233 CNO Report 26 JUL 2016

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Release Date 26 JUL 2016

Draft Report Compiled by

Ralph Turchiano

www.clinicalnews.org

 

In this Issue:

1. Boosting the potency of a broccoli-related compound yields a possible treatment for mac D

2. Hops extract studied to prevent breast cancer

3. Study: Gut bacteria can cause, predict and prevent rheumatoid arthritis

4. Study shows a new role for B-complex vitamins in promoting stem cell proliferation

5. Thumb-sucking and nail-biting have a positive side

6. Milestone study on pomegranate anti-aging mechanism reported by Amazentis SA and EPFL

7. Viruses revealed to be a major driver of human evolution

8. How to increase the fat burned during exercise

9. Lower risk of bowel cancer death linked to high omega 3 intake after diagnosis

10. Virgin olive oil and hypertension

11. Infections, antibiotic use linked to manic episodes in people with serious mental illness

12. Cinnamon may be fragrant medicine for the brain

13. Saint Louis University research: Plant compounds give ‘1-2’ punch to colon cancer

14. Protein in breast milk reduces infection risk in premature infants

Public Release: 6-Jul-2016

Boosting the potency of a broccoli-related compound yields a possible treatment for mac D

Buck Institute study also shows that palmitoleic acid protects the retina from environmental damage in mouse models of disease

Buck Institute for Research on Aging

Buck researchers boosted the potency of a broccoli-related compound by ten times and identified it as a possible treatment for age-related macular degeneration (AMD), the leading cause of vision loss affecting more than 10 million older Americans. The research, published in Scientific Reports, also highlights the role of lipid metabolism in maintaining the health of the retina, reporting that palmitoleic acid also had protective effects on retinal cells in culture and in mice.

The “good-for-you” compound in broccoli which prompted the inquiry is indole-3-carbinol (I3C), which is currently being studied for cancer prevention. I3C helps clear cells of environmental toxins by activating the aryl hydrocarbon receptor (AhR) protein which upregulates pathways involved in chemical detoxification. AhR, which declines with age, is important for detoxifying the retina. Previous studies show that AhR-deficient mice develop a condition which looks extremely similar to AMD. When contemplating the possibility of boosting AhR via broccoli’s I3C, Buck faculty and lead author Arvind Ramanathan, PhD, knew there was a challenge – I3C is weak activator of AhR. So he used the chemical scaffold of I3C to do a ‘virtual’ screen of a publicly-available database of millions of compounds to find those that were related to I3C but would bind to AhR with more strength. His team came up with 2,2?-aminophenyl indole (2AI) which is ten times more potent than I3C.

“2AI protected human retinal cells in culture from stress,” said Ramanathan. “And it also protected retinal cells in mice from light-mediated damage. We are very excited about the potential for 2AI and look forward to developing it further.” Ramanathan is also excited about the possibility of finding more potent versions of other naturally occurring molecules that show health benefits for age-related diseases. “You would have to eat an unreasonable amount of broccoli and other cruciferous vegetables to get enough of a protective effect to impact AMD,” he said. “This method allows us to capitalize on nature’s wisdom to find related molecules that can deliver therapeutic benefit.”

“2AI prevented cell death in the retinas of mice that were exposed to light stress,” said Buck faculty and co-senior author Deepak Lamba, MBBS, PhD, who is developing stem-cell based therapies for degenerative eye diseases. “Our next step is to study the functional outcomes of treatment with 2AI, something I am eager to do because environmental stress is the major contributor to age-related vision loss.”

Ramanathan said data from the study suggests that at least some of the protective effects of the AhR activation may come via lipids. “We know that eating a diet rich in fish and omega fatty acids reduces the risk of AMD, even though we don’t fully understand the mechanisms involved.” Ramanathan said in this study, 2AI increased levels of the omega-7 lipid palmitoleic acid (PA) suggesting it could be a downstream signal in the anti-inflammatory pathway. Ramanathan said injecting PA also had protective effects on retinal cells in culture and in mice. PA is found in a variety of food including nuts, fish, dairy and vegetable oils. It is found at high concentrations in macadamia and sea buckthorn oil.

Hops extract studied to prevent breast cancer

University of Illinois at Chicago

An enriched hops extract activates a chemical pathway in cells that could help prevent breast cancer, according to new laboratory findings from the UIC/NIH Center for Botanical Dietary Supplements Research at the University of Illinois at Chicago.

Natural botanical dietary supplements such as hops have become increasingly popular among women for postmenopausal symptoms, as they are perceived as a safer alternative to hormone therapy, which has been linked to increased risk of breast cancer. However, the efficacy and potential toxicity of botanicals are still being studied.

Researchers led by Judy Bolton, professor and head of medicinal chemistry and pharmacognosy in the UIC College of Pharmacy, applied hops extract to two different breast cell lines to see if they would affect estrogen metabolism, a key mechanism in breast cancer. One compound, 6-prenylnarigenin, or 6-PN, increased a detoxification pathway in the cells that has been linked to a lower risk for breast cancer.

“We need to further explore this possibility, but our results suggest that 6-PN could have anti-cancer effects,” Bolton said.

In addition to 6-PN, Bolton and her colleagues studied 8-prenylnarigenin (8-PN), isoxanthohumol (IX) and xanthohumol (XH) for their effects on estrogen metabolism in breast cells. According to Bolton, 8-PN showed only a slight increase of metabolism in breast cells, while the other two compounds did not have significant effects in either cell line.

