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Biofeedback on abnormal mechanics lowers risk for stress fractures, pain under kneecap

More than seven out of 10 runners will sustain an injury over the course of a year, many of these injuries preventable without any adverse effects on running distance or performance, according to Dr. Irene Davis, director of the Running Injury Lab at the University of Delaware, and director of Research for Drayer Physical Therapy Institute.

In earlier studies, Dr. Davis identified the specific gait mechanics associated with common injuries. Now, in a study reported at the Experimental Biology meeting in Washington, DC, she explains how she successfully retrained runners to change their faulty gaits in eight half hour sessions, reducing leg shock by 50 percent and completely eliminating pain under the kneecap.

Her Experimental Biology presentation on April 30 is part of the scientific program of the American Association of Anatomists.

In the laboratory, Dr. Davis uses sophisticated biofeedback devices and monitors, but she says she does similar - and also effective - retraining in the physical therapy clinic at the University of Delaware using basic mechanical information, mirrors and advice to listen to the sound of one’s own feet hitting the ground.

The two studies underway in Dr. Davis' laboratory now are with runners who were selected for the study because they were experiencing or had been identified as high risk for one of the two most common running-related injuries: tibial stress fractures (microfractures of the lower leg bone) and patellofemoral pain syndrome (pain under the kneecap).

Each runner undergoes an analysis of their gait. Runners then come to the laboratory for two days, take a day off, return for two, until they have had eight retraining sessions on a special treadmill. The first sessions last 15 minutes, and the final ones 30 minutes. Runners are not allowed to run outside the laboratory during retraining for fear of reinforcing old gait habits.

Dr. Davis’s earlier gait mechanics research had found that individuals with tibial stress fractures tend to land harder when each foot hits the ground, and in fact about half of the at-risk runners who have completed the study so far already had experienced microfractures. During their retraining sessions, the runners wore a shock measuring device on their lower legs while they ran on a tread mill. A monitor on the front of the treadmill showed the force of each footstrike measured against a line of what a normal, healthy footstrike should look like. The runners’ task was to constantly adjust the force with which each of their own feet hit the ground to keep it at or below the line on the screen.

With this feedback, all runners immediately were able to modify the hardness of their footstrike to meet the desired level, but all reported that the softer footstrike level did not "feel normal." By the end of the eighth session, however, even when they were receiving relatively little feedback, all runners had adjusted the force of their footstrike by half. Furthermore, they reported that they found the new gait now felt more normal.

The runners experiencing pain under the kneecap followed the same protocol. Dr. Davis’ earlier gait mechanics studies had found that individuals with kneecap pain (patellofemoral pain syndrome) demonstrate poor hip stability, hips rotating inward, causing a knock-kneed type running gait. On the laboratory treadmill, these runners watched a monitor that compared their gait, measured by markers on their legs, to a normal angular curve.

By keeping their knees apart, not letting them collapse inward, they soon were able to make the two images merge. Before retraining, the group had classified their kneecap pain from five to seven on a ten point scale, ten being the worst. In every case, after retraining, the runners reported zero pain.

A month after the retraining, during which runners had resumed their regular running schedule, they returned to the laboratory treadmill. All had retained the lessons learned.

Dr. Davis recommends that runners without access to gait analysis and biofeedback do a little of what she does in the clinic at the University of Delaware.

"For people with or at risk for stress microfractures, we ask them to listen to their footstrikes and simply make the sound softer," says Dr. Davis. "For people with pain under the kneecap, we tell them to run in place in front of a mirror and concentrate on keeping their knees apart."

In the meantime, back at the laboratory, she is continuing to recruit patients into the study. Funded by both the Department of Defense and the National Institutes for Health in the interest of helping individuals to remain physical fit throughout their lives, the studies eventually will include 60 runners. Data reported at the Experimental Biology 2007 meeting were for five patients in each group.

Although the American Society for Nutrition’s popular “controversy session” at Experimental Biology 2007 focuses on the health effects of coffee drinking, panel chair Dr. James Coughlin, a toxicology/safety consultant at Coughlin & Associates, says that recent advances in epidemiologic and experimental knowledge have transformed many of the negative health myths about coffee drinking into validated health benefits.

Indeed, panel co-chair Dan Steffen, who follows coffee and health issues in the Scientific and Regulatory Affairs group of Kraft Foods, note that the “controversy” is often to educate a wider audience about this transformation in understanding.

Coffee is among the most widely consumed beverages in the world, and Dr. Coughlin says that the preponderance of scientific evidence - some by the panelists - suggests that moderate coffee consumption (3-5 cups per day) may be associated with reduced risk of certain disease conditions, such as Parkinson’s disease. Some research in neuropharamacology suggests that one cup of coffee can halve the risk of Parkinson’s disease. Other studies have found it reduces the risk of Alzheimer's disease, kidney stones, gallstones, depression and even suicide.

Dr. Coughlin and two distinguished researchers discussed some of the benefits - and a couple of the remaining increased risk factors (possible increase in blood pressure and plasma homocysteine) - on April 30 at the Experimental Biology meeting in Washington, DC.

Dr. Rob van Dam, an epidemiologist at the Harvard School of Public Health and the Harvard Medical School, studies the link between diet and the development of type 2 diabetes. Worldwide, an estimated 171 million persons have diabetes, mostly type 2 diabetes, and an alarming increase to 366 million persons is expected for the year 2030. While increased physical activity and restriction of energy intake can substantially reduce risk of type 2 diabetes, he believes insight into the role of other lifestyle factors may contribute to additional prevention strategies for type 2 diabetes.

In recent epidemiological studies in the U.S., Europe and Japan, persons who were heavy coffee consumers had a lower risk of type 2 diabetes than persons who consumed little coffee. Interestingly, he says, associations were similar for caffeinated and decaffeinated coffee, suggesting that coffee components other than caffeine may be beneficial for glucose metabolism.

Coffee contains hundreds of components including substantial amounts of chlorogenic acid, caffeine, magnesium, potassium, vitamin B3, trigonelline, and lignans. Limited evidence suggests that coffee may improve glucose metabolism by reducing the rate of intestinal glucose absorption and by stimulating the secretion of the gut hormone glucagon-like peptide-1 (GLP-1) that is beneficial for the secretion of insulin. However, most mechanistic research on coffee and glucose metabolism has been done in animals and in lab tubes and therefore metabolic studies in humans are currently being conducted. Further research may lead to the development or selection of coffee types with improved health effects.

Dr. Lenore Arab, a nutritional epidemiologist in the David Geffen School of Medicine at UCLA, notes that the first coffee controversy dates back 430 years when in 1570 some monks petitioned the pope to condemn this drink, so popular among Muslims. Pope Clement VIII, liking how it kept the monks from falling sleep during mass, purportedly blessed it instead. The rest, including the United States’ wholesale conversion to coffee following the Boston Tea Party, is history.

In reviewing the latest epidemiologic literature on cancers and coffee, Dr. Arab has found there to be close to 400 studies of the associations between coffee consumption and cancers various at various sites. The earlier controversy with regard to colon cancer was based on flawed analyses, she says. More thorough analyses and the accumulation of evidence suggest no negative effect on the incidence of colon cancer, and possible protective effects for adenomas of the colon as well as for rectal cancer and liver cancer. Mechanisms which might contribute to a possible anticarcinogenic effect include reduction in cholesterol, bile acid and neutral sterol secretion in the colon, increased colonic motility and reduced exposure of epithelium to carcinogens, the ability of diterpenes to reduce genotoxicity of carcinogens, and lower DNA adduct formation, and the ability of caffeic acid and chlorogenic acid to decreased DNA methylation. In other cancers - breast, ovarian, and prostate - the evidence is not suggestive of either risk or protection. There are two areas, says Dr. Arab, in which there is some evidence of increased risk: leukemia and stomach cancer. The evidence for the former is intriguing, for the latter insubstantial. She concludes that a systematic review of the newer data for liver, rectal, stomach cancer and for childhood leukemia is due.

High doses of phytochemicals in teas and supplements could be unhealthy

Chemical Research in Toxicology

Those phytochemicals — natural plant-based compounds that give fruits and vegetables a reputation as healthy food — could be unhealthy if consumed in high doses in dietary supplements, teas or other preparations, scientists in New Jersey have concluded after a review of studies on the topic.

In their article, scheduled for the current issue of ACS's Chemical Research in Toxicology, a monthly journal, Chung S. Yang and colleagues analyze available data on the toxic potential of polyphenols. That group of dietary phytochemicals includes flavonoids, whose suggested beneficial effects in fruits and vegetables include prevention of heart disease and cancer. The data was from studies done in humans and laboratory animals.

The report cites specific examples of toxic effects, including reports of liver, kidney, and intestinal toxicity related to consumption of high doses of green tea-based dietary supplements. The risk of such toxicity may be greater in individuals taking certain medications, or with genetic traits, that increase the bioavailability of phytochemicals, the researchers said. Citing the need for new studies on the topic, the report concludes: "Only when such data are compared to the evidence for beneficial health effects can a balanced judgment be made regarding the potential utility of these compounds for disease prevention and treatment."



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A handful of pistachios may lower cholesterol and provide the antioxidants usually found in leafy green vegetables and brightly colored fruit, according to a team of researchers.

"Pistachio amounts of 1.5 ounces and 3 ounces – one to two handfuls – reduced risk for cardiovascular disease by significantly reducing LDL cholesterol levels and the higher dose significantly reduced lipoprotein ratios," says Sarah K. Gebauer, graduate student in integrative biosciences, Penn State, to attendees at the Experimental Biology meeting today (April 30) in Washington, D.C.

The researchers conducted a randomized, crossover design, controlled feeding experiment to test the effects of pistachios added to a heart healthy moderate-fat diet on cardiovascular disease risk factors. Controlled feeding experiments provide all the food eaten by study subjects for the duration of the study segment.

