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Hopkins scientists expand their 20-year mission to understand the disease-deterring benefits of a potent plant compound found in broccoli.
It began as a shopping trip.
One evening two decades ago, Paul Talalay handed a twenty-dollar bill to Hans Prochaska, an M.D./Ph.D. student in his molecular pharmacology lab, and sent him to nearby Northeast Market to buy a variety of fruits and vegetables.
In the pale green solutions extracted from those vegetables, Talalay discovered a compound that demonstrated a powerful ability to protect cells from the sort of damage that can instigate cancer. The compound, sulforaphane, was particularly abundant in broccoli and other cruciferous vegetables, such as cabbage, kale and Brussels sprouts. Sulforaphane was subsequently shown to be especially abundant in sprouted broccoli seeds.
Since then, dozens of journal articles have flowed from the discovery, and sulforaphane is now the subject of weekly journal articles. “I could not have predicted it would have had such a profound scientific influence,” says Talalay.
At the same time, backed by evidence from his lab and others, Talalay has broadened the scope of his vision. It’s not only cancer that sulforaphane might guard against; it’s the broad array of chronic diseases—a concept he calls “chemoprotection.”
To develop this concept, Talalay is now expanding the Center for Chemoprotection, which is based within the Institute for Basic Biomedical Sciences (IBBS). Supported by a recent influx of funds from philanthropic sources, as well as the IBBS and school of medicine, the Center will quadruple its lab and office space and hire several new faculty members. “ The university needs an interdisciplinary program that transcends disease categories and has as its main focus the prevention, delay of onset, or slowing of the progression of chronic disease associated with aging,” says Talalay.
The shopping expedition undertaken by Prochaska that launched all of this began as a scientific conjecture. Epidemiological studies had shown, says Talalay, that people who eat a lot of fruits and vegetables have lower rates of cancer. At the same time, Talalay had conducted studies that showed cells themselves possess a network of enzymes that can act as endogenous defenses against the everyday ravages that can assault a cell: oxidative stress, toxic DNA-damaging chemicals, inflammation, and solar radiation.
Putting those two facts together, Talalay hypothesized that certain chemicals in fruits and vegetables activate these enzymes or their genes, inducing them to ramp up activity that normally functions at less-than-maximum capacity. Sulforaphane turned out to be a potent inducer of these protective enzymes.
Talalay then persuaded Jed Fahey, a plant physiologist who later earned his doctorate in human nutrition, to help develop the principle of exploiting cruciferous vegetables for chemoprotection. Fahey set up a greenhouse for growing the plants they’d need on the top floor of The Johns Hopkins Hospital.
“The idea was not embraced by the mainstream,” says Fahey, a research associate in Pharmacology who holds a joint appointment at the School of Public Health. Indeed, says Talalay, colleagues took him aside and said that he was jeopardizing his reputation by focusing on cancer prevention rather than treatment.
However, subsequent research has, in a sense, vindicated Talalay’s views. There is growing recognition that prevention of cancer and other chronic diseases must become a central strategy in health management, he says.
Over the years, studies have accumulated in support of Talalay’s hypothesis. One set of research focused on Helicobacter pylori, a bacterium that is strongly associated with inflammation of the stomach lining, ulcers and stomach cancer. In animal studies, says Fahey, they’ve found that broccoli sprout extract confers “dramatic protection” against H. pylori infection and associated gastritis and inflammation.
They also conducted a study involving 48 patients with H. pylori infections, in which half the volunteers ate 2.5 ounces of broccoli sprouts per day for two months and half ate the equivalent amount of alfalfa sprouts (which do not contain sulforaphane). During the experiment, biomarkers of infection dropped significantly in the volunteers eating the broccoli sprouts but not in those receiving alfalfa sprouts—indirect evidence of reduced infection and inflammation.
Other studies have provided hints that sulforaphane might also thwart a variety of other cancers, including cancer of the liver, bladder, breast and prostate.
But now, says Talalay, limiting the principle of chemoprotection to cancer was a mistake. The factors that assault cells—oxidation, DNA-damaging chemicals, radiation and inflammation—are fundamental to all chronic diseases. So sulforaphane or compounds like it could protect cells and tissues against the host of diseases associated with those ravages.
Mounting evidence supports that notion, says Talalay.
In one study, scientists in the United Kingdom examined whether sulforaphane might protect blood vessel cells from the vascular damage that can occur in diabetes as glucose levels surge. The researchers bathed blood vessel cells in a high-sugar solution. They then added sulforaphane and found that the compound dramatically decreased the level of oxygen free radicals, reactive species that can damage cells, and boosted levels of protective enzymes.
Others studies provide evidence that sulforaphane-containing broccoli sprouts might also confer protection against asthma, chronic obstructive pulmonary disease or other respiratory illnesses. In another clinical study that is now under way, Talalay and Fahey are investigating whether a broccoli sprout extract can prevent radiation dermatitis in breast cancer patients undergoing radiation treatment. Overall, more than a dozen clinical trials at various institutions are examining the health protective benefits of broccoli sprouts.
Fahey and Talalay emphasize, however, that there are limitations to the implications of these findings. Much of the evidence in favor of sulforaphane comes from indirect evidence—biomarkers that correspond with reduced disease risk, for instance—not the same as showing that people who eat broccoli sprouts have lower rates of particular diseases. Still, everywhere they’ve looked, they’ve found that sulforaphane enhances the cell’s ability to protect itself against disease.
For now, says Talalay, “the imagination of how these chemicals might be applied appears to have no limits.”
Under a licensing agreement between Brassica Protection Products and the Johns Hopkins University, Paul Talalay and Jed Fahey are entitled to shares of royalty received by the university on sales of Brassica’s broccoli sprouts and other products. They are founders of, and advisors to, Brassica, and Talalay’s son is the company’s chief executive officer. The terms of these arrangements are being managed by the university in accordance with its conflict of interest policies.
Paul Talalay and Jed Fahey of Pharmacology and Molecular Sciences on the virtues of eating more vegetables
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