Scientists Zero In on Health Benefits of Berry Pigments

Article by Don Goldberg

Scientists Zero In on Health Benefits of Berry Pigments

by Dr. Paul Gross - Berrydoctor.com

For many years, “eat a colorful diet” has been the advice of physicians and nutritionists, yet a pandemic of poor diets linked to rising rates of obesity, diabetes, cancer, and chronic inflammatory, pain and cardiovascular diseases has swept across the world.
Recognizing the urgent need to redirect consumer attention toward healthier eating habits and lifestyles, various scientific and consumer organizations have released advisories for eating higher amounts of whole natural foods, including color-rich plants like berries. Colorful plants not only contain good levels of essential nutrients like vitamin C and fiber, but also harbor among the richest amounts of  phenolic pigments in Nature.
During June 11-12, 2007 at Oregon State University in Corvallis, Oregon, 27 international scientists gave presentations on recent research discoveries about berry pigments and their potential health benefits at the 2nd International Symposium on Berry Health Benefits. The first symposium was held in 2005, also in Corvallis.
Each of the presenters discussed new discoveries about berry nutrients, particularly anthocyanins, a large class of pigments among plants. Anthocyanins make up the bright blue, violet, red and purple colors of berries, other fruits, vegetables and flowers, bearing names derived from their flower origins: petunidin, peonidin, rosinidin, and cyanidin are a few among some 400 hundred anthocyanin pigments in the plant world. Blueberries, blackberries, black and red raspberries, black and red currants, red grapes and red wines contain dozens of different anthocyanins per fruit. Because of this, berries are considered an elite category of fruit.

Color Your Diet. The meeting was highlighted by the keynote address of David Heber, MD, PhD, University of California-Los Angeles Center for Human Nutrition, author of the popular 2001 book, What Color Is Your Diet? (3). Although 6 years old, the message from Heber's book is ever more important today: a colorful diet of plant foods is needed to fortify yourself with nutrients and antioxidants, rather than the brown-white diet of burgers, potatoes and bleached processed foods so commonly preferred in many countries.

Anthocyanin Antioxidants. In the plant itself, pigments are a defensive shield against the ultraviolet radiation of sunlight, bacteria, viruses, fungi and oxidative reactions. They are the valued antioxidant plant chemicals, providing the plant a way of protecting its seeds against oxidative radicals produced during photosynthesis and exposure to sun and pests. The colors have a more visible role of also attracting pollinators for reproductive purposes, drawing predators to eat the fruit and disperse seeds for germination elsewhere.
For human consumers, however, the colors offer a simple guide to shopping for healthful foods and meal preparation. Berry scientists are helping to educate the public about these offered benefits.
As recently as 2005, international scientific groups met to discuss the potential health properties of berry flavonoids – the parent class for anthocyanins -- at a conference (2) attended by G. Mazza, of Agriculture and AgriFood Canada (AAFC). In Oregon, Dr. Mazza presented a summary of research work showing the broad positive health effects demonstrated for anthocyanins in various organ systems, particularly the heart and blood vessels.
Laboratory Research Shows That Anthocyanins:
• reduce the coagulation of blood platelets, inhibiting formation of blood clots involved in stroke, pulmonary embolism, peripheral vascular disease and heart attack
• promote higher levels of “good” cholesterol, HDL
• inhibit oxidation of “bad” cholesterol, LDL
• neutralize oxygen radicals
• down-regulate enzymes leading to inflammatory reactions that cause pain and stimulate other diseases

