Past News Items - January 2017

Mitochondrial dysfunction is the root cause of many diseases that are bewildering in their variety and complexity. They include rare genetic disorders in children, some forms of heart disease, and most likely many cases of Parkinson's disease.

Research on mitochondria started already in the late 19th century, but there are still many unsolved issues concerning their composition, their function, and their relevance to health and disease. Director Howy Jacobs and his research group at the Institute of Biotechnology are among many scientists worldwide who seek to answer the open questions, in their daily work. Their main aim is to understand how mitochondria interact with other cellular components to maintain physiological homeostasis, and how mitochondrial defects lead to pathological states.

"Mitochondria arose as a bacterial intruder in ancient cells, and much of their biology has to be understood in this light. They retain a degree of autonomy, and still manufacture some of their most crucial components, which are encoded by the mitochondrial DNA, a relic of the intruder's original genome. Understanding how mitochondria are put together is important, if we are ever going to be able to intervene to correct their malfunction," explains Jacobs.

"It's of course worthwhile studying mitochondria in order to understand fundamental processes of the cell and of evolution. The disease angle isn't the only motivation. But naturally, I am very happy that our research has turned out to be important for medicine, and could one day lead to new treatments," says Jacobs.

"In any case, at least for me, science is addictive," Jacob states.

A back-up system to protect cells from mitochondrial damage

Since this research been going on for well over a century, it's clear that mitochondria only give up their mysteries rather slowly.

"For the past decade our focus has been on a particular 'back-up' system found in the mitochondria of lower organisms, but which has been lost during the evolution of complex animals such as humans or fruit flies. This back-up system kicks in when the regular energy-generating system of the mitochondria is overloaded, damaged or poisoned, protecting the cell against the harmful stresses of having a malfunctioning 'engine'. Indeed, mitochondria can be thought of rather like a car engine, that burns fuel (food molecules), and recovers the energy in a useful form to drive the processes of life. A malfunctioning engine imparts less energy but also creates toxic by-products as a result of incomplete combustion. Mitochondria are very similar," Jacob clarifies.

Jacob's team has transplanted the back-up or 'alternative' respiratory machinery from the mitochondria of lower organisms to human cells, showing that it can protect against pathological stresses, and even lethal poisons like cyanide, that target the mitochondria.

"This could have medical applications even within the next decade. But part of our work is still focused on very basic processes inside mitochondria. And there are always new surprises, sometimes relating to topics that have been neglected or have been impossible to study until the right tools became available," says Jacobs

An example is Jacob's current work in collaboration with a team in Paris, to try to measure the actual temperature at which the mitochondrial engine operates.

Science at the edge

One issue that scientists will have to grapple with in future is how far they are prepared to go to apply genetic knowledge to human disease.

"Until now, the human genome has been considered sacrosanct, and any direct or permanent manipulation of it has been regarded as unethical. However, the time is gradually approaching when we will acquire the means to prevent disease or reverse disease processes when they occur, by making such changes to the genome," Jacobs predicts.

"This obviously opens a major ethical dilemma," states Jacobs.

Is it ethical to engineer 'improvements' to what has evolved naturally, sometimes without being able to predict all the consequences? But equally, is it ethical to withhold life-saving technologies that can prevent suffering?

SOURCE Helsingin yliopisto (University of Helsinki)

Released: 01/30/16

Research Suggests Way to Improve Stroke Treatments

The standard of care for treating strokes caused by blood clots involves the therapeutic infusion of tissue plasminogen activator (tPA), which can help to dissolve the clots and restore blood flow. This "thrombolytic" treatment carries the risk of bleeding and swelling in the brain, and it must be administered within three hours after the start of the stroke, which sharply limits its clinical benefits.

Working with animal models, researchers at Joslin Diabetes Center now have demonstrated the potential of giving a drug in combination with tPA that might improve stroke outcomes and increase the window of opportunity for the therapy.

Drugs that target a protein called plasma kallikrein, as well as an activator protein called factor XII, "may provide the opportunity to make tPA safer by reducing these complications and increasing its efficacy in opening blood vessels," says Edward Feener, PhD, corresponding author on a paper about the work published in the journal Blood.

About 800,000 people in the United States suffer a stroke each year, and about 87 percent are ischemic strokes, in which blood flow is blocked by a clot.

Fabrício Simão, PhD, who is lead author on the Blood paper, and colleagues in the Feener lab demonstrated that tPA boosts the activity of plasma kallikrein in both human and mouse plasma.

The Joslin scientists next experimented with mouse models in which blood clots were induced in the brain and then treated with tPA. Animals that were also given a plasma kallikrein inhibitor, and animals that were genetically modified to produce lower amounts of the protein, showed significantly less bleeding, brain swelling, and damaged brain areas than control animals without plasma kallikrein blockade.

The researchers traced the biological mechanisms by which tPA activates plasma kallikren, via the Factor XII protein, which promotes coagulation. Plasma kallikrein is known to activate the kallikrein kinin system, a pathway that has been implicated in stroke complications including brain swelling and breakdown of the blood-brain barrier. (Previous studies by other investigators have shown that administration of tPA therapy to stroke patients activates the kallikrein kinin system in their blood.)