Breast cancer is one of the most commonly diagnosed cancers in women in the U.S.; about one in eight U.S. women will develop invasive breast cancer over their lifetime. An estimated 246,660 new cases of invasive breast cancer and 61,000 new cases of non-invasive breast cancer are expected in women in the U.S. this year, according to the American Cancer Society.

The incidence of breast cancer began decreasing in 2000, after increasing during the previous two decades. Just from 2002 to 2003, the incidence declined by 7 percent. Some think the drop was partly due to reduced use of hormone replacement therapy, or HRT, after results of the Women’s Health Initiative suggested a link between HRT and increased breast cancer risk. Estrogen exposure has long been linked with postmenopausal breast cancer risk, especially since the 2002 report, Bolton said.

Public Release: 11-Jul-2016

Study: Gut bacteria can cause, predict and prevent rheumatoid arthritis

Mayo Clinic

ROCHESTER, Minn. — The bacteria in your gut do more than break down your food. They also can predict susceptibility to rheumatoid arthritis, suggests Veena Taneja, Ph.D., an immunologist at Mayo Clinic’s Center for Individualized Medicine. Dr. Taneja recently published two studies — one in Genome Medicine and one in Arthritis and Rheumatology — connecting the dots between gut microbiota and rheumatoid arthritis.

More than 1.5 million Americans have rheumatoid arthritis, a disorder that causes painful swelling in the joints. Scientists have a limited understanding of the processes that trigger the disease. Dr. Taneja and her team identified intestinal bacteria as a possible cause; their studies indicate that testing for specific microbiota in the gut can help physicians predict and prevent the onset of rheumatoid arthritis.

“These are exciting discoveries that we may be able to use to personalize treatment for patients,” Dr. Taneja says.

The paper published in Genome Medicine summarizes a study of rheumatoid arthritis patients, their relatives and a healthy control group. The study aimed to find a biomarker — or a substance that indicates a disease, condition or phenomena — that predicts susceptibility to rheumatoid arthritis. They noted that an abundance of certain rare bacterial lineages causes a microbial imbalance that is found in rheumatoid arthritis patients.

“Using genomic sequencing technology, we were able to pin down some gut microbes that were normally rare and of low abundance in healthy individuals, but expanded in patients with rheumatoid arthritis,” Dr. Taneja says.

Implications for predicting and preventing rheumatoid arthritis

After further research in mice and, eventually, humans, intestinal microbiota and metabolic signatures could help scientists build a predictive profile for who is likely to develop rheumatoid arthritis and the course the disease will take, Dr. Taneja says.

Based on mouse studies, researchers found an association between the gut microbe Collinsella and the arthritis phenotype. The presence of these bacteria may lead to new ways to diagnose patients and to reduce the imbalance that causes rheumatoid arthritis before or in its early stages, according to John Davis III, M.D., and Eric Matteson, M.D., Mayo Clinic rheumatologists and study co-authors. Continued research could lead to preventive treatments.

Possibility for more effective treatment with fewer side effects

The second paper, published in Arthritis and Rheumatology, explored another facet of gut bacteria. Dr. Taneja treated one group of arthritis-susceptible mice with a bacterium, Prevotella histicola, and compared that to a group that had no treatment. The study found that mice treated with the bacterium had decreased symptom frequency and severity, and fewer inflammatory conditions associated with rheumatoid arthritis. The treatment produced fewer side effects, such as weight gain and villous atrophy — a condition that prevents the gut from absorbing nutrients — that may be linked with other, more traditional treatments.

While human trials have not yet taken place, the mice’s immune systems and arthritis mimic humans, and shows promise for similar, positive effects. Since this bacterium is a part of healthy human gut, treatment is less likely to have side effects, says study co-author Joseph Murray, M.D., a Mayo Clinic gastroenterologist.

Rheumatoid arthritis is an autoimmune disorder; it occurs when the body mistakenly attacks itself. The body breaks down tissues around joints, causing swelling that can erode bone and deform the joints. The disease can damage other parts of the body, including the skin, eyes, heart, lung and blood vessels.

Public Release: 11-Jul-2016

Study shows a new role for B-complex vitamins in promoting stem cell proliferation

University of Georgia

Athens, Ga. – Folates can stimulate stem cell proliferation independently of their role as vitamins, according to a collaborative study from the University of Georgia and Tufts University, which used an in vitro culture and animal model system in their findings.

Folates, whether supplemental B vitamins or natural folates found in food, are essential for the proper functioning of all cells in the body and are critical to prevent birth defects.

The study, published July 11 in Developmental Cell, shows for the first time that an adult stem cell population is controlled by an external factor arising from outside the animal–bacterial folate. In this case, that animal was a small roundworm model organism known as Caenorhabditis elegans.

“Our study shows that germ stem cells in Caenorhabditis elegans are stimulated to divide by a specific folate that comes from their bacterial diet,” said the study’s co-senior author Edward Kipreos, a professor in UGA’s Franklin College of Arts and Sciences. “Folates are essential B-group vitamins. However, we show that the ability of a specific folate to stimulate germ cells is independent of its role as a vitamin, implying that it acts directly as a signaling molecule.”

Naturally occurring folates exist in many chemical forms; folates are found in food, as well as in metabolically active forms in the human body. Folic acid is the major synthetic form found in fortified foods and vitamin supplements.

“Since its discovery in 1945, folate has been the subject of many studies that resulted in more than 50,000 publications. The finding in this study is the first of its kind because it presents evidence that folate is involved in roles other than those that were known before,” said the study’s co-senior author Jacob Selhub, director of the Vitamin Metabolism Laboratory at Tufts University.

