219 CNO Report 30 NOV 2015


clip_image002CNO Report 219

Release Date 30 NOV 2015

Draft Report Compiled by

Ralph Turchiano




In This Issue:

1.       Moderate coffee drinking may lower risk of premature death

2.       Endurance athletes who ‘go against the grain’ become incredible fat-burners

3.       How to eliminate pain tied to tooth decay

4.       Coconut oil shows promise in the prevention of deadly bloodstream infection

5.       Light therapy effective for depression: UBC study

6.       Safe form of estrogen helped multiple sclerosis patients avoid relapses in UCLA led clinical trial


Public Release: 16-Nov-2015

Moderate coffee drinking may lower risk of premature death


Boston, MA – People who drink about three to five cups of coffee a day may be less likely to die prematurely from some illnesses than those who don’t drink or drink less coffee, according to a new study by Harvard T.H. Chan School of Public Health researchers and colleagues. Drinkers of both caffeinated and decaffeinated coffee saw benefits, including a lower risk of death from cardiovascular disease, neurological diseases, type 2 diabetes, and suicide.

“Bioactive compounds in coffee reduce insulin resistance and systematic inflammation,” said first author Ming Ding, a doctoral student in the Department of Nutrition. “That could explain some of our findings. However, more studies are needed to investigate the biological mechanisms producing these effects.”

The study will appear online in Circulation on November 16, 2015.

Researchers analyzed health data gathered from participants in three large ongoing studies: 74,890 women in the Nurses’ Health Study; 93,054 women in the Nurses’ Health Study 2; and 40,557 men in the Health Professionals Follow-up Study. Coffee drinking was assessed using validated food questionnaires every four years over about 30 years. During the study period, 19,524 women and 12,432 men died from a range of causes.

In the whole study population, moderate coffee consumption was associated with reduced risk of death from cardiovascular disease, diabetes, neurological diseases such as Parkinson’s disease, and suicide. Coffee consumption was not associated with cancer deaths. The analyses took into consideration potential confounding factors such as smoking, body mass index, physical activity, alcohol consumption, and other dietary factors.

“This study provides further evidence that moderate consumption of coffee may confer health benefits in terms of reducing premature death due to several diseases,” said senior author Frank Hu, professor of nutrition and epidemiology. “These data support the 2015 Dietary Guidelines Advisory Report that concluded that ‘moderate coffee consumption can be incorporated into a healthy dietary pattern.'”

Public Release: 17-Nov-2015

Endurance athletes who ‘go against the grain’ become incredible fat-burners

Elite performance on a diet with minimal carbs represents a paradigm shift in sports nutrition

COLUMBUS, Ohio – Elite endurance athletes who eat very few carbohydrates burned more than twice as much fat as high-carb athletes during maximum exertion and prolonged exercise in a new study – the highest fat-burning rates under these conditions ever seen by researchers.

The study, the first to profile elite athletes habitually eating very low-carbohydrate diets, involved 20 ultra-endurance runners age 21-45 who were top competitors in running events of 50 kilometers (31 miles) or more.

“These low-carb athletes were spectacular fat burners,” said lead researcher Jeff Volek, professor of human sciences at The Ohio State University. “Their peak fat burning and the amount of fat burned while running for three hours on a treadmill was dramatically higher than what the high-carb athletes were able to burn.

“This represents a real paradigm shift in sports nutrition, and I don’t use that term lightly,” he said. “Maybe we’ve got it all backwards and we need to re-examine everything we’ve been telling athletes for the last 40 years about loading up on carbs. Clearly it’s not as straightforward as we used to think.”

The 10 low-carb athletes ate a diet consisting of 10 percent carbs, 19 percent protein and 70 percent fat. Ten high-carb athletes got more than half their calories from carbs, with a ratio of 59 percent carbs, 14 percent protein and 25 percent fat.

In all other respects, the athletes were similar: elite status, age, performance, training history and maximum oxygen capacity. “They all had the same engine, so to speak,” Volek said.

Scientists measured gas exchange repeatedly during a test determining the athletes’ maximum oxygen intake to gauge carb- and fat-burning rates. On average, the low-carb runners’ peak fat-burning rate was 2.3-fold higher than the rate for high-carb athletes: 1.5 versus .67 grams per minute.

