259CNO28OCT2018

CNO Report # 259

Release Date: 23 NOV 2018

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

 

In this issue:

1.       Low copper levels linked to fatter fat cells

2.       Nutrients may reduce blood glucose levels

3.       Eating leafy greens could help prevent macular degeneration

4.       The smell of lavender is relaxing, science confirms

5.       Cannabis pain relief without the ‘high’

6.       Brain-eating amoebae halted by silver nanoparticles

7.       Importance of infant diet in establishing a healthy gut

8.       Anti-aging molecule NAD+ gets a boost from blocking an enzyme

9.       Late night snacker? Make it cottage cheese

10.   Fermented dairy products may protect against heart attack

11.   Rose geranium oil may ease common painful nasal symptoms linked to cancer treatment

12.   Plant-based or vegan diet may be best for keeping type 2 diabetes in check

13.   Study links cottonseed oil with lower cholesterol

14.   Drinking coffee may reduce your chances of developing Alzheimer’s, Parkinson’s

15.   Trial finds diet rich in fish helps fight asthma

16.   VITAL study: How vitamin D and fish oil affect risk of heart attack, stroke and cancer

17.   Low carb diets can help maintain weight loss by increasing number of calories burned

18.   Weightlifting is good for your heart and it doesn’t take much

19.   Probiotics increase bone volume in healthy mice

20.   New research finds omega-3 fatty acids reduce the risk of premature birth

21.   Sugar supplement slows tumor growth and can improve cancer treatment

22.   Antioxidants may prevent cognitive impairment in diabetes

23.   Routine vitamin B12 screening may prevent irreversible nerve damage in type-2 diabetes

 

Public Release: 11-Oct-2018

Low copper levels linked to fatter fat cells

Johns Hopkins researchers have found that low levels of cellular copper appear to make fat cells fatter by altering how cells process their main metabolic fuels, such as fat and sugar

Johns Hopkins Medicine

In studies of mouse cells, Johns Hopkins researchers have found that low levels of cellular copper appear to make fat cells fatter by altering how cells process their main metabolic fuels, such as fat and sugar.

The discovery, they say, adds to evidence that copper homeostasis could one day be a therapeutic target for metabolic disorders, including obesity. The researchers caution that although links between copper and obesity in humans have been reported, more work needs to be done to better understand the connection. In the western world, dietary copper deficiency is not common, except in pregnancy, and the main health risks are associated with genetic disorders of copper misbalance. A diet incorporating vegetables, nuts and even chocolate usually contains enough copper to maintain healthy copper levels.

Copper is essential to human biology and helps to facilitate many processes, from the formation of pigments in hair and eye color to new blood vessels. The mineral is also important to cognition. Copper imbalances have been associated with several neurological disorders, and altered copper levels were linked to depression and changes in sleep pattern, according to Svetlana Lutsenko, Ph.D., professor of physiology at the Johns Hopkins University School of Medicine and a senior researcher on the study.

“We have seen over and over again that when there is a copper misbalance in a tissue, there are significant effects on its health,” says Lutsenko.

The study, described in the Sept. 17 edition of the journal PLOS Biology, summarizes the research team’s efforts to describe the role of copper balance in the physiology of fat-storing cells, called adipocytes. Haojun Yang, lead author on the paper and a graduate student in cellular and molecular physiology at the Johns Hopkins University School of Medicine, tackled this question as part of her Ph.D. study.

The researchers wanted to understand how adipocytes used copper. They did this by first growing mouse fat cell precursors in the laboratory that could be chemically signaled to grow into mature adipocytes — the kind used to store fuel.

The researchers monitored the cells’ copper uptake and the proteins they produced during this developmental process.

Lutsenko and her team found that during maturation, adipocytes ingested twice the amount of copper as the precursors. They also found that several copper-containing proteins were more abundant, especially an enzyme called semicarbazide-sensitive amine oxidase (SSAO), which was extraordinarily “upregulated,” appearing at levels up to 70 times higher than in the precursor cells. Past studies have shown that SSAO is copper-dependent, and is uniquely abundant in adipose tissue, but it remained unclear how cellular copper levels affect SSAO and how SSAO activity is linked to adipocyte metabolism, Lutsenko says. “We were intrigued to see that these components correlated,” Yang says.

To test whether the cells’ copper consumption affected SSAO’s function, Yang limited copper availability during adipocyte maturation. She found that the lack of copper did not keep the cells from developing into mature fat cells, but, unexpectedly, the copper-deprived cells grew to more than twice the size of their healthy counterparts and contained more fatty molecules, called lipids, than cells developing under copper-adequate conditions.

“This test showed that copper was important to healthy development and metabolism of adipocytes,” says Lutsenko.

To determine whether loss of the copper-dependent SSAO activity was responsible for the change in size and fat accumulation by the copper-deprived cells, Yang engineered cells that lacked the enzyme entirely using genetic editing and monitored their development. When chemically induced to become mature fat cells, these lab-grown mouse cells looked remarkably similar to cells deprived of copper in the earlier experiments — they grew to about twice the size of normal cells and contained more lipid.

This result affirmed that cellular copper levels were essential to SSAO function and that inactivating this enzyme caused fat cells to grow abnormally, the researchers said.

What still remained unclear, however, was how these cells accumulated that much lipid.

“In normal cells, the intake of the two cellular fuels, lipid and sugar, are balanced,” says Yang. “It appeared that something about copper deficiency shifted that balance toward fat accumulation.”

The researchers knew from previous studies that SSAO had insulinlike effects, causing the cells to consume more sugars. They hypothesized that hindering the enzyme’s function may force the cells to switch fuel sources.

To test this hypothesis, the researchers compared the protein profiles of three lines of cells: normal fat cells, cells without SSAO, and cells with SSAO genetically removed and then “rescued” by adding the protein back in. They looked for differences in protein expression and sugar or lipid intake as these cells matured. Yang repeated her earlier experiments with these cells, inducing them to develop into mature fat cells and analyzing their protein composition three, six and nine days after induction.

Overall, she identified 7,000 proteins that were present in all three cell types. By narrowing down these results to those proteins affected by the presence of functional SSAO, Yang found changes in abundance of approximately 200 proteins that all fell within 17 cellular pathways that regulated metabolism. Most significant changes were observed for proteins that absorbed and processed sugar, which were less abundant, and proteins that facilitated uptake and processing of lipids that were more abundant in cells lacking SSAO.

“This showed that SSAO is vital to many metabolic functions, including the switch between absorbing sugars to absorbing fats,” Yang says.

The researchers report they are now planning studies to monitor SSAO in the bloodstream of humans with fatty liver disease and diabetes, because SSAO appears in elevated levels in the blood of such individuals. “We suspect that SSAO may help regulate fuel selection in other tissues,” says Yang.

Public Release: 10-Oct-2018

Nutrients may reduce blood glucose levels

Study in cells and animals shows that one amino acid can provide brief beneficial effects

Joslin Diabetes Center

BOSTON – (October 10, 2018) – Type 2 diabetes is driven by many metabolic pathways, with some pathways driven by amino acids, the molecular building blocks for proteins. Scientists at Joslin Diabetes Center now have shown that one amino acid, alanine, may produce a short-term lowering of glucose levels by altering energy metabolism in the cell.

“Our study shows that it’s possible we can use specific nutrients, in this case amino acids, to change metabolism in a cell, and these changes in metabolism can change how cells take up and release glucose in a beneficial way,” says Mary-Elizabeth Patti, MD, an investigator in Joslin’s Section on Integrative Physiology and Metabolism and senior author on a paper about the work recently published in Molecular Metabolism.

Performed in cells and in mice, her group’s research began with an attempt to see what nutrients might activate a key protein called AMP kinase (AMPK), says Patti, who is also an associate professor of medicine at Harvard Medical School.

“AMPK is an enzyme in cells throughout the body that is activated when nutrient supplies are low, or in response to exercise,” she explains. “AMPK then causes a lot of beneficial changes in the cell, turning on genes that serve to increase energy production. AMPK is a good thing, and it also can be activated by a variety of treatments for type 2 diabetes, such as metformin.”

That raised a question for Patti and her colleagues: Could an amino acid switch on this beneficial enzyme?

The investigators began their study by testing many amino acids in rat liver cells (the liver is a crucial organ in glucose metabolism). “Alanine was the one amino acid that was consistently able to activate AMPK,” Patti says.

