254 CNO REPORT 23 APR 2018

254CNO23APR2018

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CNO Report # 254

Release Date:  23 APR 2018

Draft Report Compiled by

Ralph Turchiano

www.clinicalnews.org

 

 

 

 

In This issue:

1.       Artificial sweetener Splenda could intensify symptoms in those with Crohn’s disease

2.       Study shows omega-3 levels better predictors of death risk than serum cholesterol

3.       Consuming low-calorie sweeteners may predispose overweight individuals to diabetes

4.       High omega-6 levels can protect against premature death

5.       Researchers link dietary supplement DHA to higher fat-free body mass in children

6.       Antioxidants and amino acids could play role in the treatment of psychosis

7.       Study suggests method to boost growth of blood vessels and muscle

8.       Dietary supplement shows promise for reversing cardiovascular aging

9.       New health benefits discovered in berry pigment

10.   The relevance of GABA for diabetes is highlighted in two new studies

11.   Study explores carbohydrates’ impact on head, neck cancers

12.   Regular nut intake linked to lower risk of heart rhythm irregularity (atrial fibrillation)

13.   Raw fruit and vegetables provide better mental health outcomes: Otago research

14.   Novel antioxidant makes old blood vessels seem young again

15.   Study predicts 2018 flu vaccine will have 20 percent efficacy

16.   Growing evidence that probiotics are good for your liver

17.   The bugs in your gut could make you weak in the knees

18.   Could eating moss be good for your gut?

19.   Hemp shows potential for treating ovarian cancer

 

Public Release: 15-Mar-2018

Artificial sweetener Splenda could intensify symptoms in those with Crohn’s disease

Promotes ‘bad’ bacteria and intestinal inflammation; findings may guide dietary habits in human patients

Case Western Reserve University

Credit: CWRU School of Medicine

In a study that has implications for humans with inflammatory diseases, researchers from Case Western Reserve University School of Medicine and colleagues have found that, given over a six-week period, the artificial sweetener sucralose, known by the brand name Splenda, worsens gut inflammation in mice with Crohn’s-like disease, but had no substantive effect on those without the condition. Crohn’s disease is an inflammatory bowel disease of the digestive tract, which can lead to abdominal pain, severe diarrhea, bloody stools, weight loss, and fatigue. About 10-15 percent of human patients report that sweeteners worsen their disease.

The new findings, recently published in Inflammatory Bowel Diseases, revealed increases in the numbers of Proteobacteria, a large phylum [group] of microbes, in the intestines of mice drinking water supplemented with Splenda. Half of the mice studied, belonging to a genetic line that suffers a form of Crohn’s disease were more affected than the remaining half of mice, which belong to a healthy mouse line. Splenda produced intestinal overgrowth of E. coli (a member of the Proteobacteria group) and increased bacterial penetration into the gut wall, but only in Crohn’s disease-like mice.

The researchers also found that Splenda ingestion results in increased myeloperoxidase activity in the intestines of mice with the bowel disease, but not in the healthy mice. Myeloperoxidase is an enzyme in leukocytes (white blood cells) that is effective in killing various microorganisms. The inference is that the increased presence of E. coli intensified the myeloperoxidase activity in the bowel as the body sought to fight off the invader. The findings suggest that consumption of Splenda may increase myeloperoxidase production only in individuals with a pro-inflammatory predisposition, such as Crohn’s disease or other forms of inflammatory bowel disease patients. As part of this process, inflammation and its attendant consequences could exacerbate the symptoms of Crohn’s disease.

“Our findings suggest that patients with Crohn’s disease should think carefully about consuming Splenda or similar products containing sucralose and maltodextrin,” said the study’s lead author, Alex Rodriguez-Palacios, DVM, MSc, DVSc, PhD, assistant professor of medicine at Case Western Reserve School of Medicine. “Several studies have examined the ingredients found in this widely available product, separately. Here, we used Splenda as a means to test the combined effect of the commercial ingredients and used one of the best animal models of ileal Crohn’s disease.” This study demonstrates that the sweetener induces changes in gut bacteria and gut wall immune cell reactivity, which could result in inflammation or disease flare ups in susceptible people. On the other hand, the study suggests that individuals free of intestinal diseases may not need to be overly concerned.”

Splenda, which was introduced in 1998, includes a thought-to-be indigestible artificial sweetener called sucralose and a digestible sweetener called maltodextrin. It is about 600 times as sweet as sugar and has become one of the most popular artificial sweeteners on the market. “This is perhaps the closest we can get to provide experimental evidence that these ingredients together induce biological changes known to cause inflammation which could be harmful over time to susceptible animal subjects,” said Rodriguez-Palacios. “Our next step would be to run experiments directly in patients, but that is more difficult to conduct given the large variability that is inherent to human genetics, microbiome and diet.”

Proteobacteria– the guilty party

Proteobacteria include a wide variety of pathogens, such as E. coli, Salmonella, and Legionellales (which causes Legionnaires’ disease.) A certain amount of these bacteria are normal in the body, and not harmful. Overgrowth, or excessive amounts, contributes to many health problems. Proteobacteria have previously been linked with various intestinal-tract diseases in several species, including humans. Most Proteobacteria have an outer membrane composed of lipopolysaccharides, which when present in the body, generally trigger powerful immune responses, including inflammation. Inflammation is the normal response of the body’s immune system to injuries and invading organisms. During the process of combating the invader [“antigen”], symptoms such as pain, warmth, swelling, and redness can occur. If the invader, such as E. coli, is successfully repelled, the symptoms dissipate. But if the invader is not eradicated from the body, chronic inflammation may develop, or persist, as it is the case in inflammatory bowel diseases.

“Our findings were due solely to the administration of a minor component of the diet,” said the study’s senior author Fabio Cominelli, MD, PhD, professor of medicine, at Case Western Reserve School of Medicine and chief of gastroenterology at UH Cleveland Medical Center. “This suggests that other dietary habits or additives may lead to similar microbiota alterations. For instance, diet emulsifiers used as food additives have also been shown recently to alter the gut microbiota and promote colitis in mice. Other scenarios could put Crohn’s disease patients at risk of having exaggerated inflammation as well. This could include unexpected foodborne bacterial infections which would further recruit myeloperoxidase-containing leukocytes to the intestinal tract and the resultant inflammation.”

In addition to illustrating the experimental role of a sucralose-maltodextrin based artificial sweetener in promoting intestinal dysbiosis [a microbial imbalance] and myeloperoxidase activity, the studies indicate that it might be possible to measure Proteobacteria and myeloperoxidase as simultaneous fecal biomarkers in patients to monitor their gut (disease/health) adjustment to their diets.

Public Release: 15-Mar-2018

Study shows omega-3 levels better predictors of death risk than serum cholesterol

Results showed that the risk for death from any cause was reduced by about 33% comparing in participants with highest omega-3 blood levels

Study shows omega-3 levels are better predictors of risk for death than serum cholesterol

A recent study published in the Journal of Clinical Lipidology looked at the value of measuring blood levels of EPA and DHA omega-3 fatty acids to assess an individual’s risk for developing certain diseases. In this new report from Harris and colleagues, the “Omega-3 Index” (the EPA+DHA content of red blood cell membranes) was measured in 2500 participants in the Offspring cohort of the Framingham Heart Study. (This group is largely made up of the children of the original Framingham study which began in 1948.) The results showed that the risk for death from any cause was reduced by about 33% comparing the lowest Omega-3 Index participants to the highest.

