Monday, April 24, 2017

Chili peppers and marijuana calm the gut


You wouldn't think chili peppers and marijuana have much in common. But when eaten, both interact with the same receptor in our stomachs, according to a paper by UConn researchers published in the April 24 issue of the journal Proceedings of the National Academy of Sciences. The research could lead to new therapies for diabetes and colitis, and opens up intriguing questions about the relationship between the immune system, the gut and the brain.

Touch a chili pepper to your mouth and you feel heat. And biochemically, you aren't wrong. The capsaicin chemical in the pepper binds to a receptor that triggers a nerve that fires off to your brain: hot! Those same receptors are found throughout the gastrointestinal tract, for reasons that have been mysterious.

Curious, UConn researchers fed capsaicin to mice, and found the mice fed with the spice had less inflammation in their guts. The researchers actually cured mice with Type 1 diabetes by feeding them chili pepper. When they looked carefully at what was happening at a molecular level, the researchers saw that the capsaicin was binding to a receptor called TRPV1, which is found on specialized cells throughout the gastrointestinal tract. When capsaicin binds to it, TRPV1 causes cells to make anandamide. Anandamide is a compound chemically akin to the cannabinoids in marijuana. It was the anandamide that caused the immune system to calm down. And the researchers found they could get the same gut-calming results by feeding the mice anandamide directly.

The brain also has receptors for anandamide. It's these receptors that react with the cannabinoids in marijuana to get people high. Scientists have long wondered why people even have receptors for cannabinoids in their brains. They don't seem to interact with vital bodily functions that way opiate receptors do, for example.

"This allows you to imagine ways the immune system and the brain might talk to each other. They share a common language," says Pramod Srivastava, Professor of Immunology and Medicine at UConn Health School of Medicine. And one word of that common language is anandamide.

Srivastava and his colleagues don't know how or why anandamide might relay messages between the immune system and the brain. But they have found out the details of how it heals the gut. The molecule reacts with both TRPV1 (to produce more anandamide) and another receptor to call in a type of macrophage, immune cells that subdue inflammation. The macrophage population and activity level increases when anandamide levels increase. The effects pervade the entire upper gut, including the esophagus, stomach and pancreas. They are still working with mice to see whether it also affects disorders in the bowels, such as colitis. And there are many other questions yet to be explored: what is the exact molecular pathway? Other receptors also react with anandamide; what do they do? How does ingesting weed affect the gut and the brain?

It's difficult to get federal license to experiment on people with marijuana, but the legalization of pot in certain states means there's a different way to see if regular ingestion of cannabinoids affects gut inflammation in humans.

"I'm hoping to work with the public health authority in Colorado to see if there has been an effect on the severity of colitis among regular users of edible weed," since pot became legal there in 2012, Srivastava says. If the epidemiological data shows a significant change, that would make a testable case that anandamide or other cannabinoids could be used as therapeutic drugs to treat certain disorders of the stomach, pancreas, intestines and colon.

It seems a little ironic that both chili peppers and marijuana could make the gut chill out. But how useful if it's true.


Total fruit and vegetable consumption is higher among consumers of frozen fruits and vegetables


New research presented today via poster presentation at the 2017 Experimental Biology meeting shows consumers who eat frozen fruits and vegetables eat more fruits and vegetables overall. In fact, consumers of frozen fruits and vegetables also have significantly greater intakes of key nutrients, such as potassium, fiber and calcium.

The study, presented by Maureen Storey, PhD, and supported by the Frozen Food Foundation, analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011-2014. When consumers of frozen fruits and vegetables were compared to non-consumers of frozen fruits and vegetables, the study results show:

  • Frozen fruit and vegetable consumers eat more total fruits and vegetables than non-consumers;
  • Consumers of frozen fruits and vegetables have significantly higher intakes of nutrients of concern - potassium, dietary fiber, calcium, and vitamin D; and
  • Adult consumers of frozen fruits and vegetables have significantly lower BMI than non-consumers.
"At a time when Americans are only eating half of the recommended daily intake of fruits and vegetables, our research shows that eating frozen fruits and vegetables can help fill the gap in fruit and vegetable consumption," said Dr. Storey. "In addition to increased consumption of nutrients of concern, frozen fruit and vegetable consumers also had a higher intake of vitamins A and C."