Participants began the study by eating an Average American Diet consisting of 35 percent total fat and 11 percent saturated fat for two weeks. They then tested three diets for four weeks each with a two-week break between each diet.

All three diets were variations on the Step I Diet, a cholesterol-lowering diet in general use. The diets included a Step I Diet without pistachios which had 25 percent total fat and 8 percent saturated fat; a Step I Diet including 1.5 ounces of pistachios per day which had 30 percent total fat and 8 percent saturated fat, and a Step I Diet including three ounces of pistachios per day which had 34 percent total fat and 8 percent saturated fat. The researchers added pistachios into the diets by including about half the amount of pistachios as a snack and by incorporating the rest into such foods as pistachio muffins, granola and pistachio pesto.

"We had really good compliance and participants were generally pleased with the diets," says Gebauer.

Standard blood tests determined the various cholesterol levels in the participant’s blood after each diet. Researchers found that 3 ounces of pistachios reduced the amounts of total cholesterol in the blood by 8.4 percent and low-density lipoprotein (LDL), the so-called bad cholesterol, by 11.6 percent. The study also found that non-high density lipoproteins (non-HDL) decreased by 11.2 percent. Non-HDL levels are considered reliable predictors of cardiovascular disease risk.

The three-ounce pistachio diet also decreased the ratios of total cholesterol to HDL, LDL to HDL and non-HDL to HDL and apolipoprotein B, which are all measures of cardiovascular disease risk. "We were pleased to see a difference between the two doses of pistachios for the lipoprotein ratios because it would appear that pistachios are causing the effect and that they act in a dose dependent way," says Gebauer.

In addition, during this study researchers, researchers looked at the effects of these diets on oxidized LDL and on antioxidants in the blood.

"We were trying to see if the increased levels of antioxidants provided by pistachios could reduce inflammation and oxidation," says Gebauer. Pistachios contain more lutein, – normally found in dark leafy vegetables -- beta carotene – a precursor to vitamin A – and gamma tocopherol – the major form of vitamin E – than other nuts. It is oxidized LDL and other lipproteins that contribute to plaque formation in arteries.

The researchers reported that both the 1.5 and 3 ounce pistachio diets reduced oxidized LDL compared with the baseline diet. Pistachio-enriched diets also resulted in significantly higher levels of lutein in the blood. The increased lutein from the 3-ounce pistachio diet correlated with a reduction in oxidized LDL which may indicate that the lutein in pistachio nuts improves the risk of cardiovascular disease by reducing serum oxidized LDL.

"Our study has shown that pistachios, eaten with a heart healthy diet, may decrease a person's CVD risk profile," says Dr. Penny Kris-Etherton, distinguished professor of nutrition and primary investigator of the study.

Eating pistachios may reduce your body's response to the stresses of everyday life, according to a Penn State study.

"A ten-year follow-up study of young men showed that those who had larger cardiovascular responses to stress in the lab, were more likely to contract hypertension later in life," says Dr. Sheila G. West, associate professor of biobehavioral health. "Elevated reactions to stressors are partly genetic, but can be changed by diet and exercise. Lifestyle changes can make the biological reactions to stress smaller."

West and her colleagues investigated the effects of pistachios on standardized stressors on subjects who had high cholesterol, but normal blood pressure. They used a randomized, crossover controlled feeding study design and all three diets all contained the same number of calories. After a two-week run-in diet containing 35 percent fat and 11 percent saturated fats, each test diet lasted for four weeks during which time participants ate only foods supplied by the study. The researchers reported the results of this study at Experimental Biology 2007 today (April 30) in Washington, D.C.

The diets included a Step I Diet – a standard heart healthy diet with 25 percent fat and 8 percent saturated fat, a diet containing 1.5 ounces of pistachios that was a Step I Diet with 30 percent total fat and 8 percent saturated fat and a diet containing 3 ounces of pistachios that was a Step I Diet containing 34 percent fat and 8 percent saturated fat. At the end of each four-week diet regime, the researchers measured blood pressure and total peripheral vascular resistance at rest and during two stress tests.

The two tests consisted of a physical test and a psychological test. The physical test consists of putting one foot in a bucket of ice water for 2.5 minutes. The psychological test asks participants to listen to two numbers, add them in their head and say the answer. Then they hear another number and they must add it to the second number they heard, not the sum they spoke.

"The ice water is a stimulus for the sympathetic nervous system, but it is very different form the stressors we encounter every day," says West. "We also wanted to see if the reaction occurred when the stress was nonphysical, so we used the math test."

The researchers found that both pistachio containing diets reduced the stress effects on blood pressure, but that the 1.5 ounce pistachio diet reduced systolic blood pressure by 4.8 millimeters of mercury while the 3-ounce pistachio diet only reduced systolic blood pressure by 2.4 millimeters of mercury. The diets had no effect on normal, resting blood pressure.

"When we only look at blood pressure, these results are confusing," says West. "If it is the pistachios, why is it not dose related?"

When the researchers looked at total peripheral vascular resistance, it was clear that the 3-ounce diet caused greater relaxation of arteries. Because the body tightly regulates blood pressure, rather than allowing blood pressure to drop further, the heart compensated by pumping more forcefully.

"The relaxation of blood vessels after the 3-ounce pistachio diet likely reduced the workload on the heart," says West. "This pattern of change would be beneficial if it is maintained long term. It is possible that other foods that are high in unsaturated fat and antioxidants would have a similar effect."

Incorporating macadamia nuts into a heart healthy diet can reduce cardiovascular disease risks according to Penn State researchers.

"We looked at macadamia nuts because they are not currently included in the health claim for tree nuts, while other tree nuts are recommended as part of a healthy diet," says Dr. Amy E. Griel, recent Ph.D. recipient in nutritional sciences. "Macadamia nuts have higher levels of monounsaturated fats, like those found in olive oil compared with other tree nuts."

The researchers used a controlled feeding study to compare a heart-healthy diet with 1.5 ounces – a small handful – of macadamia nuts to a standard American diet. The participants had slightly elevated cholesterol levels, normal blood pressure and were not taking lipid lowering drugs. Researchers randomly assigned participants to either the macadamia nut diet or the standard American diet and provided all meals for the participants for five weeks. The participants then switched diets and continued eating only food provided by the researchers for another five weeks.

The Healthy Heart diet with macadamia nuts did reduce total cholesterol, low-density lipoprotein cholesterol and triglyceride levels compared with the standard American diet.

"We observed a reduction in LDL similar to that seen with other tree nuts like walnuts and almonds," says Griel.

Individual calorie levels were used for each participant so that they did not gain or lose weight during the study. Both diets were matched for total fat, containing 33 percent calories from total fat. The Heart Healthy diet with macadamia nuts had 7 percent saturated fat, 18 percent monounsaturated fat and 5 percent polyunsaturated fat. The standard American diet had 13 percent saturated fat, 11 percent monounsaturated fat and 5 percent polyunsaturated fat.

The macadamia nut diet included macadamia nuts as a snack, mixed into meals, as a salad topping and in cookies and muffins.

"The total fat was the same in both diets," says Griel. "We substituted the macadamia nuts for other sources of fat and protein in the diet. For example, we could switch skim milk for 2 percent milk and add some macadamia nuts."

Macadamia nuts are native to Australia, but were imported to Hawaii and thrived. The first commercials crop of Hawaiian macadamia nuts was harvested in 1956.

Study May Explain Why Alcohol Consumption Boosts Breast Cancer Risk

For the first time, scientists have used a laboratory mouse model to mimic the development of human alcohol-induced breast cancer. The results are part of a new study, Chronic Alcohol Consumption Increases Tumor Growth and Amgiogenesis of Breast Cancer in Female Mice.

Background
Alcohol (EtOH) consumption – even moderate – is a well-established risk factor for breast cancer in women. A recent study showed that 60 percent of female breast cancers worldwide were attributable to alcohol consumption. Nevertheless, the mechanisms of alcohol-induced breast cancer are poorly understood.

The definitive biological effects and molecular mechanisms of EtOH on progression and malignancy of breast cancer have not been investigated using a mammalian breast cancer model that mimics the human disease. Scientists have suggested that the possible mechanisms involved include the agitation of estrogen metabolism and response; cell mutation by the EtOH metabolite acetaldehyde; oxidative damage; and one-carbon metabolism pathways through reduced folic acid.

Methodology
To date, there has not been an animal model that faithfully mimics the human disease with respect to characteristics of breast cancer, immunocompetence, and physiologically relevant EtOH intake. The researchers addressed and overcame the obstacles and developed a novel mouse breast cancer model. The model mimics human breast cancer disease in which the estrogen receptor-positive breast adenocarcinoma cells were subcutaneously injected near the pad of the fourth mammary gland of female immunocompetant mice (C57BL/6). The six-week-old female mice were fed with moderate EtOH (one percent in drinking water) for four weeks, the equivalent of two drinks per day in humans. The control mice received regular drinking water only.

In the second week of the experiment, mouse breast cancer cells (5x105 E0771) were injected at cite referenced above. At the end of the experiment, the tumors were isolated to measure tumor size, examine intratumoral microvessel (IM) density via CD 31 immunohistochemistry staining, and assessing VEGF protein levels via ELISA. These steps were taken to determine the effects of EtOH intake in physiologically relevant doses on tumor growth and angiogenesis in mouse breast cancer.

Results
The researchers found:

- that moderate alcohol consumption significantly increased the tumor size of breast cancer in mice, which was a 1.96-fold increase in tumor weight vs. control mice;

- that alcohol intake caused a 1.28-fold increase in tumor microvessel density vs. the control group;

- a significant increase in tissue protein levels of VEGF were found in the tumors of the mice treated with EtOH vs. control group;

- EtOH intake did not cause significant changes in the body weight of the mice.

Conclusions
This study presents the first animal model to confirm that alcohol consumption stimulates tumor growth and malignancy of breast cancer, and reveals some of the mechanisms of alcohol-induced breast cancer. The findings demonstrate that even moderate alcohol consumption significantly stimulates tumor growth of breast cancer and that induction of tumor angiogenesis and VEGF expressions are mechanisms which are associated with the progression of this deadly disease.