The researchers then confirmed that AMPK was producing some of its usual metabolic effects after alanine activation. Additionally, the activation could be seen in human and mouse liver cells as well as rat liver cells, and was present with either high or low levels of glucose in the cells.

Next, scientists gave alanine by mouth to mice and found that levels of AMPK rose in the animals. Moreover, if mice ate alanine before they received a dose of glucose, their resulting blood glucose levels were significantly lower. And while glucose metabolism often behaves quite differently in lean mice than in obese mice, this mechanism was seen in both groups of mice.

Following up, the Joslin team found that the glucose lowering didn’t seem to be driven by increases in insulin secretion or decreases in secretion of glucagon, a hormone that increases glucose. Instead, AMPK was boosting glucose uptake in the liver and decreasing glucose release. Further experiments in cells demonstrated that the activated enzyme was altering the Krebs cycle, a central component of cell metabolism.

“All these data together suggest that amino acids, and specifically alanine, may be a unique potential way to modify glucose metabolism,” Patti sums up. “If it eventually turns out that you can do that by taking an oral drug as a pre-treatment before a meal, that would be of interest. However, this is early-stage research, and we need to test the concept both in mice and ultimately in humans.”

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Yusuke Adachi of Joslin and Ajinomoto Company was first author on the paper. Other Joslin contributors included Ana Luisa De Sousa-Coelho, Charlie Aoun, Sandra Weimer, Hirokazu Takahashi, Chris Doherty and Laurie Goodyear. Co-authors also included Ikue Harata and Yasushi Noguchi of Ajinomoto, Xu Shi and Robert Gerszten of Beth Israel Deaconess Medical Center, and Karina Gonzalez Herrera and Marcia Haigis of Harvard Medical School. Lead funding came from Ajinomoto, the American Diabetes Association and the Lilly and Graetz Foundations.

About Joslin Diabetes Center

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is an independent, non-profit institution affiliated with Harvard Medical School, and one of only 11 NIH-designated Diabetes Research Centers in the U.S. For more information, visit http://www.joslin.org or follow @joslindiabetes One Joslin Place, Boston, MA 617-309-2400

Public Release: 18-Oct-2018

Eating leafy greens could help prevent macular degeneration

Westmead Institute for Medical Research

A new study has shown that eating vegetable nitrates, found mainly in green leafy vegetables and beetroot, could help reduce your risk of developing early-stage age-related macular degeneration (AMD).

Researchers at the Westmead Institute for Medical Research interviewed more than 2,000 Australian adults aged over 49 and followed them over a 15-year period.

The research showed that people who ate between 100 to 142 mgs of vegetable nitrates each day had a 35% lower risk of developing early AMD than people who ate less than 69mgs of vegetable nitrates each day.

Lead Researcher Associate Professor Bamini Gopinath from the Westmead Institute and the University of Sydney said the link between vegetable nitrates and macular degeneration could have important implications.

“This is the first time the effects of dietary nitrates on macular degeneration risk has been measured.

“Essentially we found that people who ate 100 to 142 mgs of vegetable nitrates every day had a reduced risk of developing early signs of macular degeneration compared with people who ate fewer nitrates.

“If our findings are confirmed, incorporating a range of foods rich in dietary nitrates – like green leafy vegetables and beetroot – could be a simple strategy to reduce the risk of early macular degeneration,” Associate Professor Gopinath said.

Spinach has approximately 20mg of nitrate per 100g, while beetroot has nearly 15mg of nitrate per 100g.

The research did not show any additional benefits for people who exceeded 142mgs of dietary nitrate each day. It also did not show any significant connections between vegetable nitrates and late stage AMD, or between non-vegetable nitrates and AMD risk.

One in seven Australians over 50 have some signs of macular degeneration.

Age is the strongest known risk factor and the disease is more likely to occur after the age of 50.

There is currently no cure for the disease.

The research compiled data from the Blue Mountains Eye Study, a benchmark population-based study that started in 1992.

It is one of the world’s largest epidemiology studies, measuring diet and lifestyle factors against health outcomes and a range of chronic diseases.

“Our research aims to understand why eye diseases occur, as well as the genetic and environmental conditions that may threaten vision,” Associate Professor Gopinath concluded.

Public Release: 23-Oct-2018

The smell of lavender is relaxing, science confirms

A new study shows that the famous relaxing effects of lavender rely on sense of smell — and that the active compound linalool could be used medically to treat anxiety

Frontiers

Lavender works its relaxing magic all around us: from garden borders to bath bombs to fabric softener. But why not in our hospitals and clinics? And what is the science behind the magic?

Research published in Frontiers in Behavioral Neuroscience shows for the first time that the vaporized lavender compound linalool must be smelt – not absorbed in the lungs- to exert its calming effects, which could be used to relieve preoperative stress and anxiety disorders.

Soothing scents

“In folk medicine, it has long been believed that odorous compounds derived from plant extracts can relieve anxiety,” says co-author Dr Hideki Kashiwadani of Kagoshima University, Japan.

Modern medicine has overlooked these scented settlers, despite a need for safer alternatives to current anxiolytic (anxiety-relieving) drugs like benzodiazepines.

Numerous studies now confirm the potent relaxing effects of linalool, a fragrant alcohol found in lavender extracts.

“However, the sites of action of linalool were usually not addressed in these studies,” Kashiwadani points out.

Many assumed that absorption into bloodstream via the airway led to direct effects on brain cell receptors such as GABAARs – also the target of benzodiazepines. But establishing the true mechanism of linalool’s relaxing effects is a key step in moving towards clinical use in humans.

A nose for success

Kashiwadani and colleagues tested mice to see whether it is the smell of linalool – i.e. stimulation of olfactory (odor-sensitive) neurons in the nose – that triggers relaxation.

“We observed the behavior of mice exposed to linalool vapor, to determine its anxiolytic effects. As in previous studies, we found that linalool odor has an anxiolytic effect in normal mice. Notably, this did not impair their movement.” This contrasts with benzodiazepines, and linalool injections, whose effects on movement are similar to those of alcohol.

However, crucially there was no anxiolytic effect in anosmic mice – whose olfactory neurons have been destroyed – indicating that the relaxation in normal mice was triggered by olfactory signals evoked by linalool odor.

What’s more, the anxiolytic effect in normal mice disappeared when they were pretreated with flumazenil, which blocks benzodiazepine-responsive GABAA receptors.

“When combined, these results suggest that linalool does not act directly on GABAA receptors like benzodiazepines do – but must activate them via olfactory neurons in the nose in order to produce its relaxing effects,” explains Kashiwadani.

Coming to theaters near you

“Our study also opens the possibility that relaxation seen in mice fed or injected with linalool could in fact be due to the smell of the compound emitted in their exhaled breath.”

Similar studies are therefore needed to establish the targets, safety and efficacy of linalool administered via different routes, before a move to human trials.

“These findings nonetheless bring us closer to clinical use of linalool to relieve anxiety – in surgery for example, where pretreatment with anxiolytics can alleviate preoperative stress and thus help to place patients under general anesthesia more smoothly. Vaporized linalool could also provide a safe alternative for patients who have difficulties with oral or suppository administration of anxiolytics, such as infants or confused elders.”

Public Release: 24-Oct-2018

Cannabis pain relief without the ‘high’

Canadian researchers pinpoint the mechanism of cannabidiol for safe pain relief without side effects

McGill University Health Centre

In the wake of cannabis legalization, a team of scientists at the Research Institute of the McGill University Health Centre (MUHC) and McGill University have delivered encouraging news for chronic pain sufferers by pinpointing the effective dose of marijuana plant extract cannabidiol (CBD) for safe pain relief without the typical “high” or euphoria produced by the THC. The findings of their study have been published in the journal PAIN (The Journal of the International Association for the Study of Pain).

Cannabis indica and sativa are the two main cannabis strains that produce the pharmacological principles known as tetrahydrocannabinol (THC) and cannabidiol (CBD). Dr. Gabriella Gobbi’s team demonstrated that CBD does not act on the CB1 cannabinoid receptors like THC but through the mechanism that binds specific receptors involved in anxiety (serotonin 5-HT1A) and pain (vanilloid TRPV1). Researchers were able to extrapolate the exact dosage of CBD displaying analgesic and antianxiety properties without the risk of addiction and euphoria classically produced by the THC.