The U.S. Department of Agriculture and U.S. Department of Health and Human Services 2015-2020 Dietary Guidelines for Americans (DGAs) define calcium, potassium, dietary fiber and vitamin D as nutrients of public health concern because low intakes are associated with health concerns. Specifically, the guidelines attribute low intake of fiber and potassium to decreased fruit and vegetable consumption.

"This research adds substantiation to the growing body of evidence that supports the important role frozen fruits and vegetables can play to help Americans meet daily intake recommendations set by the DGAs," said Frozen Food Foundation President and CEO Alison Bodor. "While this research focused on fruits and vegetables, frozen foods and beverages also provide consumers with nutritious and convenient meals options while minimizing food waste."


Daily consumption of sodas, fruit juices and artificially sweetened sodas affect brain


Data from the Framingham Heart Study (FHS) has shown that people who more frequently consume sugary beverages such as sodas and fruit juices are more likely to have poorer memory, smaller overall brain volumes and smaller hippocampal volumes--an area of the brain important for memory. Researchers also found that people who drank diet soda daily were almost three times as likely to develop stroke and dementia when compared to those who did not consume diet soda.

These findings appear separately in the journals Alzheimer's & Dementia and the journal Stroke.

"Our findings indicate an association between higher sugary beverage intake and brain atrophy, including lower brain volume and poorer memory," explained corresponding author Matthew Pase, PhD, fellow in the department of neurology at Boston University School of Medicine (BUSM) and investigator at the FHS.

"We also found that people drinking diet soda daily were almost three times as likely to develop stroke and dementia. This included a higher risk of ischemic stroke, where blood vessels in the brain become obstructed and Alzheimer's disease dementia, the most common form of dementia," he said.

Excess sugar is known to have adverse effects on health. Diet soft drinks are often touted as a healthier alternative to regular soda. However both sugar and artificially-sweetened beverage consumption has been linked to cardiometabolic risk factors, which increases the risk of cerebrovascular disease and dementia.

In these studies approximately 4,000 participants over the age of 30 from the community-based FHS were examined using Magnetic Resonance Imaging (MRI) and cognitive testing to measure the relationship between beverage intake and brain volumes as well as thinking and memory. The researchers then monitored 2,888 participants age 45 and over for the development of a stroke and 1,484 participants age 60 and older for dementia for 10 years.

The researchers point out that preexisting conditions such as cardiovascular disease, diabetes and high blood pressure did not completely explain their findings. For example, people who more frequently consumed diet soda were also more likely to be diabetic, which is thought to increase the risk of dementia. However, even after excluding diabetics from the study, diet soda consumption was still associated with the risk of dementia.

Although the researchers suggest that people should be cautious about regularly consuming either diet sodas or sugary beverages, it is premature to say their observations represent cause and effect. Future studies are needed to test whether giving people artificial sweeteners causes adverse effects on the brain.


Want to stay mentally healthy in older age?


Stimulating the brain by taking on leadership roles at work or staying on in education help people stay mentally healthy in later life, according to new research.

The large-scale investigation published in the journal PLOS Medicine and led by the University of Exeter, used data from more than 2,000 mentally fit people over the age of 65, examined the theory that experiences in early or mid life which challenge the brain make people more resilient to changes resulting from age or illness - they have higher "cognitive reserve".

The analysis, funded by the Economic and Social Research Council (ESRC) found that people with higher levels of reserve are more likely to stay mentally fit for longer, making the brain more resilient to illnesses such as dementia.

The research team included collaborators from the universities of Bangor, Newcastle and Cambridge.

Linda Clare, Professor of Clinical Psychology of Ageing and Dementia at the University of Exeter, said: "Losing mental ability is not inevitable in later life. We know that we can all take action to increase our chances of maintaining our own mental health, through healthy living and engaging in stimulating activities. It's important that we understand how and why this occurs, so we can give people meaningful and effective measures to take control of living full and active lives into older age.