All of the individuals in the present study were free of known cardiovascular disease (CVD) at baseline. The researchers primarily focused on total mortality (death from any cause) as an endpoint, but also tracked death from CVD, cancer and other causes. In addition, they reported the associations between Omega-3 Index levels and a risk for any CVD event – fatal or not, heart attack or stroke. The population was 66 years of age at baseline and there were a few more females than males. The study followed these individuals for disease outcomes until about age 73. The results were statistically adjusted for a wide variety of factors that could influence the outcomes

According to the study, which was funded by the National Institutes of Health (NIH), a higher Omega-3 Index was associated with a lower risk for total CVD events, total coronary heart disease events, and total strokes. The category most strongly associated with the Omega-3 Index was non-CV, non-cancer deaths – deaths from all other causes. This would suggest a wide spectrum of beneficial actions of EPA and DHA in the body that are not just linked with one pathological process (like plaque build up in arteries).

The link between higher omega-3 blood levels and lower risk for death has been reported in at least three other studies, but what was novel about this most recent study from Framingham was a comparison the authors did between serum cholesterol and the Omega-3 Index, two “risk factors” for heart disease. “We all know that the serum cholesterol level is a major risk factor for CHD, and since the latter is a major cause of death in the Western world, it would be reasonable to expect that a high cholesterol level would portend higher risk for premature death,” said lead author Dr. William Harris. “This did not turn out to be the case here. When baseline serum cholesterol levels were substituted for the Omega-3 Index in the same multi-variable models, the former was not significantly associated with any of the tracked outcomes whereas the latter was related to 4 of the 5 outcomes assessed.” Future studies are needed to try to replicate this finding and to determine if it is time to begin including the Omega-3 Index in routine blood screens along with cholesterol and glucose.

Public Release: 18-Mar-2018

Consuming low-calorie sweeteners may predispose overweight individuals to diabetes

The Endocrine Society

CHICAGO–Consumption of low-calorie sweeteners could promote metabolic syndrome and predispose people to prediabetes and diabetes, particularly in individuals with obesity, a new study on human fat-derived stem cells and fat samples suggests. The research results will be presented Sunday, March 18, at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

Metabolic syndrome is a group of risk factors–high blood pressure, high blood sugar, unhealthy cholesterol levels and abdominal fat–that double the risk of blood vessel and heart disease, which can lead to heart attacks and strokes. They increase the risk of diabetes by three to five times.

“Our stem cell-based studies indicate that low-calorie sweeteners promote additional fat accumulation within cells compared with cells not exposed to these substances, in a dose-dependent fashion–meaning that as the dose of sucralose is increased more cells showed increased fat droplet accumulation,” said Sabyasachi Sen, M.D., Associate Professor of Medicine at George Washington University in Washington, D.C. “This most likely occurs by increasing glucose entry into cells through increased activity of genes called glucose transporters.”

In addition to stem cells, the researchers also studied human fat samples collected from individuals with obesity who consumed low-calorie sweeteners. They found similar changes in gene expression in the same genes with increased activity of glucose transporters in both the stem cells and the fat cells, Sen noted.

He noted these findings are of greatest concern for people who have obesity and prediabetes or diabetes, since they are already at heightened risk of heart attacks and strokes. “We think the effect is more pronounced in overweight and obese people rather than their normal weight counterparts because they have more insulin resistance and may have more glucose in their blood,” he said.

Sen and his colleagues tested sucralose, a popular low-calorie sweetener, on stem cells–cells that could change into mature fat, muscle, cartilage or bone cells–taken from human fat tissue. They placed these cells in Petri dishes for 12 days in media that promotes fat production, to mimic an environment that promotes obesity.

At a 0.2-millimolar sucralose dose similar to the concentration found in the blood of people with high consumption of low-calorie sweeteners–equal to four cans of diet soda per day–the researchers said they observed increased expression of genes that are markers of fat production and inflammation.

With this evidence, the investigators then conducted a separate experiment. They analyzed biopsy samples of abdominal fat obtained from 18 subjects who said they consumed low-calorie sweeteners (mainly sucralose and a trace of aspartame, and/or acesulfame potassium).

Four of the subjects were healthy weight, and fourteen had obesity. In the healthy weight subjects, the difference in gene expressions were not significant. However, in the subjects with obesity or overweight, the researchers noted significant evidence of increased glucose (sugar) transport into cells and overexpression of known fat-producing genes, compared with fat biopsy samples from subjects who did not consume low-calorie sweeteners.

Sen previously conducted the same study on a total of eight subjects with similar results. “Because we found the same results with the, larger sample size, we have much more confidence that low-calorie sweeteners are causing metabolic dysfunction,” Sen said.

In a new cell culture study, Sen found that sucralose appears to promote oxygen radical accumulation – a highly reactive particles that can cause disease and inflammation inside cells. These oxygen radicals interfere with cell activity and slow down metabolism, which promotes accumulation of fat in the cell. “This provides another explanation of how sucralose may interfere with metabolism,” he said.

Public Release: 19-Mar-2018

High omega-6 levels can protect against premature death

University of Eastern Finland

Could omega-6 fatty acids protect you against premature death? The answer is yes, according to a new University of Eastern Finland study. While protecting against death, omega-6 fatty acids also keep cardiovascular diseases at bay.

“Linoleic acid is the most common polyunsaturated omega-6 fatty acid. We discovered that the higher the blood linoleic acid level, the smaller the risk of premature death,” says Adjunct Professor Jyrki Virtanen from the University of Eastern Finland, reporting the findings in the American Journal of Clinical Nutrition.

Although omega-6 polyunsaturated fatty acids are known for their beneficial effect on blood cholesterol levels, it has been speculated that they may increase the risk of several chronic diseases by promoting low-grade inflammation, among other things. The reasoning behind this speculation is that in the human body, linoleic acid is converted into arachidonic acid (also an omega-6 fatty acid) which, in turn, is converted into various inflammation-promoting compounds. However, omega-6 fatty acids also increase the production of anti-inflammatory compounds, and this is why it is challenging to determine the associations of dietary factors with the risk of developing disease merely by focusing on their effects on disease risk factors.

Ongoing at the University of Eastern Finland, the Kuopio Ischaemic Heart Disease Risk Factor Study, KIHD, determined the blood fatty acid levels of 2,480 men between 42 and 60 years of age at the onset of the study, in 1984-1989. During an average follow-up of 22 years, 1,143 men died of disease-related causes, and deaths due to an accident or other reasons were excluded from the study.

When the researchers divided the study participants into five different groups based on their blood linoleic acid level, they discovered that the risk of premature death was 43% lower in the group with the highest level, when compared to the group with the lowest level. A more detailed analysis of the causes of death showed that a similar association exists for death due to cardiovascular diseases, as well as for death due to some other reason than cardiovascular diseases or cancer. However, no association was observed for death due to cancer. Similar, although slightly weaker, associations were also observed for the blood arachidonic acid level. Another significant finding of the study is that the outcome is very similar regardless of whether the study participants suffered from cardiovascular diseases, cancer or diabetes at the onset of the study.

The study backs up findings from earlier population-based studies which have linked a higher dietary intake of linoleic acid and a higher blood linoleic acid level to a smaller risk of cardiovascular diseases and type 2 diabetes, without increasing the risk of cancer, for example. The observed association of arachidonic acid with a reduced risk of death is a new finding.

The blood linoleic acid level is determined by a person’s diet, and the main sources of linoleic acid are vegetable oils, plant-based spreads, nuts and seeds. However, a person’s diet will affect his or her blood arachidonic acid level only a little.

Public Release: 21-Mar-2018

Researchers link dietary supplement DHA to higher fat-free body mass in children

University of Kansas

LAWRENCE — University of Kansas researchers have reported that pregnant women who consumed a supplement of DHA (docosahexaenoic acid), a nutrient added to U.S. infant formulas since 2002, tend to have children with higher fat-free body mass at 5 years old.

