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February 28, 2011
Fish oil helps prevent chemotherapy-induced muscle loss
An article published online on February 28, 2011 in the American Cancer Society journal Cancer reports a protective effect for fish oil against the loss of muscle tissue and weight that can occur during treatment with chemotherapeutic drugs. The phenomenon of muscle and weight loss caused by chemotherapy significantly reduces quality of life and survival, and can interfere with the ability of patients to receive further treatment.
Vera Mazurak, PhD of the University of Alberta in Edmonton and her colleagues conducted a clinical trial of non-small cell lung cancer patients receiving their initial chemotherapy treatments, in which 16 participants received fish oil providing 2.2 grams of the omega-3 fatty acid eicosapentaenoic acid (EPA) per day and 24 patients were not given fish oil. Weight was measured and blood samples were analyzed at the beginning and throughout treatment, which averaged 10 weeks. Computed tomography was used to evaluate fat and muscle tissue.
While the group that did not receive fish oil lost an average of 2.3 kilograms, patients that received fish oil were able to maintain their weight. Sixty-nine percent of those who supplemented with fish oil gained or maintained muscle, compared to 29 percent of those who did not receive it. Those whose EPA levels increased the most experienced the greatest muscle gains, and those who did not receive EPA lost, on average 1 kilogram muscle. Fat mass did not differ between groups.
"Fish oil may prevent loss of weight and muscle by interfering with some of the pathways that are altered in advanced cancer," Dr Mazurak stated. "This holds great promise because currently there is no effective treatment for cancer-related malnutrition.”
February 25, 2011
Reduced vitamin D levels linked to childhood allergies
An article published online in the Journal of Allergy and Clinical Immunology on February 16, 2011 reports the finding of assistant professor of medicine Michal L. Melamed MD, MHS of the Albert Einstein College of Medicine of Yeshiva University and her colleagues of an association between decreased serum vitamin D levels and a greater risk of allergies in children.
The current study evaluated data from 3,136 children and adolescents and 3,454 adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2005-2006, which was designed to assess the health and nutrition of children and adults living in the United States via interviews, physical examinations and lab tests. Blood samples were analyzed for 25-hydroxyvitamin D levels and sensitivity to 17 different allergens.
While no association between vitamin D levels and allergies was observed in adults, a reduction in serum vitamin D was correlated with sensitivity to 11 environmental and food allergens in children. Children who were classified as deficient in vitamin D with levels of less than 15 nanograms per milliliter or less were 2.4 times as likely to be diagnosed with peanut allergy as those whose levels were sufficient at over 30 nanograms per milliliter, and their risk of oak allergy was 4.75 times as high. Although the association does not prove a causative effect for vitamin D deficiency in allergy, Dr Melamed cautions that children need to be sure to consume an adequate amount of vitamin D. The authors recommend further research to confirm the findings.
February 23, 2011
Resveratrol helps cancer cells overcome resistance to common drug
An article published in the February 28, 2011 issue of the journal Cancer Letters reports the finding of researchers at Ohio’s Cleveland Clinic of a benefit for resveratrol in suppressing the growth of breast cancer tumor cells that have become resistant to the drug rapamycin, an immunosuppression drug that has been used to treat cancer. Results from other research involving resveratrol, a compound found in red wine, grapes and other plant foods, suggest an anticancer effect for several types of malignancies.
A team led by Charis Eng, MD, PhD, who is the Chair of the Genomic Medicine Institute of Cleveland Clinic’s Lerner Research Institute tested the effect of resveratrol and rapamycin separately and in varying combinations on three human breast cancer cell lines. They found dose-dependent effects for both compounds and an additive effect for a combination of the two, which induced 50 percent growth inhibition in all lines when administered in low concentrations. It was determined that a tumor suppressing gene known as PTEN contributes to resveratrol’s growth suppressive effects.
"Rapamycin has been used in clinical trials as a cancer treatment,” Dr Eng stated. “Unfortunately, after a while, the cancer cells develop resistance to rapamycin." "Our findings show that resveratrol seems to mitigate rapamycin-induced drug resistance in breast cancers, at least in the laboratory,” she reported. “ If these observations hold true in the clinic setting, then enjoying a glass of red wine or eating a bowl of boiled peanuts – which has a higher resveratrol content than red wine – before rapamycin treatment for cancer might be a prudent approach."
February 21, 2011
Lithium lengthens life span
An article published online on February 7, 2011 in the European Journal of Nutrition reports the discovery of Dr Michael Ristow of the University of Jena in Germany and his colleagues in Japan of an association between increased life expectancy and a greater intake of the element lithium.
Acting the finding of an earlier study which showed that a high concentration of lithium extended the life span of the roundworm Caenorhabditis elegans, the researchers sought to determine whether lower concentrations could impact human lifespan. “The dosage that has been analyzed back then . . . is clearly beyond the physiologically relevant range and may be poisonous for human beings," Dr Ristow noted.