Breeding Better Berries. Work from Ancona, Italy by M. Battino and colleagues highlighted progress toward identifying anthocyanins from strawberries, measuring their antioxidant strength, then breeding strawberry cultivars to bear richer concentrations of the best antioxidant anthocyanins. Such research is an important tool for providing horticultural scientists with the right hybrids for new breeding material and, in the future, the public with favored berry fruit having optimized levels of anthocyanins (11).
Developing these capabilities further, the US Department of Agriculture group in Corvallis and Parma, ID (M. Dossett, C. Finn, J. Lee) presented work showing that black raspberries, an anthocyanin-enriched berry fruit (so intense with anthocyanins that the USDA used its juice for decades as an indelible, safe meat stamp), could be bred for higher anthocyanin profiles, especially in progenies from wild strains that had exceptional anthocyanin contents.
Also shown at the meeting by A. Penia-Neira and colleagues (Santiago, Chile) was new research about  strawberry leaves as excellent sources of anthocyanins, indicating potential for broader use of berry plant components for diets and nutraceuticals
.
Distribution in the Body and Bioavailability. Anthocyanin-rich plant foods contain up to several hundred mg of active chemicals per each 100 g serving, but most of that intake is degraded in the digestive tract within hours of a meal (10). Compounding the problem of measuring anthocyanins in vivo is that these chemicals are stable in an acidic environment (pH 3.5), but destabilize, degrade or bind together (called polymerization) as pH rises in the blood (pH 7.4).  To what degree effective anthocyanins remain and in what specific organs were research topics discussed at the conference, with seven speakers providing the following highlights
1. W. Kalt et al. (AAFC-Nova Scotia) showed that daily feeding of blueberries to pigs over an 8 week period delivered anthocyanins to all organs examined, with the interesting discovery that some anthocyanins, e.g. malvidin, were deposited in tissues proportionately more than their content in the fruit; this result may indicate active uptake and tissue binding of malvidin and certain other anthocyanins
2. R. Koli and colleagues (Finland) tested uptake from a bilberry-rich diet in patients with cardiovascular disease, showing that indicators specifically in the heart and coronary vascular functions were improved from the berry diet
3. M.A. Lila (University of Illinois) presented evidence that blueberry extracts fed to mice resulted in higher levels of the energy molecule, ATP, specifically in glial cells in vitro, indicating selectivity of uptake by an energy-demanding cell line
4. in studies of anthocyanin-rich fruits, such as blackcurrants, T. McGhie (New Zealand) showed that retention and bioavailability of ingested berry phenolics was only 1-4% of the total hours after ingestion and that plasma antioxidant capacity did not increase, results that reveal difficulties in interpreting the fate and function of anthocyanins in vivo
5. the McGhie study differed, however, from research by R. Prior et al. (USDA-ARS Arkansas) who showed recently that consumption of blueberries or red grapes increased plasma anthocyanin content and antioxidant capacity of human subjects (10)
6. despite the above evidence for significant body elimination of consumed anthocyanins from antioxidant-rich foods like berries, A. Crozier (University of Glasgow, Scotland) gave evidence from hamster studies that lipid deposition in major arteries like the aorta could be substantially prevented by berry anthocyanins, a finding pertinent and timely, according to Crozier, for enjoying the famous Wimbledon treat of strawberries in double cream!
7. several discussions addressed the possibility of an anthocyanin-specific receptor in certain organs or even at the level of blood vessels, an hypothesis tested by Matsumoto et al. (Japan) who showed that the blackcurrant anthocyanin, delphinidin-3-glucoside, may stimulate endothelin receptors in the eye ciliary muscles. This effect could release the endothelium-dependent relaxing factor, nitric oxide, which, if proved as a mechanism, would be an exciting result certain to stimulate new research on anthocyanin binding, receptor identification for the large number of commonly consumed anthocyanims, their uptake mechanisms and organ distribution.

Processing Effects on Anthocyanins (or What Happens To Anthocyanins When Juice Is Manufactured?  Important to expanding applications for berries in the food and beverage industries,  preservation of anthocyanins was a research area summarized by L. Howard  and colleagues (University of Arkansas, USDA-ARS). Freezing of berries followed by frozen storage preserves anthocyanins most effectively, whereas major anthocyanin losses occur from heat processing needed to make juices or pasteurization of purees and canned products.
During heating, anthocyanins bind together, making polymers that actually enhance the richness of colors but lower individual anthocyanin contents, even though total antioxidant strength is maintained. Howard showed that the presscake (residual pomace after juicing), often discussed as a valuable but undeveloped biomaterial for functional foods and nutraceuticals, retained appreciable anthocyanin levels.
Cancer. In just the past two years, the pace of science showing human health benefits has accelerated in a way no more evident than the prodigious research output by the cancer research team at Ohio State University led by G.D. Stoner and L.A. Kresty.  Dietary freeze-dried black raspberries were shown to inhibit chemically induced cancer of the rat esophagus by 30-60% and of the colon by up to 80%. Effective at both the initiation and promotion/progression stages of tumor development, black raspberries are a practical research tool and a promising therapeutic source, as they contain the richest contents of anthocyanins among native North American berries (15).