The Developmental Origins of Health and Disease relates to effects of maternal and early life programming on later health. The findings of the experimental study, presented in the most recent issue of the American Journal of Clinical Nutrition, suggest that improving maternal DHA nutrition has a favorable programming effect on the fetus that influences body composition in early childhood.

“DHA is a nutrient found in the highest concentrations in oily fish such as salmon and tuna, foods many Americans don’t eat a lot of, so they tend to get low intakes,” said Susan Carlson, professor in the Department of Dietetics & Nutrition in the School of Health Professions. “Because U.S. intakes are low and because DHA is highly concentrated in the brain where it increases dramatically in the last trimester of pregnancy and the first two years of life, I have had a long interest in whether more of this nutrient is needed for optimal health during early development. DHA can be delivered to the fetus by increasing maternal intake during pregnancy and to the breast-fed infant by increasing maternal intake during lactation, which increases DHA in mothers’ milk.”

Women with low-risk pregnancies in the Kansas City area were enrolled in the study at KU Medical Center’s Maternal and Child Nutrition and Development Lab between March 2006 and September 2009. Half were randomly assigned to a prenatal DHA supplement of 600 milligrams, and half were given a placebo.

Five years later, children resulting from those pregnancies were tested using the BodPod, which uses air-displacement to determine body fat and fat-free mass. The researchers found the children whose mothers took the DHA supplement during pregnancy had an average of 1.3 pounds more fat-free mass but the same amount of fat at age 5 compared with the placebo group.

“While we don’t know the mechanism for the finding, DHA is an omega-3 fatty acid. We do know that the balance of omega-3 and omega-6 fatty acids early in development can influence the balance of muscle and fat cells,” Carlson said. “The number of muscle fibers is believed to be set by term birth.” Carlson’s co-author, John Colombo, professor of psychology and director of KU’s Life Span Institute, noted the paper makes two important contributions to the field.

“The first contribution is about the effects of DHA,” he said. “We’ve known for a long time that DHA is associated with improvements in visual, cognitive and behavioral development in early life, but these results suggest that DHA may also have a role in promoting a leaner, healthier growth outcome for children.

“The second contribution is actually more profound. If you think about it, our results show the conditions that children experienced during the time that their mothers were pregnant with them are associated with their physical characteristics almost six years later. To me, that’s astonishing — staggering, really. Those of us working in the field of developmental science are seeing results that suggest the prenatal environment and prenatal conditions have meaningful, long-term effects on human development. Quite simply, these results add to that mounting evidence. I think we’ll learn that much more of how we ‘end up’ may be strongly influenced or determined by what happens before we are born.”

The study’s other authors are Brandon Hidaka, Jocelyn Thodosoff, Elizabeth Kerling and Holly Hull of the Department of Dietetics & Nutrition at the University of Kansas Medical Center.

Carlson said the results agreed with another study undertaken in the United Kingdom, and she suggested pregnant women seeking to increase their intake of DHA wouldn’t have to look far to find good sources.

“There are currently many prenatal supplements with DHA,” she said. “They also can increase their intake of oily fish like salmon and tuna.”

Public Release: 22-Mar-2018

Antioxidants and amino acids could play role in the treatment of psychosis

The systematic review involved eight independent clinical trials of nutrient supplementation in 457 young people

NICM, Western Sydney University

A recent scientific paper has revealed that some nutrients found in food may help reduce the symptoms of psychotic illness, when used in the early stages of treatment.

The systematic review, led by Dr. Firth, Research Fellow at NICM Health Research Institute, Western Sydney University and honorary Research Fellow at The University of Manchester, examined if nutrient supplementation could provide effective ‘add on’ treatment for young people with psychosis.

The team brought together data from eight independent clinical trials of nutrient supplementation in 457 young people in the early stages of psychotic illness, such as schizophrenia.

The review is published in Early Intervention in Psychiatry.

Researchers found that certain nutrient supplements, used alongside standard treatment, may improve mental health in young people with psychosis more than standard treatment alone.

The study by Firth and colleagues is the first evaluation of nutrient supplementation trials in ‘first-episode psychosis’ (FEP).

Dr Firth said “Nutrient supplementation in the treatment of mental illness is something which can be surrounded by both cynicism and ‘hype’.

“We conducted this review just to see if there is any ‘real evidence’ if such nutrients can actually help young people with psychosis.

“Certainly, there is early indication that certain nutrients may be beneficial, not to replace standard treatment, but as an ‘add-on’ treatment for some patients.”

One nutrient reviewed was Taurine, an amino-acid found in foods such as shellfish and turkey.

A clinical trial conducted in Melbourne in 121 young patients with psychosis found that 4 grams of Taurine per day reduced psychotic symptoms within just 12 weeks.

Certain antioxidant supplements, such as n-acetyl cysteine and vitamin C, may also be effective – particularly for patients with high levels of ‘oxidative stress’.

Studies on omega-3 supplements showed that although these appear to improve brain health in young people with psychosis, the evidence for actually reducing psychotic symptoms is conflicting.

“We have to be careful to replicate the results of these initial studies before jumping to firm conclusions,” Dr Firth said.

Now, the team are aiming to do just that: launching a new clinical trial in which all of the potentially beneficial nutrients are combined within a single supplement, and provided to young people with psychosis.

He added: “Individual nutrients appear to have moderate effects on mental health, at best.

“A combined nutrient intervention, explicitly designed from the evidence-base in psychosis, may therefore confer larger and more beneficial effects for young people with this condition.

“We will be testing this in Sydney, Australia in 2018, to learn more about the potential role of nutrition in mental health for the future.”

Public Release: 22-Mar-2018

Study suggests method to boost growth of blood vessels and muscle

Activating proteins linked to longevity may help to increase endurance and combat frailty in the elderly

Massachusetts Institute of Technology

 

CAMBRIDGE, MA — As we get older, our endurance declines, in part because our blood vessels lose some of their capacity to deliver oxygen and nutrients to muscle tissue. An MIT-led research team has now found that it can reverse this age-related endurance loss in mice by treating them with a compound that promotes new blood vessel growth.

The study found that the compound, which re-activates longevity-linked proteins called sirtuins, promotes the growth of blood vessels and muscle, boosting the endurance of elderly mice by up to 80 percent.

If the findings translate to humans, this restoration of muscle mass could help to combat some of the effects of age-related frailty, which often lead to osteoporosis and other debilitating conditions.

“We’ll have to see if this plays out in people, but you may actually be able to rescue muscle mass in an aging population by this kind of intervention,” says Leonard Guarente, the Novartis Professor of Biology at MIT and one of the senior authors of the study. “There’s a lot of crosstalk between muscle and bone, so losing muscle mass ultimately can lead to loss of bone, osteoporosis, and frailty, which is a major problem in aging.”

The first author of the paper, which appears in Cell on March 22, is Abhirup Das, a former postdoc in Guarente’s lab who is now at the University of New South Wales in Australia. Other senior authors of the paper are David Sinclair, a professor at Harvard Medical School and the University of New South Wales, and Zolt Arany, a professor at the University of Pennsylvania.

Race against time

In the early 1990s, Guarente discovered that sirtuins, a class of proteins found in nearly all animals, protect against the effects of aging in yeast. Since then, similar effects have been seen in many other organisms.

In their latest study, Guarente and his colleagues decided to explore the role of sirtuins in endothelial cells, which line the inside of blood vessels. To do that, they deleted the gene for SIRT1, which encodes the major mammalian sirtuin, in endothelial cells of mice. They found that at 6 months of age, these mice had reduced capillary density and could run only half as far as normal 6-month-old mice.

The researchers then decided to see what would happen if they boosted sirtuin levels in normal mice as they aged. They treated the mice with a compound called NMN, which is a precursor to NAD, a coenzyme that activates SIRT1. NAD levels normally drop as animals age, which is believed to be caused by a combination of reduced NAD production and faster NAD degradation.

