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268 CNO REPORT 19 FEB 2020

In This Issue:

  1. Consumption of chili pepper cuts down the risk of death from a heart or cerebral attack
  2. Could some people with schizophrenia in poorer nations simply have a vitamin deficiency?
  3. Chemical compound found in essential oils improves wound healing, IU study finds
  4. Compound in green tea plant shows potential for fighting TB, finds NTU-led research team
  5. Watermelon supplements bring health benefits to obese mice
  6. Acid reflux affects nearly a third of US adults weekly
  7. Your DNA is not your destiny — or a good predictor of your health
  8. Glutamine may decrease obesity-linked inflammation
  9. Low-fat diet linked to lower testosterone levels in men
  10. Tea drinkers live longer
  11. Gut bacteria could guard against Parkinson’s, study finds
  12. Blue light can help heal mild traumatic brain injury
  13. Vitamin C-B1-steroid combo linked to lower septic shock mortality in kids
  14. Can lithium halt progression of Alzheimer’s disease?
  15. Vitamin D supplementation linked to potential improvements in blood pressure in children
  16. The scent of a rose improves learning during sleep
  17. Study: Antioxidant flavonol linked to lower risk of Alzheimer’s dementia
  18. Natural compound in vegetables helps fight fatty liver disease
  19. Antioxidant reverses BPD-induced fertility damage in worms
  20. Prebiotics help mice fight melanoma by activating anti-tumor immunity
  21. Vitamin E effective, safe for fatty liver in HIV patients
  22. Green tea extract combined with exercise reduces fatty liver disease in mice
  23. Vitamin C may shorten ventilation in critically ill patients
  24. Cocoa could bring sweet relief to walking pain for people with peripheral artery disease
  25. EPA fails to follow landmark law to protect children from pesticides in food
  26. Postmenopause vitamin D deficiency associated with disc degeneration and lower back pain
  27. Research reverses the reproductive clock in mice
  28. Low folate levels can indicate malnutrition in hospital patients

268CNOADDENDUM

NEWS RELEASE 16-DEC-2019

Consumption of chili pepper cuts down the risk of death from a heart or cerebral attack

Chili pepper is a common guest in Italians kitchens, and over the centuries it has been praised for its supposed therapeutic virtues. Now an Italian research shows that people who consume it on a regular basis have a mortality risk for every cause reduced by 23% compared to those who do not like it. The study, published in the Journal of the American College of Cardiology (JACC), has been conducted by the Department of Epidemiology and Prevention of I.R.C.C.S. Neuromed in Pozzilli, Italy, in collaboration with the Department of Oncology and Molecular Medicine of the Istituto Superiore di Sanità in Rome, the University of Insubria in Varese and the Mediterranean Cardiocentro in Naples.

The research examined 22,811 citizens of Molise region, in Italy, participating in the Moli-sani study. Following their health status for an average period of about 8 years, and comparing it with their eating habits, Neuromed researchers observed that, in people regularly consuming chili pepper (4 times a week or more), the risk of dying of a heart attack was cut down by 40%. Risk reduction for cerebrovascular mortality was even higher since it resulted more than halved.

“An interesting fact – says Marialaura Bonaccio, Neuromed epidemiologist and first author of the publication – is that protection from mortality risk was independent of the type of diet people followed. In other words, someone can follow the healthy Mediterranean diet, someone else can eat less healthily, but for all of them chili pepper has a protective effect”.

The Moli-sani study is the first to explore the properties of this spice in relation to the risk of death in a European and Mediterranean population.

“Chili pepper – comments Licia Iacoviello, Director of the Department of Epidemiology and Prevention at the I.R.C.C.S. Neuromed and Professor of Hygiene and Public Health at the Università dell’Insubria of Varese – is a fundamental component of our food culture. We see it hanging on Italian balconies, and even depicted in jewels. Over the centuries, beneficial properties of all kinds have been associated with its consumption, mostly on the basis of anecdotes or traditions, if not magic. It is important now that research deals with it in a serious way, providing rigor and scientific evidence. And now, as already observed in China and in the United States, we know that the various plants of the capsicum species, although consumed in different ways throughout the world, can exert a protective action towards our health”.

New researches will be now necessary to understand the biochemical mechanisms through which the chili pepper and its “relatives” (all united by the presence of a substance called capsaicin), scattered in all the corners of the globe, act. But for the time being, spicy food lovers surely have one more reason to maintain their habit.

NEWS RELEASE 12-DEC-2019

Could some people with schizophrenia in poorer nations simply have a vitamin deficiency?

Four unsolved mysteries around schizophrenia have long plagued the medical community, but a new hypothesis identifying a common link between them and an almost forgotten epidemic of a disease called pellagra could have profound implications for our understanding of psychosis in poorer nations. The new hypothesis has implications for how a subgroup of people with active psychosis could be potentially screened, treated, and cured.

The idea behind the hypothesis occurred to Esme Fuller-Thomson, professor at the University of Toronto’s Factor-Inwentash Faculty of Social Work (FIFSW) after learning about recent research conducted in South India. This study newly identified a link between schizophrenia and a variant of the gene NAPRT1, which lowers the body’s ability to use niacin, or Vitamin B3, which naturally occurs in meat, poultry, fish, and eggs.

“When I read this study a light bulb went on in my head,” says Fuller-Thomson, who published the hypothesis in the journal Schizophrenia Research this month with doctoral student, Rukshan Mehta. “This seems to be the missing link that explains all these medical mysteries.”

The researchers speculate that there is a critical interaction between an expectant mother’s prenatal niacin deficiency due to malnourishment and the NAPRT1 variant that impedes the fetus’ ability to use niacin. This interaction between the gene and the prenatal environment may predispose the offspring to develop a psychotic disorder.

Several studies indicate that the offspring of mothers who experience famine in their first trimester of pregnancy have double the chance of developing schizophrenia. Most researchers assume nutrient deficiency must be playing a role, but the particular nutrient has yet to be identified. Fuller Thomson now speculates that niacin may be the key nutrient involved.

The identification of the NAPRT1 risk variant also provides some insights into a second medical mystery: Normally when people are given high doses of niacin, their skin reddens and can tingle, burn, or itch; however, many individuals with schizophrenia experience limited or no flushing to the same high dose amount. The presence of a gene inhibiting the uptake of niacin may explain why people with schizophrenia do not show the same reddening of the skin in response to large doses: they simply have a lower ability to absorb the vitamin.

Pellagra could be an important part of the puzzle as well. Between 1906 to 1940, almost 3 million Americans developed pellagra due to a niacin deficient diet. The symptoms include dermatitis, dementia, and death. In four to ten percent of cases, active psychosis develops, which mimics schizophrenia. Pellagra became the leading cause of death in psychiatric hospitals in the Southern United States in that era.

“Treatment with niacin quickly and permanently cures the disease including the psychosis and the dermatitis,” reported co-author Rukshan Mehta, an MSW graduate of the FIFSW who is currently a doctoral candidate in Nutrition & Health Sciences at Emory University. “By 1941, flour was fortified with niacin in the USA and the disease was soon after largely eradicated.”

Today, diagnosis of pellagra is rare, but Fuller-Thomson and Mehta wonder if it might be going undetected in the developing world.

In most cases of pellagra, a bad rash is the first symptom, and this is usually how the disorder is diagnosed. The researchers hypothesize that individuals with psychosis and the risky gene variant may not present with dermatitis. This would result in the patients being misclassified as having schizophrenia instead of the easily treatable psychosis associated with niacin deficiency.

Fuller-Thomson and Mehta’s hypothesis also provides new insights into the most perplexing of the medical mysteries associated with schizophrenia: studies by the World Health Organization show that patients with schizophrenia in the developing world recover at a markedly higher rate than those in western nations, despite the fact that those in the west receive more extensive medical interventions.?If some of the schizophrenia patients in the developing world were, in fact, undiagnosed pellagra cases, their psychosis may have been cured inadvertently by simply spending time in a hospital where nutritious niacin-rich food such as meat and eggs are provided.

The final medical mystery has been generating debate for half a century. Six randomized controlled trials conducted in Saskatchewan, Canada in the 1950s found excellent results treating patients with schizophrenia with high doses of niacin, but multiple efforts to replicate the study in the 1970s found the intervention ineffective.

The 1950s Canadian studies were conducted among patients born in the Great Depression before niacin fortification of flour was adopted. “It is highly probable that those with schizophrenia in Saskatchewan had malnourished, niacin-deficient mothers,” says Fuller-Thomson. “If the patients’ psychosis was due to undiagnosed pellagra, of course the niacin treatment would be effective. The pregnant mothers of the participants in the later study benefited from universal niacin fortification and therefore the patients were unlikely to have pellagra.”

The researchers emphasize that both a correct diagnosis and medical supervision of niacin treatment for pellagra are essential. “Taking high dose niacin can cause life-threatening problems if not properly monitored,” cautions Fuller-Thomson.

“We acknowledge that this hypothesis is highly speculative, but feel further exploration of these ideas are warranted,” says Fuller-Thomson.?”In cases where the psychosis is due to pellagra, these patients could be inexpensively, quickly, and permanently cured with high dose niacin, allowing them to live a healthy normal life.”

NEWS RELEASE 18-DEC-2019

Chemical compound found in essential oils improves wound healing, IU study finds

INDIANA UNIVERSITY

CREDIT: PHOTO COURTESY OF SACHIKO KOYAMA

BLOOMINGTON, Ind. — Indiana University researchers have discovered that a chemical compound found in essential oils improves the healing process in mice when it is topically applied to a skin wound — a finding that could lead to improved treatments for skin injuries in humans.

IU scientists also reported that skin tissue treated with the chemical compound, beta-carophyllene — which is found in lavender, rosemary and ylang ylang, as well as various herbs and spices such as black pepper — showed increased cell growth and cell migration critical to wound healing. They also observed increased gene expression of hair follicle stem cells in the treated tissue. The scientists did not find any involvement of the olfactory system in the wound healing.

Their research was published Dec. 16 in the journal PLOS ONE.

“This is the first finding at the chemical-compound level showing improved wound healing in addition to changes in gene expression in the skin,” said Sachiko Koyama, corresponding author on the paper, who, at the time of this research, was an associate scientist at the IU School of Medicine and is currently a visiting scientist in the IU College of Arts and Sciences’ Department of Biology. “The way gene expression changed also suggests not only improved wound healing but also the possibility of less scar formation and a more full recovery.

“It’s an example that essential oils work; however, it’s not through our sense of smell.”

Essential oils are natural, concentrated oils extracted from plants. Their use by humans dates back to ancient Egypt, but the scented oils have experienced a resurgence in popularity in the U.S. over the past few years, with many people using them for aromatherapy.

Koyama, whose original field of study is pheromones, said she wasn’t interested in essential oils at first. The project started when she saw several students studying the wound healing process in mice in the Medical Sciences Program at the IU School of Medicine-Bloomington. Having previously worked in the IU College of Arts and Sciences’ Department of Psychological and Brain Sciences, where scientists are working with cannabinoid receptors, Koyama knew that beta-caryophyllene activates not only olfactory receptors but also cannabinoid receptor 2 (CB2), which has anti-inflammatory impact when it is activated.

“In the wound healing process, there are several stages, starting from the inflammatory phase, followed by the cell proliferation stage and the remodeling stage,” she said. “I thought maybe wound healing would be accelerated if inflammation was suppressed, stimulating an earlier switch from the inflammatory stage to the next stage.”

