi-stage carcinogenesis, particularly in prostate cancer,¹⁰ and also has cardioprotective effects.¹¹

It is not only drinks of the alcohol variety that have shown promising benefitsthe same attributes have been found in tea (black, green, white, etc.). Tea flavonoids have been seen to reduce a persons risk of dying after a heart attack, possibly due to their ability to inhibit oxidation of LDL (bad) cholesterol.¹² Even in the cancer realm, teas flavonoids are making their presence known: Epigallocatechingallate (EGCG) has been seen to shut down the key molecules that tobacco uses to foster cancer. ¹³ And, in numerous experiments, EGCG has demonstrated protection against dental caries.¹⁴

Just as teas EGCG has been linked to health benefits, so have isoflavones. Red clovers isoflavones have been implicated as potential preventive agents for the development and prevalence of non-malignant prostate diseases.¹⁵ And in womens health, one month of supplementing with 86 mg/d of red clover isoflavones had a positive effect on HDL cholesterol in both pre- and post-menopausal women.¹⁶ In addition, soys isoflavones, especially genistein, have been seen to ameliorate damage caused by proteins that foster Alzheimers.¹⁷

Another cancer-fighter in the flavonoids grouping is French maritime pine bark extractchronic exposure to cigarette smoke for 75 days revealed that Pycnogenol significantly reduced mutagenicity by up to 48 percent and decreased pathological changes in lung tissue.¹⁸ Pycnogenol has also been seen to benefit mildly hypertensive patients.¹⁹

On the berry side of botanicals, cranberrys proanthocyanidins have been identified as the active component responsible for inhibiting the adhesion of certain bacteria to cell walls. This is the newest hypothesis regarding cranberrys ability to prevent urinary tract infections (UTIs). In fact, cranberry has been seen to decrease the number of symptomatic UTIs over a 12-month period in women.²⁰ Cranberry has the highest total antioxidant activity, followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit and pineapple.²¹

Another beneficial berry is bilberry. In particular, bilberry (Vaccinium myrtillus) may have a hand in reducing age-related macular degeneration (AMD) risk.²² In a study using Italy-based Indenas Mirtoselect, a standardized bilberry fruit extract containing 36-percent anthocyanosides, the extract helped recover reduced visual function caused by overuse of the eyes, improving subjective symptoms such as vision with sparks, dimming of eyesight and ocular fatigue in computer operators, office workers and students compared with patients treated with a placebo.²³

The anthocyanidins found in bilberry include cyanidin, delphinidin, petunidin, malvidin and pelargonin. According to Los Angeles-based OptiPure/Soft Gel Technologies, makers of VmA25+, bilberry extracts with 25-percent anthocyanidins have demonstrated significant vasoprotective and antiedema properties in animal studies.

Flavonoids from one kind of berry are good, but flavonoids from multiple berries may be better. OptiBerry, a patent-pending, sixberry anthocyanin extract from Benecia, Calif.-based InterHealth Nutraceuticals, has demonstrated anti-angiogenic properties in both in vitro and in vivo research.²⁴

The Applications

Putting flavonoids into a cereal or even a water is on the rise, especially as manufacturers realize that customers are looking for convenient ways to get their recommended five servings of fruits and vegetables a day.

The conventional food industry has been known in the past to remove phytonutrients via selective breeding and a variety of debittering processes in order to remove the bitter taste these compounds inherently possess. According to a paper presented at the 226th American Chemical Society, adding flavonoids during food processing can actually produce better-tasting products. By understanding how health-promoting flavonoids alter flavor generation, we can learn how to produce healthier foods that taste good, too, said Devin Peterson, Ph.D., lead researcher from Pennsylvania State University, University Park. He added, Our research has shown that in food and beverage products that are heated for safety or preservation, flavonoids can limit the generation of off-flavors, such as the scalded or cooked taste of ultrapasteurized milk. Weve also found that it may be possible to enhance some good flavor pathways while limiting others, including less desirable smells, by the addition of flavonoids.

