230CNO22MAY2016
CNO Report 230
Release Date 30 May 2016
Draft Report Compiled by
Ralph Turchiano
In this Issue:
1. Common antacid linked to accelerated vascular aging
2. Fruit discovery could provide new treatments for obesity, type 2 diabetes and cardiovascular disease
3. Omega-3 lowers childhood aggression in short term, Penn research shows
4. Another reason for wine lovers to toast resveratrol
5. Exercise, more than diet, key to preventing obesity
6. Selenium deficiency linked to deadly heart disease affecting pregnant women
7. Melatonin reduces blood pressure and tunes up disrupted circadian rhythms in the elderly
8. Mouse study finds link between gut bacteria and neurogenesis
9. Sugar substitutes may cut calories, but no health benefits for individuals with obesity: York U
10. Clinical trial demonstrates success of low FODMAP diet
11. Exercise, future anticancer therapy?
12. The taste or smell of foods can affect aging, say scientists
13. Vitamin nicotinamide riboside protects mice from diabetes complications
Public Release: 10-May-2016
Common antacid linked to accelerated vascular aging
Research supports observations of increased risk for heart disease, dementia and kidney disease
Houston Methodist
Chronic use of some drugs for heartburn and gastroesophageal reflux (GERD) speeds up the aging of blood vessels, according to a published paper in Circulation Research (early online), an American Heart Association journal. This accelerated aging in humans could lead to increased cardiovascular disease, vascular dementia and renal failure.
[Click here for video with John Cooke, M.D., Ph.D.]
These findings by a Houston Methodist Research Institute team are a progression of the work that John Cooke, M.D., Ph.D., began more than five years ago, and support recent epidemiological and retrospective studies that observed associations between the long-term use of proton pump inhibitors (PPIs) and an increased risk of heart attack, renal failure and dementia.
PPIs like esomeprazole (Nexium) are widely used for the treatment of GERD. These medications are sold over-the-counter in the United States so medical supervision is not required. While these drugs are effective when taken as prescribed, they were not approved for long-term use and evidence suggests that up to 70 percent of PPI use may be inappropriate.
Cooke, the paper’s senior author, and team showed that chronic exposure to PPIs accelerated biological aging in human endothelial cells which line the inside of blood vessels. When healthy, human endothelial cells create a Teflon-like coating that prevents blood from sticking. When older and diseased, the endothelium becomes more like Velcro, with blood elements sticking to the vessel to form blockages.
“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” Cooke said. “The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”
Cooke suspects that this may be the unifying mechanism that explains the increased risk of heart attack, renal failure and dementia observed in long-term PPI users.
“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks. However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”
Cooke’s earlier work identified at a molecular level that PPIs might cause long-term cardiovascular disease and increase a patient’s heart attack risk. That work led to a collaborative study with Stanford University colleagues (PLOS ONE, June 2015) to show that in two large populations of patients, adults who used PPIs were between 16 to 21 percent more likely to experience a heart attack than people who didn’t use the commonly prescribed antacid drugs.
Cooke, who holds the Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, said while PPIs were shown to affect vascular aging, H2 blockers like ranitidine did not adversely affect the endothelium. Brand examples of H2 blockers are Zantac and Tagamet.
The FDA estimates about 1 in 14 Americans have used a PPI. In 2009, PPIs were the third-most taken type of drug in the U.S., and are believed to account for $13 billion in annual global sales. In addition to GERD and heartburn, PPIs treat a wide range of disorders, including infection by the ulcer-causing bacterium Helicobacter pylori, Zollinger-Ellison syndrome, and Barrett’s esophagus. PPIs come in a variety of forms, always ending with the suffix “-prazole,” and other brand examples include Prilosec and PrevAcid.
Public Release: 11-May-2016
Fruit discovery could provide new treatments for obesity, type 2 diabetes and cardiovascular disease
Two compounds found in red grapes and oranges combined could treat diseases, researchers are hoping pharmaceutical companies will use new compound combination in breakthrough drugs
University of Warwick
A combination of two compounds found in red grapes and oranges could be used to improve the health of people with diabetes, and reduce cases of obesity and heart disease.
The find has been made by University of Warwick researchers who now hope that their discovery will be developed to provide a treatment for patients.
Professor Thornalley who led research said: “This is an incredibly exciting development and could have a massive impact on our ability to treat these diseases. As well as helping to treat diabetes and heart disease it could defuse the obesity time bomb.”
The research ‘Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation’ has been published in the journal Diabetes, and received funding from the UK’s innovation agency, Innovate UK. The project was a collaboration between the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust.
A team led by Paul Thornalley, Professor in Systems Biology at Warwick Medical School, studied two compounds found in fruits but not usually found together. The compounds are trans-resveratrol (tRES) – found in red grapes, and hesperetin (HESP) – found in oranges. When given jointly at pharmaceutical doses the compounds acted in tandem to decrease blood glucose, improve the action of insulin and improve the health of arteries.
