CNO Report # 252
Release Date: 29 JAN 2018
Draft Report Compiled by
In this issue:
1. Berry gives boost to cervical cancer therapy
2. Bifidobacterium or fiber protect against deterioration of the inner colonic mucus layer
3. High doses of vitamin D rapidly reduce arterial stiffness
4. Redefining knowledge of elderly people throughout history
5. Proper exercise can reverse damage from heart aging
6. Cancer targeted with reusable ‘stinging nettle’ treatment
7. Women run faster after taking newly developed supplement, study finds
8. Prebiotics in infant formula could improve learning and memory and alter brain chemistry
9. Dietary fiber protects against obesity and metabolic syndrome, study finds
10. Powerful food-derived antioxidant can halt, prevent fatty liver disease in mice
11. Vitamin D supplements could ease painful IBS symptoms
Public Release: 29-Dec-2017
Berry gives boost to cervical cancer therapy
In vitro study combines radiation therapy, blueberry extract to improve treatment
University of Missouri-Columbia
According to the Centers for Disease Control and Prevention, approximately 12,000 women in the United States are diagnosed with cervical cancer each year. One of the most common treatments for cervical cancer is radiation. While radiation therapy destroys cancer cells, it also destroys nearby healthy cells. University of Missouri School of Medicine researchers studied in vitro human cancer cells to show that combining blueberry extract with radiation can increase the treatment’s effectiveness.
“Radiation therapy uses high-energy X-rays and other particles such as gamma rays to destroy cancer cells,” said Yujiang Fang, M.D., Ph.D., a visiting professor at the MU School of Medicine and lead author of the study. “For some cancers, such as late-stage cervical cancer, radiation is a good treatment option. However, collateral damage to healthy cells always occurs. Based on previous research, we studied blueberry extract to verify it could be used as a radiosensitizer.”
Radiosensitizers are non-toxic chemicals that make cancer cells more responsive to radiation therapy. In a previous study, Fang and his research team showed that resveratrol, a compound in red grapes, could be used as a radiosensitizer for treating prostate cancer. Blueberries also contain resveratrol.
“In addition to resveratrol, blueberries also contain flavonoids,” said Fang, who also has appointments as an academic pathologist and assistant professor of microbiology and immunology at Des Moines University in Iowa. “Flavonoids are chemicals that may have antioxidant, anti-inflammatory and antibacterial properties.”
The researchers used human cervical cancer cell lines to mimic clinical treatment. The cell lines were divided into four groups that included a control group, a group that received only radiation, a group that received only blueberry extract, and a group that received both radiation and the extract.
“Our team used three different measures to confirm results of the study,” Fang said. “Radiation decreased cancer cells by approximately 20 percent. Interestingly, the cell group that received only blueberry extract had a 25 percent decrease in cancer. However, the biggest decline in cancer cells occurred in the radiation and extract group, with a decrease of about 70 percent.”
Fang explained that the mechanism that makes blueberry extract a radiosensitizer also reduces the abnormal explosion of cell growth ? which is what cancer is.
“Cancer cells avoid death by remodeling themselves,” Fang said. “Along with reducing cell proliferation, the extract also ‘tricks’ cancer cells into dying. So it inhibits the birth and promotes the death of cancer cells.”
Fang said an animal study is the next step to confirm that his team can achieve the same results.
“Blueberries are very common and found all over the world,” Fang said. “They are readily accessible and inexpensive. As a natural treatment option for boosting the effectiveness of existing therapies, I feel they would be enthusiastically accepted.”
The study, “Blueberry as a Potential Radiosensitizer for Treating Cervical Cancer,” recently was published in Pathology and Oncology Magazine. The study was supported by the Department of Surgery at the MU School of Medicine and through Des Moines University grants (IOER 05-14-01, IOER 112-3749 and IOER 112-3113). The authors of the study declare that they have no conflict of interest.
blic Release: 2-Jan-2018
Bifidobacterium or fiber protect against deterioration of the inner colonic mucus layer
University of Gothenburg
If you are concerned about your health, you should also think about what your gut bacteria consume. Dietary fiber is a key source for their nutrition. Thus the quantity of fiber in your diet influences your weight, blood glucose level and sensitivty to insulin is well-established. The latest research from Sahlgrenska Academy shows that colonic health is also affected.
Cell Host & Microbe recently published a study by scientists at Sahlgranska Academy to clarify the mechanisms for how fiber contributes to colonic health. Meanwhile, many people in contemporary society appear to be heading in a different direction altogether.
“Average fiber consumption has declined drastically in developed countries over the past few decades,” Fredrik Bäckhed, Professor of Molecular Medicine, says. He studies the role of gut bacteria in metabolic disorders.
Various kinds of fiber are found in fruit, legumes, vegetables and whole grain products. Insufficient fiber consumption combined with a high-fat, high-carbohydrate diet is associated with a greater risk of inflammatory bowel disease, weight gain and diabetes.
Mice in the current study were put on a low-fiber diet. They developed defects in the inner colonic mucus layer after only three days characterized by increased bacterial penetrability, a potential risk for inflammatory bowel disease and other disorders.
“Our results demonstrate that the inner mucus layer separate gut bacteria from the body’s cells,” Gunnar C. Hansson, Professor of Medical and Physiological Chemistry and director of the study, says. “We clearly illustrated the rapid, process by which the mucus layer responds to dietary modifications and subsequent bacterial changes.”
In a second experiment, the mice fed fiber-depleted diet received a transplant of gut bacteria from a normally fed animal and regained some of the lost protective effect.
A dietary supplement of friendly bifidobacteria stimulated growth of the mucus layer but did not prevent bacteria in the gut microbiota from approaching the body’s cells. A supplement of inulin, a type of dietary fiber, addressed the latter problem but not the former.