Alcohol Increases Hormone Levels, Raising Breast Cancer Risk

Article date: 2001/05/24

Drinking a daily glass of wine may ward off heart problems, but the opposite may be true when it comes to breast cancer. Even small amounts of alcohol may increase hormone levels circulating in the blood that could raise breast cancer risk — especially in postmenopausal women, according to a new study published in the Journal of the National Cancer Institute (Vol. 93, No. 9, 710–715).

Some studies have shown that alcohol consumption may increase the risk of breast cancer, but researchers are unclear as to what exactly causes the increased risk. Researchers led by Joanne Dorgan, MPH, PhD, and her colleagues at the Fox Chase Cancer Center in Philadelphia, investigated whether small amounts of alcohol could boost levels of hormones thought to increase breast cancer risk.

Dorgan’s team studied 51 healthy postmenopausal women who were not taking hormone replacement therapy (HRT), i.e. synthetic estrogens. Each participant went through three 8-week periods in which she consumed 15 or 30 grams of alcohol (the equivalent of one or two drinks) per day, or an alcohol-free drink. At the end of each 8-week period, the researchers measured levels of sex hormones — including estrogen, testosterone, and progesterone — in the women’s blood.

Women who consumed 15 grams of alcohol per day showed a 7.5% increase in a breakdown product of estrogen called estrone sulfate, compared to women not drinking alcohol. Women who consumed 30 grams of alcohol per day showed an even greater increase (10.7%), compared to women not drinking alcohol. Similar increases were seen in another hormone called dehydroepiandrosterone sulfate (DHEAS).

Even One Drink a Day Could Increase Risk

"Our results, suggest that even one drink a day could increase breast cancer risk," Dorgan says, pointing out that hormone levels appeared to increase as the number of drinks increased.

"Most people agree that at higher levels of intake — such as more than three drinks a day — alcohol increases breast cancer risk," says Dorgan. "At lower levels, there is some controversy, which is one of the reasons we did this study," she says.

The study authors note that this is the first study to evaluate under controlled conditions the effects of chronic, moderate alcohol ingestion on levels of serum estrogens and androgens in postmenopausal women.

Dorgan recommends that women might want to consider discussing with their physicians whether they should or should not drink at all. "A physician can advise a woman by taking into account her individual situation," she says.

Cancer and Heart Disease Guidelines Conflict

Michael Thun, MD, vice president of epidemiology and surveillance for the American Cancer Society (ACS), advises "the most important thing to understand is that even at levels of moderate drinking — not exceeding one drink of alcohol daily — the current evidence suggests that there is some increase in breast cancer risk."

"One drink of alcohol a day, however, may reduce the risk of heart disease, so the net effect on a woman’s health depends to a large extent on her age and her risk of breast cancer, and of heart disease," Thun says, noting that alcohol is the one case in which cancer and heart guidelines are in conflict.

"The risk of breast cancer and other cancers increases as alcohol consumption increases," Thun notes. "But after menopause, the reduction in risk of heart attacks and strokes associated with one or two drinks a day is greater than the increase in breast cancer risk for nearly all women," he qualifies.

A new study from the University of Michigan Health System suggests that a compound in green tea may provide therapeutic benefits to people with rheumatoid arthritis.

The study, presented April 29 at the Experimental Biology 2007 in Washington, D.C., looks at a potent anti-inflammatory compound derived from green tea. Researchers found that the compound – called epigallocatechin-3-gallate (EGCG) – inhibited the production of several molecules in the immune system that contribute to inflammation and joint damage in people with rheumatoid arthritis.

The compound from green tea also was found to suppress the inflammatory products in the connective tissue of people with rheumatoid arthritis.

“Our research is a very promising step in the search for therapies for the joint destruction experienced by people who have rheumatoid arthritis,” says Salah-uddin Ahmed, Ph.D., lead researcher on the study. Ahmed, a research investigator with the Division of Rheumatology at the U-M Health System, was selected to present the research at the Experimental Biology meeting as the recipient of the Young Scientist Travel Award, given by the American Society for Pharmacology and Experimental Therapeutics. This study was also selected by the American Society for Nutrition to be featured in a press release.

To conduct the research, the scientists isolated cells called synovial fibroblasts from the joints of patients with rheumatoid arthritis. These fibroblasts – cells that form a lining of the tissue surrounding the capsule of the joints – then were cultured in a growth medium and incubated with the green tea compound.

The fibroblasts were then stimulated with pro-inflammatory cytokine IL-1β, a protein of the immune system known to play an important role in causing joint destruction in people with rheumatoid arthritis.

The researchers looked at whether the green tea compound has the capability to block the activity of two potent molecules, IL-6 and cyclooxygenase-2 (COX-2), which also are actively involved in causing bone erosion in the joints of people with rheumatoid arthritis.

When untreated cells were stimulated with IL-1β, a sequence of molecular events occurred that resulted in production of the bone-destructive molecules. But the scientists found that pre-incubation with EGCG was capable of inhibiting the production of these molecules. EGCG also inhibited the production of prostaglandin E2, a hormone-like substance that causes inflammation in the joints.

The cell signaling pathways that regulate levels of these immune system molecules under both normal and rheumatoid arthritis situations are well studied, and the researchers were able to trace the effects of the green tea compound infusion to see that it worked by inhibiting these pathways.

Ahmed says that these studies suggest that EGCG or molecules that could be derived synthetically from the EGCG found in green tea may be of therapeutic value by inhibiting the joint destruction in rheumatoid arthritis.

Previously, Ahmed and other researchers made another promising finding when EGCG-pretreated synovial fibroblasts were stimulated with the cytokine IL-1β to study the protective effect of this green tea compound. Compared to untreated synovial fibroblasts, the cells treated with EGCG markedly blocked the ability of IL-1β to produce the proteins and enzymes that infiltrate the joints of persons with rheumatoid arthritis and cause cartilage degradation.

The laboratory now is focused on the inhibitory role of EGCG in gene expression. The scientists plan to test EGCG in animal models of rheumatoid arthritis to see if it provides similar therapeutic or preventive effects. Ahmed believes that the outcome of these studies will form a strong foundation for future testing of green tea compound in humans with rheumatoid arthritis.

A Cherry on Top: Animal Study Suggests Tart Cherries Can Alter Factors Linked to Heart Disease and Diabetes

Tart cherries may be good for more than just making pie, according to new data from an animal study conducted by University of Michigan Health System researchers.

In a study involving rats, the researchers report that animals that received powdered tart cherries in their diet had lower total cholesterol, lower blood sugar, less fat storage in the liver, lower oxidative stress and increased production of a molecule that helps the body handle fat and sugar, compared with rats that didn't receive cherries as part of an otherwise similar diet. All of the rats had a predisposition toward high cholesterol and pre-diabetes, but not obesity.

All the measures on which the two groups of animals differed are linked to metabolic syndrome, a collection of risk factors linked to high rates of heart disease and Type 2 diabetes. Tens of millions of Americans have metabolic syndrome; most don't know it.

The researchers say the correlation between cherry intake and significant changes in metabolic measurements suggest a positive effect from the high concentrations of antioxidant compounds called anthocyanins that are found in tart cherries. The new results were given today in an oral presentation at the Experimental Biology 2007 meeting in Washington, D.C.

It's not yet known if cherry-rich diets might have a similar impact in humans, but a U-M team will soon launch a small clinical trial to start to find out. Meanwhile, additional research is being carried out in animals prone to both obesity and diabetes.

The study's lead author is E. Mitchell Seymour, M.S., a U-M research associate and supervisor of the U-M Cardioprotection Research Laboratory, which studies the potential preventive benefits of antioxidant-rich foods. Support for the new study comes from an unrestricted grant from the Cherry Marketing Institute, a trade association for the cherry industry. CMI has no influence on the design, conduct or analysis of any U-M research it funds.

Seymour and the laboratory's director, U-M cardiac surgeon Steven Bolling, M.D., caution that their results cannot be directly translated into humans. But they are encouraged by the positive signs seen in the new data.

- "Rats fed tart cherries as 1 percent of their total diet had reduced markers of metabolic syndrome," says Seymour. "Previous research by other groups studied pure anthocyanin compounds rather than anthocyanin-containing whole foods, and they used concentrations of anthocyanins that would be very difficult if not impossible to obtain in the diet."

Cherries and metabolic syndrome risk factors

He continues, "We are interested in a whole-foods approach, using amounts of fruit that are relevant to human diets. We are enthusiastic about the findings that tart cherries conferred these beneficial effects at such a modest daily intake."

The potential for protective effects from antioxidant-rich foods and food extracts is a promising area of research, says Bolling, who is the Gayle Halperin Kahn Professor of Integrative Medicine, a professor of cardiac surgery, co-director of U-M Integrative Medicine and member of the U-M Cardiovascular Center.

- These data from whole tart cherries join other findings that suggest a correlation between anthocyanin intake and reductions in cardiovascular and metabolic risk factors," he says. "But there is still a long way to go before we can advocate any course of action for humans.

Still, the growing body of knowledge is encouraging."

Bolling and Seymour performed the study using 48 male Dahl Salt-Sensitive rats, which are bred for their susceptibility to salt-linked high blood pressure, high cholesterol and impaired glucose tolerance.

For 90 days beginning in their sixth week of life, the rats were fed either a carbohydrate-enriched diet or a diet that, by weight, included 1 percent cherries or 10 percent cherries. The higher cherry dose was used to look for any toxic effects; none were seen.

The cherries were Montmorency tart cherries grown in northern Michigan, frozen, and powdered. Michigan is the nation's largest producer of tart cherries, which are used in pies and jams as well as juice. They are different from the sweet Bing cherries that are often eaten raw, and have higher concentrations of antioxidant anthocyanins than sweet cherries.

