More reasons to eat your broccoli
Love it or hate it, broccoli is touted as a superfood, offering an array of health benefits. And it's about to get even more super.
University of Illinois researchers have identified candidate genes controlling the accumulation of phenolic compounds in broccoli. Consumption of phenolic compounds, including certain flavonoids, is associated with a lower risk of coronary heart disease, type II diabetes, asthma, and several types of cancer.
"Phenolic compounds have good antioxidant activity, and there is increasing evidence that this antioxidant activity affects biochemical pathways affiliated with inflammation in mammals. We need inflammation because it's a response to disease or damage, but it's also associated with initiation of a number of degenerative diseases. People whose diets consist of a certain level of these compounds will have a lesser risk of contracting these diseases," explains U of I geneticist Jack Juvik.
The researchers crossed two broccoli lines and tested their progeny in terms of total phenolic content and their ability to neutralize oxygen radicals in cellular assays. They then used a genetic technique called quantitative trait locus analysis to search for the genes involved in generating phenolics in the most promising progeny.
By identifying the genes involved in accumulating these compounds, the researchers are one step closer to breeding broccoli and related Brassica vegetables like kale and cabbage with mega-doses of phenolic compounds.
"It's going to take awhile," Juvik notes. "This work is a step in that direction, but is not the final answer. We plan to take the candidate genes we identified here and use them in a breeding program to improve the health benefits of these vegetables. Meanwhile, we'll have to make sure yield, appearance, and taste are maintained as well."
The good news is that phenolic compounds are flavorless and stable, meaning the vegetables can be cooked without losing health-promoting qualities.
Once these vegetables are consumed, the phenolic compounds are absorbed and targeted to certain areas of the body or concentrated in the liver. Flavonoids spread through the bloodstream, reducing inflammation through their antioxidant activity.
"These are things we can't make ourselves, so we have to get them from our diets," Juvik says. "The compounds don't stick around forever, so we need to eat broccoli or some other Brassica vegetable every three or four days to lower the risk of cancers and other degenerative diseases."
Broccoli and garlic fight melanoma, prostate cancer and leukemia
Cancer types such as melanoma, prostate cancer and certain types of leukaemia weaken the body by over-activating the natural immune system. Researchers from the University of Copenhagen have now demonstrated that selenium – naturally found in, e.g., garlic and broccoli – slows down the immune over-response. In the long term, this may improve cancer treatment. The findings have been published in the Journal of Biological Chemistry.
The immune system is designed to remove things not normally found in the body. Cells undergoing change, e.g. precursors of cancer cells, are therefore normally recognised and removed by the immune system. Unfortunately, the different cancer cells contain mechanisms that block the immune system's ability to recognise them, allowing them to freely continue cance.
Certain cancer cells overexpress immunostimulatory molecules in liquid form. Such over-stimulation has a negative impact on the immune system:
You can say that the stimulating molecules over-activate the immune system and cause it to collapse, and we are, of course, interested in blocking this mechanism. We have now shown that certain selenium compounds, which are naturally found in, e.g., garlic and broccoli, effectively block the special immunostimulatory molecule that plays a serious role for aggressive cancers such as melanoma, prostate cancer and certain types of leukaemia.
Broccoli Sprout Beverage Enhances Detoxification of Air Pollutants
A clinical trial involving nearly 300 Chinese men and women residing in one of China’s most polluted regions found that daily consumption of a half cup of broccoli sprout beverage produced rapid, significant and sustained higher levels of excretion of benzene, a known human carcinogen, and acrolein, a lung irritant. Researchers from the Johns Hopkins Bloomberg School of Public Health, working with colleagues at several U.S. and Chinese institutions, used the broccoli sprout beverage to provide sulforaphane, a plant compound already demonstrated to have cancer preventive properties in animal studies. The study was published in the June 9, 2014 online edition of the journal Cancer Prevention Research.
“Air pollution is a complex and pervasive public health problem,” notes John Groopman, PhD, Anna M. Baetjer Professor of Environmental Health at the Johns Hopkins Bloomberg School of Public Health and one of the study’s co-authors. “To address this problem comprehensively, in addition to the engineering solutions to reduce regional pollution emissions, we need to translate our basic science into strategies to protect individuals from these exposures. This study supports the development of food-based strategies as part of this overall prevention effort.”
Air pollution, an increasing global problem, causes as many as seven million deaths a year worldwide, according to the World Health Organization, and has in recent years reached perilous levels in many parts of China. Last year, the International Agency for Research on Cancer classified air pollution and particulate matter (PM) from air pollution as carcinogenic to humans. Diets rich in cruciferous vegetables, of which broccoli is one, have been found to reduce risk of chronic degenerative diseases, including cancer. Broccoli sprouts are a source of glucoraphanin, a compound that generates sulforaphane when the plant is chewed or the beverage swallowed. It acts to increase enzymes that enhance the body’s capacity to expunge these types of the pollutants.
The 12-week trial included 291 participants who live in a rural farming community in Jiangsu Province, China, approximately 50 miles north of Shanghai, one of China’s more heavily industrialized regions. Participants in the control group drank a beverage made of sterilized water, pineapple and lime juice while the beverage for the treatment group additionally contained a dissolved freeze-dried powder made from broccoli sprouts that contained glucoraphanin and sulforaphane. Sixty-two men (21%) and 229 women (79%) with a median age of 53 (ranging from 21 to 65) years were enrolled in the study. Urine and blood samples were taken over the course of the trial to measure the fate of the inhaled air pollutants.
The research team found that among participants receiving the broccoli sprout beverage, the rate of excretion of the carcinogen benzene increased 61% beginning the first day and continuing throughout the 12-week period. In addition, the rate of excretion of the irritant acrolein, rapidly and durably increased 23% during the 12-week trial. Secondary analyses by the investigators indicated that the sulforaphane may be exerting its protective actions by activating a signaling molecule, NRF2, that elevates the capacity of cells to adapt to and survive a broad range of environmental toxins. This strategy may also be effective for some contaminants in water and food.
“This study points to a frugal, simple and safe means that can be taken by individuals to possibly reduce some of the long-term health risks associated with air pollution,” notes Thomas Kensler, PhD, professor at the Johns Hopkins Bloomberg School and one of the study’s co-authors. “This while government leaders and policy makers define and implement more effective regulatory policies to improve air quality.”
