Berries: Beyond Antioxidants

Lately, the news media have found berries hard to resist and have widely reported their many health benefits in newspapers, magazines, and on TV. Considerable interest has been generated in the potential perks of berry consumption, and consumers have happily devoured the combination of common sense (didn’t Grandma insist berries were good for you?) and reliable scientific research that explains how these powerful little packages improve health. With interest in berry-based food and supplement development on the rise, it is important for brands and consumers alike to understand the relevant science, formulations, and measurement technologies if there is any chance of separating hope from hype.

As more research comes to light, a trend will emerge: Consumers will ask, “What specific berry compounds will help me improve my health?” This is a step up from the current level of inquiry (e.g., what is an elderberry and what does it do for me?). While berry science has boomed in the last 10 years, it still lags behind what we know after more than three decades of research in soy, polyunsaturated fatty acids (PUFAs), probiotics, or carotenoids. However, a look at the history of these products gives us a clear snapshot of the future market potential for berries and berry compounds-especially when linked to a more focused, concrete understanding of the health benefits of relevant berry phytonutrients.

Just as we now link lycopene to prevention of prostate cancer and lutein to eye health, consumers and formulators will look beyond berries as “general” antioxidants and make stronger connections with what anthocyanins, proanthocyanidins, and other berry compounds can do for them. This ventures far beyond the current hoopla surrounding the term “superfruits” and the “highest ORAC of the month” phenomenon-a term that few people genuinely understand.

GREATER UNDERSTANDING = CONSUMER CONFIDENCE

This shift in understanding will effectively create an identifiable market for the class of compounds known as berry phytonutrients. Current estimates of the ingredient market for berry compounds as a health ingredient category are nebulous at best, and further complicated by statistics for juice concentrates and natural colors. However, the historical development of other ingredients such as carotenoids, PUFAs, and probiotics as a market class within health ingredients can, as mentioned above, provide a useful insight into the market potential.

The market for carotenoids developed from their use as a natural yel­low to orange color. Research into carotenoids further delineated their usefulness as antioxidants, expanding their marketability. Both researchers and the market can now distinguish the effect (and hence the need) for a particular carotenoid, be it beta-carotene as a provitamin A or lutein for eye health, creating an estimated $380 million ingredient class.

Research in PUFA science also led to marketable results: The recognition that we don’t eat enough unsaturated fats has led to research linking docosahexaenoic acid (DHA) to brain health, DHA and eicosapentaenoic acid (EPA) to cardiovascular support, arachidonic acid to infant development, and so on-all potentially lucrative additions to a market already estimated at $590 million.

So we see similar signs of berry compounds’ progress to a distinctive market class. Not only will we better understand the effect of berry compounds, such as anthocyanins, on overall health, but we will link the specific type and shape to functionality, creating more market opportunity.

SOME OF THE BASICS: WHAT’S IN A BERRY?

Berries are comprised of potent profiles of phytonutrients, including flavonoids (anthocyanins, proantho­cyan­idins, phenolic acids, flavanols, etc.), fatty acids, phyto­sterols, lectins, and an interesting array of vitamins and minerals. In recent years, much scientific research has focused on fruits and vegetables with high concen­trations of flavonoids, courtesy of a growing body of evidence supporting their anti­oxidant activity and related health benefits.

Ron Prior, PhD, a researcher at the USDA’s Arkansas Children’s Nutrition Center (Little Rock, AR) who has conducted a significant body of research correlating the relationship between the composition of agricultural produce and the effects on health, noted in his findings that “among all common fruits and vegetables in the diet, berries, especially those with dark blue and red colors, have the highest anti­oxidant capacities.”1 This mention of color is important because anthocy­anins, a class of flavonoids, are also responsible for the red to dark blue pigmentation in many plants. These anthocyanins, along with proanthocyanidins, are among the major phytochemicals common across berries and are known to be effective antioxidants.

Antioxidants are, as if we don’t all know by now, substances that reduce oxidative damage caused by free rad­icals at the cellular level. They are at the tip of biological processes that would mitigate the decline of cellular functions that lead to diseases such as cancer, cardiovascular disease, neurodegener­ation, and aging. It is exciting for those of us who consume and produce ber­ries and their derivatives to know that berries have such promise. But the biological processes are complex, and researchers remain unsure of all the factors that enable antioxidants to curtail (or prevent) disease.

A current practice is to measure an­tioxidant capacity using methods such as oxygen radical absorbance capacity (ORAC), trolox-equivaent antioxidant capacity (TEAC), and ferric-reducing ability of plasma (FRAP). These tools improved upon the quantification of the compounds in natural products by giving us the added dimension of measuring antioxidant activity, but they are insufficient for what we really need, which is identification of the actual effects on body function or a disease state. For this we need to pro­gress to better physiological assays and clinical trials. In the meantime, the industry works with the methods we have at hand.