This accelerated the wound healing process, she said, but the resulting change in gene expression indicates that the improved healing is not merely achieved through activation of the CB2 receptor.

“It’s possibly more complicated,” Koyama said. “Our findings suggest the involvements of some other routes in addition to CB2. I hope to clarify the mechanisms of action in the near future.”

Although the study’s results are promising, Koyama said she wouldn’t recommend that people start treating their injuries with just any essential oils, as her research applies to a very specific chemical compound with known purity, diluted in a specific concentration.

“It’s not very precise to use the essential oils themselves because there are differences,” she said. “Even if you say you used lavender, when the lavender was harvested, where it was harvested, how it was stored — all of this makes a difference in the chemical composition.”

Koyama said further research is required to figure out how beta-carophyllene might be used to develop new treatments for skin wounds in humans. She said she hopes to better understand the mechanisms that accelerate the healing process and to find a combination of chemical compounds that could be used together to accelerate drug delivery and chemical stability, which is important for avoiding or suppressing allergic responses caused by oxidation of the chemical compounds.

“We still need thorough scientific studies at the chemical-compound level and also to test the combinations of these chemical compounds,” Koyama said. “For example, there are studies showing that linalool — another compound found in lavender — can suppress anxiety through the olfactory system. There could be the best combinations of chemical compounds at specific ratios, and we might be able to do prescriptions of aroma chemical compounds, depending on the specific treatment goals.

“There are many things to test before we can start using it clinically, but our results are very promising and exciting; someday in the near future, we may be able to develop a drug and drug delivery methods using the chemical compounds found in essential oils.”

NEWS RELEASE 17-DEC-2019

Compound in green tea plant shows potential for fighting TB, finds NTU-led research team

NANYANG TECHNOLOGICAL UNIVERSITY

An antioxidant found in the green tea plant could become key to tackling tuberculosis one day, a team of international scientists led by Nanyang Technological University, Singapore (NTU Singapore) has found.

Through laboratory investigations, the team led by NTU Professor Gerhard Grüber discovered how the prominent compound, known as epigallocatechin gallate (EGCG), can inhibit the growth of a tuberculosis-causing bacteria strain.

The EGCG does so by binding to an enzyme that provides biological energy for cellular activity. The process results in a dip in the amount of energy the bacteria has for its cellular processes vital for growth and stability, such as cell wall formation.

The team, which includes NTU Associate Professor Roderick Bates, National University of Singapore (NUS) Professor Thomas Dick, and collaborators from the US and New Zealand, also identified the exact sites on the enzyme at which the EGCG needs to bind to in order to affect energy production in the bacterial cell.

The findings were published in the journal Scientific Reports in November. A patent has been filed for the identification of the EGCG as a possible form of treatment for tuberculosis.

These findings could pave the way for the creation of novel drugs to combat tuberculosis, one of the most deadly infectious diseases in the world. Southeast Asia accounts for 41 per cent of the world’s tuberculosis cases, with 4 million new cases every year.

While there are already drugs that target mycobacterium tuberculosis (M. tuberculosis) – the bacteria that causes the airborne disease – new ones are needed because the bacteria is increasingly showing resistance to many of the drugs.

Professor Gerhard Grüber from the NTU School of Biological Sciences said: “Though tuberculosis is curable, the success of current drugs on the market is increasingly being overshadowed by the bacteria’s clinical resistance. Our discovery of the EGCG’s ability to inhibit the growth of M. tuberculosis will allow us to look at how we can improve the potency of this compound in green tea, and other similar compounds, to develop new drugs to tackle this airborne disease.”

How EGCG disrupts tuberculosis

Cells require energy for vital processes such as cell wall formation to take place. They get their energy from an energy storage molecule made by an enzyme called ATP synthase. Without energy for essential cellular activity, a cell loses its stability and eventually dies.

To determine the factors affecting the production of ATP synthase, and thus the amount of energy a bacterial cell has for growth, the NTU-led team studied mycobacterium smegmatis and mycobacterium bovis, both of which belong to the same family as M. tuberculosis. These mycobacterial strains share a similar structural composition.

The team first found that alterations to the genetic code for ATP synthase resulted in an enzyme that produced fewer energy storage molecules in the bacterial cells, slower cell growth, and an altered colony shape.

With this data, the scientists then screened for and found 20 compounds that could possibly bind to ATP synthase and cause the same blocking effect, and then tested them for their efficacy. Only EGCG, a natural antioxidant that occurs in a large amount in green tea, showed it had the same crucial effect of reducing energy storage molecules in the bacterial cell.

The NTU-led team is now looking at optimising the activity of EGCG for increased efficiency and potency in fighting the tuberculosis bacteria. Their ultimate goal is to develop a drug cocktail that will tackle multi-drug resistant tuberculosis.

NEWS RELEASE 19-DEC-2019

Watermelon supplements bring health benefits to obese mice

OREGON STATE UNIVERSITY

CORVALLIS, Ore. – Eating watermelon in the form of powdered supplements helped adult obese mice avoid some detrimental health effects of an unhealthy diet, according to a new Oregon State University study.

The study is published in the Journal of Nutrition.

A significant next step in this research would be a human clinical trial, said study co-author Neil Shay, professor of food science in OSU’s College of Agricultural Sciences.

In the study, 10-week-old male laboratory mice were fed either a low-fat or high-fat diet over a 10-week period. Groups of high-fat-fed mice were given watermelon supplements in the form of a powder made from a freeze-dried process. The amount of water melon flesh supplement was equivalent to 1½ human servings a day, and the skin and rind supplement were equivalent to the amount in a typical dietary fiber supplement.

At the beginning and end of the trial, the researchers recorded the body weight and glucose tolerance of each mouse. Mice that were fed a high-fat diet supplemented with watermelon products had significantly better blood glucose levels than the mice on the high-fat-only diet.

An elevated blood-glucose level may be an indicator of Type 2 diabetes, a disease in which the body doesn’t make enough or properly use insulin, a hormone that turns food into energy. Type 2 is the most common form of diabetes in the United States.

The researchers also saw a significant increase in the family of beneficial bacteria in the mice that were given powder supplements, Shay said.

“Even though the two groups of mice were eating the same amount of fat and sugar, that consumption of 1½ servings of watermelon flesh or 2% of high-fiber rind or skin products had significant effects,” Shay said.

The study was funded by the National Watermelon Promotion Board, an industry group that is seeking new ways to use byproducts such as skin and rind that end up as food waste.

Worldwide production of watermelon topped 117 million metric tons in 2016. In Oregon, watermelon is a multimillion industry in the lower Umatilla basin near Hermiston. Despite all that fruit, there hasn’t been much research into the health impacts of watermelon, said Shay, who studies the compounds of fruits and vegetables and their influence on heart disease and diabetes.

This is the latest OSU study led by Shay that revealed health benefits of certain foods in laboratory mice. One study showed that walnuts helped improve metabolism and another showed that raspberries curbed weight gain even when they were fed a high-fat diet.

NEWS RELEASE 19-DEC-2019

Your DNA is not your destiny — or a good predictor of your health

New study from the University of Alberta suggests that diseases such as many cancers, diabetes, and Alzheimer’s have a genetic contribution of 5 to 10 per cent at most

In most cases, your genes have less than five per cent to do with your risk of developing a particular disease, according to new research by University of Alberta scientists.

In the largest meta-analysis ever conducted, scientists have examined two decades of data from studies that examine the relationships between common gene mutations, also known as single nucleotide polymorphisms (SNPs), and different diseases and conditions. And the results show that the links between most human diseases and genetics are shaky at best.

“Simply put, DNA is not your destiny, and SNPs are duds for disease prediction,” said David Wishart, professor in the University of Alberta’s Department of Biological Sciences and the Department of Computing Science and co-author on the study. “The vast majority of diseases, including many cancers, diabetes, and Alzheimer’s disease, have a genetic contribution of 5 to 10 per cent at best.”

The study also highlights some notable exceptions, including Crohn’s disease, celiac disease, and macular degeneration, which have a genetic contribution of approximately 40 to 50 per cent.

“Despite these rare exceptions, it is becoming increasingly clear that the risks for getting most diseases arise from your metabolism, your environment, your lifestyle, or your exposure to various kinds of nutrients, chemicals, bacteria, or viruses,” explained Wishart.

Wishart and his research collaborators suggest that measuring metabolites, chemicals, proteins, or the microbiome provides a much more accurate measure of human disease risk and are also more accurate for diagnosis. The findings fly in the face of many modern gene testing businesses models, which suggest that gene testing can accurately predict someone’s risk for disease.

“The bottom line is that if you want to have an accurate measure of your health, your propensity for disease or what you can do about it, it’s better to measure your metabolites, your microbes or your proteins–not your genes,” added Wishart. “This research also highlights the need to understand our environment and the safety or quality of our food, air, and water.”

NEWS RELEASE 19-DEC-2019

Acid reflux affects nearly a third of US adults weekly

LOS ANGELES (Dec. 19, 2019) — Gastroesophageal reflux disease (GERD), a digestive disorder that causes heartburn and other uncomfortable symptoms, may affect nearly a third of U.S. adults each week, and most of those who take certain popular medications for it still have symptoms, according to a new Cedars-Sinai study.

Also known as acid reflux, GERD is caused by gastric acid from the stomach flowing back up into a person’s food pipe, or esophagus. This backup can happen when the lower esophageal sphincter, a muscle that briefly opens to let food into the stomach and closes to take food inside, relaxes too often or too long. Besides causing the burning sensation in the throat and chest known as heartburn, GERD can damage tissues and cause food to be regurgitated.

For their research, published today in the journal Gastroenterology, investigators conducted an online survey of more than 71,000 people age 18 or over across the U.S., asking them if they experienced specific GERD symptoms and how often, and if they were taking drugs for it.

“Our study is among the largest and most diverse population-based studies on gastrointestinal symptoms ever conducted,” said Brennan Spiegel, MD, MSHS, director of Cedars-Sinai’s Health Service Research, professor of Medicine and corresponding author of the journal article. Most previous published research on GERD, which found a somewhat lower incidence of the disease than this study did, was conducted within limited geographic areas or with a less representative sampling of U.S. adults, he explained.

An important feature of the new study was its finding that more than half of GERD patients who took popular over-the-counter drugs known as proton pump inhibitors, designed to reduce the amount of acid in the stomach, still reported persistent symptoms.

The survey also indicated that certain categories of people, including younger people, women, Latinos, and people with irritable bowel syndrome or Crohn’s disease, were less likely to respond to proton pump inhibitors.

“Given the significant effect of GERD on quality of life for millions of Americans, further research and development of new therapies are needed to help patients whose disease does not respond to proton pump inhibitors,” said Spiegel, who also directs the Cedars-Sinai Center for Outcomes Research and Education.

The investigators conducted their nationwide survey in October and November 2015 using MyGiHealth, a mobile app that asked respondents to select any symptoms they had experienced in the past week or “ever experienced.” Investigators measured the severity of patients’ symptoms, using validated questionairres from the National Institutes of Health. The symptoms included GERD-relevant ones — such as heartburn, acid reflux, or gastroesophageal reflux — plus other general gastrointestinal symptoms such as abdominal pain, constipation and nausea.

Out of 71,812 people who responded to the survey, 44.1% reported experiencing GERD symptoms in the past and 30.9% in the last week. More than a third of the GERD sufferers said they were currently on therapy, mostly involving proton pump inhibitors. Of those taking daily proton pump inhibitors, 54.1% reported persistent GERD symptoms.

