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267 CNO REPORT 25 NOV 2019

267CNO07OCT2019

In this issue:

  1. Green tea could hold the key to reducing antibiotic resistance
  2. Probiotic supplements may enhance weight loss in obese children
  3. CBD may alleviate seizures, benefit behaviors in people with neurodevelopmental conditions
  4. Study explains molecular mechanism of botanical folk medicines used to treat hypertension
  5. Type 2 diabetes remission possible with ‘achievable’ weight loss, say researchers
  6. In major meta-analysis, omega-3 fish oil supplements linked with lower cardiovascular risk
  7. Common nutrient supplementation may hold the answers to combatting Alzheimer’s disease
  8. Canadians told to stop taking aspirin to prevent first heart attack, stroke
  9. High fiber diet associated with reduced CV risk in hypertension, type 2 diabetes patients
  10. Metabolic discovery may help in fight against heart disease, diabetes
  11. Randomized controlled trial suggests healthier diet may directly reduce depression
  12. Humans have salamander-like ability to regrow cartilage in joints
  13. Coffee bean extracts alleviate inflammation, insulin resistance in mouse cells
  14. Habitual tea drinking modulates brain efficiency: Evidence from brain connectivity evaluation
  15. New NEWS RELEASE 16-OCT-2019
  16. Aҫaí berry extracts fight malaria in mice study may have the reason why heart medication gives muscle pain
  17. Creatine powers T cells’ fight against cancer
  18. Potato as effective as carbohydrate gels for boosting athletic performance, study finds
  19. Ketogenic diet helps tame flu virus
  20. Forget the Chardonnay, pass me the grape stems! Anti-tumor activity in prostate cancer cells
  21. Omega-3 fish oil as effective for attention as ADHD drugs for some children

 

NEWS RELEASE 23-SEP-2019

Green tea could hold the key to reducing antibiotic resistance

UNIVERSITY OF SURREY

Scientists at the University of Surrey have discovered that a natural antioxidant commonly found in green tea can help eliminate antibiotic resistant bacteria.

The study, published in the Journal of Medical Microbiology, found that epigallocatechin (EGCG) can restore the activity of aztreonam, an antibiotic commonly used to treat infections caused by the bacterial pathogen Pseudomonas aeruginosa.

  1. aeruginosais associated with serious respiratory tract and bloodstream infections and in recent years has become resistant to many major classes of antibiotics. Currently a combination of antibiotics is used to fight P. aeruginosa.

However, these infections are becoming increasingly difficult to treat, as resistance to last line antibiotics is being observed.

To assess the synergy of EGCG and aztreonam, researchers conducted in vitro tests to analyse how they interacted with the P. aeruginosa, individually and in combination. The Surrey team found that the combination of aztreonam and EGCG was significantly more effective at reducing P. aeruginosa numbers than either agent alone.

This synergistic activity was also confirmed in vivo using Galleria mellonella (Greater Wax Moth larvae), with survival rates being significantly higher in those treated with the combination than those treated with EGCG or aztreonam alone. Furthermore, minimal to no toxicity was observed in human skin cells and in Galleria mellonella larvae.

Researchers believe that in P. aeruginosa, EGCG may facilitate increased uptake of aztreonam by increasing permeability in the bacteria. Another potential mechanism is EGCG’s interference with a biochemical pathway linked to antibiotic susceptibility.

Lead author Dr Jonathan Betts, Senior Research Fellow in the School of Veterinary Medicine at the University of Surrey, said:

“Antimicrobial resistance (AMR) is a serious threat to global public health. Without effective antibiotics, the success of medical treatments will be compromised. We urgently need to develop novel antibiotics in the fight against AMR. Natural products such as EGCG, used in combination with currently licenced antibiotics, may be a way of improving their effectiveness and clinically useful lifespan.”

Professor Roberto La Ragione, Head of the Department of Pathology and Infectious Diseases in the School of Veterinary Medicine at the University of Surrey, said:

“The World Health Organisation has listed antibiotic resistant Pseudomonas aeruginosa as a critical threat to human health. We have shown that we can successfully eliminate such threats with the use of natural products, in combination with antibiotics already in use. Further development of these alternatives to antibiotics may allow them to be used in clinical settings in the future.”

NEWS RELEASE 19-SEP-2019

Probiotic supplements may enhance weight loss in obese children

Conference abstract, randomized controlled study, people

EUROPEAN SOCIETY FOR PAEDIATRIC ENDOCRINOLOGY

Probiotic supplements may enhance weight loss and improve the metabolic health of obese children folowing a diet and exercise plan, according to research presented today at the 58th Annual European Society for Paediatric Endocrinology Meeting. The findings of this small trial suggest that probiotic supplements may help obese children lose body weight and also reduce their risk of future metabolic conditions, including type 2 diabetes and heart disease.

Obesity in childhood and adolescence represents a major, growing, health problem worldwide, which can lead to the development of expensive, serious and debilitating complications, including heart disease and type 2 diabetes. Probiotics are live microorganisms thought to have health benefits through improving or restoring the diversity of our gut bacteria, also known as the microbiome. Although some studies have reported benefits of probiotic consumption for health and weight loss in adults, its effectiveness has not been fully investigated in obese children.

In this study, Professor Rui-Min Chen and colleagues at Fuzhou Children’s Hospital of Fujian, China, conducted a randomised, double-blind trial of probiotic effects on the health of obese children, aged 6-14 years old. All 54 study participants were following a reduced-calorie diet combined with an exercise regime. Their body weight and markers of metabolic health (blood lipid levels, blood glucose levels, insulin levels and inflammatory markers) were measured before and at the end of the 12 week study. Children treated with probiotic supplements lost significantly more weight and had lower levels of markers that indicate poor metabolic health.

Prof Chen states, “Our findings suggest that probiotic supplementation may help with weight loss and improve metabolic health in obese children, and that this may be an effective strategy for the prevention and treatment of obesity in the future.”

Although Prof Chen, cautions, “More work is needed to confirm these findings, our number of participants was small and limited to the Fuijan area. Other studies have also reported no benefits from probiotic treatment in obese children but these were much shorter in duration. So, further investigation is needed before any medical recommendations can be made.”

The team now plan to conduct larger trials examining the effect of probiotics on the metabolic health of obese children, and to extend their investigations to analyse how they alter the gut, with the aim of better understanding the link between gut bacteria and obesity risk.

Prof Chen comments, “Childhood obesity is a growing problem that needs early intervention to prevent long-term health problems; microbiome-based treatments could be a new and more effective strategy for tackling this serious epidemic.”

NEWS RELEASE 18-SEP-2019

CBD may alleviate seizures, benefit behaviors in people with neurodevelopmental conditions

UNC School of Medicine researchers led by Ben Philpot, PhD, and Bin Gu, PhD, found that cannabidiol had anti-seizure effects and behavior benefits in animal models of Angelman syndrome, a neurodevelopmental disorder.

UNIVERSITY OF NORTH CAROLINA HEALTH CARE

 

CHAPEL HILL, NC – September 18, 2019 – A marijuana plant extract, also known as cannabidiol (CBD), is being commonly used to improve anxiety, sleep problems, pain, and many other neurological conditions. Now UNC School of Medicine researchers show it may alleviate seizures and normalize brain rhythms in Angelman syndrome, a rare neurodevelopmental condition.

Published in the Journal of Clinical Investigation, the research conducted using Angelman syndrome animal models shows that CBD could benefit kids and adults with this serious condition, which is characterized by intellectual disability, lack of speech, brain rhythm dysfunction, and deleterious and often drug-resistant epilepsy.