“Grains in the U.S. and a few other countries are currently supplemented with folates,” Kipreos said. “Folate supplementation has been an important contributor in reducing the number of neural tube birth defects. However, a vitamin-independent role of folates may provide a secondary pathway, the nature and biological impact of which for humans are yet to be determined.”

The study describes how a specific folate receptor, FOLR-1, in C. elegans is required for the stimulation of germ stem cell growth.

The research team observed a process in C. elegans in which the action of FOLR-1 is required to promote germ cell tumors that may be similar to the way folate receptors promote the progression of certain cancers in humans. With a few exceptions, folate receptors are not essential for the transport of folates into cells for use as vitamins, but may act to stimulate cell division.

As a part of the published findings, the researchers created the first system that allows C. elegans germ cells to be cultured in vitro.

“This technique provides an important new tool for the study of this major genetic model organism,” Kipreos said.

Public Release: 11-Jul-2016

Thumb-sucking and nail-biting have a positive side

Study finds these children less likely to develop allergies

Hamilton, ON July 11, 2016 — Children who are thumb-suckers or nail-biters are less likely to develop allergic sensitivities, new research has found.

And, if they have both ‘bad habits’, they are even less likely to be allergic to such things as house dust mites, grass, cats, dogs, horses or airborne fungi.

The research, published in the journal Pediatrics today, was completed by researchers of New Zealand’s Dunedin School of Medicine, assisted by professor Malcolm Sears of McMaster University’s Michael G. DeGroote School of Medicine, and formerly from Dunedin.

“Our findings are consistent with the hygiene theory that early exposure to dirt or germs reduces the risk of developing allergies,” said Sears, who is also a researcher for the Firestone Institute for Respiratory Health at McMaster and St. Joseph’s Healthcare Hamilton. “While we don’t recommend that these habits should be encouraged, there does appear to be a positive side to these habits.”

The researchers were testing the idea that the common childhood habits of thumb-sucking and nail-biting would increase microbial exposures, affecting the immune system and reducing the development of allergic reactions also known as atopic sensitization.

The habits of thumb-sucking and nail-biting were measured in a longitudinal birth cohort of more than 1,000 New Zealand children at ages 5, 7, 9 and 11; and atopic sensitization was measured by skin-prick testing at 13 and 32 years old.

The researchers found 31 per cent of children were frequent thumb suckers or nail biters.

Among all children at 13 years old, 45% showed atopic sensitization, but among those with one oral habit, only 40% had allergies. Among those with both habits, only 31% had allergies. This trend was sustained into adulthood, and showed no difference depending on smoking in the household, ownership of cats or dogs; or exposure to house dust mites.

However, the study did not find associations between the oral habits and development of asthma or hay fever.

Public Release: 11-Jul-2016

Milestone study on pomegranate anti-aging mechanism reported by Amazentis SA and EPFL

Breakthrough findings on urolithin A, a pomegranate metabolite, on muscle aging, published in Nature Medicine; Amazentis announces first human clinical trial

Amazentis SA

Lausanne, Switzerland, July 11, 2016 — Amazentis SA, an innovative life sciences company applying scientific breakthroughs in nutrition to manage health conditions linked to aging, announced today a collaborative publication in Nature Medicine with the École Polytechnique Fédérale de Lausanne (EPFL), demonstrating that the Company’s lead product candidate, urolithin A, improves mitochondrial and muscle function, resulting in enhanced muscle strength and endurance during aging. Amazentis is presently evaluating urolithin A in a first human clinical trial with results expected in 2017.

Urolithin A is generated by gut microflora as a natural metabolite of ellagitannins, a class of compounds found in the pomegranate and other fruits and nuts. “We are excited to publish the first data that demonstrate the effects of this gut metabolite on mitochondrial and muscle function,” commented Johan Auwerx, Professor at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, and lead author. “We believe this research is a milestone in current anti-aging efforts, which have previously focused on traditional pharmaceutical modalities, and illustrates the opportunity of rigorously tested nutritional bioactive agents that we consider to have outstanding potential for human health.”

Urolithin A: a potent gut metabolite to rejuvenate mitochondria and reverse muscle aging

Oral administration of urolithin A leads to an improved mitochondrial function by stimulating mitophagy, a process by which damaged mitochondria are recycled to permit a renewal with healthy mitochondria.

“Mitophagy declines in cells as we age, and the reduction in mitochondrial function in the muscles of the elderly is thought to be one of the main causes of age-related muscle impairment. We believe our research, uncovering the health benefits of urolithin A, holds promise in reversing muscle aging,” stated Patrick Aebischer, co-author on the article, EPFL President and Chairman and co-founder of Amazentis.

The results are being reported in the current issue of Nature Medicine in an article titled, “Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents” (doi:10.1038/nm.4132, http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4132.html).

Age-related muscle decline: a compelling market opportunity for urolithin A

Declining skeletal muscle mass and the resulting loss of strength are hallmarks of aging. These changes can become debilitating and lead to a condition termed sarcopenia, which is thought to affect 30% of those over 60 years old and greater than 50% of individuals over 80 years. Current estimates in the United States project there will be greater than 75 million adults over 60 years by the year 2020.

The resulting reductions in quality of life and independence as a result of muscle decline constitute a growing healthcare issue in the aging population. There are currently no pharmaceutical therapies to treat age-related decline in muscle function and sarcopenia. Nutritional strategies have had limited impact to date, and new scientifically validated solutions are urgently needed.

