The Gary Null Show - 09.07.21

Pomegranate peel has protective effects against enteropathogenic bacteria

US Department of Agriculture, August 31, 2021

A recent study by the U.S. Department of Agriculture revealed that pomegranate peel extract contains bioactive compounds that have potential antibacterial activity. The study’s findings were published in the journal Nutrition Research.

• Pomegranate fruit peel is considered an agricultural waste product. However, it is a rich source of polyphenols like punicalins, punicalagins and ellagic acids.
• Earlier studies have shown that products derived from pomegranates have health benefits, including antibacterial activity, in vitro.
• There is limited evidence, however, of their antibacterial activity in vivo.
• For this study, researchers sought to determine the antibacterial properties of pomegranate peel extract in vivo. In particular, they focused on the punicalin, punicalagin and ellagic acid present in the peel extract.
• The researchers infected C3H/He mice with the bacterial pathogen Citrobacter rodentium, a bacterium that mimics the enteropathogenic bacterium, Escherichia coli. Prior to infection, the mice were orally treated with water or pomegranate peel extract.
• Twelve days after infection, the researchers examined C. rodentium colonization of the colon and spleen, as well as changes in tissue and gene expression. Fecal excretions were also analyzed for C. rodentium.
• The results revealed that the pomegranate peel extract reduced weight loss and mortality induced by C. rodentium infection.
• The extract also reduced C. rodentium colonization of the spleen.
• Additionally, pomegranate peel extract decreased the extent of damage in the colon caused by C. rodentium infection.

In sum, pomegranate fruit peel extract contains bioactive compounds that can help reduce the severity of C. rodentium infection in vivo.

 

Vitamin D may protect against young-onset colorectal cancer

Dana-Farber Cancer Institute and Harvard  School of Public Health, September 1, 2021

Consuming higher amounts of Vitamin D - mainly from dietary sources - may help protect against developing young-onset colorectal cancer or precancerous colon polyps, according to the first study to show such an association.

The study, recently published online in the journal Gastroenterology, by scientists from Dana-Farber Cancer Institute, the Harvard T.H. Chan School of Public Health, and other institutions, could potentially lead to recommendations for higher vitamin D intake as an inexpensive complement to screening tests as a colorectal cancer prevention strategy for adults younger than age 50.

While the overall incidence of colorectal cancer has been declining, cases have been increasing in younger adults - a worrisome trend that has yet to be explained. The authors of the study, including senior co-authors Kimmie Ng, MD, MPH, of Dana-Farber, and Edward Giovannucci, MD, DSc., of the T.H. Chan School, noted that vitamin D intake from food sources such as fish, mushrooms, eggs, and milk has decreased in the past several decades. There is growing evidence of an association between vitamin D and risk of colorectal cancer mortality. However, prior to the current study, no research has examined whether total vitamin D intake is associated with the risk of young-onset colorectal cancer.

“Vitamin D has known activity against colorectal cancer in laboratory studies. Because vitamin D deficiency has been steadily increasing over the past few years, we wondered whether this could be contributing to the rising rates of colorectal cancer in young individuals,” said Ng, director of the Young-Onset Colorectal Cancer Center at Dana-Farber. “We found that total vitamin D intake of 300 IU per day or more - roughly equivalent to three 8-oz. glasses of milk - was associated with an approximately 50% lower risk of developing young-onset colorectal cancer.”

The results of the study were obtained by calculating the total vitamin D intake - both from dietary sources and supplements - of 94,205 women participating in the Nurses’ Health Study II (NHS II). This study is a prospective cohort study of nurses aged 25 to 42 years that began in 1989. The women are followed every two years by questionnaires on demographics, diet and lifestyle factors, and medical and other health-related information. The researchers focused on a primary endpoint - young-onset colorectal cancer, diagnosed before 50 years of age. They also asked on a follow-up questionnaire whether they had had a colonoscopy or sigmoidoscopy where colorectal polyps (which may be precursors to colorectal cancer) were found.