“We found in animal models of chronic pain that low doses of CBD administered for seven days alleviate both pain and anxiety, two symptoms often associated in neuropathic or chronic pain,” says first author of the study Danilo De Gregorio, a post-doctoral fellow at McGill University in Dr. Gobbi’s laboratory.

Lead author Dr. Gobbi, a researcher in the Brain Repair and Integrative Neuroscience (BRaIN) Program of the RI-MUHC, sees this as advancement for the evidence-based application of cannabis in medicine with CBD offering a safe alternative to THC and opioids for chronic pain, such as back pain, sciatica, diabetic, cancer and post-trauma pain.

“Our findings elucidate the mechanism of action of CBD and show that it can be used as medicine without the dangerous side effects of the THC,” says Dr. Gobbi, who is also Professor of Psychiatry at the Faculty of Medicine at McGill University and staff psychiatrist at the MUHC. “This research is a new advancement for an evidence-based application of cannabis in medicine.”

Despite widespread public usage, little clinical studies exist on CBD, which became legal in Canada on October 17, 2018, following the passage of Canada’s Cannabis Act.

“There is some data showing that CBD provides pain relief for humans but more robust clinical trials are needed ,” says Dr. Gobbi, a recent grant recipient for her study of the pharmalogical effects of CBD.

Public Release: 24-Oct-2018

Brain-eating amoebae halted by silver nanoparticles

American Chemical Society

Halloween is just around the corner, and some people will celebrate by watching scary movies about brain-eating zombies. But even more frightening are real-life parasites that feed on the human brain, and they can be harder to kill than their horror-movie counterparts. Now, researchers have developed silver nanoparticles coated with anti-seizure drugs that can kill brain-eating amoebae while sparing human cells. The researchers report their results in ACS Chemical Neuroscience.

Although infections with brain-eating amoebae (Naegleria fowleri) are rare, they are almost always deadly. Most cases result from inhaling warm, dirty water in ponds, hot springs or unchlorinated swimming pools. Another species, Acanthamoeba castellanii, can cause blindness by entering the eyes through dirty contact lenses. Common treatments include antimicrobial drugs, but they often cause severe side effects because of the high doses required for them to enter the brain. Ayaz Anwar and colleagues wondered if three anti-seizure drugs — diazepam, phenobarbitone and phenytoin — could kill amoebae, alone or in combination with silver nanoparticles. The drugs are already approved by the U.S. Food and Drug Administration and are known to cross the blood-brain barrier. The researchers reasoned that they might be more effective when attached to silver nanoparticles, which can improve the delivery of some drugs and also have their own antimicrobial effects.

The team chemically attached the drugs to silver nanoparticles and examined their ability to kill amoebae. They found that each of the three drugs alone could kill N. fowleri and A. castellanii, but they worked much better when bound to silver nanoparticles. The drug-nanoparticle combos protected human cells from the microbes, increasing their survival rate compared with untreated infected human cells. The researchers propose that these repurposed drugs, aided by the nanoparticles, might kill amoebae by binding to protein receptors or ion channels on the single-celled organism’s membrane.

Public Release: 24-Oct-2018

Importance of infant diet in establishing a healthy gut

Newcastle University

A child has until the age of two-and-a-half to establish healthy gut bacteria – with little change after this point, new research has revealed.

The study also reinforced the important role breastfeeding plays in providing good gut bacteria to babies during the early stages of their life.

The team, involving Newcastle University, UK, identified that the bacterium, Bifidobacterium, was abundant in breast milk and declined rapidly after breastfeeding stopped.

The research, published today in the journal Nature, is one of the largest clinical microbiome studies in babies to date.

Key bacteria

Dr Christopher Stewart, from Newcastle University’s Institute of Cellular Medicine, co-led the research, which used a cohort of patients involved in the pioneering TEDDY (The Environmental Determinants of Diabetes in the Young) study.

Bifidobacterium is regarded as beneficial and is one of the main bacteria used in probiotics, owing to its potential therapeutic properties.

It is hoped that this research will enable a greater understanding into what can be done to produce the same benefits of breastfeeding when breast milk is not available.

Dr Stewart said: “Breastfeeding has long been understood to be good for infants and epidemiological evidence shows being breastfed early in life is associated with lower risk of many later life diseases, such as allergy and obesity.

“Targeting the nutrients in breast milk that encourage the growth of healthy bacteria in the infant gut, or providing probiotic containing Bifidobacterium, represent important avenues for future research aimed at restoring the beneficial properties of being breastfed when breast milk is not available.”

The research revealed that once infants were weaned there was a rapid turnover in the bacterial community and a loss of most of the Bifidobacterium, replaced by bacteria within the Firmicutes phyla. Firmicutes are typical of an adult microbiome and the appearance of these bacteria once breastfeeding was stopped occurred much quicker than experts expected.

Dr Stewart said: “Because a diet without breast milk delivers different nutrients to the gut, this rapid turnover in the bacterial community is likely to be in response to the new food sources promoting the growth of a different community.

“Remarkably, from this point on, the microbiome progressed quickly towards being stable, where the bacteria in the gut will potentially remain for the rest of that individual’s life.”

Microbiome development

Scientists used sequencing-based approaches to analyse 12,500 stool samples from 903 children in the TEDDY study, collected monthly from children aged three to 46 months old. Microbiome composition and diversity changed over time in three distinct phases: the developmental phase (3-14 months), transitional phase (15-30 months) and stable phase (31 months onwards).

Vaginal birth was associated with a temporary increase in Bacteroides bacteria. Siblings, exposure to pets, and geographical location were also factors in the differences between microbiome profiles.

Dr Joseph Petrosino, director of the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine, Texas, USA, was group leader of the microbiome study.

He said: “We know that the first few years of life are important for microbiome establishment. You are born with very few microbes, and microbial communities assemble on and in your body through those first years of your life.

“In this study, we took a closer look at the establishment of the microbiome over the first few years of life, and the early life exposures associated with that sequence of events, in this amazing cohort.”

In a sister paper in the same journal, experts from the Broad Institute analysed nearly 11,000 stool samples from 783 infants in the TEDDY study to characterise the early gut microbiome in children progressing to type 1 diabetes. They report that the microbiomes of infants without type 1 diabetes harbour more genes related to fermentation and short-chain fatty-acid synthesis that, in combination with previous evidence, are associated with a protective effect.

Public Release: 24-Oct-2018

Anti-aging molecule NAD+ gets a boost from blocking an enzyme

Ecole Polytechnique Fédérale de Lausanne

Nicotinamide adenine dinucleotide (NAD+) is a major player in nutrition today. Studies have shown that NAD+ concentrations decrease during aging and that recovering the body’s levels of NAD+ can prolong both health span and even life span, making it the focus of much research in nutritional science, medicine, and even pharmaceutics.

In terms of biology, NAD+ is what is known as a “co-enzyme” – a necessary molecule that helps an enzyme carry out its respective reaction in the cell. NAD+ is a common co-enzyme for multiple metabolic enzymes across all living cells, meaning that it is heavily involved in producing energy and keeping cells alive and healthy.

Publishing in Nature, scientists lead by Johan Auwerx at EPFL’s Interfaculty Institute of Bioengineering in collaboration with TES Pharma have found a new way of increasing NAD+ in the kidney and liver by blocking an enzyme competing with its production.

The de novo synthesis of NAD+ in the cell begins with the amino acid tryptophan. One of the key enzymes involved in this process is ACMSD, which limits the amount of NAD+ produced by the de novo synthesis pathway.

The scientists were able to show that ACMSD controls the levels of NAD+ in the cell through a mechanism that doesn’t seem to have changed during evolution: case-in-point, the researchers found that, in both the earthworm Caenorhabditis elegans and mice, blocking the enzyme resulted in higher NAD+ levels and enhanced mitochondrial function.

The inactivation of ACMSD also increased the activity of Sirtuin 1, an enzyme that NAD+ works with in its role as co-enzyme. Sirtuin 1 is known to play major roles in mitochondrial well-being, and as a result, the boost of NAD+ levels ultimately enhanced mitochondrial function.

The team then used two potent and selective inhibitors of ACMSD, developed by TES Pharma. “Since the enzyme is mostly found in the kidney and liver, we wanted to test the capacity of the ACMSD inhibitors to protect these organs from injury,” explains Elena Katsyuba, first author of the paper.

