Category Archives: Food

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Study Reveals Missing Link Between High-fat Diet, Microbiota and Heart Disease (Food)

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A high-fat diet disrupts the biology of the gut’s inner lining and its microbial communities—and promotes the production of a metabolite that may contribute to heart disease, according to a study published Aug. 13 in the journal Science.

The discoveries in animal models support a key role for the intestines and microbiota in the development of cardiovascular disease, said Mariana Byndloss, DVM, Ph.D., assistant professor of Pathology, Microbiology and Immunology at Vanderbilt University Medical Center.

The intestines, she noted, have been relatively understudied by scientists seeking to understand the impact of obesity.

“Before COVID, obesity and metabolic syndrome were considered the pandemic of the 21st century. Right now, roughly 40% of the U.S. population is obese, and that percentage is predicted to climb,” Byndloss said. “Our research has revealed a previously unexplored mechanism for how diet and obesity can increase risk of cardiovascular disease—by affecting the relationship between our intestines and the microbes that live in our gut.”

In previous studies, Byndloss and Andreas Bäumler, Ph.D., at the University of California at Davis, found that the epithelial cells lining the intestines and gut microbes share a mutually beneficial relationship that promotes a healthy gut environment. They wondered if diseases like obesity affect this relationship.

The collaborating research teams found that a high-fat diet causes inflammation and damages intestinal epithelial cells in animal models. The high-fat diet impairs the function of energy-generating mitochondria, Byndloss explained, causing the intestinal cells to produce more oxygen and nitrate.

These factors, in turn, stimulate the growth of harmful Enterobacteriaceae microbes, such as E. coli, and boost bacterial production of a metabolite called TMA (trimethylamine). The liver converts TMA to TMAO (trimethylamine-N-oxide), which has been implicated in promoting atherosclerosis and increasing the relative risk for all-cause mortality in patients.

“It was known that exposure to a high-fat diet causes dysbiosis—an imbalance in the microbiota favoring harmful microbes, but we didn’t know why or how this was happening,” Byndloss said. “We show one way that diet directly affects the host and promotes the growth of bad microbes.”

The researchers demonstrated that a drug currently approved for treatment of inflammatory bowel disease restored the function of intestinal epithelial cells and blunted the increase in TMAO in the animal models. The drug, called 5-aminosalicylic acid, activates mitochondrial bioenergetics in the intestinal epithelium.

“This is evidence that it’s possible to prevent the negative outcomes associated with a high-fat diet,” Byndloss said. A drug such as 5-aminosalicylic acid might be used in conjunction with a probiotic to both restore a healthy intestinal environment and boost beneficial microbe levels, she added.

“Only by fully understanding the relationship between the host—us—and gut microbes during health and disease are we going to be able to design therapies that will be effective in controlling obesity and obesity-associated outcomes like cardiovascular disease.”

Byndloss and her team plan to extend their studies into animal models of cardiovascular disease. They also are exploring the role of the host-microbe relationship in the development of other diseases including colorectal cancer.

Featured image: Mariana Byndloss and Woongjae Yoo are exploring the connections between diet, gut microbes and heart disease. Credit: VUMC

Reference: High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine-N-oxide, Science (2021). DOI: 10.1126/science.aba3683

Provided by Vanderbilt University Medical Center

Food

Providing Vitamins to Women Who Mainly Eat Polished White Rice Can Boost Infant Health (Food)

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Polished white rice is a staple of diets in Southeast Asia, which poses a serious public health problem because the grain has been stripped of its vitamins and minerals during processing, according to new research by UO scientists.

White rice lacks thiamine, also known as vitamin B1, an essential nutrient for humans because it helps the body’s cells convert carbohydrates into energy. Thiamine deficiency can lead to cognitive and physical impairments, particularly in infants of breast-feeding mothers who lack the nutrient.

A new study led by psychologists at the UO found that providing thiamine supplements to breast-feeding mothers in Cambodia can help protect the neurocognitive development of their infants and especially benefits their language development.

UO psychologist Jeffrey Measelle is the lead author of the study, published in the Annals of the New York Academy of Sciences, and Dare Baldwin, also a psychology professor, is a co-author. The study is one piece of a large interdisciplinary clinical trial involving researchers from Canada, France, Australia, Cambodia and the United States. The two UO psychologists have been colleagues for many years but this is the first time they’ve worked together on a research project.