During the period from 1991 to 2015 the researchers documented 111 cases of young-onset colorectal cancer and 3,317 colorectal polyps. Analysis showed that higher total vitamin D intake was associated with a significantly reduced risk of early-onset colorectal cancer. The same link was found between higher vitamin D intake and risk of colon polyps detected before age 50.

The association was stronger for dietary vitamin D - principally from dairy products - than from vitamin D supplements. The study authors said that finding could be due to chance or to unknown factors that are not yet understood.

Interestingly, the researchers didn’t find a significant association between total vitamin D intake and risk of colorectal cancer diagnosed after age 50. The findings were not able to explain this inconsistency, and the scientists said further research in a larger sample is necessary to determine if the protective effect of vitamin D is actually stronger in young-onset colorectal cancer.

In any case, the investigators concluded that higher total vitamin D intake is associated with decreased risks of young-onset colorectal cancer and precursors (polyps). “Our results further support that vitamin D may be important in younger adults for health and possibly colorectal cancer prevention,” said Ng. “It is critical to understand the risk factors that are associated with young-onset colorectal cancer so that we can make informed recommendations about diet and lifestyle, as well as identify high risk individuals to target for earlier screening.”

 

 

Choosing personal exercise goals, then tackling them immediately is key to sustaining change

University of Pennsylvania, September 1, 2021

When people set their own exercise goals – and then pursue them immediately – it’s more likely to result in lasting positive changes, according to a new study at the Perelman School of Medicine at the University of Pennsylvania. The results of this research are especially important because they were found among an underserved population that is at particularly high risk of having or developing heart conditions. The study was published in JAMA Cardiology.

“Most behavior change programs involve goal-setting, but the best way to design that process is unknown,” said lead author Mitesh Patel, MD, MBA, an associate professor of Medicine at Penn and vice president for Clinical Transformation at Ascension. “Our clinical trial demonstrated that physical activity increased the most when patients chose their goals rather than being assigned them, and when the goals started immediately rather than starting lower and gradually increasing over time. These findings are particularly important because the patients were from lower-income neighborhoods and may face a number of challenges in achieving health goals.”

This study consisted of 500 patients from low-income neighborhoods, mainly in West Philadelphia but also elsewhere in and outside of the city. Participants either had a cardiovascular disease or were assessed to have a near-10 percent risk of developing one within a decade. These high-risk patients stood to greatly gain from increased physical activity.

Patel’s previous work at the Penn Medicine Nudge Unit often focused on the use of gamification, a concept used to create behavioral change by turning it into a game. The work usually tested whether playing a game attached to physical activity goals could make significant increases against not playing a game, or between different versions of a game.

As with past studies, every participant was given a wearable step tracker that recorded their daily step counts through Penn’s Way to Health platform. But what set this study apart from many of its predecessors was that the main outcomes of the research were less about participation in the games themselves and more about how goals were established, as well as when participants were encouraged to pursue them.

Once every participant got their wearable step counter, they were given a week or two to get used to it. This time period also functioned as a baseline-setting period for everyone’s pre-intervention daily step count. After that, participants were randomly assigned to the control group, which didn’t have step goals or games attached, or one of the gaming groups with goals.

Those in the gamified group also went through two other sets of random assignments. One determined whether they’d have input on their step goal, or whether they’d just be assigned a standard one. The second decided whether each participant would immediately start working toward their goals (for the entire 16-week intervention), or whether they’d ramp up to it, with minor increases in goals, until the full goals kicked in at week nine.

After analyzing the results, the researchers saw that the only group of participants who achieved significant increases in activity were those who chose their own goals and started immediately. They had the highest average increase in their steps compared to the group with no goals, roughly 1,384 steps per day. And, in addition to raw step counts, the study also measured periods of sustained, high activity, amounting to an average increase of 4.1 minutes daily.

Comparatively, those who were assigned their goals or had full goals delayed for half the intervention only increased their daily steps above the control group’s average by between 500 and 600 steps.

“Individuals who select their own goals are more likely to be intrinsically motivated to follow through on them,” said Kevin Volpp, MD, PhD, director of the Center for Health Incentives and Behavioral Economics. “They feel like the goal is theirs and this likely enables greater engagement.”