The compounds act by increasing a protein called glyoxalase 1 (Glo1) in the body which neutralises a damaging sugar-derived compound called methylglyoxal (MG). MG is a major contributor to the damaging effects of sugar. Increased MG accumulation with a high energy diet intake is a driver of insulin resistance leading to type 2 diabetes, and also damages blood vessels and impairs handling of cholesterol associated with increased risk of cardiovascular diseases. Blocking MG improved health in overweight and obese people and will likely help patients with diabetes and high risk of cardiovascular disease too. It has already been proven experimentally that blocking MG improves health impairment in obesity and type 1 and type 2 diabetes.
Although the same compounds are found naturally in some fruits, the amounts and type required for health improvement cannot be obtained from increased fruit consumption. The compounds that increase Glo1 and are called a ‘Glo1 inducer’. Pharmaceutical doses for patients with obesity, diabetes and high risk of heart disease could be given to patients in capsule form.
Professor Thornalley increased Glo1 expression in cell culture. He then tested the formulation in a randomised, placebo-controlled crossover clinical trial.
Thirty-two overweight and obese people within the 18-80 age range who had a BMI between 25-40 took part in the trial. They were given the supplement in capsule form once a day for eight weeks. They were asked to maintain their usual diet and their food intake was monitored via a dietary questionnaire and they were also asked not to alter their daily physical activity. Changes to their sugar levels were assessed by blood samples, artery health measured by artery wall flexibility and other assessments by analysis of blood markers.
The team found that the highly overweight subjects who had BMIs of over 27.5 with treatment displayed increased Glo1 activity, decreased glucose levels, improved working of insulin, improved artery function and decreased blood vessel inflammation. There was no effect of placebo.
Professor Thornalley said: “Obesity, type 2 diabetes and cardiovascular disease are at epidemic levels in Westernised countries. Glo1 deficiency has been identified as a driver of health problems in obesity, diabetes and cardiovascular disease.”
“Diabetic kidney disease will be the initial target to prove effective treatment for which we are currently seeking commercial investors and partners. Our new pharmaceutical is safe and expected to be an effective add-on treatment taken with current therapy.
“The key steps to discovery were to focus on increasing Glo1 and then to combine tRES and HESP together in the formulation for effective treatment.
“As exciting as our breakthrough is it is important to stress that physical activity, diet, other lifestyle factors and current treatments should be adhered to.”
Professor Martin O Weickert, Consultant in Diabetes and Endocrinology at UHCW NHS Trust, and co-applicant for the grant, said: “We were really excited to participate in this study with Warwick Medical School, as taking part in world-leading research makes a real difference to our patients both now and in the future.
“As well as the positive effects for the UHCW patients who took part in the trial, we hope this study will lead to new treatments to help patients with diabetes and cardiovascular diseases all over the world.”
Prof. Thornalley and his team are now hoping manufacturers will want to explore the use of the compound as pharmaceutical products.
Public Release: 13-May-2016
Omega-3 lowers childhood aggression in short term, Penn research shows
University of Pennsylvania
Incorporating omega-3, vitamins and mineral supplements into the diets of children with extreme aggression can reduce this problem behavior in the short term, especially its more impulsive, emotional form, according to University of Pennsylvania researchers who published their findings in the Journal of Child Psychology and Psychiatry.
Adrian Raine, the Richard Perry University Professor of Criminology, Psychology and Psychiatry, has spent his career looking at how the brain’s biological functioning affects antisocial behavior. He focuses specifically on understanding these actions and learning how to modify them, whether with something benign like a child acting out or with something extreme, in the case of a homicidal killer.
“How do you change the brain to make people better?” he asked. “How can we improve brain functioning to improve behavior?”
These questions formed the foundation for work Raine had previously done with adolescents on the African island of Mauritius. In a randomized control trial, one group received omega-3 supplements for six months, the other didn’t. Those taking the fish oil saw a reduction in aggressive and antisocial behavior.
“That was my starting point,” he said. “I was really excited about the results we published there.”
Mauritius, however, is a tropical climate and a different culture from the United States, so Raine, a Penn Integrates Knowledge Professor, decided to test a new version of the study in Philadelphia, to aim for more broadly applicable outcomes. He partnered with Therese Richmond, the Andrea B. Laporte Professor of Nursing and associate dean for research and innovation, and several other Penn faculty, including Rose Cheney of the Perelman School of Medicine and Jill Portnoy of the Criminology Department in the School of Arts & Sciences.
The Philadelphia randomized control study placed 290 11- and 12-year-olds with a history of violence into four groups: The first received omega-3 in the form of juice, as well as multivitamins and calcium for three months. For that same duration, a second group participated in cognitive behavioral therapy, or CBT, which included meeting weekly for an hour, with time split between the child, the parent and with both together.
“Sessions focused on the links between thoughts, feelings and behaviors and also practicing alternative actions the children could take to deal with difficult situations rather than to emotionally react to something,” said Richmond, who supervised the clinical trial. “It’s helping the child build a toolbox of ways to interact with others. For example, if I’m angry, how might I cope with anger other than physically striking out?”All participants got homework, too.
A third group in the study took the supplements and participated in CBT, and a fourth received resources and information targeted at reducing aggressive behavior. Blood samples at the experiment’s start and conclusion measured omega-3 levels in each child.