It is important to be aware that while flavonoids dont require considerable processing for tablet or capsule forms, more processing is needed when putting a flavonoid into a food or beverage, and exposing the nutrients to heat can make them lose their oxidative punch. As such, a manufacturer looking into using a flavonoid in a functional food or beverage should make sure the ingredient has been shown to be stable under such conditions.

A manufacturer should also be aware that certain flavonoids impart discoloration and a possible change in flavor in the end product, depending on the concentration. [Most bilberry] extracts contain a large amount of active anthocyanidins that can color foods and precipitate proteins, said Kenn Israel, director of marketing at OptiPure/Soft Gel Technologies. Natraceutical S.A., makers of a cocoa bean powder low in fat and high in dietary fiber, reported the final color of the powder can be controlled and modified during manufacturing.

Grape seed extract is one flavonoid rearing its head in the unlikeliest of places, including in cereal, nutrition bars and yogurts. Once relegated to super-antioxidants and stand-alone formulas, these extracts are popping up in 100-percent juice beverages in order to raise a juices antioxidant capacity to be at the same level as wine. Grape seed extract is also being used in smart waters to boost their health benefits without a boost in calories.

I would say the number of products out is limited and mainly in the health food sector rather than the mainstream, said Ron Martin, vice president of sales and marketing at Polyphenolics. I expect this to change in the next few years, but it will take an educational effort to the public to make this happen.

Luckily, it looks like consumers are becoming more aware of the particular health benefits fruits imparteven if they dont know the flavonoid responsible for the benefit. Most consumers would acknowledge that grape products, including wine and juices, provide cardiovascular benefits, said Steve Anderson, vice president of San Joaquin Valley Concentrates. Over the next couple of years, it is quite likely that sales to food/beverage manufacturers will exceed supplements.

Supplements have been the main cash cow for soy isoflavones, but manufacturers are currently trying to incorporate more of these healthy flavonoids into foods and beverages. According to Lee Knudson, product manager for Minneapolis-based Cargills AdvantaSoy isoflavone business, We can help customers develop products like juice or energy drinks, whether they want to promote the general benefits of soy or the isoflavone-specific benefits. He added that Cargills in-house development team works with manufacturers to put isoflavones into new applications. Were also looking into marrying isoflavones to other flavonoids linked with womens health, such as cranberry and bilberry extracts. By putting such a relationship together, the customer doesnt need a significant amount of education on the ingredients, since the knowledge base is already there.

For an ingredient like cranberry extract, using a flavonoid can refresh the image of a traditional food or beverage. The interest and value to retail manufacturers is that they can piggyback on their preexisting marketing and position with a new and improved version that offers increased benefits, said Doug Klaiber, general manager to Wareham, Mass.-based Decas Botanical Synergies, makers of NutriCran Bio-100.

Thats not to say supplement sales will be hurt by functional food and beverage applications. According to Dean Mosca, president of Ontario-based Proprietary Nutritionals, marketers of CranMax cranberry extract, There is a large market for women and seniors that are looking for an effective, off-the-shelf supplement that can reduce the symptoms of UTIs and promote urinary tract health.

There are some flavonoids that have not received GRAS status for food and beverages but still hold potential in the supplement industry. Teavigo from Switzerland-based DSM Nutritional Products contains 94-percent EGCG and .01-percent caffeine. It is in the midst of obtaining GRAS status, although it has been used overseas in Asia and has been tested as an ingredient in cereal bars, soft drinks, gum and water. In supplement form, Teavigo is being targeted for weight-loss, heart health and metabolic syndrome products.

With the world of flavonoids becoming more crowded with up-andcomers from the tea, cranberry and soy families, a manufacturer should be rest assured that these nutrients are here to stayand consumer awareness and research surrounding each flavonoid are growing. Some 10 years ago, a flavonoid described as a potent antioxidant was attractive for the consumer, Schonlau said. Today, clinical research has to demonstrate a substance works for specific health concerns.

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