"People who engage in stimulating activity which stretches the brain, challenging it to use different strategies that exercise a variety of networks, have higher 'Cognitive reserve'. This builds a buffer in the brain, making it more resilient. It means signs of decline only become evident at a higher threshold of illness or decay than when this buffer is absent."

The research team analysed data from 2,315 mentally fit participants aged over 65 years who took part in the first wave of interviews for the Cognitive Function and Ageing Study Wales (CFAS-Wales).

They analysed whether a healthy lifestyle was associated with better performance on a mental ability test. They found that a healthy diet, more physical activity, more social and mentally stimulating activity and moderate alcohol consumption all seemed to boost cognitive performance.

Professor Bob Woods of Bangor University, who leads the CFAS Wales study, said: "We found that people with a healthier lifestyle had better scores on tests of mental ability, and this was partly accounted for by their level of cognitive reserve.

"Our results highlight the important of policies and measures that encourage older people to make changes in their diet, exercise more, and engage in more socially oriented and mentally stimulating activities."

Professor Fiona Matthews of Newcastle University, who is principal statistician on the CFAS studies, said "Many of the factors found here to be important are not only healthy for our brain, but also help at younger age avoiding heart disease".

Professor Clare is supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula (NIHR PenCLAHRC).

Testing our the efficacy of brain stimulation is part one aspect of the PROTECT (Platform for Research Online to investigate Genetics and Cognition in Ageing) trial, which involves Professor Clare. It has already recruited 20,000 people over the age of 50. They are taking part in Exeter-led research to establish which lifestyle measures can make a meaningful difference to keep people stay physically and mentally active in older age.


Skip the soda, opt for the stairs to feel more energized



A midday jolt of caffeine isn't as powerful as walking up and down some stairs, according to new research from the University of Georgia.

In a new study published in the journal Physiology and Behavior, researchers in the UGA College of Education found that 10 minutes of walking up and down stairs at a regular pace was more likely to make participants feel energized than ingesting 50 milligrams of caffeine--about the equivalent to the amount in a can of soda.

"We found, in both the caffeine and the placebo conditions, that there was not much change in how they felt," said Patrick J. O'Connor, a professor in the department of kinesiology who co-authored the study with former graduate student Derek Randolph. "But with exercise they did feel more energetic and vigorous. It was a temporary feeling, felt immediately after the exercise, but with the 50 milligrams of caffeine, we didn't get as big an effect."

The study aimed to simulate the hurdles faced in a typical office setting, where workers spend hours sitting and staring at computer screens and don't have time for a longer bout of exercise during the day. For the study, participants on separate days either ingested capsules containing caffeine or a placebo, or spent 10 minutes walking up and down stairs--about 30 floors total--at a low-intensity pace.

O'Connor wanted to compare an exercise that could be achieved by people in an office setting, where they have access to stairs and a little time to be active, but not enough time to change into workout gear, shower and change back into work clothes.

"Office workers can go outside and walk, but weather can be less than ideal. It has never rained on me while walking the stairs," said O'Connor. "And a lot of people working in office buildings have access to stairs, so it's an option to keep some fitness while taking a short break from work."

Study participants were female college students who described themselves as chronically sleep deprived--getting less than 6½ hours per night. To test the effects of caffeine versus the exercise, each group took some verbal and computer-based tests to gauge how they felt and how well they performed certain cognitive tasks. Neither caffeine nor exercise caused large improvements in attention or memory, but stair walking was associated with a small increase in motivation for work.

O'Connor added that there is still much research to be done on the specific benefits of exercising on the stairs, especially for just 10 minutes. But even a brief bout of stair walking can enhance feelings of energy without reducing cognitive function. "You may not have time to go for a swim, but you might have 10 minutes to walk up and down the stairs."


Both sugary and diet drinks correlated with accelerated brain aging


Americans love sugar. Together we consumed nearly 11 million metric tons of it in 2016, according to the US Department of Agriculture, much of it in the form of sugar-sweetened beverages like sports drinks and soda.