After 18-month-old mice were treated with NMN for two months, their capillary density was restored to levels typically seen in young mice, and they experienced a 56 to 80 percent improvement in endurance. Beneficial effects were also seen in mice up to 32 months of age (comparable to humans in their 80s).

“In normal aging, the number of blood vessels goes down, so you lose the capacity to deliver nutrients and oxygen to tissues like muscle, and that contributes to decline,” Guarente says. “The effect of the precursors that boost NAD is to counteract the decline that occurs with normal aging, to reactivate SIRT1, and to restore function in endothelial cells to give rise to more blood vessels.”

These effects were enhanced when the researchers treated the mice with both NMN and hydrogen sulfide, another sirtuin activator.

Benefits of exercise

The researchers also found that SIRT1 activity in endothelial cells is critical for the beneficial effects of exercise in young mice. In mice, exercise generally stimulates growth of new blood vessels and boosts muscle mass. However, when the researchers knocked out SIRT1 in endothelial cells of 10-month-old mice, then put them on a four-week treadmill running program, they found that the exercise did not produce the same gains seen in normal 10-month-old mice on the same training plan.

If validated in humans, the findings would suggest that boosting sirtuin levels may help older people retain their muscle mass with exercise, Guarente says. Studies in humans have shown that age-related muscle loss can be partially staved off with exercise, especially weight training.

“What this paper would suggest is that you may actually be able to rescue muscle mass in an aging population by this kind of intervention with an NAD precursor,” Guarente says.

In 2014, Guarente started a company called Elysium Health, which sells a dietary supplement containing a different precursor of NAD, known as NR, as well as a compound called pterostilbene, which is an activator of SIRT1.

Public Release: 29-Mar-2018

Dietary supplement shows promise for reversing cardiovascular aging

‘NR’ shown to mimic caloric restriction, boost arterial health

University of Colorado at Boulder

Scientists have long known that restricting calories can fend off physiological signs of aging, with studies in fruit flies, roundworms, rodents and even people showing that chronically slashing intake by about a third can reap myriad health benefits and, in some cases, extend lifespan.

From a public health perspective, that advice would be impractical for many and dangerous for some.

But a new University of Colorado Boulder study published today indicates that when people consume a natural dietary supplement called nicotinomide riboside (NR) daily, it mimics caloric restriction, aka “CR,” kick-starting the same key chemical pathways responsible for its health benefits.

Supplementation also tends to improve blood pressure and arterial health, particularly in those with mild hypertension, the study found.

“This was the first ever study to give this novel compound to humans over a period of time,” said senior author Doug Seals, a professor and researcher in the Department of Integrative Physiology. “We found that it is well tolerated and appears to activate some of the same key biological pathways that calorie restriction does.”

For the study, published in the journal Nature Communications, Seals and lead author Chris Martens, then a postdoctoral fellow at CU Boulder, included 24 lean and healthy men and women ages 55 to 79 from the Boulder area.

Half were given a placebo for six weeks, then took a 500 mg twice-daily dose of nicotinamide riboside (NR) chloride (NIAGEN). The other half took NR for the first six weeks, followed by placebo.

The researchers took blood samples and other physiological measurements at the end of each treatment period.

Participants reported no serious adverse effects.

The researchers found that 1,000 mg daily of NR boosted levels of another compound called nicotinamide adenine dinucleotide (NAD+) by 60 percent. NAD+ is required for activation of enzymes called sirtuins, which are largely credited with the beneficial effects of calorie restriction. It’s involved in a host of metabolic actions throughout the body, but it tends to decline with age.

Research suggests that as an evolutionary survival mechanism, the body conserves NAD+ when subjected to calorie restriction. But only recently have scientists begun to explore the idea of supplementing with so-called “NAD+-precursors” like NR to promote healthy aging.

“The idea is that by supplementing older adults with NR, we are not only restoring something that is lost with aging (NAD+), but we could potentially be ramping up the activity of enzymes responsible for helping protect our bodies from stress,” Martens said.

The new study also found that in 13 participants with elevated blood pressure or stage 1 hypertension (120-139/80-89 mmHg), systolic blood pressure was about 10 points lower after supplementation. A drop of that magnitude could translate to a 25 percent reduction in heart attack risk.

“If this magnitude of systolic blood pressure reduction with NR supplementation is confirmed in a larger clinical trial, such an effect could have broad biomedical implications,” the authors note.

Ultimately, the authors say, such CR-mimicking compounds could provide an additional option–alongside the dietary changes and exercise currently recommended–for people whose blood pressure is not yet high enough to warrant medication but who are still at risk for a heart attack.

They stress that the study was small and “pilot in nature.”

“We are not able to make any definitive claims that this compound is safe or going to be effective for specific segments of the population,” said Martens, now an assistant professor at the University of Delaware. “What this paper provides us with is a really good stepping stone for future work.”

Martens and Seals have applied for a grant to conduct a larger clinical trial looking specifically at the impact of NR supplementation on blood pressure and arterial health. Martens is also launching a separate trial looking at the impact NR has on older adults with mild cognitive impairment, a precursor to Alzheimer’s disease.

###

The study was partially funded by grants from the National Institutes of Health and the American Federation for Aging Research. ChromaDex, the maker of NIAGEN provided supplements and some financial support.

Public Release: 5-Apr-2018

New health benefits discovered in berry pigment

University of Eastern Finland

Naturally occurring pigments in berries, also known as anthocyanins, increase the function of the sirtuin 6 enzyme in cancer cells, a new study from the University of Eastern Finland shows. The regulation of this enzyme could open up new avenues for cancer treatment. The findings were published in Scientific Reports.

Sirtuins are enzymes regulating the expression of genes that control the function of cells through key cellular signalling pathways. Ageing causes changes in sirtuin function, and these changes contribute to the development of various diseases. Sirtuin 6, or SIRT6 for short, is a less well-known enzyme that is also linked to glucose metabolism.

Berries get their red, blue or purple colour from natural pigments, anthocyanins.

“The most interesting results of our study relate to cyanidin, which is an anthocyanin found abundantly in wild bilberry, blackcurrant and lingonberry,” says Minna Rahnasto-Rilla, Doctor of Pharmacy, the lead author of the article.

Cyanidin increased SIRT6 enzyme levels in human colorectal cancer cells, and it was also discovered to decrease the expression of the Twist1 and GLUT1 cancer genes, while increasing the expression of the tumour suppressor FoXO3 gene in cells.

The researchers also designed a computer-based model that allowed them to predict how different flavonoid compounds in plants can regulate the SIRT6 enzyme.

The findings indicate that anthocyanins increase the activation of SIRT6, which may play a role in cancer pathogenesis. The study also lays a foundation for the development of new drugs that regulate SIRT6 function.

Working at the School of Pharmacy of the University of Eastern Finland, the Sirtuin Research Group studies whether anthocyanins found in berries could activate SIRT6 function and, consequently, reduce the expression of cancer genes and cancer cell growth. The group also develops new compounds targeting the epigenetic regulation of gene function.

The Finnish-American study included researchers from the University of Eastern Finland and the National Institute on Ageing in the US. The study was funded by the Academy of Finland, the Finnish Cultural Foundation, and the US National Institute of Health.

Maija Lahtela-Kakkonen, Docent, University of Eastern Finland, School of Pharmacy, tel. +358403553692, maija.lahtela-kakkonen@uef.fi

Public Release: 5-Apr-2018

The relevance of GABA for diabetes is highlighted in two new studies

Uppsala University

Dynamic interactions between the nervous system, hormones and the immune system are normally on-going but in diabetes the balance is disturbed. The two studies published in EBioMedicine by an international research team from Uppsala University highlight the importance of the neurotransmitter gamma-aminobutyric acid in both Type 1 and Type 2 diabetes.