The clinical trial targeting prevention is notable in that it evaluated a possible means to reduce the body burden of toxins following unavoidable exposures to pollutants. The majority of clinical trials involve treatments of diseases that have already presented or advanced into later stages. Further clinical trials, to evaluate optimal dosage and frequency of the broccoli sprout beverage, are planned in the same general region of China.
Broccoli Fights Osteoarthritis
A compound found in broccoli could be key to preventing or slowing the progress of the most common form of arthritis, according to new research led by the University of East Anglia (UEA).
Results from the laboratory study show that sulforaphane slows down the destruction of cartilage in joints associated with painful and often debilitating osteoarthritis. The researchers found that mice fed a diet rich in the compound had significantly less cartilage damage and osteoarthritis than those that were not.
The study, which also examined human cartilage cells and cow cartilage tissue, was funded by medical research charity Arthritis Research UK, the Biotechnology and Biological Sciences Research Council's (BBSRC) Diet and Health Research Industry Club (DRINC) and The Dunhill Medical Trust.
Sulforaphane is released when eating cruciferous vegetables such as Brussels sprouts and cabbage, but particularly broccoli. Previous research has suggested that sulforaphane has anti-cancer and anti-inflammatory properties, but this is the first major study into its effects on joint health.
The researchers discovered that sulforaphane blocks the enzymes that cause joint destruction by stopping a key molecule known to cause inflammation. They wanted to find out if the compound got into joints in sufficient amounts to be effective and their findings are published today in the journal Arthritis & Rheumatism.
More than 8.5 million people in the UK have osteoarthritis, a degenerative disease affecting the hands, feet, spine, hips and knees in particular. According to Arthritis Research UK, the annual cost of the condition to the NHS is £5.2 billion. In 2011, more than 77,000 knee and 66,000 hip replacements were carried out due to osteoarthritis -- approximately one every four minutes.
Aging and obesity are the most common contributors to the condition and due to their effects, the number of people in the UK consulting a GP about knee osteoarthritis alone could rise from 4.7 million in 2010 to 8.3 million by 2035. Currently one in five people over the age of 45 has osteoarthritis in their knee. There is no cure or effective treatment for the disease other than pain relief, which is often inadequate, or joint replacement.
The study involved researchers from UEA's schools of Biological Sciences, Pharmacy and Norwich Medical School, along with the University of Oxford and Norfolk and Norwich University Hospital.
Researchers from the School of Biological Sciences and Norwich Medical School are now embarking on a small scale trial in osteoarthritis patients due to have knee replacement surgery, to see if eating broccoli has similar effects on the human joint. If successful, they hope it will lead to funding for a large scale clinical trial to show the effect of broccoli on osteoarthritis, joint function and pain itself.
Ian Clark, professor of musculoskeletal biology at UEA and the lead researcher, said: "The results from this study are very promising. We have shown that this works in the three laboratory models we have tried, in cartilage cells, tissue and mice. We now want to show this works in humans. It would be very powerful if we could.
"As well as treating those who already have the condition, you need to be able to tell healthy people how to protect their joints into the future. There is currently no way in to the disease pharmaceutically and you cannot give healthy people drugs unnecessarily, so this is where diet could be a safe alternative.
"Although surgery is very successful, it is not really an answer. Once you have osteoarthritis, being able to slow its progress and the progression to surgery is really important. Prevention would be preferable and changes to lifestyle, like diet, may be the only way to do that."
Prof Clark added: "Osteoarthritis is a major cause of disability. It is a huge health burden but a huge financial burden too, which will get worse in an increasingly aging and obese population such as ours.
"This study is important because it is about how diet might work in osteoarthritis. Once you know that you can look at other dietary compounds which could protect the joint and ultimately you can advise people what they should be eating for joint health. Developing new strategies for combating age-related diseases such as osteoarthritis is vital, both to improve the quality of life for sufferers and to reduce the economic burden on society."
Arthritis Research UK's medical director Prof Alan Silman said: "This is an interesting study with promising results as it suggests that a common vegetable, broccoli, might have health benefits for people with osteoarthritis and even possibly protect people from developing the disease in the first place.
"Until now research has failed to show that food or diet can play any part in reducing the progression of osteoarthritis, so if these findings can be replicated in humans, it would be quite a breakthrough. We know that exercise and keeping to a healthy weight can improve people's symptoms and reduce the chances of the disease progressing, but this adds another layer in our understanding of how diet could play its part."
Steaming Broccoli Preserves Potential Power to Fight Cancer
The way you prepare broccoli and related vegetables can alter their potentially cancer-fighting powers, new research shows.
Broccoli and other cruciferous vegetables are a good source of sulforaphane, a phytochemical (naturally occurring plant compound) that has shown strong anti-cancer properties in lab studies.
However, the enzyme myrosinase in broccoli is needed for sulforaphane to form. If the myrosinase is destroyed, sulforaphane cannot form.
Researchers compared boiled, microwaved and steamed broccoli, and found that steaming broccoli for up to five minutes was the best way to retain its myrosinase. Boiling and microwaving broccoli for one minute or less destroyed the majority of the enzyme, according to Elizabeth Jeffery, a researcher at University of Illinois at Urbana-Champaign.
Jeffery also found that if you do eat well-cooked broccoli, you can still get sulforaphane to form by adding raw foods containing myrosinase to your meal. Study participants ate a broccoli supplement with no active myrosinase. When some of them ate a second food with myrosinase, their blood and urine levels of sulforaphane were significantly higher than those who did not eat the second food with myrosinase.
The findings were presented at the November, 2013 annual meeting of the American Institute for Cancer Research in Bethesda, Md. Findings presented at medical meetings should be viewed as preliminary until published in a peer-reviewed journal.
"Mustard, radish, arugula, wasabi and other uncooked cruciferous vegetables such as coleslaw all contain myrosinase, and we've seen this can restore the formation of sulforaphane," Jeffery said in an institute news release.
Previous research has found that:
* Crushing or chopping garlic, and then waiting 10 to 15 minutes before exposing it to heat allows its inactive compounds to convert into the active, protective phytochemical known as allicin.
