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  • Focus on omega 3 over calories urged
  • Omega-3 fatty acids improve amyloid clearance
  • New guideline okays calcium intake of up to 2.5 grams daily
  • Nicotinamide riboside shows promise for Duchenne muscular dystrophy
  • Research explains role of alpha lipoic acid in treatment of diabetic neuropathy
  • Mediterranean diet, caffeine, fruit may help lower the risk of age-related macular degeneration
  • Trial confirms nicotinamide riboside boosts NAD+ metabolism, sirtuin enzymes
  • Coenzyme Q10 increases antioxidant enzymes, lowers inflammation in liver cancer patients
  • Prenatal vitamin D supplementation linked with fewer ADHD symptoms
  • Raspberries, ellagic acid reveal benefits in two studies
  • Vitamin E could help protect older men from pneumonia
  • Lower systolic BP predicted to save over 100,000 US lives per year
  • Vitamin D supplementation extends life in mouse model of Huntington's disease
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    Focus on omega 3 over calories urged

    neuropathy October 31 2016. To help manage the obesity pandemic, governments should focus on the restoration of an optimal balance of omega 6 to omega 3 fatty acids rather than on calories, according to an editorial appearing recently in the journal Open Heart.

    An imbalance in the amount of omega-6 and omega-3 fatty acids consumed is a relatively new phenomenon that was never a part of human evolution, note authors Artemis Simopoulos of the Center for Genetics, Nutrition, and Health in Washington DC, and James DiNicolantonio of Saint Luke's Mid America Heart Institute in Kansas City, Missouri.  Historically, humans have consumed equal amounts of omega 6 and omega 3, rather than the current ratio of approximately 16:1.

    As high omega 6 vegetable oil production increased, the switch of animal feed from grass to grain led to the elevation of omega 6 in meat, eggs and dairy products, which caused a profound imbalance of omega 6 to omega 3 fatty acids in the diet.  An optimal balance of these fatty acids is critical to human prenatal development and the prevention and management of chronic diseases. Too much omega 6 promotes inflammation, blood clots, and increased white adipose tissue which, unlike brown adipose tissue, is associated with obesity.

    "The scientific evidence to balance the omega 6 to omega 3 ratio is robust and necessary for normal growth and development, prevention and treatment of obesity and its comorbidities, including diabetes, cardiovascular disease and cancer," Drs Simopoulos and DiNicolantonio write. "It is the responsibility of governments and international organizations to establish nutrition policies based on science and not continue along the same path of focusing exclusively on calories and energy expenditure, which have failed miserably over the past 30 years."

     

     

     

     

    Omega-3 fatty acids improve amyloid clearance

    neuropathy October 28 2016. An article published online on October 7, 2016 in The FASEB Journal reports the finding of Chinese researchers of an ability of omega 3 polyunsaturated fatty acids to promote the brain's clearance of amyloid beta, a toxic protein that accumulates in the form of plaque in Alzheimer's disease patients. Omega 3 fatty acids accomplish this by improving the function of the glymphatic system, a functional waste clearance pathway for the central nervous system.

    By comparing normal mice to mice genetically modified to express high brain levels of omega 3 fatty acids, researchers Huixia Ren and colleagues observed that higher omega 3 levels enhanced the glymphatic system's clearance function, including its ability to remove brain amyloid beta. Glymphatic system function was also boosted in normal mice supplemented with fish oil (a significant source of omega 3 fatty acids), in comparison with mice that did not receive omega 3. "The results of the present study prove a novel mechanism by which omega-3 polyunsaturated fatty acids exert protective roles in reducing amyloid beta accumulation via mediating the glymphatic system function," the authors conclude.

    "These now-famous fatty acids have been the subject of major studies both in academia and industry," observed Thoru Pederson, PhD, who is Editor-in-Chief of The FASEB Journal. "Just when we thought we had heard everything, here is something new, and it is provocative indeed. This study should not turn attention away from the roles of these substances in maintaining vascular health, but neither should they restrict our view. The brain is an extremely vascularized organ, while we might also bear in mind that omega-3 fatty acids may impact neurons, glia, and astrocytes themselves."

     

     

     

     

    New guideline okays calcium intake of up to 2.5 grams daily

    neuropathy October 26 2016. On October 25, 2016, Annals of Internal Medicine revealed a new evidence-based guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology which states that calcium from supplements or food that doesn't exceed the tolerable upper intake level of 2,000 to 2,500 mg per day is safe for the heart.