Upon consumption of pomegranate juice, compounds known as ellagitannins are broken down in the stomach and then transformed by intestinal bacteria into urolithin A. This biotransformation has been shown to vary widely across individuals, with some showing high or low conversion rates, while others have different compositions of microflora and are unable to perform the conversion. Consequently, supplementing individuals with products designed to deliver carefully calibrated doses of urolithin A can overcome this natural diversity in gut microflora found in the general population.

Amazentis has established a technology portfolio and proprietary knowhow around urolithin A, enabling the manufacture and development of advanced nutrition products for oral delivery.

Chris Rinsch, Ph.D., a co-author and CEO and co-founder of Amazentis, commented, “Based on the rigorous science being published in Nature Medicine, we have advanced our lead product delivering urolithin A into clinical trials. We believe that this discovery will open the door to a new approach for managing muscle decline by rejuvenating mitochondria. Our vision is to translate breakthrough scientific discoveries in nutrition into clinically validated consumer health products that address today’s unmet needs in an aging population.”

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Public Release: 13-Jul-2016

Viruses revealed to be a major driver of human evolution

Study tracking protein adaptation over millions of years yields insights relevant to fighting today’s viruses

Genetics Society of America

BETHESDA, MD – The constant battle between pathogens and their hosts has long been recognized as a key driver of evolution, but until now scientists have not had the tools to look at these patterns globally across species and genomes. In a new study, researchers apply big-data analysis to reveal the full extent of viruses’ impact on the evolution of humans and other mammals.

Their findings suggest an astonishing 30 percent of all protein adaptations since humans’ divergence with chimpanzees have been driven by viruses.

“When you have a pandemic or an epidemic at some point in evolution, the population that is targeted by the virus either adapts, or goes extinct. We knew that, but what really surprised us is the strength and clarity of the pattern we found,” said David Enard, Ph.D., a postdoctoral fellow at Stanford University and the study’s first author. “This is the first time that viruses have been shown to have such a strong impact on adaptation.”

The study was recently published in the journal eLife and will be presented at The Allied Genetics Conference, a meeting hosted by the Genetics Society of America, on July 14.

Proteins perform a vast array of functions that keep our cells ticking. By revealing how small tweaks in protein shape and composition have helped humans and other mammals respond to viruses, the study could help researchers find new therapeutic leads against today’s viral threats.

“We’re learning which parts of the cell have been used to fight viruses in the past, presumably without detrimental effects on the organism,” said the study’s senior author, Dmitri Petrov, Ph.D., Michelle and Kevin Douglas Professor of Biology and Associate Chair of the Biology Department at Stanford. “That should give us an insight on the pressure points and help us find proteins to investigate for new therapies.”

Previous research on the interactions between viruses and proteins has focused almost exclusively on individual proteins that are directly involved in the immune response–the most logical place you would expect to find adaptations driven by viruses. This is the first study to take a global look at all types of proteins.

“The big advancement here is that it’s not only very specialized immune proteins that adapt against viruses,” said Enard. “Pretty much any type of protein that comes into contact with viruses can participate in the adaptation against viruses. It turns out that there is at least as much adaptation outside of the immune response as within it.”

The team’s first step was to identify all the proteins that are known to physically interact with viruses. After painstakingly reviewing tens of thousands of scientific abstracts, Enard culled the list to about 1,300 proteins of interest. His next step was to build big-data algorithms to scour genomic databases and compare the evolution of virus-interacting proteins to that of other proteins.

The results revealed that adaptations have occurred three times as frequently in virus-interacting proteins compared with other proteins.

“We’re all interested in how it is that we and other organisms have evolved, and in the pressures that made us what we are,” said Petrov. “The discovery that this constant battle with viruses has shaped us in every aspect–not just the few proteins that fight infections, but everything–is profound. All organisms have been living with viruses for billions of years; this work shows that those interactions have affected every part of the cell.”

Viruses hijack nearly every function of a host organism’s cells in order to replicate and spread, so it makes sense that they would drive the evolution of the cellular machinery to a greater extent than other evolutionary pressures such as predation or environmental conditions. The study sheds light on some longstanding biological mysteries, such as why closely-related species have evolved different machinery to perform identical cellular functions, like DNA replication or the production of membranes. Researchers previously did not know what evolutionary force could have caused such changes. “This paper is the first with data that is large enough and clean enough to explain a lot of these puzzles in one fell swoop,” said Petrov.

The team is now using the findings to dig deeper into past viral epidemics, hoping for insights to help fight disease today. For example, HIV-like viruses have swept through the populations of our ancestors as well as other animal species at multiple points throughout evolutionary history. Looking at the effects of such viruses on specific populations could yield a new understanding of our constant war with viruses–and how we might win the next big battle.

Public Release: 19-Jul-2016

How to increase the fat burned during exercise

FECYT – Spanish Foundation for Science and Technology

When we exercise, our body’s oxidation of fat and carbohydrates depends on the intensity and duration of the activity. A new study analyses the effect of consuming an alkaloid, p-synephrine, on the burning of lipids and refutes the value of “miracle” diets: it is not possible to lose more than a kilogramme of fat per month.

New research published in the British Journal of Clinical Pharmacology analyses p-synephrine’s role in burning fat during rest and exercise. This alkaloid can be found in nature (although at low concentrations) in a wide variety of citrus fruits such as oranges, mandarins and grapefruits, and commercially (at greater concentrations) as extract of bitter orange (Citrus aurantium).