The current study evaluated the effect on mortality of varying amounts of lithium found in the tap water of 18 Japanese municipalities. “We found that the mortality rate was considerably lower in those municipalities with more lithium in the drinking water," Dr Ristow revealed.
The team then exposed roundworms to two comparable concentrations of lithium. While no effect was observed in association with the low concentration, the high dose was associated with a longer life span. "The average longevity of the worms is higher after they have been treated with lithium at this dosage," Dr Ristow observed.
"The scientific community doesn't know much about the physiological function of lithium," Dr Ristow stated. "From previous studies we know already that a higher uptake of lithium through drinking water is associated with an improvement of psychological well-being and with decreased suicide rates.”The authors conclude that “Given the long-standing psychiatric experience with high-dose lithium supplementation in humans, these findings raise the possibility that readily available low-dose lithium supplementation at non-toxic doses may not only promote mental health and impair suicide risk but also may reduce overall mortality in humans.”
February 18, 2011
Mechanism revealed for antioxidants' cancer benefit
In an article published in the February 15, 2011 issue of the journal Cancer Biology & Therapy, researchers from Thomas Jefferson University report their finding of a mechanism supporting the effectiveness of antioxidant compounds in the treatment of cancer.
In previous research, Jefferson Medical College professor of cancer biology Michael P. Lisanti, MD, PhD and his associates discovered that the presence of the tumor suppressor protein caveolin-1 predicts breast cancer outcome. The protein was also observed to have a role oxidative stress, however, the origin of that stress was unknown. In the current experiment, Dr Lisanti's team confirmed that a loss of Cav-1 results in increased mitochondrial oxidative stress within the environmental framework of tumors, which significantly increased tumor mass and volume.
"Antioxidants have been associated with cancer reducing effects—beta carotene, for example—but the mechanisms, the genetic evidence, has been lacking," Dr Lisanti remarked. "Now we have genetic proof that mitochondrial oxidative stress is important for driving tumor growth. This means we need to make anticancer drugs that specially target this type of oxidative stress. And there are already antioxidant drugs out there on the market as dietary supplements, like N-acetylcysteine."
"Currently, anticancer drugs targeting oxidative stress are not used because is it commonly thought they will reduce the effectiveness of certain chemotherapies, which increase oxidative stress," he observed. "We are not taking advantage of the available drugs that reduce oxidative stress and autophagy, including metformin, chloroquine and N-acetylcysteine. Now that we have genetic proof that oxidative stress and resulting autophagy are important for driving tumor growth, we should reconsider using antioxidants and autophagy inhibitors as anticancer agents."
February 16, 2011
High omega-3 fatty acid diet could offset genetic predisposition to Alzheimer’s disease
Findings to be presented at a conference in Barcelona next month suggest that consuming a diet that contains fish oil could help carriers of the apoE4 gene avoid developing Alzheimer’s disease. Apolipoprotein E4 is a brain protein produced by a variant of the apoE gene which appears in half of all persons with Alzheimer’s disease and in 15 percent of the general population. Although four other molecules are known to influence the development of Alzheimer’s disease, apoE4 is the most prevalent genetic risk factor.
Professor Daniel Michaelson of Tel Aviv University's Department of Neurobiology and colleagues divided mice with and without apoE4 to receive a normal diet, a high cholesterol diet or a diet containing a high amount of fish oil. After four months, the animals underwent cognitive testing and their brains were examined for the presence of amyloid beta, a compound that accumulates in Alzheimer’s disease patients.
In comparison with animals that did not have the gene, the team found a higher level of amyloid beta in apoE4 mice that received the high cholesterol or control diets which did not occur in apoE4 mice that were given fish oil. Cognitive performance worsened in both groups on the high cholesterol diet, but improved in the apoE4 mice that received fish oil.
“The deficient memory of the mice with the bad gene which are kept on ‘regular’ and on ‘bad’ diets, is corrected by subjecting these mice to a good diet,” Professor Michaelson concluded. "The main take-away message here is that good diets can alleviate the effects of bad genes. Of course nutritionists have had this general idea for a while, but it's nice to be able to show that this approach can be applied to specifically counteract the negative effects of Alzheimer's disease-related genes.”
February 14, 2011
Resveratrol rivals calorie restriction’s benefits in primates
The findings of French researchers, described in an article published online on January 31, 2011 in PLoS One provides more evidence for the calorie restriction mimetic benefits of resveratrol, a compound found in red grapes and wine.