“Immediately after three months of the nutritional intervention rich in omega-3s, we found a decrease in the children’s reporting of their aggressive behavior,” Richmond said. The team also followed up three and six months later.
At the first check-in, participants getting the combination of CBT and omega-3s reported less aggression than the control group and the therapy-only group. By the final check-in, however, any positive effects had dissipated. What remains unknown is whether continued use of omega-3s would lead to a long-term reduction in antisocial behavior.
There were other minor limitations to the research. For one, self-reporting completed by parents and children didn’t line up. The 11- and 12-year-olds in the omega-3 and CBT-supplement groups noted fewer aggressive behaviors; their parents said such tendencies hadn’t changed. Also, some participants dropped out before the study had finished.
Despite these challenges, Raine, Richmond and their colleagues said the findings provide some important insight.
“No matter what program you use, could adding omega-3s to your treatment help?” Raine asked. “This suggests it could.”
And though the work answers some questions, it also creates new ones, which returns to a larger point regarding the mind-action connection: It’s complicated.
“We can’t oversimplify the complexity of antisocial behavior. There are many causes,” Raine said. “It’s not just the brain. Is it a piece of the jigsaw puzzle? I think it is.”
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Funding for the research came from the Pennsylvania Department of Health, the Clinical & Translational Research Center at the Perelman School of Medicine and the National Institute on Alcohol Abuse and Alcoholism.
Public Release: 13-May-2016
Another reason for wine lovers to toast resveratrol
Resveratrol found in red wine could help counteract the negative impact of high fat/high sugar diets
Frontiers
Red wine lovers have a new reason to celebrate. Researchers have found a new health benefit of resveratrol, which occurs naturally in blueberries, raspberries, mulberries, grape skins and consequently in red wine.
While studying the effects of resveratrol in the diet of rhesus monkeys, Dr. J.P. Hyatt, an associate professor at Georgetown University, and his team of researchers hypothesized that a resveratrol supplement would counteract the negative impact of a high fat/high sugar diet on the hind leg muscles. In previous animal studies, resveratrol has already shown to increase the life span of mice and slow the onset of diabetes. In one study, it mirrored the positive effects of aerobic exercise in mice, which were fed a high fat/high sugar diet.
For Dr. Hyatt’s current study, which was published in the open access journal Frontiers in Physiology, a control group of rhesus monkeys was fed a healthy diet and another group was fed a high fat/high sugar diet, half of which also received a resveratrol supplement and half of which did not. The researchers wanted to know how different parts of the body responded to the benefits of resveratrol – specifically the muscles in the back of the leg.
Three types of muscles were examined: a “slow” muscle, a “fast” muscle and a “mixed” muscle. The study showed that each muscle responded differently to the diet and to the addition of resveratrol.
The soleus muscle, a large muscle spanning from the knee to the heel, is considered a “slow” muscle used extensively in standing and walking. Of the three lower hind leg muscles analyzed for this study, the soleus was the most effected by the high fat/high sugar diet and also most effected by the resveratrol supplements; this may be partially due to the fact that, on a daily basis, it is used much more than the other two muscles.
In the soleus muscle, myosin, a protein which helps muscles contract, and determines its slow or fast properties, shifted from more slow to more fast with a high fat/ high sugar diet. The addition of resveratrol to the diet counteracted this shift.
The plantaris muscle, a 5-10 cm long muscle along the back of the calf, did not have a negative response to the high fat/high sugar diet, but it did have a positive response to the addition of resveratrol, with a fast to slow myosin shift. The third muscle was not affected by the diet or addition of resveratrol.
Hyatt said it would be reasonable to expect other slow muscles to respond similarly to the soleus muscle when exposed to a high fat/high sugar diet and resveratrol.
“The maintenance or addition of slow characteristics in soleus and plantaris muscles, respectively, implies that these muscles are far more fatigue resistant than those without resveratrol. Skeletal muscles that are phenotypically slower can sustain longer periods of activity and could contribute to improved physical activity, mobility, or stability, especially in elderly individuals,” he said, when asked if this study could be applied to humans.
While these results are encouraging, and there might be a temptation to continue eating a high fat/high sugar diet and simply add a glass of red wine or a cup of fruit to one’s daily consumption, the researchers stress the importance of a healthy diet cannot be overemphasized. But for now there’s one more reason to have a glass of red wine.
Public Release: 16-May-2016
Exercise, more than diet, key to preventing obesity
Study featured in the American College of Sports Medicine finds exercise has significant impact on fat tissue, metabolism and gut microbes
University of Missouri-Columbia
COLUMBIA, Mo. – Two factors–metabolism and gut microbes – have been credited by researchers as key players in the fight against obesity. However, there is an ongoing debate about whether exercise or diet better promotes metabolism and healthy shifts in gut microbes, the microscopic organisms in our intestines that break down food and can contribute to decreased obesity. New research from the University of Missouri confirms exercise plays a significant role in the fight against obesity.