* Cooking tomatoes and other foods that contain lycopene allows our body to more easily absorb the beneficial phytochemical.
* Boiling vegetables for a long time means you lose water-soluble vitamins, such as vitamin C, folate and niacin that leach into the water.
"As we're learning, food processing isn't just what happens to food before it reaches the grocery shelves," AICR associate director of nutrition programs Alice Bender said in the news release. "This research highlights that what you do in your kitchen can make those fruits and vegetables on your plate even more cancer-protective."
Cruciferous vegetables give cancer-fighting help
Chemicals in cruciferous vegetables, such as broccoli, watercress, cabbage and cauliflower, appear to not only stop human prostate cancer cells from growing in mice but also may cut off the formation of blood vessels that "feed" tumors, says a University of Pittsburgh Cancer Institute study.
"The contribution of diet and nutrition to cancer risk, prevention and treatment has been a major focus of research in recent years because certain nutrients in vegetables and dietary agents appear to protect the body against diseases such as cancer," said Shivendra Singh, Ph.D., lead investigator and professor of pharmacology and urology at the University of Pittsburgh School of Medicine. "From epidemiologic data, we know that increased consumption of vegetables reduces the risk for certain types of cancer, but now we are beginning to understand the mechanisms by which certain vegetables like broccoli may help our bodies fight cancer and other diseases."
Dr. Singh’s study is based on phytochemicals, called isothiocyanates (ITCs), found in several cruciferous vegetables and generated when vegetables are either cut or chewed. His laboratory has found that phenethyl-ITC, or PEITC, is highly effective in suppressing the growth of human prostate cancer cells at concentrations achievable through dietary intake.
The current study follows previous research in which Dr. Singh’s laboratory found that mice grafted with human prostate tumors that received a small amount of PEITC daily for 31 days had significantly reduced tumor size when compared to a control group of mice. Now the researchers have shown that treating cells in culture with PEITC inhibits angiogenesis, a process that plays an important role in the growth and spread of cancer by forming new blood vessels that pass oxygen and nutrients to tumor cells.
"Angiogenesis is a major issue in cancer metastases," said Dr. Singh. "Our results provide promising preliminary evidence that constituents of many edible cruciferous vegetables may slow down, or even halt, this process."
Broccoli, Cauliflower, and Cabbage Combat Breast Cancer
Women should go for the broccoli when the relish tray comes around during holiday celebrations this season.
While it has been known for some time that eating cruciferous vegetables, such as broccoli, cauliflower, and cabbage, can help prevent breast cancer, the mechanism by which the active substances in these vegetables inhibit cell proliferation was unknown - until now.
Scientists in the UC Santa Barbara laboratories of Leslie Wilson, professor of biochemistry and pharmacology, and Mary Ann Jordan, adjunct professor in the Department of Molecular, Cellular, and Developmental Biology, have shown how the healing power of these vegetables works at the cellular level. Their research is published in the journal Carcinogenesis (December, 2008).
"Breast cancer, the second leading cause of cancer deaths in women, can be protected against by eating cruciferous vegetables such as cabbage and near relatives of cabbage such as broccoli and cauliflower," said first author Olga Azarenko, who is a graduate student at UCSB. "These vegetables contain compounds called isothiocyanates which we believe to be responsible for the cancer-preventive and anti-carcinogenic activities in these vegetables. Broccoli and broccoli sprouts have the highest amount of the isothiocyanates.
"Our paper focuses on the anti-cancer activity of one of these compounds, called sulforaphane, or SFN," Azarenko added. "It has already been shown to reduce the incidence and rate of chemically induced mammary tumors in animals. It inhibits the growth of cultured human breast cancer cells, leading to cell death."
Azarenko made the surprising discovery that SFN inhibits the proliferation of human tumor cells by a mechanism similar to the way that the anticancer drugs taxol and vincristine inhibit cell division during mitosis. Mitosis is the process in which the duplicated DNA in the form of chromosomes is accurately distributed to the two daughter cells when a cell divides.
Hundreds of tiny tube-like structures, called microtubules, make up the machinery that cells use to separate the chromosomes. SFN, like the more powerful anticancer agents, interferes with microtubule functioning during mitosis in a similar manner to the more powerful anticancer drugs. However SFN is much weaker than these other plant-based drugs, and thus much less toxic.
"SFN may be an effective cancer preventive agent because it inhibits the proliferation and kills precancerous cells," said Wilson. It is also possible that it could be used as an addition to taxol and other similar drugs to increase effective killing of tumor cells without increased toxicity.
Eating Cruciferous Vegetables May Improve Breast Cancer Survival
A study by Vanderbilt-Ingram Cancer Center and Shanghai Center for Disease Control and Prevention investigators reveals that breast cancer survivors who eat more cruciferous vegetables may have improved survival. The study of women in China was presented by postdoctoral fellow Sarah J. Nechuta, Ph.D., M.P.H., at the American Association for Cancer Research Annual Meeting in Chicago, Ill. (April, 2012)
"Breast cancer survivors can follow the general nutritional guidelines of eating vegetables daily and may consider increasing intake of cruciferous vegetables, such as greens, cabbage, cauliflower and broccoli, as part of a healthy diet," said Nechuta.
Nechuta, Xiao Ou Shu, M.D., Ph.D., and colleagues investigated the role of cruciferous vegetables in breast cancer survival among women in the Shanghai Breast Cancer Survival Study, a prospective study of 4,886 Chinese breast cancer survivors who were diagnosed with stage 1 to stage 4 breast cancer from 2002 to 2006. Shu, Ingram Professor of Cancer Research, is the principal investigator of the Shanghai Breast Cancer Survival Study.
After adjusting for demographics, clinical characteristics and lifestyle factors, the researchers found cruciferous vegetable intake during the first 36 months after breast cancer diagnosis was associated with a reduced risk for total mortality, breast cancer-specific mortality and disease recurrence.
Survival rates were influenced by vegetable consumption in a dose-response pattern. As women ate more of these vegetables, their risk of death or cancer recurrence decreased.
Women who were in the highest quartiles of intake of vegetables per day had a 62 percent reduced risk of total mortality, 62 percent reduced risk of breast cancer mortality, and 35 percent reduced risk of breast cancer recurrence, compared to women with the lowest quartile of intake."