Researchers at the Centre National de la Recherche Scientifique divided 33 adult mouse lemurs to receive a control diet that allowed them to eat as much as they liked, a diet containing 70 percent of the calories contained in the average control diet, or the control diet plus 200 milligrams resveratrol per kilogram body weight per day for 18 months. Three tests of cognitive function, two tests of motor function, one emotional test and a blood test for cortisol were administered at the end of the treatment period.
While no differences were noted in some of the test results, an in increase in spontaneous locomotor activity was observed in the calorie restricted and resveratrol-supplemented groups compared to the control group, as well as an increase in working memory. Only resveratrol supplementation was significantly associated with increased spatial memory performance as evaluated in one test of cognitive function. Tests that evaluated stress failed to find that calorie restriction or resveratrol was stressful to the animals that received the therapies.“The present results show, for the first time in an adult primate, a positive effect of resveratrol on cognitive function (in both executive function and spatial memory),” the authors announce. “These observations allow us to suggest that resveratrol could be a good candidate to mimic long-term calorie restriction effects. The present results obtained in adult animals are promising with regard to possible positive effects during aging and also support the growing evidences that nutritional interventions can have beneficial effects on brain functions even in adults.”
February 11, 2011
Curcumin compound helps repair stroke damage
The American Heart Association International Stroke Conference held in Los Angeles was the site of a presentation by Paul A. Lapchak, PhD on February 9, 2011 concerning a compound derived from curcumin that helps protect and regenerate brain cells subsequent to stroke.
Ischemic stroke occurs when an artery that nourishes the brain becomes blocked, depriving the organ of blood and oxygen, which results in the destruction of brain cells. The current treatment for stroke, tissue plasminogen activator (tPA), dissolves blood clots that block arteries, interrupting the destructive process that occurs after the event, however, Dr Lapchak notes that a cocktail of drugs or a drug capable of targeting a number of mechanisms is necessary to correct the multiple pathways damaged by stroke.
Dr Lapchak and his associates at the Salk Institute for Biological Studies tested the curcumin compound, known as CNB-001, in a rabbit model of stroke and found that it was effective when administered up to an hour after the event, which correlates with the three hour window of effectiveness for tPA in humans. While tPA works by dissolving the clots that cause ischemic stroke, thereby restoring blood flow, CNB-001 diminishes stroke-induced motor deficits by repairing four major pathways, one of which plays a role in the growth and survival of neurons. "CNB-001 has many of the same benefits of curcumin but appears to be a better choice of compound for acute stroke because it crosses the blood-brain barrier, is quickly distributed in the brain, and moderates several critical mechanisms involved in neuronal survival," said Dr Lapchak, who is the director of Translational Research in the Department of Neurology at Cedars-Sinai Medical Center. He added that his team anticipates clinical trials involving CNB-001 in the near future.
February 09, 2011
Researchers explore omega-3 mechanisms in neovascular eye disease
An article in the February 9, 2011 issue of Science Translational Medicine unveils a mechanism for omega-3 fatty acids in protecting the eye against retinopathy (which affects people with diabetes), as well as age-related macular degeneration (AMD). Both diseases are characterized by abnormal, leaky blood vessel growth. Neovascular eye diseases are currently treated with the drugs Macugen or Lucentis, but can still lead to blindness.
In previous research, Lois Smith, MD, PhD and her associates at Children's Hospital Boston found half the amount of pathologic blood vessel growth in the retinas of mice that received diets enriched with omega-3 fatty acids compared to animals given diets rich in omega-6 fatty acids. A reduction in inflammatory signaling was also observed in the omega-3 group. The current investigation revealed that omega-3 fatty acids promote the growth of healthy vessels while having an antiantiogenic effect on abnormal ones. Dr Smith's team attributes the beneficial action to the DHA metabolite 4-HDHA, produced by the enzyme 5-lipoxygenase (5-LOX). They also demonstrated that COX enzymes are not involved in the breakdown of omega-3 fatty acids, meaning that COX inhibitors such as aspirin won't interfere with the omega-3's actions. "This is important for people with diabetes, who often take aspirin to prevent heart disease, and also for elderly people with AMD who have a propensity for heart disease," Dr Smith noted.
"The cost of omega-3 supplementation is about $10 a month, versus up to $4,000 a month for anti-VEGF (vascular endothelial growth factor) therapy," she remarked. "Our new findings give us new information on how omega-3s work that makes them an even more promising option." "We found the good guys, now we'll look for the bad ones," she concluded. "If we find the pathways, maybe we can selectively block the bad metabolites. We would hope to start with drugs that are already available."
February 07, 2011
Researchers shed light on how omega-3 fatty acids fight depression
French and Basque researchers report online on January 30, 2011 in the journal Nature Neuroscience that insufficient omega-3 polyunsaturated fatty acid intake alters the functioning of the endocannabinoid system, a group of lipids and their receptors that are involved in mood, pain sensations and other processes.