Arguably the ORAC method is the most commonly used for measuring antioxidant capacity; for this reason it is important to be aware of the pitfalls and misuses of the method. For instance, there are significant variations in the assay itself. We have seen as much as 25% variation in values coming from the same independent lab on the same lot, completed in the same lab run. The researchers themselves have cautioned against overreliance on published studies for comparative pur­poses, noting that changes in methods, limited sample sizes, variations in growing conditions of the produce, and wide variations in antioxidant activity between cultivars (varieties of the species) make it difficult to form a valid comparison. An example of the latter is blueberries, which have high ORAC values on the average, but some cultivars have very little antioxidant activity. Who knows what cultivar is on their plate?

More troubling is how values of an­tioxidant activity are used in advertising. Too often, ads proclaiming a particular fruit to have “the highest an­ti­oxidant activity” are sponsored by a manufacturer or grower’s association that may change the unit of measure or serving size, ignore the difference be­tween fresh and dry weight, and/or ignore more recent analyses-therefore casting their fruit or product in the most flattering light.

Right now, based on review of independent, published studies, we believe the chokeberry (Aronia melanocarpa) is the commercially available berry with the highest ORAC value. However, this doesn’t mean that somewhere out there, probably in the backwoods of Alaska, there isn’t a berry that comes in with a higher ORAC value. The more important question is this: How much do ORAC and the other methods really matter?

They are, after all, chemical assays that give us a benchmark of an ingredient’s radical scavenging potential, appropriately used for this purpose. But they do not tell us what happens physiologically.

BEYOND ANTIOXIDANTS

Far more exciting is newer research showing the measurable effects that specific compounds, such as anthocyanins or proanthocyanidins, have on an actual condition-whether that be evidence of a broad benefit, such as actual cell protection, or on a disease state, such as a reduction of a brain tumor or a mediation of arterial flow. This type of information takes us be­yond the fact that the berry has anti­oxidant activity to the far more compelling story of how we can use berries to specifically improve and maintain our health, and in what form or doses. This will enable the review and ap­proval of health claims, which not only validates the body of research surrounding the effect of a natural compound on health, but also creates a strong tool of communication for public confidence and awareness.

Health claims will thus contribute to the trend of berry phytonutrients toward an identifiable class of health ingredients. However, a strong health claim requires both the evidence of a good clinical effect and a plausible mechanism of action.

The breakthroughs in berry research in the last decade have already been advanced in part due to improvements in analytical methods-for example, allowing better characterization and more-accurate quantification of berry compounds, including an understanding of how they are metabolized in the body so they can be marked and quantified in tissues, urine, and blood. This accumulation of knowledge leads us to better identification of the functional differences in berry phytonutrients.

One example is the work of Amy Howell, PhD, who researches the health effects of berry phytonutrients at Rutgers University in New Jersey. Most notably, she and her collabo­rators have, over many years, conclusively identified that cranberry’s ability to prevent urinary tract infections is attributable to a specific configuration of proanthocyanidins.2 That said, she still believes there are important interactions within cranberry compounds that make this effect possible.

Another example is the work of Ohio State University’s (Columbus, OH) Monica Guisti, PhD, in looking at the how the chemical composition of berry anthocyanins affects colon cancer. She and her collaborators’ cumulative results suggest that the chemoprotective effect can be enhanced when the structure of the anthocyanin is acylated or otherwise changed.3 Armed with this kind of knowledge, companies can develop better-targeted berry ingredients to enhance a certain effect on disease or functionality.

Still, there is much we don’t understand. For instance, we are pleasantly mystified by the fact that in some cases-such as inflammatory response-the more you fractionate and isolate specific compounds, the greater the response, whereas in other areas like antiviral response, the effect seems to fall apart with greater fractionation of the compounds.

A question we are frequently asked at Artemis (Fort Wayne, IN) regards the differences among berries. There is not a straightforward answer, as there are both commonalities and important differences. Here’s an example, which we believe also illustrates how the consumer will shift from “berry thinking” to “compound thinking”: A few years back, interesting research was conducted showing cherry to be more effective than aspirin in relieving pain and inflammation. The compound directly associated with this effect was cyanidin-3-glucoside, an anthocyanin common to many berries and other fruits. This finding generated a tidal wave of products promoting cherry as an antiinflammatory agent.

As the body of research progressed, it was found that this effect could be seen in the same compound from other berries. Most notably, elderberries from particular cultivars were significantly higher in quantities of cyanidin-3-glucoside. From a product development standpoint, this made elderberry a better candidate for achieving this effect, especially in terms of cost-benefit. Due to the different quantities in the raw material, getting cyanidin-3-glucoside from cherries can be like squeezing water from a stone as compared with the abundant supply in elderberry.

In the end, where you get the desired effect is largely a matter of personal preference. Among the factors to consider are taste, the integrity of the extract, the real quantity of the active compound, cost, and your trust in the food/supplement manufacturer. For instance, many people prefer to eat cherries, but when it comes to a supplement for antiinflammation, we advise reaching for a standardized elderberry extract. This is be­cause a standardized extract, if properly labeled, can more clearly link the amount of active ingredient in studies to what is being consumed.