“There is an unmet need for better treatments for kids with Angelman syndrome to help them live fuller lives and to aid their families and caregivers,” said Ben Philpot, PhD, Kenan Distinguished Professor of Cell Biology and Physiology and associate director of the UNC Neuroscience Center. “Our results show CBD could help the medical community safely meet this need.”

CBD, which is a major phytocannabinoid constituent of cannabis, has already shown to have anti-epileptic, anti-anxiety, and anti-psychotic effects. And in 2018, the FDA approved CBD for the treatment of seizures associated with two rare forms of epilepsy, but little is known about the potential anti-seizure and behavioral effects of CBD on Angelman symptom.

The Philpot lab is a leader in the creation of genetically modified mouse models of neurodevelopmental disorders, and they use these models to identify new treatments for various diseases, such as Rett, Pitt-Hopkins, and Angelman syndromes.

In experiments led by first author Bin Gu, PhD, a postdoctoral fellow in the Philpot lab, the UNC-Chapel Hill researchers systematically tested the beneficial effects of CBD on seizures, motor deficits, and brain activity abnormalities – as measured by EEG – in mice that genetically model Angelman syndrome, with the expectation that this information could guide eventual clinical use.

The researchers found that a single injection of CBD substantially lessened seizure severity in mice when the seizures were experimentally triggered by elevated body temperature or loud sounds. A typical anti-convulsant dose of CBD (100 mg/kg) caused mild sedation in mice but had little effect on motor coordination or balance. CBD also restored the normal brain rhythms which are commonly impaired in Angelman syndrome.

“We’re confident our study provides the preclinical framework necessary to better guide the rational development of CBD as a therapy to help lessen seizures associated with Angelman syndrome and other neurodevelopmental disorders,” Gu said.

Philpot and Gu added that patients and families should always seek advice from their physician before taking any CBD products, and that a human clinical trial is needed to fully understand its efficacy and safety.

NEWS RELEASE 30-SEP-2019

Study explains molecular mechanism of botanical folk medicines used to treat hypertension

Lavender, fennel and chamomile among herbs discovered to act upon a shared therapeutic target in blood vessels

UNIVERSITY OF CALIFORNIA – IRVINE

Irvine, Calif. – September 30, 2019 – Common herbs, including lavender, fennel and chamomile, have a long history of use as folk medicines used to lower blood pressure. In a new study, University of California, Irvine researchers explain the molecular mechanisms that make them work.

Published today in Proceedings of the National Academy of Sciences (PNAS), the study illustrates how many of the known traditional botanical plants used to lower blood pressure activate a specific potassium channel (KCNQ5) in blood vessels. KCNQ5, together with other potassium channels including KCNQ1 and KCNQ4, is expressed in vascular smooth muscle. When activated, KCNQ5 relaxes blood vessels, making it a logical mechanism for at least part of the hypotensive actions of certain botanical folk medicines.

“We found KCNQ5 activation to be a unifying molecular mechanism shared by a diverse range of botanical hypotensive folk medicines. Lavandula angustifolia, commonly called lavender, was among those we studied. We discovered it to be among the most efficacious KCNQ5 potassium channel activators, along with fennel seed extract and chamomile,” said Geoff Abbott, PhD, professor of physiology and biophysics at the UCI School of Medicine and senior investigator on the study.

Interestingly, the KCNQ5-selective potassium channel activation feature found in the botanicals is lacking in the modern synthetic pharmacopeia. Until now, it seems to have eluded conventional screening methods utilizing chemical libraries, which may account for why it is not a recognized feature of synthetic blood pressure medications.

“Our discovery of these botanical KCNQ5-selective potassium channel openers may enable development of future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy,” said Abbott.

Documented use of botanical folk medicines stretches back as far as recorded human history. There is DNA evidence, dating back 48,000 years, that suggests the consumption of plants for medicinal use by Homo neanderthalensis. Archaeological evidence, dating back 800,000 years, even suggests non-food usage of plants by Homo erectus or similar species. Today, evidence of the efficacy of botanical folk medicines ranges from anecdotal to clinical trials, however the underlying molecular mechanisms often remain elusive.

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NEWS RELEASE 30-SEP-2019

Type 2 diabetes remission possible with ‘achievable’ weight loss, say researchers

UNIVERSITY OF CAMBRIDGE

People who achieve weight loss of 10% or more in the first five years following diagnosis with type 2 diabetes have the greatest chance of seeing their disease go into remission, according to a study led by the University of Cambridge.

The findings suggest that it is possible to recover from the disease without intensive lifestyle interventions or extreme calorie restrictions.

Type 2 diabetes affects 400 million people worldwide and increases the risk of heart disease, stroke, blindness and amputations. While the disease can be managed through a combination of positive lifestyle changes and medication, it is also possible for the high blood glucose levels that define diabetes to return to normal – through significant calorie restriction and weight loss. An intensive low-calorie diet involving a total daily intake of 700 calories (less than one cheeseburger) for 8 weeks has been associated with remission in almost nine out of ten people with recently diagnosed diabetes and in a half of people with longstanding disease.

However, there is little evidence to show whether the same effect can be achieved by people undergoing less intensive interventions, which are more feasible and potentially scalable to the wider population. To answer this question, a team led by researchers at the University of Cambridge studied data from the ADDITION-Cambridge trial, a prospective cohort study of 867 people with newly diagnosed diabetes aged 40 and 69 years recruited from general practices in the eastern region.

The research was funded by Wellcome, the Medical Research Council and the National Institute for Health Research.

The researchers found that 257 participants (30%) participants were in remission at five-year follow-up. People who achieved weight loss of 10% or more within the first five years after diagnosis were more than twice as likely to go into remission compared to people who maintained the same weight.

“We’ve known for some time now that it’s possible to send diabetes into remission using fairly drastic measures such as intensive weight loss programmes and extreme calorie restriction,” says Dr Hajira Dambha-Miller from the Department of Public Health and Primary Care.

“These interventions can be very challenging to individuals and difficult to achieve. But, our results suggest that it may be possible to get rid of diabetes, for at least five years, with a more modest weight loss of 10%. This will be more motivating and hence more achievable for many people.”

Senior author Professor Simon Griffin of the MRC Epidemiology Unit added: “This reinforces the importance of managing one’s weight, which can be achieved through changes in diet and increasing physical activity. Type 2 diabetes, while a chronic disease, can lead to significant complications, but as our study shows, can be controlled and even reversed.”

In order to clarify the best way to help patients with type 2 diabetes achieve sustained weight loss, the team is currently undertaking a study called GLoW (Glucose Lowering through Weight management). The study compares the current education programme offered by the NHS to people after they have been diagnosed, with a programme delivered by WW (formerly Weight Watchers®). The team is looking to recruit individuals who have been diagnosed with type 2 diabetes within the last three years, have not attended a structured education programme and are able to visit one of our testing centres in Wisbech, Ely or Addenbrooke’s Hospital. Further details can be found at the GLOW Study website.

NEWS RELEASE 30-SEP-2019

In major meta-analysis, omega-3 fish oil supplements linked with lower cardiovascular risk

HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH

Boston, MA – People who received omega-3 fish oil supplements in randomized clinical trials had lower risks of heart attack and other cardiovascular disease (CVD) events compared with those who were given placebo, according to a new meta-analysis from Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital. Researchers found an association between daily omega-3 supplementation and reduced risk of most CVD outcomes, including heart attack, death from coronary heart disease, and death from CVD, but did not see benefit for stroke. In addition, higher doses of omega-3 fish oil supplements appeared to provide even greater risk reduction.