“The MyGiHealth digital platform allowed us to efficiently recruit a large, highly diverse, representative population in a very short period of time,” said Christopher Almario, MD, MSHPM, assistant professor of Medicine at Cedars-Sinai. Yet it also carried potential limitations because individuals with limited computer skills or poor access to the internet may be underrepresented, he explained. In addition, since the study was described as a “GI Survey” to potential respondents, it may have led to overestimating GERD prevalence since those without gastrointestinal issues may have opted not to complete the survey.

NEWS RELEASE 19-DEC-2019

Glutamine may decrease obesity-linked inflammation

KAROLINSKA INSTITUTET

Glutamine could help people with obesity reduce inflammation of fat tissue and reduce fat mass, according to a new study at Karolinska Institutet in Sweden and the University of Oxford in the U.K. The researchers also show how glutamine levels can alter gene expression in several different cell types. However, more research is needed before glutamine supplementation may be recommended as a treatment for obesity. The study is published in the journal Cell Metabolism.

Glutamine is an important amino acid with many key functions such as providing energy and maintaining good intestinal health. It also has anti-inflammatory effects on for example white blood cells and T-cells that are important for the immune system.

In the current study, the researchers examined how the metabolic processes differed in fat tissue collected from the abdomen of 52 obese and 29 non-obese women. They identified glutamine as the amino acid that displayed the largest differences when comparing the two groups. People with obesity had on average lower levels of glutamine in their fat tissue than normal-weight people. Lower glutamine-levels were also associated with larger fat cell size and higher body fat percentage independently of body-mass index (BMI), according to the study.

“Our results suggest that treatment with glutamine could be of value against obesity and insulin resistance,” says Mikael Ryden, professor and senior physician at the Department of Medicine in Huddinge, Karolinska Institutet, and the study’s corresponding author. “We know, however, that glutamine is also important for cell division and the metabolism of cancer and therefore, more research on possible long-term side effects is needed before glutamine may be recommended as a dietary supplement to help treat obesity and its complications.”

The researchers also showed through a combination of animal and cell analyses that glutamine levels influenced the expression of different genes and that low glutamine levels induced an increase in the expression of pro-inflammatory genes in the fat tissue. Obese mice injected with glutamine for two weeks had less fat tissue inflammation than mice who received a control saline solution. Their body fat mass, fat cell volume and blood glucose levels were also reduced. In an analysis of cultured human fat cells, the expression of pro-inflammatory genes and the lipid content were attenuated after incubation with increasing concentrations of glutamine. The largest effect was observed after treatment with 5-20 millimolar (mM) glutamine for 11 days, according to the study.

The researchers also studied in detail what happens inside the fat cell when glutamine levels are altered. They found that glutamine impacts a mechanism called O-GlcNAcylation that can control epigenetic changes, that is changes in gene expression caused by environmental and lifestyle factors rather than by alterations in our underlying DNA sequence. People with obesity had higher levels of O-GlcNAcylation in their fat tissue while mice and human cells treated with glutamine had lower levels of O-GlcNAcylation in the cell nucleus.

“Our study shows that glutamine is anti-inflammatory in the fat tissue by changing the gene expression in several different cell types,” says Mikael Ryden. “This means that a lack of glutamine, which may occur during long-term obesity, could lead to epigenetic changes that fuel inflammation in the body.”

Further research is needed to fully understand which genes and cellular processes are affected the most, according to the researchers.

NEWS RELEASE 10-JAN-2020

Low-fat diet linked to lower testosterone levels in men

WOLTERS KLUWER HEALTH

January 10, 2020 – For the many men diagnosed with testosterone deficiency, losing weight can help increase testosterone levels. But certain diets – specifically a low-fat diet – may be associated with a small but significant reduction in testosterone, suggests a study in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The Journal is published in the Lippincott portfolio by Wolters Kluwer.

“We found that men who adhered to a fat restrictive diet had lower serum testosterone than men on a nonrestrictive diet,” according to the report by Jake Fantus, MD, of the Section of Urology, Department of Surgery, University of Chicago Medicine and colleagues from the Department of Urology, Northwestern University Feinberg School of Medicine, and the Department of Surgery, NorthShore University Health System. “However,” the researchers add, “the clinical significance of small differences in serum T across diets is unclear.”

Best Diet for Low Testosterone? No Single Right Answer Yet

Dr. Fantus and colleagues analyzed data on more than 3,100 men from a nationwide health study (the National Health and Nutrition Examination Survey, or NHANES). All participants had available data on diet and serum testosterone level.

Based on two-day diet history, 14.6 percent of men met criteria for a low-fat diet, as defined by the American Heart Association (AHA). Another 24.4 percent of men followed a Mediterranean diet high in fruits, vegetables, and whole grains but low in animal protein and dairy products. Only a few men met criteria for the AHA low-carbohydrate diet, so this group was excluded from the analysis.

The average serum testosterone level was 435.5 ng/dL (nanograms per deciliter). Serum testosterone was lower in men on the two restrictive diets: average 411 ng/dL for those on a low-fat diet and 413 ng/dL for those on the Mediterranean diet.

The associations were adjusted for other factors that can affect testosterone, including age, body mass index, physical activity, and medical conditions. After adjustment, the low-fat diet was significantly associated with reduced serum testosterone, although the Mediterranean diet was not.

Overall, 26.8 percent of men had testosterone levels less than 300 ng/dL. Despite the difference in average testosterone levels, the proportion of men with low testosterone was similar across all diet groups.

Low testosterone is highly prevalent in the United States, as approximately 500,000 men are diagnosed with testosterone deficiency each year. Testosterone deficiency can lead to problems, including decreased energy and libido, along with physiological alterations, including increased body fat and reduced bone mineral density.

In addition to medications, treatment for low testosterone often includes lifestyle modifications, such as exercise and weight loss. But the effects of diet on testosterone levels have been unclear. Because testosterone is a steroid hormone derived from cholesterol, changes in fat intake could alter testosterone levels. This new analysis of how diet affects serum testosterone provides evidence that a low-fat diet is associated with lower testosterone levels, compared to an unrestricted diet.

So what diet is best for men with testosterone deficiency? The answer remains unknown, according to the authors. In overweight or obese men, the health benefits of a low-fat diet likely far exceed the small reduction in serum testosterone. In contrast, for men who are not overweight, avoiding a low-fat diet “may be a reasonable component” of a multifaceted approach to increasing serum testosterone.

Dr. Fantus and coauthors note that further studies will be needed to corroborate their findings, and to clarify the mechanism by which restrictive diets reduce testosterone. But due to the difficulties of large-scale dietary studies, definitive trials are unlikely to be performed. “Therefore, our data represent a valuable approach towards answering this important question,” the authors conclude.

NEWS RELEASE 9-JAN-2020

Tea drinkers live longer

EUROPEAN SOCIETY OF CARDIOLOGY

Sophia Antipolis, 9 January 2020: Drinking tea at least three times a week is linked with a longer and healthier life, according to a study published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).1

“Habitual tea consumption is associated with lower risks of cardiovascular disease and all-cause death,” said first author Dr. Xinyan Wang, Chinese Academy of Medical Sciences, Beijing, China. “The favourable health effects are the most robust for green tea and for long-term habitual tea drinkers.”

The analysis included 100,902 participants of the China-PAR project2 with no history of heart attack, stroke, or cancer. Participants were classified into two groups: habitual tea drinkers (three or more times a week) and never or non-habitual tea drinkers (less than three times a week) and followed-up for a median of 7.3 years.

Habitual tea consumption was associated with more healthy years of life and longer life expectancy.

For example, the analyses estimated that 50-year-old habitual tea drinkers would develop coronary heart disease and stroke 1.41 years later and live 1.26 years longer than those who never or seldom drank tea.

Compared with never or non-habitual tea drinkers, habitual tea consumers had a 20% lower risk of incident heart disease and stroke, 22% lower risk of fatal heart disease and stroke, and 15% decreased risk of all-cause death.

The potential influence of changes in tea drinking behaviour were analysed in a subset of 14,081 participants with assessments at two time points. The average duration between the two surveys was 8.2 years, and the median follow-up after the second survey was 5.3 years.

Habitual tea drinkers who maintained their habit in both surveys had a 39% lower risk of incident heart disease and stroke, 56% lower risk of fatal heart disease and stroke, and 29% decreased risk of all-cause death compared to consistent never or non-habitual tea drinkers.

Senior author Dr. Dongfeng Gu, Chinese Academy of Medical Sciences, said: “The protective effects of tea were most pronounced among the consistent habitual tea drinking group. Mechanism studies have suggested that the main bioactive compounds in tea, namely polyphenols, are not stored in the body long-term. Thus, frequent tea intake over an extended period may be necessary for the cardioprotective effect.”

In a subanalysis by type of tea, drinking green tea was linked with approximately 25% lower risks for incident heart disease and stroke, fatal heart disease and stroke, and all-cause death. However, no significant associations were observed for black tea.

Dr. Gu noted that a preference for green tea is unique to East Asia. “In our study population, 49% of habitual tea drinkers consumed green tea most frequently, while only 8% preferred black tea. The small proportion of habitual black tea drinkers might make it more difficult to observe robust associations, but our findings hint at a differential effect between tea types.”

Two factors may be at play. First, green tea is a rich source of polyphenols which protect against cardiovascular disease and its risk factors including high blood pressure and dyslipidaemia. Black tea is fully fermented and during this process polyphenols are oxidised into pigments and may lose their antioxidant effects. Second, black tea is often served with milk, which previous research has shown may counteract the favourable health effects of tea on vascular function.

Gender-specific analyses showed that the protective effects of habitual tea consumption were pronounced and robust across different outcomes for men, but only modest for women. Dr. Wang said: “One reason might be that 48% of men were habitual tea consumers compared to just 20% of women. Secondly, women had much lower incidence of, and mortality from, heart disease and stroke. These differences made it more likely to find statistically significant results among men.”

She added: “The China-PAR project is ongoing, and with more person-years of follow-up among women the associations may become more pronounced.”

The authors concluded that randomised trials are warranted to confirm the findings and provide evidence for dietary guidelines and lifestyle recommendations.

NEWS RELEASE 14-JAN-2020

Gut bacteria could guard against Parkinson’s, study finds

PARKINSON’S UK

A common bacteria that boosts digestive health can slow – and even reverse – build-up of a protein associated with Parkinson’s, new research suggests.

Building on previous research linking brain function to gut bacteria, this study in a Parkinson’s model of roundworms, identified a probiotic – or so-called good bacteria – which prevents the formation of toxic clumps that starve the brain of dopamine, a key chemical that coordinates movement. These new findings could pave the way for future studies that gauge how supplements such as probiotics impact the condition.

In the brains of people with Parkinson’s, alpha-synuclein protein misfolds and builds up, forming toxic clumps. These clumps are associated with the death of nerve cells responsible for producing dopamine. The loss of these cells causes the motor symptoms associated with Parkinson’s, including freezing, tremors and slowness of movement.

The researchers from the Universities of Edinburgh and Dundee used roundworms altered to produce the human version of alpha-synuclein that forms clumps. They fed these worms with different types of over-the-counter probiotics to see if bacteria in them could affect the formation of toxic clumps.

The scientists found that a probiotic called Bacillus subtilis had a remarkable protective effect against the build-up of this protein and also cleared some of the already formed protein clumps. This improved the movement symptoms in the roundworms. The researchers also found that the bacteria was able to prevent the formation of toxic alpha-synuclein clumps by producing chemicals that change how enzymes in cells process specific fats called sphingolipids.