This is not always easy to do. Sometimes we don’t know the active ingredient or the appropriate dosage, or in some cases which method to use to quantify certain compounds. With the evolution of more specificity in dosages, manufacturers should be obligated to clarify that their supplements do, in fact, deliver effective dosages. Again, we can look at the development of another class of compounds to shed light on where berry phytonutrients stand now and where they can end up. In the early days of probiotics there was also much discrepancy about how to report the active ingredients. Manufacturers would often use grams of Acidophilus, whereas it is now clear that the sensible way to quantify probiotic activity is the number of live cells or colony forming units (CFU).

In today’s market, berry phytonutrient labeling is fraught with information that is hard to make sense of. For example, on given elderberry supplements, one might see various amounts of the following as listed ingredients: “elderberry powder 4:1,” “elderberry extract,” 25% elderberry extract,” “elderberry,” and even “elderberry concentrate.” Not one of these descriptors thoroughly explains how much of the active ingredient(s) within elderberry is being consumed per serving-leading to confusion and skepticism. Similarly confusing is when a serving size is 1 capsule but the package directions recommend 1 or 2 capsules 4 to 6 times per day. This is why Artemis encourages standardized reporting of berry supplement ingredients and doses, giving the consumers more-straightforward ingredient information.

SO WHAT’S THE BEST BERRY?

The short answer is-there is no simple, straightforward answer. We routinely test berries and berry products not only for characterization and quality control, but in collaboration with leading independent health and nutritional researchers. We compare berries to evaluate their functional effects in a number of areas. We maximize performance by developing combinations across fractions and species. If pressed to answer the question, we would cite the chokeberry as a nutritional dynamo. In our experience, chokeberry is typically-though not always-the top performer in many biological assays. But it’s still an incomplete answer.

First, assays are just that-assays that give an “indication of performance in the body.” It also does not take into account final product formulation, taste, and cost. And sometimes being the “top” performer is not significantly different from the next runner-up. It should be noted here that berries as a group often perform very well in biomedical assays, with only slight differences. But the most important factor is that we don’t have to choose just one berry.

Jim Joseph, PhD, a researcher at the USDA Center for Human Nutrition & Aging (Boston), once pointed out to us that God is the greatest pharmacist of all, and He gave us a plethora of delightful fruit choices, all with specific health benefits that are sometimes common across fruit but also sometimes unique in supporting a particular health function. We are, after all, designed to be hunter/gatherers.

After years in the industry with a heavy corporate emphasis on looking at research, we are convinced that the answer is to eat as many different fruits as possible. Enjoy the benefits of modern distribution channels that allow you to savor products containing the Brazilian açai berry, the New Zealand black currant, or the Indian kokum, as well as the fresh apples, oranges, raspberries, and blueberries you love. Eat them as often as you can and as raw as you can, reserving enhanced extracts and processed fruit concentrates and powders for supplementation when needed.

THE FUTURE IS “BERRY” BRIGHT

Given what we are learning about the health benefits of berries, it is alarming to see the statistics on how little fruits and vegetables (let alone just berries!) are consumed in the United States. The research community is bringing to light how much the population has to gain from increasing its consumption of fruit. We are hopeful that credible science and ethical communication of that science can go far in convincing the public to eat more fruit for general health. We also see evidence that consumers will increasingly reach for supplements of berry phytonutrients for specific healthcare concerns. We are skeptical of claims that a powder or a pill can deliver the same total benefit as raw fruit. However, the research is showing that quantifiable amounts of micronutrients can have a measurable impact on a particular condition, and these amounts can in fact be delivered in a supplement as well as in foods.

We already see consumers reaching for cranberry proanthocyanidins for urinary tract infection, elderberry phyto­nutrients to combat a cold or flu, and black currant to improve eye health. With current research continuing to link specific berry compounds to specific healthcare concerns, we can foresee a time when the market will acknowledge a particular anthocyanin structure to mitigate the chances for neurodegenerative disease, cancer, cardiovascular disease, diabetes, and to support immune function, vision, athletic performance, weight loss, and so on. And for anyone who has ever wondered how something so little can do so much good, we say berries truly are nature’s perfect little packages.

References

1. X Wu et al., “Characterization of Anthocyanins and Proanthocyanidins in Some Cultivars of Ribes, Aronia, Sambucus and Their Antioxidant Capacity,” Journal of Agriculture and Food Chemistry, vol. 52, no. 26 (November 24, 2004): 7846–56.

2. A Howell et al., “A-type Cranberry Proanthocyanidins and Uropathogenic Bacterial Anti-Adhesion Activity,” Phytochemistry, vol. 66, no. 18 (September 2005): 2281–2291.

3. P Jing et al., “Effects of Chemical Composition on the Chemoprotection and Added Value of Anthocyanin-Rich Commodities,” (poster presented at the annual meeting of the Institute of Food Technologists, 2006).

Jan A. Mills is president of Artemis International Inc. (Fort Wayne, IN). For more information, contact Artemis by visiting www.artemis-international.com or calling 260/436-6899.