The research was initiated by Olivier J Manzoni of INSERM and Sophie Layé of the University of Bordeaux, France who later collaborated with scientists at the University of the Basque Country. “We have observed that, in mice subjected to a diet low in omega-3 polyunsaturated fatty acids, they have lower omega-3 brain levels, and this fact is associated with an alteration in the functioning of the endocannabinoid system,” revealed University of the Basque Country coauthor Susana Mato who is a researcher in the Ramón y Cajal programme of the Neurosciences Department of the Faculty of Medicine and Odontology. She confirmed “the existence of a deficit in the signalling of the CB1 cannabinoid receptor in the prefrontal cortex of the brain. This protein—the CB1 cannabinoid receptor—has been linked, over the last decade and in various studies, to depressive disorders.”
“Certain forms of synaptic plasticity—a change in the efficiency of neuronal communication—measured by the brain’s endocannabinoid system, disappear specifically from certain zones of the brains of mice with omega-3 deficit,” added Dr Rafael Rodríguez-Puertas, also of the University of the Basque Country. “Thanks to the results of this research new possibilities are opened up for undertaking deeper research, such as how diet modifies the functioning of the brain in general and the endocannabinoid system in particular, and how this is linked to mental disorders.”
February 04, 2011
Resveratrol inhibits pancreatic cancer stem cell properties
An article published on January 31, 2011 in the journal PLoS One reports that resveratrol, an antioxidant compound found in grapes and other plant foods, can modify the characteristics of pancreatic cancer stem cells, which could help prevent the development of the disease.
In their introduction, Sharmila Shankar and colleagues at the University of Kansas Medical Center note that malignancies contain a small amount of tumor-forming cancer stem cells that are not destroyed by current chemotherapeutic drugs. Although resveratrol has shown anticancer effects, the compound’s effects on pancreatic cancer stem cells had not been evaluated.
The researchers discovered a dose-dependent inhibitory effect for resveratrol on the viability of human pancreatic cancer stem cells in culture. Resveratrol also reduced the growth of stem cell colonies, indicating an inhibitory effect for the compound on the cells’ ability to self-renew. Furthermore, resveratrol was demonstrated to induce apoptosis in the cancer stem cells, inhibit transcription factors required for maintaining the cells’ pluripotency, and suppress a drug resistance gene.
When resveratrol was administered to KrasG12D mice that are bred to develop spontaneous tumors of the pancreas, the compound reduced the tumors’ growth and development. Resveratrol was shown to completely eradicate pancreatic cancer stem cells in the mice after ten months of treatment. An inhibitory effect for resveratrol on the self-renewal capacity of pancreatic cancer stem cells isolated from untreated mice was also observed.
“Our study demonstrates, for the first time, that cancer preventive agent resveratrol can inhibit the self-renewal capacity of pancreatic cancer stem cells derived from human primary tumors and KrasG12D mice in vitro,” the authors write. “We were unable to observe any pancreatic cancer stem cells in KrasG12D mice treated with resveratrol.”“These data suggest that resveratrol can be used for the prevention and/or treatment of pancreatic cancer,” they conclude.
February 02, 2011
Finding may explain why studies fail to find cardioprotective effects for folic acid
An article published online on February 2, 2011 in the journal PLoS One explains why the B vitamin folic acid may be effective for primary prevention of heart attack but has failed to show a protective benefit among subjects who have already experienced the event.
Folic acid supplementation lowers homocysteine, which, when elevated, has been associated with an increased risk of heart attack and stroke.
David S. Wald and his associates at the Wolfson Institute of Preventive Medicine at Barts and The London School of Medicine and Dentistry updated a previous meta-analysis by including new studies that analyzed the association between a specific mutation in the methylenetetrahydrofolate reductase gene, which increases homocysteine, and ischemic heart disease. They also updated a review of 14 trials that evaluated the effect of homocysteine reduction by B vitamins on coronary events.
In the first meta-analysis, individuals with the mutation and elevated homocysteine continued to have a significantly increased risk of ischemic heart disease compared to those without the variant. Yet the analysis of randomized trials did not associate vitamin supplementation with homocysteine reduction. However, when the researchers included the use of antiplatelet therapy such as aspirin in their analysis, they found that the risk reduction associated with decreased homocysteine would have been 15 percent if no one had been taking the drugs, rather than 6 percent. The authors explain that a reduction in homocysteine helps prevent platelet aggregation, which aspirin also accomplishes, so those already using aspirin as routinely prescribed for the prevention of a second cardiovascular event would experience no further benefit from reducing homocysteine with folic acid.
"The explanation has important implications," Dr Wald stated. "The negative clinical trial evidence should not close the door on folic acid – folic acid may still be of benefit in people who have not had a heart attack because they will generally not be taking aspirin.”
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