Both inhibitors were shown to preserve kidney and liver function in animal models of acute kidney injury and of non-alcoholic fatty liver disease, offering much promise for their future therapeutic potential in humans. “The fact that ACMSD is exclusively present only in the liver and kidneys reduces the risk of negative repercussions of its loss on other organs,” says Katsyuba. “Put simply, the enzyme will not be missed by an organ that does not have it anyway.”

“Given the beneficial health effects of boosting NAD+ levels that we have seen in worm and mouse models of disease, we are looking forward to bringing these compounds soon to the clinic to the benefit of patients suffering from liver and kidney diseases, two areas with a large unmet clinical need,” says Johan Auwerx.

Public Release: 25-Oct-2018

Late night snacker? Make it cottage cheese

New research shows protein before bed supports metabolism, muscle recovery

Florida State University

TALLAHASSEE, Fla. — Eager to eat a snack before bedtime? A protein-filled snack like cottage cheese is the way to go, say Florida State University researchers.

Associate Professor of Nutrition, Food and Exercise Sciences Michael Ormsbee and former FSU graduate student Samantha Leyh found that consuming 30 grams of protein about 30 minutes before bed appears to have a positive effect on muscle quality, metabolism and overall health. And for those who have sworn off eating at night, there is no gain in body fat.

Their findings are published in the British Journal of Nutrition.

Study participants — active young women in their early 20s — ate samples of cottage cheese 30 to 60 minutes before bedtime. Researchers specifically wanted to see if this food may have an impact on metabolic rate and muscle recovery.

This is one of the first nutrition studies where participants consumed a whole food as opposed to a protein shake or some form of supplement.

“Until now, we presumed that whole foods would act similarly to the data on supplemental protein, but we had no real evidence,” Ormsbee said. “This is important because it adds to the body of literature that indicates that whole foods work just as well as protein supplementation, and it gives people options for presleep nutrition that go beyond powders and shaker bottles.”

Leyh, who is now a research dietitian with the Air Force, said the results serve as a foundation for future research on precise metabolic responses to whole food consumption.

“While protein supplements absolutely have their place, it is important to begin pooling data for foods and understanding the role they can play in these situations,” Leyh said. “Like the additive and synergistic effects of vitamins and minerals when consumed in whole food form such as fruits or veggies, perhaps whole food sources may follow suit. While we can’t generalize for all whole foods as we have only utilized cottage cheese, this research will hopefully open the door to future studies doing just that.”

Ormsbee said that his research team will start examining more presleep food options and longer-term studies to learn more about the optimal food choices that can aid individuals in recovery from exercise, repair and regeneration of muscle and overall health.

“There is much more to uncover in this area of study,” he said.

Public Release: 30-Oct-2018

Fermented dairy products may protect against heart attack

University of Eastern Finland

Men who eat plenty of fermented dairy products have a smaller risk of incident coronary heart disease than men who eat less of these products, according to a new study from the University of Eastern Finland. A very high consumption of non-fermented dairy products, on the other hand, was associated with an increased risk of incident coronary heart disease. The findings were published in the British Journal of Nutrition.

Earlier studies have shown that fermented dairy products have more positive effects on blood lipid profiles and on the risk of heart disease than other dairy products. Examples of fermented dairy products include cheese, yoghurt, quark, kefir and sour milk. However, research into the topic remains scarce.

The Kuopio Ischaemic Heart Disease Risk Factor Study ongoing at the University of Eastern Finland explored the associations of fermented and non-fermented dairy products with the risk of incident coronary heart disease. Approximately 2,000 men participated in the study. Their dietary habits were assessed at the beginning of the study in 1984-1989, and they were followed up for an average of 20 years. During this follow-up, 472 men experienced an incident coronary heart disease event.

The study participants were divided into groups on the basis of how much they ate different dairy products, and the researchers compared the groups with the highest and lowest consumption, while also taking various lifestyle and nutrition factors into consideration.

When the study participants were divided into four groups on the basis of their consumption of fermented dairy products with less than 3.5% fat, the risk of incident coronary heart disease was 26% lower in the highest consumption group compared to the lowest consumption group. Sour milk was the most commonly used low-fat fermented dairy product. The consumption of high-fat fermented dairy products, such as cheese, was not associated with the risk of incident coronary heart disease.

However, the researchers found that a very high consumption on non-fermented dairy products was associated with an increased risk of incident coronary heart disease. Milk was the most commonly used product in this category, and a very high consumption was defined as an average daily milk intake of 0.9 litres. Lower consumption levels were not associated with the risk.

“Here in Finland, people’s habits of consuming different dairy products have changed over the past decades. For instance, the consumption of milk and sour milk have declined, while many fermented dairy products, such as yoghurt, quark and cheeses, have gained in popularity,” Adjunct Professor Jyrki Virtanen from the University of Eastern Finland says.

The new study provides further evidence on the health benefits that fermented dairy products may have over non-fermented ones. All the mechanisms are not understood yet, but they may be linked to compounds forming during the fermentation process.

Public Release: 30-Oct-2018

Rose geranium oil may ease common painful nasal symptoms linked to cancer treatment

Small study builds on anecdotal evidence, but larger scale research needed, say authors

BMJ

The findings build on anecdotal evidence for the use of rose geranium oil to treat nasal vestibulitis, which affects the lining of the nostrils, causing them to become excessively tender, bleed, and form scabs.

But larger scale research would be needed to see whether the oil could become a viable treatment option, caution the authors.

Nasal vestibulitis is a side effect of cancer drug treatment, and is particularly common in people treated with a class of drugs called taxanes, which stop cell division, and/or vascular endothelial growth factors, or VEGFs for short, which stunt the formation of new blood vessels, so stifling tumour growth.

As yet, there is no recognised treatment for this unpleasant chemotherapy side effect and little guidance for doctors on how best to help affected patients.

Taking their cue from the anecdotal evidence, the authors set out to see if the oil might ease the symptoms of nasal vestibulitis in 40 women on chemotherapy for breast cancer between 2007 and 2017.

Over half (58%) were being treated with taxanes; the rest were being treated with a range of broad spectrum and targeted cancer drugs.

The most common nasal symptoms were bleeding (65%) and discomfort (63%), but other symptoms included dryness (30%), scabbing (13%), and sores (25%).

Each of the women was given a rose geranium oil spray in a sesame oil base and asked to use it, as needed. They were asked to score the severity of symptoms before and after use and to fill in a survey on their experience of using the oil.

The average severity score was just under 3 (out of 4), corresponding to ‘moderately severe’ symptoms.Twenty one women responded to the survey, one of whom didn’t use the oil as her symptoms resolved when she stopped chemotherapy.

Among the 20 respondents, half said they used the oil daily, with 45 per cent saying they used it several times a day.

All of them said it had helped ease their symptoms: the scores of 11 (55%) women indicated that they had derived moderate benefit; the scores of six (30%) indicated substantial benefit; and in two cases (10%), the symptoms cleared up completely.

This is an observational study, and as such, can’t establish cause. And the authors note that their findings are limited by the low response rate to the survey. Further research is needed, they emphasise.

But they nevertheless write: “Rose geranium in sesame oil nasal spray appears to be quite useful for patients who experience nasal vestibulitis from cancer-directed therapy.”

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Public Release: 30-Oct-2018

Plant-based or vegan diet may be best for keeping type 2 diabetes in check

It is linked to improved wellbeing, quality of life, weight loss and lower blood glucose

BMJ

This diet is associated with improved psychological wellbeing, a reduction in some of the known risk factors for type 2 diabetes, and possibly some of those linked to cardiovascular disease, one of the main causes of early death in people with the condition, the findings indicate.

The International Diabetes Federation estimates that 642 million people will be living with diabetes by 2040. In the UK around 4.5 million people have been diagnosed with it; in the US the equivalent figure is more than 30 million.

Nearly 15 per cent of all global deaths are attributed to diabetes; and it killed 5 million people before the age of 60 in 2015. It is also frequently associated with depression, which in turn affects how well blood glucose levels are controlled.

While a predominantly plant-based diet-rich in fruits, vegetables, nuts, legumes, and seeds with no (vegan) or few animal products-has been linked to a significantly lower risk of developing type 2 diabetes, it’s not clear if it might also be linked to improved mood and wellbeing.

To try and find out, the researchers trawled through the available evidence and found 11 relevant English language clinical trials, published between 1999 and 2017, comparing plant-based diets with other types of diet. The studies involved a total of 433 people in their mid-50s, on average.