The study will be published online September 30, 2019 in the Journal of the American Heart Association.

“This meta-analysis provides the most up-to-date evidence regarding the effects of omega-3 supplementation on risk of multiple CVD outcomes. We found significant protective effects of daily omega-3 supplementation against most CVD outcome risks and the associations appeared to be in a dose-response manner,” said first author Yang Hu, a postdoctoral fellow in the Department of Nutrition at Harvard Chan School.

While observational studies have shown an association between fish consumption and lower heart disease risk, results from randomized controlled trials (RCTs) have been inconsistent. Two reviews published last year did not find clear evidence for benefit.

In this new analysis, the researchers did an updated meta-analysis that included three recently completed large-scale trials, which increased the sample size by 64%. The total population analyzed by Hu and colleagues included more than 120,000 adults in 13 randomized trials worldwide. The analysis included the VITAL trial, the largest randomized trial of omega-3s to date.

The findings showed that people who took daily omega-3 fish oil supplements, compared with those who took a placebo, lowered their risk for most CVD outcomes except stroke, including an 8% reduced risk for heart attack and coronary heart disease (CHD) death. The association was particularly evident at higher doses of omega-3 fish oil supplementation. This finding may suggest that marine omega-3 supplementation dosage above the 840 mg/day used in most randomized clinical trials may provide greater reductions in CVD risk. Given that several million people experience these CVD events worldwide each year, even small reductions in risk can translate into hundreds of thousands of heart attacks and CVD deaths avoided, according to the researchers.

“Although public health recommendations should focus on increasing fish consumption, having an overall heart-healthy diet, being physically active, and having other healthy lifestyle practices, this study suggests that omega-3 supplementation may have a role in appropriate patients,” said senior author JoAnn Manson, chief of the Division of Preve

NEWS RELEASE 27-SEP-2019

Common nutrient supplementation may hold the answers to combatting Alzheimer’s disease

ARIZONA STATE UNIVERSITY

In a new study, Biodesign researchers reveal that a lifelong dietary regimen of choline holds the potential to prevent Alzheimer’s disease (AD).

Choline is a safe and easy-to-administer nutrient that is naturally present in some foods and can be used as a dietary supplement. Lead author Ramon Velazquez and his colleagues at the ASU-Banner Neurodegenerative Disease Research Center (NDRC) looked into whether this nutrient could alleviate the effects of Alzheimer’s.

Earlier this year, Velazquez and colleagues found transgenerational benefits of AD-like symptoms in mice whose mothers were supplemented with choline. The latest work expands this line of research by exploring the effects of choline administered in adulthood rather than in fetal mice.

The study focuses on female mice bred to develop AD-like symptoms. Given the higher prevalence of AD in human females, the study sought to establish the findings in female mice. Results showed that when these mice are given high choline in their diet throughout life, they exhibit improvements in spatial memory, compared with those receiving a normal choline regimen.

Notably, findings published in July 2019 from a group in China found benefits of lifelong choline supplementation in male mice with AD-like symptoms. “Our results nicely replicate findings by this group in females,” Velazquez says.

Intriguingly, the beneficial effects of lifelong choline supplementation reduce the activation of microglia. Microglia are specialized cells that rid the brain of deleterious debris. Although they naturally occur to keep the brain healthy, if they are overactivated, brain inflammation and neuronal death, common symptoms of AD, will occur.

The observed reductions in disease-associated microglia, which are present in various neurodegenerative diseases, offer exciting new avenues of research and suggest ways of treating a broad range of disorders, including traumatic brain injuries, multiple sclerosis and Parkinson’s disease.

The findings appear in the current issue of the journal Aging Cell.

Supplementing the brain with additional choline

Choline acts to protect the brain from Alzheimer’s disease in at least two ways, both of which are explored in the new study. First, choline blocks the production of amyloid-beta plaques. Amyloid-beta plaques are the hallmark pathology observed in Alzheimer’s disease.

Secondly, choline supplementation reduces the activation of microglia. Over-activation of microglia causes brain inflammation and can eventually lead to neuronal death, thereby compromising cognitive function. Choline supplementation reduces the activation of microglia, offering further protection from the ravages of AD.

Mechanistically, the reductions in microglia activation are driven by alteration of two key receptors, the alpha7 nicotinic acetylcholine and Sigma-1 receptor. A new report this year found that choline can act as an agonist for Sigma-1 receptors. These results confirm that lifelong choline supplementation can alter the expression of the Sigma-1 receptor, which thereby attenuates microglia activation. (An agonist is a substance that activates a given receptor.)

The devastating decline

In the scientific community, it is well understood that Alzheimer’s disease causes harm to the brain long before clinical symptoms are made evident. And once these symptoms are identified, it is too late – the disease has become irreversible. In addition to causing disorientation and memory loss, the disease causes loss of motor control in those who are afflicted.

Approximately 6 million individuals are living with AD in the U.S. currently, and the disease is projected to afflict 14 million Americans in the next four decades. Economically, the costs associated with managing Alzheimer’s are expected to exceed $20 trillion in the same time span.

To develop more effective treatments, we first need to understand the disease itself, which is one of the tallest orders facing modern medicine today.

Women are at a particular increased risk of developing Alzheimer’s disease. This study shows that the simple addition of choline in the diet throughout life may reduce AD pathology in those most affected by the disease. Additionally, these results have implications for other neurodegenerative afflictions where activated microglia are rampant says Velazquez.

Guidelines for dietary choline

Prior research concerning Alzheimer’s has indicated that there is no one factor at play. Rather, a multitude of factors that are believed to contribute to the development of the disease, including genetics, age and lifestyle. Additionally, studies suggest that diet can have a significant effect in increasing or lowering the risk of cognitive decline.

A recent report suggested that plant-based diets may be determinantal due to the lack of important nutrients, including choline. Another recent report found that the increase in cases of dementia in the United Kingdom may be associated with a lack of recommendations for choline in the diet throughout life. In fact, as of August 2019, AD and other forms of dementia are now the leading cause of death in England and Wales.

The current established adequate intake level of choline for adult women (>19yrs of age) is 425mg/day, and 550mg/day for adult men. A converging line of evidence indicates that even the current recommended daily intake (RDI) may not be optimal for a proper aging process, especially in women. This is relevant, given the higher incidence of AD seen in women. This suggests that additional choline in diet may be beneficial in preventing neuropathological changes associated with the aging brain.

The tolerable upper limit (TUL) of choline unlikely to cause side effects for adult females and males (>19yrs of age) is 3500mg/day, which is 8.24 times higher than the 425mg/day recommendation for females and 6.36 times higher than the 550mg/day recommendation for males. “Our choline supplemented diet regimen was only 4.5 times the RDI, which is well below the TUL and makes this a safe strategy”, Velazquez says.

Choline can be found in various foods. According to the United States Department of Agriculture (USDA), high levels of choline are found in chicken liver (3oz; 247mg), eggs (1 large egg with yolk;147mg), beef grass-fed steak (3oz; 55mg), wheat germ (1oz toast; 51mg), milk (8oz; 38mg), and Brussel sprouts (1/2 cup; 32mg). Additionally, vitamin supplements containing choline, for example choline bitartrate and choline chloride, are widely available at affordable costs. The vitamin supplements containing choline are particularly relevant for those who are on plant-based diets.

Effects of choline

All plant and animal cells require choline to maintain their structural integrity. It has long been recognized that choline is particularly important for brain function.