“There is very little scientific information on this substance’s effects on metabolism and the oxidation of energy substrates during exercise or on the side effects of the continued consumption of this substance,” SINC was told by Juan Del Coso, a researcher from Camilo José Cela University and a lead author of the paper.

Because of its chemical similarity to ephedrine (a nervous system stimulant), and the substance’s activation of β3 adrenergic receptors, it has become a popular food supplement, typically included in weight loss products.

“The advantage of p-synephrine is its reduced activation of β1 y β2 receptors and consequent weak influence in raising arterial tension and heart rate, which mean the substance has fewer side effects than other adrenaline stimulators,” Del Coso adds.

The purpose of the investigation was to determine the effects of acute intake of 3 mg p-synephrine per kg body mass on energy metabolism and the rate of fat and carbohydrate oxidation during rest and exercise.

In a randomised, placebo-controlled, double-blind, experimental study, 18 subjects underwent two experimental trials: after consuming p-synephrine (3 mg/kg) and after taking a placebo (control test).

An hour alter ingesting the substance, energy expenditure and arterial tension were measured before and after physical activity, in this case using a static bike. Acute p-synephrine ingestion had no effect on energy expenditure, heart rate or arterial pressure.

“However, the substance produced a notable change in substrate utilisation during exercise: p-synephrine ingestion pre-exercise increased the rate of fat oxidation and reduced carbohydrate oxidation at low and moderate intensity,” the expert explains.

In fact, p-synephrine increased individuals’ maximum capacity to burn fat, although it did not change the intensity at which this was attained. This data suggests that p-synephrine supplements could be useful to increase fat oxidation by of 7 g per hour of exercise.

There is no such thing as a “miracle” diet

The maximum rate found for fat oxidation during exercise, in this case in cyclists, was 0.7 g/min. That would suggest that in a best-case scenario, an individual could burn 42 g of fat after an hour of exercise at that level of intensity.

“This means the weight changes we experience when we start exercising are not based on fat loss, but mainly on fluid loss. This is why the majority of ‘miracle’ diets and slimming programmes produce a ‘rebound’ effect due to the recovery of the lost fluid,” the researcher argues.

Real weight change, based on the oxidation of fat through exercise (and diet) causes a real loss of 200-300 g per week, a little over 1 kg per month.

“That should be the aim: to lose a kilo per month, but a kilo of fat. It’s less attention-catching than miracle diet slogans, but scientifically speaking, effective change would be at that rate,” he points out. “That said, the rate of loss could increase with p-synephrine, but always combining the substance with exercise.”

The authors highlight the need for further study to determine the effects of the long-term use of this substance on energy production, metabolism at rest and substrate utilisation during exercise.

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Citation: Jorge Gutiérrez-Hellín y Juan Del Coso. ‘Acute p-synephrine ingestion increases fat oxidation rate during exercise’. British Journal of Clinical Pharmacology (2016).

Public Release: 19-Jul-2016

Lower risk of bowel cancer death linked to high omega 3 intake after diagnosis

People with the disease may benefit from boosting dietary oily fish content, say researchers

BMJ

A high dietary intake of omega 3 fatty acids, derived from oily fish, may help to lower the risk of death from bowel cancer in patients diagnosed with the disease, suggests research published online in the journal Gut.

If the findings can be reproduced in other studies, patients with bowel cancer might benefit from boosting their oily fish intake to help prolong their survival, say the researchers.

Previous experimental research has shown that omega 3 polyunsaturated fatty acids (PUFAs)–namely, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA)–can suppress tumour growth and curb blood supply to malignant cells (angiogenesis).

The researchers base their findings on the participants of two large long term studies: the Nurses’ Health Study of 121,700 US registered female nurses, aged between 30 and 55 in 1976; and the Health Professionals Follow Up Study of 51, 529 male health professionals, aged between 40 and 75 in 1986.

All participants filled in a detailed questionnaire about their medical history and lifestyle factors when they joined the studies, and this was repeated every two years subsequently.

The information requested included any diagnosis of bowel cancer and other potentially influential factors, such as height, weight, smoking status, regular use of aspirin and non-steroidal inflammatory drugs, and exercise taken.

Data on what they ate were collected and updated every four years, using Food Frequency Questionnaires, with categories for each nutrient ranging from ‘never or less than once a month,’ to 6 or more times a day.’

The completeness of the data was above 95% for each of the questionnaires in both studies through to 2010.

Among 1659 participants who developed bowel cancer, 561 died; 169 of these were classified as deaths from the disease during an average monitoring period of 10.5 years. Other major causes of death included cardiovascular disease (153) and other cancers (113).

Participants with a higher dietary intake of omega 3 from oily fish were more likely to be physically active, take multivitamins, drink alcohol and to consume more vitamin D and fibre. They were also less likely to smoke–all factors associated with a lower risk of bowel cancer.

But those who had been diagnosed with bowel cancer and whose diets contained higher levels of marine omega 3 had a lower risk of dying from the disease. Omega 3 intake, however, was not linked to a lower risk of death, overall.

The extent of the reduced risk seemed to be linked to dose, with higher doses associated with lower risk, the findings showed. This held true even after taking account of intake prior to the diagnosis, as well as other potentially influential factors.

Compared with patients who consumed less than 0.1 g of omega 3 fatty acids daily, those who consumed at least 0.3 g daily after their diagnosis, had a 41% lower risk of dying from their disease.

This reduced risk applied to food sources and supplements, although few people used omega 3 fish oil supplements, the researchers point out.

The association between marine omega 3 intake and lowered risk of death seemed to be particularly evident among those who were tall, had a BMI below 25, or who didn’t take regular aspirin.