    The updated guideline is the result of a review of 4 randomized trials and 27 studies conducted by a team from Tufts University Medical School. Among clinical trials there was no statistically significant difference in cardiovascular disease risk or mortality between subjects who received calcium in comparison with the placebo groups. No cohort study conclusively linked calcium intake—whether from diet, supplements or both—to cardiovascular disease or mortality from any cause.

    "On the basis of our assessments of internal validity, precision of risk estimates, and consistency of results from randomized trials and prospective cohort studies, we conclude that calcium intake (from either food or supplement sources) at levels within the recommended tolerable upper intake range are not associated with cardiovascular disease risks in generally healthy adults," Mei Chung, MPH, PhD, and colleagues write. "Although a few trials and cohort studies reported increased risks with higher calcium intake, risk estimates in most of those studies were small (±10% relative risk) and not considered clinically important, even if they were statistically significant."

    "Our systematic review, which synthesizes data from trials and cohort studies, has implications for a new evidence-based approach to establish dietary reference intake values that include chronic disease and long-term outcomes, for which direct evidence from randomized trials often is lacking," they conclude. "In the absence of direct evidence from trials, synthesis of large population-based cohort studies may improve the strength of evidence and provide complementary data for clinical or policy decision making."

     

     

     

     

    Nicotinamide riboside shows promise for Duchenne muscular dystrophy

    neuropathy October 24 2016. Research reported in the October 19, 2016 issue of Science Translational Medicine reveals a potential benefit for nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), in Duchenne muscular dystrophy.

    People with Duchenne muscular dystrophy are unable to produce a protein known as dystrophin that is needed by the cells of the muscles. The lack of dystrophin causes an inflammatory response that destroys muscle tissue.

    John Auwerx of École Polytechnique Fédérale de Lausannein Switzerland and colleagues demonstrated that the inflammation causes a second cycle of events inside the cells that leads to a shortage of NAD+. Since NAD+ acts as a fuel for the mitochondria, NAD+ deficiency weakens the muscle. These dysfunctional mitochondria contribute to the inflammation that causes muscle loss.

    In a genetically modified roundworm model of muscular dystrophy, Dr Auwerx and his team discovered that administering high doses of NR prevented the development of disease symptoms. In a mouse model of the disease, muscular inflammation was lower and existing lesions reduced in association with receiving NR.

    "In the animals that we tested, the quantities were so large they could not be administered through diet," Dr Auwerx noted. "To see if our strategy works on humans, we will have to use massive doses of synthetic molecules."

    "We have good reason to think that humans will also respond to this treatment and that we'll be able to reduce inflammation," he predicted. "But we don't know to what extent. It's important to remember that we're not going after the primary cause of the disease, dystrophin deficiency. Regardless, it would still be quite an accomplishment if we can prolong the patient's life by several years and increase their comfort."

     

     

     

     

    Research explains role of alpha lipoic acid in treatment of diabetic neuropathy

    neuropathy October 21 2016. Buck Institute researchers have identified a sensor in the body for methylgloxal (MGO), a compound formed from glucose that reacts with protein, DNA and lipids to form advanced glycation endproducts (AGEs) implicated in diabetic neuropathy and other diabetes complications. The sensor—a protein known as TRPA1 and its pathway--responds to high levels of MGO and detoxifies it. In a genetically modified roundworm (C. elegans) model of diabetic neuropathy, adding alpha lipoic acid or podocarpic acid to their diets increased TRPA-1 activity.

    "TRP (transient receptor potential) ion channels are evolutionarily conserved proteins that function in sensing many stimuli," explained Jyotiska Chaudhuri, PhD, who, along with Neelanjan Bose, PhD, is a co-first author of the report. "Of them, TRPA1 is a well-known mechanosensory receptor that responds to many noxious stimuli - including pain. Because our model exhibited mechanosensory phenotypes we examined if it played a role in diabetic neuropathy."

    Commenting on their findings, which were reported on October 20, 2016 in Current Biology, Dr Bose revealed that "The worms were no longer hypersensitive to touch; they moved normally, they exhibited no neuronal damage and lived a long healthy life. Our work demonstrates that TRPA1 activity is critical in limiting diabetic complications."

    "We realize that it is a huge leap between humans and C. elegans, but it's important to note that the pathway involved in neuropathy is conserved among species," commented senior researcher Pankaj Kapahi, PhD. "We now have a good model and a novel pathway that allows us to study many of the complications of diabetes."

    In addition to alpha lipoic acid, cinnamon, garlic, and wasabi also activate TRPA1. "There is some evidence that people who eat spicy food are protected against diabetes," Dr Kapahi noted. "Maybe it's because of TRPA-1."