By the end of the study, the rats that received the 1-percent cherry diet had total cholesterol, triglyceride, glucose and insulin levels that were significantly lower than those of the rats that did not receive cherries. The same was true for those on the 10-percent cherry diet, compared with rats that received a diet with an equivalently high level of carbohydrates not from cherries.

The researchers also measured plasma TEAC, a measure of antioxidant capacity in the blood on which a higher reading means better ability to neutralize damaging free radical molecules produced in the body during metabolism. The rats that received cherries had higher antioxidant capacity, indicating lower oxidative stress in their bodies, than those that did not.

In addition to blood measures, the researchers measured the level of fat in the livers of the rats, and the genetic expression of PPAR (peroxisome proliferator-activating receptor) in the liver.

The "fatty liver" measure is important because the storage of excess energy as fat in the liver is a common effect in metabolic syndrome - and because it feeds the vicious cycle of increased cholesterol and decreased response to insulin that can lead to cardiovascular disease and Type 2 diabetes.

Meanwhile, the measure of PPAR messenger RNA in the liver reflects the readiness of the liver tissue to express functional PPAR. PPAR is important to the process by which the body burns fat instead of storing it, and it is important in the formation of blood lipids like LDL, typically known as the "bad cholesterol". Drugs in the classes known as thiazolidinediones and glitazars activate PPAR and are often used to manage high cholesterol and risk for Type 2 diabetes.

In the current study, the rats that received cherries had both a lower level of fat in their livers, and a higher expression of the PPAR gene, than those that did not - and the correlation between the two was dose-dependent.

Now, the Cardioprotection Laboratory team has embarked on a new study in rats that have Type 2 diabetes, both with and without obesity and in the presence of low-fat and high-fat diets. They will look at whether tart cherries have an impact on the storage of fat in fat tissue and in muscle, and on the production of specific blood lipids like LDL and HDL. In addition, they will characterize cherries chemically, to assess the levels of phytochemicals in whole cherries, cherry juice and dry cherries.

Meanwhile, U-M Integrative Medicine co-director Sara Warber. M.D., an assistant professor of family medicine at the U-M Medical School, will lead a pilot clinical trial of whole tart cherries in humans. The study will enroll healthy individuals who will spend a night at the U-M General Clinical Research Center, and have their blood tested multiple times to look for the breakdown products of cherries.

A new study shows that aspirin therapy for coronary artery disease is four times more likely to be ineffective in women compared to men with the same medical history.

Historically, studies have shown that aspirin therapy is less effective in women than in men, but it has remained unclear how much less effective and whether this affects patient outcomes, said Michael Dorsch, clinical pharmacist and adjunct clinical instructor at the University of Michigan College of Pharmacy.

Dorsch is the lead author of the paper, "Aspirin Resistance in Patients with Stable Coronary Artery Disease," which appears online today in the Annals of Pharmacotherapy.

Originally, Dorsch and his team set out to determine if patients with a history of heart attacks were more apt to be aspirin resistant than those with coronary artery disease but no history of heart attack. They found that gender and not medical history was a predictor for aspirin resistance, Dorsch said. The results surprised him.

"I was surprised by how big of a difference it was for females," said Dorsch, who has appointments at the U-M Health System and the U-M College of Pharmacy, and started the study as a resident at the University of North Carolina. "This is another piece of information that affirms we need more studies in women."

Aspirin therapy is a cornerstone in managing heart disease because it inhibits blood clotting. Aspirin therapy can reduce the risk of a nonfatal heart attack or stroke by about 23 percent, and an estimated 20 million men and women take a low dose of aspirin (81-325 mg daily) to control heart disease. But despite its effectiveness, there is evidence that aspirin is less effective in some patients, and researchers don't really know why. This can be frightening because most doctors do not check for aspirin resistance before prescribing aspirin therapy and therefore presume it's working in the patient when it may not be, he said.

There isn't enough evidence to show if people who are aspirin resistant can simply take larger doses, but Dorsch warns that people taking aspirin on the advice of a doctor shouldn't stop therapy on account of these results.

Not only did the study quantify how much more effective aspirin therapy is for men than for women, it is also the first study that Dorsch knows of to measure aspirin resistance in men and women with stable coronary artery disease. Previous studies have looked at the impact of aspirin therapy on people who have had a heart attack.

For the study, researchers randomly selected 100 patients who were visiting their cardiologist for a regularly scheduled appointment. All had coronary artery disease but only half had a history of heart attack. Researchers used a device called VerifyNow Aspirin Assay to test the percentage of platelet reactivity after blood samples were exposed to a chemical that causes clotting.

Aspirin works by causing platelet inhibition in the blood, which means that platelets cannot stick together and this slows the formation of blood clots that cause a heart attack or stroke.

"This does happen in women, but it doesn't happen in as many women and it's not as effective," Dorsch said. The testing device uses an optical sensor to "see" what percentage of the platelets in the blood sample clump together. Anything less than 40 percent platelet inhibition is considered aspirin resistant.

"We really don't know the mechanism," Dorsch said. "It could be that women have a more active platelet system in the body so it's less likely that platelet action would be inhibited."

In the future, researchers hope to look at aspirin therapy outcomes in women only and see if those outcomes can be changed. The majority of testing for aspirin therapy has been on men, so not much is known about how women respond.

"Heart disease is the number one killer of women in the United States. Future research should be aimed at finding out the cause of this increase in aspirin resistance and the effect on outcomes in women with heart disease." Dorsch said.

Compelling evidence that herbs and spices found prevalent in many popular dishes can help ward off disease remains elusive but, according to the latest issue of Food Technology magazine, some small clinical trials raise the question of whether some positive health influence exists.

“Throughout recorded history, spices and herbs have been valued for their curative powers,” writes Roger A. Clemens, Ph.D., spokesperson for the Institute of Food Technologists and functional food expert with IFT. “The use of herbs and spices to treat or prevent [health conditions] is almost universal among non-industrialized societies.”

However, Clemens and co-author Peter Pressman, M.D., diet and health expert with IFT and a practicing internist, note that nearly 70 clinical studies on spices and their affect on cardiovascular health and cholesterol have yielded inconsistent results.

Some extracts of ginger, peppers, mint, and other flavorings exhibit natural anti-inflammatory properties in some cell and animal studies, while antioxidants found in oregano, dill, garlic and elsewhere may affect some cancer processes, the article states.

The key drawback for identifying spices’ actual influence on health may be in the relatively small amount that’s ordinarily added to food, the authors surmise. “The classic definition of spice is a substance used in nutritionally insignificant quantities for the purpose of flavoring,” they write.

Clemens and Pressman concur that existing studies linking herbs and spices to health maintenance are intriguing, and that larger studies that account for amounts eaten and body responses must be conducted to assess the true value of herbs and spices on cardiovascular disease, cancer, diabetes, and general health.

For many men with early-stage prostate cancer, sorting out the treatment options can be overwhelming. Yet they feel pressured to choose a course of therapy quickly. The first issue of a new quarterly bulletin about prostate disease published by Harvard Medical School says that the most important thing to do is to take your time and make sure you explore all treatment choices thoroughly.

The inaugural issue of Perspectives on Prostate Disease explains that treatment decisions can be complicated for a number of reasons. First, there’s no one-size-fits-all treatment for early-stage prostate cancer. Even the experts do not agree about which men with such cancers should be treated, which therapy is best—or whether, for some tumors, treatment is even necessary. Indeed, doctors are now advising many patients to undertake a program of “active surveillance” rather than pursue aggressive treatment. The choice can become even more difficult when a man takes into account the side effects of treatment, which can be devastating to his quality of life.

Marc B. Garnick, M.D., Harvard oncologist and editor-in-chief of Perspectives, says, “For all these reasons, I encourage patients to ask detailed questions and perform due diligence to ensure that they are making the right decisions about their medical care. Due diligence begins with having the confidence to question your physician about treatment recommendations—after all, you are the person who has to live with the results.”

Garnick recommends men also consider these questions:
• Will you be able to deal with impotence if it occurs? What about incontinence?
• How will the possible side effects of treatment affect your relationship with your partner—and your sense of self?

It’s vital to think about these issues carefully: Studies show that 30% to 70% of men treated with surgery or radiation therapy experience impotence, and at least 1% to 2% experience urinary incontinence—and some experts think the true numbers are much higher. According to Garnick, truly informed patients are much better able to deal with adverse consequences than patients who don’t have the all the facts, or who rush into making a decision.

Also covered in the 48-page first issue of this quarterly bulletin:
• When to consider active surveillance
• A patient’s story: Why one man opted for lifestyle changes instead of treatment
• A patient’s story: Why one man chose robotic-assisted laparoscopic prostatectomy
• Medication for benign prostatic hyperplasia: When to consider a change
• Harvard experts discuss drug treatments for benign prostatic hyperplasia
• A guide to finding the studies cited in the newsletter, so you can evaluate the evidence for yourself.

In each issue of Perspectives on Prostate Disease, you’ll find:
• Roundtable discussions: Join a group of Harvard physicians as they debate key issues in the diagnosis and treatment of prostate disease.
• Patient interviews: Benefit from the shared experiences of men who have confronted prostate disease.
• Prostate disease news and research findings: Be among the first to know about breakthroughs you won’t hear about on the news.
A year’s subscription to Perspectives on Prostate Disease is available for $99 (for print and electronic versions; $89 for electronic only) from Harvard Health Publications, the publishing division of Harvard Medical School. Order it online at http://www.health.harvard.edu/POPD or by calling 1-877–649–9457 (toll free).

Probiotics, the “good” bacteria in many dietary supplements, might counteract an unpleasant side effect for children on antibiotics, according to a new systematic review.

Antibiotics commonly used to treat children with conditions such as respiratory tract and skin infections can cause antibiotic-associated diarrhea (AAD). Estimates indicate that between 11 percent and 40 percent of children taking antibiotics suffer from AAD.