Nechuta noted that cruciferous vegetable consumption habits differ between China and the United States and suggested this fact be considered when generalizing these results to U.S. breast cancer survivors.
"Commonly consumed cruciferous vegetables in China include turnips, Chinese cabbage/bok choy and greens, while broccoli and Brussels sprouts are the more commonly consumed cruciferous vegetables in the United States and other Western countries," she said. "The amount of intake among Chinese women is also much higher than that of U.S. women."
Cruciferous vegetables contain phytochemicals known as isothiocyanates and indoles which appear to have a protective effect against some types of cancer.
Nechuta said the level of these bioactive compounds, proposed to play a role in the anticancer effects of cruciferous vegetables, depends on both the amount and type of cruciferous vegetables consumed.
She said there is a need for future studies that measure the bioactive compounds in these vegetables and the host factors that may influence the effects of these compounds to improve the understanding of the association between cruciferous vegetable consumption and breast cancer outcomes.
Broccoli, cabbage and cauliflower fight breast cancer
When your mother told you to eat your vegetables it appears that maternal wisdom had a scientific basis. Researchers have discovered a possible link between a diet rich in certain vegetables and a decreased risk for breast cancer. The study appears in the American Journal of Clinical Nutrition.
Cruciferous vegetables contain some compounds that may have a cancer-inhibitory effect.
While there was only a small positive relationship between a diet high in these vegetables and a reduction in breast cancer risk for the overall study population, there was a striking risk reduction – 50 percent – among women with a certain genetic profile. Researchers identified three forms of the GSTP1 genotype among the cancer patients: Ille/Ile, Ile/Val and Val/Val.
“Women who consumed more of these cruciferous vegetables and who also had the Val/Val genetic polymorphism had a lower breast cancer risk. So we cautiously interpreted this as diet being a factor that may reduce the impact of genetic susceptibility in overall breast cancer risk,” said Fowke.
Studies by other researchers have suggested cruciferous vegetables may reduce the risk of lung, stomach, colorectal and bladder cancers.
Cruciferous vegetables & soy vs breast/ ovarian cancers
We all know that eating fruits, vegetables and soy products provides essential nutrition for a healthy lifestyle, while obesity leads to the opposite. Yet proving the effect of nutrition, or obesity, on cancer is an experimental challenge and a focus for scientists. According to emerging evidence being presented at the 2007 Annual Meeting of the American Association for Cancer Research, eating well might still be one of the more pleasurable ways to prevent cancer and promote good health.
Eating such foods as broccoli and soy are believed to offer some protection against cancer, but how this occurs is not well-understood. Now, in laboratory experiments, researchers at the University of California, Los Angeles, have discovered a biological mechanism whereby two compounds in these foods might lower the invasive and metastatic potential of breast and ovarian cancer cells.
They found that diindolylmethane (DIM), a compound resulting from digestion of cruciferous vegetables, and genistein, a major isoflavone in soy, reduce production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.
When applying purified versions of DIM and genistein to motile cancer cells, the researchers could literally watch these cells come to a near halt. When either compound was applied, migration and invasion were substantially reduced.
"We think these compounds might slow or prevent the metastasis of breast and ovarian cancer, which would greatly increase the effectiveness of current treatments," said Erin Hsu, a graduate student in molecular toxicology. "But we need to test that notion in animals before we can be more definitive."
Both DIM and genistein are already being developed for use as a preventive and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are necessary, the researchers say.
The researchers looked at the potential of DIM and genistein to interfere with the "CXCR4/CXCL12 axis," which is known to play a central role in the metastasis of breast cancer and is also thought to play a role in the development of ovarian cancer. Primary cancer cells express very high levels of the CXCR4 chemokine receptor on the surface of their cells, and the organs to which these cancers metastasize secrete high levels of the CXCL12 chemokine ligand. This attraction stimulates the invasive properties of cancer cells and acts like a homing device, drawing the cancer cells to the organs they metastasize to.
When breast and ovarian cancer cell lines are exposed to purified DIM or genistein, levels of CXCR4 and CXCL12 messenger RNAs and proteins decrease in a dose-dependent manner, compared to untreated cells, according to Hsu.
To assess whether the compounds had any effect on the metastatic potential of the cells, the researchers placed the cells in one end of a compartment and watched how they moved toward CXCL12 at the other end. "The cells degrade the extracellular matrix in the upper compartment in order to move toward CXCL12 in the lower compartment, a system that represents a cell culture model for invasiveness," she said.
But if the cells are treated with either DIM or genistein, movement toward CXCL12 is reduced by at least 80 percent compared to untreated cells, the researchers say.
Hsu says that this same chemotactic attraction is thought to play a role in the development of more than 23 different types of cancer, and, so far, they have found that messenger RNA expression of CXCR4 and CXCL12 is substantially reduced when melanoma and prostate cancer cells are treated with the two compounds.
"We have also tested other phytochemicals and seen similar effects, indicating that this mechanism may mediate protective effects of other vegetable products as well," Hsu said.
The amount of DIM and genistein used in this study is probably comparable to use of a high dose of supplements, and is likely not achievable through consumption of food alone, the researchers say.
Sulforaphane – from broccoli, cauliflower and cabbage – may improve some symptoms of autism spectrum disorders
According to an article in Anti-Cancer Agents in Medicinal Chemistry sulforaphane also has huge cancer chemopreventive potential.
A small study led by investigators at MassGeneral Hospital for Children (MGHfC) and Johns Hopkins University School of Medicine has found evidence that daily treatment with sulforaphane – a molecule found in foods such as broccoli, cauliflower and cabbage – may improve some symptoms of autism spectrum disorders. In their report being published online in PNAS Early Edition, the investigators describe how participants receiving a daily dose of sulforaphane showed improvement in both behavioral and communication assessments in as little as four weeks. The authors stress that the results of this pilot study – conducted at the MGHfC-affiliated Lurie Center for Autism – must be confirmed in larger investigations before any conclusions can be drawn about sulforaphane's therapeutic benefit.