The study didn’t end when the researchers turned the games off. Participants kept their activity trackers, and in the eight weeks following the intervention, the group that chose their goals and started immediately kept up their progress. In fact, they achieved almost the exact same average in steps – just three less than during the active games.

“It is exciting to see that the group that increased their activity levels by the most steps maintained those levels during follow-up,” Patel said. “This indicates that gamification with self-chosen and immediate goals helped these patients form a new habit.”

Many programs, whether offered through work or by health insurance companies, offer incentives for boosts in physical activity. But these goals are often fairly static and assigned based on round numbers. Patel, Volpp, and colleagues believe this research suggests that adjusting goal setting in these programs can have a significant impact. And if these adjustments lead to gains among people with lower incomes, whom cardiovascular disease kill at 76 percent higher rates, that could be particularly important.          

“Goal-setting is a fundamental element of almost every physical activity program, whether through a smartphone app or in a workplace wellness program,” Volpp said. “Our findings reveal a simple approach that could be used to improve the impact of these programs and the health of their patients.”

 

Comparing seniors who relocate long-distance shows that where you live affects your longevity

Massachusetts Institute of Technology, September 1, 2021

Would you like to live longer? It turns out that where you live, not just how you live, can make a big difference.

That's the finding of an innovative study co-authored by an MIT economist, which examines senior citizens across the U.S. and concludes that some locations enhance longevity more than others, potentially for multiple reasons.

The results show that when a 65-year-old moves from a metro area in the 10th percentile, in terms of how much those areas enhance longevity, to a metro area the 90th percentile, it increases that person's life expectancy by 1.1 years. That is a notable boost, given that mean life expectancy for 65-year-olds in the U.S. is 83.3 years.

"There's a substantively important causal effect of where you live as an elderly adult on mortality and life expectancy across the United States," says Amy Finkelstein, a professor in MIT's Department of Economics and co-author of a newly published paper detailing the findings.

Researchers have long observed significant regional variation in life expectancy in the U.S., and often attributed it to "health capital"—tendencies toward obesity, smoking, and related behavioral factors in the regional populations. But by analyzing the impact of moving, the current study can isolate and quantify the effect that the location itself has on residents.

As such, the research delivers important new information about large-scale drivers of U.S. health outcomes—and raises the question of what it is about different places that affects the elderly's life expectancy. One clear possibility is the nature of available medical care. Other possible drivers of longevity include climate, pollution, crime, traffic safety, and more.

"We wanted to separate out the role of people's prior experiences and behaviors—or health capital—from the role of place or environment," Finkelstein says.

The paper, "Place-Based Drivers of Mortality: Evidence of Migration," is published in the August issue of the American Economic Review. The co-authors are Finkelstein, the John and Jennie S. MacDonald Professor of Economics at MIT, and Matthew Gentzkow and Heidi Williams, who are both professors of economics at Stanford University.

To conduct the study, Finkelstein, Gentzkow, and Williams analyzed Medicare records from 1999 to 2014, focusing on U.S. residents between the ages of 65 and 99. Ultimately the research team studied 6.3 million Medicare beneficiaries. About 2 million of those moved from one U.S. "commuting zone" to another, and the rest were a random 10 percent sample of people who had not moved over the 15-year study period. (The U.S. Census Bureau defines about 700 commuting zones nationally.)

A central element of the study involves seeing how different people who were originally from the same locations fared when moving to different destinations. In effect, says Finkelstein, "The idea is to take two elderly people from a given origin, say, Boston. One moves to low-mortality Minneapolis, one moves to high-mortality Houston. We then compare thow long each lives after they move."

Different people have different health profiles before they move, of course. But Medicare records include detailed claims data, so the researchers applied records of 27 different illnesses and conditions—ranging from lung cancer and diabetes to depression—to a standard mortality risk model, to categorize the overall health of seniors when they move. Using these "very, very rich pre-move measures of their health," Finkelstein notes, the researchers tried to account for pre-existing health levels of seniors from the same location who moved to different places.