“Low-fiber diets alter bacterial composition and influence what they produce,” Professor Hansson says. “The result can be greater penetrability that affects the body’s cells.”
The researchers believe that fiber supplements as a method of treatment need to be investigated further. Simply enriching food with refined fiber is not recommended before more has been learned about its complex interplay with food, bacteria and the body’s cells.
Public Release: 2-Jan-2018
High doses of vitamin D rapidly reduce arterial stiffness
Medical College of Georgia at Augusta University
AUGUSTA, Ga. (Jan. 2, 2018) – In just four months, high-doses of vitamin D reduce arterial stiffness in young, overweight/obese, vitamin-deficient, but otherwise still healthy African-Americans, researchers say.
Rigid artery walls are an independent predictor of cardiovascular- related disease and death and vitamin D deficiency appears to be a contributor, says Dr. Yanbin Dong, geneticist and cardiologist at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University.
So researchers looked at baseline and again 16 weeks later in 70 African-Americans ages 13-45 – all of whom had some degree of arterial stiffness – taking varying doses of the vitamin best known for its role in bone health.
In what appears to be the first randomized trial of its kind, they found that arterial stiffness was improved by vitamin D supplementation in a dose-response manner in this population, they write in the journal PLOS ONE.
Overweight/obese blacks are at increased risk for vitamin D deficiency because darker skin absorbs less sunlight – the skin makes vitamin D in response to sun exposure – and fat tends to sequester vitamin D for no apparent purpose, says Dong, the study’s corresponding author.
Participants taking 4,000 international units – more than six times the daily 600 IUs the Institute of Medicine currently recommends for most adults and children – received the most benefit, says Dr. Anas Raed, research resident in the MCG Department of Medicine and the study’s first author.
The dose, now considered the highest, safe upper dose of the vitamin by the Institute of Medicine, reduced arterial stiffness the most and the fastest: 10.4 percent in four months. “It significantly and rapidly reduced stiffness,” Raed says.
Two thousand IUs decreased stiffness by 2 percent in that timeframe. At 600 IUs, arterial stiffness actually increased slightly – .1 percent – and the placebo group experienced a 2.3 percent increase in arterial stiffness over the timeframe.
They used the non-invasive, gold standard pulse wave velocity to assess arterial stiffness. Reported measures were from the carotid artery in the neck to the femoral artery, a major blood vessel, which supplies the lower body with blood. The American Heart Association considers this the primary outcome measurement of arterial stiffness.
When the heart beats, it generates a waveform, and with a healthy heart and vasculature there are fewer and smaller waves. The test essentially measures the speed at which the blood is moving, and in this case, fast is not good, Raed says.
“When your arteries are more stiff, you have higher pulse wave velocity, which increases your risk of cardiometabolic disease in the future,” says Raed.
The varying doses, as well as the placebo participants took, were all packaged the same so neither they or the investigators knew which dose, if any, they were getting until the study was complete. Both placebo and supplements were given once monthly – rather than daily at home – at the GPI to ensure consistent compliance.
Dong was also corresponding author on a study published in 2015 in the journal BioMed Central Obesity that showed, in this same group of individuals, both 2,000 and 4,000 IUs restored more desirable vitamin D blood levels of 30 nanograms per milliliter.
The 4,000 upper-limit dose restored healthy blood level quicker – by eight weeks – and was also better at suppressing parathyroid hormone, which works against vitamin D’s efforts to improve bone health by absorbing calcium, they reported.
While heart disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention, blacks have higher rates of cardiovascular disease and death than whites and the disease tends to occur earlier in life. The authors write that arterial stiffness and vitamin D deficiency might be potential contributors.
While just how vitamin D is good for our arteries isn’t completely understood, it appears to impact blood vessel health in many ways. Laboratory studies have shown that mice missing a vitamin D receptor have higher activation of the renin-angiotensin-aldosterone system, says Raed. Activation of this system increases blood vessel constriction, which can contribute to arterial stiffness. Vitamin D also can suppress vascular smooth muscle cell proliferation, activation of garbage-eating macrophages and calcification formation, all of which can thicken blood vessel walls and hinder flexibility. Vitamin D also reduces inflammation, an underlying mechanism for obesity related development of coronary artery disease, says Raed.
Now it’s time to do a larger-scale study, particularly in high-risk populations, and follow participants’ progress for longer periods, Dong and Raed say. “A year would give us even more data and ideas,” Raed adds.
Dong notes that pulse wave velocity and blood pressure measures are complimentary but not interchangeable. “We think maybe in the future, when you go to your physician, he or she might check your arterial stiffness as another indicator of how healthy you are,” Raed says.
There were no measurable differences in weight or blood pressure measurements over the 16-week study period.
The Institute of Medicine currently recommends a daily intake of 800 IUs of vitamin D for those age 70 and older. For adolescents and adults, they recommend 4,000 IUs as the upper daily limit; 2,000 was a previous upper limit.
More than 80 percent of Americans, the majority of whom spend their days indoors, have vitamin D insufficiency or deficiency. Dong, an expert in vitamin D and a professor in the MCG Department of Population Health Sciences, says about 15 minutes daily in the “young” sun – between 10 a.m. and 2 p.m. – but before your skin starts to get pink, is the best source of vitamin D.
Foods like milk, milk products like cheese and yogurt, fatty fish like mackerel and sardines, some greens like kale and collards and fortified cereals also are good sources. The researchers say a vitamin D supplement is an inexpensive and safe option for most of us.
Public Release: 3-Jan-2018
Redefining knowledge of elderly people throughout history
Australian National University
An archaeologist from The Australian National University (ANU) is set to redefine what we know about elderly people in cultures throughout history, and dispel the myth that most people didn’t live much past 40 prior to modern medicine.