The Food & Drug Administration has approved a plasma kallikrein inhibitor for the treatment of hereditary angioedema. Additional inhibitors targeting this pathway are under development by multiple pharmaceutical companies for this genetic disease and other conditions, including diabetic macular edema. These new findings suggest additional potential therapeutic opportunities for plasma kallikrein inhibitors in thrombolytic therapy.

SOURCE Joslin Diabetes Center

Journal Reference

Fabrício Simão, Tuna Ustunkaya, Allen C. Clermont, Edward P. Feener. Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke. Blood, January 2017 DOI: 10.1182/blood-2016-09-740670

Released: 01/27/16

The Type, Not Just the Amount, of Sugar Consumption Matters in Risk of Health Problems

The type of sugar you eat—and not just calorie count—may determine your risk for chronic disease. A new study is the first of its kind to compare the effects of two types of sugar on metabolic and vascular function. The paper is published ahead of print in the American Journal of Physiology—Heart and Circulatory Physiology.

Female rats were given a liquid solution of either glucose (a form of sugar found naturally in the body after carbohydrates are broken down) or fructose (sugar found in fruit and fruit juices) in addition to their normal diet of solid food. The rats received the sweetened solutions for eight weeks, roughly equivalent to a person eating large amounts of sugar for six years. The sugar-fed rats were compared with a control group that received plain drinking water in addition to their food supply.

Researchers found that although both sugar-fed groups consumed more calories than the control group, the total calorie intake of the glucose-fed rats was higher than the rats that were given fructose. Another surprising observation was that “despite this difference, only the fructose group exhibited a significant increase in final body weight,” wrote the research team.

In addition to higher weight gain, the fructose group showed more markers of vascular disease and liver damage than the glucose group. These included high triglycerides, increased liver weight, decreased fat burning in the liver (a factor that can contribute to fatty liver) and impaired relaxation of the aorta, which can affect blood pressure.

These findings suggest that an increase in the amount of calories consumed due to sweeteners is not the only factor involved in long-term health risks. The type of sugar may also play a role in increasing risk factors for heart disease, diabetes, and other chronic diseases.

Read the full article, “Type of Supplemented Simple Sugar, Not Merely Calorie Intake, Determines Adverse Effects on Metabolism and Aortic Function in Female Rats,” published ahead of print in the American Journal of Physiology—Heart and Circulatory Physiology.

SOURCE American Physiological Society (APS)

Released: 01/27/16

High-fiber diet keeps gut microbes from eating the colon's lining, protects against infection, animal study shows

It sounds like the plot of a 1950s science fiction movie: normal, helpful bacteria that begin to eat their host from within, because they don't get what they want.

But new research shows that's exactly what happens when microbes inside the digestive system don't get the natural fiber that they rely on for food.

Starved, they begin to munch on the natural layer of mucus that lines the gut, eroding it to the point where dangerous invading bacteria can infect the colon wall.

In a new paper in Cell, an international team of researchers show the impact of fiber deprivation on the guts of specially raised mice. The mice were born and raised with no gut microbes of their own, then received a transplant of 14 bacteria that normally grow in the human gut. Scientists know the full genetic signature of each one, making it possible to track their activity over time.

The findings have implications for understanding not only the role of fiber in a normal diet, but also the potential of using fiber to counter the effects of digestive tract disorders.

"The lesson we're learning from studying the interaction of fiber, gut microbes and the intestinal barrier system is that if you don't feed them, they can eat you," says Eric Martens, PhD, an associate professor of microbiology at the University of Michigan Medical School who led the research along with his former postdoctoral fellow Mahesh Desai, PhD, now at the Luxembourg Institute of Health.

Using U-M's special gnotobiotic, or germ-free, mouse facility and advanced genetic techniques that allowed them to determine which bacteria were present and active under different conditions, they studied the impact of diets with different fiber content and those with no fiber. They also infected some of the mice with a bacterial strain that does to mice what certain strains of Escherichia coli can do to humans—cause gut infections that lead to irritation, inflammation, diarrhea, and more.

The result: the mucus layer stayed thick, and the infection didn't take full hold, in mice that received a diet that was about 15 percent fiber from minimally processed grains and plants. But when the researchers substituted a diet with no fiber in it, even for a few days, some of the microbes in their guts began to munch on the mucus.

They also tried a diet that was rich in prebiotic fiber—purified forms of soluble fiber similar to what some processed foods and supplements currently contain. This diet resulted in the same erosion of the mucus layer as observed in the lack of fiber.

The researchers also saw that the mix of bacteria changed depending on what the mice were being fed, even day by day. Some species of bacteria in the transplanted microbiome were more common—meaning they had reproduced more—in low-fiber conditions, others in high-fiber conditions.

And the four bacteria strains that flourished most in low-fiber and no-fiber conditions were the only ones that make enzymes that are capable of breaking down the long molecules called glycoproteins that make up the mucus layer.

