A small, pilot study in 50 people in Japan suggests that eating two and a half ounces of broccoli sprouts daily for two months may confer some protection against a rampant stomach bug that causes gastritis, ulcers and even stomach cancer.Citing their new "demonstration of principle" study, a Johns Hopkins researcher and an international team of scientists caution that eating sprouts containing sulforaphane did not cure infection by the bacterium Helicobacter pylori (H. pylori). They do not suggest that eating this or any amount of broccoli sprouts will protect anyone from stomach cancer or cure GI diseases.
However, the study does show that eating a daily dose of broccoli sprouts reduced by more than 40 percent the level of HpSA, a highly specific measure of the presence of components of H. pylori shed into the stool of infected people. There was no HpSA level change in control subjects who ate alfalfa sprouts. The HpSA levels returned to pretreatment levels eight weeks after people stopped eating the broccoli sprouts, suggesting that although they reduce H. pylori colonization, they do not eradicate it.
"The highlight of the study is that we identified a food that, if eaten regularly, might potentially have an effect on the cause of a lot of gastric problems and perhaps even ultimately help prevent stomach cancer," says Jed W. Fahey, M.S., Sc.D., an author of the paper who is a nutritional biochemist in the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at the Johns Hopkins University School of Medicine.
The discovery that sulforaphane is a potent antibiotic against H. pylori was reported in 2002 by Fahey and colleagues at Johns Hopkins. "Broccoli sprouts have a much higher concentration of sulforaphane than mature heads," Fahey explains, adding that further investigation is needed to affirm the results of this clinical trial and move the research forward. The study, published April 6 in Cancer Prevention Research, builds on earlier test-tube and mouse studies at Johns Hopkins and elsewhere about the potential value of sulforaphane, a naturally occurring biochemical found in relative abundance in fresh broccoli sprouts. Sulforaphane appears to trigger cells in the body, including in the gastrointestinal tract, to produce enzymes that protect against oxygen radicals, DNA-damaging chemicals, and inflammation.
In the new report, the team also shows that when H. pylori-infected mice sipped broccoli-sprout smoothies for eight weeks, there was up to a fourfold increase in the activity of two of these key enzymes that protect cells against oxidative damage. In addition, the number of Helicobacter bacteria in the mice's stomachs decreased by almost a hundredfold it did not change in infected control animals that drank plain water. The researchers also noted a greater than 50 percent reduction in inflammation of the primary target of this bacterium – the body of the stomach – in treated mice but not in controls.
In a related experiment, the team fed the same dose of broccoli sprouts for the same amount of time to H. pylori-infected mice that had been genetically engineered to lack the Nrf2 gene that activates protective enzymes. "These knock-out mice didn't respond," Fahey says, which confirms previous findings for a role of Nrf2 in protection against H. pylori-induced inflammation and gastritis.
Classified a carcinogen by the World Health Organization, H. pylori is a gastrointestinal tract germ that manages to thrive in the lining of the stomach despite the strength of natural acids there that rival that of car batteries. Afflicting several billion people – roughly half of the world's population – this corkscrew-shaped bacterium has long been associated with stomach ulcers, which now are frequently cured by antibiotics. Research strongly suggests that the bacteria also are linked to high rates of stomach cancer in some countries, that strains resistant to standard antibiotics are prevalent, and that multiple courses of standard antibiotics do not always eliminate the infection.
Working in Japan where there is high incidence of chronic H. pylori-infection, the research team gave 25 H. pylori-infected subjects two and a half ounces (70 grams) per day of broccoli sprouts for two months. Another 25 infected people consumed an equivalent amount of alfalfa sprouts which, although rich in phytochemicals, don't contain sulforaphane.
The researchers assessed the severity of Helicobacter infection at the start of the study, after four and eight weeks of treatment, and again eight weeks after intervention was stopped. They used breath tests to assess colonization by H. pylori bacteria and blood tests to judge the severity of inflammation in the stomach lining; in addition, they looked for antigens in stool samples to help determine the extent of the infections.
"We know that a dose of a couple ounces a day of broccoli sprouts is enough to elevate the body's protective enzymes," Fahey says. "That is the mechanism by which we think a lot of the chemoprotective effects are occurring.
"What we don't know is whether it's going to prevent people from getting stomach cancer. But the fact that the levels of infection and inflammation were reduced suggests the likelihood of getting gastritis and ulcers and cancer is probably reduced."
In disclosure of a potential conflict of interest, Fahey is a cofounder of, but holds no equity in, a company that is licensed by The Johns Hopkins University to produce broccoli sprouts. A portion of the proceeds is used to help support cancer research, but no such funds were provided to support this study.
"It's exciting that a chronic bacterial infection that poses great hazards to hundreds of millions of people globally can be ameliorated by a specific dietary strategy," says Paul Talalay, M.D., John Jacob Abel Distinguished Service Professor of Pharmacology and Experimental Therapeutics and director of the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at Johns Hopkins' Institute for Basic Biomedical Sciences.
Talalay directs the lab where, in 1992, his team discovered the health-promoting properties of sulforaphane. A longtime proponent of cancer prevention and chemoprotection, Talalay eats fresh broccoli sprouts regularly, as does Fahey.
"I like them," Fahey says. "I eat them all the time, but not every day. Variety is the spice of life: I eat blueberries on the other days."