GABA is synthesized by an enzyme called GAD from the amino acid glutamate in nerve cells but also, importantly, in the insulin-producing beta cells in pancreatic islets. GAD has two forms, GAD65 and GAD67. In type 1 diabetes, beta cells are destroyed while type 2 diabetes is associated with impaired beta cell function and insulin resistance.

Patients with type 1 diabetes often have antibodies to GAD65. However, there has been no strong link between GABA and type 2 diabetes until recently when it was shown that GABA is important for maintaining and potentially also in the making of new beta cells.

The two current studies, now published in EBioMedicine, reinforce the image of GABA’s importance, for both types of diabetes. The scientists used ion channels that GABA opens, the GABAA receptors, as a biological sensor for GABA, and were able to determine the effective, physiological GABA concentration levels in human pancreatic islets. They also showed that these ion channels became more sensitive to GABA in type 2 diabetes and that GABA helps regulate insulin secretion (Article 1).

The scientists then isolated immune cells from human blood and studied the effects GABA had on these cells. They show that GABA inhibited the cells and reduced the secretion of a large number of inflammatory molecules (Article 2).

The anti-inflammatory effect of GABA may be vital in the pancreatic islets since as long as GABA is present, toxic white blood cells can be inhibited, thus increasing the survival of the insulin-secreting beta cells. When the beta cells decrease in number and disappear from the islets as happens in Type 1 diabetes, then GABA consequently is also decreased and, thereby, the GABA protective shielding of the beta cells. When inflammatory molecules increase in strength, it may weaken and even kill the remaining beta cells.

In ongoing studies, the scientists now focus on clarifying the GABA signaling mechanisms in the immune cells and in the human beta cells. They will also study how existing drugs can increase, decrease or mimic the effects of GABA, says Bryndis Birnir.

Public Release: 12-Apr-2018

Study explores carbohydrates’ impact on head, neck cancers

University of Illinois at Urbana-Champaign

CHAMPAIGN, Ill. — Consuming high amounts of carbohydrates and various forms of sugar during the year prior to treatment for head and neck cancer may increase patients’ risks of cancer recurrence and mortality, a new study reports.

However, eating moderate amounts of fats and starchy foods such as whole grains, potatoes and legumes after treatment could have protective benefits, reducing patients’ risks of disease recurrence and death, said lead author Anna E. Arthur, a professor of food science and human nutrition at the University of Illinois.

In the study, researchers tracked the pre- and post-treatment diets and health outcomes of more than 400 cancer patients. Participants were followed for an average of 26 months after they were first diagnosed and treated for squamous-cell carcinoma of the head or neck; all were patients of the University of Michigan Head and Neck Specialized Program of Research Excellence. The study was published recently in the International Journal of Cancer.

Participants’ typical intake of food, beverages and supplements was assessed for the year prior to diagnosis and for one year post-treatment using the Harvard Food Frequency Questionnaire. Patients who consumed the lowest amounts of simple carbohydrates – which included refined grains, desserts and sugar-sweetened beverages – consumed about 1.3 servings daily, compared with about 4.4 servings by patients who were considered high intake.

Patients who consumed the most total carbohydrates and sugars – in the forms of sucrose, fructose, lactose and maltose – in the year preceding cancer treatment were at greater risk of mortality from any cause during the follow-up period, Arthur said.

Among the study population, the most commonly diagnosed cancers were in the oral cavity and the oropharynx, which includes the tonsils, the base of the tongue and surrounding tissues. More than 69 percent of participants were diagnosed when the disease was at stage 3 or stage 4. Patients’ average age at diagnosis was about 61.

During the follow-up period, more than 17 percent of patients experienced recurrence of their cancer, and 42 patients died from it. Another 70 participants died from other causes, according to the study.

Associations among carbohydrate intake and patient outcomes differed by cancer type and stage, Arthur said.

Higher mortality rates were found among people with oral cavity cancer who consumed the greatest amounts of total carbohydrates, total sugars and simple carbohydrates, but the researchers found no such associations among people who had oropharyngeal cancers.

Likewise, high carbohydrate consumption and glycemic load were significantly associated with increased risk of mortality from any cause among people with cancers in stages 1 to 3, but not in patients with stage 4 cancers.

“Although in this study we found that higher total carbohydrate and total sugar were associated with higher mortality in head and neck cancer patients, because of the study design we can’t say that there’s a definitive cause-effect relationship,” said Arthur, who also is an oncology dietitian nutritionist with the Carle Cancer Center at Carle Foundation Hospital in Urbana, Illinois. “The next step would be to conduct a randomized clinical trial to test whether carbohydrate restriction has a protective effect on survival rates.”

Consuming a moderate amount – about 67 grams – of various forms of fat and starchy foods daily after cancer treatment appeared to provide some beneficial effects, lowering participants’ risks of mortality and cancer recurrence.

“Our results, along with the findings of other studies, suggest that diet composition can affect cancer outcomes,” said co-author Amy M. Goss, a professor of nutrition sciences at the University of Alabama, Birmingham. “We’d like to determine if this is true using a prospective, intervention study design and identify the underlying mechanisms. For example, how does cutting back on sugar and other dietary sources of glucose affect cancer growth?”

The study is believed to be the first to provide observational data on the therapeutic potential of carbohydrate-restricted, higher fat diets on head and neck squamous-cell cancers. Five-year survival rates among these patients continue to be low, in part because these cancers are often detected in later stages, putting patients at high risk of recurrence.

“This observational study is noteworthy because it focuses on a serious cancer that is difficult to treat, and little is known about how nutrition can best help a patient battling it,” said co-author Dr. Laura Q. Rogers, a professor of nutrition sciences at Alabama, Birmingham. “This study reiterates the importance of additional intervention studies that test optimal diet recommendations for cancer survivors.”

Public Release: 16-Apr-2018

Regular nut intake linked to lower risk of heart rhythm irregularity (atrial fibrillation)

May also lessen heart failure risk, although association not as clear-cut

BMJ

Eating several servings of nuts every week may help lower the risk of developing the heart rhythm irregularity, atrial fibrillation, also known as heart flutter, finds research published online in the journal Heart.

This level of consumption may also lessen the risk of developing heart failure, although the findings are less consistent, the research indicates.

Previous studies have suggested that eating nuts regularly is associated with a lower risk of heart disease/stroke and associated death, but it’s not clear which particular aspects of cardiovascular disease nut consumption may be linked to.

To explore this in more depth, the researchers drew on the completed Food Frequency Questionnaire responses and lifestyle information from more than 61,000 Swedish 45-83 year olds. Their cardiovascular health was then tracked for 17 years (to the end of 2014) or until death, whichever came first.

People who ate nuts tended to be better educated and to have healthier lifestyles than those who didn’t include nuts in their diet. They were less likely to smoke or to have a history of high blood pressure. And they were leaner, more physically active, drank more alcohol and ate more fruit and vegetables.

During the monitoring period, there were 4983 heart attacks, of which 917 were fatal; 3160 cases of heart failure; 7550 cases of atrial fibrillation; 972 cases of aortic valve narrowing; 983 abdominal aortic aneurysms (a bulge or swelling in the aorta, a major artery); and 3782 cases of stroke caused by a blood clot (ischaemic) and 543 caused by a brain bleed (intracerebral haemorrhage).

Nut consumption was associated with a lower risk of heart attack, heart failure, atrial fibrillation and abdominal aortic aneurysm, after taking account of age and sex.

But when several potentially influential known risk factors were accounted for, including lifestyle, general diet, diabetes, and family history, only associations with atrial fibrillation and with heart failure emerged.

The more often nuts were included in the diet, the lower was the associated risk of atrial fibrillation, the findings showed.

