WSU lab a national model

Phytochemicals … “5 A Day — The Color Way” proclaim some plastic produce bags. “Now with Lutein!” heralds a bottle of Centrum vitamins.

Since the 1920s, plants have been considered essential to human and animal health, mainly for the vitamin A provided in their richly colored betacarotene. As a young researcher in animal science, however, Boon Chew decided to challenge that thinking in 1979. His resulting 20 years of research on antioxidants, nutrition and immunology have revolutionized the pet food industry worldwide and greatly impacted human health. Chew and his team at WSU also have been recognized by sponsors — such as the Iams pet food company — as a model not only for their research techniques and findings, but also for the way they care for their animals and how they handle them when the studies are completed.

Professor Chew and assistant research professor Jean Soon Park, Department of Food Science and Human Nutrition, are internationally known for their research on carotenoids, which are naturally occurring plant pigments that create the brilliant colors seen in flowers and vegetables, as well as the pink in flamingos and the red in salmon. Carotenoids are also a group of antioxidants, which includes names increasingly familiar in the media: betacarotene, lutein, lycopene, astaxanthin and others.

Work began with bovine mastitis
Originally, Chew came to Washington State University to undertake research in the most economically devastating disease of food animals at the time — bovine mastitis. As he studied this inflammatory disease in dairy cows, Chew asked himself how he could stimulate the immune system to help prevent mastitis. Realizing that “dry” cows often got the worst cases of mastitis, he thought something might be lacking in their diet and discovered they were, indeed, fed the worst forage — i.e. newspaper, stems and straw.

In contrast, the best hay went to pregnant heifers and lactating cows.

Thinking the problem could be tied to betacarotene, Chew devised a series of experiments that led to the discovery that the nutrient does enhance the immune system and that dry cows fed betacarotene have a much lower rate of mastitis. With this model in hand, Chew launched into groundbreaking studies on nutrition, cancer and inflammatory disease.

Wondering why carotenoids were so prevalent in nature and why we eat greater quantities of them than we could ever use as vitamin A, Chew and his associates set out to see if carotenoids were not important for other functions in animal and human health.

At the time, 20 years ago, there was virtually no data available on any species about carotenoid utilization. It was important to establish a foundation of basic research data before further study could progress.

Once Chew could demonstrate that carotenoids were absorbed by the digestive system and subsequently into cells in the bloodstream, he was able to run trials to see if the compounds affected the immune system. Amazingly, he discovered carotenoids work positively with the immune system to decrease inflammation and could, therefore, lead to possible new treatments for certain diseases.

In their studies, Chew and Park focus primarily on breast (mammary) cancer and inflammatory diseases such as rheumatoid arthritis.

“Age related, chronic diseases are associated with free radical oxidative attack,” said Chew. “Every day, oxygen is utilized by our bodies to produce cellular energy, which in turn, creates free radical byproducts. As we age, the cumulative effect of a lifetime of free radical attacks leads to cellular mutations and damage which can lead to cancer, autoimmune disease and degenerative diseases.”

Some of this damage is compensated for by our own natural production of antioxidants — enzymes capable of deactivating the free radicals. But under conditions of stress, said Chew, our bodies may not be able to provide adequate protection to combat all the harmful effects. It is here that providing dietary antioxidants is useful to help prevent disease.

Lutein studies yield cancer answers
When Park came to WSU from Seoul, South Korea, in 1995, her goal was to pursue nutrition and immunology research.

She looked around for opportunities for two years before meeting Chew, who offered her a chance to work on carotenoids — specifically lutein.

“I thought he meant lutein in egg yolks, and I said that too much cholesterol was not good!” she laughed. “But he said no, lutein is also in plants, and he asked if I was willing to work on it.”

Chew showed her a picture of a marigold, the commercial source of lutein, and she then agreed to do it. The rest is history as Park developed a highly successful breast cancer model, using lutein, first in mice and then dogs.

Initially, she established an optimal dose of the carotenoid that would inhibit mammary tumor growth in mice. Then, looking at molecular mechanisms behind anticancer activity, she discovered that lutein could regulate the genes that inhibit or stimulate cancer growth. She found that lutein stimulated the inhibition side and suppressed the growth side.