Measelle said he’s been working on public health issues in Southeast Asia for a number of years, and he and Baldwin were seeking funding from the Bill & Melinda Gates Foundation for further research. The foundation was particularly interested in acute thiamine deficiency in infants, known as infantile beriberi, that causes cognitive damage and can kill babies.

The foundation connected Measelle and Baldwin with nutritionist Kyly Whitfield and colleagues at Mount Saint Vincent University in Nova Scotia. The nutritionists had been investigating the benefits of supplement techniques and wanted to know the best methods for measuring cognitive development in infants, which is where Measelle and Baldwin came in.

The researchers recruited 335 healthy mothers of breastfed newborns in Kampong, Cambodia. Two weeks after giving birth, women were randomly assigned to one of four treatment groups to receive one capsule a day of varying amounts of thiamine: 0 milligrams, 1.2 milligrams, 2.4 milligrams and 10 milligrams. Supplementation began when infants were two weeks old, and continued until they were 24 weeks. Neurocognitive assessments took place when infants were two weeks, 12 weeks, 24 weeks and at a 52-week follow-up, using multiple methods of measuring cognitive development.

Analysis of the results indicated that the highest dose of 10 milligrams per day provided significant benefits for infants’ language development but generally not for motor or visual reception development. Preliminary evidence also suggests that infants’ neurocognitive development may benefit most if the mother begins taking supplements while pregnant.

“For me personally, given that much of my work is focused on prenatal development,” Measelle said, “we need to go back to an earlier stage and protect fetal development during pregnancy so when the infant is born, they start at a better place and keep going.”

The researchers also concluded infants would benefit from continued thiamine supplementation beyond six months.

“If we can protect the first 1,000 days of life, that would help to cover what is arguably the most critical period of development,” Measelle said.

Thiamine deficiency is rare in western societies because it’s readily available in the diet in the form of legumes, whole grains, pork and other foods. In Southeast Asia, a bowl of rice for an entire day might be all that some can afford to eat, Baldwin said. And unfortunately, a commonly available type of fish that is eaten in Cambodia actually depletes thiamine.

In Cambodia, roughly 50 percent of adults are stunted because of malnutrition, the outward sign of micronutrient deficiencies, including thiamine deficiency, that also compromises immune systems, brain development and cognitive function, Baldwin said.

One idea to get more thiamine into the diets of Cambodians would be to fortify salt with the nutrient, just as salt has been fortified with iodine in the United States since the 1920s. Getting the correct dose will require more research, Measelle and Baldwin said.

Cambodian scientists and public health officials are supportive of the researchers’ work, Measelle said.

“They know babies are vulnerable and all too often dying because of thiamine deficiencies,” he said. “We have a strong partnership with our Cambodian colleagues and we’re already talking about the next phases of work.”

Reference: Jeffrey R. Measelle et al, Thiamine supplementation holds neurocognitive benefits for breastfed infants during the first year of life, Annals of the New York Academy of Sciences (2021). DOI: 10.1111/nyas.14610

Provided by University of Oregon

Food

Low Glycaemic Diet Shows Meaningful Improvements For People With Diabetes (Food)

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For people with diabetes, sticking to a low glycaemic diet results in small but important improvements in blood sugar levels, cholesterol, weight and other risk factors, finds a study published by The BMJ today.

These improvements were seen over and above existing drug or insulin therapy, suggesting that a low glycaemic diet might be especially helpful as add-on treatment to help those with diabetes better achieve their targets, say the researchers.

The glycaemic index (GI) rates how quickly different foods affect blood sugar levels and research has shown that low-GI foods, such as vegetables, most fruits, pulses and wholegrains, can help keep blood sugar levels steady and reduce the risk of heart disease in people with diabetes.

A low GI or GL (glycaemic load) diet is therefore recommended for people with diabetes by clinical guidelines across the world. However, the last European Association for the Study of Diabetes (EASD) guidelines were published over 15 years ago and several trials have been published since then.

So researchers set out to summarise the effect of low GI/GL dietary patterns on blood sugar control and other known risk factors in diabetes to help inform the update of the EASD guidelines for nutrition treatment.

Their results are based on 27 randomised controlled trials published up to May 2021 investigating the effect of diets with low GI/GL in diabetes for three or more weeks.