Eight of the trials assessed the impact of a vegan diet and six included patients being given information on optimal nutrition to help them better understand the benefits of a plant based diet. The trials lasted for an average of 23 weeks.

A systematic critical analysis of the results showed that quality of life-both physical and emotional-improved only in those patients on a plant based/vegan diet. Similarly, depressive symptoms improved significantly only in these groups.

Nerve pain (neuropathy) eased in both the plant based and comparator diet groups, but more so in the former. And the loss of temperature control in the feet in those on the comparator diets suggests that eating predominantly plant based foods may have slowed the progressive nerve damage associated with diabetes, say the researchers.

Average (HbA1c) and fasting blood glucose levels fell more sharply in those who cut out or ate very few animal products and these participants lost nearly twice as much weight: 5.23 kg vs 2.83 kg. The fall in blood fats–a known risk factor for cardiovascular disease–was also greater in those on plant based/vegan diets.

The researchers point out several caveats to their findings, including the small sample sizes of the studies they reviewed and the reliance of the data on participant recall. But this review is the first to attempt to look at the psychological impact of a plant based diet in people with type 2 diabetes, and it draws on research from five different countries, they say.

In six of the studies, those following a plant based/vegan diet were able to cut down or discontinue the drugs they were taking for their diabetes and associated underlying conditions, such as high blood pressure.

Overall, the results indicated that even though the plant based diets were more difficult to follow, at least to begin with, participants stuck to them better than those in the comparator groups.

“Based on the evidence of the research analysis by this systematic review, it can be concluded that plant-based diets accompanied by educational interventions can significantly improve psychological health, quality of life, HbA1c levels and weight, and therefore the management of diabetes,” write the researchers.

“Furthermore, plant-based diets could potentially improve diabetic neuropathic pain and the levels of total cholesterol, [low density lipoprotein] cholesterol and triglycerides in [type 2 diabetes].

Public Release: 31-Oct-2018

Study links cottonseed oil with lower cholesterol

University of Georgia

Athens, Ga. – Researchers at the University of Georgia have found that a high-fat diet enriched with cottonseed oil drastically improved cholesterol profiles in young adult men.

The researchers conducted a five-day outpatient feeding trial of 15 healthy, normal weight men to test the effects of diets enriched with cottonseed oil and olive oil on lipid profiles.

Participants showed significant reductions in cholesterol and triglycerides in the cottonseed oil trial compared to minimal changes on the olive oil-enriched diet.

The results appear in the journal Nutrition Research.

“One of the reasons these results were so surprising is because of the magnitude of change observed with the cottonseed oil diet,” said Jamie Cooper, an associate professor in the UGA College of Family and Consumer Sciences’ department of foods and nutrition and the corresponding author of the journal article. “To see this amount of change in such a short period of time is exciting.”

The subjects, all healthy men between the ages of 18 and 45, were provided high-fat meals for five days in two separate, tightly controlled trials, the only difference being the use of either cottonseed oil or olive oil in the meals.

Participants showed an average decrease of 8 percent in total cholesterol on the cottonseed oil diet, along with a 15 percent decrease in low-density lipoprotein, or LDL (the “bad” cholesterol) and a 30 percent decrease in triglycerides.

This diet also increased high-density lipoproteins, or HDL (the “good” cholesterol) by 8 percent.

Researchers suggested a fatty acid unique to cottonseed oil, dihydrosterculic acid, may help prevent the accumulation of triglycerides, a type of fat, in the body.

“By doing that, it pushes the body to burn more of that fat because it can’t store it properly, so you have less lipid and cholesterol accumulation,” Cooper said.

That mechanism, in addition to the high polyunsatured fat and omega-6 content of cottonseed oil, seems to be a key component to the beneficial effects on lipid profiles, Cooper said.

Researchers plan to expand the study to include older adults with high cholesterol as well as a longer feeding intervention.

Public Release: 5-Nov-2018

Drinking coffee may reduce your chances of developing Alzheimer’s, Parkinson’s

 

University Health Network

TORONTO – Approximately 500 billion cups of coffee are consumed worldwide each year.

A new study out of the Krembil Brain Institute, part of the Krembil Research Institute, suggests there could be more to that morning jolt of goodness than a boost in energy and attention. Drinking coffee may also protect you against developing both Alzheimer’s and Parkinson’s disease.

“Coffee consumption does seem to have some correlation to a decreased risk of developing Alzheimer’s disease and Parkinson’s disease,” says Dr. Donald Weaver, Co-director of the Krembil Brain Institute. “But we wanted to investigate why that is — which compounds are involved and how they may impact age-related cognitive decline.”

Dr. Weaver enlisted Dr. Ross Mancini, a research fellow in medicinal chemistry and Yanfei Wang, a biologist, to help. The team chose to investigate three different types of coffee – light roast, dark roast, and decaffeinated dark roast.

“The caffeinated and de-caffeinated dark roast both had identical potencies in our initial experimental tests,” says Dr. Mancini. “So we observed early on that its protective effect could not be due to caffeine.”

Dr. Mancini then identified a group of compounds known as phenylindanes, which emerge as a result of the roasting process for coffee beans. Phenylindanes are unique in that they are the only compound investigated in the study that prevent – or rather, inhibit – both beta amyloid and tau, two protein fragments common in Alzheimer’s and Parkinson’s, from clumping. “So phenylindanes are a dual-inhibitor. Very interesting, we were not expecting that.” says Dr. Weaver.

As roasting leads to higher quantities of phenylindanes, dark roasted coffee appears to be more protective than light roasted coffee.

“It’s the first time anybody’s investigated how phenylindanes interact with the proteins that are responsible for Alzheimer’s and Parkinson’s,” says Dr. Mancini. “The next step would be to investigate how beneficial these compounds are, and whether they have the ability to enter the bloodstream, or cross the blood-brain barrier.”

The fact that it’s a natural compound vs. synthetic is also a major advantage, says Dr. Weaver.

“Mother Nature is a much better chemist than we are and Mother Nature is able to make these compounds. If you have a complicated compound, it’s nicer to grow it in a crop, harvest the crop, grind the crop out and extract it than try to make it.”

But, he admits, there is much more research needed before it can translate into potential therapeutic options.

“What this study does is take the epidemiological evidence and try to refine it and to demonstrate that there are indeed components within coffee that are beneficial to warding off cognitive decline. It’s interesting but are we suggesting that coffee is a cure? Absolutely not.”

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About the Krembil Research Institute

The Krembil Research Institute (or “Krembil”) is one of the principal research institutes of the University Health Network. The Krembil is focused on research programs dedicated to brain & spine, arthritis and vision disorders with a goal to alleviate debilitating chronic disease through basic, translational and clinical research. Krembil is located at the Toronto Western Hospital in downtown Toronto. For more information, visit http://www.uhn.ca/Research/Research_Institutes/Krembil

About University Health Network

University Health Network consists of Toronto General and Toronto Western Hospitals, the Princess Margaret Cancer Centre, Toronto Rehabilitation Institute, and The Michener Institute of Education at UHN. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has the largest hospital-based research program in Canada, with major research in cardiology, transplantation, neurosciences, oncology, surgical innovation, infectious diseases, genomic medicine and rehabilitation medicine. University Health Network is a research hospital affiliated with the University of Toronto. http://www.uhn.ca

 

Public Release: 4-Nov-2018

Trial finds diet rich in fish helps fight asthma

 

La Trobe University

A clinical trial led by La Trobe University has shown eating fish such as salmon, trout and sardines as part of a healthy diet can reduce asthma symptoms in children.

The international study found children with asthma who followed a healthy Mediterranean diet enriched with fatty fish had improved lung function after six months.

Lead researcher Maria Papamichael from La Trobe said the findings added to a growing body of evidence that a healthy diet could be a potential therapy for childhood asthma.

“We already know that a diet high in fat, sugar and salt can influence the development and progression of asthma in children and now we have evidence that it’s also possible to manage asthma symptoms through healthy eating,” Ms Papamichael said.

“Fatty fish is high in omega-3 fatty acids which have anti-inflammatory properties. Our study shows eating fish just twice a week can significantly decrease lung inflammation in children with asthma.”

Co-researcher and Head of La Trobe’s School of Allied Health, Professor Catherine Itsiopoulos, said the results were promising.