In addition to looking at bacteria based on genetic information, the researchers could see which fiber-digesting enzymes the bacteria were making. They detected more than 1,600 different enzymes capable of degrading carbohydrates—similar to the complexity in the normal human gut.

Just like the mix of bacteria, the mix of enzymes changed depending on what the mice were being fed, with even occasional fiber deprivation leading to more production of mucus-degrading enzymes.

Images of the mucus layer, and the "goblet" cells of the colon wall that produce the mucus constantly, showed the layer was thinner the less fiber the mice received. While mucus is constantly being produced and degraded in a normal gut, the change in bacteria activity under the lowest-fiber conditions meant that the pace of eating was faster than the pace of production—almost like an overzealous harvesting of trees outpacing the planting of new ones.

When the researchers infected the mice with Citrobacter rodentium, the E. coli-like bacteria, they observed that these dangerous bacteria flourished more in the guts of mice fed a fiber-free diet. Many of those mice began to show signs of illness and lost weight.

When the scientists looked at samples of their gut tissue, they saw not only a much thinner or even patchy mucus later—they also saw inflammation across a wide area. Mice that had received a fiber-rich diet before being infected also had some inflammation but across a much smaller area.

Martens notes that in addition to the gnotobiotic facility, the research was possible because of the microbe DNA and RNA sequencing capability built up through the Medical School's Host Microbiome Initiative, as well as the computing capability to plow through all the sequence data.

"Having all the resources here was the key to making this work, and the fact that it was all across the street from our lab allowed us to pin it all together," he says. He also notes the role of U-M colleagues led by Gabriel Nunez and Nobuhiko Kamada in providing the C. rodentium pathogen model, and of French collaborators from the Aix-Marseille Université in studying the enzymes in the mouse gut.

Going forward, Martens and Desai intend to look at the impact of different prebiotic fiber mixes, and of diets with more intermittent natural fiber content over a longer period. They also want to look for biomarkers that could tell them about the status of the mucus layer in human guts?such as the abundance of mucus-digesting bacteria strains, and the effect of low fiber on chronic disease such as inflammatory bowel disease.

"While this work was in mice, the take-home message from this work for humans amplifies everything that doctors and nutritionists have been telling us for decades: Eat a lot of fiber from diverse natural sources," says Martens. "Your diet directly influences your microbiota, and from there it may influence the status of your gut's mucus layer and tendency toward disease. But it's an open question of whether we can cure our cultural lack of fiber with something more purified and easy to ingest than a lot of broccoli."

SOURCE University of Michigan Health System

Journal Reference

Mahesh S. Desai et al. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell, November 2016 DOI: 10.1016/j.cell.2016.10.043

Released: 01/20/16

Aligning SNAP Benefits with the Dietary Guidelines Produces Nutrient Gains and Cost Savings, According to New Review from the Physicians Committee for Responsible Medicine

More than a dozen nutrition researchers are asking the United States Department of Agriculture (USDA) to align the recommendations for healthful eating, outlined in the 2015-2020 Dietary Guidelines for Americans, with Supplemental Nutrition Assistance Program (SNAP) benefits.

The findings appear in the American Journal of Preventive Medicine as a 103-page supplement, entitled "The Supplemental Nutrition Assistance Program's Role in Addressing Nutrition-Related Health Issues." Two study authors, Neal Barnard, MD, FACC, and Susan Levin, MS, RD, CSSD, find this alignment can help SNAP participants double nutrient intake and may save the USDA $26 billion each year. The savings can be reinvested into the program to further alleviate food insecurity.

The SNAP program uses $74 million annually to provide 45 million Americans living at or below 130 percent of the poverty level with electronic benefits to purchase food. Half of SNAP recipients are children and teens. SNAP benefits can be used to purchase any food item, except for hot and prepared entrées, alcoholic beverages, and vitamins.

"Our goal is to blend nutrition science and nutrition guidance into federal food assistance programs, especially SNAP, which one in seven Americans relies on for nourishment," notes Susan Levin, MS, RD, CSSD, a study author and the director of nutrition education at the nonprofit Physicians Committee. "As our diets have changed over 50 years, our federal food policies should follow suit."

Compared to higher income populations, SNAP recipients are 70 percent more likely to have type 2 diabetes and 19 percent more likely to have hypertension. Compared to income-eligible populations, SNAP recipients struggle with higher rates of obesity and metabolic syndrome.

Fifty-five percent of SNAP benefits apply to meats, sweetened beverages, prepared foods, and desserts, cheese, salty snacks, candy, and sugar, while just 23.9 percent are spent on fruits, vegetables, grains, nuts, beans, seeds, and spices. Americans in every income bracket fall short on plant-based eating patterns. Only 13 percent of adults meet the USDA's recommended fruit and vegetable intake.

More than 86 percent of health care spending in America is used to treat or prevent chronic lifestyle disease. The United States spends half a trillion, more than $560 billion each year, to treat type 2 diabetes, heart disease, and stroke. Medical costs for type 2 diabetes are twice the amount for someone without the disease. Diabetes is now the most expensive disease to treat.