The trials involved a total of 1,617 participants with type 1 or 2 diabetes, who were predominantly middle aged, overweight or obese with moderately controlled type 2 diabetes treated with drugs or insulin.

The trials were of varying quality, but the researchers were able to assess the certainty of evidence using the recognised GRADE system.

The results show that low-GI/GL dietary patterns were associated with small but clinically meaningful reductions in blood sugar levels (HbA1c) compared with higher-GI/GL control diets.

Reductions also occurred in other risk factors including fasting glucose (blood sugar levels after a period of fasting), LDL cholesterol, body weight, and C-reactive protein (a chemical associated with inflammation), but not blood insulin levels, HDL cholesterol, waist circumference, or blood pressure.

The certainty of evidence was high for reduction in blood sugar levels and moderate for most other outcomes, suggesting the available evidence provides a good indication of the likely benefit in this population.

The researchers point to some limitations that may have affected their results, such as imprecision in the evidence for the effect of low GI/GL dietary patterns on LDL cholesterol and waist circumference, and the small number of available trial comparisons for blood pressure and inflammatory markers.

However, they say their findings show that low GI/GL dietary patterns “are considered an acceptable and safe dietary strategy that can produce small meaningful reductions in the primary target for glycaemic control in diabetes, HbA1c, fasting glucose, and other established cardiometabolic risk factors.”

“Our synthesis supports existing recommendations for the use of low GI/GL dietary patterns in the management of diabetes,” they conclude.

Reference: Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials, BMJ (2021). DOI: 10.1136/bmj.n1651

Provided by British Medical Journal

Food

Low-fiber Diet May Lead to Gut Infection Even if You’re Not Overweight (Food)

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Diet, more than body mass, may play a role in the risk for gut infection, and eating more fiber could be the key to prevention. The study is published ahead of print in the American Journal of Physiology-Endocrinology and Metabolism.

“One takeaway from this study is that people who are leaner may have similar risks of gut infection to obese adults if they don’t eat enough fiber.”

Obesity is associated with developing chronic conditions such as type 2 diabetes, heart disease and fatty liver disease. Previous research suggests being overweight can also raise the risk and severity of bacterial infection. However, less is known about whether following a diet that tends to cause obesity is enough to increase bacterial infection risks without being obese.

Researchers from Canada examined the effects of diet and obesity on a mouse model of a bacterial infection caused by excess adherent-invasive Escherichia coli (AIEC) in the intestinal tract. AIEC is a microorganism that may cause harm only under certain circumstances. People who have the inflammatory bowel disorder Crohn’s disease may have too much AIEC (called an expansion) in their digestive tract, which can be exacerbated by antibiotic use. Previous studies have found that obesity and related factors, such as a high-fat and high-sugar diet, may change the composition of the gut microbiome enough to increase the risk of inflammation and infection. The typical Western diet containing highly processed foods also tends to be low in fiber. However, it’s not clear if this type of diet is enough to predispose people to bacterial infection.

Obese mice followed two high-fat (60% and 45% fat), low-fiber diets. All of the animals developed AIEC expansion in the colon. The mice on the 60% fat diet had a higher body mass than those eating the 45% fat chow, but there was no significant difference in the amount of AIEC (AIEC burden) in their systems. “These data suggested that an aspect of diet composition rather than the magnitude of host obesity was sufficient to promote intestinal AIEC expansion,” the researchers wrote.

The research team fed lean mice a high-fat diet on a short-term basis before significant obesity occurred to explore the effect of diet on AIEC burden. After the animals were exposed to AIEC, the lean mice eating the high-fat diet had more AIEC expansion than the controls (lean mice on a normal diet). These results “indicate that diet can regulate AIEC infectious burden independent of changes in body mass leading to obesity,” the researchers wrote. Finally, the research team found that mice on a low-fat, low-fiber diet had higher AIEC burden than those eating a normal diet, suggesting that dietary fat was not the key ingredient, but “ingestion of lower dietary fiber is sufficient to promote expansion of AIEC throughout the gut.”

One takeaway from this study is that people who are leaner may have similar risks of gut infection if they don’t eat enough fiber. “Our data show that dietary fiber is a standalone factor,” the researchers wrote.

Read the full article, “Low dietary fiber promotes enteric expansion of a Crohn’s disease-associated pathobiont independent of obesity,” published ahead of print in the American Journal of Physiology-Endocrinology and Metabolism.