Parents have routinely given children over-the-counter diarrhea medicines, such as Kaopectate or Imodium A-D, but some are turning to other remedies. One alternative has been to give probiotics — dietary supplements containing healthy bacteria or yeasts that can help to restore the body’s natural balance.

The systematic review aimed to assess whether probiotics actually reduce the incidence of AAD in children and if children should take probiotics over common diarrhea medications on a routine basis.

“Probiotics offer an excellent safety profile in healthy children and seem to be effective in preventing AAD in children,” said review co-author Sunita Vohra, M.D. “Public interest in natural health products is high and given how commonly diarrhea occurs in children prescribed antibiotics, we think that many families will be interested in our findings.”

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

AAD occurs when antibiotics disturb the body’s natural balance of “good” and “bad” bacteria and thereby interfere with normal digestion. AAD symptoms include frequent watery bowel movements and abdominal cramps. Those with severe cases can suffer from dehydration and electrolyte imbalances.

The Cochrane reviewers analyzed 10 studies that tested 1,986 children from birth to 18 years old, who received antibiotics to treat a medical condition along with probiotics to prevent AAD. Children were given between five and 15 days of oral antibiotics such as amoxicillin, cefotaximine and erythromycin.

The probiotics given to children included Lactobacillus GG, Lactobacillus sporogenes, Streptococcus thermophilus and Saccharomyces boulardii. Daily doses varied from 20 billion to 40 billion colony-forming units.

The studies used various methods to compare children who received probiotics to those who received another type of treatment— a placebo, conventional antidiarrheal medications or no treatment at all.

“Conventional antidiarrheal medications may also be effective, but unless the diarrhea is severe, parents and health care providers are generally averse to prescribing a second medication,” said Vohra, associate professor in the department of pediatrics at the University of Alberta in Canada.

Results from nine studies found that probiotics reduced the incidence of AAD, and four studies reported that probiotics shortened the average duration of diarrhea symptoms by about three-quarters of a day.

Choosing between over-the-counter medicines and probiotics may not be the issue for parents and children in some parts of the world, according to Alfred Bartlett, M.D., a pediatrician and senior advisor for child survival at the U.S. Agency for International Development.

Bartlett said his agency’s work in numerous countries has shown that replacing fluids to prevent dehydration, providing proper nutrition and administering zinc supplements have proven key to treating diarrhea in children.

“There’s been on-again-off-again talk about probiotics for diarrhea, but the science is not solid enough to make a major program investment in more research,” Bartlett said. “In comparison, there have been multiple trials done around the world that have proven fluids, feeding and zinc are effective.”

Although the Cochrane findings were statistically significant, the reviewers concluded that there was not sufficient evidence to advise physicians to recommend probiotics to prevent AAD routinely. They did reveal, however, that Lactobacillus GG or Saccharomyces boulardii appear to be the most effective. According to Vohra, these supplements will garner more attention in the future

“In modern medical school curriculum, physicians have not been taught extensively about many natural health products and probiotics have generally been overlooked,” Vohra said. “This is changing, and we are aware of at least some hospitals that now carry probiotics on formulary.”

Older adults who don’t get enough vitamin D – either from their diets or exposure to the sun – may be at increased risk for poor physical performance and disability, according to new research from Wake Forest University School of Medicine and colleagues.

“With a growing older population, we need to identify better ways to reduce the risk of disability,” said lead author Denise Houston, Ph.D. “Our study showed a significant relationship between low vitamin D levels in older adults and poorer physical performance.”

The results are reported in the April issue of the Journal of Gerontology: Medical Sciences.

About one-fourth of people over age 60 have low vitamin D levels. Previous research has shown that vitamin D not only plays a role in bone health, but possibly also in protecting against diabetes, cancer, colds and tuberculosis.

“Recent findings showing the importance of vitamin D status on multiple health outcomes underscore the need for more research on the effects of low vitamin D levels in elderly populations,” said Houston, an instructor in internal medicine - gerontology.

Vitamin D is naturally produced when skin is exposed to the sun’s ultraviolet rays. Foods such as fortified milk, juice and cereals also contain vitamin D, but it is difficult to get enough through diet alone, said Houston.

Older adults are particularly prone to low vitamin D levels because they may get less exposure to sunlight and because their skin is less efficient in producing vitamin D from sun exposure compared to younger adults. Older adults also may not get enough vitamin D from dietary sources.

“There is a growing awareness that the prevalence of low vitamin D levels is common among the elderly,” said Houston.

For the current study, researchers analyzed data from the InCHIANTI study, which evaluated factors contributing to the decline of mobility in late life. The study involved 976 people who were 65 years and older from two towns in the Chianti area of Italy. The mean age of participants was 74.8 years. Data were collected from Sept. 1998 through March 2000.

Participants completed a short physical performance test of their walking speed, ability to stand from a chair and ability to maintain their balance in progressively more challenging positions. In addition, handgrip strength, a predictor of future disability, was measured using a hand-held dynamometer.

The researchers found that physical performance and grip strength were about five to 10 percent lower in those who had low levels of vitamin D. After looking at other variables that could influence the results, such as body mass index, physical activity, the season of the year, mental abilities, health conditions and anemia, the results held true.

The study wasn’t designed to evaluate whether low vitamin D levels actually cause poor physical performance, but the results suggest the need for additional research in this area, said Houston. She said vitamin D plays an important role in muscle function, so it is plausible that low levels of the vitamin could result in lower muscle strength and physical performance.

“But it’s also possible that those with poor physical performance had less exposure to sunlight resulting in low vitamin D levels,” she said.

Current recommendations call for people from age 50 to 69 to get 400 international units (IUs) of vitamin D per day and for those over age 70 to get 600 IUs. Many researchers, however, suggest that higher amounts may be needed.

“Higher amounts of vitamin D may be needed for the preservation of muscle strength and physical function as well as other conditions such as cancer prevention,” said Houston. “The current recommendations are based primarily on vitamin D’s effects on bone health.”

Also see "new-studies-back-vitamin-d-for-cancer prevention":
http://healthnewsreport.blogspot.com/2007/02/2-new-studies-back-vitamin-d-for-cancer.html

The risk of developing Parkinson’s disease may be reduced with moderate to vigorous exercise or other recreational activities, according to research that will be presented at the American Academy of Neurology’s 59th Annual Meeting in Boston, April 28 – May 5, 2007.

The study followed more than 143,000 people with an average age of 63 over 10 years. In that time, 413 people developed Parkinson’s disease. Researchers found that those with moderate to vigorous activity levels were 40 percent less likely to develop Parkinson’s disease than those with no or light activity levels. Those with moderate to vigorous activity were exercising an average of a half hour per day or more.

“This study does not prove that exercise caused the lowered risk of Parkinson’s disease – it’s possible that something else lowers the risk,” said the study’s lead author Evan L. Thacker, SM, from the Harvard School of Public Health in Boston, MA. “But considering all of the other benefits of exercise, it certainly doesn’t hurt to make sure you get some moderate or vigorous exercise several times a week.”

The researchers also looked at the participants’ activity level at age 40 and found that there was no significant relationship between the level of physical activity at age 40 and the risk of developing Parkinson’s disease.

“If exercise truly does provide some protection against Parkinson’s disease, the protection may be relatively short term,” Thacker said. “However, in a previous study with a similar prospective design activity in early adulthood was related to lower risk for Parkinson’s disease, so the jury’s still out on this one.”

Study shows food preparation may play a bigger role in chronic disease than was previously thought

How your food is cooked may be as important to your health as the food itself. Researchers now know more about a new class of toxins that might soon become as important a risk factor for heart disease and metabolic disorders as trans fats.

This class of toxins, called advanced glycation end products (AGEs), are absorbed into the body through the consumption of grilled, fried, or broiled animal products, such as meats and cheeses. AGEs, which are also produced when food products are sterilized and pasteurized, have been linked to inflammation, insulin resistance, diabetes, vascular and kidney disease, and Alzheimer’s disease.

A new study at Mount Sinai School of Medicine reveals that AGE levels are elevated in the blood of healthy people, and even more so in older individuals than in younger people. Of particular interest was the finding that a major determinant of the blood levels of AGEs is the amount of AGEs in the diet, not dietary calories, sugar, or fat. The study, which was done in collaboration with, and supported by, the National Institute on Aging (NIA), is published in the April issue of the Journal of Gerontology: Medical Sciences.

"AGEs are quite deceptive, since they also give our food desirable tastes and smells," says Helen Vlassara, MD, senior study author, Director of the Division of Experimental Diabetes and Aging, and Professor of Medicine and Geriatrics at Mount Sinai School of Medicine. "So, consuming high amounts of grilled, broiled, or fried food means consuming significant amounts of AGEs, and AGEs in excess are toxic. People should be given information about their AGE intake and be advised to consider their intake in the same way they would think about their trans fats and salt intake. They should be warned about their AGE levels the way they are about their cholesterol levels or cigarette smoking."

Inflammation and oxidative stress are more common in older age, so the goal of the study was to assess whether AGEs played a significant role in age-related inflammation and oxidative stress by measuring AGE levels in both young and older individuals. The study involved 172 healthy men and women who were divided into two age groups—those between the ages of 18 and 45 and those between the ages of 60 and 80. Dr. Vlassara and her team also wanted to assess whether AGE levels correlated with dietary intake. To do this, her team recorded the patient’s body weight, body fat, three-day dietary information, and collected blood samples to measure biomarkers of inflammation, such as C-reactive protein (CRP). Blood samples were used to test for two common AGEs, called carboxymethyllysine (CML) and methylglyoxal (MG), which latch on to proteins and fats.

The blood tests showed that AGE levels were 35 percent higher in individuals age 65 and older compared with those younger than age 45. The study also showed that in all of the participants, the higher the consumption of foods rich in AGEs, the higher the blood levels of AGEs, and higher the levels of CRP and other markers of inflammation.