More than half of SNAP recipients support this alignment, according to recent surveys. Between 55 and 88 percent favor program expansion and incentivizes for healthful food purchases.

For interactive content or an interview with Dr. Barnard or Susan Levin, MS, RD, CSSD, please contact Jessica Frost at 202-527-7342 or jfrost@pcrm.org.

The Physicians Committee is a nonprofit organization, founded in 1985 by Neal Barnard, M.D., F.A.C.C., that promotes preventive nutrition, conducts clinical research, and encourages higher standards for ethics and effectiveness in research.

SOURCE Physicians Committee for Responsible Medicine

Released: 01/20/16

Autism Researchers Discover Genetic 'Rosetta Stone'

Distinct sets of genetic defects in a single neuronal protein can lead either to infantile epilepsy or to autism spectrum disorders (ASDs), depending on whether the respective mutations boost the protein's function or sabotage it, according to a new study by UC San Francisco researchers. Tracing how these particular genetic defects lead to more general changes in brain function could unlock fundamental mysteries about how events early in brain development lead to autism, the authors say.

"The genetics of neuropsychiatric disease is often complicated, but here we have a single gene in which specific mutations can cause either infantile seizures or autism in a consistent and predictable manner," said Stephan Sanders, MD, PhD, an assistant professor of psychiatry at UCSF and member of the UCSF Weill Institute for Neurosciences who is co-senior author of the new study. "This gives us an opportunity to understand both what these disorders have in common and what makes them different."

The findings are a first step towards understanding how different subtle changes in neural function in utero could lead to the development of either a seizure-prone brain or an autistic brain in infancy, the authors say. The study also further implicates the gene responsible for these changes—called SCN2A—as the single human gene with the strongest evidence for a causal role in driving ASDs.

Matthew W. State, MD, PhD, the Oberndorf Family Distinguished Professor and chair of psychiatry at UCSF, first discovered the link between autism and SCN2A. According to State, who was not directly involved with the new study: "In autism research, understanding why mutations in a single gene can lead not only to ASDs, but to a wide range of other neurodevelopment disorders has emerged as a central question for the field. This new work provides critical clues that begin to unravel this mystery and could serve as a molecular 'Rosetta Stone' to illuminate autism pathology."

The study was published online January 26 in Biological Psychiatry.

Genome sequencing points to SCN2A mutations as strongest known genetic drivers of autism

The advent of whole-exome genome sequencing and the amassing of large, well-defined study populations such as the Simons Simplex Collection (SSC) and the research cohorts assembled by the Autism Sequencing Consortium (ASC), have allowed researchers to make tremendous progress in recent years in identifying genetic risk factors for autism, said Sanders: "In the past four years we've gone from not really knowing how to find autism genes to having a long list of mutations linked to the disorder."

As a graduate student and postdoctoral researcher at Yale University working in State's lab, Sanders led collaborations that searched for autism-linked genetic mutations by conducting large whole-exome genomic screens of more than 4,000 autistic children and their families participating in the SSC and ASC consortia. In studies published in 2012, 2014, and 2015, State, Sanders and collaborators found that de novo genetic mutations—spontaneous mutations not inherited from parents—play a role in the development of ASDs in at least 20 percent of all cases of autism, many more than previously recognized.

These studies led to the identification of 65 genes with a strong likelihood of contributing to autism when mutated and implicated SCN2A as the human gene with the second strongest evidence for a causal role in driving ASDs. Analyses of additional SCN2A mutations in the current paper, confirm this result and elevate SCN2A to the single strongest case for a genetic driver of ASD.

Autism-associated SCN2A mutations impede signaling in the developing brain

SCN2A was in fact one of the first ASD-associated genes to be discovered. It encodes a sodium channel protein called NaV1.2 that is crucial to neurons' ability to communicate electrically, especially during early brain development.

In addition to its strong association with autism, SCN2A had also previously been implicated in epilepsy. When Sanders came to UCSF in 2015, he began collaborating with neurophysiologist Kevin Bender, PhD, an assistant professor of neurology and co-senior author of the study, to examine the mechanisms of how mutations SCN2A alter neuronal function to lead to these two different diseases.

"Fortunately, the function of sodium channels is easy to test in the lab," said Bender, who is also a member of UCSF's Center for Integrative Neuroscience, Kavli Institute for Fundamental Neuroscience, and Weill Institute for Neurosciences. "Often you see mutations that are associated with a disease but you're not really sure what the gene is supposed to do or how the mutations change its function. But neuroscientists have been studying sodium channels since the 1950s—the experiments are extremely clear.

Bender's team measured how 12 SCN2A mutations observed in children with ASD affected the electrical properties of NaV1.2 channels in cultured human cells in the lab. As predicted, based on the mutations' location on the protein, all 12 reduced the function of the sodium channel, but in a variety of different ways, ranging from stopping the channel from being made at all to simply blocking the pore through which sodium needs to flow for the channel to function.