Knowing that cancer begins with one cell dividing uncontrollably, Park also looked at the genes controlling apoptosis, or programmed cell death. She discovered that lutein suppressed the antiapoptotic gene that told cells not to die — allowing them to grow wildly — thereby inhibiting tumor growth.

Another mechanism promoting cancer growth is angiogenesis, or recruitment of new blood vessels to feed the tumor. Park was also able to prove that lutein helped decrease the number of new vessels.

“There are many other possible mechanisms involved here,” said Park, “and we are just looking at a few things to contribute to the total body of knowledge on the anticancer activity of carotenoids.”

Dog, cat studies revolutionary
Greatly impressed with this study, the Iams Company, along with other manufacturing and pharmaceutical companies, encouraged Park and Chew to branch out into dog and cat studies as models for human disease.

“The canine breast cancer model is the best animal model for the study of breast cancer in humans,” said Chew.

“The demographics also are similar — like humans, the average dog and cat is living longer, so we are seeing more chronic age-related diseases such as cancer, inflammatory disease, eye disease such as macular degeneration and declining cognitive brain function.”

Due to the difficulty of using live dogs for these studies, canine mammary cancer cell lines are used instead. These lines are being tested using the antioxidants lutein, betacarotene and astaxanthine. “Though there are about 700 carotenoids in nature, only about six of them are actively absorbed by people and animals,” said Chew.

The result of this collaborative effort at WSU has led to an overall change in the picture of pet nutrition. When Park and Chew published a report about five years ago showing that cats could absorb betacarotene in their intestines, they were flooded with phone calls from people across the world, including zoos in Chicago and Washington, D.C.

It had been accepted for almost a century that cats are true carnivores and only needed red meat for a healthy diet.

“But we have domesticated the animals and only feed them what we think they need,” said Chew. “In the wild, what do they eat first? Do they go for the T-bone steak? No! They eat the gut contents and internal organs.”

As the zoos began feeding their cats fresh vegetables, the results were an unequivocal increase in reproductive success, overall health and activity.Iams and other pet food companies have eagerly adopted the results of Chew and Park’s research and used them to enhance their pet food formulations. Iams also helps fund the WSU research projects as well as donating pet food for the beagle and cat colonies used in these studies.

“The role of the Iams pet food company in this research cannot be overemphasized,” said Chew. “Iams is very committed to research and development that will help improve the health and well being of cats and dogs,” he said, “and we are very fortunate to be supported in part by them.”

The ultimate antioxidant
Concerning the overall impact of his research, Chew said, “We see that humans and animals are living longer, healthier and more productive lives with improved nutrition and care. Thanks to marketing efforts, the availability of research information is changing our lifestyle and increasing our nutritional awareness.”

As the trend continues, the public may soon see marketing campaigns promoting “Astaxanthin as the Ultimate Antioxidant.” Chew recently presented the world’s first study on the effects of astaxanthin on the human immune system at the U.S. Nutra sponsored symposium in Las Vegas.

He was able to show that astaxanthin not only stimulates the immune response in people but also greatly decreases the amount of DNA damage as well.

“Our study was so well accepted — the excitement generated was incredible,” said Chew. “This compound is no magic bullet, but it’s a given that we will certainly be continuing our funded research of its human and animal applications.”

Colorful carotenoids work together
More and more studies have shown that eating a diet rich in colorful fruits and vegetables may decrease the risk of cancer and other diseases. Not only do they provide a wide range of vitamins and minerals but also a pharmacopoeia of phytochemicals, such as antioxidants.

In general, the darker colored varieties pack more punch, i.e. raisins, prunes, blueberries, blackberries, strawberries, raspberries, kale, spinach, broccoli, brussels sprouts, beets, grapes, plums, oranges, corn etc.

The carotenoid lutein, also shown to help prevent macular degeneration in eyes, is found in many green vegetables, especially spinach and kale, but also corn, eggs and fruit. Lycopene, known to fight prostate cancer, is found in tomatoes. Astaxanthin is found in salmon, trout, shrimp and lobster.

Carotenoids have been shown to work synergistically — eating several of them together will enhance their protective action more than eating one alone. So now’s the time to be creative — how does a spinach, orange and shrimp salad sound for lunch?

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