Provided by American Physiological Society

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Moderate Drinking Linked to Fewer Heart Attacks in People With Heart Disease (Food)

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Light to moderate drinking may be associated with a decreased risk of heart attack, stroke, angina or death among those with cardiovascular disease, finds a new study led by a UCL researcher.

The new BMC Medicine meta-analysis study suggest that drinking up to 105 grams of alcohol per week – equivalent to 13 UK units of alcohol, less than six pints of medium-strength beer or just over one bottle of wine – could potentially confer some protective benefits.

Lead author, PhD student Chengyi Ding (UCL Institute of Epidemiology & Health Care), said: “Our findings suggest that people with cardiovascular disease may not need to stop drinking in order to prevent additional heart attacks, strokes or angina, but that they may wish to consider lowering their weekly alcohol intake. As alcohol consumption is associated with an increased risk of developing other illnesses, those with cardiovascular disease who do not drink should not be encouraged to take up drinking.”

The researchers found that, among people with cardiovascular disease, those who drank up to 15 grams of alcohol per day – equivalent to less than two UK units, with one unit equal to half a pint of medium-strength beer or half a standard glass of wine – had a lower risk of recurrent heart attack, stroke, angina or death, compared to those who did not drink. They also found that those who drank more than 62 grams of alcohol per day – close to eight UK units – did not have an increased risk of recurrent heart attack, stroke, angina or death, compared to those who did not drink alcohol.

While drinking up to 15 grams of alcohol per day was associated with lower risks of heart attack, stroke, angina or death, the researchers found that those with the lowest risk drank between six and eight grams of alcohol per day – equivalent to less than one UK unit. Those who drank six grams of alcohol per day had a 50% lower risk of recurrent heart attack, angina or stroke than those who did not drink. Those who drank eight grams per day had a 27% lower risk of death due to heart attack, stroke or angina, and those who drank seven grams per day had a 21% lower risk of death due to any cause, compared to those who did not drink.

The authors estimated the risk of heart attack, stroke, angina and death for 48,423 adults with cardiovascular disease, using data obtained from the UK Biobank, the Health Survey for England, the Scottish Health Survey and from 12 previous studies. Participants reported their average alcohol consumption and data on subsequent heart attacks, strokes, angina or death, over a period of up to 20 years, were obtained from health, hospital admission and death registry records.

The authors caution that their findings may overestimate the reduced risk of recurrent heart attack, stroke, angina and death for moderate drinkers with cardiovascular disease. This is due to the under-representation of heavy drinkers and categorisation of former drinkers who may have quit drinking due to ill health as non-drinkers in some of the datasets included in their analyses.

The researchers say that for secondary prevention of CVD, current drinkers may not need to stop drinking but should be informed that the lowest risk of mortality and having another cardiovascular event is likely to be associated with lower levels of drinking, that is up to approximately 105g/week. However, they caution that non-drinking patients should not be encouraged to take up light drinking because of well-known adverse effects on other health outcomes, such as cancers.

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Millet-based Diet Can Lower Risk of Type 2 Diabetes And Help Manage Blood Glucose Levels (Food)

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A new study has shown that eating millets can reduce the risk of developing type 2 diabetes and helps manage blood glucose levels in people with diabetes, indicating the potential to design appropriate meals with millets for diabetic and pre-diabetic people as well as for non-diabetic people as a preventive approach.

Drawing on research from 11 countries, the study published in Frontiers in Nutrition shows that diabetic people who consumed millet as part of their daily diet saw their blood glucose levels drop 12-15% (fasting and post-meal), and blood glucose levels went from diabetic to pre-diabetes levels. The HbA1c (blood glucose bound to hemoglobin) levels lowered on average 17% for pre-diabetic individuals, and the levels went from pre-diabetic to normal status. These findings affirm that eating millets can lead to a better glycemic response.

The authors reviewed 80 published studies on humans of which 65 were eligible for a meta-analysis involving about 1,000 human subjects, making this analysis the largest systematic review on the topic to date.

Dr. S Anitha, the study’s lead author and a Senior Nutrition Scientist at ICRISAT said:

“No one knew there were so many scientific studies undertaken on millets’ effect on diabetes and these benefits were often contested. This systematic review of the studies published in scientific journals has proven that millets can keep blood glucose levels in check and reduce the risk of diabetes. It has also shown just how well these smart foods do it.”