Eating a serving of nuts one to three times a month was associated with a lowered risk of just 3 percent, rising to 12 percent when eating them once or twice a week, and to 18 percent when eating them three or more times a week.

The findings for heart failure were less consistent: moderate, but not high, weekly nut consumption was associated with a 20 percent lower risk.

Each additional portion of nuts eaten during the week was associated with a 4 percent lowering in atrial fibrillation risk.

Eating nuts regularly was not associated with a lower risk of the narrowing of the valve serving the heart’s largest artery, the aorta, or with the risk of stroke.

This is an observational study, and as such, cannot establish causation. And the researchers emphasise that those who ate nuts had fewer cardiovascular risk factors to start with, which may have affected the findings.

But the strength of the study lies in its large size and the large number of cardiovascular disease cases reported during the monitoring period, they say.

Nuts are a rich source of healthy fats, minerals, and antioxidants, all of which may aid cardiovascular health, they explain.

“Nut consumption or factors associated with this nutritional behaviour may play a role in reducing the risk of atrial fibrillation and possibly heart failure,” they write.

And they suggest: “Since only a small proportion of this population had moderate (about 5%) or high (less than 2%) nut consumption, even a small increase in nut consumption may have large potential to lead to a reduction in incidence of atrial fibrillation and heart failure in this population.”

Public Release: 15-Apr-2018

Raw fruit and vegetables provide better mental health outcomes: Otago research

University of Otago

Seeking the feel good factor? Go natural.

That is the simple message from University of Otago researchers who have discovered raw fruit and vegetables may be better for your mental health than cooked, canned and processed fruit and vegetables.

Dr Tamlin Conner, Psychology Senior Lecturer and lead author, says public health campaigns have historically focused on aspects of quantity for the consumption of fruit and vegetables (such as 5+ a day).

However, the study, just published in Frontiers in Psychology, found that for mental health in particular, it may also be important to consider the way in which produce was prepared and consumed.

“Our research has highlighted that the consumption of fruit and vegetables in their ‘unmodified’ state is more strongly associated with better mental health compared to cooked/canned/processed fruit and vegetables,” she says.

Dr Conner believes this could be because the cooking and processing of fruit and vegetables has the potential to diminish nutrient levels.

“This likely limits the delivery of nutrients that are essential for optimal emotional functioning.”

For the study, more than 400 young adults from New Zealand and the United States aged 18 to 25 were surveyed. This age group was chosen as young adults typically have the lowest fruit and vegetable consumption of all age groups and are at high risk for mental health disorders.

The group’s typical consumption of raw versus cooked and processed fruits and vegetables were assessed, alongside their negative and positive mental health, and lifestyle and demographic variables that could affect the association between fruit and vegetable intake and mental health (such as exercise, sleep, unhealthy diet, chronic health conditions, socioeconomic status, ethnicity, and gender).

“Controlling for the covariates, raw fruit and vegetable consumption predicted lower levels of mental illness symptomology, such as depression, and improved levels of psychological wellbeing including positive mood, life satisfaction and flourishing. These mental health benefits were significantly reduced for cooked, canned, and processed fruits and vegetables.

“This research is increasingly vital as lifestyle approaches such as dietary change may provide an accessible, safe, and adjuvant approach to improving mental health,” Dr Conner says.

* The top 10 raw foods related to better mental health were: carrots, bananas, apples, dark leafy greens such as spinach, grapefruit, lettuce, citrus fruits, fresh berries, cucumber, and kiwifruit.

Public Release: 19-Apr-2018

Novel antioxidant makes old blood vessels seem young again

University of Colorado at Boulder

Older adults who take a novel antioxidant that specifically targets cellular powerhouses, or mitochondria, see age-related vascular changes reverse by the equivalent of 15 to 20 years within six weeks, according to new University of Colorado Boulder research.

The study, published this week in the American Heart Association journal Hypertension, adds to a growing body of evidence suggesting pharmaceutical-grade nutritional supplements, or nutraceuticals, could play an important role in preventing heart disease-the nation’s No. 1 killer. It also resurrects the notion that oral antioxidants, which have been broadly dismissed as ineffective in recent years, could reap measurable health benefits if properly targeted, the authors say.

“This is the first clinical trial to assess the impact of a mitochondrial-specific antioxidant on vascular function in humans,” said lead author Matthew Rossman, a postdoctoral researcher in the department of integrative physiology. “It suggests that therapies like this may hold real promise for reducing the risk of age-related cardiovascular disease.”

For the study, Rossman and senior author Doug Seals, director of the Integrative Physiology of Aging Laboratory, recruited 20 healthy men and women age 60 to 79 from the Boulder area.

Half took 20 milligrams per day of a supplement called MitoQ, made by chemically altering the naturally-occurring antioxidant Coenzyme Q10 to make it cling to mitochondria inside cells.

The other half took a placebo.

After six weeks, researchers assessed how well the lining of blood vessels, or the endothelium, functioned, by measuring how much subjects’ arteries dilated with increased blood flow.

Then, after a two-week “wash out” period of taking nothing, the two groups switched, with the placebo group taking the supplement, and vice versa. The tests were repeated.

The researchers found that when taking the supplement, dilation of subjects’ arteries improved by 42 percent, making their blood vessels, at least by that measure, look like those of someone 15 to 20 years younger. An improvement of that magnitude, if sustained, is associated with about a 13 percent reduction in heart disease, Rossman said. The study also showed that the improvement in dilation was due to a reduction in oxidative stress.

In participants who, under placebo conditions, had stiffer arteries, supplementation was associated with reduced stiffness.

Blood vessels grow stiff with age largely as a result of oxidative stress, the excess production of metabolic byproducts called free radicals which can damage the endothelium and impair its function. During youth, bodies produce enough antioxidants to quench those free radicals. But with age, the balance tips, as mitochondria and other cellular processes produce excess free radicals and the body’s antioxidant defenses can’t keep up, Rossman said.

Oral antioxidant supplements like vitamin C and vitamin E fell out of favor after studies showed them to be ineffective.

“This study breathes new life into the discredited theory that supplementing the diet with antioxidants can improve health,” said Seals. “It suggests that targeting a specific source-mitochondria-may be a better way to reduce oxidative stress and improve cardiovascular health with aging.”

Public Release: 19-Apr-2018

Study predicts 2018 flu vaccine will have 20 percent efficacy

Rice U. study finds egg adaptations will limit efficacy of new flu vaccine

Rice University

A Rice University study predicts that this fall’s flu vaccine — a new H3N2 formulation for the first time since 2015 — will likely have the same reduced efficacy against the dominant circulating strain of influenza A as the vaccine given in 2016 and 2017 due to viral mutations related to vaccine production in eggs.

The Rice method, known as pEpitope (pronounced PEE-epih-tope), was invented more than 10 years ago as a fast, inexpensive way of gauging the effectiveness of proposed flu vaccine formulations. The latest pEpitope study, which is available online this week in Clinical Infectious Diseases, suggests pEpitope is a more accurate predictor of vaccine efficacy than long-relied-upon ferret tests, particularly for data gathered in the past decade. The pEpitope method accounts for 77 percent of what impacts efficacy of the vaccine in humans.

pEpitope is a computational method that measures critical differences in the genetic sequences of flu strains. In the new study, the method accurately predicted vaccine efficacy rates for more than 40 years of flu records. These included the past two flu seasons in which vaccines offered only limited protection against the most widely circulating strain of influenza A.

“The vaccine has been changed for 2018-19, but unfortunately it still contains two critical mutations that arise from the egg-based vaccine production process,” said Michael Deem, Rice’s John W. Cox Professor in Biochemical and Genetic Engineering and professor of physics and astronomy. “Our study found that these same mutations halved the efficacy of flu vaccines in the past two seasons, and we expect they will lower the efficacy of the next vaccine in a similar manner.”