“Some have claimed that exercise may not play a significant role in weight loss, as exercise can increase appetite resulting in greater food intake and potentially reduce activity throughout the day,” said Vicki Vieira-Potter, assistant professor of nutrition and exercise physiology at MU. “The purpose of this study was to look at exercise independently from weight loss and to determine other metabolic benefits associated with physical activity. Our team aimed to tease out what effects on adipose, or fat tissue, were due to weight loss from diet, and what could be attributed to exercise.”
Vieira-Potter and her research team divided young rats prone to obesity into three groups to study the impact of exercise on their metabolic function and fat tissue. All three of the rat groups were fed a high-fat diet. Two of the groups were sedentary while the third group was able to exercise using running wheels. Of the two sedentary groups, one was allowed to eat as much of the high-fat food as they wanted, while the other group were fed controlled portions of the food in order to match the weight reduction caused by exercise. The exercising rats were allowed to eat as much as they wanted.
Several weeks later, all rats were moved to specialized cages where researchers could measure their metabolism and physical activity. Researchers found the sedentary rats with unlimited food access were obese, unlike the sedentary rats fed a reduced amount of the same diet and the rats that exercised, which was expected. Notably, the researchers also found that the exercising rats were metabolically healthier than both of the sedentary groups, and they developed different gut microbes than the other groups, despite eating the exact same amount of food as the sedentary group with unlimited food access.
“Overall, the exercising rats had higher metabolic rates, were more active even when not running on their wheels and experienced shifts in their gut microbes, perhaps putting them in in a better position to avoid future weight gain compared to the other groups,” Vieira-Potter said. “These findings confirm that exercise is an important component of overall health and is critically important in the fight against obesity, especially during the juvenile period.”
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The study, “Comparison of Diet vs. Exercise on Metabolic Function and Gut Microbiota in Obese Rats,” was published in Medicine and Science in Sports and Exercise, a journal of the American College of Sports Medicine. The MU Research Board, the MU Research Council, the Sears Trust Research Foundation and the National Institutes of Health provided funds for the study. Vieira-Potter’s future research will further study how exercise-mediated fat tissue changes may explain its unique metabolic effects. She and her colleagues on the study are also investigating the relationship between gut microbes and exercise and how that relationship impacts obesity.
The Department of Nutrition and Exercise Physiology is jointly administered by the College of Agriculture, Food and Natural Resources, the College of Human Environmental Sciences and the School of Medicine.
Public Release: 16-May-2016
Selenium deficiency linked to deadly heart disease affecting pregnant women
Umea University
Researchers have found a close link between selenium deficiency and Peripartum Cardiomyopathy (PPCM), a heart disease that affects pregnant women and recent mothers. The study of patients in Nigeria also showed that rural women were three times more likely to develop the disease, according to a doctoral dissertation at Umeå University.
Kamilu Karaye, a doctoral student at Department of Public Health and Clinical Medicine, carried out studies of 54 PPCM patients and 77 controls in three referral hospitals in Kano, Nigeria. The results show that 77 percent of the PPCM patients had critically low selenium blood levels. Researchers also found that rural residency was a factor that increased the chance of having PPCM by almost threefold.
“Before this study, we suspected that selenium deficiency could be a possible risk factor for PPCM,” says Kamilu Karaye. “If proven further in larger studies, our observation about the link between selenium deficiency and PPCM could lead to the development of a cure for the disease, at least in some of the patients around the study area, by selenium supplementation of foods.”
PPCM is a heart disease affecting mostly pregnant women and young mothers, usually manifesting from the last months of the pregnancy until five months after the birth. Many of the women affected are of African descent. In northern Nigeria, PPCM could affect 1 in every few hundred pregnancies. The causes of PPCM are still not well understood, but the disease leads to a dilation of the heart’s left and right ventricular chambers, resulting in a weakening of the heart contractions and even death.
In a follow-up one year after diagnosis, 41.4 percent of the patients in the study had died, two thirds of them within the first 6 months of diagnosis. One year after diagnosis, many of the PPCM patients had significant improvement in heart function in their left and right ventricular chambers. 47.1 percent of the patients still alive had significant improvement of left ventricular function. Heart dysfunction in the right ventricle was found in 71.1 percent of the patients at diagnosis. In follow-up at 6 months and one year, only 36.4 percent and 18.8 percent respectively had the same problem, implying significant right ventricular functional recovery.
The study also showed that that electrocardiographic (ECG) indices could be used to diagnose PPCM with 83.8 percent accuracy, prior to confirmatory investigations.
“It is important to understand that PPCM is a ‘killer disease’ in sub-Saharan Africa and that the first six months of the disease seem to be of critical significance. Therefore, all hands should be on deck to medically support the affected patients during this critical period,” says Kamilu Karaye, who also works as a Consultant Cardiologist in Aminu Kano Teaching Hospital, in Kano, Nigeria.
Kamilu Musa Karaye was born and works in Kano, Nigeria, and is presently a Professor of Medicine in Bayero University and Consultant Cardiologist in Aminu Kano Teaching Hospital. His passion for PPCM was borne out of his personal observations on the disease, and the fact that it is still not well understood.Melatonin reduces blood pressure and tunes up disrupted circadian rhythms in the elderly
Increased blood pressure and reduced robustness of circadian rhythms are frequently reported in elderly subjects. The present study was aimed to investigate whether such changes can be reversed by daily melatonin ingestion.