“Following a traditional Mediterranean diet that is high in plant-based foods and oily fish could be an easy, safe and effective way to reduce asthma symptoms in children,” Professor Itsiopoulos said.

Associate Professor Bircan Erbas, from La Trobe’s School of Psychology and Public Health, is an expert in asthma and allergies, who co-supervised the trial.

“Asthma is the most common respiratory disease in young people and one of the leading reasons for hospitalisations and trips to emergency for children,” Associate Professor Erbas said.

“Unfortunately, the rate of asthma worldwide remains high. It is imperative that we identify new therapies that we can use alongside conventional asthma medications.”

The clinical trial involved 64 children from Athens in Greece, aged 5 to 12 who had mild asthma. Researchers from Australia and Greece divided the children into two groups and instructed around half to eat two meals of cooked fatty fish (of at least 150 grams) as part of the Greek Mediterranean diet every week for six months. The remaining children followed their normal diet.

At the end of the trial, they found the group who ate fish had reduced their bronchial inflammation by 14 units. Above 10 units is significant under international guidelines.

Public Release: 10-Nov-2018

VITAL study: How vitamin D and fish oil affect risk of heart attack, stroke and cancer

Findings show omega-3 fatty acids reduced risk of heart attacks, especially among African Americans; vitamin D reduced cancer deaths over time

Brigham and Women’s Hospital

Boston, MA — For years, it’s remained an open question: What effects do dietary supplements such as high doses of vitamin D or omega-3 fatty acids derived from fish oil have on the risk of diseases such as heart attack, stroke and cancer? While there have been hints along the way, until now, no randomized clinical trial of a general population, especially a racially diverse population, has been large enough to adequately address these questions. Brigham and Women’s Hospital investigators leading the VITamin D and OmegA-3 TriaL (VITAL) conducted a rigorous placebo-controlled trial over the course of 5.3 years, gleaning a treasure trove of information on the effects of both supplements. The team found that omega-3 fish oil reduced heart attack rates but did not affect risk of stroke or cancer. In addition, vitamin D did not significantly affect heart attack, stroke or cancer incidence but was associated with a decrease in cancer deaths that started one to two years after participants began treatment. Results from VITAL were presented by JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham, at the American Heart Association Scientific Sessions 2018, and published simultaneously in the New England Journal of Medicine.

The VITAL study population was racially and ethnically diverse, and 20 percent of the participants were African American. The team found that the reduction of heart attack risk among those taking omega-3s was especially pronounced among African American participants, with a 77 percent reduction observed.

“VITAL is one of only a few randomized trials that has had a diverse study population, and African Americans have not been well studied in previous trials of omega-3 supplements. We found that omega-3 supplements were associated with a dramatic reduction in risk of heart attacks among African Americans in our study. If this finding is confirmed and replicated, it may point to a very promising approach to reducing coronary risk among African Americans,” said Manson. “We found that omega-3s were associated with a reduction in risk of heart attacks across our study population, especially among participants who had lower than average fish intake (less than 1 1/2 servings per week). In addition, VITAL results showed that with time, vitamin D supplements may lower risk of cancer death. We plan to follow these participants for the next several years to see if this signal becomes stronger.”

VITAL, a randomized, double-blind, placebo-controlled trial, enrolled 25,871 men and women age 50 and older from across the U.S., including 5,106 African Americans. Eligible participants had no history of cancer, heart attack, stroke, or other forms of cardiovascular disease at the time of enrollment.

While earlier trials have examined whether fish oil or other supplements may prevent heart attack or stroke in patients with a history of heart disease or at very high risk of such disease, VITAL is the first large trial of omega-3 fatty acids for primary prevention – that is, preventing the first occurrence – of heart disease in a general population.

VITAL was designed to test the independent effects of vitamin D and omega-3 supplements, as well as to test for synergy between the two. Participants were divided into four groups: vitamin D (2000 IU/day of vitamin D? [cholecalciferol]) plus omega-3s (1g/day of Omacor [known as Lovaza in the U.S.]); vitamin D plus placebo omega-3s; omega-3s plus placebo vitamin D; and placebos for both.

Researchers compared those who received active omega-3s with those who received placebo. After a median of five years of treatment, 805 participants had suffered a major adverse cardiovascular event, such as a heart attack or stroke (386 in the omega-3 group and 419 in the placebo group). While these rates did not statistically differ, VITAL found a significant 28 percent reduction in risk of heart attack among participants taking the omega-3 fatty acid supplements (145 cases in the omega-3 group and 200 in the placebo group). This effect was greater among people who had lower fish intake (a 40 percent reduction). No significant differences were seen for cancer outcomes.

The research team also examined the effect of vitamin D on cancer rates. A total of 1,617 participants were diagnosed with cancer by the end of the study; 793 had been taking vitamin D and 824 had been taking the placebo – a non-significant difference. Rates of specific forms of cancer – including breast, prostate and colorectal cancer – did not differ significantly between groups. However, when the team examined rates after participants had been taking supplements for at least two years, they found that cancer deaths were significantly reduced by 25 percent among those taking vitamin D. No differences were seen for cardiovascular outcomes with vitamin D.

No serious side effects, such as bleeding, high blood calcium levels, or gastrointestinal symptoms were found with either supplement. The two supplements did not appear to interact with each other or have synergistic effects. In addition to cardiovascular disease and cancer outcomes, VITAL will report on the effects of vitamin D and omega-3s on rates of diabetes, cognitive function, autoimmune disease, respiratory infections, depression and more in the months ahead.

“Over the next six months, we will have even more results to share that may help clinicians and patients understand the benefits and risks of taking omega-3 and vitamin D supplements,” said Manson. “Medical and public health authorities may look at the study results and decide if clinical guidelines should be updated. In the meantime, if you’re already taking one or both of these supplements, there’s no clear reason to stop. If you want to consider starting, our recommendation is to talk with your health care provider, but this does not need to be done on an urgent basis.”

Public Release: 14-Nov-2018

Low carb diets can help maintain weight loss by increasing number of calories burned

Effect may improve the success of obesity treatment

BMJ

The researchers say this effect may improve the success of obesity treatment, especially among people with high insulin secretion (insulin level 30 minutes after consuming a standard amount of glucose).

It is well known that energy expenditure declines with weight loss, as the body adapts by slowing metabolism and burning fewer calories, often resulting in weight regain. But little is known about how dietary composition influences this adaptive response over the long term.

One theory (known as the carbohydrate-insulin model) is that recent increases in the consumption of processed, high glycemic load foods trigger hormonal changes that increase hunger and make people more likely to gain weight.

To better understand the role of dietary composition on energy expenditure, researchers led by Cara Ebbeling and David Ludwig at Boston Children’s Hospital set out to compare the effects of diets varying in carbohydrate to fat ratio on energy expenditure over a 20-week period.

The trial involved 234 overweight adults aged 18 to 65 years with a body mass index (BMI) of 25 or higher who took part in an initial weight loss diet for about 10 weeks.

Of these, 164 achieved the target weight loss of around 10% of body weight and were then randomly assigned to follow either a high (60%), moderate (40%), or low (20%) carbohydrate diet for 20 weeks.

Each participant was provided with fully prepared meals with a similar protein and fat content. The researchers then tracked participants’ weight and measured energy expenditure to compare how the different groups burned calories at the same weight.

After adjusting for potentially influential factors, they found that over the 20 weeks, total energy expenditure was significantly greater in participants on the low carbohydrate diet compared with the high carbohydrate diet.

Participants on the low carbohydrate diet burned 209 to 278 kilocalories a day more than those on the high carbohydrate diet – or about 50 to 70 kilocalories a day increase for every 10% decrease in the contribution of carbohydrate to total energy intake.

In those with the highest insulin secretion at the start of the study, the difference in total energy expenditure between the low and high carbohydrate diets was even greater – up to 478 kilocalories a day, consistent with the carbohydrate-insulin model.

If this effect persisted “it would translate into an estimated 10 kg weight loss after three years, assuming no change in calorie intake,” write the authors.

Hormones involved in energy balance (ghrelin and leptin) changed in a potentially advantageous manner in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet.

The authors point to some study limitations and cannot rule out the possibility that some of the observed effects may be due to other unmeasured factors. Nevertheless, they say this large trial shows that dietary composition seems to affect energy expenditure independently of body weight.

“A low glycemic load, high fat diet might facilitate weight loss maintenance beyond the conventional focus on restricting energy intake and encouraging physical activity,” they conclude. And they call for additional research to explore these effects further and develop appropriate behavioral and environmental interventions for translation to public health.