Millets, including sorghum, were consumed as staple cereals in many parts of the world until half a century ago. Investments in a few crops such as rice, wheat and maize, have edged nutritious and climate-smart crops like millets out of the plate.

Professor Ian Givens, a co-author of the study and Director at University of Reading’s Institute of Food, Nutrition and Health (IFNH) said:

“Awareness of this ancient grain is just starting to spread globally, and our review shows millets having a promising role in managing and preventing type 2 diabetes. In the largest review and analysis of research into different types of millet compared to other grains such as refined rice, maize and wheat we found that millets outperform their comparison crops with lower GI and lower blood glucose levels in participants.”  

According to the International Diabetes Association, diabetes is increasing in all regions of the world. India, China and the USA have the highest numbers of people with diabetes. Africa has the largest forecasted increase of 143% from 2019 to 2045, the Middle East and North Africa 96% and South East Asia 74%. The authors urge the diversification of staples with millets to keep diabetes in check, especially across Asia and Africa.

Strengthening the case for reintroducing millets as staples, the study found that millets have a low average glycemic index (GI) of 52.7, about 36% lower GI than milled rice and refined wheat, and about 14-37 GI points lower compared to maize. All 11 types of millets studied could be defined as either low (<55) or medium (55-69) GI, with the GI as an indicator of how much and how soon a food increases blood sugar level. The review concluded that even after boiling, baking and steaming (most common ways of cooking grains) millets had lower GI than rice, wheat and maize.

Dr. Jacqueline Hughes, Director General, ICRISAT said:

“The global health crisis of undernutrition and over-nutrition coexisting is a sign that our food systems need fixing. Greater diversity both on-farm and on-plate is the key to transforming food systems. On-farm diversity is a risk mitigating strategy for farmers in the face of climate change while on-plate diversity helps counter lifestyle diseases such as diabetes. Millets are part of the solution to mitigate the challenges associated with malnutrition, human health, natural resource degradation, and climate change. Trans-disciplinary research involving multiple stakeholders is required to create resilient, sustainable and nutritious food systems.” 

Professor Paul Inman, Pro-Vice-Chancellor (International) of the University of Reading, said:

“The rapidly accelerating threats of climate change and global health crises, including obesity and diabetes, require everyone to pull together in action. The partnership between ICRISAT and the University of Reading is doing exactly this, bringing together our world leading expertise in human nutrition with ICRISAT’s long established role as a leader in agricultural research for rural development.”

The study also identified information gaps and highlighted a need for collaborations to have one major diabetes study covering all types of millets and all major ways of processing with consistent testing methodologies. Structured comprehensive information will be highly valuable globally, taking the scientific knowledge in this area to the highest level.

Ms. Joanna Kane-Potaka, a co-author from ICRISAT and Executive Director of the Smart Food initiative said:

“This study is first in a series of studies that has been worked on for the last four years as a part of the Smart Food initiative led by ICRISAT that will be progressively released in 2021. Included are systematic reviews with meta-analyses of the impacts of millets on: diabetes, anemia and iron requirements, cholesterol and cardiovascular diseases and calcium deficiencies as well as a review on zinc levels. As part of this, ICRISAT and the Institute for Food Nutrition and Health at the University of Reading have formed a strategic partnership to research and promote the Smart Food vision of making our diets healthier, more sustainable on the environment and good for those who produce it.”

This research is part of a special edition and theme section in the Frontiers journal – Smart Food for Healthy, Sustainable and Resilient Food System. 

Full citation:

Anitha S, Kane-Potaka J, Tsusaka TW, Botha R, Rajendran A, Givens DI, Parasannanavar DJ, Subramaniam K, Prasad KDV, Vetriventhan M and Bhandari RK (2021) A Systematic Review and Meta-Analysis of the Potential of Millets for Managing and Reducing the Risk of Developing Diabetes Mellitus. Front. Nutr. 8:687428. doi: 10.3389/fnut.2021.687428

Provided by University of Reading

Biology, Food

Fighting Off Food Poisoning Depends On the Time Of Day (Food / Biology)

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Levels of natural antimicrobial molecule fluctuate on a circadian rhythm prompted by resident gut bacteria, study shows

The body’s ability to prevent food poisoning by producing a natural antimicrobial compound increases during the day, when exposure to noxious bacteria is most likely, a new study by UT Southwestern scientists suggests. The findings, published online in Cell, could eventually lead to timed therapies and vaccination regimens designed to maximize this immune response.