The study by Goya ME, Xue F, et al, published in the journal Cell Reports, was funded by Parkinson’s UK, the EMBO and the European Commission. It is the latest in a number of recent studies which have found a link between brain function and the thousands of different kinds of bacteria living in the digestive system, known as the gut microbiome. Other studies into mice have found that the gut microbiome has an impact on the motor symptoms.

Lead researcher, Dr Maria Doitsidou, from the Centre for Discovery Brain Sciences at the University of Edinburgh, said: “The results provide an opportunity to investigate how changing the bacteria that make up our gut microbiome affects Parkinson’s. The next steps are to confirm these results in mice, followed by fast-tracked clinical trials since the probiotic we tested is already commercially available.”

Dr Beckie Port, Research Manager at Parkinson’s UK, said: “Parkinson’s is the fastest growing neurological condition in the world. Currently there is no treatment that can slow, reverse or protect someone from its progression but by funding projects like this, we’re bringing forward the day when there will be.

“Changes in the microorganisms in the gut are believed to play a role in the initiation of Parkinson’s in some cases and are linked to certain symptoms, that’s why there is ongoing research into gut health and probiotics.

“The results from this study are exciting as they show a link between bacteria in the gut and the protein at the heart of Parkinson’s, alpha synuclein. Studies that identify bacteria that are beneficial in Parkinson’s have the potential to not only improve symptoms but could even protect people from developing the condition in the first place.”

NEWS RELEASE 15-JAN-2020

Blue light can help heal mild traumatic brain injury

The Department of Defense has a vested interest in the new University of Arizona-led research, but the results have implications for civilians as well

UNIVERSITY OF ARIZONA

Early morning blue light exposure therapy can aid the healing process of people impact by mild traumatic brain injury, according to new research from the University of Arizona.

“Daily exposure to blue wavelength light each morning helps to re-entrain the circadian rhythm so that people get better, more regular sleep. This is likely true for everybody, but we recently demonstrated it in people recovering from mild traumatic brain injury, or mTBI. That improvement in sleep was translated into improvements in cognitive function, reduced daytime sleepiness and actual brain repair,” said William D. “Scott” Killgore, psychiatry professor in the College of Medicine – Tucson and lead author on a new study published in the journal Neurobiology of Disease.

Mild traumatic brain injuries, or concussions, are often the result of falls, fights, car accidents and sports participation. Among other threats, military personnel can also experience mTBI from exposure to explosive blasts: Shockwaves strike the soft tissue of the gut and push a burst of pressure into the brain, causing microscopic damage to blood vessels and brain tissue, Killgore said.

“Your brain is about the consistency of thick Jell-O,” he said. “Imagine a bowl of Jell-O getting hit from a punch or slamming against the steering wheel in a car accident. What’s it doing? It’s absorbing that shock and bouncing around. During that impact, microscopic brain cells thinner than a strand of hair can easily stretch and tear and rip from the force.”

Those with a concussion or mTBI can momentarily see stars, become disoriented, or even briefly lose consciousness following the injury; however, loss of consciousness doesn’t always happen and many people who sustain a concussion are able to walk it off without realizing they have a mild brain injury, according to Killgore. Headaches, attention problems and mental fogginess are commonly reported after head injuries and can persist for weeks or months for some people.

Few, if any, effective treatments for mTBI exist. The U.S. Army Medical Research and Development Command funded the research to find alternatives to medicinal methods of mTBI recovery.

“About 50% of people with mTBI also complain that they have sleep problems after an injury,” Killgore said.

Recent research has shown that the brain repairs itself during sleep, so Killgore and his co-authors – John Vanuk, Bradley Shane, Mareen Weber and Sahil Bajaj, all from the Department of Psychiatry – sought to determine if improved sleep led to a faster recovery.

In a randomized clinical trial, adults with mTBI used a cube-like device that shines bright blue light (with a peak wavelength of 469 nm) at participants from their desk or tables for 30 minutes early each morning for six weeks. Control groups were exposed to bright amber light.

“Blue light suppresses brain production of a chemical called melatonin,” Killgore said. “You don’t want melatonin in the morning because it makes you drowsy and prepares the brain to sleep. When you are exposed to blue light in the morning, it shifts your brain’s biological clock so that in the evening, your melatonin will kick in earlier and help you to fall asleep and stay asleep.”

People get the most restorative sleep when it aligns with their natural circadian rhythm of melatonin – the body’s sleep-wake cycle associated with night and day.

“The circadian rhythm is one of the most powerful influences on human behavior,” Killgore said. “Humans evolved on a planet for millions of years with a 24-hour light/dark cycle, and that’s deeply engrained in all our cells. If we can get you sleeping regularly, at the same time each day, that’s much better because the body and the brain can more effectively coordinate all these repair processes.”

As a result of the blue light treatment, participants fell asleep and woke an average of one hour earlier than before the trial and were less sleepy during the daytime. Participants improved their speed and efficiency in brain processing and showed an increase in volume in the pulvinar nucleus, an area of the brain responsible for visual attention. Neural connections and communication flow between the pulvinar nucleus and other parts of the brain that drive alertness and cognition were also strengthened.

“We think we’re facilitating brain healing by promoting better sleep and circadian alignment, and as these systems heal, these brain areas are communicating with each other more effectively. That could be what’s translating into improvements in cognition and less daytime sleepiness,” Killgore said.

Blue light from computers, smartphones and TV screens often gives blue light a bad rap. But according to Killgore, “when it comes to light, timing is critical. Light is not necessarily good or bad in-and-of-itself. Like caffeine, it all comes down to when you use it. It can be terrible for your sleep if you’re consuming coffee at 10 o’clock at night, but it may be great for your alertness if you have it in the morning.”

He and his team plan to continue their research to see if blue light improves sleep quality and how light therapy might affect emotional and psychiatric disorders. Killgore believes that most people, whether injured or healthy, could benefit from correctly timed morning blue light exposure, a theory he hopes to prove for certain in future studies.

EWS RELEASE 21-JAN-2020

Vitamin C-B1-steroid combo linked to lower septic shock mortality in kids

First pediatric study reports promising outcomes

ANN & ROBERT H. LURIE CHILDREN’S HOSPITAL OF CHICAGO

Treating septic shock in children with a combination of intravenous vitamin C, vitamin B1 and hydrocortisone (a commonly used steroid) is associated with lower mortality, according to a study from Ann & Robert H. Lurie Children’s Hospital of Chicago. This is the first pediatric study of the safe and relatively inexpensive treatment for septic shock, and the preliminary data supports the promising outcomes seen in adults. Findings were published in the American Journal of Respiratory and Critical Care Medicine.

Septic shock is the result of a severe systemic response to infection causing organ failure and dangerously low blood pressure. It is one of the leading causes of death in critically ill children.

“We were surprised and excited to see a substantial reduction in mortality after treating septic shock in children with a high dose of vitamin C combined with vitamin B1 and hydrocortisone,” says lead author Eric Wald, MD, MSCI, critical care physician at Lurie Children’s and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “While based on a retrospective analysis, our results are especially compelling in that they are very similar to the positive outcomes found in a recent randomized controlled trial of vitamin C treatment for septic shock in adults.”

In their retrospective study, Dr. Wald and colleagues matched 43 patients with septic shock who received the vitamin C-B1-hydrocortisone treatment with 43 patients of similar clinical profile who did not receive it (control group), and with 43 patients who received hydrocortisone only as adjunctive therapy. They found that while controls had mortality of 28 percent at 30 days, mortality in patients treated with the vitamin C combination protocol dropped to 9 percent in the same period. Treatment with hydrocortisone alone did not improve mortality (30 percent at 30 days). Similar reductions in mortality were seen at 90 days (14 percent with vitamin C protocol vs. 35 percent in controls and 37 percent in the hydrocortisone only group).

“While it is still unclear why vitamin C appears to reduce mortality from septic shock and we need to dig deeper to understand the mechanism, our results are incredibly promising,” says Dr. Wald. “We hope to encourage larger, multi-center studies in children with septic shock to confirm our data.”

NEWS RELEASE 24-JAN-2020

Can lithium halt progression of Alzheimer’s disease?

McGill researchers’ findings show that may be the case

MCGILL UNIVERSITY

There remains a controversy in scientific circles today regarding the value of lithium therapy in treating Alzheimer’s disease. Much of this stems from the fact that because the information gathered to date has been obtained using a multitude of differential approaches, conditions, formulations, timing and dosages of treatment, results are difficult to compare. In addition, continued treatments with high dosage of lithium render a number of serious adverse effects making this approach impracticable for long term treatments especially in the elderly.

In a new study, however, a team of researchers at McGill University led by Dr. Claudio Cuello of the Department of Pharmacology and Therapeutics, has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology such as amyloid plaques and of recovering lost cognitive abilities. The findings are published in the most recent edition of the Journal of Alzheimer’s Disease.

Building on their previous work

“The recruitment of Edward Wilson, a graduate student with a solid background in psychology, made all the difference,” explains Dr. Cuello, the study’s senior author, reflecting on the origins of this work. With Wilson, they first investigated the conventional lithium formulation and applied it initially in rats at a dosage similar to that used in clinical practice for mood disorders. The results of the initial tentative studies with conventional lithium formulations and dosage were disappointing however, as the rats rapidly displayed a number of adverse effects. The research avenue was interrupted but renewed when an encapsulated lithium formulation was identified that was reported to have some beneficial effects in a Huntington disease mouse model.

The new lithium formulation was then applied to a rat transgenic model expressing human mutated proteins causative of Alzheimer’s, an animal model they had created and characterized. This rat develops features of the human Alzheimer’s disease, including a progressive accumulation of amyloid plaques in the brain and concurrent cognitive deficits.

“Microdoses of lithium at concentrations hundreds of times lower than applied in the clinic for mood disorders were administered at early amyloid pathology stages in the Alzheimer’s-like transgenic rat. These results were remarkably positive and were published in 2017 in Translational Psychiatry and they stimulated us to continue working with this approach on a more advanced pathology,” notes Dr. Cuello.

Encouraged by these earlier results, the researchers set out to apply the same lithium formulation at later stages of the disease to their transgenic rat modelling neuropathological aspects of Alzheimer’s disease. This study found that beneficial outcomes in diminishing pathology and improving cognition can also be achieved at more advanced stages, akin to late preclinical stages of the disease, when amyloid plaques are already present in the brain and when cognition starts to decline.

“From a practical point of view our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications,” says Dr. Cuello. “While it is unlikely that any medication will revert the irreversible brain damage at the clinical stages of Alzheimer’s it is very likely that a treatment with microdoses of encapsulated lithium should have tangible beneficial effects at early, preclinical stages of the disease.”

Moving forward

Dr. Cuello sees two avenues to build further on these most recent findings. The first involves investigating combination therapies using this lithium formulation in concert with other interesting drug candidates. To that end he is pursuing opportunities working with Dr. Sonia Do Carmo, the Charles E. Frosst-Merck Research Associate in his lab.

He also believes that there is an excellent opportunity to launch initial clinical trials of this formulation with populations with detectable preclinical Alzheimer’s pathology or with populations genetically predisposed to Alzheimer’s, such as adult individuals with Down Syndrome. While many pharmaceutical companies have moved away from these types of trials, Dr. Cuello is hopeful of finding industrial or financial partners to make this happen, and, ultimately, provide a glimmer of hope for an effective treatment for those suffering from Alzheimer’s disease.