Christine Cave, a PhD Scholar with the ANU School of Archaeology and Anthropology, has developed a new method for determining the age-of-death for skeletal remains based on how worn the teeth are.
Using her method, which she developed by analysing the wear on teeth and comparing with living populations of comparable cultures, she examined the skeletal remains of three Anglo-Saxon English cemeteries for people buried between the years 475 and 625.
Her research determined that it was not uncommon for people to live to old age.
“People sometimes think that in those days if you lived to 40 that was about as good as it got. But that’s not true.
“For people living traditional lives without modern medicine or markets the most common age of death is about 70, and that is remarkably similar across all different cultures.”
Ms Cave said the myth has been built up due to deficiencies in the way older people are categorised in archaeological studies.
“Older people have been very much ignored in archaeological studies and part of the reason for that has been the inability to identify them,” she said.
“When you are determining the age of children you use developmental points like tooth eruption or the fusion of bones that all happen at a certain age.
“Once people are fully grown it becomes increasingly difficult to determine their age from skeletal remains, which is why most studies just have a highest age category of 40 plus or 45 plus.
“So effectively they don’t distinguish between a fit and healthy 40 year old and a frail 95 year old.
“It’s meaningless if you are trying to study elderly people.”
Ms Cave said the new method will give archaeologists a more accurate view of past societies and what life was like for older people.
For those in the three cemeteries she studied, which were Greater Chesterford in Essex, Mill Hill in Kent, and Worthy Park in Hampshire, she found a marked difference in the way male and female people of old age were buried.
“Women were more likely to be given prominent burials if they died young, but were much less likely to be given one if they were old,” she said.
“The higher status men are generally buried with weapons, like a spear and a shield or occasionally a sword.
“Women were buried with jewellery, like brooches, beads and pins. This highlights their beauty which helps explain why most of the high-status burials for women were for those who were quite young.”
Ms Cave’s study “Sex and the Elderly” was published in the Journal of Anthropological Archaeology.
Public Release: 8-Jan-2018
Proper exercise can reverse damage from heart aging
UT Southwestern Medical Center
DALLAS – Jan. 8, 2018 – Exercise can reverse damage to sedentary, aging hearts and help prevent risk of future heart failure – if it’s enough exercise, and if it’s begun in time, according to a new study by cardiologists at UT Southwestern and Texas Health Resources.
To reap the most benefit, the exercise regimen should begin by late middle age (before age 65), when the heart apparently retains some plasticity and ability to remodel itself, according to the findings by researchers at the Institute for Exercise and Environmental Medicine (IEEM), which is a collaboration between UT Southwestern Medical Center and Texas Health Presbyterian Hospital Dallas.
And the exercise needs to be performed four to five times a week. Two to three times a week was not enough, the researchers found in an earlier study.
“Based on a series of studies performed by our team over the past 5 years, this ‘dose’ of exercise has become my prescription for life,” said senior author Dr. Benjamin Levine, Director of the Institute and Professor of Internal Medicine at UT Southwestern. “I think people should be able to do this as part of their personal hygiene – just like brushing your teeth and taking a shower.”
The regimen included exercising four to five times a week, generally in 30-minute sessions, plus warmup and cool-down:
- One of the weekly sessions included a high-intensity 30-minute workout, such as aerobic interval sessions in which heart rate tops 95 percent of peak rate for 4 minutes, with 3 minutes of recovery, repeated four times (a so-called “4 x 4”).
- Each interval session was followed by a recovery session performed at relatively low intensity.
- One day’s session lasted an hour and was of moderate intensity. (As a “prescription for life,” Levine said this longer session could be a fun activity such as tennis, aerobic dancing, walking, or biking.)
- One or two other sessions were performed each week at a moderate intensity, meaning the participant would break a sweat, be a little short of breath, but still be able to carry on a conversation — the “talk test.” In the study, exercise sessions were individually prescribed based on exercise tests and heart rate monitoring.
- One or two weekly strength training sessions using weights or exercise machines were included on a separate day, or after an endurance session.
Study participants built up to those levels, beginning with three, 30-minute, moderate exercise sessions for the first 3 months and peaked at 10 months when two high-intensity aerobic intervals were added.
The more than 50 participants in the study were divided into two groups, one of which received two years of supervised exercise training and the other group, a control group, which participated in yoga and balance training.
At the end of the two-year study, those who had exercised showed an 18 percent improvement in their maximum oxygen intake during exercise and a more than 25 percent improvement in compliance, or elasticity, of the left ventricular muscle of the heart, Dr. Levine noted. He compared the change in the heart to a stretchy, new rubber band versus one that has gotten stiff sitting in a drawer.
Sedentary aging can lead to a stiffening of the muscle in the heart’s left ventricle, the chamber that pumps oxygen-rich blood back out to the body, he explained.
“When the muscle stiffens, you get high pressure and the heart chamber doesn’t fill as well with blood. In its most severe form, blood can back up into the lungs. That’s when heart failure develops,” said Dr. Levine, who holds the S. Finley Ewing Chair for Wellness at Texas Health Dallas and the Harry S. Moss Heart Chair for Cardiovascular Research. He also holds the Distinguished Professorship in Exercise Sciences at UT Southwestern, which is celebrating its 75th anniversary this year.
Earlier research by UT Southwestern cardiologists showed that left ventricular stiffening often shows up in middle age in people who don’t exercise and aren’t fit, leaving them with small, stiff chambers that can’t pump blood as well.
However, the researchers also found that the heart chamber in competitive masters-level athletes remains large and elastic, and that even four to five days of committed exercise over decades is enough for noncompetitive athletes to reap most of this benefit.
In the current study, researchers wanted to know if exercise can restore the heart’s elasticity in previously sedentary individuals – especially if begun in late middle age. Previous studies from Dr. Levine’s research program have shown substantial improvements in cardiac compliance in young individuals after a year of training, but surprisingly little change if the training was started after age 65.
