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Calorie restriction okay for bones
Leanne M. Redman, PhD, and her associates at Pennington Biomedical Research Center in Baton Rouge assigned 46 healthy, overweight men and women to one of the following six month regimens: a control diet, a diet containing 25 percent fewer calories than the amount expended daily, a 25 percent calorie deficit achieved by consuming fewer calories and exercising five days per week, and a low (890) calorie diet to be switched to a maintenance plan when 15 percent weight loss was achieved. All of the diets provided the recommended amounts of vitamins and minerals. Bone mineral density and blood markers of bone resorption and formation were ascertained at the beginning and end of the treatment period. At the end of six months, the control group had lost an average of 1 percent of their body weight, compared with 10 percent in both calorie restriction groups and 13.9 percent in the low calorie group. While markers of bone resorption were increased in all but the control group, bone formation remained unchanged in all but those who practiced calorie restriction without exercise. None of the groups showed a reduction in bone mineral density compared to the control subjects. "We speculate that in young individuals undergoing calorie restriction, minor adjustments in bone occur as a normal physiological adaptation to the reduced body mass," the authors write. Further studies of longer duration are warranted and should include an assessment of bone architecture to ensure that bone quality is preserved with weight loss." —D Dye Ellagic acid’s anticancer mechanisms identified
Mouad Edderkaoui and colleagues at the West Los Angeles Veterans Administration Healthcare Center administered three concentrations of ellagic acid to two human pancreatic cancer cell lines. Pancreatic cancer is known to be resistant to standard forms of treatment. Apoptosis, cell proliferation, and other factors were measured after 48 hours of the cells' exposure to ellagic acid. Ellagic acid was found to dose-dependently increase apoptosis in the first pancreatic cancer cell line. Significant ellagic acid-induced apoptosis was also observed in the second cell line, although the association was not dose-dependent. Cell proliferation was reduced 20 fold by the highest concentration of ellagic acid in the first cell line, and was dose-dependently reduced, although to a lesser extent, in the second line. The researchers found that ellagic acid induced apoptosis in both cell lines by reducing the binding activity of the prosurvival transcription factor nuclear factor-kappa beta. "Our results . . . indicate that ellagic acid is a powerful phenolic compound with proapoptotic and antiproliferation effects in cancer cells," the authors conclude. "There is an increasing interest in the use of natural products for cancer treatments," they write. "Our results suggest a potential therapeutic role for ellagic acid in the treatment of pancreatic cancer. —D Dye Curcumin may be beneficial for hemorrhagic stroke prevention and treatment
Approximately 17 percent of strokes are hemorrhagic, as opposed to the more common ischemic stroke. Hemorrhagic stroke occurs when blood vessels rupture in the brain, leading to blood clot formation. Surgery is often employed to remove the blood clot, however not all patients are good candidates. Timing is known to be of critical importance in the successful treatment of hemorrhagic stroke. "Usually, patients can experience other symptoms like seizures, vision or cognitive problems, so they come to the (emergency room) fairly quickly under most circumstances," remarked Medical College of Georgia researcher Dr Kirsnan Dhandapani. "Many patients also arrive due to head trauma and are seen within an hour or so. However, treating these injuries, even after an hour, can be tricky." For the current research, curcumin was injected into the abdomen of animals in which hemorrhagic stroke was induced, resulting in a reduction in the resultant blood clot formation. The researchers speculate that curcumin's potent anti-inflammatory and antioxidant properties could be the mechanisms involved. "We found that curcumin significantly decreases the size of a blood clot, but we're not sure why it happens," co-researcher and second-year medical student Jay McCracken admitted. Although Dr Dhandapani believes that curcumin will need to be administered intravenously to stroke patients, the researchers predict that the compound could additionally be used for stroke prevention. They plan to develop a concentrated tablet form of curcumin for individuals who have an increased hemorrhagic stroke risk. —D Dye Frequent dark chocolate consumption linked with reduced inflammation