NEWS RELEASE 21-JAN-2020

Vitamin D supplementation linked to potential improvements in blood pressure in children

UNIVERSITY OF PITTSBURGH

PITTSBURGH, Jan. 21, 2020 – Overweight and obese vitamin D-deficient children who took a relatively high dose of vitamin D every day for six months had lower blood pressure and improved insulin sensitivity than their peers who took a lower dose, according to the results of a UPMC Children’s Hospital of Pittsburgh clinical trial reported in The American Journal of Clinical Nutrition.

However, the study did not show improvements in other markers of cardiovascular and metabolic health, a finding that indicates vitamin D supplementation alone may not be the cure-all for improving the heart health of children at highest risk for diabetes and heart disease.

“Current recommendations for taking vitamin D are pegged to optimal bone health,” said lead author Kumaravel Rajakumar, M.D., M.S., professor of pediatrics at the University of Pittsburgh School of Medicine. “But we know vitamin D is involved in more than building healthy bones. It can turn on and off genes that direct our cells to regulate blood glucose levels, and immune and vascular function.”

Rajakumar and his colleagues enrolled 225 healthy, but vitamin D-deficient, 10- to 18-year-old children in Pittsburgh who were overweight or obese in the clinical trial, and 211 of them were black. People with darker skin have higher amounts of melanin pigment in their skin and are more likely than their lighter-skinned counterparts to be vitamin D deficient. This is because vitamin D is made in the body when the skin is directly exposed to sunlight, and melanin in the skin acts as a natural sunscreen and inhibits vitamin D production. Overweight and obese children also have a higher risk of vitamin D deficiency, as well as developing diabetes and heart disease.

The children were split into three groups and given pills that appeared identical, but contained different quantities of vitamin D, which is measured in international units, or IUs. One group received a 600 IU tablet daily, which is the current recommended daily dietary allowance. The other two groups received either a 1,000 IU or 2,000 IU tablet daily, still well below the 4,000 IU daily maximum considered safe for children in this age range. During the trial, neither the participants, nor their doctors, knew which dose each child was receiving.

Blood tests showed that the higher the daily dose of vitamin D, the greater the improvement in the participants’ blood concentration of vitamin D. By the conclusion of the trial, none of the groups was considered vitamin D deficient.

After six months, the children receiving the daily 2,000 IU vitamin D supplement had a reduced fasting blood glucose level and improved insulin sensitivity — both of which reduce susceptibility to diabetes and improve cardiovascular health. After six months, the children receiving 1,000 IUs of vitamin D daily had lower blood pressure. High blood pressure is bad because it increases risk of heart attack, stroke and kidney disease.

The study did not reveal any significant changes in measures of the health of the membrane that lines the blood vessels or arterial stiffness — both of which are strong indicators of heart health and were the primary measures that the researchers were seeking to influence with vitamin D supplementation.

“There are many reasons we might not have seen changes in endothelial function or arterial stiffness,” said Rajakumar, who also is a pediatrician at UPMC Children’s Hospital. “Maybe vitamin D simply doesn’t influence these, or perhaps we didn’t reach and maintain a level of vitamin D to cause an effect. It could also be that our trial didn’t run long enough. However, treatment of vitamin D deficiency with these higher daily doses can have a positive impact on cardiometabolic health of children, without negative side effects.”

NEWS RELEASE 31-JAN-2020

The scent of a rose improves learning during sleep

UNIVERSITY OF FREIBURG

Effortless learning during sleep is the dream of many people. The supportive effect of smells on learning success when presented both during learning and sleep was first proven in an extensive sleep laboratory study. Researchers at the University of Freiburg – Medical Center, the Freiburg Institute for Frontier Areas of Psychology and Mental Health (IGPP) and the Faculty of Biology at the University of Freiburg have now shown that this effect can be also achieved very easily outside the lab. For the study, pupils in two school classes learned English vocabulary – with and without scent sticks during the learning period and also at night. The students remembered the vocabulary much better with a scent. The study was published in the Nature Group’s Open Access journal Scientific Reports on 27 January 2020.

“We showed that the supportive effect of fragrances works very reliably in everyday life and can be used in a targeted way,” said study leader PD Dr. Jürgen Kornmeier, head of the Perception and Cognition Research Group at the Freiburg-based IGPP and scientist at the Department of Psychiatry and Psychotherapy at the University of Freiburg – Medical Center in Germany.

The smell of roses when learning and sleeping

For the study, first author and student teacher Franziska Neumann conducted several experiments with 54 students from two 6th grade classes of a school in southern Germany. The young participants from the test group were asked to place rose-scented incense sticks on their desks at home while learning English vocabulary and on the bedside table next to the bed at night. In another experiment, they also placed the incense sticks on the table next to them during a vocabulary test at school during an English test. The results were compared with test results in which no incense sticks were used during one or more phases.

“The students showed a significant increase in learning success by about 30 percent if the incense sticks were used during both the learning and sleeping phases,” says Neumann. The results also suggest that the additional use of the incense sticks during the vocabulary test promotes memory.

Findings are suitable for everyday use

“One particular finding beyond the seminal initial study was, that the fragrance also works when it is present all night,” says Kornmeier. “This makes the findings suitable for everyday use.” Previous studies had assumed that the fragrance needs to be only present during a particularly sensitive sleeping phase. However, since this sleep phase needs to be determined by an effortful measurement of brain activity by means of an electroencephalogram (EEG) in the sleep laboratory, this finding was not suitable for everyday use. “Our study shows that we can make learning during sleep easier. And who would have thought that our nose could help considerably in this,” says Kornmeier.

NEWS RELEASE 29-JAN-2020

Study: Antioxidant flavonol linked to lower risk of Alzheimer’s dementia

Fruits, vegetables, tea may be helpful

AMERICAN ACADEMY OF NEUROLOGY

MINNEAPOLIS – People who eat or drink more foods with the antioxidant flavonol, which is found in nearly all fruits and vegetables as well as tea, may be less likely to develop Alzheimer’s dementia years later, according to a study published in the January 29, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“More research is needed to confirm these results, but these are promising findings,” said study author Thomas M. Holland, MD, of Rush University in Chicago. “Eating more fruits and vegetables and drinking more tea could be a fairly inexpensive and easy way for people to help stave off Alzheimer’s dementia. With the elderly population increasing worldwide, any decrease in the number of people with this devastating disease, or even delaying it for a few years, could have an enormous benefit on public health.”

Flavonols are a type of flavonoid, a group of phytochemicals found in plant pigments known for its beneficial effects on health.

The study involved 921 people with an average age of 81 who did not have Alzheimer’s dementia. The people filled out a questionnaire each year on how often they ate certain foods. They were also asked about other factors, such as their level of education, how much time they spent doing physical activities and how much time they spent doing mentally engaging activities such as reading and playing games.

The people were tested yearly to see if they had developed Alzheimer’s dementia. They were followed for an average of six years. The researchers used various tests to determine that 220 people developed Alzheimer’s dementia during the study.

The people were divided into five groups based on how much flavonol they had in their diet. The average amount of flavonol intake in US adults is about 16 to 20 milligrams per day. In the study, the lowest group had intake of about 5.3 mg per day and the highest group consumed an average of 15.3 mg per day.

The study found that people in the highest group were 48 percent less likely to later develop Alzheimer’s dementia than the people in the lowest group after adjusting for genetic predisposition and demographic and lifestyle factors. Of the 186 people in the highest group, 28 people, or 15 percent, developed Alzheimer’s dementia, compared to 54 people, or 30 percent, of the 182 people in the lowest group.

The results were the same after researchers adjusted for other factors that could affect the risk of Alzheimer’s dementia, such as, diabetes, previous heart attack, stroke and high blood pressure.

The study also broke the flavonols down into four types: isorhamnetin, kaempferol, myricetin and quercetin. The top food contributors for each category were: pears, olive oil, wine and tomato sauce for isorhamnetin; kale, beans, tea, spinach and broccoli for kaempferol; tea, wine, kale, oranges and tomatoes for myricetin; and tomatoes, kale, apples and tea for quercetin.

People who had high intake of isorhamnetin were 38 percent less likely to develop Alzheimer’s. Those with high intake of kaempferol were 51 percent less likely to develop dementia. And those with high intake of myricetin were also 38 percent less likely to develop dementia. Quercetin was not tied to a lower risk of Alzheimer’s dementia.

Holland noted that the study shows an association between dietary flavonols and Alzheimer’s risk but does not prove that flavonols directly cause a reduction in disease risk.

Other limitations of the study are that the food frequency questionnaire, although valid, was self-reported, so people may not accurately remember what they eat, and the majority of participants were white people, so the results may not reflect the general population.

NEWS RELEASE 6-FEB-2020

Natural compound in vegetables helps fight fatty liver disease

New research shows how indole can reduce inflammation, fatty deposits

TEXAS A&M AGRILIFE COMMUNICATIONS

A new study led by Texas A&M AgriLife Research scientists shows how a natural compound found in many well-known and widely consumed vegetables can also be used to fight fatty liver disease.

The study demonstrates how non-alcoholic fatty liver disease, or NAFLD, can be controlled by indole, a natural compound found in gut bacteria – and in cruciferous vegetables such as cabbage, kale, cauliflower and Brussels sprouts. It also addresses how this natural compound may lead to new treatments or preventive measures for NAFLD.

The study was recently published in Hepatology and can be found on PubMed.gov.

“Based on this research, we believe healthy foods with high capacity for indole production are essential for preventing NAFLD and are beneficial for improving the health of those with it,” said Chaodong Wu, M.D., Ph.D., a Texas A&M AgriLife Research Faculty Fellow and principal investigator for the study. “This is another example where altering the diet can help prevent or treat disease and improve the well-being of the individual.”

About NAFLD and indole

NAFLD occurs when the liver becomes “marbled” with fat, sometimes due to unhealthy nutrition, such as excessive intake of saturated fats. If not properly addressed, this condition can lead to life-threatening liver disease, including cirrhosis or liver cancer.

Many diverse factors contribute to NAFLD. Fatty liver is seven to 10 times more common in people with obesity than in the general population. In addition, obesity causes inflammation in the body. Driving this inflammation are macrophages, types of white blood cells that normally battle infection. This inflammation exacerbates liver damage in those with liver disease.

Gut bacteria can also have an effect – either positive or negative — on the progression of fatty liver disease. These bacteria produce many different compounds, one of which is indole. This product of the amino acid tryptophan has been identified by clinical nutritionists and nutrition scientists as likely having preventive and therapeutic benefits to people with NAFLD.

The National Cancer Institute also notes the benefits of indole-3-carbinol found in cruciferous vegetables, including their anti-inflammatory and cancer-fighting properties.

A comprehensive and multi-level study on fatty liver disease

The present study examined the effect of indole concentrations on people, animal models and individual cells to help determine indole’s effect on liver inflammation and its potential benefits to people with NAFLD. It investigated the extent to which indole alleviates non-alcoholic fatty liver disease, incorporating previous findings on gut bacteria, intestinal inflammation and liver inflammation. It also incorporated investigation into how indole improves fatty liver in animal models.

For the study, researchers investigated the effects of indole on individuals with fatty livers. As research collaborator Qifu Li, M.D., was also a physician at Chongqing Medical University in China, the team decided he should lead the clinical research using Chinese participants.

In 137 subjects, the research team discovered people with a higher body mass index tended to have lower levels of indole in their blood. Additionally, the indole levels in those who were clinically obese were significantly lower than those who were considered lean. And in those with lower indole levels, there was also a higher amount of fat deposition in the liver.

This result will likely extend to other ethnicities, Li noted, though ethnic background may have some influence on gut bacteria populations and the exact levels of metabolites.