Public Release: 13-Nov-2018

Weightlifting is good for your heart and it doesn’t take much

Iowa State University

AMES, Iowa – Lifting weights for less than an hour a week may reduce your risk for a heart attack or stroke by 40 to 70 percent, according to a new Iowa State University study. Spending more than an hour in the weight room did not yield any additional benefit, the researchers found.

“People may think they need to spend a lot of time lifting weights, but just two sets of bench presses that take less than 5 minutes could be effective,” said DC (Duck-chul) Lee, associate professor of kinesiology.

The results – some of the first to look at resistance exercise and cardiovascular disease – show benefits of strength training are independent of running, walking or other aerobic activity. In other words, you do not have to meet the recommended guidelines for aerobic physical activity to lower your risk; weight training alone is enough. The study is published in Medicine and Science in Sports and Exercise.

Lee and his colleagues analyzed data of nearly 13,000 adults in the Aerobics Center Longitudinal Study. They measured three health outcomes: cardiovascular events such as heart attack and stroke that did not result in death, all cardiovascular events including death and any type of death. Lee says resistance exercise reduced the risk for all three.

“The results are encouraging, but will people make weightlifting part of their lifestyle? Will they do it and stick with it? That’s the million-dollar question,” Lee said.

Barriers to resistance training

The researchers recognize that unlike aerobic activity, resistance exercise is not as easy to incorporate into our daily routine. Lee says people can move more by walking or biking to the office or taking the steps, but there are few natural activities associated with lifting. And while people may have a treadmill or stationary bike at home, they likely do not have access to a variety of weight machines.

For these reasons, Lee says a gym membership may be beneficial. Not only does it offer more options for resistance exercise, but in a previous study Lee found people with a gym membership exercised more. While this latest study looked specifically at use of free weights and weight machines, Lee says people will still benefit from other resistance exercises or any muscle-strengthening activities.

“Lifting any weight that increases resistance on your muscles is the key,” Lee said. “My muscle doesn’t know the difference if I’m digging in the yard, carrying heavy shopping bags or lifting a dumbbell.”

Other benefits of strength training

Much of the research on strength training has focused on bone health, physical function and quality of life in older adults. When it comes to reducing the risk for cardiovascular disease, most people think of running or other cardio activity. Lee says weight lifting is just as good for your heart, and there are other benefits.

Using the same dataset, Lee and his colleagues looked at the relationship between resistance exercise and diabetes as well as hypercholesterolemia, or high cholesterol. The two studies, published in Mayo Clinic Proceedings, found resistance exercise lowered the risk for both.

Less than an hour of weekly resistance exercise (compared with no resistance exercise) was associated with a 29 percent lower risk of developing metabolic syndrome, which increases risk of heart disease, stroke and diabetes. The risk of hypercholesterolemia was 32 percent lower. The results for both studies also were independent of aerobic exercise.

“Muscle is the power plant to burn calories. Building muscle helps move your joints and bones, but also there are metabolic benefits. I don’t think this is well appreciated,” Lee said. “If you build muscle, even if you’re not aerobically active, you burn more energy because you have more muscl

Public Release: 13-Nov-2018

Probiotics increase bone volume in healthy mice

Cell Press

 

A widely-used probiotic stimulates bone formation in young female mice, according to a study published November 13th in the journal Immunity. In response to treatment with Lactobacillus rhamnosus GG (LGG), other intestinal microbes produced a metabolite called butyrate, which in turn activated bone-enhancing immune cells, including regulatory T cells.

“The significance of the study is that probiotics are, at least in mice, an effective means to increase bone density,” says senior study author Roberto Pacifici of Emory University. “Clinical trials are in progress to validate the efficacy of probiotics in humans.”

Fractures due to osteoporosis can have devastating consequences. For example, complications of hip fractures lead to mortality rates of 24%-30% during the first year following injury, and almost 50% rates of permanent disability. Unfortunately, most cases of osteoporosis remain untreated or ineffectively treated due to the cost and side effects of currently available drugs. There is an urgent need to identify and develop inexpensive, safe, and effective interventions for both the prevention and treatment of osteoporosis.

Small-scale studies in patients with osteoporosis have reported positive results from dietary supplementation with probiotics. In animals, probiotics can prevent disease-related bone loss, but their influence on the healthy skeleton remains less clear. “Because their mechanism of action in bone is unknown, they are regarded as some kind of alternative, esoteric, unproven treatment,” Pacifici says. “Our goal was to identify a biological mechanism of action of probiotics, a mechanism that makes sense to traditional scientists, hoping that this will make probiotics a mainstream treatment.”

In the new study, Pacifici and colleagues found that oral LGG supplementation for four weeks increased bone formation in female mice by stimulating the growth of butyrate-producing gut bacteria, including Clostridia. Notably, LGG supplementation did not increase bone mass in mice raised in a germ-free environment, suggesting that this probiotic indirectly exerts its effects through the metabolic activity of other microbes that normally inhabit the intestines.

Supplementation with either LGG or butyrate induced the expansion of regulatory T cells in the intestine and in bone marrow – the spongy tissue inside some bones. This caused T cells in the bone marrow to secrete a protein called Wnt10b, which is known to be critical for bone development. By contrast, treatments that inhibited the expansion of regulatory T cells prevented bone formation induced by LGG and butyrate.

“We were surprised by the potency of the gut microbiome in regulating bone and by the complexity of the mechanism of action of probiotics,” Pacifici says. “In general, there is a lot of interest in the concept that the gut bacteria regulate the function of distant organs. How this happens is largely unknown. We described a detailed mechanism by which changes in the composition of the gut microbiome induced by probiotics affect a distant system like the skeleton.”

Lactobacillus is the most common genus of bacteria with reported probiotic activities. According to the authors, the findings are likely to generalize beyond LGG to other bacteria that also produce lactic acid. But it remains to be determined whether other types of probiotics work in the same way.

“The controversies about probiotics are: Do they work for real, and which one is the best?” Pacifici says. “We show that they work for real in bone. Which one is the best remains unknown. However, the emerging concept is that the number of bacteria in a dose of probiotic may be as important or even more important than the type of probiotic used. It is possible that the response to probiotics might be influenced by mouse strain, gender, and age.”

Moving forward, the researchers will explore the role of the microbiota in bone diseases other than osteoporosis. They also plan to determine whether butyrate supplementation could prevent and treat osteoporosis, and whether probiotics could improve skeletal health in various disease states. In the future, the use of probiotics or butyrate to increase the number of regulatory T cells may find wider applications, such as in transplant medicine or as a treatment for inflammatory and autoimmune conditions.

“Our findings will need to be validated in human studies,” Pacific says. “If successful, this research could substantiate the use of butyrate or probiotics as a novel, safe, and inexpensive treatment for optimizing skeletal development in young people and to prevent osteoporosis in older people.”

Public Release: 15-Nov-2018

New research finds omega-3 fatty acids reduce the risk of premature birth

Wiley

A new Cochrane Review published today has found that increasing the intake of omega-3 long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy reduces the risk of premature births.

Premature birth is the leading cause of death for children under 5 years old worldwide, accounting for close to one million deaths annually. Premature babies are at higher risk of a range of long-term conditions including visual impairment, developmental delay and learning difficulties.

“We know premature birth is a critical global health issue, with an estimated 15 million babies born too early each year,” explains Associate Professor Philippa Middleton from Cochrane Pregnancy and Childbirth and the South Australian Health and Medical Research Institute (SAHMRI). “While the length of most pregnancies is between 38 and 42 weeks, premature babies are those born before the 37-week mark – and the earlier a baby is born, the greater the risk of death or poor health.”

Associate Professor Middleton and a team of Cochrane researchers have been looking closely at long-chain omega-3 fats and their role in reducing the risk of premature births – particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) found in fatty fish and fish oil supplements. They looked at 70 randomised trials and found that for pregnant women, increasing the daily intake of long-chain omega-3s:

• lowers the risk of having a premature baby (less than 37 weeks) by 11% (from 134 per 1000 to 119 per 1000 births)
• lowers the risk of having an early premature baby (less than 34 weeks) by 42% (from 46 per 1000 to 27 per 1000 births)
• reduces the risk of having a small baby (less than 2500g) by 10%

“There are not many options for preventing premature birth, so these new findings are very important for pregnant women, babies and the health professionals who care for them,” Associate Professor Middleton says. “We don’t yet fully understand the causes of premature labour, so predicting and preventing early birth has always been a challenge. This is one of the reasons omega-3 supplementation in pregnancy is of such great interest to researchers around the world.”