Bentham Science Publishers
The older we get, the more likely our circadian rhythms are disrupted. For example, blood pressure (BP), not only tends to increase but as well become more irregular. Luckily, as we show in our research, melatonin helps to ameliorate both trends.
63 senior respondents of a mean age of 80 were studied during 3 consecutive weeks. First week control data were collected for 7 successive days. Over the next 2 weeks, the seniors were administered a low dose of melatonin (1.5 mg) each day by night at 10:30 p.m. On the third week data were monitored again.
Melatonin significantly reduced BP. The hypotensive effect was dependent on time. The maximum systolic BP lowering effect of melatonin falls between 3:00 and 8:00 in the morning, the time of the highest risk of heart attacks and strokes. Nighttime and morning BP decreased more profoundly on average -8/3.5 mm Hg for SBP/DBP, respectively.
Moreover, the higher the mean systolic BP was during the first week, the more it dropped on the second week of melatonin administration. Melatonin also decreased the overall variability in BP.
Melatonin ws effective in synchronizing disrupted circadian rhythms of BP, heart rate and body temperature, making these circadian rhythms smoother and less irregular. None of these effects was found in 34 placebo treated seniors, thus ruling out the possibility that rhythms could be improved just because of regular schedule and presence of medical personal who took measurements.
In conclusion, melatonin can be of great value for aged people suffering from hypertension as an adjuvant substance complementing basic medication as it is able to stabilize circadian BP, heart rate profiles and their phase relationships. The improvement of circadian pacemaker functions may also provide a new strategy in the treatment of hypertension.
Public Release: 19-May-2016
Mouse study finds link between gut bacteria and neurogenesis
Cell Press
Antibiotics strong enough to kill off gut bacteria can also stop the growth of new brain cells in the hippocampus, a section of the brain associated with memory, reports a study in mice published May 19 in Cell Reports. Researchers also uncovered a clue to why– a type of white blood cell seems to act as a communicator between the brain, the immune system, and the gut.
“We found prolonged antibiotic treatment might impact brain function,” says senior author Susanne Asu Wolf of the Max-Delbrueck-Center for Molecular Medicine in Berlin, Germany. “But probiotics and exercise can balance brain plasticity and should be considered as a real treatment option.”
Wolf first saw clues that the immune system could influence the health and growth of brain cells through research into T cells nearly 10 years ago. But there were few studies that found a link from the brain to the immune system and back to the gut.
In the new study, the researchers gave a group of mice enough antibiotics for them to become nearly free of intestinal microbes. Compared to untreated mice, the mice who lost their healthy gut bacteria performed worse in memory tests and showed a loss of neurogenesis (new brain cells) in a section of their hippocampus that typically produces new brain cells throughout an individual’s lifetime. At the same time that the mice experienced memory and neurogenesis loss, the research team detected a lower level of white blood cells (specifically monocytes) marked with Ly6Chi in the brain, blood, and bone marrow. So researchers tested whether it was indeed the Ly6Chi monocytes behind the changes in neurogenesis and memory.
In another experiment, the research team compared untreated mice to mice that had healthy gut bacteria levels but low levels of Ly6Chi either due to genetics or due to treatment with antibodies that target Ly6Chi cells. In both cases, mice with low Ly6Chi levels showed the same memory and neurogenesis deficits as mice in the other experiment who had lost gut bacteria. Furthermore, if the researchers replaced the Ly6Chi levels in mice treated with antibiotics, then memory and neurogenesis improved.
“For us it was impressive to find these Ly6Chi cells that travel from the periphery to the brain, and if there’s something wrong in the microbiome, Ly6Chi acts as a communicating cell,” says Wolf.
Luckily, the adverse side effects of the antibiotics could be reversed. Mice who received probiotics or who exercised on a wheel after receiving antibiotics regained memory and neurogenesis. “The magnitude of the action of probiotics on Ly6Chi cells, neurogenesis, and cognition impressed me,” she says.
But one result in the experiment raised more questions about the gut’s bacteria and the link between Ly6Chi and the brain. While probiotics helped the mice regain memory, fecal transplants to restore a healthy gut bacteria did not have an effect.
“It was surprising that the normal fecal transplant recovered the broad gut bacteria, but did not recover neurogenesis,” says Wolf. “This might be a hint towards direct effects of antibiotics on neurogenesis without using the detour through the gut. To decipher this we might treat germ free mice without gut flora with antibiotics and see what is different.”
In the future, researchers also hope to see more clinical trials investigating whether probiotic treatments will improve symptoms in patients with neurodegenerative and psychiatric disorders.”We could measure the outcome in mood, psychiatric symptoms, microbiome composition and immune cell function before and after probiotic treatment,” says Wolf.
Public Release: 24-May-2016
Sugar substitutes may cut calories, but no health benefits for individuals with obesity: York U
The study suggests that the bacteria in the gut may be able to break down artificial sweeteners, resulting in negative health effects
York University
TORONTO, May 24, 2016 — Artificial sweeteners help individuals with obesity to cut calories and lose weight but may have negative health effects, according to researchers at York University’s Faculty of Health.