The research is published online in the journal Metabolism: Clinical and Experimental.

Volek has been studying the effects of low-carb eating – and ketogenic diets specifically – for years, particularly in the context of obesity and diabetes. But he has always been interested in how such a diet might augment physical performance and recovery. Ketogenic diets are those that reduce carbohydrates enough to allow the body to access its fat stores as the primary source of fuel. Lowering carbs and increasing fat intake leads to the conversion of fat into ketones, molecules that can be used by cells throughout the body, especially the brain, as an alternative to glucose.

It can take weeks or longer for the human body to fully adjust to a ketogenic diet, so the low-carb athletes in the study were eligible only if they had been restricting carbs for at least six months. Their average time on a ketogenic diet was 20 months.

“The goal was to characterize their metabolic response to a standardized exercise test,” Volek said. “This is the first time we’ve had the opportunity to peek under the hood at what a long-term low-carb, fat-adapted athlete looks like.”

Over two days, researchers subjected the athletes to tests to determine peak fat burning during a brief high-intensity workout and metabolic characteristics during prolonged exercise.

On day one, the athletes ran on a treadmill to determine their maximum oxygen consumption and peak fat-burning rates. On day two, the athletes ran on a treadmill for three hours at an intensity equal to 64 percent of their maximum oxygen capacity. During this test, they drank water but took in no nutrition – before the run, athletes consumed either low- or high-carb nutrition shakes consisting of about 340 calories.

During the endurance run, the two groups did not differ significantly in oxygen consumption, ratings of perceived exertion or calorie expenditure. However, fat-burning rates during prolonged exercise were again about twice as high in the low-carb athletes, and the average contribution of fat during exercise in the low-carb and high-carb groups was 88 percent and 56 percent, respectively.

“The low-carb guys go beyond what you can achieve with good genetics and extensive training,” Volek said. “The high-carb runners were very healthy, and were awesome fat burners by conventional standards – yet their peak fat burning is less than half that of endurance athletes eating low-carb diets. This shows that we have far underestimated how much fat humans can burn. There is a large reserve capacity that can only be tapped if carbs are restricted.

“So far, this has been a grassroots movement. Athletes on their own have been going against the grain, so to speak, and experiencing a lot of success. I think it’s mainly taken off in the ultra-endurance world because the self-perceived benefits are so high there, but many other athletes competing in a variety of events and various sports teams are experimenting with carb restricting,” Volek said.

Another key finding: Despite their low intake of carbs, these fat-burning athletes had normal muscle glycogen levels – the storage form of carbohydrates – at rest. They also broke down roughly the same level of glycogen as the high-carb runners during the long run, and synthesized the same amount of glycogen in their muscles during recovery as the high-carb athletes.

“This was completely unexpected, but now that we have observed it we have some novel ideas why this is the case. We can only speculate on the mechanism behind it,” Volek said.

Muscle glycogen was discovered in the 1960s to be a critical energy source for athletes, which led to decades of emphasis on high-carb diets to support energy needs during intense exercise. But Volek said the body has an elegant system to support glycogen levels even when carbohydrates are limited in the diet.

“The blue print for becoming ‘fat- or keto-adapted’ is hard wired into our genetic code. However, traditional ‘healthy’ diets with carbohydrates as the dominant nutrient prevent this alternative metabolic operating system from ever booting up.

“Restricting carbs allows the program to reboot and enable many athletes to achieve improved levels of health and performance” he said.

Public Release: 16-Nov-2015

How to eliminate pain tied to tooth decay

University of Southern California

Dual discoveries at USC propose a promising method to regrow nonliving hard tissue, lessening or even eliminating pain associated with tooth decay, which the National Institutes of Health calls the most prevalent chronic disease.

Janet Moradian-Oldak, a professor at the Herman Ostrow School of Dentistry of USC, has investigated methods to regrow tooth enamel for the past two decades. The process is especially tricky because unlike bone, mature enamel cannot rejuvenate. Tooth enamel is a nonliving tissue.