"Over the years there have been several anecdotal reports that children with autism can have improvements in social interaction and sometimes language skills when they have a fever," explains Andrew Zimmerman, MD, a co-corresponding author of the current report who also published a 2007 paper documenting the fever effect. "We investigated what might be behind that on a cellular level and postulated that it results from fever's activation of the cellular stress response, in which protective cellular mechanisms that are usually held in reserve are turned on through activation of gene transcription." Affiliated with the MGHfC Department of Neurology, Zimmerman is now based at UMass Memorial Medical Center.
Sulforaphane was first isolated in the 1990s by Paul Talalay, MD – co-corresponding author of the PNAS Early Edition paper and now a professor of Pharmacology and Molecular Sciences at Johns Hopkins – and his group also found that the chemical supports key aspects of the cell stress response. Zimmerman, who was based at Hopkins when he published the fever paper, approached members of Talalay's team to propose investigating sulforaphane's possible benefits for treating autism. While the mechanism underlying autism and other disorders on the autism spectrum remain largely unknown, several molecular abnormalities – including some related to the cellular stress response – have been identified. After Zimmerman moved to MGHfC in 2010, the trial was initiated at the Lurie Center in Lexington, Mass.
The study enrolled 44 young men, ages 13 to 27, who had been diagnosed with moderate to severe autism spectrum disorder. Participants were randomly assigned to a daily dose of either sulforaphane – extracted from broccoli sprouts – or a placebo, with neither investigators, participants nor their caregivers knowing who was receiving the study drug. Participants were assessed using standardized measurements of behavior and social interaction – some completed by caregivers, some by study staff – at the outset of the study and at 4, 10 and 18 weeks after treatment began. Treatment was discontinued after 18 weeks, and additional assessments of 22 participants were conducted 4 weeks later.
Study lead author Kanwaljit Singh, MD, MPH – of MGHfC, the Lurie Center and UMass – says that among the 40 participants who returned for at least one evaluation, the average scores for each of the assessments were significantly better for the 26 participants receiving sulforaphane than for the 14 who received a placebo. Even at the 4-week visit, some caregivers reported a noticeable behavioral improvement, and by the end of the study period, both study staff and family members correctly guessed the assignments of many participants. Overall, 17 of the 26 participants who received sulforaphane were judged by their caregivers to have improvements in behavior, social interaction and calmness while on active treatment.
After 18 weeks of treatment, the average scores on two assessments – the Aberrant Behavior Checklist and Social Responsiveness Scale – of those who received sulforaphane had decreased 34 and 17 percent, respectively – indicating improvement in factors such as irritability, lethargy, repetitive movements, hyperactivity, communication, motivation and mannerisms. Assessments using the Clinical Global Impression scale indicated that 46 percent of sulforaphane recipients exhibited noticeable improvement in social interaction, 54 percent in aberrant behaviors, and 42 percent in verbal communication. Most but not all of the improvements had disappeared by the 22-week reassessment, supporting the probability that changes had been the result of sulforaphane treatment.
"When we broke the code that revealed who was receiving sulforaphane and who got the placebo, the results weren't surprising to us, since the improvements were so noticeable," says Zimmerman, now a professor of Pediatric Neurology at UMass. "The improvements seen on the Social Responsiveness Scale were particularly remarkable, and I've been told this is the first time that any statistically significant improvement on the SRS has been seen for a drug study in autism spectrum disorder.
"But it's important to note that the improvements didn't affect everyone – about one third had no improvement – and the study must be repeated in a larger group of adults and in children, something we're hoping to organize soon," he adds. "Ultimately we need to get at the biology underlying the effects we have seen and study it at a cellular level. I think that will be done, and I hope it will teach us a lot about this still poorly understood disorder."
Broccoli may help protect against respiratory conditions like asthma
Here's another reason to eat your broccoli: UCLA researchers report that a naturally occurring compound found in broccoli and other cruciferous vegetables may help protect against respiratory inflammation that causes conditions like asthma, allergic rhinitis and chronic obstructive pulmonary disease.
Published in the journal Clinical Immunology, the research shows that sulforaphane, a chemical in broccoli, triggers an increase of antioxidant enzymes in the human airway that offers protection against the onslaught of free radicals that we breathe in every day in polluted air, pollen, diesel exhaust and tobacco smoke. A supercharged form of oxygen, free radicals can cause oxidative tissue damage, which leads to inflammation and respiratory conditions like asthma.
"This is one of the first studies showing that broccoli sprouts — a readily available food source — offered potent biologic effects in stimulating an antioxidant response in humans," said Dr. Marc Riedl, the study's principal investigator and an assistant professor of clinical immunology and allergy at the David Geffen School of Medicine at UCLA.
"We found a two- to three-fold increase in antioxidant enzymes in the nasal airway cells of study participants who had eaten a preparation of broccoli sprouts," Riedl said. "This strategy may offer protection against inflammatory processes and could lead to potential treatments for a variety of respiratory conditions."
The UCLA team worked with 65 volunteers who were given varying oral doses of either broccoli or alfalfa sprout preparations for three days. Broccoli sprouts are the richest natural source of sulforaphane; the alfalfa sprouts, which do not contain the compound, served as a placebo.
Rinses of nasal passages were collected at the beginning and end of the study to assess the gene expression of antioxidant enzymes in cells of the upper airways. Researchers found significant increases of antioxidant enzymes at broccoli sprout doses of 100 grams and higher, compared with the placebo group.
The maximum broccoli sprout dosage of 200 grams generated a 101-percent increase of an antioxidant enzyme called GSTP1 and a 199-percent increase of another key enzyme called NQO1.
"A major advantage of sulforaphane is that it appears to increase a broad array of antioxidant enzymes, which may help the compound's effectiveness in blocking the harmful effects of air pollution," Riedl said.
According to the authors, no serious side effects occurred in study participants receiving broccoli sprouts, demonstrating that this may be an effective, safe antioxidant strategy to help reduce the inflammatory impact of free radicals.
Riedl notes that more research needs to be done to examine the benefits of sulforaphane for specific respiratory conditions. It is too early to recommend a particular dosage.
Riedl recommends including broccoli and other cruciferous vegetables as part of a healthy diet.
Broccoli may help boost the aging immune system
UCLA researchers have found that a chemical in broccoli and other cruciferous vegetables may hold a key to restoring the body's immunity, which declines as we age.