In addition to Fahey, the authors of the paper are Akinori Yanaka, Atsushi Fukumoto, Mari Nakayama and Souta Inoue, Tokyo University of Science, Japan; Masayuki Yamamoto, Songhua Zhang, Masafumi Tauchi, Hideo Suzuki and Ichinosuke Hyodo, University of Tsukuba, Japan.
Broccoli Sprouts May Prevent Stomach Cancer By Defeating Helicobacter Pylori
New Link In Liver Cancer
Liver damage can be triggered by various insults, including hepatitis infection or alcohol-induced cirrhosis. In severe cases, this damage can lead to cancer. A new study by researchers at the National Institutes of Health and Osaka University reveals how one protein helps decide the fate of damaged livers in mice.Liver cells rely on signals triggered by growth hormone to survive and multiply—functions that go haywire in cancer. Normally, growth hormone works by activating a signaling network inside liver cells that includes a protein called STAT5. When the researchers removed STAT5 from liver cells, cancer ensued.
The normally protective effect of STAT5 was traced to its ability to hitch itself to a damage-inducing protein called TGFbeta and trigger its destruction. Without STAT5, TGFbeta levels soared, and growth hormone activated a related protein, STAT3, which is known to promote tumor growth.
TGFbeta and STAT5 appear to be adversaries in the liver, according to the study. STAT5 protects the liver by breaking down TGFbeta. But when TGFbeta is abundant—as occurs in people with chronic liver damage—growth hormone activates the cancer-promoting STAT3 instead of the protective STAT5. These results might help explain how chronic liver damage can eventually lead to cancer.
The study will be published online on March 30th in the Journal of Experimental Medicine.
Sleep May Help Clear Brain For New Learning
A new theory about sleep's benefits for the brain gets a boost from fruit flies in the journal Science. Researchers at Washington University School of Medicine in St. Louis found evidence that sleep, already recognized as a promoter of long-term memories, also helps clear room in the brain for new learning.The critical question: How many synapses, or junctures where nerve cells communicate with each other, are modified by sleep? Neurologists believe creation of new synapses is one key way the brain encodes memories and learning, but this cannot continue unabated and may be where sleep comes in.
"There are a number of reasons why the brain can't indefinitely add synapses, including the finite spatial constraints of the skull," says senior author Paul Shaw, Ph.D., assistant professor of neurobiology at Washington University School of Medicine in St. Louis. "We were able to track the creation of new synapses in fruit flies during learning experiences, and to show that sleep pushed that number back down."
Scientists don't yet know how the synapses are eliminated. According to theory, only the less important connections are trimmed back, while connections encoding important memories are maintained.
Many aspects of fly sleep are similar to human sleep; for example, flies and humans deprived of sleep one day will try to make up for the loss by sleeping more the next day. Because the human brain is much more complex, Shaw uses the flies as models for answering questions about sleep and memory.
Sleep is a recognized promoter of learning, but three years ago Shaw turned that association around and revealed that learning increases the need for sleep in the fruit fly. In a 2006 paper in Science, he and his colleagues found that two separate scenarios, each of which gave the fruit fly's brain a workout, increased the need for sleep.
The first scenario was inspired by human research linking an enriched environment to improved memory and other brain functions. Scientists found that flies raised in an enhanced social environment—a test tube full of other flies—slept approximately 2-3 hours longer than flies raised in isolation.
Researchers also gave male fruit flies their first exposure to female fruit flies, but with a catch—the females were either already mated or were actually male flies altered to emit female pheromones. Either fly rebuffed the test fly's attempts to mate. The test flies were then kept in isolation for two days and exposed to receptive female flies. Test flies that remembered their prior failures didn't try to mate again; they also slept more. Researchers concluded that these flies had encoded memories of their prior experience, more directly proving the connection between sleep and new memories.
Scientists repeated these tests for the new study, but this time they used flies genetically altered to make it possible to track the development of new synapses, the junctures at which brain cells communicate.
"The biggest surprise was that out of 200,000 fly brain cells, only 16 were required for the formation of new memories, " says first author Jeffrey Donlea, a graduate student. "These sixteen are lateral ventral neurons, which are part of the circadian circuitry that let the fly brain perform certain behaviors at particular times of day."
When flies slept, the number of new synapses formed during social enrichment decreased. When researchers deprived them of their sleep, the decline did not occur.
Donlea identified three genes essential to the links between learning and increased need for sleep: rutabaga, period and blistered. Flies lacking any of those genes did not have increased need for sleep after social enrichment or the mating test.
Blistered is the fruit fly equivalent to a human gene known as serum response factor (SRF). Scientists have previously linked SRF to plasticity, a term for brain change that includes both learning and memory and the general ability of the brain to rewire itself to adapt to injury or changing needs.
The new study shows that SRF could offer an important advantage for scientists hoping to study plasticity: unlike other genes connected to plasticity, it's not also associated with cell survival.
"That's going to be very helpful to our efforts to study plasticity, because it removes a large confounding factor," says co-author Naren Ramanan, Ph.D., assistant professor of neurobiology. "We can alter SRF activity and not have to worry about whether the resulting changes in brain function come from changes in plasticity or from dying cells."
Shaw plans further investigations of the connections between memory and sleep, including the question of how increased synapses induce the need for sleep.
"Right now a lot of people are worried about their jobs and the economy, and some are no doubt losing sleep over these concerns," Shaw says. "But these data suggest the best thing you can do to make sure you stay sharp and increase your chances of keeping your job is to make getting enough sleep a top priority."
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