The researchers used this data to inform computer models of how the various channel mutations seen in children with ASD—as well as previously studied mutations seen in babies with infantile seizures—would impact the signaling properties of brain cells. They found that unlike mutations observed in patients with infantile seizures, which made model neurons more excitable, the mutations seen in children with ASD made it much harder for model neurons to send electrical signals.

"It was remarkable to see how consistently neuronal function was disrupted by these different mutations seen in patients with autism," said Roy Ben-Shalom, PhD, a post-doctoral researcher in the Bender lab who was lead author on the new paper. "The mutations all affected the channel in slightly different ways, but they ended up affecting neurons in almost exactly the same way."

Additional simulations of the effects of NaV1.2 defects on immature versus mature neurons indicated that autism-associated mutations would only have a major impact in the developing brain—since neurons transition away from relying on NaV1.2 channels as they mature—a finding consistent with the idea that the neurological changes that trigger in autism occur early in the womb or before one year of age, as previously proposed by Bender, Sanders, and colleagues.

SCN2A defects could be key to unlocking autism's mysteries

This study represents a first step in understanding how SCN2A mutations lead to autism and developmental delay, which the authors hope will both be immediately helpful to the families of patients with these mutations and also lead to better understanding of the mechanisms of ASD more generally.

"These findings solidify SCN2A's status as one of the most important genes in autism," Bender said. "They give us a place to start exploring exactly how changes in early brain development lead to this condition."

A key next step, the researchers say, is understanding whether the severity of autism and developmental delay can be predicted by the specific SCN2A mutation a patient has, research that will require close collaboration between scientists and families affected by these mutations.

The new study is a perfect example of the power of the cross-disciplinary mindset of the new UCSF Weill Institute for Neuroscience, Sanders said: "Kevin and I came at this question from completely different angles—from genetics and from neurophysiology. When you bring people together from different backgrounds, as the Weill Institute does, you end up finding stories like this: a result as clear as night and day, but one we never would have seen without this collaboration."

SOURCE University of California - San Francisco

Journal Reference:

Roy Ben-Shalom, Caroline M. Keeshen, Kiara N. Berrios, Joon Y. An, Stephan J. Sanders, Kevin J. Bender. Opposing effects on NaV1.2 function underlie differences between SCN2A variants observed in individuals with autism spectrum disorder or infantile seizures. Biological Psychiatry, 2017; DOI: 10.1016/j.biopsych.2017.01.009

Released: 01/17/16

Every Meal Triggers Inflammation

When we eat, we do not just take in nutrients—we also consume a significant quantity of bacteria. The body is faced with the challenge of simultaneously distributing the ingested glucose and fighting these bacteria. This triggers an inflammatory response that activates the immune systems of healthy individuals and has a protective effect, as doctors from the University and the University Hospital Basel have proven for the first time. In overweight individuals, however, this inflammatory response fails so dramatically that it can lead to diabetes.

It is well known that type 2 diabetes (or adult-onset diabetes) leads to chronic inflammation with a range of negative impacts. A number of clinical studies have therefore treated diabetes by impeding the over-production of a substance involved in this process, Interleukin-1beta (IL-1beta). In diabetes patients, this messenger substance triggers chronic inflammation and causes insulin-producing beta cells to die off.

Activation of the immune system

This inflammation does have some positive aspects, however, as was recently reported in the journal Nature Immunology by researchers from the Department of Biomedicine at the University and the University Hospital Basel. In healthy individuals, short-term inflammatory responses play an important role in sugar uptake and the activation of the immune system.

In their work, Professor Marc Donath, Head of the Department of Endocrinology, Diabetes and Metabolism at the University Hospital Basel and his research team demonstrate that the number of macrophages (a type of immune cell) around the intestines increases during meal times. These so-called "scavenger cells" produce the messenger substance IL-1beta in varying amounts, depending on the concentration of glucose in the blood. This, in turn, stimulates insulin production in pancreatic beta cells. The insulin then causes the macrophages to increase IL-1beta production. Insulin and IL-1beta work together to regulate blood sugar levels, while the messenger substance IL-1beta ensures that the immune system is supplied with glucose and thus remains active.

Bacteria and nutrients

According to the researchers, this mechanism of the metabolism and immune system is dependent on the bacteria and nutrients that are ingested during meals. With sufficient nutrients, the immune system is able to adequately combat foreign bacteria. Conversely, when there is a lack of nutrients, the few remaining calories must be conserved for important life functions at the expense of an immune response. This may go some way towards explaining why infectious diseases occur more frequently in times of famine.

Story Source Universität Basel

Journal Reference

Erez Dror, Elise Dalmas, Daniel T Meier, Stephan Wueest, Julien Thévenet, Constanze Thienel, Katharina Timper, Thierry M Nordmann, Shuyang Traub, Friederike Schulze, Flurin Item, David Vallois, Francois Pattou, Julie Kerr-Conte, Vanessa Lavallard, Thierry Berney, Bernard Thorens, Daniel Konrad, Marianne Böni-Schnetzler & Marc Y Donath. Postprandial macrophage-derived IL-1β stimulates insulin and both synergistically promote glucose disposal and inflammation. Nature Immunology, January 2017 DOI: 10.1038/ni.3659

Released: 01/17/16

New Urine Test Can Quickly Detect Whether a Person Has a Healthy Diet

Scientists have developed a urine test that measures the health of a person's diet.