Full efficacy data for the 2017-2018 flu season are still being compiled, but pEpitope has predicted it will be around 19 percent against H3N2, the type of influenza A that infected most people in the U.S. in each of the past two years. The Food and Drug Administration chose the same vaccine formulation in 2017 and 2016, in part because the dominant circulating strain stayed the same. In 2016, the vaccine had an efficacy of 20 percent, almost identical to the efficacy of 19 percent predicted by pEpitope.

Efficacy is the measure of how effective a vaccine is at protecting the overall population. A 20 percent efficacy means that in a population, 20 percent fewer vaccinated people will get the flu compared to the unvaccinated people.

Annual flu vaccines are formulated to protect against one type of influenza B and two strains of influenza A, one H3N2 strain and one H1N1 strain. The H and N refer to hemagglutinin and neuraminidase, two proteins that cover the outside of invading flu particles that can cause infection when inhaled. The human immune system targets these particles for destruction based on their H and N sequences, and flu viruses constantly evolve the sequence of amino acids in these proteins to evade detection.

Most flu vaccines are produced with a decades-old process that involves culturing viruses in hundreds of millions of chicken eggs. Because the strain of flu that infects people is often difficult to grow in eggs, vaccine producers must make compromises to produce enough egg-based vaccine in time for fall flu shots. Unintended effects of this process have reduced vaccine efficacy against H3N2 the past two years, Deem said.

“Very often there are egg adaptations,” he said. “There were a couple of these in the vaccine strain the past two seasons that wound up making it a little bit different from the actual circulating virus strain.”

While other papers have examined these mutations using expensive and time-consuming experiments on live ferrets and laboratory cell cultures, Deem and Melia Bonomo used the pEpitope method to rapidly calculate how much the egg-passage mutations would decrease vaccine efficacy in humans.

“In fact, it’s pretty substantial,” said Bonomo, a doctoral student in applied physics. “The original strain used as a reference for the vaccine was basically a perfect match to the dominant circulating strain, and the predicted efficacy would have been around 47 percent. We found that the mutations in two amino acids out of more than 300 in one key region of the hemagglutinin protein were enough to lower efficacy to 19 percent against all circulating strains.”

Deem said egg adaptations like those that reduced the efficacy of vaccines in 2016 and 2017 are unavoidable as long as flu vaccines are produced in eggs. He and Bonomo compared the efficacy of the egg-based vaccine with an experimental vaccine produced from insect cells via reverse genetics. The cell-based vaccine, which did not have the egg-passage mutations, had a predicted efficacy of 47 percent, the average value of a perfectly matched H3N2 vaccine, Deem said.

For decades, scientists have relied upon ferret models to gauge how flu viruses and flu vaccines will behave in people. But Deem said ferret studies over the past 10 years have been considerably less predictive of human effects than they were in the preceding three decades, and it is unclear why.

“It’s been apparent over the last 10 years that egg adaptations have affected the efficacy of flu vaccines,” he said. “It’s also been apparent that the ferrets have done a really bad job of predicting the reduction of the efficacy due to the egg adaptations. Additionally, it’s been difficult to get data from ferrets because the ferrets’ immune systems have not recognized the vaccines particularly well over the past 10 years.”

Deem said the ferret-based measures are one-third as predictive as the pEpitope method that has consistent performance over decades of flu data.

“When we look at our model over all data and over the last 10 years, we get the same answer,” Deem said. “Whether we use the last 10 years of data or the last 50 years, our theory is very robust.”

The DOI of the Clinical Infectious Diseases paper is: 10.1093/cid/ciy323

Public Release: 19-Apr-2018

The bugs in your gut could make you weak in the knees

A prebiotic may alter the obese microbiome and protect against osteoarthritis

University of Rochester Medical Center

Bacteria in the gut, known as the gut microbiome, could be the culprit behind arthritis and joint pain that plagues people who are obese, according to a new study published today in JCI Insight.

Osteoarthritis, a common side effect of obesity, is the greatest cause of disability in the US, affecting 31 million people. Sometimes called “wear and tear” arthritis, osteoarthritis in people who are obese was long assumed to simply be a consequence of undue stress on joints. But researchers at the University of Rochester Medical Center provide the first evidence that bacteria in the gut – governed by diet – could be the key driving force behind osteoarthritis.

The scientists found that obese mice had more harmful bacteria in their guts compared to lean mice, which caused inflammation throughout their bodies, leading to very rapid joint deterioration. While a common prebiotic supplement did not help the mice shed weight, it completely reversed other symptoms, making the guts and joints of obese mice indistinguishable from lean mice.

What a Western, High Fat Diet Can Do

The URMC team, led by Michael Zuscik, Ph.D., associate professor of Orthopaedics in the Center for Musculoskeletal Research (CMSR), Robert Mooney, Ph.D., professor of Pathology and Laboratory Medicine, and Steven Gill, Ph.D., associate professor of Microbiology and Immunology, fed mice a high fat diet akin to a Western ‘cheeseburger and milkshake’ diet.

Just 12 weeks of the high fat diet made mice obese and diabetic, nearly doubling their body fat percentage compared to mice fed a low fat, healthy diet. Their colons were dominated by pro-inflammatory bacteria, and almost completely lacked certain beneficial, probiotic bacteria, like the common yogurt additive Bifidobateria.

The changes in the gut microbiomes of the mice coincided with signs of body-wide inflammation, including in their knees where the researchers induced osteoarthritis with a meniscal tear, a common athletic injury known to cause osteoarthritis. Compared to lean mice, osteoarthritis progressed much more quickly in the obese mice, with nearly all of their cartilage disappearing within 12 weeks of the tear.

“Cartilage is both a cushion and lubricant, supporting friction-free joint movements,” said Zuscik. “When you lose that, it’s bone on bone, rock on rock. It’s the end of the line and you have to replace the whole joint. Preventing that from happening is what we, as osteoarthritis researchers, strive to do – to keep that cartilage.”

Can You Eat Your Cake and Protect Your Joints, Too?

Surprisingly, the effects of obesity on gut bacteria, inflammation, and osteoarthritis were completely prevented when the high fat diet of obese mice was supplemented with a common prebiotic, called oligofructose. The knee cartilage of obese mice who ate the oligofructose supplement was indistinguishable from that of the lean mice.

Prebiotics, like oligofructose, cannot be digested by rodents or humans, but they are welcome treats for certain types of beneficial gut bacteria, like Bifidobacteria. Colonies of those bacteria chowed down and grew, taking over the guts of obese mice and crowding out bad actors, like pro-inflammatory bacteria. This, in turn, decreased systemic inflammation and slowed cartilage breakdown in the mice’s osteoarthritic knees.

Oligofructose even made the obese mice less diabetic, but there was one thing the dietary supplement didn’t change: body weight.

Obese mice who were given oligofructose remained obese, bearing the same load on their joints, yet their joints were healthier. Just reducing inflammation was enough to protect joint cartilage from degeneration, supporting the idea that inflammation – not biomechanical forces – drive osteoarthritis and joint degeneration.

“That reinforces the idea that osteoarthritis is another secondary complication of obesity – just like diabetes, heart disease, and stroke, which all have inflammation as part of their cause,” said Mooney. “Perhaps, they all share a similar root, and the microbiome might be that common root.”

Before You Head to the Vitamin Shop

Though there are parallels between mouse and human microbiomes, the bacteria that protected mice from obesity-related osteoarthritis may differ from the bacteria that could help humans. Zuscik, Mooney and Gill aim to collaborate with researchers in the Military and Veteran Microbiome: Consortium for Research and Education at the U.S. Department of Veteran’s Affairs to move this research into humans.