To further determine the impact of indole, the research team used animal models fed a low-fat diet as a control and high-fat diet to simulate the effects of NAFLD.

“The comparisons of animal models fed a low-fat diet and high-fat diet gave us a better understanding of how indole is relevant to NAFLD,” said Gianfranco Alpini, M.D., a study collaborator and former distinguished professor of Texas A&M Health Science Center, now the director of the Indiana Center for Liver Research.

Alpini said treatment of NAFLD-mimicking animal models with indole significantly decreased fat accumulation and inflammation in the liver.

The research team also studied how indole affected individual cells.

Shannon Glaser, M.D., a professor of Texas A&M Health Science Center, said that in addition to reducing the amount of fat in liver cells, indole also acts on cells in the intestine, which send out molecular signals that dampen inflammation.

“The link between the gut and the liver adds another layer of complexity to studies on non-alcoholic fatty liver disease, and future studies are very much needed to fully understand the role of indole,” Glaser said.

Additional nutrition research needed

“Foods with a high capacity of indole production or medicines that mimic its effects may be new therapies for treatment of NAFLD,” Wu said, adding prevention is another important aspect to consider.

“Preventing NAFLD’s development and progression may depend on nutritional approaches to ensure that gut microbes allow indole and other metabolites to function effectively,” he said. “Future research is needed to investigate how certain diets may be able to achieve this.”

Wu said in future research he hopes to collaborate with food scientists and clinical nutritionists to examine what healthy foods can alter gut microbiota and increase indole production.

NEWS RELEASE 6-FEB-2020

Antioxidant reverses BPD-induced fertility damage in worms

HARVARD MEDICAL SCHOOL

From plastics to pesticides, it seems like every week delivers fresh news about the dangers of endocrine disruptors–chemicals in the environment that alter the body’s hormones and can lead to reproductive, developmental, neurologic and immune problems and cancer.

Industry regulation and individual consumer choice can reduce exposure to such chemicals, but there are few options to counteract damage that has already occurred.

Now new research conducted in worms suggests a path toward changing that.

A naturally occurring antioxidant known as Coenzyme Q10, or CoQ10, reversed most of the reproductive harms caused by exposure to the plasticizer BPA (bisphenol A) in Caenorhabditis elegans worms, according to a study led by the lab of Monica Colaiácovo, professor of genetics in the Blavatnik Institute at Harvard Medical School.

The findings, published Feb. 6 in Genetics, provide the first evidence that at least some BPA-induced fertility damage can be undone.

“Chemicals are so prevalent in our environment that it was critical for us to focus first on identifying which ones are toxic and how they may affect human reproductive health,” said Colaiácovo, senior author of the study.

“Now, as we continue to screen for and study how chemicals affect reproductive health, we can also ask the next really important question: Given that we’re all exposed, how can we mitigate those effects in order to improve fertility and have healthier births?”

CoQ10 is produced by the body and can be found in many foods, particularly meat and fish. It is also available in over-the-counter dietary supplements, but those are neither regulated nor FDA-approved for any health conditions, and they occasionally cause side effects.

Although CoQ10 is already being recommended in some fertility clinics in the U.S. and Canada, the research team cautions that their findings must be replicated in further animal studies and in human clinical trials before the enzyme is prescribed for BPA-induced fertility damage.

Colaiácovo’s lab has documented the reproductive repercussions of many environmental chemicals in worms, including BPA.

When work from her lab and others suggested that BPA hampers reproductive health in part by causing oxidative damage, “it made sense to look at antioxidants” for help, she said.

The team started with CoQ10 because it’s readily available in stores, inexpensive and relatively safe, so if it proved effective in animal models, it would be well positioned for testing in people, said Colaiácovo.

The Kaneka Corporation, an international chemical manufacturer, provided the compound for the study. It did not contribute funding. None of the study authors stand to benefit financially from increased sales of CoQ10, Colaiácovo confirmed.

The researchers exposed groups of C. elegans worms to BPA, CoQ10 and a solvent called DMSO, alone and in various combinations. The timing of BPA and CoQ10 exposures were designed to approximate those in humans, and BPA levels detected inside the worms were proportional to the amounts found in the general human population.

The researchers found that CoQ10 improved or reversed multiple types of damage caused by BPA. Worms treated with the antioxidant had lower rates of egg cell death, fewer double-strand DNA breaks and fewer chromosome abnormalities during egg cell division, and lower levels of oxidative stress in egg cells. Early embryos also had fewer instances of abnormal chromosome numbers and other defects.

In humans, these types of abnormalities can lead to infertility, miscarriage and birth defects.

“CoQ10 rescued a lot of the defects we’d reported before,” said Colaiácovo. “It’s exciting to consider that we could be looking at a simple, low-cost intervention.”

  1. eleganshas proved a useful model organism for studying countless aspects of basic biology. Many of the reproductive abnormalities caused by exposure to environmental toxins observed in worms are also seen in mammals from mice to primates, said Colaiácovo, boosting hope that the CoQ10 findings will similarly translate.

Nevertheless, humans are not big worms, and people should not rush out and start taking CoQ10 as an anti-BPA agent without consulting a doctor, the study authors said.

For one thing, the researchers used “very pure,” quality controlled CoQ10, while store-bought supplements vary in CoQ10 content and do not always contain the amounts stated on labels, previous analyses have found.

“Our study underscores the need for tighter regulation and dedicated research on the biological effects of supplements,” said Colaiácovo.

For Colaiácovo, the findings offer a glimmer of hope amid a flood of concerning findings.

“When we uncover evidence of toxicity from yet another chemical, often there is a feeling of ‘Here we go again,'” she said. “But it’s important to see what we can learn from it. I want us to figure out solutions.”

NEWS RELEASE 11-FEB-2020

Prebiotics help mice fight melanoma by activating anti-tumor immunity

SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

LA JOLLA, CALIF. – Feb. 11, 2020 – Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that two prebiotics, mucin and inulin, slowed the growth of melanoma in mice by boosting the immune system’s ability to fight cancer. In contrast to probiotics, which are live bacterial strains, prebiotics are “food” for bacteria and stimulate the growth of diverse beneficial populations. The study, published today in Cell Reports, provides further evidence that gut microbes have a role in shaping the immune response to cancer, and supports efforts to target the gut microbiome to enhance the efficacy of cancer therapy.

The research specifically opens new avenues to address important unmet clinical needs in melanoma, as it highlights the possible impact of prebiotics on tumor growth control and therapy resistance.

“Earlier studies have demonstrated that prebiotics limit tumor growth, but until now the mechanism by which they do so has been unclear,” says Ze’ev Ronai, Ph.D., professor in Sanford Burnham Prebys’ Tumor Initiation and Maintenance Program and senior author of the study. “Our study shows for the first time that prebiotics limit cancer growth by enhancing anti-tumor immunity. The study supports further exploration of the potential benefits of prebiotics in treating cancer or augmenting current therapies.”

Ronai cautions that these findings require much more study before considering any evaluation in people with cancer.

“Prebiotics represent a powerful tool to restructure gut microbiomes and identify bacteria that contribute to anti-cancer immunity,” says Scott Peterson, Ph.D., professor in Sanford Burnham Prebys’ Tumor Microenvironment and Cancer Immunology Program and co-corresponding author of the study. “The scientific advances we are making here are getting us closer to the idea of implementing prebiotics in cutting-edge cancer treatments.”

Adds Jennifer Wargo, M.D., associate professor of Surgical Oncology and Genomic Medicine at the University of Texas MD Anderson Cancer Center, “Immunotherapies and targeted treatments such as MEK inhibitors are helping people with melanoma, but not everyone. While some patients respond to therapy, others do not. In addition, many patients develop resistance to treatment which requires alternate medicine combinations. Manipulating the microbiome with prebiotics might be a helpful addition to current treatment regimens, and today’s finding should be further tested in independent models and systems.”

In the study, the scientists set out to identify specific prebiotics that promote the growth of good bacteria and activate anti-tumor immunity. Based on previous studies conducted in a lab dish, they homed in on mucin, a protein that is part of the mucus found in our intestine and other tissues; and inulin, a fiber found in plants such as asparagus and onions.

The researchers then embarked on a series of studies that involved feeding healthy mice either mucin or inulin in their water and food, respectively, and then transplanting melanoma or colon cancer cells to determine the effect of the prebiotics. Their experiments showed that:

  • Growth of melanoma was slowed in the mice that received either mucin or inulin, while growth of a colon cancer cell line was slowed only in mice that received inulin.
  • Mice with melanoma that received either prebiotic showed an increase in the proportion of immune system cells that had infiltrated the tumor–indicating that the prebiotics enhanced the immune system’s ability to attack the cancer.
  • The microbiota communities of the mice that received the prebiotics were altered. Importantly, mucin and inulin created different, distinct bacterial populations, although in both cases they were able to induce anti-tumor immunity–indicating that the distinct mode of action by these prebiotics is beneficial for stimulating anti-tumor immunity.
  • NRAS-mutant melanoma is treated with an MEK inhibitor drug, which often results in tumors that develop resistance to this drug. Mice carrying NRAS-mutant melanoma that received inulin were able to delay the development of resistance to treatment with an MEK inhibitor.
  • Mice with a “cold” BRAF-mutant melanoma tumor, meaning it partially responds to immune checkpoint therapy, were as responsive to the prebiotics as immune checkpoint therapy.

“Our findings are a step forward in our understanding of how certain prebiotics affect tumor growth, but we are far from applying these to humans,” says Ronai. “Future studies need to be conducted in more complex animal models of different genetic backgrounds and ages to address the complex nature of human tumors before we may consider evaluating these prebiotics in people.”

NEWS RELEASE 14-FEB-2020

Vitamin E effective, safe for fatty liver in HIV patients

MCGILL UNIVERSITY

A type of fatty liver disease that commonly affects patients with HIV can be safely treated with vitamin E, a McGill-led study has found.

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) and is characterized by liver inflammation and cell damage. It is a potentially dangerous condition that can progress to cirrhosis or liver cancer.

“Vitamin E has been shown to improve fatty liver in the general population,” says the study’s lead author Dr. Giada Sebastiani, Associate Professor in the Department of Medicine, McGill University and scientist at the Research Institute of the McGill University Health Centre. “Here we provide evidence for its beneficial effect and safety in people living with HIV, who have a higher prevalence of fatty liver disease.”

The study appears in the February 1, 2020 issue of the journal AIDS.

Dr. Sebastiani notes that NAFLD currently affects up to 48% of Canadians living with HIV and 25% of the general population, while NASH affects about one third of patients with NAFLD. There are several theories to explain the high prevalence of fatty liver among HIV-positive patients, explains Dr. Sebastiani: “It is possibly due to HIV-related inflammation, the antiretroviral drugs that they have to take lifelong, and to very frequent metabolic problems, such as diabetes and high lipids. Unfortunately, there is no approved therapy for fatty liver in people living with HIV.”

In the study, 27 patients with HIV and NASH were given vitamin E in an easily-tolerated dose of two pills per day. “We found that vitamin E improved both liver transaminases (the main blood tests for liver function) and liver fat measured by a non-invasive ultrasonographic test,” says Dr. Sebastiani. “These improvements were even more marked than those reported in the HIV-uninfected population.” Although she suspected vitamin E would reduce inflammation and fat in the HIV-positive group, Dr. Sebastiani was pleasantly surprised by the size of the effect.