To start the study, researchers recruited 53 participants, ages 45 to 64. Many came from the Dallas Heart Study, which includes 6,000 Dallas residents and is the only single-center heart study of its size and multiethnic composition. The Dallas Heart Study is designed to improve the diagnosis, prevention, and treatment of heart disease.
Public Release: 9-Jan-2018
Cancer targeted with reusable ‘stinging nettle’ treatment
Cancer cells can be destroyed more effectively and selectively with a unique new reusable treatment, activated with a substance found in stinging nettles and ants – thanks to new research by the University of Warwick.
University of Warwick
Cancer cells can be destroyed more effectively and selectively with a unique new reusable treatment, activated with a substance found in stinging nettles and ants – thanks to new research by the University of Warwick.
Led by Professor Peter J. Sadler from Warwick’s Department of Chemistry, researchers have developed a new line of attack against cancer: an organic-osmium compound, which is triggered using a non-toxic dose of sodium formate, a natural product found in many organisms, including nettles and ants.
Named JPC11, it targets a metabolic process which cancer cells rely on to survive and multiply. It does this by converting a key substance used by cancer cells to provide the energy they need for rapid division (pyruvate) into an unnatural lactate – leading to the cells’ destruction.
Uniquely, this chemo-catalyst treatment can be recycled and reused within a cancer cell to attack it repeatedly.
This unprecedented functional ability to recycle and reuse the compound within cancer cells could lead to future anticancer drugs being administered in smaller, more effective, and potentially less toxic doses – decreasing the side-effects of chemotherapy.
The researchers have been focusing on the potential to use this compound on ovarian and prostate cancers.
Ovarian cancers are becoming increasingly resistant to existing chemotherapy drugs (such as the platinum drug, cisplatin). Since this new research functions in a totally new and unique way, it may overcome this acquired resistance and widen the spectrum of anticancer activity.
Importantly, the development opens up a possibility for a more selective cancer treatment as JPC11 was observed to specifically target the biochemistry of cancer cells, leaving healthy cells largely untouched – another improvement compared to existing platinum-based drugs, which can also attack non-cancerous cells.
Dr James Coverdale, a Research Fellow from Warwick’s Department of Chemistry, commented:
“This is a significant step in the fight against cancer. Manipulating and applying well-established chemistry in a biological context provides a highly selective strategy for killing cancer cells.
“We have discovered that chemo-catalyst JPC11 has a unique mechanism of action – and we hope that this will lead to more effective, selective and safer treatments in the future.”
Professor Peter Sadler, a medicinal chemist at the University of Warwick commented:
“Platinum compounds are the most widely used drugs for cancer chemotherapy, but we urgently need to respond to the challenges of circumventing resistance and side-effects. Our lab is focussed on the discovery of truly novel anticancer drugs which can kill cells in totally new ways. Chemo-catalysts, especially those with immunogenic properties, might provide a breakthrough.
“It will take time to progress from the lab to the clinic, but we are fortunate to have a talented enthusiastic, international team working with colleagues in Warwick Cancer Research Centre across the borderlines of chemistry, cell and systems biology and cancer medicine who are determined to succeed.”
Professor Martin Wills, catalyst specialist at the University of Warwick, commented:
“Although asymmetric catalytic hydrogenation processes are well developed in the materials industry, this research provides the first ever example of it being achieved inside cells using a synthetic catalyst.”
Handedness (molecular asymmetry) is critical to the function of bio-molecules in the body. Proteins, enzymes and our DNA, for example – are handed. Only the correct hand works, in the same way that a right hand does not fit a left-hand glove.
In this case, the osmium compound JPC11, with sodium formate, can selectively produce a molecule of a specific ‘handedness’ – thus manipulating how cancer cells grow.
Dr Coverdale explained:
“The ‘handedness’ of molecules is critical in the body. Our hands are near-identical, but are mirror images of each other. The same can be true of molecules, and in some cases, having the wrong handed molecule can have profound biological consequences.
“We believe that manipulation of the ‘handedness’ of molecules in cells could provide a new strategy for fighting diseases.”
It was funded by the European Research Council, Science City (Advantage West Midlands and the European Regional Development Fund), The University of Warwick, Bruker Daltonics, the Engineering and Physical Research Council and Cancer Research UK.
Public Release: 18-Jan-2018
Women run faster after taking newly developed supplement, study finds
Combo of minerals and other nutrients might boost performance
Ohio State University
COLUMBUS, Ohio – A new study found that women who took a specially prepared blend of minerals and nutrients for a month saw their 3-mile run times drop by almost a minute.
The women who took the supplement also saw improvements in distance covered in 25 minutes on a stationary bike and a third test in which they stepped on and off a bench, according to research from The Ohio State University.
The small study of young women, published in the Journal of the International Society of Sports Nutrition, compared the performance of those who took the supplement with a control group that took a placebo.
In an initial experiment including 28 women, half of whom took the supplement, researchers found that those in the study group saw their 3-mile run times drop from 26.5 minutes on average to 25.6 minutes. Stationary bike distance covered in 25 minutes increased to an average of 6.5 miles, compared to 6 miles at the start of the study. Steps in the step test increased to almost 44 from about 40. All of the changes were statistically significant and were not seen in the placebo group.
A second follow-up experiment – designed to see if the first was reproducible and test a lower dose of one of the nutrients – included 36 women and found a 41-second average decrease in run times.
“We know that young women, in particular, often have micro-deficiencies in nutrients and that those nutrients play a role in how cells work during exercise,” said Robert DiSilvestro, lead author of the study and a professor of human nutrition at Ohio State.
“They tend to eat less meat than men, and menstruation also plays an important role in mineral loss,” he said.