     

     

     

     

    Mediterranean diet, caffeine, fruit may help lower the risk of age-related macular degeneration

    AMD October 19 2016. Research presented on October 16, 2016 at the 120th annual meeting of the American Academy of Ophthalmology has associated a Mediterranean diet, fruit and caffeine as with a lower risk of age-related macular degeneration (AMD).

    The current study included 883 subjects aged 55 or older residing in central Portugal between 2013 and 2015, among whom 449 individuals had early stage macular degeneration. Dietary questionnaire responses were scored on adherence to a Mediterranean diet, which is high in vegetables, fruit, legumes, nuts, whole grains, healthy fats and fish, and relatively low in red meat and butter.

    Among subjects whose scores indicated greater adherence to the diet, there was a 35% lower risk of having AMD compared to those who lacked close adherence. When fruit intake was examined, those who consumed five ounces or more daily had a 15% lower AMD risk than those who consumed less. Higher intake of antioxidants that included vitamins C and E, beta-carotene and caffeine was also associated with protection against AMD. Among subjects who consumed approximately 78 milligrams caffeine per day (the equivalent of a shot of espresso) 54.4% did not have AMD. The study is the first to identify that caffeine as protective against the disease.

    "This research adds to the evidence that a healthy, fruit-rich diet is important to health, including helping to protect against macular degeneration," stated lead author Rufino Silva, MD, PhD, who is a professor of ophthalmology at the University of Coimbra, Portugal; ophthalmologist working at the Centro Hospitalar e Universitário de Coimbra; and investigator at the Association for Innovation and Biomedical Research on Light and Image. "We also think this work is a stepping stone towards effective preventive medicine in AMD."

     

     

     

     

    Trial confirms nicotinamide riboside boosts NAD+ metabolism, sirtuin enzymes

    NAD+ October 17 2016. On October 10, 2016 Nature Communications reported the results of the first controlled clinical trial of nicotinamide riboside (NR), a form of vitamin B3. Researchers at the University of Iowa determined that the compound was more effective than NR precursors niacin and niacinamide at increasing the metabolite nicotinamide adenine dinucleotide (NAD+) and sirtuin enzymes, both associated with longevity.

    In 2004, Charles Brenner, PhD, discovered that nicotinamide riboside occurs in milk and that it can convert to NAD+ in humans. After conducting experiments in rodents, he tested it on himself by consuming a gram daily for a week, accompanied by blood testing that revealed a 2.7 fold increase in NAD+. He further discovered a 45-fold increase in the metabolite NAAD. "While this was unexpected, I thought it might be useful," Dr Brenner stated. "NAD+ is an abundant metabolite and it is sometimes hard to see the needle move on levels of abundant metabolites. But when you can look at a low-abundance metabolite that goes from undetectable to easily detectable, there is a great signal to noise ratio, meaning that NAAD levels could be a useful biomarker for tracking increases in NAD+ in human trials."

    Acting on findings in mice, 12 human subjects were given 100 mg, 300 mg or 1,000 mg NR in different sequences with a week between each dose. Blood and urine samples collected before after each phase were analyzed for NAD+ and its metabolites. The trial revealed that nicotinamide was better than niacin at elevating NAD+ and that NR was superior to nicotinamide. When the compounds' ability to stimulate the activity of sirtuin enzymes was evaluated, niacin was better than nicotinamide and NR was again the most effective. The trial also revealed that NAAD is a biomarker of NR supplementation.

    "This trial shows that oral NR safely boosts human NAD+ metabolism," Dr Brenner reported. "Because the levels of supplementation in mice that produce beneficial effects are achievable in people, it appears than health benefits of NR will be translatable to humans safely."

     

     

     

     

    Coenzyme Q10 increases antioxidant enzymes, lowers inflammation in liver cancer patients

    CoQ10 October 14 2016. An article published on October 6, 2016 in Nutrition Journal reports a benefit for supplementation with coenzyme Q10 (CoQ10) among men and women who underwent surgery for hepatocellular carcinoma (HCC, or liver cancer).

    "A case-control study has recently found that patients with HCC had significantly higher levels of oxidative stress, inflammation, and lower antioxidant capacities," note authors Hsiao-Tien Liu and colleagues at Taiwan's Chung Shan Medical University. "Consequently, it is worth trying an agent that can lower oxidative stress and reduce inflammation in patients with HCC."

    Forty-one patients who were diagnosed with primary HCC following tumor removal were randomized to receive 150 milligrams CoQ10 or a placebo twice daily for two weeks. Blood samples collected before treatment and at weeks 4, 8 and 12 were analyzed for levels of CoQ10 and vitamin E, malondialdehyde (MDA, a marker of oxidative stress), activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), and the inflammation markers high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha and interleukin-6.