The five-minute test measures biological markers in urine created by the breakdown of foods such as red meat, chicken, fish, and fruit and vegetables.

The analysis, developed by researchers from Imperial College London, Newcastle University, and Aberystwyth University, also gives an indication of how much fat, sugar, fiber, and protein a person has eaten.

Although the work is at an early stage, the team hope that with future development the test will be able to track patients' diets. It could even be used in weight loss programs to monitor food intake.

Evidence suggests people inaccurately record their own diets, and under-report unhealthy food while over-reporting fruit and vegetable intake—and that the likelihood of inaccuracies in food diaries increases if a person is overweight or obese.

Professor Gary Frost, senior author of the study from the Department of Medicine at Imperial said: "A major weakness in all nutrition and diet studies is that we have no true measure of what people eat. We rely solely on people keeping logs of their daily diets—but studies suggest around 60 percent of people misreport what they eat to some extent. This test could be the first independent indicator of the quality of a person's diet—and what they are really eating."

In study, published in the journal Lancet Diabetes and Endocrinology and conducted at the MRC-NIHR National Phenome Centre, the researchers asked 19 volunteers to follow four different diets, ranging from very healthy to very unhealthy (see notes to editors). These were formulated using World Health Organization dietary guidelines, which advise on the best diets to prevent conditions such as obesity, diabetes, and heart disease.

The volunteers strictly followed these diets for three days while in a London research facility, throughout which the scientists collected urine samples in the morning, afternoon, and evening.

The research team then assessed the urine for hundreds of compounds, called metabolites, produced when certain foods are broken down in the body.

These included compounds that indicate red meat, chicken, fish, fruit, and vegetables, as well as giving a picture of the amount of protein, fat, fiber, and sugar eaten. They also included compounds that point to specific foods such as citrus fruits, grapes, and green leafy vegetables.

From this information the researchers were able to develop a urine metabolite profile that indicated a healthy, balanced diet with a good intake of fruit and vegetables. The idea is this 'healthy diet' profile could be compared to the diet profile from an individual's urine, to provide an instant indicator of whether they are eating healthily.

The scientists then tested the accuracy of the test on data from a previous study. This included 225 UK volunteers as well as 66 people from Denmark. All of the volunteers had provided urine samples, and kept information on their daily diets.

Analysis of these urine samples enabled the researchers in the current study to accurately predict the diet of the 291 volunteers.

Professor John Mathers, co-author from the Human Nutrition Research Centre at Newcastle University, said: "For the first time, this research offers an objective way of assessing the overall healthiness of people's diets without all the hassles, biases, and errors of recording what they've eaten."

The team now hope to refine the technology by testing it on larger numbers of people. They also need to further assess the accuracy of the test on an average person's diet, outside of a research setting.

Dr Isabel Garcia-Perez, co-author from the Faculty of Medicine at Imperial explained: "We need to develop the test further so we can monitor the diet based on a single urine sample, as well as increase the sensitivity. This will eventually provide a tool for personalized dietary monitoring to help maintain a healthy lifestyle. We're not at the stage yet where the test can tell us a person ate 15 chips yesterday and two sausages, but it's on the way."

The team added the technology may one day be used alongside weight loss programs, as well as patient rehabilitation, for instance to help heart attack patients follow a healthy diet.

Professor Elaine Holmes, co-author from the Department of Surgery and Cancer at Imperial added: "We are hoping to make this test available to the public within the next two years. The idea would be to collect a urine sample at home and deliver it to a local center for analysis. We envisage the tool being used by dieticians to help guide their patients' dietary needs, or even by individuals who are interested in finding out more about the relationship between diet and their health."

Dr Des Walsh, head of population and systems medicine at the Medical Research Council said: "Though this research is still in its early stages, it's grappling with essential methods in food and diet studies where advances are really needed. Measuring what we eat and drink more accurately will widen the benefits of nutrition research, developing better evidence-based interventions to improve individual's health and reduce obesity."

Professor John Draper, co-author from Aberystwyth University, added: "The future challenge is to apply the technology developed in this laboratory study in a community setting and objectively monitor diet in the home. The teams in Aberystwyth and Newcastle have been doing just this and the results are looking very promising."