Stoner's work on laboratory cancer models has shown that black raspberry anthocyanins inhibit promotion and progression of tumor cells by
1)      stalling the growth of pre-malignant cells
2)      accelerating the rate of cell turnover, called apoptosis, effectively making the cancer cells die faster
3)      reducing inflammatory mediators that may have a role in tumor onset
4)      inhibiting the growth of new blood vessels that nourish tumors, a process called angiogenesis
5)      minimizing cancer-induced DNA damage.

On a molecular level, berry anthocyanins turn off genes involved with proliferation, apoptosis, inflammation and angiogenesis. Stoner's group has taken the black raspberry to the next pivotal level of research – the human clinical trial – for which they have several approved studies underway to examine chemopreventive effects of black raspberries and cranberries on tumors in the esophagus (throat), prostate and colon (13).
Similar anti-cancer studies of anthocyanins from blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry at UCLA are under the direction of N. Seeram and D. Heber. The UCLA group has shown an enhanced, synergistic anti-cancer activity of berry anthocyanins with other berry antioxidants called proanthocyanidins and flavonols (12).

Aging and Neurological Diseases.  Following last year's publication of the Kame Project showing that regular dark fruit juice consumption could lower risk against Alzheimer's disease (1), attention toward the potential anti-aging roles of berry phenolics including anthocyanins has also increased, a message highlighted at this meeting through the decades-long efforts of J.A. Joseph and colleagues (Tufts University; USDA-ARS). Dr. Joseph presented evidence that long-term blueberry or strawberry consumption improved motor control, memory and learning of new tasks in mice and aged rats. Preliminary results indicate the beneficial effects of anthocyanins are due not only to antioxidant protection against stress, but also to neurogenesis, enhanced neuronal signaling capabilities and improved communication among neurons (5).

Inflammation.  Dr. Joseph's other studies on inflammatory mediators in glial cells of the rat brain showed that blueberry extracts could attenuate brain inflammation (6) by inhibiting production of nitric oxide as well as the cytokines, interleukin-1beta and tumor necrosis factor-alpha. Also, messenger RNA levels and activity of the inflammatory enzyme, cyclooxygenase-2 (COX-2), were reduced by blueberries.
These same mechanisms may be at work to inhibit onset of atherosclerosis which involves oxidation of LDL, as discussed by J.D. Reed (University of Wisconsin). Using Concord grapes and cranberries, Dr. Reed demonstrated that berry anthocyanins and their cousin chemicals, proanthocyanidins attenuate, 1) platelet aggregation, 2) high arterial blood pressure, 3) total serum cholesterol levels and 4) development of vascular atheroma in laboratory animals. Inhibiting COX-2 and LDL oxidation was an important mechanism for prevention of foam cells that stimulate vascular plaques to form.

Diabetes.  One of the conference's most provocative reports was by T. Tsuba (Chubu University, Japan) who showed that anthocyanins
1)      inhibit enlargement of individual fat cells called adipocytes
2)      suppress insulin resistance causing the rise in blood glucose (“hyperglycemia”) and insulin levels following a meal (curtailing appetite)
3)      stimulate expression of cytokines related to adipocytes and
4)      deter development of obesity in mice.
The effects were mediated via anthocyanin upregulation of  genes for fat metabolism (14), providing preliminary evidence that dietary anthocyanins stimulate mechanisms countering weight gain and obesity. Specifically, a dietary anthocyanin called cyanidin-3-glucoside inhibited post-meal hyperglycemia and insulin-sensitivity in diabetic mice, providing a foundation for the possible use of anthocyanin-rich foods in treating diabetes and obesity.