Much to the researchers’ surprise, the study also showed that AGE levels could be very high in young healthy people. In fact, high AGE levels found in some healthy adults in this study were on par with AGE levels observed in diabetic patients in their earlier studies. The fact that healthy adults had levels similar to those seen in diabetic patients may suggest that early and prolonged exposure to these substances in the diet could accelerate the onset of diseases. Dr. Vlassara notes that the availability and consumption of AGE-rich foods is high and correlates with rising rates of diabetes and heart disease.

"Excessive intake of fried, broiled, and grilled foods can overload the body’s natural capacity to remove AGEs," Dr. Vlassara notes, "so they accumulate in our tissues, and take over the body’s own built-in defenses, pushing them toward a state of inflammation. Over time, this can precipitate disease or early aging." Once AGEs enter the body, it becomes more difficult to get them out, especially as people age. Older people have a reduced capacity for removing AGEs from the body, the researchers explain, most likely because kidney function slows down as the body ages.

As Dr. Vlassara cautions, "although the accumulation of AGEs pose an immediate and significant health threat to the older adult population, they are also an invisible, lingering danger especially for younger people and this needs to be addressed. AGE levels should be shown on nutrition labels so everyone is aware of them when buying or preparing meals – and our studies explain why."

A Simple Solution: Steam, Boil, Stew Despite the ubiquity of AGEs, Dr. Vlassara and her team offer simple, safe, and economic solutions that echo the recommendations given concerning trans fats—watch what you eat. New methods of cooking to reduce AGE intake, particularly steaming, boiling or making stews, can make a difference. "Keeping the heat down and maintaining the water content in food reduces AGE levels," Dr. Vlassara says. A 50 percent reduction in AGE intake could have a significant and positive impact on overall health and may even help extend one’s lifespan, according to Dr. Vlassara. In other studies, the team has found that cutting AGE intake in half, but maintaining a diet comprised of the same calories and fat, increased the lifespan of animals when compared with animals fed their usual diet.

At the moment, changing one’s approaches to cooking is the only defense against excessive AGE consumption. There is no routine clinical test to inform individuals of their blood or dietary AGE levels nor established treatment to reduce high AGE blood levels. "The concept that food-related AGE intake is harmful is new to the general public," says Dr. Vlassara, "and scientists are now seeing how AGE intake fits with the current trends of disease epidemics. Hopefully, these wake-up signals, together with other gathering evidence at the cellular and molecular level, will accelerate our efforts to develop effective measures against excessive dietary AGEs. This issue, however, should be dealt with as an important health hazard now, rather than later."

Corn, oats, cherries and red wine’s high melatonin content can help delay ageing

- A study carried out by researchers from the University of Granada’s Institute of Biotechnology proves that consuming melatonin neutralizes oxidative damage and delays the neurodegenerative process of ageing.
- In this study researchers used normal and genetically-modified mice which were subjected to accelerated cell ageing, although their results can also be applied to humans.

C@MPUS DIGITAL The Spanish Ageing Research Network (Red Nacional de Investigación del Envejecimiento), funded by Carlos III Health Institute and headed by professor Darío Acuña Castroviejo, from the University of Granada (Universidad de Granada), is very near to achieving one of today’s Science greatest goals: allowing humans to age in the best possible health conditions.

As well as from the UGR, researchers from the Spanish universities of Seville, Oviedo, Saragossa, Barcelona and Reus also took part in this study, concluding that the consumption of melatonin – a natural substance produced in small amounts by human beings and present in many types of food – delays the oxidative damage and inflammatory processes typical of the old age. Melatonin can be found in small amounts in some fruits and vegetables, like onions, cherries and bananas, and in cereals like corn, oats and rice, as well as in some aromatic plants, such as mint, lemon verbena, sage or thyme, and in red wine.

UGR participation in this study was leaded by professor Darío Acuña Castroviejo, member of the Institute of Biotechnology and lecturer at this University’s department of Physiology. Professor Acuña Castroviejo also coordinates the Spanish Ageing Research Network. Both normal and genetically-modified mice, with an accelerated cell ageing, were analysed. "We proved", says professor Acuña Castroviejo, “that the first signs of ageing in animal tissues start at the age of five months [in mice] – equivalent to 30 human years of age – due to an increase in free radicals (oxygen and nitrogen), which cause an inflammatory reaction.”

The UGR researcher points out that such oxidative stress also has effects in animals’ blood, as blood cells have been proven to be “more fragile with the years and, therefore, their cell membranes become easier to break".

Use in mice

The authors of this innovative finding administered small amounts of melatonin to mice and observed that not only did this substance neutralize the oxidative stress and the inflammatory process caused by ageing, but it also delayed its effects, thus increasing longevity. In particular, the University of Granada’s goal was to analyse the mitochondrial function in mice and check their mitochondrial capacity to produce ATP – adenosine triphosphate – a molecule whose mission is to store the energy every cell needs to carry out its functions.

Professor Acuña Castroviejo highlights that chronic administration of melatonin in animals from the moment they stop producing this substance – five months of age in mice – helps counteract all age-related processes. Therefore, daily melatonin intake in humans from the age of 30 or 40 could prevent – or, at least, delay – illnesses related to ageing, free radicals and inflammatory processes, such as many neurodegenerative disorders (e.g. Parkinson's disease) and complications linked to other illnesses, like diabetes.

The researcher is confident that the Spanish Ministry of Health will soon legalise the use of melatonin since, being a substance naturally produced by the body, it cannot be patented and the drug industry would not make much profit out of its artificial production. However, “while the substance becomes legalised, humans should try to increase melatonin consumption through food", recommends professor Acuña Castroviejo.

The results of this study have been published in some of the world’s most prestigious medical journals, such as Free Radical Research, Experimental Gerontology, Journal of Pineal Research and Frontiers in Bioscience.

The U.S. Food and Drug Administration (FDA) has caused an unnecessary scare about some pain relievers by adding a warning to drugs that are safe, says Curt Furberg, M.D., Ph.D., from Wake Forest University School of Medicine. At the same time, he says the agency has failed to recognize the harm of a pain reliever that should be taken off the market.

"The FDA is adding 'black box' warnings to all prescription and over-the-counter pain relievers – even to naproxen – which the evidence shows is safe," said Furberg, who serves on the FDA Drug Safety and Risk Management Advisory Committee. "This is based on the false assumption that all nonsteroidal anti-inflammatory drugs increase the risk of heart attacks. In fact, there are major differences between these agents."

In a commentary published by Trials (http://www.trialsjournal.com/content/8/1/13), an online journal of BioMed Central, Furberg says the FDA has failed to recognize current scientific evidence when it made decisions on the safety of nonsteroidal anti-inflammatory drugs (NSAIDs) that are often used to treat the pain or inflammation from arthritis.

The most commonly used NSAIDs are ibuprofen (Advil®), naproxen (Aleve®), and diclofenac (Voltaren®). There are more than a dozen others, including drugs such as celecoxib (Celebrex®) that are in a special class known as selective COX-2 inhibitors because of the hormone they target. The other NSAIDs are known as "non-selective."

Furberg said while the evidence for the non-selective NSAIDs is somewhat limited, an analysis combining several small studies found that high doses (500 mg twice daily) of Aleve were not associated with an increased risk of heart attacks compared to a placebo, or an inactive pill.

On the other hand, high doses of Advil (800 mg three times a day) and Voltaren (75 mg twice daily) were associated with rates of heart attack that were 51 percent and 63 percent higher, respectively, than placebo. An analysis of a large number of trials comparing COX-2 inhibitors to other NSAIDs found similar results – that Voltaren was estimated to increase vascular risk by about 70 percent over Aleve.

"Naproxen does not increase the risk of heart attacks and ought to be a painkiller of choice," said Furberg. "On the other hand, Voltaren carries the same risk as the harmful COX-2 inhibitors Bextra® and Vioxx®, which have been taken off the market.

"The FDA has failed to recognize the evidence that the risk of heart attack varies substantially among this group of drugs and that Voltaren has the highest risk of all. Since it is the most commonly used NSAID, the unrecognized harm it has caused worldwide could be enormous."

The European Regulatory Agency has reviewed the same evidence that the FDA considered and reached entirely different conclusions, said Furberg. He said this suggests that the decisions are not based on scientific evidence.

With Celebrex, the FDA didn't follow the recommendations of its Advisory Committee to substantially restrict the drug's use. Instead, it required only a "vaguely worded" black box warning, said Furberg. European countries require clear warnings for patients at high risk of heart attacks and have said COX-2 inhibitors should not be taken by patients with heart disease.

With the non-selective NSAIDs, Europe has given a "clean bill of health" to the agents and the FDA has judged them to have similar risks to Celebrex and is adding "black box" warnings.

"Decisions by regulatory agencies are expected to follow explicit regulations and should be evidence-based," said Furberg. "Scientific studies point to clinically important differences among the non-selective NSAIDs, which the FDA has not recognized. It's time for the FDA to set the record straight."

Antioxidant found in many foods and red wine is potent and selective killer of leukemia cells

University of Pittsburgh researchers show compound kills leukemia cells while sparing normal, healthy cells

A naturally occurring compound found in many fruits and vegetables as well as red wine, selectively kills leukemia cells in culture while showing no discernible toxicity against healthy cells, according to a study by researchers at the University of Pittsburgh School of Medicine. These findings, which were published online March 20 in the Journal of Biological Chemistry and will be in press on May 4, offer hope for a more selective, less toxic therapy for leukemia.

“Current treatments for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for many years afterward. So, there is an intensive search for more targeted therapies for leukemia worldwide,” said corresponding author Xiao-Ming Yin, M.D., Ph.D., associate professor of pathology, University of Pittsburgh School of Medicine.

Leukemia is not a single disease but a number of related cancers that start in the blood-forming cells of the bone marrow. Meaning literally “white blood” in Greek, leukemia occurs when there is an excess of abnormal white blood cells. There are both acute and chronic forms of leukemia, each with many subtypes that vary in their response to treatment. According to the National Cancer Institute, about 44,000 new leukemia cases will be diagnosed in the United States in 2007, and there will be about 22,000 leukemia-related deaths.