John F. Brooks II, Ph.D. © UT Southwestern Medical Center

“This study shows that our immune systems are not turned on all the time, which is an unexpected result,” says study leader John F. Brooks II, Ph.D., a postdoctoral fellow in the laboratory of Lora Hooper, Ph.D., study co-leader and professor of immunology and microbiology at UTSW. “Our findings suggest that there are peak times in which the body is more primed to fight infections.”

Researchers have long known that virtually all animals follow circadian cycles that are tied to sunrise and sunset. These cycles allow animals to anticipate and prepare for changes in their environment. Disrupting circadian rhythms can have serious health consequences; for example, chronic sleep disruption is related to increased intestinal infection in humans. However, why this occurs has been unclear.

Lora Hooper, Ph.D. ©UT Southwestern Medical Center

Brooks, Hooper, and their colleagues suspected that antibacterial immunity might change in the intestines on a circadian cycle. To investigate this idea, the researchers looked for rhythms in the expression of natural antimicrobial agents produced in the gut of mice to fight foodborne illness. The researchers saw that in normal lab mice, one of these antimicrobial molecules – known as regenerating islet-derived protein 3g (REG3G) – was more abundant at night, when these nocturnal animals are active, and less so during the day, when mice sleep. However, in mice raised to have no gut bacteria, REG3G was essentially absent throughout both the day and the night.

Searching for the microbial components driving the rhythmic pattern, the researchers found that mice with cycling amounts of REG3G had large resident populations of segmented filamentous bacteria in their guts – microbes typically present in rodents, nonhuman primates, and humans – that have a unique ability to attach to the intestinal lining and change their hosts’ gene activity. Further experiments showed that these bacteria attached to the animals’ intestinal lining during feeding, probably to siphon off nutrients. When they attached, REG3G production ramped up in the intestines.

This cycling had significant consequences for the ability of mice to fight off infection. When the researchers infected normal mice with bacteria, the animals had higher bacterial burdens and rates of death if they were exposed at sunset than at sunrise. Mice that can’t make antimicrobial proteins, including REG3G, had similarly high rates of bacterial burden and death regardless of when they were infected.

If further research shows this phenomenon also occurs in humans, scientists may eventually be able to capitalize on it by timing the administration of synthetic antibiotics for intestinal infections and oral vaccines or finding new ways to avoid intestinal infections altogether.

“These results make me think twice about waking up in the middle of the night and raiding the refrigerator,” Hooper says. “It may be more dangerous to eat bacteria-laden potato salad when your gut defenses are lowest.”

Other UTSW researchers who contributed to this study include Cassie L. Behrendt, Kelly A. Ruhn, Syann Lee, Prithvi Raj, and Joseph S. Takahashi.

This work was supported by grants from the National Institutes of Health (R01 DK070855), The Welch Foundation (I-1874), and the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases.

Hooper holds the Jonathan W. Uhr, M.D. Distinguished Chair in Immunology, the Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell, and is an investigator of the Howard Hughes Medical Institute.

Takahashi holds the Loyd B. Sands Distinguished Chair in Neuroscience and is an investigator of the Howard Hughes Medical Institute.

Brooks is a recipient of the highly competitive Howard Hughes Medical Institute Hanna Gray Fellowship.

Featured image: Scanning electron micrograph shows segmented filamentous bacteria attaching to the intestinal surface of a mouse. More bacteria attach during the night than during the day. Credit: John F. Brooks II

Reference: John F. Brooks et al, The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock, Cell (2021). DOI: 10.1016/j.cell.2021.07.001

Provided by UT Southwestern Medical Center

Food, Neuroscience

Eating For Hunger Or Pleasure Involves Regulating Different Brain Circuits (Food / Neuroscience)

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Many times we eat, not because we are hungry, but because of social pressures or because the food is so appetizing, that, even though we are full, we just want another bite.