Infections. The clearest clinical evidence for a health benefit of berries has come from numerous previous studies showing antibacterial and anti-adhesion properties of cranberry juice (4). Work by R. Puupponen-Pimiä (Finland) showed that adherence of bacteria to epithelial surfaces (example, female urinary tract and bladder) is a prerequisite for colonization and infection by many pathogens. Berry phenolics including anthocyanins have activity against salmonella and staphylococcus, Helicobacter pylori and Bacillus cereus, Campylobacter jejuni and Candida albicans (9) which collectively are pathogens causing common female infections. Cloudberry, a nordic Rubus species, strawberry and red raspberry provided the strongest anti-bacterial effects.

Potential mechanisms for such antimicrobial effects by berry pigments include
¶ inhibition of bacterial proliferation
• destabilization (disintegration) of cytoplasmic membranes on bacterial cells
• increased permeability of the bacterial cell plasma membrane, possibly causing loss of cell volume control leading to its destruction
• inhibition of extracellular enzymes involved in promoting bacterial infections
• direct actions on microbial metabolism and deprivation of substrates required for microbial growth
• anti-adherence of bacteria to epithelial cell walls, inhibiting colonization and infection of many pathogens.

This Finnish group has initiated a human clinical trial examining the ability of berries to inhibit pathogens in patients with intestinal and urinary tract infections.

Public Advisory. The industrialized world's preference for a colorless diet of meat, potatoes and highly processed foods means that many consumers miss a variety of dietary sources that could contribute to health and fitness. "Today's dietary problems are an accident of nature," explained keynote speaker, Dr. D. Heber. "Our ancestors evolved on a diverse plant-based diet of dozens of plant food sources, but the typical American diet has changed tremendously just over the past 100 years. Plant food preferences in the United States now are limited to just a few, such as potatoes, apples and wheat. On one hand, we're eating more unhealthy foods in larger amounts just because it's the cheapest and easiest way to eat. Today, there's a much wider variety of nutrient-rich berries, fruits and vegetables available to us. When you consider the impact on lifestyle and high cost of treating illnesses that could be avoided by eating more colorful and nutritious foods, the public needs to make changes for healthier living. "

What the Public Can Do
• According to Heber, to change diets from empty off-white to well-colored, consumers can begin with some simple substitutions:
• yellow corn instead of white
• sweet potatoes (or the purple potatoes now available in some supermarkets) instead of russetts
• pink grapefruit instead of white
• romaine lettuce instead of iceberg
• cabernet wine instead of chardonnay
• Guinness instead of Bud!
• eat whole foods that have had the least amount of processing, e.g., whole grains instead of breads, cereals and snack foods made from refined white flours
• brown rice instead of white
• baked potatoes with the skin intact instead of fries
• real fruit instead of Skittles!
• in short, try to eat berries and other colorful whole foods each day!

Heber said: “It doesn't really matter if you get something from every color group each day; just eat as wide a variety of colored foods as possible and try to get the recommended 5-9 daily servings of colorful produce. Berries are an easy way of getting these pigments. Of course, the more fruit and vegetables you eat, the more of these crucial compounds like pigment anthocyanins you'll absorb.”
“While there's no way to know the phytonutrient content of a given piece of produce, choose items like berries that have the deepest color and seem both fresh and ripe (or flash-frozen, which can be equally nutritious) to assure your pigment intake.”
"If you know nothing else, you can put together a good diet with color alone," Heber said. "It isn't a magic bullet, but if you want to maximize nutrients and antioxidants in your food, this is a good way to start."

About the Author Paul M. Gross, PhD, received his doctorate in physiology from the University of Glasgow, Scotland and trained in neuroscience at the Laboratory of Cerebral Metabolism, National Institutes of Health, Bethesda, MD. A former Research Scholar for the Heart and Stroke Foundation of Ontario, he published 85 peer-reviewed journal reports and book chapters over a 25 year career in medical science, and was recipient of the Karger Memorial Award, Switzerland, for publications on brain capillaries. Dr. Gross is on the steering committee of the International Berry Health Association. He is senior author of a 2006 book on the Chinese wolfberry (goji, Booksurge Publishing, Amazon.com, http://wolfberry.org) and is publisher of The Berry Doctor's Journal, http://berrydoctor.com providing free information on berry science and nutrition.
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