For the study, Licia Iacoviello and colleagues selected 2,141 participants in the Moli-Sani Project, an ongoing study of men and women aged 35 and older. Chocolate was reported as not having been consumed during the past year by 1317 subjects, while 824 reported being regular dark chocolate consumers . Serum high-sensitivity C-reactive protein and other factors were measured upon enrollment, and body mass index, blood pressure, and physical activity levels were determined. Dark chocolate consumers tended to be younger, with lower systolic blood pressure and body mass index compared to nonconsumers, however, adjustment for these factors failed to modify the observed association between reduced C-reactive protein levels and increased dark chocolate consumption. Participants who reported consuming up to one serving of dark chocolate every 3 days had significantly lower CRP levels than those who consumed no chocolate or those who consumed higher amounts. The failure of higher intake levels to further reduce CRP was speculated to be due to the increased intake of calories and saturated fats that accompany chocolate, which would offset the beneficial effects of its polyphenol content. The reduction in CRP values observed in the current study among dark chocolate consumers is associated with a 26 percent lower risk of a cardiovascular event in men and a 33 percent lower risk in women compared to the risk experienced by nonconsumers. "The present study, by showing a significant inverse association between dark chocolate and serum CRP, adds new insight into the relationship between flavonoid-rich foods, inflammation, and cardiovascular protection." the authors conclude. —D Dye Calorie restriction early in life helps protect against later muscle loss
Christiaan Leeuwenburgh, PhD and his associates at the University of Florida compared rats that received diets in which they were allowed to eat as much as they wanted, or diets that provided 40 percent fewer calories beginning at 4 months of age though the remainder of their lives. Muscle mass, grip strength, and muscle nucleic acid oxidative stress and non-heme iron levels were measured at at 8, 18, 29 and 37 months of age. Muscle non-heme iron has been found to be elevated with aging, which could be a factor in muscle loss. Among animals that received unrestricted diets, muscle-to-body weight ratio declined with age to a significantly greater degree compared to the restricted rats. The decrease in grip strength that occurred with time in the unrestricted group was delayed until 37 months in the restricted group. Additionally, muscle RNA damage was notably lower in restricted compared to unrestricted older rats. In animals that received restricted diets, muscle mitochondrial iron levels did not change over time, however, increasing amounts of iron were found in the muscle cell mitochondria of the unrestricted group. Excessive free radical formation resulting from high iron levels can cause mitochondria to self-destruct, leading to cell death and, potentially, muscle atrophy. "We become less efficient at an old age and we need to understand why this is," Dr Leeuwenburgh commented. "One thing, maybe, is the accumulation of redox-active metals in cells. If the mitochondria become unhappy or are ready to kick the bucket, they have proteins in the inner and outer membranes that they can open up and commit suicide," he explained. "Muscle is critical for your overall well-being," Dr Leeuwenburgh stressed. "Muscle is an incredible source of reserves." —D Dye Harvard researchers estimate over half of premature deaths from chronic disease in women could be avoided by improved lifestyle
Dr Rob van Dam and colleagues at the Harvard School of Public Health evaluated data from 77,782 women between the ages of 34 and 59 who participated in the Nurses Health Study from 1980 through June, 2004. Questionnaires completed in 1980 were used to calculate nutritional intake and body mass index. Other questionnaires administered every two years provided information on smoking status, alcohol intake, disease treatment, and exercise habits. The team documented 8,882 deaths over the 24 year follow-up period, which included 4,527 from cancer and 1,790 from cardiovascular disease. While they estimate that 28 percent of these deaths could have been avoided by not smoking, the addition of three healthy lifestyle practices--maintaining a healthy weight, exercising regularly and consuming a healthy diet--would have increased this figure to 55 percent. Although light to moderate alcohol consumption was the fifth healthy lifestyle factor examined in the study, it failed to further reduce the risk of dying when added to the other factors, although it was found to be associated with a reduction in cardiovascular deaths. Although the effect of these lifestyle practices are well known, few studies have examined their combined benefit in a relatively young population. "Our results indicate that a healthy diet and regular physical activity have important health benefits independent of reducing adiposity," the authors note. "Even modest differences in lifestyle can have a substantial impact on reducing mortality rates," they conclude. —D Dye Meta-analysis finds Mediterranean diet associated with reduction in deaths in up to 18 years of follow-up