Dr. Sebastiani notes that because the study did not have the benefit of a control group, and the study group was small and had a short follow-up (24 weeks), it’s considered a pilot project. “We would be interested in conducting a larger randomized controlled trial, with a longer follow-up,” she says.

Dr. Sebastiani came to McGill seven years ago from Italy with the goal of establishing a world-class research program focused on fatty liver and non-invasive diagnostic tools for liver disease. In the intervening years, cases of fatty liver disease, which was previously associated only with alcohol abuse, have exploded, particularly among obese Canadians. Dr. Sebastiani predicts that NAFLD will become the leading cause of liver transplants in the next 10 years.

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“Vitamin E is an effective treatment for non-alcoholic steatohepatitis in HIV mono-infected patients,” by G. Sebastiani, P. Ghali, M. Klein, et al, was published February 1, 2020 in the journal AIDS. doi: 10.1097/QAD.0000000000002412

NEWS RELEASE 14-FEB-2020

Green tea extract combined with exercise reduces fatty liver disease in mice

Although untested in human trials, results suggest a potential health strategy

PENN STATE

The combination of green tea extract and exercise reduced the severity of obesity-related fatty liver disease by 75% in mice fed a high-fat diet, according to Penn State researchers, whose recent study may point to a potential health strategy for people.

The outcome is important, explained Joshua Lambert, associate professor of food science, because nonalcoholic fatty liver disease is a significant global health problem that is expected to worsen. Because of the high prevalence of risk factors such as obesity and type 2 diabetes, fatty liver disease is forecast to afflict more than 100 million people by 2030. And there are currently no validated therapies for the disease.

In the study, mice fed a high-fat diet for 16 weeks that consumed green tea extract and exercised regularly by running on a wheel were found to have just a quarter of the lipid deposits in their livers compared to those seen in the livers of a control group of mice. Mice that were treated with green tea extract alone or exercise alone had roughly half as much fat in their livers as the control group.

In addition to analyzing the liver tissues of mice in the study, which was published recently in the Journal of Nutritional Biochemistry, researchers also measured the protein and fat content in their feces. They found that the mice that consumed green tea extract and exercised had higher fecal lipid and protein levels.

“By examining the livers of these mice after the study concluded and by screening their feces during the research, we saw that the mice that consumed green tea extract and exercised actually were processing nutrients differently — their bodies were handling food differently,” Lambert said.

“We think the polyphenols in green tea interact with digestive enzymes secreted in the small intestine and partially inhibit the breakdown of carbohydrates, fat and protein in food,” he added. “So, if a mouse doesn’t digest the fat in its diet, that fat and the calories associated with it pass through the mouse’s digestive system, and a certain amount of it ends up coming out in its feces.”

It may be significant, Lambert explained, that mice treated with both green tea extract and exercise had higher expression of genes related to the formation of new mitochondria. That gene expression is important, he said, because it provides markers that will help researchers understand the mechanism by which green tea polyphenols and exercise might work together to mitigate fatty liver deposits.

“We measured the expression of genes that we know are related to energy metabolism and play an important role in energy utilization,” Lambert said. “In the mice that had the combination treatment, we saw an increase in the expression of genes that wasn’t there before they consumed green tea extract and exercised.”

More research is needed to see if there is a synergy created by green tea extract and exercise working together to reduce fat deposited in the liver, or if the effects are simply additive, Lambert pointed out. His research group in the College of Agricultural Sciences for 12 years has studied the health benefits of polyphenols — often called antioxidants — from green tea, cocoa, avocados and other sources.

In previous related research, Lambert and colleagues demonstrated that green tea extract and exercise together sharply reduced body mass and improved cardiovascular health of high-fat-fed mice. But because no human trials assessing the health benefits and risks of green tea combined with exercise have been conducted, he urges caution for people who decide to experiment with the health strategy on their own.

“I believe people should engage in more physical activity, and replacing high-calorie beverages with decaffeinated, diet green tea — which has no calories — is a smart move,” he said. “Combining the two might have health benefits for people, but we don’t have the clinical data yet.”

NEWS RELEASE 14-FEB-2020

Vitamin C may shorten ventilation in critically ill patients

UNIVERSITY OF HELSINKI

Vitamin C administration shortened the duration of mechanical ventilation in critical care patients, but the effect depended on the severity of illness.

In five controlled trials including 471 patients requiring ventilation for over 10 hours, vitamin C shortened ventilation time on average by 25% according to a meta-analysis published in Journal of Intensive Care.

Vitamin C has numerous biochemical effects. It can influence the cardiovascular system through its involvement in the synthesis of norepinephrine and vasopressin, and energy metabolism through its participation in the synthesis of carnitine. In randomized trials, vitamin C has lowered blood pressure, decreased the incidence of atrial fibrillation and decreased bronchoconstriction. A previous meta-analysis of 12 controlled trials found that vitamin C reduced ICU stay on average by 8%.

Critical care patients often have very low vitamin C plasma levels. In healthy people, 0.1 grams per day of vitamin C is usually sufficient to maintain a normal plasma level. However, much higher doses, in the order of grams per day, are needed for critically ill patients to increase their plasma vitamin C levels to within the normal range. Therefore, high vitamin C doses may be needed to compensate for the increased metabolism in critically ill patients.

Harri Hemilä from the University of Helsinki, Finland, and Elizabeth Chalker from the University of Sydney, Australia, carried out a systematic review of vitamin C for mechanically ventilated critical care patients. They identified 9 relevant controlled trials, and 8 of them were included in the meta-analysis.

On average, vitamin C administration shortened ventilation time by 14%, but the effect of vitamin C depended on the duration of ventilation. Patients who are more seriously ill require longer ventilation than those who are not as sick. Therefore, Hemilä and Chalker hypothesized that the effect of vitamin C might be greater in trials with sicker patients who need longer ventilation.

Vitamin C had no effect when ventilation lasted for 10 hours or less. However, in 5 trials including 471 patients who required ventilation for over 10 hours, dosage of 1 to 6 g/day of vitamin C shortened ventilation time on average by 25%.

“Vitamin C is a safe, low-cost essential nutrient. Given the strong evidence of benefit for more severely ill critical care patients along with the evidence of very low vitamin C levels in such patients, ICU patients may benefit from the administration of vitamin C. Further studies are needed to determine optimal protocols for its administration. Future trials should directly compare different dosage levels,” says Dr. Hemilä.

NEWS RELEASE 14-FEB-2020

Cocoa could bring sweet relief to walking pain for people with peripheral artery disease

Circulation Research journal report

AMERICAN HEART ASSOCIATION

DALLAS, February 14, 2020 — Consumption of cocoa may improve walking performance for patients with peripheral artery disease, according to the results of a small, preliminary, phase II research trial published today in the American Heart Association’s journal Circulation Research.

In a small study of 44 peripheral artery disease patients over age 60, those who drank a beverage containing flavanol-rich cocoa three times a day for six months were able to walk up to 42.6 meters further in a 6-minute walking test, compared to those who drank the same number and type of beverages without cocoa. Those who drank the flavanol-rich cocoa also had improved blood flow to their calves and some improved muscle function compared to the placebo group.

Peripheral artery disease or PAD, a narrowing of the arteries that reduces blood flow from the heart to the legs, affects over 8.5 million people 40 years of age and older nationwide. The most common symptoms are pain, tightness, cramping, weakness or other discomfort in leg muscles in while walking.

“Few therapies are available for improving walking performance in people with PAD,” said lead study author Mary McDermott, M.D., the Jeremiah Stamler professor of medicine and preventive medicine at the Feinberg School of Medicine at Northwestern University in Chicago. “In addition to reduced blood flow to the legs, people with peripheral artery disease have been shown to have damaged mitochondria in their calf muscles, perhaps caused by the reduced blood flow. Mitochondria are known as the powerhouse of the cell, converting food to energy. Previous research has shown that better mitochondrial health and activity are associated with better walking performance and improving the health of damaged mitochondria could lead to walking improvements.”

Researchers hypothesized that epicatechin, a major flavanol component of cocoa, may increase mitochondrial activity and muscle health in the calves of patients with lower extremity peripheral artery disease, potentially improving patient walking ability. Epicatechins and flavanols also have the potential to improve blood flow.

Study participants were randomly assigned to drink milk or water mixed with the contents of a powder packet containing flavanol-rich cocoa (15 grams of cocoa and 75 mgs of epicatechin daily) or a placebo powder packet without cocoa or epicatechin three times daily over six months. Walking performance was measured at the beginning of the study and at six months, with a 6-minute walking measured test twice – 2.5 hours after drinking the beverage and at 24 hours after drinking the beverage. Participants were also given a treadmill walking test and had the blood flow to their legs measured using magnetic resonance imaging (MRI). Participants who consented had a calf muscle biopsy to evaluate muscle health.

The cocoa used in the study is commonly available natural unsweetened cocoa powder., which is rich in the flavanol epicatechin, found in larger quantities in dark chocolate (>85% cacao) than in milk chocolate. Regular chocolate would not be expected to have the same effect.

Researchers found that the patients who consumed cocoa showed significant improvement – walking an average of almost 43 meters further in the 6-minute walking test compared to their baseline results during the test performed at 2.5 hours after the final study beverage. Researchers also found increased mitochondrial activity, increased capillary density, and other improvements to muscle health in those who consumed the cocoa. Patients who drank the placebo beverage had a decline of 24.2 meters in their walking distance at 2.5 hours after the final study beverage compared to their baseline results. This is consistent with other studies, in which people with PAD without treatment have declines in their six-minute walk distance over time.

Cocoa appeared to have no effect on treadmill walking performance. However, McDermott said the treadmill walking and the 6-mile walking test are distinct measures of walking endurance and do not respond identically to the same therapy. The improvement in 6-minute distance walking better reflects the type of walking required in daily life, and therefore, these results are a more relevant outcome for patients with PAD.

“While we expected the improvements in walking, we were particularly pleased to see that cocoa treatment was also associated with increased capillary density, limb perfusion, mitochondrial activity, and an additional measure of overall skeletal muscle health,” McDermott said. “If our results are confirmed in a larger trial, these findings suggest that cocoa, a relatively inexpensive, safe and accessible product, could potentially produce significant improvements in calf muscle health, blood flow, and walking performance for PAD patients.”

Limits to this pilot study include: a small sample size; an imbalance between the two study groups in the number of participants of each sex, race and in body mass index; and a lack of data for overall dietary consumption.

“Patients with PAD have difficulty walking that is as bad as people with advanced heart failure. Leg muscles don’t get enough blood supply in PAD leading to injury and in this study, cocoa appeared to be protecting the muscle and improving metabolism,” said Naomi Hamburg, M.D., FAHA, Chair of the American Heart Association’s Peripheral Vascular Disease Council and author of an editorial on the study that also appears in this issue. “We know that exercise therapy helps people with PAD walk farther, and this early study suggests that cocoa may turn out to be a new way to treat people with PAD. We will need larger studies to confirm whether cocoa is an effective treatment for PAD, but maybe, someday, if the research supports it, we may be able to write a prescription for chocolate for our patients with PAD.”

The study was funded by the National Institute on Aging, the intramural office of the National Institute on Aging and the Office of Dietary Supplements of the National Institutes of Health. The cocoa beverage and matching placebo were provided by The Hershey Company. In addition, Mars Incorporated performed measures of epicatechin metabolites, valerolactones and theobromine in blood taken from participants in the study.