Overeating, whether it is guided by hunger or pleasure, typically leads to obesity, which affects about 42% of the adults in the U.S., according to the Centers for Disease Control and Prevention. Looking to contribute to the development of effective treatments for obesity, an international team led by researchers at Baylor College of Medicine investigated in an animal model how the brain regulates feeding triggered by hunger or other factors.

Led by Dr. Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor, the team discovered that although the brain regulates both types of feeding behavior through serotonin-producing neurons in the midbrain, each type of feeding is wired by its own independent circuit that does not influence the other type of feeding. The researchers also identified two serotonin receptors and two ion channels that can affect the feeding behaviors, opening the possibility that modulating their activities might help regulate overeating. The study appears in the journal Molecular Psychiatry.

Mapping the roads that control feeding behavior in the brain

Xu and his colleagues identified two distinct brain circuits formed by serotonin-producing neurons in the midbrain. One of the circuits extends to the hypothalamus, while the other projects into another region of the midbrain. These circuits play very distinct roles in regulating feeding.

“We discovered that the circuit that projects to the hypothalamus primarily regulates hunger-driven feeding, but does not influence the non-hunger driven feeding behavior,” Xu said. “The other circuit that projects into the midbrain regulates primarily the non-hunger driven feeding, but not the feeding behavior triggered by hunger. This indicates that, at the circuit level, the brain wires the two types of feeding behavior differently.”

The other significant contribution of this work refers to the identification of potential molecular targets associated with the circuits that could be used to treat overeating.

“One potential target is serotonin receptors, which are molecules that mediate the functions of the neurotransmitter serotonin produced by the neurons,” Xu explained. “We found that two receptors, serotonin 2C receptor and serotonin 1B receptor, are involved in both types of feeding behavior. Our data suggests that combining compounds directed at both receptors might produce a synergistic benefit by suppressing feeding.”

In addition, the team identified ion channels associated with the circuits that also might offer an opportunity to regulate the feeding behaviors. “One is the GABA A receptor, a chloride channel, found to be important in regulating serotonin circuits during hunger-driven feeding, but not during non-hunger driven feeding,” Xu said.

The other is a potassium channel that influences feeding triggered by hunger-independent cues, but not hunger-driven feeding. “There is a clear segregation of these two ion channels,” Xu said. “They have distinct functions in feeding behavior, which suggests they also could be target candidates to regulate overeating.”

The findings have encouraged the researchers to conduct future studies to identify more molecules that could modulate the activity of the ion channels to produce anti-overeating effects in animal models. “We also want to explore how external factors related to nutrition might affect ion channel functions at the molecular level,” Xu said.

The following authors also contributed to this work: Yanlin He, Xing Cai, Hailan Liu, Kristine M. Conde, Pingwen Xu, Yongxiang Li, Chunmei Wang, Meng Yu, Yang He, Hesong Liu, Chen Liang, Tingting Yang, Yongjie Yang, Kaifan Yu, Julia Wang, Rong Zheng, Feng Liu, Zheng Sun, Lora Heisler, Qi Wu, Qingchun Tong, Canjun Zhu and Gang Shu. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, South China Agricultural University, University of Texas Health at San Antonio, University of Aberdeen and University of Texas Health Science Center at Houston.

The investigators were supported by grants from the NIH (R01DK114279, R01DK109934, R21NS108091, R01ES027544, R01DK111436, R00DK107008, R01DK109194, R56DK109194, P01DK113954, R01DK115761, R01DK117281, R01DK125480, R01DK120858, K01DK119471 and P20GM135002).

Further support was provided by USDA/CRIS (51000-064-01 S), American Diabetes Association (1-17-PDF-138, 7-13-JF-61 and 1-15-BS-184), American Heart Association awards (16POST27260254), the Pew Charitable Trust awards (0026188), Baylor Collaborative Faculty Research Investment Program grants, the Faculty Start-up grants from USDA/ARS, the Biotechnology and Biological Sciences Research Council (BB/K001418/1 and BB/NO17838/1), the Medical Research Council (MC/PC/15077), a Pew Scholarship of Biomedical Sciences and a Kavli Scholarship.

Reference: He, Y., Cai, X., Liu, H. et al. 5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding. Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01220-z

Provided by BCM

Food

Study Shows Diet Causes 84% Drop in Troublesome Menopausal Symptoms—without Drugs (Food)

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A new study, published by the North American Menopause Society in the journal Menopause, found a plant-based diet rich in soy reduces moderate-to-severe hot flashes by 84%, from nearly five per day to fewer than one per day. During the 12-week study, nearly 60% of women became totally free of moderate-to-severe hot flashes. Overall hot flashes (including mild ones) decreased by 79%.