The human body uses choline to produce acetylcholine, a neurotransmitter responsible for functioning memory, muscle control and mood. Choline also is used to build cell membranes and plays a vital role in regulating gene expression. Additionally, a new report in Jan 2019 found that choline acts as an agonist for Sigma-1 receptors, which are implicated in AD pathogenesis.

In this study, researchers used a water maze to determine whether the mice with AD-like symptoms that received lifelong supplemental choline exhibited improvements in spatial memory. It was found that this was indeed the case, and subsequent examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed changes in toxic amyloid-beta and reductions in microglia activation, which reduces brain inflammation.

Due to alterations of key microglia receptors induced by choline, the improvements in behavior may be attributed to reduced microglia activation. “We found that lifelong choline supplementation altered the alpha7 nicotinic acetylcholine and Sigma-1 receptor, which may have resulted in the reduction of diseased associated activated microglia,” Velazquez said. These receptors regulate CNS immune response and their dysregulation contributes to AD pathogenesis.

The study’s significance establishes beneficial effects of nutrient supplementation in females throughout life. “Our work nicely complements recent work showing benefits in male AD-mice on a lifelong choline supplementation regimen.” “No one has shown lifelong benefits of choline supplementation in female AD-mice.” “That’s what is novel about our work.”

Choline is an attractive candidate for prevention of AD as it is considered a very safe alternative, compared with many pharmaceuticals. “At 4.5 times the RDI (recommended daily intake), we are well under the tolerable upper limit, making this a safe preventive therapeutic strategy.”

Although the results improve the understanding of the disease, the authors suggest that clinical trials will be necessary to confirm whether choline can be used as a viable treatment in the future.

NEWS RELEASE 2-OCT-2019

Canadians told to stop taking aspirin to prevent first heart attack, stroke

Canadian family physicians warned potential harm of daily dose outweighs benefits

UNIVERSITY OF ALBERTA FACULTY OF MEDICINE & DENTISTRY

If you’ve never had a heart attack or stroke, you likely should not be taking aspirin to prevent them, according to new research.

“This is the most significant practice-changing evidence to come out in the past year,” said Michael Kolber, a family medicine professor at the University of Alberta and co-author of a paper published in Canadian Family Physician, along with recent University of Calgary family medicine graduate Paul Fritsch.

Kolber and Fritsch reviewed three large, randomized, placebo-controlled studies published in 2018 that showed the risk of major internal bleeding associated with taking an aspirin a day is higher than any preventative benefits.

“These aren’t nosebleeds or bleeding gums,” Fritsch said. “These are major internal bleeds where the patients need hospitalization and perhaps a blood transfusion, so they’re of major clinical, and also personal, significance.”

Fritsch said one of the studies also showed an increase in deaths from all causes, and in particular cancer deaths, among the patients who took aspirin, which is also called acetylsalicylic acid or ASA.

The advice to take a daily aspirin to prevent heart disease became dogma in the 1990s but it was based on flawed research, according to Kolber.

In an earlier study, Kolber found that 40 per cent of Albertans over the age of 50 take aspirin to prevent cardiovascular disease, even though most have never had a cardiovascular event. He noted that aspirin is still considered beneficial for those who do have heart disease.

“We really see an aspirin gap,” said Kolber. “There are a lot of people taking aspirin for primary prevention who don’t need it, and there’s a group of people who already have cardiovascular disease who aren’t taking it, and they should be.”

Kolber advises those who have never had a heart problem to use other preventive measures.

“Instead of just taking a daily aspirin like we’ve been taught for a generation, we would recommend patients stop smoking, exercise, track their blood pressure and consider the Mediterranean diet.”

Kolber said people with elevated future cardiovascular risk might consider taking a statin, which lowers cholesterol.

“The evidence for those measures is far superior to the evidence for aspirin,” he said.

Kolber and Fritsch’s findings were distributed electronically through Tools for Practice, evidence summaries compiled by the U of A’s evidence-based medicine team, PEER (Patients, Experience, Evidence, Research). They are read by 40,000 health-care professionals around the world and funded by the Alberta College of Family Physicians and the Canadian College of Family Physicians.

NEWS RELEASE 3-OCT-2019

High fiber diet associated with reduced CV risk in hypertension, type 2 diabetes patients

Medical nutrition therapy paired with medical treatment may reduce future heart disease

AMERICAN COLLEGE OF CARDIOLOGY

Patients with hypertension and Type 2 diabetes who consume a high fiber diet had improvement in their blood pressure, cholesterol and fasting glucose, according to a study presented at the American College of Cardiology (ACC) Middle East Conference 2019 together with the 10th Emirates Cardiac Society Congress. The conference is Oct. 3-5 in Dubai, United Arab Emirates.

Hypertension and diabetes are major risk factors for future cardiovascular disease. Diet also plays a role in the severity of cardiovascular disease. Researchers from Care Well Heart and Super Specialty Hospital in Amritsar, India, investigated the relation between a high fiber diet and its impact on cardiovascular disease risk factors.

According to guidelines from the National Institute of Nutrition and the Indian Council of Medical Research, the recommended dietary allowance (RDA) for dietary fiber is 40gm/2000kcal. Patients in this study had Type 2 diabetes and a calorie intake of 1,200-1,500kcal, causing their RDA for fiber to be 24-30gm. The fiber intake of these patients was increased up to 20 to 25 percent from the recommended allowances for them to be consuming a high fiber diet.

The study tracked 200 participants’ fiber intake for six months and included check-ups at the start of the study, three months and six months. Participants were provided diet prescriptions, which included detailed lists of different food groups with portion sizes in regional languages. Qualified dietitians provided the information through regular counseling sessions and used audio-visual aids to ensure understanding among study participants.

The researchers tracked participants’ fiber intake several ways, including having patients send photos of their meals on WhatsApp–which not only helped in knowing their fiber intake but also helped approximate portion sizes–and telephone calls three times a week during which detailed dietary recall was taken.

“Comprehensive evaluation of etiological effects of dietary factors on cardiometabolic outcomes, their quantitative effects and corresponding optimal intakes are well-established,” said Rohit Kapoor, MD, medical director of Care Well Heart and Super Specialty Hospital and lead author of the study. “This study helps us determine three important things for this patient population. Firstly, a high fiber diet is important in cases of diabetes and hypertension to prevent future cardiovascular disease. Secondly, medical nutrition therapy and regular counseling sessions also hold great importance in treating and prevention of diabetes and hypertension. Thirdly, this type of diet in combination with medical treatment can improve dyslipidemia, pulse wave velocity, waist-to-hip ratio and hypertension.”

Participants on a high fiber diet experienced significant improvement in several cardiovascular risk factors, including a 9 percent reduction in serum cholesterol, 23 percent reduction in triglycerides, 15 percent reduction of systolic blood pressure and a 28 percent reduction of fasting glucose. The researchers found a high fiber diet is inversely related with cardiovascular risk factors and plays a protective role against cardiovascular disease.

NEWS RELEASE 2-OCT-2019

Metabolic discovery may help in fight against heart disease, diabetes

CORNELL UNIVERSITY

 

ITHACA, N.Y. – Researchers at Cornell University have uncovered a key step in how the human body metabolizes sugar, which could lead to better treatment and prevention of heart disease, obesity and Type 2 diabetes.

Martha S. Field, assistant professor of nutritional sciences, has further characterized the human metabolic pathway by identifying two enzymes that convert the sugar erythrose into erythritol.

This reaction represents the final step in the conversion of glucose to erythritol in human metabolism.

“Your normal diet contains fruits, vegetables and beans and you will inevitably ingest sugar alcohols,” said Field, who is the senior author on the paper. Knowing how the body makes sugar alcohols opens up an array of new possibilities for treatment and prevention of heart disease and Type 2 diabetes.