The a-ha moment came Oct. 22 when, in collaboration with lead author Sauma Prajapati of USC and other colleagues, she published a study in the Biomaterials journal saying matrix metalloproteinase-20, an enzyme found only in teeth, chops up amelogenin proteins, which facilitate organized enamel crystal formation. MMP-20 clears the way for hard material to usurp vacated space.

Her team is the first to define the function of an enzyme for preventing protein occlusion inside a crystal, she said.

“MMP-20 is released at a very early stage of enamel formation,” said Moradian-Oldak, the study’s senior author. “MMP-20 chops up proteins during the crystallization of enamel. Together with other enzymes, it gets rid of ‘sludge’ so the enamel making cells in the body can add more mineral and make enamel, the hardest bioceramic in the human body.”

Dental restoration

Moradian-Oldak will couple the MMP-20 discovery with another study published Nov. 2 in the Journal of Biomedical Engineering and Informatics, which concluded an amelogenin-chitosan hydrogel could repair early tooth decay by growing an enamel-like layer that reduces lesions by up to 70 percent.

“Recognizing MMP-20’s function in biomineralization is one of the first steps to learning how dental enamel forms in nature,” said Qichao Ruan, lead author of the hydrogel study and a postdoctoral research associate in the Center for Craniofacial Molecular Biology at USC. “The findings regarding MMP-20 not only help us to further understand the mechanisms of enamel formation but [they] also can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair.”

The Food and Drug Administration has not yet approved any type of enamel regrowing gel. USC is in pre-clinical trials. Moradian-Oldak said one day people may be able to use an overnight mouth guard or teeth strips saturated with hydrogel to regrow enamel-like substances and reduce teeth sensitivity.

Finding the right fix

Products such as toothpaste and mouthwash containing fluoride and casein phosphopeptide-amorphous calcium phosphate promote remineralization of initial enamel lesions; however, they need to be used regularly and are more of a tire patch than a real solution, Moradian-Oldak said. It plugs up the problem so people don’t feel pain. The gel, however, fills the cracks and holes with an enamel-like substance.

In the United States, 92 percent of adults aged 20 to 64 have had dental decay in their permanent teeth, Moradian-Oldak said. Grinding teeth at night, gum recession and the disappearance of enamel over a lifetime due to demineralizing acidic food and drink are all common problems people everywhere face.

When tested in an environment that mimics an oral cavity’s biochemical processes, the gel created a robust attachment, eliminating the threat of secondary cavities in the same spot, Ruan said. The gel could be more effective than traditional crowns, whose adhesion weakens over time, he added.

“Besides biocompatibility and biodegradability, the gel has unique antimicrobial and adhesion properties that are important for dental applications,” Ruan said.

Public Release: 18-Nov-2015

Coconut oil shows promise in the prevention of deadly bloodstream infection

American Society for Microbiology

Washington, DC – November 18, 2015 – Coconut oil may be effective at combating infection with Candida albicans, according to a study published November 18th in the American Society for Microbiology’s new open access journal mSphere. The study found that coconut oil consumption reduced gastrointestinal colonization by C. albicans in mice.

“We found that diet can be an effective way to reduce the amount of Candida in the mouse,” said lead study author Carol Kumamoto, PhD, professor of molecular biology and microbiology, Tufts University School of Medicine. “The extension of this finding to the human population is something that needs to be addressed in the future.”

C. albicans is part of the normal gut microbiome of humans and some animals. In immunocompromised individuals and older adults, however, C. albicans can leave the gut, enter the bloodstream, and cause invasive infection affecting organs including the kidneys, liver, spleen, lungs, brain, and heart valves. Roughly 40% to 50% of individuals who have systemic C. albicans infection will die from it. “People who get this disease are very sick and generally in the hospital. We are talking about cancer patients, people who receive transplants, premature infants, intensive care unit patients with catheters, and sometimes the elderly,” said Dr. Kumamoto. “Candida is one of the most common causes of bloodstream infections in hospitalized patients.”

Clinicians can use antifungal drugs to prevent C. albicans infection in some high-risk patients, but this isn’t ideal because it can contribute to the emergence of drug resistant strains. Previous research has shown that changes to diet, including changes in the amount and type of fat, can alter gastrointestinal microbiota. In vitro studies have shown that coconut oil, in particular, has antifungal properties.