DiSilvestro is working toward developing and selling a supplement, based on this and previous research. It’s expected to cost between $35 and $40 for a month’s supply. The study was supported by the Gatorade Sports Science Institute, but the company is not involved in the commercialization efforts.
The minerals in the study included forms of iron, copper and zinc along with two other nutrients – carnitine (derived from an amino acid) and phosphatidylserine (made up of fatty acids and amino acids.)
“I decided to start with minerals that are commonly low – or thought to be low in many diets – and brought in some of the supporting cast. These two nutrients, which are needed for cell function, are made by our bodies but also come from food we eat,” DiSilvestro said.
In the study, those who took the supplement combo were asked to sprinkle it into a beverage of their choice twice a day. (In the second round of study, DiSilvestro’s team delivered the combo in capsule form.) The amount of nutrients in the supplements was well below a level that could cause harmful side effects, he said, and none was observed in this study.
Participants were recreational athletes 18 to 30 years old who had regularly done aerobic exercise at least two to three hours a week for six months. They also had to be runners.
“We wanted people who could already run three miles without it being a terrible burden,” DiSilvestro said.
He and his collaborators compared the women’s athletic performance at the start of the study to performance at the end of a 30-day study period.
“The run-time drops in people at this stage of life were pretty large when they took the supplement. And in the placebo group, we saw little change,” DiSilvestro said.
Stationary biking and the step tests were included because the women didn’t typically perform these activities. These measures also gauged whether there might be benefits that extended beyond the running, when the women were more physically tired. (They ran first, then biked, then performed the step test.)
Though it’s less common for men to have mild deficiencies in these nutrients, with the exception of copper, DiSilvestro said he’s interested in whether he might see benefits in vegetarian men. Another potential area for study is in longer-distance running.
Public Release: 17-Jan-2018
Prebiotics in infant formula could improve learning and memory and alter brain chemistry
University of Illinois College of Agricultural, Consumer and Environmental Sciences
URBANA, Ill. – Nearly every American who has become a parent in the last decade has heard the slogan, “breast milk is best,” and has likely been encouraged to offer breast milk to newborns. Among other things, breast milk contains natural sources of prebiotics: small, indigestible fiber molecules that promote the growth of good bacteria in the baby’s gut. Yet for many families, breastfeeding is difficult or impossible. Fortunately, modern infant formulas are getting closer to the real thing with the help of University of Illinois researchers.
In a recent study from the Piglet Nutrition and Cognition Lab at U of I, scientists worked with piglets to show prebiotics included in infant formula can enhance memory and exploratory behavior.
“When we provide prebiotics in formula, our results confirm that we can not only benefit gut health, which is known, but we can also influence brain development,” says Ryan Dilger, associate professor in the Department of Animal Sciences, Division of Nutritional Sciences, and Neuroscience Program at U of I. “We can actually change the way piglets learn and remember by influencing bacteria in the colon.”
Piglets are widely considered a more informative model for human infants than mice and rats; their digestive systems, behavioral responses, and brain development are remarkably similar to human infants. Therefore, researchers are increasingly turning to piglets to test hypotheses in pre-clinical trials related to human health, especially in the context of gut microbes and brain development.
“There hasn’t been a lot of work looking at the gut-brain axis in humans, but a lot of rodent work is showing those connections. This is taking it to an animal model that is a lot closer to human infants and asking if that connection still exists and if we can tease out possible mechanisms,” says Stephen Fleming, lead author of the study and a doctoral student in the Neuroscience Program at U of I.
In early 2016, Dilger and his colleagues worked with piglets to show that a combination of innovative formula components, including prebiotics, may play a role in brain development and behavior. In their new study, the team concentrated solely on the effects of prebiotics.
Starting on the second day of life, piglets were given a cow’s milk-based infant formula supplemented with polydextrose (PDX), a synthetic carbohydrate with prebiotic activity, and galactooligosaccharide (GOS), a naturally occurring prebiotic. When the piglets were 25 days old, Fleming took them through several learning, memory, and stress tests. After 33 days, blood, brain, and intestinal tissues were collected for analysis.
The test for learning and memory gave piglets a chance to play with dog toys: one they’d seen before and one brand-new toy. If they spent more time with the new toy, that was an indication that the piglet recognized it as new and preferred it. This “novel object recognition” test improves on classic maze tests commonly used in rodent studies.
“If you’re trying to test for memory, this test is closer to what we’d do with an infant. After all, we don’t generally train infants on mazes,” Fleming says. “We know from previous research this test works for pigs, but this is the first published example of using it in a nutrition context.”
Pigs fed PDX and GOS spent more time playing with new objects than pigs who didn’t receive the prebiotic supplements. The preference for novel objects, an indication of natural curiosity, is a sign of healthy brain development and points towards positive development of learning and memory.
When prebiotics are working the way they should, good bacteria increase in abundance. One way to tell is by looking at metabolic end-products – volatile fatty acids (VFAs) – excreted by bacteria during digestion of prebiotic fibers.
“Volatile fatty acids are a global indicator for whether prebiotics had an effect on the overall population of bacteria. For example, we might want to see an increase in Lactobacillus and other beneficial bacteria that produce butyrate,” Dilger explains. Volatile fatty acid (VFA) concentrations in the colon, blood, and brain were changed in pigs receiving PDX and GOS compared with control pigs.
Recent evidence suggests that bacterial VFAs could be getting into the blood and traveling to the brain, where they could potentially affect mood and behavior.
“We found that, yes, VFAs are absorbed in the blood of pigs that were fed PDX/GOS. And, yes, they do get into the brain,” Fleming explains. “But when we looked at the relationship between these VFAs and the results of our behavior tests, there did not appear to be a clear connection.”