Previous research had shown that elevated levels of erythritol in blood plasma are associated with future increased fat storage and weigh gain, so erythritol serves as a biomarker for weigh gain, possible heart disease and diabetes.

“That raises the question: Are elevated levels of erythritol in plasma a causal factor in weight gain, and, if so, could this newly discovered metabolism be a path toward intervention in our fight to combat obesity?” she said.

NEWS RELEASE 9-OCT-2019

Randomized controlled trial suggests healthier diet may directly reduce depression

Even a brief period of healthy eating may provide longer-term improvements in mood

Young adults with depression whose diet is usually unhealthy showed significantly fewer symptoms of depression after eating a healthy diet for three weeks, according to a study published October 9, 2019 in the open-access journal PLOS ONE by Heather Francis from Macquarie University, Australia, and colleagues.

While much research has shown that eating a healthy diet rich in fruit, vegetables, fish, and lean meat is associated with a reduced risk of depression, there have been very few randomized controlled trials directly examining the link between the two, including for young adults, who are establishing health patterns and are also at higher risk for depression.

Francis and colleagues studied 76 university students (17-35 years old) exhibiting moderate-to-high depression symptoms and following a poor diet based on the Australian Guide to Healthy Eating (high in processed foods, sugar, and saturated fats). They randomized participants into a “diet change” group or a “regular diet” group. The diet change group was given brief instructions on improving their diet, as well as a healthy food hamper and $60 towards future groceries. Each group member also received two subsequent check-ins via phone call. The regular diet group did not get any diet instructions and were simply asked to return after the three weeks were up. Before and after the intervention, the researchers assessed participants’ scores for depression, anxiety and overall mood, and their performance on several learning and reasoning tasks.

At the end of the three weeks, the diet change group had successfully maintained a healthy diet and showed significant improvement in mood, with depression scores shifting into the normal range. The regular diet group’s depression scores remained stable in the moderate-to-high range. The diet change group also showed significantly lower anxiety scores than the regular diet group, though other measures were not significantly different between the groups.

The authors followed up with 33 of the participants after three months. In this small sample, they found that while only 21 percent of these participants fully maintained the healthy diet, those that did maintained their improvements in mood.

This study is limited in that the no change group received no intervention – ideally, this group would have received alternative diet instructions, check-ins and monetary contributions to parallel the diet change group. These findings are also derived from a small, specific population of university students. However, they provide preliminary evidence that relatively small, simple diet adjustments can directly improve depression symptoms, and that these effects can last up to three months.

The authors add: “Modifying diet to reduce processed food intake and increase consumption of fruit, vegetables, fish and olive oil improved depression symptoms in young adults. These findings add to a growing literature showing a modest change to diet is a useful adjunct therapy to reduce symptoms of depression.”

NEWS RELEASE 9-OCT-2019

Humans have salamander-like ability to regrow cartilage in joints

The process could be harnessed as a treatment for osteoarthritis

DUKE UNIVERSITY MEDICAL CENTER

DURHAM, N.C. – Contrary to popular belief, cartilage in human joints can repair itself through a process similar to that used by creatures such as salamanders and zebrafish to regenerate limbs, researchers at Duke Health found.

Publishing online Oct. 9 in the journal Science Advances, the researchers identified a mechanism for cartilage repair that appears to be more robust in ankle joints and less so in hips. The finding could potentially lead to treatments for osteoarthritis, the most common joint disorder in the world.

“We believe that an understanding of this ‘salamander-like’ regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs,” said senior author Virginia Byers Kraus, M.D., Ph.D., a professor in the departments of Medicine, Pathology and Orthopedic Surgery at Duke.

Kraus and colleagues, including lead author Ming-Feng Hsueh, Ph.D., devised a way to determine the age of proteins using internal molecular clocks integral to amino acids, which convert one form to another with predictable regularity.

Newly created proteins in tissue have few or no amino acid conversions; older proteins have many. Understanding this process enabled the researchers to use sensitive mass spectrometry to identify when key proteins in human cartilage, including collagens, were young, middle-aged or old.

They found that the age of cartilage largely depended on where it resided in the body. Cartilage in ankles is young, it’s middle-aged in the knee and old in the hips. This correlation between the age of human cartilage and its location in the body aligns with how limb repair occurs in certain animals, which more readily regenerate at the furthest tips, including the ends of legs or tails.

The finding also helps explain why injuries to people’s knees and, especially, hips take a long time to recover and often develop into arthritis, while ankle injuries heal quicker and less often become severely arthritic.

The researchers further learned that molecules called microRNA regulate this process. Not surprisingly, these microRNAs are more active in animals that are known for limb, fin or tail repair, including salamanders, zebrafish, African fresh water fish and lizards.

These microRNAs are also found in humans — an evolutionary artifact that provides the capability in humans for joint tissue repair. As in animals, microRNA activity varies significantly by its location: it was highest in ankles compared to knees and hips and higher in the top layer of cartilage compared to deeper layers of cartilage.

“We were excited to learn that the regulators of regeneration in the salamander limb appear to also be the controllers of joint tissue repair in the human limb,” Hsueh said. “We call it our ‘inner salamander’ capacity.”

The researchers said microRNAs could be developed as medicines that might prevent, slow or reverse arthritis.

“We believe we could boost these regulators to fully regenerate degenerated cartilage of an arthritic joint. If we can figure out what regulators we are missing compared with salamanders, we might even be able to add the missing components back and develop a way someday to regenerate part or all of an injured human limb,” Kraus said. “We believe this is a fundamental mechanism of repair that could be applied to many tissues, not just cartilage.”

NEWS RELEASE 11-OCT-2019

Coffee bean extracts alleviate inflammation, insulin resistance in mouse cells

UNIVERSITY OF ILLINOIS COLLEGE OF AGRICULTURAL, CONSUMER AND ENVIRONMENTAL SCIENCES

URBANA, Ill. – When coffee beans are processed and roasted the husk and silverskin of the bean are removed and unused, and often are left behind in fields by coffee producers.

Food science and human nutrition researchers at the University of Illinois are interested in the potential of inflammation-fighting compounds found in the silverskin and husk of coffee beans, not only for their benefits in alleviating chronic disease, but also in adding value to would-be “waste” products from the coffee processing industry.

A recent study, published in Food and Chemical Toxicology, shows that when fat cells of mice were treated with water-based extracts from coffee beans skins, two phenolic compounds–protocatechuic acid and gallic acid–in particular reduced fat-induced inflammation in the cells and improved glucose absorption and insulin sensitivity.

The findings show promise for these bioactive compounds, when consumed as part of the diet, as a strategy for preventing obesity-related chronic illnesses, such as Type 2 diabetes and cardiovascular disease.

“In my lab we have studied bioactive compounds from different foods, and have seen the benefits for the prevention of chronic diseases,” says Elvira Gonzalez de Mejia, professor of food science in the College of Agricultural, Consumer and Environmental Sciences at U of I, and co-author of the study. “This material from coffee beans is interesting mainly because of its composition. It’s been shown to be non-toxic. And these phenolics have a very high anti-oxidant capacity.”

For the study, the researchers looked at two types of cells, macrophages (immune response cells) and adipocytes (fat cells), and the effect of the combined compounds from the extracts, as well as the individual pure phenolics, on adipogenesis–the production and metabolism of fat cells in the body–and the related hormones. They also looked at the effect on inflammatory pathways.

When obesity-related inflammation is present, the two types of cells work together–stuck in a loop–to increase oxidative stress and interfere with glucose uptake, worsening the situation.