And increasing intake of marine omega 3 by at least 0.15 g daily after diagnosis was associated with a 70% lower risk of dying from bowel cancer; while a reduction in daily intake was associated with a 10% heightened risk of death from the disease.

Similar patterns were evident for death from all causes (13% lower and 21% higher, respectively) in those who either increased or decreased their intake after diagnosis.

This is an observational study so no firm conclusions can be drawn about cause and effect, but the researchers say that their findings provide the first line of population based evidence for the potentially positive impact of oily fish omega 3 fatty acids on bowel cancer survival.

“If replicated by other studies, our results support the clinical recommendation of increasing marine omega 3 PUFAs among patients with bowel cancer,” they conclude.

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About the journal: Gut is one of 60 specialist journals published by BMJ. The title is co-owned with the British Society of Gastroenterology. http://gut.bmj.com

Public Release: 19-Jul-2016

Virgin olive oil and hypertension

This research article by Dr. Sergio Lopez et al. is published in Current Vascular Pharmacology Journal Volume 14, Issue 6, 2016

Bentham Science Publishers

Oleic acid plus a constellation of minor constituents as a natural antihypertensive.

Consumption of virgin olive oil is good for you, but why? Scientific evidence on this issue has been accumulating for a quarter century. Epidemiological, clinical, and animal studies support that the consumption of virgin olive oil, instead of other sources of dietary fats, has antihypertensive effects.

What contains does virgin olive oil contain that makes it so healthy? Virgin olive oil is an oily fruit whose composition includes large quantities of oleic acid (a monounsaturated fatty acid) and also a variety of compounds present in lower quantities, named minor constituents, such as hydrocarbons, phytosterols, triterpenic compounds, and phenolic compounds. Both oleic acid and these minor constituents confer unique bioactive properties to virgin olive oil.

How do its components protect from hypertension? They influence on factors associated with the pathophysiology of hypertension such as vascular contractibility and protect from heart and kidney cellular loss and functionality, leading to a reduction of blood pressure.

Is it a miraculous ingredient? No, it is just a food. Virgin olive oil helps in preventing and treating hypertension but its full power arises as part of the Mediterranean dDiet in a global strategy for a healthy and long-lasting life.

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Reference: Lopez, S.; et al. (2016). Virgin Olive Oil and Hypertension, Curr. Vasc. Pharmacol., DOI: 10.2174/1570161114666160118105137

Public Release: 19-Jul-2016

Infections, antibiotic use linked to manic episodes in people with serious mental illness

Johns Hopkins Medicine

In research using patient medical records, investigators from Johns Hopkins and Sheppard Pratt Health System report that people with serious mental disorders who were hospitalized for mania were more likely to be on antibiotics to treat active infections than a group of people without a mental disorder.

Although the researchers caution that their study does not suggest cause and effect, they note that it does suggest that an infection, use of antibiotics or other factors that change the body’s natural collection of gut and other bacteria may individually or collectively contribute to behavioral changes in some people with mental disorders.

Their findings, published July 18 in Bipolar Disorders, add to evidence that the body’s immune system, the so-called gut brain axis, and the particular bacterial microbiome each person has play an integral part in the ebb and flow of psychiatric symptoms and psychiatric disorders, including bipolar disorder and schizophrenia.

“More research is needed, but ours suggests that if we can prevent infections and minimize antibiotic treatment in people with mental illness, then we might be able to prevent the occurrence of manic episodes,” says Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics at the Johns Hopkins University School of Medicine. “This means we should focus on good-quality health care and infection prevention methods for this susceptible population and pay extra attention to such things as flu shots, safe sex practices and urinary tract infections in female patients.”

Yolken says his team’s study grew out of an interest in long-observed connections among infections, the microbiome and symptoms of mental illness. For example, numerous studies have shown that experimental alterations in the microbiome of animals can alter their behavior.

Because antibiotics kill bacteria and can disrupt the makeup of the microbiome, Yolken and his research colleagues looked at records of antibiotic use in patients treated at the Sheppard Pratt– a psychiatric hospital in Baltimore — either as an inpatient or day hospital patient. Just over 64 percent of the patients were female, and all were 18 to 65. Two hundred and thirty-four people were hospitalized for mania, 101 for bipolar disorder, 70 for major depression and 197 for schizophrenia. Patients taking antibiotics were receiving a wide range of medications, including tetracycline, penicillin, sulfonamide, cephalosporin, fluoroquinolone and macrolides for skin, respiratory, urinary tract and mouth infections.

For comparison, they surveyed 555 healthy controls ruled not to have a mental disorder, including 347 women and 208 men between the ages of 20 and 60, about their current antibiotic use.

The researchers examined antibiotic usage as an indirect way to measure for the presence of infection. Antibiotic usages were assessed through medical records with the patients and through an interview with participants in the comparison group.

Of those hospitalized for mania, episodes of heightened energy and overactivity often associated with bipolar disorder — 18 participants, or 7.7 percent, were taking antibiotics, compared to only 1.3 percent of the controls. This represents a more than fivefold increase in the odds of being in the mania group if taking antibiotics. On the other hand, just over 3 percent of people hospitalized for schizophrenia, 4 percent of people hospitalized for bipolar depression and 2.9 percent of people hospitalized for major depression were taking antibiotics.

The researchers investigated whether the site of infection, such as mouth, skin or respiratory system, correlated with hospitalization, and they found that location of the infection didn’t seem to matter, although 15 women had urinary tract infections, which didn’t occur in any men.