    Not surprisingly plasma CoQ10 levels were significantly greater at weeks 4, 8 and 12 in the group that received the supplement. Antioxidant levels were higher and hs-CRP and interleukin-6 levels were lower in CoQ10-supplemented participants by the end of the study. Higher plasma coenzyme Q10 levels were significantly correlated with lower oxidative stress levels and greater antioxidant enzyme activity.

    "This clinical study is the first to demonstrate that a dose of 300 mg/day of coenzyme Q10 supplementation significantly increased antioxidant capacity and reduced the levels of inflammatory markers in patients with HCC after surgery," the authors announced. "We suggest that coenzyme Q10 supplementation could be considered as a complementary treatment strategy for patients with HCC after surgery, particularly those under higher levels of oxidative stress and inflammation."

     

     

     

     

    Prenatal vitamin D supplementation linked with fewer ADHD symptoms

    Prenatal vitamin D supplementation linked with fewer ADHD symptoms October 12 2016. An article published on September 30, 2016 in The Australia & New Zealand Journal of Psychiatry reveals the outcome of a study that found an association between higher umbilical cord blood vitamin D levels and a reduction in the risk of exhibiting attention deficit hyperactivity disorder (ADHD) symptoms in early childhood.

    The study included 1,233 members of Denmark's Odense Child Cohort, which is following 2,500 mothers and their children from early pregnancy to the children's 18th birthdays. 25-hydroxyvitamin D levels were measured in cord blood at birth. Mothers completed a Child Behavior Checklist when their children were an average of 2.7 years of age.

    "For every 10 nmol/L [4 ng/mL] increase in the vitamin D concentration in umbilical blood, the risk of a being among the 10% highest score on the ADHD symptom scale fell by 11%," reported lead researcher Niels Bilenberg, of the University of Southern Denmark. "The trend was clear: those mothers who had taken vitamin D, and had a vitamin D level in their umbilical blood over 25 nmol/L [10 ng/mL], had children with lower ADHD scores," he noted. "This was after we had corrected for other factors that could explain the link, such as the mother's age, smoking, alcohol, obesity, education, [and] number of children, psychiatric disease in the parents, child's sex, age and seasonal variation."

    "We were very surprised that the link was so clear as there was no previous awareness that this link could be identified at such an early age," added coauthors Jens Bull Aaby and Mats Mossin. "It's impossible to say which children will develop ADHD later on, but it will be interesting to further follow up those children who were at the highest end versus the normal range of the ADHD scale."

     

     

     

     

    Raspberries, ellagic acid reveal benefits in two studies

    Raspberries, ellagic acid reveal benefits in two studies October 10 2016. Articles that appeared recently in the Journal of Berry Research report that raspberries and compounds present in the fruit could help support healthy body mass and motor function, including balance, coordination and strength.

    In one study, Neil Shay and colleagues at Oregon State University fed mice a high fat, high sugar diet plus one of the following: raspberry juice concentrate, raspberry puree concentrate, raspberry fruit powder, raspberry seed extract, ellagic acid (a polyphenol that occurs in a relatively high amount in raspberries), raspberry ketone, or a combination of raspberry ketone and ellagic acid. Additional groups of animals received a high fat, high sugar diet alone or a low fat diet.

    While mice that received the high fat and sugar diet alone experienced a significant increase in body mass, the addition of raspberry juice concentrate, raspberry puree concentrate or ellagic acid plus raspberry ketone helped prevent this effect. Of note, mice that received raspberry juice concentrate experienced gains similar to those of animals given a low fat diet. "We hope that the findings from this study can help guide the design of future clinical trials," Dr Shay stated.

    In another study, Barbara Shukitt-Hale, PhD, and her associates at Tufts University's Human Nutrition Research Center on Aging gave 19 month old rats a control diet or a diet enhanced with raspberry extract for 11 weeks. Psychomotor behavior was assessed during week 7 and cognitive testing was conducted during weeks 9-10.

    Animals that received raspberry performed better on psychomotor coordination and balance, and had better muscle tone, strength and stamina than those that received a control diet. "These results may have important implications for healthy aging," stated Dr Shukitt-Hale. "While further research in humans is necessary, animal model studies are helpful in identifying deficits associated with normal aging."

     

     

     

     

    Vitamin E could help protect older men from pneumonia

    Vitamin E could help protect older men from pneumonia October 7 2016. An article that appeared on October 3, 2016 in Clinical Interventions in Aging reported a protective role for vitamin E against pneumonia in older men.