In order to block this loop and prevent chronic disease, the researchers’ goals are to eliminate or reduce as much inflammation as possible in order to allow glucose uptake to be facilitated, as well as to have healthy cells that will produce adequate insulin.

Miguel Rebollo-Hernanz, a visiting scholar in de Mejia’s lab, and lead author of the study, explains how the results provide insights into the mechanism of action of these extracts and pure compounds, and their potential efficacy for future studies in humans or animals.

For the study, the fat cells and immune cells were cultured together to recreate the “real-life” interaction between the two cells.

“We evaluated two extracts and five pure phenolics, and we observed that these phenolics, mainly protocatechuic acid and gallic acid, were able to block this fat accumulation in adipocytes mainly by stimulating lipolysis [the breakdown of fats], but also by generating ‘brown-like’ or ‘beige’ adipocytes,” Rebollo-Hernanz explains.

Significantly, these “brown-like” cells are known as fat burners, and they contain more mitochondria, an important organelle in cells that turns nutrients into energy. In the study, the researchers observed that some phenolics were able to stimulate browning of the fat cells, increasing the content of mitochondria in adipocytes, or fat cells.

“Macrophages are present in the adipose tissue and when adipose tissue grows excessively, there are interactions that stimulate inflammation and oxidative stress,” Rebollo-Hernanz says. “We saw that these phenolics were able to reduce and decrease the secretion of inflammatory factors, but also decrease oxidative stress.”

When macrophages interact with fat cells, the cells have fewer mitochondria. Having less mitochondria, they lose the capacity of burning lipids. Using these phenolics, the researchers found that this impact of macrophages on the fat cells was completely blocked. The fat cells maintained their function.

“The compounds we tested were able to inhibit inflammation in the macrophage. That means inhibiting many markers that produce inflammation to the adipocytes. Those were blocked,” de Mejia says. “Coming to the adipocytes themselves, we saw inhibition of different markers related to inflammation as well. Absorption of glucose was improved because the glucose transporters were present. And this went back and forth.

“Now we know that in the presence of these compounds we can reduce inflammation, reduce adipogenesis, and decrease the ‘loop’ that helps the two types of cells grow and develop bad compounds that will negatively affect the whole system,” she adds.

The researchers also stressed the positive impact on the environment of using the coffee bean by-products.

During coffee processing, the bean is separated from the husk, the external outer layer of the bean. After the bean is roasted, the silverskin layer is separated. “It’s a huge environmental problem because when they separate this husk after processing, it usually stays in the field fermenting, growing mold, and causing problems,” de Mejia explains. Worldwide 1,160,000 tons of husk are left in fields per year, potentially causing contamination.

Additionally, 43,000 tons of silverskin is produced each year, which, de Mejia adds, may be easier to utilize because it stays with the bean as it is exported to different countries to be roasted.

“Once producers see the value, they will treat these materials as an ingredient instead of a waste,” de Mejia says. “It will require good collaboration between academic institutions, industry, and the public sector to solve this problem, but the market is there for these products.”

NEWS RELEASE 11-OCT-2019

Habitual tea drinking modulates brain efficiency: Evidence from brain connectivity evaluation

The researchers recruited healthy older participants to two groups according to their history of tea drinking frequency and investigated both functional and structural networks to reveal the role of tea drinking on brain organization.

IMPACT JOURNALS LLC

CREDIT: JUNHUA LI JUNHUA.LI@ESSEX.AC.UK LEI FENG PCMFL@NUS.EDU.SG

The researchers recruited healthy older participants to two groups according to their history of tea drinking frequency and investigated both functional and structural networks to reveal the role of tea drinking on brain organization.

The suppression of hemispheric asymmetry in the structural connectivity network was observed as a result of tea drinking.

The authors did not observe any significant effects of tea drinking on the hemispheric asymmetry of the functional connectivity network.

Dr. Junhua Li and Dr. Lei Feng said, “Tea has been a popular beverage since antiquity, with records referring to consumption dating back to the dynasty of Shen Nong (approximately 2700 BC) in China.”

Tea is consumed in diverse ways, with brewed tea and products with a tea ingredient extremely prevalent in Asia, especially in China and Japan.

Although individual constituents of tea have been related to the roles of maintaining cognitive abilities and preventing cognitive decline, a study with behavioural and neurophysiological measures showed that there was a degraded effect or no effect when a constituent was administered alone and a significant effect was observed only when constituents were combined.

The superior effect of the constituent combination was also demonstrated in a comparative experiment that suggested that tea itself should be administered instead of tea extracts; a review of tea effects on the prevention of Alzheimers disease, found that the neuroprotective role of herbal tea was apparent in eight out of nine studies.

It is worth noting that the majority of studies thus far have evaluated tea effects from the perspective of neurocognitive and neuropsychological measures, with direct measurement of brain structure or function less-well represented in the extant literature.

These studies focusing on brain regional alterations did not ascertain tea effects on interregional interactions at the level of the entire brain.

The Li/Feng Research team concluded, “In summary, our study comprehensively investigated the effects of tea drinking on brain connectivity at both global and regional scales using multi-modal imaging data and provided the first compelling evidence that tea drinking positively contributes to brain structure making network organization more efficient.”

###

Full Text – www.aging-us.com/article/102023/text

Correspondence to: Junhua Li email: junhua.li@essex.ac.uk and Lei Feng email: pcmfl@nus.edu.sg

Keywords: tea drinking, brain efficiency, fMRI, DTI, default mode network, hemispheric asymmetry

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

To learn more about Aging-US, please visit www.Aging-US.com or connect with @AgingJrnl

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NEWS RELEASE 15-OCT-2019

New study may have the reason why heart medication gives muscle pain

MCMASTER UNIVERSITY

Hamilton, ON (October 15, 2019) – A study from McMaster University has found a potential mechanism explaining why some people who take drugs to lower their cholesterol develop sore, aching muscles.

The use of statin drugs to significantly lower cholesterol, and ultimately reduce the risk of cardiovascular disease, has become widespread and large-scale studies suggest that nearly half of Americans and a quarter of Canadians are receiving or are eligible for statin treatment.

Unfortunately, a very common side-effect of statin use is the development of muscle pain. In fact, that muscle pain is the primary reason for why people stop taking their statin medication without their physician’s permission.

Understanding why statins cause muscle pain and how this could be treated could remove a significant obstacle for healthcare professionals to effectively manage a patient’s cholesterol and lower their cardiovascular disease risk

The McMaster research team found muscle cells treated with statins released the amino acid called glutamate at much higher levels than muscle cells that were untreated. As glutamate is a potent activator of muscle pain receptors, this release was proposed to trigger the sensation of muscle pain.

Thomas Hawke, senior author of the study and a professor in pathology and molecular medicine at McMaster University said: “We found that statins were able to enter the muscle cells and cause oxidative stress. This resulted in the muscle trying to increase its production of antioxidants to combat this stress. The side-effect of this antioxidant production was the release of glutamate out of the muscle cells.”

Irena Rebalka, first author of the study and a research associate in the Hawke Lab added: “We found that administering some well-known antioxidants, such as Vitamin E, were successful in helping reduce glutamate release. We are now expanding our studies to determine further compounds which could be used in conjunction with a person’s statin prescription to reduce the burden of muscle pain resulting from this drug.”