Another surprise was a decrease in serotonin in brains of pigs fed the prebiotic. “When you hear less serotonin, there’s an immediate reaction to say, ‘Well, that’s bad,'” Fleming says. Not necessarily; those pigs didn’t show greater anxiety than control pigs during a stress test or poorer performance when given a learning and memory test. The researchers hypothesize that the prebiotics may alter levels of tryptophan, serotonin’s amino acid precursor, but it’s too early to say.
Although more work is needed to tackle remaining questions, the study adds to the growing body of research suggesting a strong and potentially modifiable link between the gut and the brain: a link that makers of infant formula should strongly consider.
“There are so many ways we can alter the composition of the microbiota and they can have very strong benefits. Promoting good ‘gut health’ remains a strong focus in the field of nutrition,” Dilger says.
Public Release: 22-Jan-2018
Dietary fiber protects against obesity and metabolic syndrome, study finds
Georgia State University
ATLANTA–Consumption of dietary fiber can prevent obesity, metabolic syndrome and adverse changes in the intestine by promoting growth of “good” bacteria in the colon, according to a study led by Georgia State University.
The researchers found enriching the diet of mice with the fermentable fiber inulin prevented metabolic syndrome that is induced by a high-fat diet, and they identified specifically how this occurs in the body. Metabolic syndrome is a cluster of conditions closely linked to obesity that includes increased blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol or triglyceride levels. When these conditions occur together, they increase a person’s risk of heart disease, stroke and diabetes.
Obesity and metabolic syndrome are associated with alterations in gut microbiota, the microorganism population that lives in the intestine. Modern changes in dietary habits, particularly the consumption of processed foods lacking fiber, are believed to affect microbiota and contribute to the increase of chronic inflammatory disease, including metabolic syndrome. Studies have found a high-fat diet destroys gut microbiota, reduces the production of epithelial cells lining the intestine and causes gut bacteria to invade intestinal epithelial cells.
This study found the fermentable fiber inulin restored gut health and protected mice against metabolic syndrome induced by a high-fat diet by restoring gut microbiota levels, increasing the production of intestinal epithelial cells and restoring expression of the protein interleukin-22 (IL-22), which prevented gut microbiota from invading epithelial cells. The findings are published in the journal Cell Host & Microbe.
“We found that manipulating dietary fiber content, particularly by adding fermentable fiber, guards against metabolic syndrome,” said Dr. Andrew Gewirtz, professor in the Institute for Biomedical Sciences at Georgia State. “This study revealed the specific mechanism used to restore gut health and suppress obesity and metabolic syndrome is the induction of IL-22 expression. These results contribute to the understanding of the mechanisms that underlie diet-induced obesity and offer insight into how fermentable fibers might promote better health.”
For four weeks, the researchers fed mice either a grain-based rodent chow, a high-fat diet (high fat and low fiber content with 5 percent cellulose as a source of fiber) or a high-fat diet supplemented with fiber (either fermentable inulin fiber or insoluble cellulose fiber). The high-fat diet is linked to an increase in obesity and conditions associated with metabolic syndrome.
They discovered a diet supplemented with inulin reduced weight gain and noticeably reduced obesity induced by a high-fat diet, which was accompanied by a reduction in the size of fat cells. Dietary enrichment with inulin also markedly lowered cholesterol levels and largely prevented dysglycemia (abnormal blood sugar levels). The researchers found insoluble cellulose fiber only modestly reduced obesity and dysglycemia.
Supplementing the high-fat diet with inulin restored gut microbiota. However, inulin didn’t restore the microbiota levels to those of mice fed a chow diet. A distinct difference in microbiota levels remained between mice fed a high-fat diet versus those fed a chow diet. Enrichment of high-fat diets with cellulose had a mild effect on microbiota levels.
In addition, the researchers found switching mice from a grain-based chow diet to a high-fat diet resulted in a loss of colon mass, which they believe contributes to low-grade inflammation and metabolic syndrome. When they switched mice back to a chow diet, the colon mass was fully restored.
Public Release: 22-Jan-2018
Powerful food-derived antioxidant can halt, prevent fatty liver disease in mice
Obese mothers often pass poor dietary impacts to offspring
University of Colorado Anschutz Medical Campus
AURORA, Colo. (Jan. 22, 2018) – As obesity continues to rise in the U.S., non-alcoholic fatty liver disease (NAFLD) has become a major public health issue, increasingly leading to cancer and liver transplants.
But new research from the University of Colorado Anschutz Medical Campus has discovered that a powerful anti-oxidant found in kiwi fruit, parsley, celery and papaya known as pyrroloquinoline quinone, or PQQ, can halt or prevent the progression of fatty liver disease in the offspring of mice fed a high-fat Western-style diet.
The study, published today in the journal Hepatology Communications, was led by Karen Jonscher, PhD, associate professor of anesthesiology and a physicist at CU Anschutz.
Growing evidence suggests that childhood obesity and fatty liver disease is influenced by maternal diet and the infant’s microbiome, the community of microorganisms inhabiting the body.
Jonscher and her colleagues found that mother mice fed a Western-style diet passed on the negative impacts of that diet to their offspring.
Jonscher’s earlier work on PQQ showed it helped turn back these detrimental effects in newborn mice in milder forms of liver disease. In this study, she demonstrated that it also works on the early offspring microbiome to prevent the development of fatty liver disease.
Over the past decade, it has become clear that the developing infant gut microbiome affects maturation of the immune system and gastrointestinal tract, metabolism, and brain development.
“Increasingly, evidence suggests that exposure to maternal obesity creates an inflammatory environment in utero. This leads to long-lasting postnatal disruptions of the offspring’s innate immune system and gut bacterial health, which may increase the risk for development of fatty liver disease,” Jonscher said.