Published in the Journal of Allergy and Clinical Immunology, the study findings show that sulforaphane, a chemical in broccoli, switches on a set of antioxidant genes and enzymes in specific immune cells, which then combat the injurious effects of molecules known as free radicals that can damage cells and lead to disease.
Free radicals are byproducts of normal body processes, such as the metabolic conversion of food into energy, and can also enter the body through small particles present in polluted air. A supercharged form of oxygen, these molecules can cause oxidative tissue damage, leading to disease — for example, triggering the inflammation process that causes clogged arteries. Oxidative damage to body tissues and organs is thought to be one of the major causes of aging.
"The mysteries of aging have always intrigued man," said Dr. Andre Nel, the study's principal investigator and chief of nanomedicine at the David Geffen School of Medicine at UCLA. "While we have known for some time that free radicals are important in aging, most of the past attention has focused on the mechanisms that produce free radicals rather than addressing the pathways used by the body to suppress their production."
A dynamic equilibrium exists in the body between the mechanisms that lead to increased free radical production and those antioxidant pathways that help combat free radicals.
"Our study contributes to the growing understanding of the importance of these antioxidant defense pathways that the body uses to fight free radicals," said Nel, a practicing clinical allergist and immunologist at the Geffen School. "Insight into these processes points to ways in which we may be able to alleviate the effects of aging."
The delicate balance between pro-oxidant and antioxidant forces in the body could determine the outcome of many disease processes that are associated with aging, including cardiovascular disease, degenerative joint diseases and diabetes, as well as the decline in efficiency of the immune system's ability to protect against infectious agents.
"As we age, the ability of the immune system to fight disease and infections and protect against cancer wears down as a result of the impact of oxygen radicals on the immune system," Nel said.
According to the UCLA study, the ability of aged tissues to reinvigorate their antioxidant defense can play an important role in reversing much of the negative impact of free radicals on the immune system. However, until this current study, the extent to which antioxidant defense can impact the aging process in the immune system was not properly understood.
"Our defense against oxidative stress damage may determine at what rate we age, how it will manifest and how to interfere in those processes," Nel said. "In particular, our study shows that a chemical present in broccoli is capable of stimulating a wide range of antioxidant defense pathways and may be able to interfere with the age-related decline in immune function."
"Dietary antioxidants have been shown to have important effects on immune function, and with further study, we may be adding broccoli and other cruciferous vegetables to that list," Nel said.
For now, Nel suggests including these vegetables as part of a healthy diet.
Nel said that these findings offer a window into how the immune system ages.
"We may find that combating free radicals is only part of the answer. It may prove to be a more multifaceted process and interplay between pro- and antioxidant forces," he said.
Consumption of raw, but not cooked, cruciferous vegetables and reduction of bladder cancer risk
While researchers have long known that cruciferous vegetables are chock full of isothiocyanates (ITCs), which are a well-known class of cancer prevention agents especially promising in bladder cancer chemoprevention, they didn’t know how much one needed to eat to reap the protective benefits.
Researchers from Roswell Park Cancer Institute report that three or more servings a month of raw cruciferous vegetables like broccoli, cabbage and cauliflower, may reduce bladder cancer risk by approximately 40 percent, overall.
The Roswell Park team surveyed the dietary habits of 275 individuals with incident, primary bladder cancer and 825 individuals without cancer. The researchers surveyed patients about their pre-diagnostic intake of raw and cooked cruciferous vegetables, their smoking habits and other cancer risk factors. They observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable consumption. When compared to smokers who ate less than three servings of raw vegetables, non-smokers who ate at least three servings a month were almost 73 percent less likely to develop bladder cancer, the researchers say.
A key factor in the research was that it’s a survey of raw cruciferous vegetables. Previous research had surveyed intake of any cruciferous vegetables – cooked or not – and results proved inconsistent. Cooking significantly reduces the availability of ITCs for absorption into the body, according to researchers.
“Cooking can reduce 60 to 90 percent of ITCs,” says Li Tang, M.D., Ph.D. of Roswell Park Cancer Institute and lead researcher on this study. “Heating destroys the enzyme that converts the precursor glucosinolates into ITCs, and also destroys ITCs already formed, which is why you need to eat raw cruciferous vegetables to receive the food’s maximum benefit.”
Broccoli Sprouts: protection against gastritis, ulcers and even stomach cancer
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."
"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.
Broccoli and cauliflower protect cells from damage
Scientists at the University of Pennsylvania School of Medicine discovered that a dietary antioxidant found in such vegetables as broccoli and cauliflower protects cells from damage caused by chemicals generated during the body’s inflammatory response to infection and injury. The finding has implications for such inflammation-based disorders as cystic fibrosis (CF), diabetes, heart disease, and neurodegeneration.
Through cell-culture studies and a synthesis of known antioxidant biochemistry, Zhe Lu, MD, PhD , Professor of Physiology, Yanping Xu , MD, PhD , Senior Research Investigator, and Szilvia Szép , PhD, postdoctoral researcher, showed that the antioxidant thiocyanate normally existing in the body protects lung cells from injuries caused by accumulations of hydrogen peroxide and hypochlorite, the active ingredient in household bleach. These potentially harmful chemicals are made by the body as a reaction to infection and injury. In addition, thiocyanate also protects cells from hypochlorite produced in reactions involving MPO, an enzyme released from germ-fighting white blood cells during inflammation. They published their finding November 2009 in the Proceedings of the National Academy of Sciences. Lu is also an Investigator of the Howard Hughes Medical Institute.
“Dr. Lu’s work throws new light on how the genetic defect underlying CF leads to the lung illnesses that are the leading cause of death,” said Bert Shapiro, Ph.D., who oversees membrane structure grants at the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS). “His team’s findings suggest that the lungs of people with the disease are more susceptible to the damaging effects of cellular oxidants. While the idea is tantalizing and creative, further testing is needed to confirm it.”
The research team demonstrated that in three additional cell types used to extend their ideas to other inflammation-related conditions – cardiovascular disease, neurodegeneration, and diabetes – thiocyanate at blood concentrations of at least 100 micromolar (micromoles per liter) greatly reduces the toxicity of MPO in cells, including those lining blood vessels. Humans naturally derive thiocyanate from some vegetables and blood levels of thiocyanate in the general population vary from 10 to 140 micromolar.