Based on previous reports that anthocyanidins, a group of naturally occurring compounds widely available in fruits and vegetables as well as red wine, have chemopreventive properties, Dr. Yin and his collaborators studied the effects and the mechanisms of the most common type of a naturally modified anthocyanidin, known as cyanidin-3-rutinoside, or C-3-R, which was extracted and purified from black raspberries, in several leukemia and lymphoma cell lines.

They found that C-3-R caused about 50 percent of a human leukemia cell line known as HL-60 to undergo programmed cell death, or apoptosis, within about 18 hours of treatment at low doses. When they more than doubled the concentration of C-3-R, virtually all of the leukemia cells became apoptotic and died. C-3-R also induced apoptosis in other human leukemia and lymphoma cell lines.

When the investigators studied the mechanism of cell death in the leukemia cells, they found that C-3-R induced the accumulation of peroxides, a highly reactive form of oxygen, which, in turn, activated a mitochondria-mediated apoptotic pathway. Mitochondria are specialized structures located within all cells in the body that contain enzymes needed by the cell to metabolize foodstuffs into energy sources. In contrast, when the researchers treated normal human blood cells with C-3-R, they did not find any increased accumulation of reactive oxygen species and there were no apparent toxic effects on these cells.

Previous studies have shown that C-3-R possesses strong antioxidant activities, a characteristic shared by other polyphenols, such as those found in green tea, which could be responsible for their chemoprevention effects. Dr. Yin’s work suggests that although C-3-R demonstrates antioxidant effects in the normal cells, it paradoxically induces an oxidative “stress” in the tumor cells. It is possible that this differential effect of C-3-R may account for its selective toxicity in the tumor cells.

According to Dr. Yin, these results indicate that C-3-R has the promising potential to be used in leukemia therapy with the advantages of being highly selective against cancer cells. “Because this compound is widely available in foods, it is very likely that it is not toxic even in purified form. Therefore, if we can reproduce these anti-cancer effects in animal studies, this will present a very promising approach for treating a variety of human leukemias and, perhaps, lymphomas as well.”

American Heart Association meeting report

College-age students who drink heavily may increase their risk for future heart disease, researchers reported at the American Heart Association's 8th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology.

In a small study, Minnesota researchers found that a group of college students who drank heavily had higher levels of C-reactive protein (CRP), a blood marker for inflammation that can increase the risk for heart disease. Increased CRP placed heavy drinkers at moderate risk for cardiovascular disease in early adulthood. Moderate drinkers had the lowest CRP levels.

"These students may be setting themselves up for an increased risk for cardiovascular disease," said Elizabeth Donovan, lead researcher of the study and an undergraduate student at the College of Saint Benedict in St. Joseph, Minn. "This highlights an additional reason to be concerned about heavy drinking in college-age individuals." While most studies of alcohol and CRP levels have focused on older people, this small study examined individuals in early adulthood.

"If high CRP levels are recognized at an early age, the person has a chance to make healthier lifestyle choices," Donovan said.

Twenty-five college-age individuals completed surveys that assessed factors that can affect CRP levels such as alcohol consumption patterns, medication use, smoking habits and recent weight loss. Researchers assigned the students to one of three groups:

non-drinkers, meaning they consumed one or less drinks one day a week;
moderate drinkers, who consumed two to five drinks of alcohol on a typical drinking day, one to two days a week; and
heavy drinkers, who consumed three or more drinks at least three or more days a week or consumed five or more drinks in one sitting at least two or more days a week.
One drink was equal to 12 ounces of beer, five ounces of wine or 1.5 ounces of hard alcohol.

Students on oral contraceptives, hormone therapy, cholesterol-lowering therapy or who had a significant recent weight loss were excluded from the study.

The average CRP for students in the study was 0.9 milligrams per liter (mg/L), placing the group as a whole at low risk. CRP levels less than 1 mg/L are associated with low risk for cardiovascular disease. CRP levels between 1 and 3 mg/L are associated with moderate risk and CRP levels above 3 mg/L are associated with high risk for future cardiovascular disease.

The researchers found that college students who were moderate drinkers had significantly lower CRP levels than heavy drinkers, with the average level at 0.58 mg/L for moderate drinkers, but rising to 1.25 mg/L for heavy drinkers. While the non- or low drinkers had CRP levels of 0.85 mg/L, the difference between them and moderate drinkers was not significant.

"A J-shaped pattern emerged indicating that even in a young, otherwise healthy population, heavy drinking is associated with elevated CRP levels," Donovan said. "CRP levels of individuals who consumed high amounts of alcohol were significantly greater than CRP levels in individuals who consumed moderate amounts. CRP levels in those who consumed no or low amounts of alcohol were greater than those who consumed moderate amounts, but the difference wasn't statistically significant."

The researchers also found these CRP relationships:

CRP levels and a high Body Mass Index were more strongly correlated in males.
Higher consumption of fruit and vegetables were associated with lower CRP levels.
Those with a family history of cardiovascular disease had higher CRP levels.
"While moderate alcohol intake appears to have some health benefits, we must advise against heavy and binge drinking," Donovan said.

Caution should be exercised in interpreting these findings as the results were from a non-random survey of a small group of college students. Researchers suggest further investigation is needed.

The American Heart Association recommends that people who drink alcohol do so in moderation. This means an average of one to two drinks per day for men and one drink per day for women. (A drink is 12 ounces beer, four ounces of wine, 1.5 ounces of 80-proof spirits, or one ounce of 100-proof spirits.).

Drinking alcohol excessively increases such dangers as alcoholism, high blood pressure, obesity, stroke, breast cancer, suicide and accidents. Also, it's not possible to predict in which people alcoholism will become a problem. So the association cautions people not to start drinking alcohol if they do not already. Consult your doctor on the benefits and risks of consuming alcohol in moderation.

Strawberries are good for you, but serving them in daiquiri form may make them even healthier, scientists show.

While exploring ways to help keep strawberries fresh during storage, researchers from Thailand and the US discovered that treating the berries with alcohol led to an increase in antioxidant capacity and free radical scavenging activity within the fruit. While such a boost helped the berries resist decay, the same compounds would also be expected to make the strawberries healthier to eat.

Dr Korakot Chanjirakul and colleagues at Kasetsart University in Thailand, in collaboration with scientists at the United States Department of Agriculture, tested the berries with ethanol and found that the treatment improved the physiology of the fruit as measured by several different laboratory tests for antioxidant activity (SCI’s Journal of the Science of Food and Agriculture, doi 10.1002/jsfa.2841).

Coloured berry fruits like strawberries contain compounds known as polyphenols and anthocyanins. Consumption of these compounds has been linked to the prevention of diseases ranging from cancer to neurodegenerative disorders. They work by helping to mop up damaging free radicals produced naturally during a person’s normal metabolism.

Those who aren’t keen on strawberry daiquiris might be relieved to know that the scientists found similar results with blackberries, meaning that a blackberry-crowned champagne cocktail might achieve the same effect.

Green tea may help protect against autoimmune disease, Medical College of Georgia researchers say.

Researchers studied an animal model for type I diabetes and primary Sjogren’s Syndrome, which damages the glands that produce tears and saliva.

They found significantly less salivary gland damage in a group treated with green tea extract, suggesting a reduction of the Sjogren’s symptom commonly referred to as dry mouth. Dry mouth can also be caused by certain drugs, radiation and other diseases.

Approximately 30 percent of elderly Americans suffer from degrees of dry mouth, says Dr. Stephen Hsu, a researcher in the MCG School of Dentistry and lead investigator on the study. Only 5 percent of the elderly in China, where green tea is widely consumed, suffer from the problem.

“Since it is an autoimmune disease, Sjogren’s Syndrome causes the body to attack itself and produce extra antibodies that mistakenly target the salivary and lacrimal glands,” he says.

There is no cure or prevention for Sjogren’s Syndrome.

Researchers studied the salivary glands of the water-consuming group and a green tea extract-consuming group to look for inflammation and the number of lymphocytes, a type of white blood cells that gather at sites of inflammation to fend off foreign cells.

The group treated with green tea had significantly fewer lymphocytes, Dr. Hsu says. Their blood also showed lower levels of autoantibodies, protein weapons produced when the immune system attacks itself, he says.

Researchers already know that one component of green tea – EGCG – helps suppress inflammation, according to Dr. Hsu.

“So, we suspected that green tea would suppress the inflammatory response of this disease. Those treated with the green tea extract beginning at three weeks, showed significantly less damage to those glands over time.”

These results, published in a recent issue of Autoimmunity, reinforced findings of a 2005 study showing a similar phenomenon in a Petrie dish, Dr. Hsu says.

Researchers also suspect that the EGCG in green tea can turn on the body’s defense system against TNF-alpha – a group of proteins and molecules involved in systemic inflammation.

TNF-alpha, which is produced by white blood cells, can reach out to target and kill cells.

“The salivary gland cells treated with EGCG had much fewer signs of cell death caused by TNF-alpha,” Dr. Hsu says. “We don’t yet know exactly how EGCG makes that happen. That will require further study. In some ways, this study gives us more questions than answers.”

Further study could help determine green tea’s protective role in other autoimmune diseases, including lupus, psoriasis, scleroderma and rheumatoid arthritis, he says.

Long-term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention

People who significantly cut back on the amount of salt in their diet could reduce their chances of developing cardiovascular disease by a quarter.

Researchers in Boston also found a reduction in salt intake could lower the risk of death from cardiovascular disease by up to a fifth.

Cardiovascular disease refers to the group of diseases linked to the heart or arteries, for example a stroke or heart disease. While there is already a substantial body of evidence showing that cutting back on salt lowers blood pressure, studies showing subsequent levels of cardiovascular disease in the population have been limited and inconclusive.