    For the current investigation, Dr Harri Hemilä of the University of Helsinki, Finland analyzed data from the Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study conducted in Finland between 1985-1993. The trial included 29,133 men between the ages of 50 to 69 years who smoked at least five cigarettes daily upon enrollment. Participants received alpha tocopherol (vitamin E), beta carotene, both supplements, or a placebo for five to eight years ending in April 1993.

    The current study was limited to 7,469 ATBC participants who started smoking at age 21 or older. Among this group, supplementation with vitamin E was associated with a 35% lower risk of developing pneumonia in comparison with those who did not receive the vitamin.  Light smokers who engaged in leisure time exercise had a 69% lower risk compared with unsupplemented members of this subgroup. The risk in this subgroup of developing pneumonia by age 74 was 12.9%.

    Among the one-third of the current study's population who quit smoking for a median period of two years, there was a 72% lower risk of pneumonia in association with vitamin E supplementation. In this group, exercisers who received vitamin E experienced an 81% lower pneumonia risk.

    Dr Hemilä observed that the benefit for vitamin E in this study was strongest for older subjects—a group at higher risk of pneumonia.

    "The current analysis of individual-level data suggests that trials on vitamin E and pneumonia on nonsmoking elderly males are warranted," he concluded.

     

     

     

     

    Lower systolic BP predicted to save over 100,000 US lives per year

    Lower systolic BP predicted to save over 100,000 US lives per year October 5 2016. Research presented at the American Heart Association's Council on Hypertension 2016 Scientific Sessions estimates that intensive treatment to lower systolic blood pressure (BP) to below 120 mmHg could save the lives of 107,500 people in the United States per year.

    The estimation was based on findings from the Systolic Blood Pressure Intervention Trial (SPRINT), which included over 9,350 hypertensive men and women at increased risk of cardiovascular disease. Trial participants received two medications with the goal of lowering systolic BP to the standard goal of 140 mmHg, or three medications with a target of 120 mmHg.  The outcome was a 27% reduction in premature mortality when systolic pressure was reduced to less than 120 mmHg in comparison with those who attained a systolic pressure of 140 mmHg.

    Using data from the National Health & Nutrition Examination Survey, Holly Kramer, MD, MPH, and colleagues determined that over 18.1 million American adults were similarly at risk. Based on SPRINT's findings, they estimated that an intensive blood pressure lowering regimen to reach a goal of systolic blood pressure of less than 120 mmHg would prevent 107,500 deaths among those in the US at risk each year, and that two-thirds of those saved would be aged 75 or older. Although intensive drug therapy for high blood pressure causes adverse effects, Dr Kramer noted that the majority of these effects can be reversed by adjusting the dose.

    "When the treatment goal was lowered to a maximum of 120 mmHg, there was a huge reduction in mortality," concluded Dr Kramer, who is an associate professor in the Department of Public Health Sciences and in the Division of Nephrology and Hypertension in the Department of Medicine of Loyola University Chicago Stritch School of Medicine. "Few other medical interventions have such a large effect."

     

     

     

     

    Vitamin D supplementation extends life in mouse model of Huntington's disease

    Vitamin D supplementation extends life in mouse model of Huntington's disease October 3 2016. A recent issue of Acta Neurobiologiae Experimentalis published the finding of researchers at Hungary's University of Szeged of an association between longer life span and supplementation with vitamin D in a transgenic mouse model of Huntington's disease, a progressive neurodegenerative disease.

    The study included 24 mice bred to develop Huntington's disease symptoms and 16 normal mice. Each group was divided to receive vitamin D3 or an inert substance five times per week. Motor status was evaluated prior to treatment and periodically over the course of the study. Treatment continued until the death of all of the members of the Huntington's disease group.

    While no effect on motor performance was observed in the Huntington disease group, vitamin D significantly increased their lifespan. Huntington's disease mice that did not receive vitamin D survived 67 to 94 days in comparison with 74 to 109 days in the treated animals--a 38% increase in median lifespan. According to the authors of the report, the increase is of a similar magnitude as that of other agents tested, including valproate and the combination of valproate and lithium. "Being the first in this field, the authors suggest the potential neuroprotective effect of vitamin D3 in a Huntington's disease model," they write. "This concept seems feasible based on the previously reported proposed protective actions of vitamin D3 against oxidative injury and neuroinflammation, in part via inhibiting the synthesis of inducible nitric oxide synthase, though the contribution of vitamin D receptor-linked neurotrophic effects as well as epigenetic modifications cannot be excluded."

    "The results support the safety and the therapeutic potential of vitamin D3 as a supplementary treatment for Huntington's disease patients, especially for those with established vitamin D3 deficiency," they conclude.

     

     

     

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