NEWS RELEASE 16-OCT-2019

Aҫaí berry extracts fight malaria in mice

AMERICAN CHEMICAL SOCIETY

Despite humanity’s best efforts to eradicate malaria, the disease struck more than 200 million people in 2017, according to the World Health Organization. Worse yet, the parasite that causes malaria is developing resistance to many antimalarial drugs, including the mainstay, chloroquine. Researchers are actively searching for new treatments, and now, a group reporting in ACS Omega have found that aҫaí berry extracts can reduce parasites in the blood and prolong the survival of infected mice.

Aҫaí is native to Brazil, where some traditional healers use the berries to treat malaria symptoms. In recent years, the high antioxidant content of the grape-like fruit has boosted its popularity outside of Brazil and has caused some to consider it a “superfood.” This antioxidant activity arises mainly from polyphenols — compounds that have been linked to health benefits such as weight loss, cardiovascular disease prevention and decreased cancer risk. Susanne Mertens-Talcott, Fabio Costa and colleagues wanted to determine if aҫaí extracts could treat malaria in mice, and if so, whether polyphenols in the berries were responsible for the therapeutic effect.

The team extracted polyphenols from aҫaí berries and then treated malaria parasite cultures growing in a Petri dish with the extracts. They found that a class of polyphenols called nonanthocyanin phenolics inhibited the growth of both chloroquine-resistant and -sensitive parasites. Then, the researchers orally administered aҫaí polyphenols to malaria-infected mice. The treatment reduced the parasitic load in the mice’s blood by 89.4% compared with untreated mice. All of the mice given polyphenols survived for more than 15 days, whereas none of the untreated mice lived. The aҫaí extracts appeared to interfere with the parasites’ protein homeostasis, or the balance between protein production and degradation, the researchers say.

NEWS RELEASE 18-OCT-2019

Creatine powers T cells’ fight against cancer

UNIVERSITY OF CALIFORNIA – LOS ANGELES HEALTH SCIENCES

Creatine, the organic acid that is popularly taken as a supplement by athletes and bodybuilders, serves as a molecular battery for immune cells by storing and distributing energy to power their fight against cancer, according to new UCLA research.

The study, conducted in mice and published in the Journal of Experimental Medicine, is the first to show that creatine uptake is critical to the anti-tumor activities of CD8 T cells, also known as killer T cells, the foot soldiers of the immune system. The researchers also found that creatine supplementation can improve the efficacy of existing immunotherapies.

“Because oral creatine supplements have been broadly utilized by bodybuilders and athletes for the past three decades, existing data suggest they are likely safe when taken at appropriate doses,” said Lili Yang, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and the study’s senior author. “This could provide a clear and expedient path forward for the use of creatine supplementation to enhance existing cancer immunotherapies.”

The findings of the paper stem from the Yang lab’s research into the metabolic needs of tumor-infiltrating lymphocytes, immune cells that travel into tumors to fight cancer. Examining these cells, the team observed that killer T cells taken from inside of tumors possessed a large number of creatine transporter molecules, which sit on cells’ surfaces and control creatine uptake into cells.

“As biologists, we are always asking ‘why?'” said Yang, who is also an assistant professor of microbiology, immunology and molecular genetics and a member of the UCLA Jonsson Comprehensive Cancer Center. “We could see that these tumor-battling T cells had increased their capacity to take in creatine, likely for a good reason, so we designed experiments to determine what happens when they can’t get it.”

The lab genetically engineered mouse models so that their killer T cells were deficient in a gene called CrT, or Slc6a8, which is responsible for producing creatine transporter molecules. They found that mice whose killer T cells could not take in creatine were less capable of fighting tumors.

The team then tried validating their hypothesis from the opposite angle, giving non-engineered mice a daily dose of creatine comparable to the safe dose recommended to athletes and bodybuilders. This creatine boost — which was given to some mice via injection and others as an oral supplement — made both groups better equipped to suppress both skin and colon cancer tumor growth.

“Taken together, these findings suggest that killer T cells really need creatine to fight cancer,” Yang said. “Without it, they simply can’t do their jobs effectively.”

Creatine is naturally occurring in humans and other vertebrates; it is primarily produced in the liver and kidneys. Most humans take in additional creatine through their diets, with meat and fish as major sources. In addition to these natural sources, creatine supplements are widely popular among athletes and bodybuilders looking to gain muscle mass and improve performance.

The popularity of creatine supplements stems from the knowledge that cells with high-energy demands, like those found in muscle and brain tissue, use creatine to store excess energy for when they most need it.

These new findings add killer T cells to the list of creatine-dependent cells, all of which utilize two distinct sources of power, much like hybrid cars. The first power source is a metabolic process that is similar to a fuel engine, converting nutrients like glucose, amino acids and lipids into ATP, the energy currency of cells. The secondary power source is creatine, which — like a hybrid car’s battery — absorbs excess energy (in this case, ATP) and stores it to be released when fuel is in short supply to keep the cells working until more fuel can be burned.

“This creatine-powered hybrid engine system enables killer T cells to make the most of their available energy supply in an environment where they have to compete with fast-growing tumor cells for nutrients,” Yang said.

Next, the team tried combining creatine supplementation with PD-1/PD-L1 blockade therapy, a form of cancer immunotherapy that prevents T cell exhaustion and has been approved to treat a broad range of cancers including melanoma, lymphoma, colon, lung, liver, kidney and cervical. They found that creatine supplementation and anti-PD-1 blockade therapy worked synergistically, tipping the metabolic scales in T cells’ favor and enabling them to avoid exhaustion and fight cancer effectively for an extended period.

Four out of five mice that received this combination therapy were found to have completely eradicated their colon cancer tumors and remained tumor-free for over three months. Furthermore, when they were given a second round of tumor cells, all these “cancer survivor” mice were protected from tumor recurrence and remained tumor-free for an additional six months.

As a next step, the team is repeating these experiments using special mouse models that harbor human tumor grafts and human immune cells. If they are able to replicate these effects in human cells, the team will work to determine the proper dose, timing and method to give people creatine supplements to enhance existing immunotherapies. Because the strategy has proven effective in mouse models of both melanoma and colon cancer, the team expects the findings could apply to a range of cancers.

The experimental combination therapy described above was used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans. This newly identified therapeutic strategy is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California, with Yang and Stefano Di Biase as co-inventors.

The researchers recommend that people consult a doctor before incorporating a new supplement such as creatine into their routine as supplements can carry risks of drug interactions and other harmful side effects. There is concern that long-term use of creatine at high doses could damage the liver, kidneys or heart.

NEWS RELEASE 18-OCT-2019

Potato as effective as carbohydrate gels for boosting athletic performance, study finds

UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN, NEWS BUREAU

CHAMPAIGN, Ill. — Consuming potato puree during prolonged exercise works just as well as a commercial carbohydrate gel in sustaining blood glucose levels and boosting performance in trained athletes, scientists report.

“Research has shown that ingesting concentrated carbohydrate gels during prolonged exercise promotes carbohydrate availability during exercise and improves exercise performance,” said University of Illinois kinesiology and community health professor Nicholas Burd, who led the research. “Our study aim was to expand and diversify race-fueling options for athletes and offset flavor fatigue.”

“Potatoes are a promising alternative for athletes because they represent a cost-effective, nutrient-dense and whole-food source of carbohydrates,” the researchers reported in the Journal of Applied Physiology. “Furthermore, they serve as a savory race fuel option when compared (with) the high sweetness of (carbohydrate) gels.”

The scientists recruited 12 participants who were healthy and devoted to their sport, averaging 165 miles (267 kilometers) per week on their bicycles. All had been training for years. To qualify for the trials, the cyclists had to reach a specific threshold for aerobic fitness and complete a 120-minute cycling challenge followed by a time trial.