“Our study shows that individuals with obesity who consume artificial sweeteners, particularly aspartame, may have worse glucose management than those who don’t take sugar substitutes,” says Professor Jennifer Kuk, obesity researcher in the School of Kinesiology and Health Science.
Normally, weight loss is associated with several improvements in health. Artificial sweeteners are often used to help individuals cut calories and manage their weight as they are not digested by the body. However, the recent study suggests that the bacteria in the gut may be able to break down artificial sweeteners, resulting in negative health effects.
“We didn’t find this adverse effect in those consuming saccharin or natural sugars,” says Kuk. “We will need to do future studies to determine whether any potentially negative health effects of artificial sweeteners outweigh the benefits for obesity reduction.”
Currently, there are many new sugar substitutes that are used in foods. The researchers note that further investigation is needed to determine if there are any health effects of using these sweeteners.
For the study, data from 2856 U.S. adults from the Third National Health and Nutrition Survey (NHANES III) was used. Individuals reported their diet over the past 24 hours and were categorized as consumers of artificial sweeteners (aspartame or saccharin), or high or low consumers of natural sugars (sugar or fructose). Diabetes risk was measured as the ability to manage blood sugars using an oral glucose tolerance test.
Public Release: 24-May-2016
Clinical trial demonstrates success of low FODMAP diet
In a first of its kind study in the US, those with IBS overcame symptoms with diet changes compared to control
University of Michigan Health System
A change in diet can improve the lives of those diagnosed with a common, but hard-to-treat gut disorder.
That’s the result of research by the University of Michigan Health System, presented at Digestive Disease Week, that studied for the first time in the United States the result of following a carefully controlled diet to improve the symptoms and quality of life for those with irritable bowel syndrome.
“This is the only methodically rigorous clinical trial to show that diet-based therapy can not only improve symptoms, but also quality of life in patients with IBS,” says U-M assistant clinical professor and gastroenterologist Shanti Eswaran, M.D., who researches the role of diet and food in functional bowel diseases such as IBS.
Irritable bowel syndrome can be highly debilitating, if not virtually paralyzing, and affect work, sleep and personal and family relationships.
Most treatments initially rely on medications that are often expensive, usually ineffective and frequently cause unwelcome side effects. And unfortunately there is no cure.
Many practitioners and patients have turned to diet as a possible treatment, but many of the dietary recommendations have not been backed by clinical trials.
The study, the largest of its kind, measured the degree of relief from low FODMAP, a frequently recommended diet, which stands for Fermentable Oligo-Di-Monosaccharides and Polyols.
This diet excludes many compounds found in wheat, certain fruits and vegetables, garlic, onions and sugar substitutes.
Over a six-week process, registered dietitians educated and monitored the progress of more than 90 IBS patients. Roughly half followed a prescribed low FODMAP diet, and half were a control group that used a common-sense regimen, cutting down on large meals, binges and known irritants such as caffeine and alcohol.
The results were impressive: More than 50 percent of the patients on the low FODMAP diet had major improvement of their abdominal pain, compared with 20 percent of the control group.
There was also more improvement of other bothersome symptoms compared to the control group: bloating, diarrhea and stool urgency.
Eswaran collaborated with William Chey, M.D., professor of internal medicine, Kenya Jackson, Sivaram G. Pillai, Samuel W. Chey and Theresa Han-Markey, M.S., R.D., at the University of Michigan on the study abstract published in Gastroenterology.
At four weeks, the proportion of patients with a meaningful improvement in IBS quality of life was significantly higher in the low FODMAP group compared to the control group — 61 percent versus 27 percent.
While the results are highly encouraging for IBS sufferers, there are a few important caveats, Eswaran says.
Because of the many unknowns about the chemical causes and triggers of IBS, the list of “bad” foods is exhaustive and elusive, and help from a dietician is highly recommended.
“Low-FODMAP is not a new treatment, but we are now convinced that it really works,” she says. “Our next step will be to more precisely determine the underlying chemistry of how and why particular foods can yield dramatically different results for different people. Meanwhile, we strongly recommend that IBS patients work with their physician and a registered dietitian to navigate the Low-FODMAP diet to take control of their IBS symptoms.”
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Eswaran received funding to conduct the research from the University of Michigan Nutritional and Obesity Center and Prometheus Diagnostics.
Public Release: 24-May-2016
Exercise, future anticancer therapy?
First international clinical trial evaluating the effect of intense physical exercise to improve survival of men with advanced prostate cancer
University of Montreal Hospital Research Centre (CRCHUM)
Montreal (Quebec), May 24, 2016 – At age 70, Alfred Roberts plays hockey twice a week. Nothing special, right? Except that for three years he has had advanced prostate cancer, which has spread to his bones. “I’ve always been active. Hockey keeps me in shape and keeps my mind off things. I’ve got friends that have played until age 80, and my goal is to beat them!” said the veteran stick handler.