Obesity, which often stems from a high-fat, high-cholesterol, sugary diet, is a major cause of NAFLD. According to the Journal of the American Medical Association, nearly 60 percent of American women of childbearing age are overweight or obese. Numerous studies suggest their children tend to have increased liver fat and a higher risk of becoming obese.
“Fatty liver disease is the number one liver disease in the world,” Jonscher said. “It is now the leading cause of liver transplants, eclipsing hepatitis in many areas of the U.S.” The researchers found that they could halt and prevent liver disease from developing in young mice by feeding their mothers PQQ.
“Our results highlight the importance of the neonatal period as a critical developmental window to protect obese offspring from the harmful effects of diet-induced lipotoxicity and potentially halt the devastating trend of increasing pediatric NAFLD associated with childhood obesity,” the study said.
Jonscher noted that more work is required to determine if these studies might apply to humans.
“But there is a possibility that people with fatty liver disease could potentially benefit,” she said. “The supplement is available online and in grocery stores but individuals should consult their doctors first before using it.”
Public Release: 23-Jan-2018
Curcumin improves memory and mood, new UCLA study says
Twice-daily supplements boosted cognitive power over 18 months
University of California – Los Angeles
Lovers of Indian food, give yourselves a second helping: Daily consumption of a certain form of curcumin — the substance that gives Indian curry its bright color — improved memory and mood in people with mild, age-related memory loss, according to the results of a study conducted by UCLA researchers.
The research, published online Jan. 19 in the American Journal of Geriatric Psychiatry, examined the effects of an easily absorbed curcumin supplement on memory performance in people without dementia, as well as curcumin’s potential impact on the microscopic plaques and tangles in the brains of people with Alzheimer’s disease.
Found in turmeric, curcumin has previously been shown to have anti-inflammatory and antioxidant properties in lab studies. It also has been suggested as a possible reason that senior citizens in India, where curcumin is a dietary staple, have a lower prevalence of Alzheimer’s disease and better cognitive performance.
“Exactly how curcumin exerts its effects is not certain, but it may be due to its ability to reduce brain in?ammation, which has been linked to both Alzheimer’s disease and major depression,” said Dr. Gary Small, director of geriatric psychiatry at UCLA’s Longevity Center and of the geriatric psychiatry division at the Semel Institute for Neuroscience and Human Behavior at UCLA, and the study’s first author.
The double-blind, placebo-controlled study involved 40 adults between the ages of 50 and 90 years who had mild memory complaints. Participants were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months.
All 40 subjects received standardized cognitive assessments at the start of the study and at six-month intervals, and monitoring of curcumin levels in their blood at the start of the study and after 18 months. Thirty of the volunteers underwent positron emission tomography, or PET scans, to determine the levels of amyloid and tau in their brains at the start of the study and after 18 months.
The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos.
The amygdala and hypothalamus are regions of the brain that control several memory and emotional functions.
Four people taking curcumin, and two taking placebos, experienced mild side effects such as abdominal pain and nausea.
The researchers plan to conduct a follow-up study with a larger number of people. That study will include some people with mild depression so the scientists can explore whether curcumin also has antidepressant effects. The larger sample also would allow them to analyze whether curcumin’s memory-enhancing effects vary according to people’s genetic risk for Alzheimer’s, their age or the extent of their cognitive problems.
“These results suggest that taking this relatively safe form of curcumin could provide meaningful cognitive benefits over the years,” said Small, UCLA’s Parlow-Solomon Professor on Aging.
The paper’s authors, in addition to Small, are Prabha Siddarth, Dr. Zhaoping Li, Karen Miller, Linda Ercoli, Natacha Emerson, Jacqueline Martinez, Koon-Pong Wong, Jie Liu, Dr. David Merrill, Dr. Stephen Chen, Susanne Henning, Nagichettiar Satyamurthy, Sung-Cheng Huang, Dr. David Heber and Jorge Barrio, all of UCLA.
The study was supported by the Ahmanson Foundation, the Marshall and Margherite McComb Foundation, the McMahan Foundation, Bob and Marion Wilson, the Fran and Ray Stark Foundation Fund for Alzheimer’s Disease Research, the U.S. Department of Energy and the National Institutes of Health.
Theravalues Corp. provided the curcumin and placebos for the trial, as well as funds for laboratory testing and for Small’s travel to present preliminary findings at the 2017 Alzheimer’s Association International Conference.
Public Release: 23-Jan-2018
Number of older people with four or more diseases will double by 2035, say researchers
A study published today in Age and Ageing, the scientific journal of the British Geriatrics Society, reports that the number of older people diagnosed with four or more diseases will double between 2015 and 2035. A third of these people will be diagnosed with dementia, depression or a cognitive impairment.
The study, conducted by researchers at Newcastle University’s Institute for Ageing, found that over the next 20 years there will be a massive expansion in the number of people suffering from multiple diseases, known as multi-morbidity. As a result two-thirds of the life expectancy gains, predicted as 3.6 years for men, 2.9 years for women, will be spent with four or more diseases.
Over the next 20 years the largest increase in diagnoses will be cancer (up by 179.4%) and diabetes (up by 118.1%) in the older population, whilst arthritis and cancer will see the greatest rise in prevalence. In the population over the age of 85 years all diseases, apart from dementia and depression, will more than double in absolute numbers between 2015 and 2035.
Professor Carol Jagger, Professor of Epidemiology of Ageing at Newcastle University’s Institute for Ageing led the study which has developed the Population Ageing and Care Simulation (PACSim) model. She said: “Much of the increase in four or more diseases, which we term complex multi-morbidity, is a result of the growth in the population aged 85 years and over. More worryingly, our model shows that future young-old adults, aged 65 to 74 years, are more likely to have two or three diseases than in the past. This is due to their higher prevalence of obesity and physical inactivity which are risk factors for multiple diseases.”