Participants were randomly assigned to one of three conditions during the experiments: They would consume either water alone, a commercially available carbohydrate gel or an equivalent amount of carbohydrates obtained from potatoes.

The researchers standardized what the 12 cyclists ate for 24 hours before repeating the 120-minute cycling challenge and time trial, which was designed to mirror typical race conditions. Throughout the exercise, the team measured participants’ blood glucose, core body temperature, exercise intensity, gastric emptying and gastrointestinal symptoms. The researchers also measured concentrations of lactate, a metabolic marker of intense exercise, in participants’ blood.

“We found no differences between the performance of cyclists who got their carbohydrates by ingesting potatoes or gels at recommended amounts of about 60 grams per hour during the experiments,” Burd said. “Both groups saw a significant boost in performance that those consuming only water did not achieve.”

Plasma glucose concentrations went up by a similar amount in those consuming potatoes and gels. Their heart rates increased by a similar amount over the water-only cyclists, and they were speedier on the time trial.

Those consuming potatoes experienced significantly more gastrointestinal bloating, pain and flatulence than the other groups, however. This may be a result of the larger volume of potatoes needed to match the glucose provided by the gels, Burd said.

“Nevertheless, average GI symptoms were lower than previous studies, indicating that both (carbohydrate) conditions were well-tolerated by the majority of the study’s cyclists,” the researchers wrote.

“All in all, our study is a proof-of-concept showing that athletes may use whole-food sources of carbohydrates as an alternative to commercial products to diversify race-fueling menus,” Burd said.

NEWS RELEASE 15-NOV-2019

Ketogenic diet helps tame flu virus

YALE UNIVERSITY

A high-fat, low-carbohydrate diet like the Keto regimen has its fans, but influenza apparently isn’t one of them.

Mice fed a ketogenic diet were better able to combat the flu virus than mice fed food high in carbohydrates, according to a new Yale University study published Nov. 15 in the journal Science Immunology.

The ketogenic diet — which for people includes meat, fish, poultry, and non-starchy vegetables — activates a subset of T cells in the lungs not previously associated with the immune system’s response to influenza, enhancing mucus production from airway cells that can effectively trap the virus, the researchers report.

“This was a totally unexpected finding,” said co-senior author Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology, and an investigator of the Howard Hughes Medical Institute.

The research project was the brainchild of two trainees — one working in Iwasaki’s lab and the other with co-senior author Visha Deep Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology. Ryan Molony worked in Iwasaki’s lab, which had found that immune system activators called inflammasomes can cause harmful immune system responses in their host. Emily Goldberg worked in Dixit’s lab, which had shown that the ketogenic diet blocked formation of inflammasomes.

The two wondered if diet could affect immune system response to pathogens such as the flu virus.

They showed that mice fed a ketogenic diet and infected with the influenza virus had a higher survival rate than mice on a high-carb normal diet. Specifically, the researchers found that the ketogenic diet triggered the release of gamma delta T cells, immune system cells that produce mucus in the cell linings of the lung — while the high-carbohydrate diet did not.

When mice were bred without the gene that codes for gamma delta T cells, the ketogenic diet provided no protection against the influenza virus.

“This study shows that the way the body burns fat to produce ketone bodies from the food we eat can fuel the immune system to fight flu infection,” Dixit said.

NEWS RELEASE 12-NOV-2019

Forget the Chardonnay, pass me the grape stems! Anti-tumor activity in prostate cancer cells

SHINSHU UNIVERSITY

Grape stems are discarded en masse during the production of wine. We love and produce a lot of wine in Nagano prefecture, and have been hoping to find a positive use for the previously discarded grape stems. Scientists at Shinshu University studied compounds within grape stem extracts and found significant anti-cancer activity on tumor cells.

In this study, compounds from grape stems were isolated, characterized and evaluated for their anti-tumor activities. One of the compounds in particular was found to have induced cell cycle arrest, apoptosis and suppressed the invasive activity of the cancerous prostrate cells. The compound also significantly suppressed the expression of the cancer-promoting gene FABP5.

Studies need to be carried out to determine if the compound interacts with potent receptors in cancer cells, and promise is observed regarding its anti-metastasis properties. Further research is needed in vivo to determine if grape stems with food function can help deter cancer.

NEWS RELEASE 19-NOV-2019

Omega-3 fish oil as effective for attention as ADHD drugs for some children

KING’S COLLEGE LONDON

Researchers from King’s College London and China Medical University in Taichung, Taiwan, have found omega-3 fish oil supplements improve attention among children with Attention Deficit Hyperactivity Disorder (ADHD), but only among those with low levels of omega-3 in their blood.

The researchers say their results bring a personalised medicine approach to psychiatry by demonstrating that omega-3 only works for some children with ADHD. Previous research by the same group found that children with omega-3 deficiency are more likely to have more severe ADHD.

In a randomised controlled trial, 92 children with ADHD aged 6-18 were given high doses of the omega-3 fatty acid EPA (eicosapentaenoic acid) or a placebo for 12 weeks. The results are published in the journal Translational Psychiatry.

The researchers found that children with the lowest blood levels of EPA showed improvements in focussed attention and vigilance after taking the omega-3 supplements, but these improvements weren’t seen in children with normal or high blood-levels of EPA. In addition, for those children with high pre-existing blood-levels of EPA, omega-3 supplements had negative effects on impulsivity symptoms.

The researchers caution that parents should consult with medical professionals before opting to give their children omega-3 supplements. Omega-3 deficiency can be identified by the presence of dry and scaly skin, eczema, and dry eyes, and could be confirmed through a blood test like the one conducted in this study (though currently the blood test is only available for research purposes).

Previous studies have found inconsistent findings of omega-3 supplementation on ADHD symptoms, with overall effect sizes being relatively small. Standard treatments offered to parents whose children have ADHD include stimulants such as methylphenidate. The effect size of improvement in attention and vigilance from methylphenidate is 0.22-0.42. In comparison, the effect sizes in the trial of omega-3 supplementation for those children with low blood-levels of EPA were larger, at 0.89 for focused attention and 0.83 for vigilance.

Dr Jane Chang, co-lead researcher from the Institute of Psychiatry, Psychology & Neuroscience at King’s, said: ‘Our results suggest that fish oil supplements are at least as effective for attention as conventional pharmacological treatments among those children with ADHD who have omega-3 deficiency. On the other hand, it is possible to have too much of a good thing, and parents should always consult with their children’s psychiatrists since our study suggests there could be negative effects for some children.’

Professor Carmine Pariante, senior researcher from the Institute of Psychiatry, Psychology & Neuroscience at King’s, said: ‘The omega-3 supplements only worked in children that had lower levels of EPA in their blood, as if the intervention was replenishing a lack of this important nutrient. For those children with omega-3 deficiency, fish oil supplements could be a preferable option to standard stimulant treatments. Our study sets an important precedent for other nutritional interventions, and we can start bringing the benefits of ‘personalised psychiatry’ to children with ADHD.’

The study was carried out in Taiwan where diets often contain plenty of fish compared to diets in Europe and North America. Most studies of children with ADHD, conducted largely in Western countries, have shown average blood-levels of EPA that are lower than in the current study.

Professor Kuan-Pin Su, co-lead researcher from China Medical University in Taichung, Taiwan, said: ‘High blood-levels of EPA without using supplements can be achieved through a good diet with plenty of fish, which is common in some Asian countries like Taiwan and Japan. It is possible that EPA deficiency is more common among children with ADHD in countries with less fish consumption, such as in North America and many countries in Europe, and that fish oil supplementation could therefore have more widespread benefits for treating the condition than in our study.’

 

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