This comparison raises the possibility, the authors point out, that without an adequate dietary supply of thiocyanate, hypochlorite produced by the body during inflammation would cause additional collateral damage to cells, thus worsening inflammatory diseases, and predisposing humans to diseases linked to MPO activity, including atherosclerosis.
Connection to CF
For over a decade Lu and colleagues have been exploring the inner workings of ion channels and how this knowledge relates to the pathology of such diseases as CF. The CF disease originates from mutations in the CF transmembrane conductance regulator (CFTR) protein, an ion channel protein in the cell membrane commonly thought to transport mainly chloride ions. It has, however, remained a mystery why a defect in a chloride-transporting channel leads to cystic fibrosis, a disease with exaggerated inflammation in both the lungs and the digestive system.
Lung injuries inflicted by excessive inflammation and recurring infection cause about ninety percent of CF patients’ symptoms and mortality. Although known as a chloride channel, CFTR also conducts thiocyanate ions, important because, in several ways, they can limit potentially harmful accumulations of hydrogen peroxide and hypochlorite, chemicals produced by the body to fight germs.
In CF patients, there is also a high incidence of diabetes, partly caused by damage to the pancreas. Type 2 diabetes is also associated with higher levels of MPO in the blood. The researchers found that the MPO-caused injuries to pancreas cells and endothelial cells used in their experiments can be greatly reduced by as little as 100 micromolar thiocyanate. Their finding raises the possibility that MPO, in the absence of adequate thiocyanate, contributes to diabetes.
In the cell-based experiments, thiocyanate at concentrations below 100 micromolar did not eliminate hypochlorite accumulation and did not fully protect against MPO toxicity. Conceivably, inadequate thiocyanate levels would aggravate MPO-produced injuries in patients suffering from inflammatory diseases, surmise the authors.
Links to Other Diseases
In other studies, MPO activity has been linked to lung cancers among smokers and also implicated in neurodegenerative diseases. Intriguingly, people with congenital MPO deficiency are less likely to develop cardiovascular diseases. The research team found that MPO-caused injuries to nerve cells, as well as to blood vessel-lining endothelial cells, can be greatly reduced by 100 micromolar thiocyanate.
Genetic defects in the CFTR predispose CF patients’ lungs to excessive inflammation entangled with recurring lung infection. Defective CFTR channels would be expected to result in lower thiocyanate concentrations in the affected regions within the respiratory, as well as the digestive systems, leaving tissues inadequately protected from accumulated hydrogen peroxide and overproduced hypochlorite.
Conceptually, delivering thiocyanate directly to the digestive and respiratory systems might be a therapy for CF disease, propose the researchers. As for the general population, individuals with low blood levels of thiocyanate may be at risk for chronic injuries by MPO, predisposing them to inflammatory or inflammation-mediated diseases.
Many investigators have proposed developing drugs that specifically inhibit MPO-catalyzed hypochlorite production to combat these diseases, but natural thiocyanate not only decreases MPO-catalyzed formation of hypochlorite but also rapidly, once it is made, neutralizes it.
“In light of the obvious implications of this protective action of thiocyanate against the cell-damaging effect of MPO activity with regard to both CF disease and general population health, my colleagues and I will vigorously investigate the potential health benefit of thiocyanate,” says Lu. He emphasizes though, “until the research community acquires a better understanding of both positive and negative impacts of thiocyanate on human health, it would be unwise for anyone to self-administer thiocyanate because like many other chemicals, thiocyanate has adverse side effects at improper doses and/or under inappropriate conditions.
Health benefits of broccoli require the whole food, not supplements
New research has found that if you want some of the many health benefits associated with eating broccoli or other cruciferous vegetables, you need to eat the real thing – a key phytochemical in these vegetables is poorly absorbed and of far less value if taken as a supplement.
The study, published by scientists in the Linus Pauling Institute at Oregon State University, is one of the first of its type to determine whether some of the healthy compounds found in cruciferous vegetables can be just as easily obtained through supplements.
The answer is no. And not only do you need to eat the whole foods, you have to go easy on cooking them.
"The issue of whether important nutrients can be obtained through whole foods or with supplements is never simple," said Emily Ho, an OSU associate professor in the OSU School of Biological and Population Health Sciences, and principal investigator with the Linus Pauling Institute.
"Some vitamins and nutrients, like the folic acid often recommended for pregnant women, are actually better-absorbed as a supplement than through food," Ho said. "Adequate levels of nutrients like vitamin D are often difficult to obtain in most diets. But the particular compounds that we believe give broccoli and related vegetables their health value need to come from the complete food."
The reason, researchers concluded, is that a necessary enzyme called myrosinase is missing from most of the supplement forms of glucosinolates, a valuable phytochemical in cruciferous vegetables. Without this enzyme found in the whole food, the study found that the body actually absorbs five times less of one important compound and eight times less of another.
Intensive cooking does pretty much the same thing, Ho said. If broccoli is cooked until it's soft and mushy, its health value plummets. However, it can still be lightly cooked for two or three minutes, or steamed until it's still a little crunchy, and retain adequate levels of the necessary enzyme.
The study was published October 2011 in the Journal of Agricultural and Food Chemistry.
Broccoli has been of particular interest to scientists because it contains the highest levels of certain glucosinolates, a class of phytochemicals that many believe may reduce the risk of prostate, breast, lung and colorectal cancer. When eaten as a raw or lightly-cooked food, enzymes in the broccoli help to break down the glucosinolates into two valuable compounds of intensive research interest – sulforaphane and erucin.
Studies have indicated that sulforaphane, in particular, may help to detoxify carcinogens, and also activate tumor suppressor genes so they can perform their proper function.
Most supplements designed to provide these glucosinolates have the enzyme inactivated, so the sulforaphane is not released as efficiently. There are a few supplements available with active myrosinase, and whose function more closely resembles that of the whole food, but they are still being tested and not widely available, Ho said.
Small amounts of the myrosinase enzyme needed to break down glucosinolates are found in the human gut, but the new research showed they accomplish that task far less effectively than does whole food consumption.