In a new NIH-funded study, Dr. Kumamoto and Alice H Lichtenstein, D.Sc., director of the Cardiovascular Nutrition Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University designed high fat diets containing coconut oil, beef tallow, soybean oil or a standard diet. Mice were fed these diets for 14 days prior to inoculation with C. albicans and 21 days following. At 21 days post inoculation, gastrointestinal colonization with C. albicans was significantly lower in the stomach contents of mice fed the coconut oil diet than mice fed the beef tallow diet (P<0.0001), soybean oil diet (P<0.0001), or the standard diet (P<0.0001). “When you compared a mouse on a high fat diet that contained either beef fat or soy bean oil to mice eating coconut oil, there was about a ten-fold drop in colonization,” said Dr. Kumamoto.

In another experiment, the researchers switched mice on the beef fat diet to the coconut oil diet. “Four days after the change in diet, the colonization changed so it looked almost exactly like what you saw in a mouse who had been on coconut oil the entire time,” said Dr. Kumamoto.

“There are two directions that we would like to take with this research now,” said Dr. Kumamoto. “One of them is finding out the mechanism of how this works. That is a big question we would like to answer. The second question is whether this can have any impact on humans.” The researchers are in discussion with Joseph Bliss, M.D., Ph.D., at Women and Infants Hospital of Rhode Island to launch a clinical trial testing coconut oil in hospitalized infants at high-risk for developing systemic candidiasis.

Public Release: 18-Nov-2015

Light therapy effective for depression: UBC study

University of British Columbia

New research finds that light therapy can treat non-seasonal depression and improve the overall wellbeing of people suffering from the disease.

“These results are very exciting because light therapy is inexpensive, easy to access and use, and comes with few side effects,” said Dr. Raymond Lam, a UBC professor and psychiatrist at the Djavad Mowafaghian Centre for Brain Health, a partnership between UBC and Vancouver Coastal Health. “Patients can easily use light therapy along with other treatments such as antidepressants and psychotherapy.”

The research, published today in JAMA Psychiatry, is the first placebo-controlled trial that shows that light therapy is an effective treatment for depression that is not brought on by seasonal affective disorder.

Lam and his colleagues followed 122 patients and evaluated whether light therapy improved the mood of patients when it was used both with and without the commonly prescribed antidepressant fluoxetine. Light therapy involved 30 minutes of exposure to a fluorescent light box soon after waking up every day for eight weeks. Some study participants were given placebo pills and placebo devices instead of the real therapies. The researchers found that light therapy helped many patients and provided the most benefit to those who were also taking antidepressants.

Depression affects one in 20 people and is among the leading causes of disability worldwide.

Depression can cause significant problems in family and personal relationships, work attendance and productivity, and overall quality of life. It is also associated with an increased risk of death.

According to the researchers, medications are effective for treating depression but only work in about 60 per cent of cases.

“More and more people are seeking help because there is less stigma about having depression,” said Lam. “It’s important to find new treatments because our current therapies don’t work for everyone. Our findings should help to improve the lives of people with depression.”


This research was funded by the Canadian Institutes of Health Research (CIHR) and involved patients from Vancouver, Toronto, Calgary and Saint John.

Public Release: 30-Nov-2015

Safe form of estrogen helped multiple sclerosis patients avoid relapses in UCLA led clinical trial

University of California – Los Angeles Health Sciences

Taking the pregnancy hormone estriol along with their conventional medications helped patients with relapsing-remitting multiple sclerosis (RRMS) avoid relapses, according to results of a Phase II randomized, placebo-controlled study led by UCLA researchers.

The study, published online in Lancet Neurology, was truly translational. The UCLA team took observations from the bedside, tested them in the laboratory and took those findings back again to patients in clinical trials, said the study’s lead author Dr. Rhonda Voskuhl, professor in the UCLA Department of Neurology and director of UCLA’s Multiple Sclerosis Program.