Hot Flashes Completers

The study, called the WAVS trial—the Women’s Study for the Alleviation of Vasomotor Symptoms–shows that diet changes can be much more powerful for treating hot flashes than scientists had thought. Vasomotor symptoms refer to night sweats, hot flashes, and flushes.

The study used no hormone medications or extracts. Instead, the research team tested a combination of a low-fat plant-based diet plus 1/2 cup of ordinary soybeans added to a salad or soup each day.

“This is a game changer for women aged 45 and over, most of whom we now know can get prompt relief from the most severe and troubling menopause symptoms without drugs,” says lead researcher Neal Barnard, MD, president of the Physicians Committee and adjunct professor at the George Washington University School of Medicine.

As many as 80% of postmenopausal women suffer from hot flashes. Heat wells up from the chest, causing flushing, sweating, and chills. At night, hot flashes interfere with sleep. Estrogen-based medications were once routinely used to treat hot flashes but have been shown to increase the risk of breast cancer and other serious problems. Isoflavoneextracts from soybeans work only modestly, leaving women and their doctors with few effective options.

Study Details

Postmenopausal women reporting two or more hot flashes per day were randomly assigned to either an intervention group—consisting of a low-fat, vegan diet, including half a cup of cooked soybeans daily—or to a control group that made no diet changes for 12 weeks. Frequency and severity of hot flashes were recorded using a mobile application, and vasomotor, psychosocial, physical, and sexual symptoms were assessed using the Menopause Specific Quality of Life Questionnaire (MENQOL).

Each participant was given a digital self-calibrating scale to track body weight day by day, a mobile app to track hot flashes in real time, and an Instant Pot to prepare soybeans at home. Each week, the group got together with the research team via Zoom.

“Previous studies have shown that soy could be beneficial, so we decided to put a diet change to the test,” says study author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee. “We believe that the combination is what is important. By the end of the study, the majority of women on a plant-based diet rich in soy reported that they no longer experienced moderate-to-extreme hot flashes at all and that they experienced significant improvements in their quality of life.”

Key Findings

hot flashes graph

Total hot flashes decreased by 79% and moderate-to-severe hot flashes decreased by 84% in the intervention group. At the study’s conclusion, 59% of intervention-group participants reported becoming free of moderate and severe hot flashes. There was no change in this variable in the control group.

In previous randomized trials, soy products have been shown to modestly reduce the frequency of hot flashes. The researchers theorize that the effect may be a result of soy products containing isoflavones, which can be metabolized by gut bacteria into equol—a nonsteroidal compound that has been shown in some studies to reduce the incidence and severity of hot flashes. Previous studies have also shown that those following vegetarian or vegan diets produce higher levels of equol. The new study showed a more robust response, using the combination of a plant-based diet plus soy.

Many study participants also reported improvements in sexual symptoms, mood, and overall energy.

 “This was basically a lifesaver for me,” said one study participant. “I’ve got my quality of life back.” Another said, “I am sleeping better, and my hot flashes diminished tremendously.” Several participants also noticed significant weight loss and better digestion.
“Before you jump to any kind of medication, I would try this route, because it’s easy,” a study participant said. “Anybody can do it.” 

The study was based on the new approach to menopausal symptoms described by Dr. Barnard in his book Your Body in Balance. After the book was released in 2020, a reader contacted Dr. Barnard to let him know that his method eliminated her hot flashes within five days. Rather than using isoflavone extracts or soy foods such as soy milk or tofu, she used whole soybeans.

Featured image credit: Gettyimages, others: PCRM

Reference: Barnard, Neal D. MD, FACC1,2; Kahleova, Hana MD, PhD1; Holtz, Danielle N. BS1; del Aguila, Fabiola PhD1; Neola, Maggie BS, RD1; Crosby, Lelia M. BA, RD1; Holubkov, Richard PhD3 The Women’s Study for the Alleviation of Vasomotor Symptoms (WAVS), Menopause: July 12, 2021 – Volume – Issue –
doi: 10.1097/GME.0000000000001812

Provided by Physicians Committee for Responsible Medicine