This research provides some of the strongest objective evidence to date that lowering the amount of salt in the diet reduces the long term risk of future cardiovascular disease, say the authors of the report.

Researchers followed up participants from two trials completed in the nineties which had been conducted to analyse the effect that reducing salt in the diet had on blood pressure.

All the participants had high-normal blood pressure (pre-hypertension). They were therefore at greater risk of developing cardiovascular disease. 744 people took part in the first Trial of Hypertension Prevention which was completed in 1990, 2382 in the second, which ended in 1995. In both trials participants reduced their sodium intake by approximately 25% - 35% alongside a control group who didn’t cut back on their salt intake.

Detailed information about cardiovascular and other health problems was sought from participants in the earlier trials. As part of this researchers found that participants who had cut back on salt during the trials tended to stick to a lower salt diet compared to those who had been in the control group. In total the researchers obtained information from 2415 (77.3%) participants, 200 of whom had reported some sort of cardiovascular problem.

The reduction in the risk of developing cardiovascular problems as a result of the sodium reduction intervention was substantial. The results showed these pre-hypertensive individuals were 25% less likely to develop cardiovascular problems over the course of the 10-15 years post-trial. There was also a 20% lower mortality rate. This risk reduction was evident in each trial.

To the authors knowledge this study is the first and only study of sufficient size and duration to assess the effects of a low salt diet on cardiovascular problems based on randomised trial data. It provides unique evidence that lowering salt in the diet might prevent cardiovascular disease.

Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults.

A diet score (range 0–55) has been developed that assesses adherence to the Mediterranean diet. For the consumption of items presumed to be close to Mediterranean dietary pattern (non-refined cereals, fruits, vegetables, legumes, olive oil, fish and potatoes) scores 0 to 5 for never, rare, frequent, very frequent, weekly and daily consumption were assigned, while for the consumption of foods presumed to be away from this pattern (red meat and products, poultry and full fat dairy products) scores on a reverse scale were assigned.

The Mediterranean diet was a strong predictor of non-occurence of these diseases.

Benefits of antidepressants appear greater than risks for children, teens

A review of previous studies indicates that the benefits of antidepressants for children and teens with depression or anxiety disorders may outweigh their risks, and that the increased risk for suicidal thoughts and attempts from using these medications is not statistically significant, according to an article in the April 18 issue of JAMA.

Previous research has indicated that the usage of antidepressants among children and adolescents is associated with an increased risk for suicidal behavior and thoughts, and resulted in the issuing of mandated label warnings on pediatric antidepressant medications by the FDA, according to background information in the article.

Jeffrey A. Bridge, Ph.D., of The Ohio State University, Columbus, and colleagues conducted a review and meta-analysis of randomized controlled trials involving the pediatric usage of antidepressants for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders, and included recent trials that had not been incorporated into previous analyses, to assess their benefits and effect on risk of suicidal thoughts and attempts. The researchers conducted a search for studies through 2006 and identified and included 27 pediatric trials for their analysis: MDD (n = 15), OCD (n = 6), and non-OCD anxiety disorders (n = 6).

The researchers found: "Consistent with the analyses of the FDA, we found evidence of an overall small but increased risk of treatment-emergent suicidal ideation/suicide attempt. However, the pooled random-effects risk differences of suicidal ideation/suicide attempt for each indication were all less than 1 percent. There were no completed suicides in these trials."

"This meta-analysis of all available randomized clinical trials of antidepressant treatment of pediatric MDD, OCD, and non-OCD anxiety disorders shows evidence of efficacy for all three indications, although the effects were strongest for non-OCD anxiety disorders, intermediate for OCD, and more modest in MDD," the authors write. Adolescents appeared to respond better than children to antidepressants in trials of both depression and anxiety.

"Some may argue that any risk of suicidal ideation/suicide attempt cannot possibly justify treatment with antidepressants for children and adolescents. Instead, we believe that the strength of evidence presented here supports the cautious and well-monitored use of antidepressant medications as one of the first-line treatment options, with the recognition that efficacy appears greatest for non-OCD anxiety disorders, intermediate for OCD, and more modest for MDD. Since the choice of treatment should be the result of a collaborative discussion between clinician, family, and patient, the information presented in this report should allow for an informed evaluation of the potential benefits and risks of these medications vs. no treatment and provide a framework for their comparison with nondrug treatments as well," the researchers conclude.

Long-term use of adult-strength aspirin linked to a moderate decreased cancer risk

A daily dose of adult-strength aspirin may modestly reduce cancer risk in populations with high rates of colorectal, prostate, and breast cancer if taken for at least five years.

The Women's Health Study trial recently reported that long-term use of low-dose aspirin (about 100mg every other day) does not reduce a woman's cancer risk, but it did not examine whether high doses of aspirin have an effect on cancer risk.

Eric Jacobs, Ph.D., of the American Cancer Society in Atlanta, and colleagues looked for associations between long-term daily aspirin use (at least 325mg/day) and cancer incidence in a group of nearly 70,000 men and 76,000 women. Aspirin use was determined by a questionnaire.

During the 12 year follow-up, nearly 18,000 men and women in the study were diagnosed with cancer. The researchers found that daily use of adult-strength aspirin for at least five years was associated with an approximately 15 percent relative reduction in overall cancer risk, though the decrease was not statistically significant in women. Additionally, aspirin use was associated with a 20 percent reduced risk of prostate cancer and a 30 percent reduced risk of colorectal cancer in men and women, compared to people who didn't take aspirin. There was no effect on risk in other cancers examined—lung cancer, bladder cancer, melanoma, leukemia, non-Hodgkins lymphoma, pancreatic cancer, and kidney cancer. Aspirin use for less than five years was not associated with decreased cancer risk.

"Our results do not have immediate clinical implications. Confirmation from randomized trials is necessary before a reduction in cancer risk could be considered a benefit of using adult-strength aspirin. Our results indicate that a randomized trial examining the effect of aspirin on cancer incidence would need to be both large and long term, probably lasting a minimum of 10 years. More evidence is needed before any such trial can be justified," the authors write.

In an accompanying editorial, Maria Elena Martinez, Ph.D., of the Arizona Cancer Center in Tucson, and E. Robert Greenberg, M.D., of the Fred Hutchinson Cancer Center in Seattle, write that, for the average person, the side effects of daily long-term aspirin use, such as intestinal bleeding or stroke, might outweigh the its benefits of cancer prevention. "However, if aspirin were shown to truly prevent a multitude of common cancers, there might be clinical situations in which daily adult-strength aspirin would be indicated," the authors write.

Omega-3 fatty acid may help prevent Alzheimer's brain lesions

Study suggests DHA-rich diet can curb onset of the disease

A type of omega-3 fatty acid may slow the growth of two brain lesions that are hallmarks of Alzheimer’s disease, UC Irvine scientists have discovered. The finding suggests that diets rich in docosahexaenoic acid (DHA) can help prevent the development of Alzheimer’s disease later in life.

This study with genetically modified mice is the first to show that DHA, an omega-3 fatty acid, can slow the accumulation of tau, a protein that leads to the development of neurofibrillary tangles. Such tangles are one of two signature brain lesions of Alzheimer’s disease. DHA also was found to reduce levels of the protein beta amyloid, which can clump in the brain and form plaques, the other Alzheimer’s lesion.

Previous studies have shown that DHA may have therapeutic value for Alzheimer’s patients, but this research is among the first to show that it may delay the onset of the disease. DHA is found in fish, eggs, organ meats, micro-algae, fortified foods and food supplements.

“We are greatly excited by these results, which show us that simple changes in diet can positively alter the way the brain works and lead to protection from Alzheimer’s disease pathology,” said Frank LaFerla, professor of neurobiology and behavior and co-author of the study.

This research appears in the April 18 issue of The Journal of Neuroscience.

LaFerla and his research team studied the effects of DHA in mice bred to develop the plaques and tangles associated with Alzheimer’s disease. Mice in the control group were given food that mimics a typical American diet, with the ratio of omega-6 fatty acids to omega-3 fatty acids being 10:1. Studies indicate that a proper ratio is important to maintain health, with the ideal being 3:1 to 5:1. Typical Western diets contain unhealthy ratios ranging from 10:1 to 30:1. Omega-6 fatty acids are found in corn, peanut and sunflower oils.

Mice in three test groups were given food with a 1:1 ratio of omega-6 fatty acids to omega-3 fatty acids. One of these groups received supplemental DHA only, and two groups received DHA plus additional omega-6 fatty acids. After three months, mice in all of the test groups had lower levels of beta amyloid and tau than mice in the control group, but at nine months, only mice on the DHA diet had lower levels of both proteins. These results suggest that DHA works better on its own than when paired with omega-6 fatty acids.

The scientists also determined the mechanism by which DHA leads to lower levels of beta amyloid. DHA, they found, leads to lower levels of presenilin, an enzyme responsible for cutting beta amyloid from its parent, the amyloid precursor protein. Without presenilin, beta amyloid cannot be generated. When clumped into plaques, beta amyloid disrupts communication between cells and leads to symptoms of Alzheimer’s disease.

This latest study adds to growing evidence that diet and lifestyle changes may reduce the risk of developing Alzheimer’s disease. LaFerla and his team have previously shown that short but repeated learning sessions can slow the physical progression of Alzheimer’s in mice, suggesting that the elderly can delay onset of the disease by keeping their minds active. The team also found that stress hormones appear to rapidly exacerbate the formation of plaques and tangles, suggesting that managing stress could slow the progression of Alzheimer’s.

“Combined with mental stimulation, exercise, other dietary intakes, and avoiding stress and smoking, we believe that people can significantly improve their odds against this disease,” said Kim Green, scientist and lead author on the DHA, learning and stress studies.

Alzheimer’s is a progressive neurodegenerative disorder that affects more than 4.5 million adults in the United States. With an aging population, that number could approach 20 million by 2050. Five percent of people older than 65 have Alzheimer’s, and up to one-half of people are affected by age 80.