The team hopes to compare veterans who have obesity-related osteoarthritis to those who don’t to further identify the connections between gut microbes and joint health. They also hope to test whether prebiotic or probiotic supplements that shape the gut microbiome can have similar effects in vets suffering from osteoarthritis as they did in mice.

“There are no treatments that can slow progression of osteoarthritis – and definitely nothing reverses it,” said first author Eric Schott, Ph.D., postdoctoral fellow in the CMSR and soon-to-be clinical research scientist at Solarea Bio, Inc. “But this study sets the stage to develop therapies that target the microbiome and actually treat the disease.”

Public Release: 22-Apr-2018

Growing evidence that probiotics are good for your liver

In mice, probiotic treatment shown to protect against liver damage from acetaminophen

Increased awareness of the importance of the microbes that live in our gut has spurred a great deal of research on the microbiome and fueled a booming probiotics industry. A new study suggests probiotics can improve not only the health of our gut but liver health, as well.

“Probiotics have been studied most intensely in the context of the gastrointestinal tract,” said Bejan Saeedi, a doctoral candidate at Emory University who conducted the research. “This study provides evidence that the effects of probiotics extend beyond the gastrointestinal tract. What makes this study unique is that it suggests a discreet molecular mechanism by which these effects are elicited.”

Saeedi will present the research at the American Society for Investigative Pathology annual meeting during the 2018 Experimental Biology meeting, held April 21-25 in San Diego.

The vast populations of microbes that reside on and inside of our bodies have been shown to play a role in numerous functions that keep our bodies healthy. Probiotics are bacteria that are consumed or administered in an effort to boost the populations of these beneficial microbes.

Saeedi and his colleagues focused their study on the probiotic Lactobacillus rhamnosus GG (known as LGG), a species common in many over-the-counter probiotic formulations. They gave mice food laced with LGG for two weeks and then examined how they responded to a high dose of acetaminophen (the active ingredient in Tylenol®).

Taking too much acetaminophen can cause serious liver damage and even death by increasing the abundance of a form of oxygen called free radicals, a process known as oxidative stress. However, the researchers found that mice receiving the probiotic treatment suffered less liver damage when presented with an overdose of acetaminophen compared with mice that did not receive probiotics.

“Administration of the probiotic LGG to mice improves the antioxidant response of the liver, protecting it from oxidative damage produced by drugs such as acetaminophen,” explained Saeedi.

The liver is a hub for removing toxins from the blood and plays an important role in the body’s processes for converting food into energy. Since it is “downstream” of the gastrointestinal tract in the digestive process, it makes sense that the composition of bacteria in the gut could affect the functioning of the liver.

Previous research by Saeedi’s colleagues has traced the molecular process by which LGG appears to protect against oxidative liver injury. That research points to the role of a protein called Nrf2, which regulates the expression of genes involved in fighting free radicals.

Other studies in mice have previously shown that LGG can protect against alcoholic liver disease and non-alcoholic fatty liver disease. Saeedi said studies in human volunteers would be needed to definitively test the potential clinical benefits of LGG in humans.

Bejan Saeedi will present this research on Sunday, April 22, from 2:45-3 p.m. in Room 4, San Diego Convention Center (abstract) and on Tuesday, April 24, from 5:30-7:30 p.m. in Ballroom 20BC (poster 150.4). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Public Release: 23-Apr-2018

Could eating moss be good for your gut?

University of Adelaide

An international team of scientists including the University of Adelaide has discovered a new complex carbohydrate in moss that could possibly be exploited for health or other uses.

The scientists, from Australia’s ARC Centre of Excellence in Plant Cell Walls and University of Rhode Island, in the US, say the polysaccharide looks a bit like the gut-friendly, health-promoting beta glucan found in oats and other cereals. A polysaccharide is a complex carbohydrate made up of sugar molecules.

Led by Professor Rachel Burton, in the University of Adelaide’s School of Agriculture, Food and Wine, and Professor Alison Roberts, University of Rhode Island, the research team was looking into the evolutionary history of the beta glucan when they made this discovery. The research has been published in The Plant Cell.

Beta glucan, another polysaccharide, is a dietary fibre that is known to have many health benefits. It is abundant in cereals such as oats and barley, but has not been found in moss despite the plants having similar relevant genes.

The researchers took one of these similar genes from moss to see if it would lead to the production of beta glucan.

“What we found was a new polysaccharide made up of the sugars glucose and arabinose – not just glucose as in beta glucan,” says Professor Burton.

“We have called it arabinoglucan and believe the way the two different sugars link together will make it structurally similar to beta glucan. We are not advocating eating moss, we are simply saying that there is great potential for this new polysaccharide as we’ve seen with others.”

Professor Burton says that while the function of the arabinoglucan is not yet known, it may have properties that can be exploited for health, industrial and medical fields, like well-known polysaccharides, such as cellulose for paper and cotton, or xylans that can be used for as dietary supplements or drug delivery.

“This discovery leads to the question: how many other polysaccharides do plants contain that we don’t yet know about?” Professor Burton says.

“We don’t know what’s there because we can’t always see it. Scientists will need new tools to be able to find them, which might include new antibodies and microscopy techniques.”

Public Release: 23-Apr-2018

Hemp shows potential for treating ovarian cancer

Researchers demonstrate hemp’s ability to slow cancer growth and uncover mechanism for its cancer-fighting ability

Experimental Biology 2018

Results from some of the first studies to examine hemp’s ability to fight cancer show that it might one day be useful as plant-based treatment for ovarian cancer. Hemp is part of the same cannabis family as marijuana but doesn’t have any psychoactive properties or cause addiction.

Sara Biela and Chase Turner, graduate students in the lab of Wasana Sumanasekera at Sullivan University College of Pharmacy in Kentucky, will present new findings tied to hemp’s anti-cancer properties at the American Society for Biochemistry and Molecular Biology annual meeting during the 2018 Experimental Biology meeting to be held April 21-25 in San Diego.

“Hemp, like marijuana, contains therapeutically valuable components such as cannabidiol, cannabinol, and tetrahydrocannabinol,” explained Biela. “However, unlike marijuana, hemp’s therapeutic ability has not been studied in detail.”

Two new studies examined the therapeutic potential of an extract known as KY-hemp, which is produced from hemp grown in Kentucky. The plant strain, growing conditions and processing techniques were all optimized to produce an extract containing substances with potential therapeutic benefit and to eliminate any residue that could contaminate the product.

In one study, the researchers found that adding various doses of KY-hemp extract to cultured ovarian cells led to significant dose-dependent slowing of cell migration. This finding indicated that the extract might be useful for stopping or slowing down metastasis — the spreading of cancer to other parts of the body.

In a second study, the researchers explored the biology of KY-hemp’s protective effects against ovarian cancer, which they had observed in previous studies. Experiments with cultured ovarian cancer cells showed that KY-hemp slowed the secretion of the interleukin IL-1 beta. Interleukins produce inflammation that can be damaging and has been linked to cancer progression. The hemp-induced slowing of IL-1 β secretion represents a possible biological mechanism responsible for KY-hemp’s anti-cancer effects.

“Our findings from this research as well as prior research show that KY hemp slows ovarian cancer comparable to or even better than the current ovarian cancer drug Cisplatin,” said Turner. “Since Cisplatin exhibits high toxicity, we anticipate that hemp would carry less side effects. However, that needed to be tested in the future.”

The researchers plan to test the extract in mice after they complete additional studies in cultured cancer cells to learn more about how it leads to cancer cell death.

Sara Biela will present at 12:45-1:30 p.m. Monday, April 23, in Exhibit Halls A-D, San Diego Convention Center (poster B400 667.7) (abstract). Chase Turner will present from 12:45-1:30 p.m. Tuesday, April 24, in Exhibit Halls A-D, SDCC (poster B355 804.41) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

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