Although broccoli has the highest levels of glucosinolates, they are also found in cauliflower, cabbage, kale and other cruciferous vegetables. The same cooking recommendations would apply to those foods to best retain their health benefits, Ho said.
Many people take a variety of vitamins, minerals and phytochemicals as supplements, and many of them are efficacious in that form, researchers say. Higher and optimal levels of popular supplements such as vitamins C, E, and fish oil, for instance, can be difficult to obtain through diet alone. Some researchers believe that millions of people around the world have deficient levels of vitamin D, because they don't get enough in their diet or through sun exposure.
But for now, if people want the real health benefits of broccoli, there's a simple guideline: Eat your vegetables.
Eat Your Broccoli: Sulforaphane Prevents Cancer
Researchers in the Linus Pauling Institute at Oregon State University have discovered yet another reason why the "sulforaphane"compound in broccoli and other cruciferous vegetables is so good for you -- it provides not just one, but two ways to prevent cancer through the complex mechanism of epigenetics.
Epigenetics, an increasing focus of research around the world, refers not just to our genetic code, but also to the way that diet, toxins and other forces can change which genes get activated, or "expressed." This can play a powerful role in everything from cancer to heart disease and other health issues.
Sulforaphane was identified years ago as one of the most critical compounds that provide much of the health benefits in cruciferous vegetables, and scientists also knew that a mechanism involved was histone deacetylases, or HDACs. This family of enzymes can interfere with the normal function of genes that suppress tumors.
HDAC inhibitors, such as sulforaphane, can help restore proper balance and prevent the development of cancer. This is one of the most promising areas of much cancer research. But the new OSU studies have found a second epigenetic mechanism, DNA methylation, which plays a similar role.
"It appears that DNA methylation and HDAC inhibition, both of which can be influenced by sulforaphane, work in concert with each other to maintain proper cell function," said Emily Ho, an associate professor in the Linus Pauling Institute and the OSU College of Public Health and Human Sciences. "They sort of work as partners and talk to each other."
This one-two punch, Ho said, is important to cell function and the control of cell division -- which, when disrupted, is a hallmark of cancer.
"Cancer is very complex and it's usually not just one thing that has gone wrong," Ho said. "It's increasingly clear that sulforaphane is a real multi-tasker. The more we find out about it, the more benefits it appears to have."
DNA methylation, Ho said, is a normal process of turning off genes, and it helps control what DNA material gets read as part of genetic communication within cells. In cancer that process gets mixed up. And of considerable interest to researchers is that these same disrupted processes appear to play a role in other neurodegenerative diseases, including cardiovascular disease, immune function, neurodegenerative disease and even aging.
The influence of sulforaphane on DNA methylation was explored by examining methylation of the gene cyclinD2.
This research, which was published February, 2012 in the journal Clinical Epigenetics, primarily studied the effect on prostate cancer cells. But the same processes are probably relevant to many other cancers as well, researchers said, including colon and breast cancer.
"With these processes, the key is balance," Ho said. "DNA methylation is a natural process, and when properly controlled is helpful. But when the balance gets mixed up it can cause havoc, and that's where some of these critical nutrients are involved. They help restore the balance."
Sulforaphane is particularly abundant in broccoli, but also found in other cruciferous vegetables such as cauliflower and kale. Both laboratory and clinical studies have shown that higher intake of cruciferous vegetables can aid in cancer prevention.
Magnesium In Green Leaves and Broccoli Helps You Remember
Those who live in industrialized countries have easy access to healthy food and nutritional supplements, but magnesium deficiencies are still common. That's a problem because new research from Tel Aviv University suggests that magnesium, a key nutrient for the functioning of memory, may be even more critical than previously thought for the neurons of children and healthy brain cells in adults.
Begun at MIT, the research started as a part of a post-doctoral project by Dr. Inna Slutsky of TAU's Sackler School of Medicine and evolved to become a multi-center experiment focused on a new magnesium supplement, magnesium-L-theronate (MgT), that effectively crosses the blood-brain barrier to inhibit calcium flux in brain neurons.
Published recently in the scientific journal Neuron, the new study found that the synthetic magnesium compound works on both young and aging animals to enhance memory or prevent its impairment. The research was carried out over a five-year period and has significant implications for the use of over-the-counter magnesium supplements.
In the study, two groups of rats ate normal diets containing a healthy amount of magnesium from natural sources. The first group was given a supplement of MgT, while the control group had only its regular diet. Behavioral tests showed that cognitive functioning improved in the rats in the first group and also demonstrated an increase of synapses in the brain — connective nerve endings that carry memories in the form of electrical impulses from one part of the brain to the other.
"We are really pleased with the positive results of our studies," says Dr. Slutsky. "But on the negative side, we've also been able to show that today's over-the-counter magnesium supplements don't really work. They do not get into the brain.
"We've developed a promising new compound which has now taken the first important step towards clinical trials by Prof. Guosong Liu, Director of the Center for Learning and Memory at Tsinghua University and cofounder of Magceutics company," she says.
While the effects were not immediate, the researchers in the study — from Tel Aviv University, MIT, the University of Toronto, and Tsighua University in Beijing — were able to assess that the new compound shows improved permeability of the blood-brain barrier. After two weeks of oral administration of the compound in mice, magnesium levels in the cerebral-spinal fluid increased.
"It seems counterintuitive to use magnesium for memory improvement because magnesium is a natural blocker of the NMDA receptor, a molecule critical for memory function. But our compound blocks the receptor only during background neuronal activity. As a result, it enhances the brain's 'plasticity' and increases the number of brain synapses that can be switched on," says Dr. Slutsky.
"Our results suggest that commercially available magnesium supplements are not effective in boosting magnesium in cerebro-spinal fluid," she says. "Magnesium is the fourth most abundant mineral in the body, but today half of all people in industrialized countries are living with magnesium deficiencies that may generally impair human health, including cognitive functioning."
Before the new compound becomes commercially available, Dr. Slutsky advises people to get their magnesium the old-fashioned way — by eating lots of green leaves, broccoli, almonds, cashews and fruit. The effects on memory won't appear overnight, she cautions, but with this persistent change in diet, memory should improve, and the effects of dementia and other cognitive impairment diseases related to aging may be considerably delayed.