Researchers in Florence, Italy selected 12 studies with a total of 1,574,299 subjects for their review. All of the studies utilized a numerical scoring system ranging from 0 to 7-9 points to rate adherence to the diet. For the 8 studies that included mortality data, the team found that for every 2 point increase in adherence to the Mediterranean diet there was a 9 percent decline in deaths. Cardiovascular disease mortality was similarly reduced, and cancer deaths were 6 percent lower with each 2 point increase. Adherence to the diet also reduced the risk of Alzheimer's and Parkinson's disease by 13 percent for every 2 points. "To the best of our knowledge, this is the first report that has systematically assessed, through meta-analysis, the possible association between adherence to a Mediterranean diet, mortality, and the occurrence of chronic diseases in the general population," the authors announce. "These results seem to be clinically relevant in terms of public health, particularly for reducing the risk of premature death in the general population, and are strictly concordant with current guidelines and recommendations from all the major scientific associations that strongly encourage a Mediterranean-like dietary pattern for primary and secondary prevention of major chronic diseases," they conclude. —D Dye Broccoli compound helps protect lungs in COPD
Johns Hopkins associate professor Shyam Biswal, PhD and colleagues measured levels of NRF2 and NRF2-dependent antioxidants, as well as NRF2's biochemical regulators in tissue samples from the lungs of smokers with and without COPD. These regulators include an inhibitor of NRF2 known as KEAP1, and DJ-1, which stabilizes it. The lungs of patients with COPD had significantly lower levels of NRF2 protein and NRF2-dependent antioxidants than those of subjects without the disease. COPD patients also had increased oxidative stress markers, and lower DJ-1 levels. In an experiment using cell culture studies in which DJ-1 was disrupted in response to cigarette smoke, the researchers found that targeting KEAP1 with sulforaphane restored NRF2-dependent antioxidants. "Therapy directed toward enhancing NRF2-regulated antioxidants may be a novel strategy for attenuating the effects of oxidative stress in the pathogenesis of COPD," the authors conclude. In an accompanying editorial entitled, "Defective antioxidant gene regulation in COPD: a case for broccoli," Peter Barnes, D.M., of London's National Heart and Lung Institute commented that "Increasing NRF2 may also restore important detoxifying enzymes to counteract other effects of tobacco smoke. This has been achieved in vitro and in vivo by isothiocyanate compounds, such as sulforaphane, which occurs naturally in broccoli." —D Dye Depression and reduced plasma EPA both predict dementia
For the current study, researchers at the Institut National de la Sante et de la Recherche Medicale (INSERM) in Bordeaux, France evaluated data from 1,214 participants in the Three-City Study from Bordeaux. The subjects were aged 65 and older, and did not have dementia upon enrollment. Blood samples collected at the beginning of the study were analyzed for plasma saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which include omega-3 and omega-6 PUFAs. Depressive symptoms were assessed via home interviews. Over the four year follow-up period, 65 subjects developed dementia. Lower plasma EPA levels were associated with a greater adjusted risk of developing the condition, as was having a higher ratio of arachidonic acid to DHA and omega-6 to omega-3 fatty acids. In their discussion of a possible role for EPA in preventing dementia, the authors remark that the fatty acid may have specific neuroprotective effects during aging. EPA may stimulate ketogenesis, which would compensate for the impairment in brain glucose uptake observed in Alzheimer's disease patients. Additionally, EPA's anti-inflammatory properties could be responsible for its neuroprotective benefit. Because dementia and depression share vascular risk factors, EPA's effect on the vasculature could help reduce both conditions. The authors suggest that depression might play a causal role in dementia rather than being a precursor of the condition. They recommend that randomized controlled trials of EPA supplements be conducted in depressed older individuals to determine whether supplementation decreases the risk of dementia in this population. —D Dye Omega-3 fatty acids lower mortality and hospital admissions in heart failure patients