SOURCE Imperial College London

Journal Reference

Isabel Garcia-Perez, Joram M Posma, Rachel Gibson, Edward S Chambers, Tue H Hansen, Henrik Vestergaard, Torben Hansen, Manfred Beckmann, Oluf Pedersen, Paul Elliott, Jeremiah Stamler, Jeremy K Nicholson, John Draper, John C Mathers, Elaine Holmes, Gary Frost. Objective assessment of dietary patterns by use of metabolic phenotyping: a randomised, controlled, crossover trial. The Lancet Diabetes & Endocrinology, 2017; DOI: 10.1016/S2213-8587(16)30419-3

Released: 01/12/16

Governor Signs Licensure Bill in Massachusetts

A major victory for naturopathic medicine and a major milestone in health care was achieved yesterday—Gov. Charlie Baker, (R-MA), signed a bill, effectively immediately, to license Naturopathic Doctors in the state. This unprecedented move was 20 years in the making, and ensures the safe practice of naturopathic medicine in Massachusetts. This is the second state to gain licensure within a year's span. Pennsylvania achieved regulation in November, 2016.

Congratulations and appreciation goes to the Massachusetts Society of Naturopathic Physicians (MSND).

"I, along with my colleagues and friends at the MSND are thrilled to join the ranks of health care providers in the state. We look forward to bringing naturopathic medicine to the residents of Massachusetts," says Amy Rothenberg, ND, president, MSND. "I applaud Gov. Baker and the legislative process that studied and vetted this profession for over 20 years and came to understand the unique role that licensed Naturopathic Doctors can play in the state. This bill allows the people of Massachusetts to access well-educated and trained Naturopathic Doctors for their expertise in both preventive medicine and natural integrative care. We are thrilled at the passage of this legislation."

"While we celebrate licensure wins in every state, we're overjoyed that residents in Massachusetts have the ability to now visit a licensed Naturopathic Doctor," said Jaclyn Chasse, ND, president, AANP. "This also is a personal win for me as a Massachusetts resident. It's hard to convey in words the enthusiasm and triumph I feel witnessing the strong advocacy efforts that Naturopathic Doctors have poured into obtaining licensure in the state."

"This is what we're here for; to help states obtain licensure," commented Ryan Cliche, executive director, AANP. "We are beyond excited at the results of the hard work and dedication shown by state leaders and its members. The AANP is thankful to Dr. Rothenberg, the MSND, AANP members, and the naturopathic community for coming together to help push this bill over the finish line. Cliche added, "The AANP and MSND have advocated for licensure in Massachusetts for the better part of 20 years and this effort will help other states also seeking licensure."

Released: 01/12/16

IFM Announces Collaboration with Dale Breseden's MPI Cognition

The Institute for Functional Medicine (IFM) is pleased to announce a new collaboration with MPI Cognition, founded by Dale Bredesen, MD, to train clinicians in the treatment of mild cognitive impairment and early Alzheimer’s disease. The program is titled Reversing Cognitive Decline: Advanced Clinical Training in Treating MCI and Early Alzheimer’s Disease, and the first offering will be March 11-12, 2017, in Huntington Beach, CA.

Alzheimer’s disease is the leading cause of dementia worldwide and is poised to become a major public health crisis. To date, there are few single treatments, pharmaceutical or otherwise, that can help with this degenerative condition. Dr. Bredesen’s research has demonstrated that a multimodal “programmatic” approach can be successful in the treatment of early stage Alzheimer’s disease and mild cognitive impairment (MCI)¹. This two-day CME program details this exciting new approach to these previously untreatable conditions.

“We are excited to partner with IFM to present this novel clinical training, since Functional Medicine is uniquely suited to identify and address the numerous issues that drive cognitive decline. There are dozens of drivers that all turn out to be critical for potential contributions to cognitive decline, and with the systems biology approach taken by Functional Medicine, identifying and treating them is intrinsic to the process,” states Dr. Bredesen.

IFM’s Chief Executive Officer, Laurie Hofmann, MPH, remarks, “IFM is pleased to be the partner of MPI for this advanced clinical training. This partnership provides Functional Medicine clinicians with the unique opportunity to complete a comprehensive coursework on the latest clinical applications of neuroscience in the treatment of these conditions.”

Robert Luby, MD, IFM’s Executive Director of Medical Education explains, “At the Reversing Cognitive Decline program, clinicians will learn how to apply a patient-specific approach for reversing cognitive decline in the early stages. Then at IFM’s 2017 Annual International Conference in June, practitioners will learn the cutting edge science and clinical techniques that leverage neuroplasticity to prevent and reverse neurodegeneration across a wide range of applications."

This will be the first in a series of trainings offered by IFM and MPI in 2017. Priority registration will be given to advanced Functional Medicine clinicians and clinicians who specialize in these specific conditions. Other clinicians are encouraged to apply should additional program seats become available. To learn more about this program, please visit IFM.org/RCD.

MPI Cognition provides advanced medical information and algorithms that assist individuals and practitioners to prevent and reverse cognitive decline. For more information about MPI Cognition, please visit mpi-cognition.com.

References

Bredesen, Aging 2014; Bredesen et al., Aging 2016.