Yolken says there are several ways that infection and antibiotic use could directly or indirectly impact psychiatric symptoms. Among the possibilities are that systemic inflammation caused by the infection itself may lead to psychiatric symptoms or, alternatively, that antibiotics disrupt the gut’s microbiome by killing off “good bacteria,” which may also affect the mind by increasing inflammation if more “bad bacteria” are present.

Yolken says that the research team is currently looking for how these connections might actually work. One study is investigating, for example, whether suppressing inflammation in the gut with probiotics in people with mental illness will reduce the recurrence of manic episodes.

Public Release: 21-Jul-2016

Cinnamon may be fragrant medicine for the brain

Veterans Affairs Research Communications

If Dr. Kalipada Pahan’s research pans out, the standard advice for failing students might one day be: Study harder and eat your cinnamon!

Pahan a researcher at Rush University and the Jesse Brown Veterans Affairs Medical Center in Chicago, has found that cinnamon turns poor learners into good ones–among mice, that is. He hopes the same will hold true for people.

His group published their latest findings online June 24, 2016, in the Journal of Neuroimmune Pharmacology.

“The increase in learning in poor-learning mice after cinnamon treatment was significant,” says Pahan. “For example, poor-learning mice took about 150 seconds to find the right hole in the Barnes maze test. On the other hand, after one month of cinnamon treatment, poor-learning mice were finding the right hole within 60 seconds.”

Pahan’s research shows that the effect appears to be due mainly to sodium benzoate–a chemical produced as cinnamon is broken down in the body.

If that chemical sounds familiar, you may have noticed it on the ingredient labels of many processed foods. Food makers use a synthetic form of it as a preservative. It is also an FDA-approved drug used to treat hyperammonemia–too much ammonia in the blood.

Though some health concerns exist regarding sodium benzoate, most experts agree it’s perfectly safe in the amounts generally consumed. One reassuring point is that it’s water-soluble and easily excreted in the urine.

Cinnamon acts as a slow-release form of sodium benzoate, says Pahan. His lab studies show that different compounds within cinnamon–including cinnamaldehyde, which gives the spice is distinctive flavor and aroma–are “metabolized into sodium benzoate in the liver. Sodium benzoate then becomes the active compound, which readily enters the brain and stimulates hippocampal plasticity.”

Those changes in the hippocampus–the brain’s main memory center–appear to be the mechanism by which cinnamon and sodium benzoate exert their benefits.

In their study, Pahan’s group first tested mice in mazes to separate the good and poor learners. Good learners made fewer wrong turns and took less time to find food.

In analyzing baseline disparities between the good and poor learners, Pahan’s team found differences in two brain proteins. The gap was all but erased when cinnamon was given.

“Little is known about the changes that occur in the brains of poor learners,” says Pahan. “We saw increases in GABRA5 and a decrease in CREB in the hippocampus of poor learners. Interestingly, these particular changes were reversed by one month of cinnamon treatment.”

The researchers also examined brain cells taken from the mice. They found that sodium benzoate enhanced the structural integrity of the cells–namely in the dendrites, the tree-like extensions of neurons that enable them to communicate with other brain cells.

Cinnamon, like many spices, has antioxidant and anti-inflammatory properties. So it could be expected to exert a range of health-boosting actions, and it does have a centuries-long history of medicinal use around the world.

But the U.S. National Center for Complementary and Integrative Health says that “high-quality clinical evidence to support the use of cinnamon for any medical condition is generally lacking.” Most of the clinical trials that have taken place have focused on the spice’s possible effect on blood sugar for people with diabetes. Little if any clinical research has been done on the spice’s possible brain-boosting properties.

Pahan hopes to change that. Based on the promising results from his group’s preclinical studies, he believes that “besides general memory improvement, cinnamon may target Alzheimer’s disease, mild cognitive impairment [a precursor to Alzheimer’s], and Parkinson’s disease as well.” He is now talking with neurologists about planning a clinical trial on Alzheimer’s.

Before you start heaping cinnamon on your oatmeal, keep a few caveats in mind.

First, most cinnamon found in the store is the Chinese variety, which contains a compound called coumarin that may be toxic to the liver in high amounts. A person would likely have to eat tons of cinnamon to run into a problem, but just the same, Pahan recommends the Ceylon or Sri Lanka type, which is coumarin-free.

Even then, don’t overdo it. “Anything in excess is toxic,” says Pahan.

What about simply inhaling the pleasant-smelling spice? Will that benefit the brain?

“Simply smelling the spice may not help because cinnamaldehyde should be metabolized into cinnamic acid and then sodium benzoate,” explains Pahan. “For metabolism [to occur], cinnamaldehyde should be within the cell.”

As for himself, Pahan isn’t waiting for clinical trials. He takes about a teaspoonful–about 3.5 grams–of cinnamon powder mixed with honey as a supplement every night.

Should the research on cinnamon continue to move forward, he envisions a similar remedy being adopted by struggling students worldwide.

“Individual differences in learning and educational performance is a global issue, he says. “In many cases, we find two students of the same background studying in the same class, and one turns out to be a poor learner and does worse than the other academically. Now we need to find a way to test this approach in poor learners. If these results are replicated in poor-learning students, it would be a remarkable advance. At present, we are not using any other spice or natural substance.”

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Pahan’s study was funded by VA, the National Institutes of Health, and the Alzheimer’s Association.