Now, new research suggests that excess sugar -- especially the fructose in sugary drinks--might damage your brain. Researchers using data from the Framingham Heart Study (FHS) found that people who drink sugary beverages frequently are more likely to have poorer memory, smaller overall brain volume, and a significantly smaller hippocampus -- an area of the brain important for learning and memory.

But before you chuck your sweet tea and reach for a diet soda, there's more: a follow-up study found that people who drank diet soda daily were almost three times as likely to develop stroke and dementia when compared to those who did not.

Researchers are quick to point out that these findings, which appear separately in the journals Alzheimer's & Dementia and Stroke, demonstrate correlation but not cause-and-effect. While researchers caution against over-consuming either diet soda or sugary drinks, more research is needed to determine how -- or if -- these drinks actually damage the brain, and how much damage may be caused by underlying vascular disease or diabetes.

"These studies are not the be-all and end-all, but it's strong data and a very strong suggestion," says Sudha Seshadri, a professor of neurology at Boston University School of Medicine (MED) and a faculty member at BU's Alzheimer's Disease Center, who is senior author on both papers. "It looks like there is not very much of an upside to having sugary drinks, and substituting the sugar with artificial sweeteners doesn't seem to help."

"Maybe good old-fashioned water is something we need to get used to," she adds.

Matthew Pase, a fellow in the MED neurology department and an investigator at the FHS who is corresponding author on both papers, says that excess sugar has long been associated with cardiovascular and metabolic diseases like obesity, heart disease, and type 2 diabetes, but little is known about its long-term effects on the human brain. He chose to study sugary drinks as a way of examining overall sugar consumption. "It's difficult to measure overall sugar intake in the diet," he says, "so we used sugary beverages as a proxy."

For the first study, published in Alzheimer's & Dementia on March 5, 2017, researchers examined data, including magnetic resonance imaging (MRI) scans and cognitive testing results, from about 4,000 people enrolled in the Framingham Heart Study's Offspring and Third-Generation cohorts. (These are the children and grandchildren of the original FHS volunteers enrolled in 1948.) The researchers looked at people who consumed more than two sugary drinks a day of any type -- soda, fruit juice, and other soft drinks -- or more than three per week of soda alone. Among that "high intake" group, they found multiple signs of accelerated brain aging, including smaller overall brain volume, poorer episodic memory, and a shrunken hippocampus, all risk factors for early-stage Alzheimer's disease. Researchers also found that higher intake of diet soda--at least one per day--was associated with smaller brain volume.

In the second study, published in Stroke on April 20, 2017, the researchers, using data only from the older Offspring cohort, looked specifically at whether participants had suffered a stroke or been diagnosed with dementia due to Alzheimer's disease. After measuring volunteers' beverage intake at three points over seven years, the researchers then monitored the volunteers for 10 years, looking for evidence of stroke in 2,888 people over age 45, and dementia in 1,484 participants over age 60. Here they found, surprisingly, no correlation between sugary beverage intake and stroke or dementia. However, they found that people who drank at least one diet soda per day were almost three times as likely to develop stroke and dementia.

Although the researchers took age, smoking, diet quality, and other factors into account, they could not completely control for preexisting conditions like diabetes, which may have developed over the course of the study and is a known risk factor for dementia. Diabetics, as a group, drink more diet soda on average, as a way to limit their sugar consumption, and some of the correlation between diet soda intake and dementia may be due to diabetes, as well as other vascular risk factors. However, such preexisting conditions cannot wholly explain the new findings.

"It was somewhat surprising that diet soda consumption led to these outcomes," says Pase, noting that while prior studies have linked diet soda intake to stroke risk, the link with dementia was not previously known. He adds that the studies did not differentiate between types of artificial sweeteners and did not account for other possible sources of artificial sweeteners. He says that scientists have put forth various hypotheses about how artificial sweeteners may cause harm, from transforming gut bacteria to altering the brain's perception of "sweet," but "we need more work to figure out the underlying mechanisms."