Several studies have demonstrated the benefits of exercise to improve the quality of life of people with cancer. But Dr. Fred Saad, urologist-oncologist and researcher at the University of Montreal Hospital Research Centre (CRCHUM), goes further. He believes that physical exercise has a direct effect on cancer, as effective as drugs, for treating patients with prostate cancer, even in advanced stages of the disease.
“Typical patients with metastases often become sedentary. It is thought that this affects cancer progression,” he said. Together with Robert Newton, professor at the Edith Cowan University Exercise Medicine Research Institute in Australia, Dr. Saad is leading the first international study which aims to demonstrate that exercise literally extends the life of patients with metastatic prostate cancer.
“Normally, patients at this stage have a life expectancy of two to three years. We want to reduce mortality by at least 22%, which represents about six months of longer survival. This is the equivalent benefit of a new drug. Exercise could therefore supplement available treatments, inexpensively,” said Dr. Saad, who is also professor at the University of Montreal’s Department of Surgery.
Dr. Saad will present an overview of this Phase 3 clinical trial at the American Society of Clinical Oncology (ASCO) Annual Meeting, which will take place in Chicago from June 3 to 7. The study, which is supported by the Movember Foundation, has already started in Ireland and Australia. In the coming weeks, some sixty hospitals across the world will begin recruiting patients. In total, nearly 900 men with advanced prostate cancer will participate.
“We will study exercise as if it were a drug added to standard treatments. All patients will be treated within the latest scientific knowledge for this type of cancer. They will continue to follow their therapies and take their medications. But half of the patients will receive psychosocial support with general recommendations on physical exercise. The other half will also follow a high intensity exercise program,” he explained.
The exercise medicine expert Professor Robert Newton has designed a specific strength and cardiovascular training program for patients in the “exercise” group. “They will have an hour of aerobic and resistance training three times a week. An exercise specialist will supervise them for the first 12 months, and then they will continue without direct supervision. We will evaluate quality of life, appetite, and treatment tolerance in relation to their improved physical condition,” said Professor Newton, who is co-director of the Edith Cowan University, Exercise Medicine Research Institute.
Blood samples and muscle biopsies will help scientists better understand the benefits of exercise. “People with cancer develop all sorts of complications related to metastases, such as fractures or severe pain. It is hoped that exercise will strengthen muscles and bones,” said Dr. Saad.
The hypothesis is that exercise has a direct impact on cancer progression in addition to helping patients better tolerate therapy. Ultimately, they will live longer. The results of this large study, which involves some one hundred researchers in Canada, the US, Australia, Ireland, the Netherlands, and the UK, will not be known for five years. Could the findings be extended to other types of cancer? It is too early to tell, but researchers are betting that exercise could well become the next anticancer therapy. Alfred Roberts is also convinced that exercise helps defy the odds: “As long as I can skate, I’ll play hockey!”
Public Release: 25-May-2016
The taste or smell of foods can affect aging, say scientists
POSTECH researchers find sensory neurons modulate aging hormone
Pohang University of Science & Technology (POSTECH)
Animals can perceive changes in many environmental factors such as temperature and the taste or smell of foods. This is achieved by specialized nerve cells called sensory neurons. Interestingly, sensory neurons have been known to control the rate of aging in various animals, including the tiny free living roundworm C. elegans.
The impairment of sensory neurons has been known to delay aging by switching on the action of a well-known anti-aging protein called FOXO. FOXO then turns on the gene’s encoding proteins that protect cells and repair damages in various body parts. However, how sensory neurons influence the activity of the anti-aging FOXO proteins in an entire animal has remained a mystery.
Prof. Seung-Jae Lee and PhD candidate Murat Artan at Pohang University of Science and Technology (POSTECH), Korea, hypothesized that the smell or taste of food acts on sensory neurons, which may produce a type of aging hormone. This aging hormone may be delivered to various body parts and may affect the action of FOXO proteins. The team discovered that the smell or taste of food can directly shorten lifespan by affecting sensory neurons that produce insulin-6, an insulin hormone-like factor. They also showed that insulin-6 from sensory neurons alters the action of FOXO in various tissues. Their findings were published in Genes & Development as the cover article.
They then attempted to turn on the function of only a pair of food-sensing sensory neurons by a blue light, a technique called optogenetics, to mimic the taste of food. Prof. Lee and Mr. Murat discovered that blue light itself can decrease the lifespan of animals through producing insulin-6 hormone that leads to the reduction of FOXO action without food taste or smell.
It has been shown that perception of food increases the level of blood insulin hormone levels in humans. In addition, many biological processes related to aging are similar in C. elegans and mammals which include humans. Therefore, the team concluded that it is unsurprising to find that food smell or taste play similar roles in the aging of mammals via sensory neurons and hormones like insulin.
Public Release: 27-May-2016
Vitamin nicotinamide riboside protects mice from diabetes complications
Nicotinamide riboside lowers blood sugar, reduces fatty liver and prevents neuropathy in models of prediabetes and type 2 diabetes
University of Iowa Health Care
A naturally occurring vitamin, nicotinamide riboside (NR), can lower blood sugar levels, reduce fatty liver, and prevent peripheral nerve damage in mouse models of prediabetes and type 2 diabetes (T2D), according to a new study by researchers at the University of Iowa and the Iowa City VA Health Care System.