NEWS RELEASE 12-FEB-2020

EPA fails to follow landmark law to protect children from pesticides in food

ENVIRONMENTAL WORKING GROUP

WASHINGTON – The landmark Food Quality Protection Act requires the Environmental Protection Agency to protect children’s health by applying an extra margin of safety to legal limits for pesticides in food. But an investigation by EWG, published this week in a peer-reviewed scientific journal, found that the EPA has failed to add the mandated children’s health safety factor to the allowable limits for almost 90 percent of the most common pesticides.

The study in Environmental Health examined the EPA’s risk assessments for 47 non-organophosphate pesticides since 2011, including those most commonly found on fresh fruits and vegetables, and found that the required additional tenfold safety factor was applied in only five cases.

“Given the potential health hazards of pesticides in our food, it is disturbing that the EPA has largely ignored the law’s requirement to ensure adequate protection for children,” said the study’s author, Olga Naidenko, Ph.D., vice president for science investigations at EWG. “The added safety factor is essential to protect children from pesticides that can cause harm to the nervous system, hormonal disruption and cancer.”

The Food Quality Protection Act of 1996, or FQPA, requires the EPA to set allowable levels for pesticides in a way that would “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue.” It was hailed as a revolutionary recognition of the fact that children are more vulnerable to the effects of chemical pesticides than adults.

“Based on the strong consensus of the pediatric and the public health communities, the FQPA stated unequivocally that regulation of toxic pesticides must focus, first and foremost, on protecting infants and children,” said Dr. Philip Landrigan, a pediatrician and epidemiologist who is director of the Program in Global Public Health and the Common Good at Boston College. “When the EPA fails to apply this principle, children may be exposed to levels of chemical pesticides that can profoundly harm their health.”

Landrigan chaired the committee that authored “Pesticides in the Diets of Infants and Children,” a 1993 report from the National Academy of Sciences. The groundbreaking study led to the FQPA’s passage with bipartisan support and the backing of both industry and environmentalists.

“The FQPA was a revolution in how we think about pesticides’ effects on children, but it does no good if the EPA doesn’t use it,” said EWG President Ken Cook. “It’s not only necessary to protect kids’ health, it’s the law, and the EPA’s failure to follow the law is an egregious betrayal of its responsibility.”

Naidenko’s study also examined EPA risk assessments for a particularly toxic class of pesticides called organophosphates, which act in the same way as nerve gases like sarin and are known to harm children’s brains and nervous systems. She found that under the Obama administration, the tenfold children’s health safety factor was proposed for all organophosphate insecticides.

By contrast, in four assessments of pyrethroid insecticides, the EPA under the Trump administration has proposed adding the FQPA safety factor to none. In human epidemiological studies conducted in the U.S. and in Denmark, exposure to pyrethroid insecticides was associated with increased risk of attention deficit hyperactivity disorder.

In 2017, the EPA reversed the Obama administration’s FQPA determination for chlorpyrifos, the most widely used organophosphate pesticide in the U.S. Despite the Trump EPA’s decision, in the wake of bans by Hawaii, California and New York, the main U.S. chlorpyrifos manufacturer recently announced it will stop making this chemical. It remains to be seen whether the Trump EPA will uphold the tenfold FQPA determination for the entire group of organophosphates.

The study also found that the Trump EPA has proposed to increase by 2.6-fold the allowable exposure to the herbicide metolachlor. The use of metolachlor has been on the rise for the past decade, with more than 60 million pounds sprayed annually, according to the U.S. Geological Survey.

Biomonitoring studies conducted by the Centers for Disease Control and Prevention and by independent researchers reported the presence of multiple pesticides and their byproducts in the American population, including herbicides such as glyphosate and 2,4-D, the bee-killing neonicotinoid insecticides, organophosphate and pyrethroid insecticides, and fungicide metabolites.

NEWS RELEASE 12-FEB-2020

Postmenopause vitamin D deficiency associated with disc degeneration and lower back pain

CLEVELAND, Ohio (February 12, 2020)–Lumbar disc degeneration and resulting lower back pain become greater concerns with age and disproportionately affect women more than men, likely as a result of decreasing estrogen levels during menopause. A new study demonstrates that vitamin D deficiency, smoking, high body mass index (BMI), and osteoporosis are risk factors for greater back pain. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Lumbar disc degeneration is a common musculoskeletal disease that often causes lower back pain. Previous studies have shown the effect of estrogen on disc degeneration, which partially explains why degeneration is more severe in postmenopausal women than in men of the same age. In addition to lower estrogen concentrations, vitamin D deficiency is common during the postmenopause period.

Vitamin D is critical in maintaining levels of calcium and phosphorus, helping to prevent bone diseases such as rickets and osteoporosis. Recent studies have shown that vitamin D deficiency is associated with lower back pain and that supplementation can relieve this pain and improve musculoskeletal strength. But few studies have been conducted regarding the role of vitamin D in spinal degeneration, especially in postmenopausal women.

This new study evaluated vitamin D status in postmenopausal women and its relationship with disc degeneration and lower back pain. It concluded that vitamin D deficiency is highly prevalent in postmenopausal women and that a serum concentration of vitamin D less than 10 ng/mL, indicating severe deficiency, should be considered an indicator of severe disc degeneration and lower back pain. It further identified additional risk factors such as smoking, high BMI, and osteoporosis for lower back pain beyond vitamin D deficiency.

Study results appear in the article “Does vitamin D status influence lumbar disc degeneration and low back pain in postmenopausal women? A retrospective, single-center study.”

“This study shows that very low vitamin D levels were linked to a greater likelihood of moderate to severe lower back pain and more severe lumbar disc degeneration, possibly because of the beneficial effects vitamin D has on nerve and muscle pain sensitivity, muscle strength and mass, and inflammation. Although not all women need vitamin D supplementation, this speaks to the importance of avoiding severe vitamin D deficiency states,” says Dr. Stephanie Faubion, NAMS medical director.

NEWS RELEASE 12-FEB-2020

Research reverses the reproductive clock in mice

UNIVERSITY OF QUEENSLAND

Researchers have lifted fertility rates in older female mice with small doses of a metabolic compound that reverses the ageing process in eggs, offering hope for some women struggling to conceive.

The University of Queensland study found a non-invasive treatment could maintain or restore the quality and number of eggs and alleviate the biggest barrier to pregnancy for older women.

A team led by UQ’s Professor Hayden Homer found the loss of egg quality through ageing was due to lower levels of a particular molecule in cells critical for generating energy.

“Quality eggs are essential for pregnancy success because they provide virtually all the building blocks required by an embryo,” Professor Homer said.

“We investigated whether the reproductive ageing process could be reversed by an oral dose of a ‘precursor’ compound – used by cells to create the molecule.”

The molecule in question is known as NAD (nicotinamide adenine dinucleotide) and the ‘precursor’ as NMN (nicotinamide mononucleotide).

Professor Homer said fertility in mice starts to decline from around one year of age due to defects in egg quality similar to changes observed in human eggs from older women.

“We treated the mice with low doses of NMN in their drinking water over four weeks, and we were able to dramatically restore egg quality and increase live births during a breeding trial,” Professor Homer said.

Professor Homer said poor egg quality had become the single biggest challenge facing human fertility in developed countries.

“This is an increasing issue as more women are embarking on pregnancy later in life, and one in four Australian women who undergo IVF treatment are aged 40 or older,” he said.

“IVF cannot improve egg quality, so the only alternative for older women at present is to use eggs donated by younger women.

“Our findings suggest there is an opportunity to restore egg quality and in turn female reproductive function using oral administration of NAD-boosting agents – which would be far less invasive than IVF. It is important to stress, however, that although promising, the potential benefits of these agents remains to be tested in clinical trials”.

NEWS RELEASE 18-FEB-2020

Low folate levels can indicate malnutrition in hospital patients

MEDICAL COLLEGE OF GEORGIA AT AUGUSTA UNIVERSITY

About 10% of patients who come to complex care hospitals may have low levels of folate and other indicators of malnutrition, investigators say.

To ensure those patients are identified and helped, those who present with gastrointestinal problems, chronic kidney disease or sepsis — all associated with malnutrition — need to have their folate levels tested on admission, they report in the journal Laboratory Medicine.

“We looked at people who had low levels and relatively normal folate levels,” says Dr. Gurmukh Singh, vice chair of pathology at the Medical College of Georgia at Augusta University. “The people with low levels had a higher incidence of gastrointestinal disorders like chronic diarrhea as well as sepsis and kidney disease. The other piece was that people who had low levels also had other markers of malnutrition.”

Singh and his colleagues were trying to come up with a recommendation for whose folate levels should be tested because of testing inconsistencies he was finding at AU Medical Center, the Augusta-based adult teaching hospital for MCG, including what happened when a low folate level was found.

The investigators compared 1,019 patients with a serum folate level of less than seven nanograms per milliliter, which they considered low, to a group of 300 patients with an intermediate level of at least 15 nanograms per milliliter. A nanogram is one billionth of a gram, and a milliliter is one thousandth of a liter.

Evidence of malnutrition they found in those with low folate levels included 25% with a lower serum albumin, the main protein of the liquid portion of blood that’s made by the liver; 55% with low levels of prealbumin, a short-lived protein made by the liver which decreases in supply when the liver isn’t getting adequate nutrition; and 11% with a deficiency in vitamin B12, which often works synergistically with folate, which is also a B vitamin. More than 62% of those with low serum folate were deficient in one or more of these malnutrition markers, the investigators say.

Their findings led them to suggest that patients with a folate level of less than seven nanograms per milliliter be evaluated for malnutrition. A state of overweight or obesity should not preclude malnutrition evaluation, they say.

The low folate group also had a significantly higher prevalence of gastrointestinal disorders, sepsis and abnormal serum creatinine. Creatinine is a breakdown product of muscle and protein that is typically eliminated by the kidneys, and high blood levels indicate kidney problems.

The investigators found no significant differences in the high and low folate groups in related factors like diabetes, drug and alcohol abuse or an existing diagnosis of malnutrition.

A complicating factor was that as many as 60% of the patients they reviewed had received a folic acid supplement before they were tested, which meant that low folate levels could be even more prevalent. That finding and other indicators of nutritional deficiency prompted the AU Health System to urge medical staff to do folic acid testing before any supplements or blood products were given, even before patients eat a hospital meal. The health system’s Medical Executive Board also approved automatic testing for prealbumin and B12 in those found to have a folate level of less than seven nanograms per milliliter.

The investigators note that B12 levels also need to be tested before a folate supplement is given. Folate and B12 have some overlap in function but both are needed, Singh says. “One cannot make up for the other and they often work together to make blood and keep the nervous system in working order,” he says.

Folate, or folic acid, is an essential nutrient, which means our bodies don’t make it, we have to consume it.

The availability of folate in so many foods means many of us likely don’t need testing or a supplement, he says. “The addition of folate to common foods like cereal has helped us compensate to some extent for even an unhealthy diet,” Singh says.

Since 1998, folic acid has been added to bread flour, cornmeal, pasta, rice, breakfast cereal and corn masa flour used to make corn tortillas and tamales, according to the National Institutes of Health Office of Dietary Supplements. Foods like eggs, legumes, asparagus, Brussels sprouts and citrus fruits are some of the healthiest foods that are naturally high in folic acid.

Low folate levels may indicate problems with absorption not just with diet, Singh says. Too little folate can result in the blood disorder megaloblastic anemia, which is characterized by weakness, trouble concentrating and even heart palpitations. Folate can help prevent birth defects like spina bifida and brain defects in developing babies.

Singh reported similar inconsistencies in testing and follow up action in a similar study in Georgia and Missouri published five years ago. He suggested then that serum folate levels be tested on admission as an indicator of nutritional status.

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