Diet high in animal protein is associated withnon-alcoholic fatty liver disease


 A large epidemiological study presented today found that a diet high in animal protein was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD), a condition in which fat builds up in the liver. These findings from The Rotterdam Study, presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, also showed that fructose consumption per se might not be as harmful as previously assumed.

NAFLD is a major health concern, because it can lead to permanent scarring (cirrhosis) and subsequently to cancer and malfunction of the liver.1 This may result in life-threatening complications for which a liver transplant is needed. Additionally, NAFLD also contributes to an increased risk of cardiovascular diseases such as diabetes mellitus and atherosclerosis. NAFLD is diagnosed when accumulation of fat in the organ exceeds 5% of hepatocytes (the cells that make up the majority of the liver).2 It is estimated that approximately 1 billion people worldwide may have NAFLD with a prevalence of 20-30% in Western countries.3 It parallels one of world's most rapidly growing health concerns, obesity, which is also one of the most important risk factors in NAFLD.3 In its early stages NAFLD can be treated through diet and lifestyle changes, such as weight loss, but it can progress to more serious liver diseases.1 However, there is still a lot of debate whether weight loss alone is enough to reverse NAFLD, while emerging evidence suggests that the composition of the diet, rather than the amount of calories consumed, might also be important in NAFLD.

"A healthy lifestyle is the cornerstone of treatment in patients with NAFLD, but specific dietary recommendations are lacking," said Louise Alferink (MD), Erasmus Medical Centre, Rotterdam, The Netherlands, and lead author of the study. "The results from this study demonstrate that animal protein is associated with NAFLD in overweight elderly people. This is in line with a recently proposed hypothesis that a Western-style diet, rich in animal proteins and refined food items, may cause low-grade disturbances to the body homeostasis, glucose metabolism and acid based balance. Another interesting finding is that, although current guidelines advise against foods containing fructose, such as soda and sugar, our results do not indicate a harmful association of mono- and disaccharides with NAFLD per se. In fact, we even found a slight beneficial association, which was attenuated when adjusted for metabolic factors. These results should be interpreted with caution, but we hypothesise that increased consumption of healthy food items within the mono- and disaccharide-group, such as fruits and vegetables rich in antioxidants, could partly explain these results."

The Rotterdam Study is an ongoing population-based study that is being conducted in The Netherlands. A total of 3,440 people were included in the study of whom 1,040 (30%) were lean (body mass index [BMI] of less than 25 kg/m2) and 2,400 (70%) were overweight (BMI of 25 kg/m2 or greater). The average age was 71 years and NAFLD, as assessed by abdominal ultrasound, was present in 1,191 (35%) of the participants. Macronutrient intake was recorded using an externally validated 389-item food frequency questionnaire and analysed in quartiles using the nutrition density method (energy percentage). Furthermore, analyses were stratified for BMI to account for BMI-related differences in eating habits and dietary measurement errors.

Significant associations between macronutrients and NAFLD were found predominantly in overweight individuals. The results showed that total protein was associated with higher odds of NAFLD (ORQ4vs.Q1 1.37; 95% CI 1.08-1.73, Ptrend=0.005) and this association was mainly driven by animal protein (ORQ4vs.Q1 1.50; 95% CI 1.17-1.92, Ptrend=0.003). After adjustments for metabolic factors, animal protein but not total protein remained significantly associated. In addition, a diet rich in mono- and disaccharides was associated with a lower probability of developing NAFLD (ORQ4vs.Q1 0.67; 95% CI 0.51-0.89, Ptrend=0.006), though this association did not remain after metabolic factors were taken into account. Finally, substitution analyses were performed to examine whether replacing one macronutrient by another (isocaloric) macronutrient was associated with NAFLD. No consistent substitution effects were found, which stresses the need for a diverse diet.

"This large population-based study indicates that increased dietary protein, in particular of animal origin, increases the likelihood of developing NAFLD and should be taken into account when counselling patients at risk of developing NAFLD," said Prof Philip Newsome, Centre for Liver Research & Professor of Experimental Hepatology, University of Birmingham, United Kingdom, and EASL Governing Board Member.