In the UK, healthcare delivery was built, and generally remains centred, on the treatment of single diseases.
Professor Jagger adds: “These findings have enormous implications for how we should consider the structure and resources for the NHS in the future. Multi-morbidity increases the likelihood of hospital admission and a longer stay, along with a higher rate of readmission, and these factors will continue to contribute to crises in the NHS.”
The authors state that patients with complex multi-morbidity need a different approach.
They conclude that a single-disease-focused model of health care is unsuitable for patients with multi-morbidity. There needs to be a focus on prevention of disease, and a bespoke healthcare service provision for patients with multi-morbidity.
The Age & Ageing paper ‘Projections of multi-morbidity in the older population in England to 2035: estimates from the Population Ageing and Care Simulation (PACSim) model’ can be viewed from 9am on 23 January here: https://academic.oup.com/ageing/article-lookup/doi/10.1093/ageing/afx201
Public Release: 23-Jan-2018
Women taking probiotics during pregnancy might have lower pre-eclampsia and premature birth risk
But timing may be crucial, findings suggest
Probiotics taken during pregnancy might help lower the risks of pre-eclampsia and premature birth, suggests observational research in the online journal BMJ Open. But timing may be crucial, the findings indicate.
Pre-eclampsia, a condition in which the mother’s body mounts an exaggerated inflammatory response, affects up to 8 percent of all pregnancies, and can lead to severe complications for both mother and baby.
Premature birth (before 37 weeks) is a leading cause of illness and disability among the children born, affecting nearly one in 10 births in the US.
A growing body of evidence suggests that the mother’s diet influences the outcome of pregnancy. And previous research has suggested that probiotics–live bacteria and yeasts thought to promote good health–might reduce certain complications of pregnancy.
To find out whether the timing of intake might be influential, the researchers used data on more than 70,000 pregnancies from the Norwegian Mother and Child Cohort Study (MoBa).
As part of the MoBa study, mums-to-be provided information on their diet, lifestyle, medical history, and other relevant background factors at 15, 22, and 30 weeks of pregnancy.
At 15 and 30 weeks, the questions included additional information on intake of different milk products containing probiotic bacteria before and during their pregnancy.
Nearly one in four (just over 23%; 6502) women said they had consumed probiotic milk products before their pregnancy; more than a third (over 37%; 11,221) had done so during early pregnancy; and a similar proportion (just over 32%; 12,784) had done so late on.
Intake of probiotic milk products was more common among older, more affluent and better educated women, who were pregnant for the first time.
Among the 37,050 women included in the pre-eclampsia analysis, the condition was diagnosed in one in 20 (5%; 1851). In 550 of these cases, it was severe. Probiotic intake was associated with a 20 percent lower risk of the condition, but only during late pregnancy.
And when differences between the severity of pre-eclampsia were looked at separately this association was significant only for those whose condition was severe.
Among the 34,458 women included in the premature birth analysis, 2858 babies were born early, some 1795 of which were spontaneous premature births, and 1065 of which were iatrogenic–in other words, caused by the consequences of medical treatment.
A significant association emerged between probiotic intake during early pregnancy and an 11 percent lower risk of premature birth, rising to 27 percent for preterm birth late in the pregnancy.
The amount of probiotic consumed didn’t seem to make any difference, the findings showed.
This is an observational study, so no firm conclusions can be drawn about cause and effect, nor were the researchers able to account for strain viability or shelf life, both of which may have influenced the findings. Further research is required, they emphasise.
Nevertheless, they conclude: “If future randomised controlled studies support a protective effect of probiotic consumption on reduced risk of pre-eclampsia and preterm delivery, recommending [it] would be a promising public health measure to prevent these adverse pregnancy outcomes.”
Public Release: 24-Jan-2018
Vitamin D supplements could ease painful IBS symptoms
University of Sheffield
Vitamin D supplements could help to ease painful Irritable Bowel Syndrome (IBS) symptoms, a new study from the University of Sheffield has found.
Scientists from the University’s Department of Oncology and Metabolism reviewed and integrated all available research on vitamin D and IBS – a condition which affects two in 10 people in the UK.
The study showed a high prevalence of vitamin D deficiency in IBS patients – regardless of their ethnicity.
The Sheffield team also assessed the possible benefits of vitamin D supplements on IBS symptoms. Whilst they believe more research still needs to be conducted, their findings suggested supplements may help to ease symptoms which can include abdominal pain, bloating, diarrhoea and constipation. Vitamin D was shown to have the most benefit on quality of life in IBS.
Lead author of the study, Dr Bernard Corfe, said: “The study provides an insight into the condition and, importantly, a new way to try to manage it.
“It is evident from the findings that all people with IBS should have their vitamin D levels tested and a large majority of them would benefit from supplements.
“IBS is a poorly understood condition which impacts severely on the quality of life of sufferers. There is no single known cause and likewise no single known cure.”
IBS is a debilitating functional disorder of the gastrointestinal (GI) tract. Little is known about why and how the condition develops, although it is known that diet and stress can make symptoms worse.
The symptoms often cause embarrassment for patients meaning many live with the condition undiagnosed.
IBS accounts for 10 per cent of visits to GP surgeries and the condition has a significant and escalating burden on society as a consequence of lost work days and time spent on regular hospital appointments.
Vitamin D is essential for general wellbeing, including bone health, immune function, mental health as well as gut health. Vitamin D inadequacy can be remedied relatively easily with supplements if diagnosed.
Low vitamin D status has already been associated with the risk of colorectal cancer and has been implicated in inflammatory bowel disease.
The new study is published today (Thursday 25 January 2018) in the European Journal of Clinical Nutrition.
The University of Sheffield’s Department of Oncology and Metabolism conducts world-class research from basic clinical and translational cancer research to life course research and basic level biology through to diseases such as diabetes and osteoporosis.