It’s long been observed that during the second half of pregnancy, women with RRMS have reduced relapses, but the reason was unclear. It is also during this period that the fetal placenta produces estriol, increasing the hormone levels in the blood. This protection during pregnancy occurs not only in MS, but also in other autoimmune diseases such as psoriasis and rheumatoid arthritis.

Voskuhl took this information to the lab. She hypothesized that increased estriol in the blood might play a role in suppressing a woman’s immune system so that the fetus is not rejected as being foreign, having half of the father’s proteins. This temporary suppression of the immune system would be good for pregnant mothers with autoimmune diseases. Her team found that treatment with estriol was protective in the MS model. That led to a successful pilot clinical trial in 2002 at UCLA and then the Phase II trial, launched in 2007 at UCLA and 15 other sites across the United States.

“The beauty of estriol is that it is not a shot and can be taken in pill form, and also that it’s not a new drug. It has decades of safety behind it,” said Voskuhl, who holds the Jack H. Skirball Chair for Multiple Sclerosis in the UCLA Department of Neurology. “Also, current MS treatments are very complex to manufacture. These findings hopefully will pave the way for oral, safe treatments that are more widely accessible, since estriol is simple and naturally occurring.”

Multiple sclerosis is an autoimmune disease of the central nervous system where immune cells from the blood attack the tissue surrounding the brain’s nerve fibers. Called myelin, this tissue is like the insulation wrapped around an electrical wire. When the myelin is damaged, it interferes with the ability of the nerves to send signals to and from the brain, resulting in symptoms including cognitive problems, difficulty with walking, poor vision and other disabilities.

In RRMS, there are clear episodes of inflammatory activity, or relapses. During a relapse, there are new or worsening symptoms, accompanied by inflammatory lesions in the brain. A relapse can continue anywhere from several days to months. Relapses are usually followed by remission, or improvement. However, some residual symptoms may remain, and after many years people with RRMS often transition to a progressive form of the disease. During the progressive phase, there are no longer relapses, but instead gradual worsening of permanent disabilities and loss of brain volume or atrophy.

In the lab, Voskuhl and her team discovered that estriol potentially provides a one-two punch against the disease, both reducing the ability of immune cells to attack the brain, while also making brain cells more resistant to damage if any immune cells do make it through. Specifically, they showed that estriol treatment improved cognition and prevented atrophy of the cognitive region of the brain. It seems that during pregnancy, estriol can both suppress the immune system and protect the brain, for not only is it important to avoid rejection of the fetus as foreign, it is also critical to protect the developing fetal brain. While these two effects may be designed to protect the fetus, they may also be exactly what the doctor ordered for women with MS.

In 2002, Voskuhl completed the pilot study, in which 10 non-pregnant women with MS were given estriol, yielding a greater than 70 percent drop in inflammatory lesions in the brain within only six months of treatment.

In the Phase II study, researchers enrolled 164 patients, with 83 allocated to the estriol group and 81 to the placebo group. Both arms continued their conventional medication, injectable glatiramer acetate. The team found that the patients taking estriol had a third to a half as many relapses compared to those taking the placebo, with this improvement occurring over and above that provided by their conventional treatment. In addition, when estriol levels were the highest, there was improved cognitive function and less atrophy of the brain area related to cognition. The treatment was well tolerated during the two years the volunteers took estriol and the only significant side effect was irregular menstruation. To date, there is no FDA approved treatment for MS that improves disabilities.

These two trials are very unique in that neither were funded by a pharmaceutical company. Rather, they were funded by the National Institutes of Health (NIH) and the National Multiple Sclerosis Society, consistent with the new NIH policy that more research should focus on sex differences in disease. Additional major funding was from the Conrad N. Hilton Foundation, whose mission it is to improve the lives of disadvantaged people throughout the world. Synthetic Biologics, Inc., provided estriol and placebo for the multicenter trial and has licensed certain rights from UCLA.

Going forward, Voskuhl hopes to see a Phase III trial conducted to replicate these findings, since this is necessary for FDA approval of estriol for MS. She continues to seek support to advance this as well as other MS research projects.

It is estimated that more than 2.1 million people are affected by MS worldwide. Approximately 85 percent of patients are diagnosed at onset with RRMS, the most common form of MS.