Professor Luigi Tavazzi and coinvestigators analyzed data from a randomized controlled trial of daily supplementation with 1000 milligrams omega-3 fatty acid ethyl esters or placebo in 6,975 chronic heart failure patients at 357 Italian centers. Participants were followed for a median of 3.9 years, during which any deaths or hospital admissions were noted. During the follow-up period, deaths occurred among 27 percent of those that received omega-3 fatty acids died compared with 29 percent of the placebo group, resulting in a 9 percent reduction in the risk of all-cause mortality. The group that received omega-3 fatty acids also experienced an 8 percent lower risk of being hospitalized for cardiovascular reasons. In the second Lancet article concerning the GISSI Heart Failure Study, a trial of the drug rosuvastatin was reported to have failed to find a significant benefit for the same outcomes. In an accompanying commentary, Dr Gregg Fonarow, of the Ahmanson-UCLA Cardiomyopathy Center in Los Angeles wrote, "For omega-3 fatty acid supplementation, benefits observed in other populations apply to patients with heart failure. For statins, the benefits, unfortunately, seem not to. Although other promising treatments for heart failure are under investigation, every effort should be made apply those therapies which are evidence-based to all eligible patients with heart failure." —D Dye Vascular cognitive impairment linked to B vitamin deficiency
Tufts Friedman School of Nutrition Science and Policy assistant professor Aron Troen, PhD and colleagues fed mice one of two diets designed to result in high homocysteine levels over a ten week period. Elevated plasma homocysteine has been linked with an increased risk of cognitive impairment. The first diet contained a high amount of the amino acid methionine, which metabolizes to homocysteine, and the second diet was deficient in folate, vitamin B6 and vitamin B12, which help convert homocysteine back to methionine. A third group received normal diets. "Mice fed a diet deficient in folate and vitamins B12 and B6 demonstrated significant deficits in spatial learning and memory compared with normal mice." Dr Troen reported. "The B vitamin-deficient mice also developed plasma homocysteine concentrations that were seven-fold higher than the concentrations observed in mice fed a normal diet." Dr Troen's team additionally observed reductions in capillary length and density in the brains of mice that received B vitamin deficient diets. Mice that were given high methionine diets experienced similar effects, but to a lesser degree. "The elevated levels of homocysteine that were associated with vascular cognitive impairment in the mice in our study are comparable to the levels that are associated in older adults with an increased risk for Alzheimer's disease and cerebrovascular disease, the latter of which manifests with conditions such as stroke and atherosclerosis," stated Irwin Rosenberg, MD, who is the director of the Nutrition and Neurocognition Laboratory at the HNRCA. "These findings may indicate that microvascular changes mediate the association between high homocysteine levels and human age-related cognitive decline." —D Dye Prenatal magnesium sulfate halves children's risk of cerebral palsy
Cerebral palsy is caused by damage to parts of the brain that control movement and coordination. The majority of cases occur due to brain injury before birth. Premature birth and low birth weight are risk factors for the disease. The Beneficial Effects of Antenatal Magnesium Sulfate (BEAM) trial included 2,240 women who were at high risk of giving birth more than two months early. Half of the participants received intravenous magnesium sulfate while the remainder received a placebo. At two years of age, cerebral palsy was diagnosed in 4.2 percent of the children of mothers who received magnesium sulfate compared to 7.3 percent of those who received a placebo, equal to a 45 percent reduction. “This is a substantial breakthrough in maternal fetal medicine that could positively impact the health of thousands of babies,” stated coauthor Alan Peaceman, MD, who is a professor of Obstetrics and Gynecology at the Northwestern University Feinberg School of Medicine. “After 10 years of studying the effects of magnesium sulfate, it has proven to be a successful method of reducing the outcome of cerebral palsy in premature births.” “Based on results of the study, in the future it is possible that women at risk of prematurely giving birth could proactively receive magnesium sulfate to reduce their child’s chances of developing cerebral palsy,” he added. “With additional research, it is possible that in the next few years this will be a standard of care.” —D Dye |
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Ellagic acid, a polyphenolic compound found in raspberries, strawberries, and pomegranates, appears to exert its anticancer benefit by dramatically reducing cell proliferation as well as by promoting programmed cell death (apoptosis), according to a report published in the June 21, 2008 issue of the 
Research conducted at the Medical College of Georgia has found that curcumin, a compound that occurs in the curry spice turmeric, reduces the size of hemorrhagic 
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