Public Release: 22-Jul-2016

Saint Louis University research: Plant compounds give ‘1-2’ punch to colon cancer

Saint Louis University

ST. LOUIS — The combination of two plant compounds that have medicinal properties – curcumin and silymarin – holds promise in treating colon cancer, according Saint Louis University research published in the June 23 issue of the Journal of Cancer.

Curcumin is the active ingredient in the spice turmeric, which is present in spicy curry dishes, and silymarin is a component of milk thistle, which has been used to treat liver disease.

The researchers and their students studied a line of colon cancer cells in a laboratory model. They found treating the cells initially with curcumin, then with silymarin was more effective in fighting cancer than treating the cells with either phytochemical alone, said Uthayashanker Ezekiel, Ph.D., corresponding author and associate professor of biomedical laboratory science at Saint Louis University.

“The combination of phytochemicals inhibited colon cancer cells from multiplying and spreading. In addition, when the colon cancer cells were pre-exposed to curcumin and then treated with silymarin, the cells underwent a high amount of cell death,” Ezekiel said.

“Phytochemicals may offer alternate therapeutic approaches to cancer treatments and avoid toxicity problems and side effects that chemotherapy can cause.”

Ezekiel noted the research is a preliminary cell study, with more research ahead before scientists know if the compounds are an effective treatment for people who have colon cancer. He saw promise in using the phytochemicals to help prevent colon cancer, which frequently is caused by lifestyle factors, such as diet.

Scientists next would need to study how the curcumin and silymarin impact the actions of molecules, such as genetic transcription and expression, that cause cells to change, Ezekiel said. Then the compounds would be studied in an animal model, then in humans.

“Concentrations of curcumin and silymarin that are too high could be harmful to people,” he said. “We still have much to learn, and for now, it’s so much safer to add a little spice to your diet and get your curcumin from foods that contain turmeric, such as curry, rather than taking high doses of the compound.”

prepares students to work with health professionals from all disciplines to ensure the best possible patient care.

Public Release: 25-Jul-2016

Protein in breast milk reduces infection risk in premature infants

Study shows need for large-scale trial of lactoferrin’s role in immune system development

University of Missouri-Columbia

COLUMBIA, Mo. (July 25, 2016) — Full-term babies receive natural protection from their mothers that helps them fight off dangerous infections. However, babies born prematurely lack protective intestinal bacteria and often are unable to be nursed, causing their infection-fighting capabilities to be underdeveloped. Now, researchers at the University of Missouri School of Medicine have found that a manufactured form of lactoferrin, a naturally occurring protein in breast milk, can help protect premature infants from a type of staph infection.

“Babies born with low levels of protective intestinal bacteria are at an increased risk of devastating and sometimes deadly infections,” said Michael Sherman, M.D., professor emeritus in the Department of Child Health at the MU School of Medicine and lead author of the study. “Our study found that giving very-low-birth-weight premature infants a manufactured form of lactoferrin can virtually eliminate the germ that causes a staph infection known as staphylococcus epidermidis.”

The researchers studied the immune systems of 120 premature infants in the neonatal intensive care units at MU Women’s and Children’s Hospital and the University of Southern California Children’s Hospital Los Angeles between July 2009 and January 2012. Infants in the trial weighed between 1 pound, 10 ounces, and 3 pounds, 4 ounces, at birth. Sixty of the infants received lactoferrin via a feeding tube twice a day for 28 days to simulate receiving mother’s milk while nursing.

To understand the protein’s role in the development of protective intestinal bacteria, the researchers examined fecal matter of the infants. The researchers found that germs responsible for the colonization of staph infection were virtually eliminated in the newborns who received lactoferrin.

“These germs are the most common cause of in-hospital bloodstream infections in premature babies, causing up to 50 percent of infections,” Sherman said. “As physicians, we’ve had limited knowledge of how lactoferrin affects the development of protective intestinal bacteria. Our study shows that it can modify germs in the bowel of infants, and those germs can protect premature babies from staph infections.”

As part of the study, lactoferrin was provided to the patients at no cost. According to Sherman, lactoferrin can cost an estimated $25 to $500 per dose, though an infection can extend an infant’s hospital stay by 10 to 14 days at a cost of $40,000 to $56,000.

Though it is too early to recommend lactoferrin as a standard treatment protocol in NICUs across the country, the researchers say more research could shed light on its role in preventing infections.

“These vulnerable babies need all the support they can get to fight off infections,” Sherman said. “Our results justify the need for a large-scale trial of lactoferrin, as well as its counterpart derived from cow milk, bovine lactoferrin.”

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The study, “Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants,” recently was published by The Journal of Pediatrics. Research reported in this publication was supported by the National Institutes of Health (HD05774) and the Gerber Foundation (PN002-1214-2708). The authors received an honorarium to serve as members of the Mead Johnson Pediatric Institute Bioactive Expert Panel to write the manuscript. The sponsor had no involvement in preparing the manuscript, and the authors are entirely and exclusively responsible for its content.

In addition to Michael Sherman, the research team included Jan Sherman, Ph.D., R.N., an associate teaching professor at the MU Sinclair School of Nursing; Roxanne Arcinue, M.D., a neonatologist at Kapiolani Medical Center for Women and Children in Honolulu, Hawaii; and Victoria Niklas, M.D., a scientist at Prolacta in Los Angeles and a clinical professor at the University of California, Los Angeles.

About the MU School of Medicine

The MU School of Medicine has improved health, education and research in Missouri and beyond for more than 165 years. MU physicians treat patients from every county in the state, and more Missouri physicians received their medical degrees from MU than from any other university. For more information, visit http://medicine.missouri.edu/.