SOURCE The Institute for Functional Medicine (IFM)

Released: 01/05/16

New Study Finds EPA and DHA Omega-3s Lower Risk of Coronary Heart Disease

EPA and DHA omega-3s reduce the risk of coronary heart disease (CHD), according to results of a new, comprehensive meta-analysis published in the Mayo Clinic Proceedings and sponsored by the Global Organization for EPA and DHA Omega-3s (GOED). Among randomized controlled trials (RCTs), there was a statistically significant reduction in CHD risk in higher risk populations, including:

16 percent in those with high triglycerides and 14 percent in those with high LDL cholesterol.

A non-statistically significant 6 percent risk reduction among all populations in RCTs, a finding supported by a statistically significant 18 percent reduced risk of CHD among prospective cohort studies.

"What makes this paper unique is that it looked at the effects of EPA and DHA on coronary heart disease specifically, which is an important nuance considering coronary heart disease accounts for half of all cardiovascular deaths in the U.S.," said Dr. Dominik Alexander, lead author and Principal Epidemiologist for EpidStat. "The 6 percent reduced risk among RCTs, coupled with an 18 percent risk reduction in prospective cohort studies—which tend to include more real-life dietary scenarios over longer periods—tell a compelling story about the importance of EPA and DHA omega-3s for cardiovascular health."

Additional study details include:

The study reviewed 18 randomized controlled trials (RCTs) and 16 prospective cohort studies, with 93,000 and 732,000 subjects, respectively.

The study examined outcomes such as myocardial infarction, sudden cardiac death, and coronary death.

The study compared the results of RCTs, which explore interventions under strict clinical conditions, to those of prospective cohort studies that are observational, and followed larger populations for longer periods of time.

"There are important public health implications related to reducing the risk of coronary heart disease, and therefore we are encouraged by the results of this comprehensive analysis," said Dr. Harry Rice, Vice President of Regulatory and Scientific Affairs for GOED. "It's also important that the observed risk reductions were even stronger in patient populations with elevated triglycerides and LDL cholesterol levels, two risk factors that affect more than one quarter of the American population."

"The results confirm that increasing omega-3s is a healthy lifestyle intervention that can contribute towards reductions in CHD risk," added Adam Ismail, Executive Director of GOED. "Remember that increasing omega-3 intakes is basically just improving the quality of one's diet slightly, like reducing the amount of sodium or increasing your dietary fiber. It is a simple, inexpensive, and achievable change that most consumers need to make to optimize their health."

An accompanying editorial in Mayo Clinic Proceedings also acknowledges the importance of the study. "The meta-analyses of Alexander and colleagues suggests that omega-3 fatty acid intake may reduce risk of adverse CHD events, especially among people with elevated levels of TGs or LDL-C.…omega-3 fatty acid intake of at least 1 gram of EPA+DHA per day, either from seafood or supplementation (as recommended by the American Heart Association), continues to be a reasonable strategy," said the authors.

Study authors did point out that further clinical trials looking specifically at CHD outcomes may continue to provide a better understanding of the promising beneficial relationship between EPA/DHA and CHD risk. Current RCTs have varying durations, different baseline CHD status for study participants, and utilize several methods for patient selection and randomization. Future studies should:

Increase patient populations to account for dropout rates in longer trials.

Extensively detail how subjects are diagnosed to create uniform diagnostic criteria.

Be appropriately powered to detect an effect in current clinical conditions.

Measure baseline omega-3 intake or status of study participants to determine the extent to which it confounds results.

The study was supported by a grant from GOED, which played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

SOURCE Global Organization for EPA and DHA Omega-3s

Released: 01/04/16

The Institute For Functional Medicine Announces Collaboration With Dale Bredesen's MPI Cognition

Alzheimer's disease is the leading cause of dementia worldwide and is poised to become a major public health crisis. To date, there are few single treatments, pharmaceutical or otherwise, that can help with this degenerative condition. Dr. Bredesen's research has demonstrated that a multimodal "programmatic" approach can be successful in the treatment of early stage Alzheimer's disease and mild cognitive impairment (MCI)¹. This two-day CME program details this exciting new approach to these previously untreatable conditions.

"We are excited to partner with IFM to present this novel clinical training, since Functional Medicine is uniquely suited to identify and address the numerous issues that drive cognitive decline. There are dozens of drivers that all turn out to be critical for potential contributions to cognitive decline, and with the systems biology approach taken by Functional Medicine, identifying and treating them is intrinsic to the process," states Dr. Bredesen.

IFM's Chief Executive Officer, Laurie Hofmann, MPH, remarks, "IFM is pleased to be the partner of MPI for this advanced clinical training. This partnership provides Functional Medicine clinicians with the unique opportunity to complete a comprehensive coursework on the latest clinical applications of neuroscience in the treatment of these conditions."

Robert Luby, MD, IFM's Executive Director of Medical Education explains, "At the Reversing Cognitive Decline program, clinicians will learn how to apply a patient-specific approach for reversing cognitive decline in the early stages. Then at IFM's 2017 Annual International Conference in June, practitioners will learn the cutting edge science and clinical techniques that leverage neuroplasticity to prevent and reverse neurodegeneration across a wide range of applications."

References
1. Bredesen, Aging 2014; Bredesen et al., Aging 2016.