The Zinc Link

By Lee Anna Sherman

When you eat a steaming bowl of tofu and bok choy while sipping a cup of rain-flower tea, you may be doing more than just having dinner. You may also be fighting cancer.

Together, the ingredients of a traditional Asian diet — soy, green tea and vegetables in the cabbage family — may create a potent anti-cancer force in the human body, says OSU nutrition scientist Emily Ho. Sorting out the biological and chemical mechanisms that explain the apparent protective power of these and other nutrients — particularly zinc — is the focus of Ho’s research.

“In the development of cancer, there’s not just one thing going wrong at the cellular level — there are a lot of different things going wrong,” says Ho, an assistant professor in the College of Health and Human Sciences and the Linus Pauling Institute. “Like a lot of chronic diseases, cancer has a complex etiology. So instead of looking for one magic bullet for cancer prevention, it makes more sense to look at a combination of nutrients.”

The Asian diet may contain the secret to preventing the most prevalent cancer among American men: prostate cancer. Ho, whose parents are Chinese-Canadian immigrants, points to the stunning gap between U.S. and Chinese rates: fewer than two cases per 100,000 Shanghai-born Chinese versus 58 cases among U.S.-born Caucasians. But even more revealing is how that gap narrows dramatically when Chinese men live in the U.S. for five years or more — catapulting to 23 cases, according to recent data published in the International Journal of Cancer Research. And even though U.S.-born Chinese have lower rates of prostate cancer than U.S.-born Caucasians (37 cases versus 58), their incidence remains staggeringly high when compared to their Chinese-born peers.

Clearly, life in America puts men at greater risk for prostate cancer. Diet is the most likely culprit, according to Ho. Along with several of her LPI colleagues, Ho is looking hard at the soy-tea-veggie synergy — and the West-East dietary gap. Americans eat just 1 to 3 milligrams of soy each day, compared to the Japanese intake of 10 to 50 milligrams. Fewer than 10 percent of Americans drink even one cup of green tea a day, while the Asian diet typically includes three or four cups. And those critical cruciferous vegetables? Only 12 grams a day in the U.S., versus 55 grams in Japan.

“In the U.S., most of the cruciferous vegetables are either cabbage or broccoli,” notes Ho. “In Asia, we eat a whole gamut of cruciferous vegetables, things like bok choy and other traditional Asian greens that are not widely consumed by the typical American family.”

In addition, she has zeroed in on a single nutrient with a unique link to the prostate: zinc. Ubiquitous in the body — found in muscles, bones, organs, cells and fluids — this trace element is most concentrated in the male reproductive system. Semen’s zinc level is 100 times higher than blood’s. And the prostate gland, which produces seminal fluid, contains the highest zinc concentration of all soft tissues.

To Ho, zinc deficiency is a likely smoking gun in the prostate cancer mystery.

“We know that as prostate cancer develops, zinc levels decrease in the epithelial cells — the cells that line the prostate gland,” she says. “But we don’t know why. It intrigues me. I want to try to figure it out.”

Ho’s fascination with the complexities and conundrums of science began when she was growing up near Toronto, the daughter of an engineer and a nurse. While other students were slogging through biology and math because they had to, she was riveted to cell diagrams and algebraic equations. It was at the University of Guelph where she found her field — along with a mentor to guide her way. A summer research internship with a biologist studying genetic mutations and antioxidants in fruit flies awakened Ho’s interest in DNA and antioxidant nutrients. That in turn led her to the nutrition department, where a professor named Tammy Bray was also doing antioxidant research. Bray’s work seemed less theoretical than the fruit fly studies, more immediately applicable, more directly linked to pressing problems. Nutrition science appealed to Ho’s pragmatic and altruistic streaks. Inspired, too, by Bray’s deep reserves of drive and dedication, she became Bray’s protege.

“Tammy definitely has one of those infectious, enthusiastic personalities,” says Ho. “She’s a tough lady to keep up with, so everyone in her lab has a really strong work ethic and a lot of passion about what they do.”

Ho followed her mentor to Ohio State University to get her Ph.D., and then went to UC Berkeley for postdoctoral work. After Bray became dean of the OSU College of Health and Human Sciences, Ho applied for a position in the Nutrition and Exercise Sciences department. “I’m very happy to have Tammy as my boss again,” says Ho, whose husband, Malcolm Lowry, is also at OSU, doing immunology research in the Microbiology Department.

Ho is attacking the prostate-cancer riddle on a number of fronts — both in the lab and in the field. Just understanding the biochemistry of zinc presents a tangle of challenges. As a component in more than 300 proteins, such as p53 — a DNA-repair protein that becomes mutated in more than half of human tumors — it clearly plays a role in fending off rogue cell growth. “We know that zinc combats oxidative damage from free radicals,” Ho says. “We know that it plays a role in DNA repair, and that it has important anti-inflammatory properties. We know that it helps shut off proliferation of mutant cells. But the mechanism for these processes is still unknown.”

The world’s best food source for zinc is the oyster. Half a dozen fried oysters will give you 100 percent of your daily requirement. Coming in second is beef, although three ounces of pot roast provide only half the zinc in six of the slippery shellfish. But as Ho cautions, loading up on any one nutrient — particularly in synthetic form as a tablet or capsule — may not be effective in promoting health and preventing disease. Her research, and that of her fellow LPI scientists, suggests that whole foods and natural, full-spectrum supplements contain not just essential nutrients, but essential combinations of nutrients. In rat studies, for instance, she and her colleagues have found soy and tea together have a much stronger anti-tumor effect than either food alone. The same two foods also combine to significantly reduce hyperplasia (rapid, abnormal enlargement) in rat prostates. “Soy and tea,” Ho says, “may inhibit signals in proteins that ultimately contribute to cancer.”

She’s looking, too, at the other key ingredient of the Asian diet — cabbage-type vegetables — in prostate-cancer risk. Collaborating with Oregon Health & Science University, she is conducting a “retrospective” study, looking back at the dietary histories of 400 to 500 older men. Of particular interest is how much broccoli, cauliflower, Brussels sprouts and other cruciferous veggies they’ve eaten. Blood will be examined, too, for tell-tale DNA changes called “epigenetic alterations,” which scientists now know can lead to abnormalities that in turn lead to cancer.

“What we’re finding,” says Ho, “is that sulforaphane, a compound that’s found in cruciferous vegetables, can help reverse some of these epigenetic alterations.”

That certain elements, minerals, vitamins and compounds occur side-by-side in nature is, Ho says, “no accident.” Teasing out the mechanisms of one microscopic substance — zinc, for instance — is daunting enough. Figuring out the interactive roles of an entire complex of substances is the holy grail of the nutrition sciences.

For Ho, that quest comes down to something very personal, something very human. “I feel like the research we do — even though it’s mostly basic science, with my students working at a lab bench with a pipette — ultimately could have a big impact on my own family and yours,” she says. “That’s what’s exciting for me.”