Still, even assessing people by 27 measures does not completely describe their health, so Finkelstein, Gentzkow, and Williams also estimated what fraction of people's health conditions they had not observed—essentially by calibrating the observed health of seniors against health capital levels in places they were moving from. They then consider how observed health varies across individuals from the same location moving to different destinations and, assuming that differences in unobserved health—such as physical mobility—vary in the same way as observed differences in health, they adjust their estimates accordingly.

All told, the study found that many urban areas on the East and West Coasts—including New York City, San Francisco, and Miami—have positive effects on longevity for seniors moving there. Some Midwestern metro areas, including Chicago, also score well.

By contrast, a large swath of the deep South has negative effects on longevity for seniors moving there, including much of Alabama, Arkansas, Louisiana, and northern Florida. Much of the Southwest, including parts of Texas, Oklahoma, New Mexico, and Arizona, fares similarly poorly.

The scholars also estimate that health capital accounts for about 70 percent of the difference in longevity across areas of the U.S., and that location effects account for about 15 percent of the variation.

"Yes, health capital is important, but yes, place effects also matter," Finkelstein says.

Other leading experts in health economics say they are impressed by the study. Jonathan Skinner, the James O. Freeman Presidential Professor of Economics, Emeritus, at Dartmouth College, says the scholars "have provided a critical insight" into the question of place effects "by considering older people who move from one place to another, thus allowing the researchers to cleanly identify the pure effect of the new location on individual health—an effect that is often different from the health of long-term residents. This is an important study that will surely be cited and will influence health policy in coming years."

The Charlotte Effect: What makes a difference?

Indeed, the significance of place effects on life expectancy is also evident in another pattern the study found. Some locations—such as Charlotte, North Carolina—have a positive effect on longevity but still have low overall life expectancy, while other places—such as Santa Fe New Mexico—have high overall life expectancy, but a below-average effect on the longevity of seniors who move there.

Again, the life expectancy of an area's population is not the same thing as that location's effect on longevity. In places where, say, smoking is highly prevalent, population-wide longevity might be subpar, but other factors might make it a place where people of average health will live longer. The question is why.

"Our [hard] evidence is about the role of place," Finkelstein says, while noting that the next logical step in this vein of research is to look for the specific factors at work. "We know something about Charlotte, North Carolina, makes a difference, but we don't yet know what."

With that in mind, Finkelstein, Gentzkow, and Williams, along with other colleagues, are working on a pair of new studies about health care practices to see what impact place-based differences may have; one study focuses on doctors, and the other looks at the prescription opioid epidemic.

In the background of this research is a high-profile academic and policy discussion about the impact of health care utilization. One perspective, associated with the Dartmouth Atlas of Health Care project, suggests that the large regional differences in health care use it has documented have little impact on mortality. But the current study, by quantifying the variable impact of place, suggest there may be, in turn, a bigger differential impact in health care utilization yet to be identified.

For her part, Finkelstein says she would welcome further studies digging into health care use or any other factor that might explain why different places have different effects on life expectancy; the key is uncovering more hard evidence, wherever it leads.

"Differences in health care across places are large and potentially important," Finkelstein says. "But there are also differences in pollution, weather, [and] other aspects. … What we need to do now is get inside the black box of 'the place' and figure out what it is about them that matters for longevity."

 

Gut bacteria influence brain development

Researchers discover biomarkers that indicate early brain injury in extreme premature infants

University of Vienna (Austria), September 3, 2021

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. "We investigated the role this axis plays in the brain development of extreme preterm infants," says the first author of the study, David Seki. "The microorganisms of the gut microbiome - which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes - are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain," explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage
"In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury," adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. "Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided."

Comprehensive study of the development of extremely premature infants
Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. "Our data show that excessive growth of the bacterium Klebsiella and the associated elevated γδ-T-cell levels can apparently exacerbate brain damage," explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. "We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process," he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods - the team examined the microbiome using 16S rRNA gene sequencing, among other methods - the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants' brains.

Research continues with two studies
The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. "How the children's motoric and cognitive skills develop only becomes apparent over several years," explains Angelika Berger. "We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. " The most important cooperation partners for the project are already on board: "The children's parents have supported us in the study with great interest and openness," says David Seki. "Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that."