The Cochrane review published today was first undertaken back in 2006, and concluded there wasn’t enough evidence to support the routine use of omega-3 fatty acid supplements during pregnancy. Over a decade on, this updated review concludes that there’s high quality evidence for omega-3 supplementation being an effective strategy for preventing preterm birth.

“Many pregnant women in the UK are already taking omega-3 supplements by personal choice rather than as a result of advice from health professionals,” says Associate Professor Middleton. “It’s worth noting though that many supplements currently on the market don’t contain the optimal dose or type of omega-3 for preventing premature birth. Our review found the optimum dose was a daily supplement containing between 500 and 1000 milligrams (mg) of long-chain omega-3 fats (containing at least 500mg of DHA) starting at 12 weeks of pregnancy.”

“Ultimately, we hope this review will make a real contribution to the evidence base we need to reduce premature births, which continue to be one of the most pressing and intractable maternal and child health problems in every country around the world.”

Public Release: 21-Nov-2018

Sugar supplement slows tumor growth and can improve cancer treatment

Cancer Research UK

Mannose sugar, a nutritional supplement, can both slow tumour growth and enhance the effects of chemotherapy in mice with multiple types of cancer.

This lab study is a step towards understanding how mannose could be used to help treat cancer.

The results of the study, which was funded by Cancer Research UK and Worldwide Cancer Research, are published in Nature, today (Wednesday).

Tumours use more glucose than normal, healthy tissues. However, it is very hard to control the amount of glucose in your body through diet alone. In this study, the researchers found that mannose can interfere with glucose to reduce how much sugar cancer cells can use*.

Professor Kevin Ryan, lead author from the Cancer Research UK Beatson Institute, said: “Tumours need a lot of glucose to grow, so limiting the amount they can use should slow cancer progression. The problem is that normal tissues need glucose as well, so we can’t completely remove it from the body. In our study, we found a dosage of mannose that could block enough glucose to slow tumour growth in mice, but not so much that normal tissues were affected. This is early research, but it is hoped that finding this perfect balance means that, in the future, mannose could be given to cancer patients to enhance chemotherapy without damaging their overall health.”

The researchers first examined how mice with pancreatic, lung or skin cancer responded when mannose was added to their drinking water and given as an oral treatment. They found that adding the supplement significantly slowed the growth of tumours and did not cause any obvious side effects.

To test how mannose could also affect cancer treatment, mice were treated with cisplatin and doxorubicin – two of the most widely used chemotherapy drugs. They found that mannose enhanced the effects of chemotherapy, slowing tumour growth, reducing the size of tumours and even increasing the lifespan of some mice.

Several other cancer types, including leukaemia, osteosarcoma, ovarian and bowel cancer, were also investigated. Researchers grew cancer cells in the lab and then treated them with mannose to see whether their growth was affected.

Some cells responded well to the treatment, while others did not. It was also found that the presence of an enzyme** that breaks down mannose in cells was a good indicator of how effective treatment was.

Professor Kevin Ryan added: “Our next step is investigating why treatment only works in some cells, so that we can work out which patients might benefit the most from this approach. We hope to start clinical trials with mannose in people as soon as possible to determine its true potential as a new cancer therapy.”

Mannose is sometimes used for short periods to treat urinary tract infections, but its long-term effects have not been investigated. It’s important that more research is conducted before mannose can be used in cancer patients.

Martin Ledwick, Cancer Research UK’s head nurse, said: “Although these results are very promising for the future of some cancer treatments, this is very early research and has not yet been tested in humans. Patients should not self-prescribe mannose as there is a real risk of negative side effects that haven’t been tested for yet. It’s important to consult with a doctor before drastically changing your diet or taking new supplements.”

Public Release: 20-Nov-2018

Antioxidants may prevent cognitive impairment in diabetes

Society for Endocrinology

Cognitive difficulties in patients with diabetes, caused by repeated episodes of low blood sugar, could be reduced with antioxidants, according to a new study presented at the Society for Endocrinology annual conference in Glasgow. The study findings suggest that stimulating antioxidant defences in mice reduces cognitive impairments caused by low blood sugar, which could help to improve the quality of life for diabetic patients.

Long-term decline in cognitive function, with everyday learning and memory tasks becoming harder and taking longer to complete, is a common consequence for patients who frequently experience low blood sugar levels when using insulin to manage their diabetes. Previous studies in mice have shown that reoccurring episodes of low blood sugar leads an accumulation of cell damaging free radicals in the brain. Whether this build-up of free radical stress directly effects cognitive function, and if the body’s own antioxidative systems, which can remove free radicals, can be harnessed to counteract these changes and improve quality of life is not known.

In this study, Dr Alison McNeilly and colleagues at the University of Dundee used insulin to induce repeated bouts of low blood sugar in a mouse model of type-1 diabetes. In the experiment, one group of mice were also dosed with the vegetable derived antioxidant sulforaphane (SFN). Mice treated with SFN showed increased expression of antioxidant markers, decreased free radical cell damage and had significantly improved cognitive ability in memory tasks.

Dr McNeilly commented, “Low blood sugar is an almost unavoidable consequence of insulin therapy. This work demonstrates that by improving the body’s own antioxidant defence system we can reverse some of the side effects associated with diabetes, such as poor cognitive function.”

Dr McNeilly and her colleagues now intend to find out if boosting the body’s antioxidative system can minimise cognitive decline associated with low blood sugar in humans, by using drugs based on the chemical structure of SFN.

Dr McNeilly said, “The concentration of SFN used in this study would not be attainable in a normal diet rich in vegetables. However, there are numerous highly potent compounds in clinical trials which may prevent cognitive impairments caused by free radicals to help diabetes patients.”

Public Release: 20-Nov-2018

Routine vitamin B12 screening may prevent irreversible nerve damage in type-2 diabetes

Society for Endocrinology

Patients with type-2 diabetes, taking metformin, should have their vitamin B12 levels assessed more regularly to avoid irreversible nerve damage, according to a new study presented at the Society for Endocrinology annual conference in Glasgow. The study findings suggest that earlier detection of vitamin B12 deficiency through routine screening of all metformin-treated, type-2 diabetes patients could reduce their risk of developing irreversible, painful and potentially disabling nerve damage.

The increasing incidence of type-2 diabetes is a serious health issue worldwide. Its prevalence is associated with poor diet and unhealthy lifestyle choices, and it is characterised by high blood glucose levels that need to be controlled by medication. Nerve damage in the periphery (e.g. face, limbs, organs) is a common complication of diabetes, with symptoms that range from numbness to pain, and can lead to debilitating loss of balance and co-ordination. Metformin is the recommended and most effective first-line drug for type-2 diabetes but its use has also been linked to vitamin B12 deficiency, which increases the risk of peripheral nerve damage. Despite the irreversibility of peripheral nerve damage, no official guidelines exist on screening vitamin B12 levels in patients treated with metformin.

In this study, Dr Kaenat Mulla and GP colleagues at Hucknall Road Medical Centre, Nottingham conducted an audit of vitamin B12 screening and deficiency among female, metformin-treated, patients with type-2 diabetes at the GP practice. The audit findings indicated that 64% of patients had not had their vitamin B12 levels checked at all, and that 9.6% of patients were deficient but only 6.4% were being treated with vitamin B12.

Dr Mulla states, “Current British Society of Haematology guidelines recommend that vitamin B12 levels are checked only when there is clinical suspicion of deficiency. However, peripheral neuropathy is irreversible and it may be too late once symptoms have developed.”

Dr Mulla and her team now plan to extend their audit to determine how best to treat patients found to be vitamin B12 deficient, and to provide further evidence that all type-2 patients on metformin should have their levels checked more regularly, for example at their annual check-up.

Dr Mulla comments, “Our findings indicate that patients with diabetes taking metformin should be checked more frequently and that we need to ensure deficiencies are adequately treated to avoid irreversible nerve damage.” However, she also cautions, “Metformin remains the best treatment for type-2 diabetes, these findings should not discourage patients from taking it, but encourage doctors to monitor vitamin B12 levels more routinely, so any deficiency can quickly be treated.”