The findings provide a scientific rationale for conducting human trials to test the effects of NR on metabolic disorders including prediabetes and T2D, as well as obesity, fatty liver disease, and neuropathies.
NR is a vitamin precursor of NAD+, an important cellular metabolite that is required for cells to convert fuel into energy, but which declines with age. NR is currently attracting a great deal of attention for its potential role in improving metabolic health and promoting healthy aging.
“There is a real fascination right now in the world of personalized nutrition, biotechnology, and pharmaceutical research to find strategies to boost NAD+ levels. NR has emerged as the lead molecule to elevate NAD+ metabolites,” says Charles Brenner, PhD, professor and Roy J. Carver Chair of Biochemistry at the University of Iowa Carver College of Medicine and lead author of the new study.
In 2004, Brenner, then at Dartmouth, discovered NR as an unanticipated vitamin precursor of NAD+. In the new study, published May 27 in the journal Scientific Reports, Brenner, together with Randy Kardon, MD, PhD, and Mark Yorek, PhD, who are jointly affiliated with University of Iowa Health Care and the Iowa City VA Health System, and Samuel Trammell, PhD, who was a graduate student in Brenner’s UI lab, tested the effects of NR supplementation on mouse models of prediabetes and type 2 diabetes.
The team studied six groups of mice: control mice on a normal chow diet with or without NR supplementation, prediabetic mice on a high-fat diet with or without NR supplementation, and T2D mice on a high-fat diet with or without NR supplement. The mice receiving NR were fed the supplement for the last eight weeks of the 21-week experiment.
As had been shown in previous studies, NR greatly protected the prediabetic and T2D mice from weight gain due to the high-fat diet. But the new study also showed that NR had other beneficial effects on whole body metabolism in the prediabetic and T2D mice. It protected high-fat fed mice from hepatic steatosis – the build-up of fat globules in the liver – which was severe in the prediabetic and T2D mice that did not receive NR. NR also reduced liver damage in the mice on high-fat diets, and greatly improved blood sugar levels in the prediabetic and T2D mice.
NR also protected against peripheral nerve damage, or neuropathy, a common, serious complication of prediabetes and T2D. Peripheral nerves control touch and pain sensing in the limbs, fingers, and toes. Damage to these nerves can be painful, and can progress to a loss of sensation that allows injuries to go unnoticed. According to the National Institute of Diabetes and Digestive and Kidney Diseases, about 60 to 70 percent of people with diabetes have some form of neuropathy. Peripheral neuropathy is a leading cause of diabetic foot ulcers and limb amputation in people with T2D.
In Brenner’s study, prediabetic and T2D mice experienced damage to their sensory nerves while the diabetic mice also experienced motor neuron deficits. NR protected the prediabetic and diabetic mice against neuropathy and maintained their normal sensitivity to heat.
“We have successfully addressed mouse models of prediabetes and type 2 diabetes with the naturally occurring vitamin NR,” says Brenner, who also is co-director of the Obesity Research and Education Initiative, professor of internal medicine, and a member of the Fraternal Order of Eagles Diabetes Research Center at the UI. “What we have seen to date in mice justifies clinical testing of NR in overweight adults and adults with diabetes.”
New tools for NR research
The study showed that a non-invasive test measuring nerve density in the mouse corneas was a sensitive and accurate biomarker of neuropathy. This test, known as corneal confocal microscopy, is already used on people in the clinic and could, therefore, be a useful tool for researchers to track the neuroprotective effects of NR in human trials.
Brenner’s team also has developed technology that allows researchers to accurately measure levels of all the NAD+ metabolites in tissues or body fluids. In the new study, this technology was, for the first time, applied to a disease model and revealed that prediabetes and T2D produced unexpected deficits in NAD+ metabolites in the liver, which were partially restored by the NR supplement.
“NAD+ metabolomics shows that NAD+ itself goes down in prediabetes and T2D, but it is not depressed as strikingly as two other metabolites: NADP+ and NADPH,” Brenner explains. “When we supplement with NR, the NAD+ bounces back but the NADP+ and NADPH levels don’t fully recover, suggesting that the disease process specifically targets these metabolites, which are required for natural resistance to reactive oxygen species (ROS). These results are consistent with research showing that the development of insulin-insensitivity is related to ROS damage and that NR boosts the body’s natural anti-oxidant defenses.”
This study was funded by grants from the Fraternal Order of Eagles Diabetes Research Center at the UI, the Roy J. Carver Charitable Trust, the National Institutes of Health, and the Department of Veterans Affairs.
Brenner invented intellectual property related to uses of NR, which has been licensed and developed by ChromaDex Corp. (NASDAQ:CDXC), the company that manufactures and distributes NR and provided the NR for this study. Brenner has also received a research grant from and serves on the scientific advisory board of ChromaDex, Inc. He is co-founder and Chief Scientific Adviser of Healthspan Research, LLC, which sells NR supplements.