 

 

Amino acid supplements may boost vascular endothelial function in older adults: Study

University of Alabama, August 28, 2021

A combination of HMB (a metabolite of leucine), glutamine and arginine may improve vascular function and blood flow in older people, says a new study.

Scientists from the University of Alabama report that a supplement containing HMB (beta-hydroxy-beta-methylbutyrate), glutamine and arginine (Juven by Abbott Nutrition) increased flow-mediated dilation (FMD - a measure of blood flow and vascular health) by 27%, whereas no changes were observed in the placebo group.

However, the researchers did not observe any changes to markers of inflammation, including high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-alpha (TNF-alpha)

“Our results indicate that 6 months of dietary supplementation with HMB, glutamine and arginine had a positive impact on vascular endothelial function in older adults,” wrote the researchers, led by Dr Amy Ellis in the European Journal of Clinical Nutrition . “These results are clinically relevant because reduced endothelial-dependent vasodilation is a known risk factor for cardiovascular diseases.

“Further investigation is warranted to elucidate mechanisms and confirm benefits of foods rich in these amino acids on cardiovascular outcomes.”

The study supported financially by the National Center for Complementary and Alternative Medicine.

Study details

Dr Ellis and her co-workers recrtuited 31 community-dwelling men and women aged between 65 and 87 to participate in their randomized, placebo-controlled trial. The participants were randomly assigned to one of two groups: The first group received the active supplements providing 3 g HMB, 14 g glutamine and 14 g arginine per day; while the second group received a placebo.

After six months of intervention, the researchers found that FMD increased in the HMB + glutamine + arginine group, but no such increases were observed in the placebo group.

While no changes in CRP or TNF-alpha levels were observed in the active supplement group, a trend towards an increase in CRP levels was observed in the placebo group, but this did not reach statistical significance, they noted.

“Although no previous studies have examined this combination of amino acids on vascular function, we hypothesized that the active ingredients of the supplement would act synergistically to improve endothelial function by reducing oxidative stress and inflammation,” wrote the researchers. “However, although we observed a trend for increasing hsCRP among the placebo group (P=0.059), no significant changes in hsCRP or TNF-alpha were observed for either group.

“Possibly, the effects of the supplement on reducing oxidative stress and inflammation were subclinical, or the high variability in these biomarkers, particularly hsCRP, among our small sample could have precluded visible differences.”

The researchers also noted that an alternate mechanism may also be responsible, adding that arginine is a precursor of the potent vasodilator nitric oxide

“Although investigation of this mechanism was beyond the scope of this study, it is feasible that the arginine in the supplement improved endothelial-dependent vasodilation by providing additional substrate for nitric oxide synthesis,” they added.

 

 

Moderate coffee drinking associated with lower risk of mortality during 11-year median follow-up

Semmelweis University (Bulgaria), September 1 2021. 

Research presented at ESC (European Society of Cardiology) Congress 2021 revealed a lower risk of dying from any cause during an 11-year median period among light to moderate coffee drinkers in comparison with men and women who had no intake.

The study included 468,629 UK Biobank participants of an average age of 56.2 years who had no indications of heart disease upon enrollment. Coffee intake was classified as none, light to moderate at 0.5 to 3 cups per day or high at over 3 cups per day. A subgroup of participants underwent magnetic resonance imaging (MRI) of the heart to assess cardiac structure and function. 

Light to moderate coffee intake during the follow-up period was associated with a 12% decrease in the risk of dying from any cause, a 17% lower risk of cardiovascular mortality and a 21% reduction in the incidence of stroke in comparison with the risks associated with not drinking coffee. 

“The imaging analysis indicated that, compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” reported study author Judit Simon, of Semmelweis University in Budapest. “This was consistent with reversing the detrimental effects of aging on the heart.”

“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” she announced. “Our results suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years. Moreover, 0.5 to 3 cups of coffee per day was independently associated with lower risks of stroke, death from cardiovascular disease, and death from any cause.”