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Intermittent fasting shows promise in improving gut health, weight management

Participants following an intermittent fasting and protein-pacing regimen, which involves evenly spaced protein intake throughout the day, saw better gut health, weight loss and metabolic responses.

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A new study by researchers from Arizona State University and their colleagues highlights a dietary strategy for significant health improvement and weight management.

Participants following an intermittent fasting and protein-pacing regimen, which involves evenly spaced protein intake throughout the day, saw better gut health, weight loss and metabolic responses. These benefits were notably greater than those seen with simple calorie restriction.

The findings, reported in the journal Nature Communications, could advance our understanding of the relationship between the gut microbiome and metabolism and improve strategies for managing obesity.

The researchers compared the effects of two low-calorie dietary interventions: a heart-healthy continuous calorie-restricted diet (based on USDA dietary recommendations), and a calorie-restricted regimen incorporating intermittent fasting and protein pacing.

The trial was conducted with 41 individuals who were overweight or obese over a period of eight weeks. Individuals in the intermittent fasting and protein-pacing group showed a decrease in symptoms of gastrointestinal problems and an increase in diversity of the gut microbiota compared with those in the calorie-restriction group.

The intermittent fasting protocol increased beneficial microbes in the gut that have been linked to a lean body type and improved overall health. Additionally, it increased the levels of certain proteins (cytokines) in the blood associated with weight loss, as well as amino acid byproducts that promote fat burning.

Intermittent fasting is an eating pattern that cycles between periods of fasting and eating. The method has recently gained popularity for its potential health benefits, including weight loss, improved metabolic health and enhanced brain function.

“Given the gut microbiota’s location and its constant interaction with the GI tract, we have been gaining a deeper understanding of its pivotal role in dietary responses these last several years,” says Alex Mohr, lead author of the new study. “While limited in duration and sample size, this comprehensive investigation — which included the analysis of the gut microbiome, cytokines, fecal short-chain fatty acids and blood metabolites — underscores the intricate interplay between diet, host metabolism and microbial communities.”

Mohr led the microbiome and molecular investigations, evaluating gut microbial composition, inflammatory molecules called cytokines, SCFAs (metabolites derived from dietary fiber, important for regulating energy balance) and the metabolome.

Mohr is a researcher with the Biodesign Center for Health Through Microbiomes at ASU. Rosa Krajmalnik-Brown, the center director, and researchers Devin Bowes, Karen Sweazea and Corrie Whisner are also contributors to the study.

Corresponding author Paul Arciero of the Department of Health and Human Physiological Sciences at Skidmore College led the clinical trial, which tracked weight loss and body composition.

The study also included contributions from ASU researchers Paniz Jasbi and Judith Klein-Seetharaman, with the School of Molecular Sciences, and Dorothy Sears and Haiwei Gu, with the College of Health Solutions.  

Diet, microbiome and weight loss

The gut microbiome refers to the diverse community of microorganisms residing in the gastrointestinal tract, including bacteria, viruses, fungi and other microbes. Numbering in the many trillions of organisms, this complex ecosystem plays a crucial role in essential bodily functions and overall health.

The gut microbiome helps break down food, produce vitamins and promote the absorption of nutrients. It plays a role in the development and function of the immune system by protecting the body against harmful pathogens. Finally, the gut microbiome keenly regulates metabolism,  impacting body weight, fat storage and insulin sensitivity.

Caloric restriction, intermittent fasting (limiting food consumption to certain windows on some days) and protein pacing (controlled protein intake at specific meals) have been shown to affect body weight and composition, but the effect of these dietary modifications on the gut microbiome has been unclear until now.

“A healthy gut microbiome is essential for overall health, particularly in managing obesity and metabolic diseases,” says Sweazea, the ASU principal investigator of this Isagenix-funded study. “The gut bacteria influence how we store fat, balance glucose levels and respond to hormones that make us feel hungry or full. Disruptions in the gut microbiota can lead to increased inflammation, insulin resistance and weight gain, underscoring the critical role of gut health in preventing and managing metabolic disorders.”

Study and findings

The clinical trial involved 27 female and 14 male participants who were overweight or obese.  Participants were divided into two groups: one following the intermittent fasting and protein pacing regimen, and the other adhering to a heart-healthy, calorie-restricted diet. Both groups were monitored over eight weeks for changes in weight, body composition, gut microbiome composition and plasma metabolomic signatures.

Participants following the intermittent fasting and protein pacing regimen experienced a significant reduction in gut symptoms and an increase in beneficial gut bacteria, particularly from the Christensenellaceae family. The study also found these microbes are associated with improved fat oxidation and metabolic health. In contrast, the calorie-restricted group showed an increase in metabolites linked to longevity-related pathways.

Despite both groups having similar average weekly energy intake, the intermittent fasting and protein pacing group achieved greater weight loss and fat reduction with an average loss of 8.81% of their initial body weights during the study. In comparison, those on a calorie-restricted diet lost an average of 5.4% body weight.

Participants who followed the intermittent fasting and protein-pacing diet experienced reductions in overall body fat, including belly fat and deep abdominal fat, and saw an increase in the percentage of lean body mass.

The study underscores the potential of intermittent fasting and protein-pacing diets in improving gut health and weight management. While further research is necessary, these findings offer a promising avenue for creating effective dietary interventions for obesity and related metabolic disorders.

“By identifying shifts in specific microbes, functional pathways and associated metabolites, this line of work holds promise for personalized health strategies as we can better tailor nutritional regimens to enhance gut function and metabolic outcomes,” Mohr says.

Additional institutions contributing to the study: Systems Precision Engineering and Advanced Research (SPEAR); Center of Translational Science, Florida International University; Isagenix International LLC; and the School of Health and Rehabilitation Sciences, Department of Sports Medicine and Nutrition, University of Pittsburgh.

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Popular prescription weight loss drugs linked to uncommon blinding condition

Patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.

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A new study led by investigators from Mass Eye and Ear found that patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.

Notably, the study found people with diabetes who had been prescribed semaglutide by their physician and then filled the prescription were more than four times more likely to be diagnosed with NAION. Those who were overweight or had obesity and prescribed this drug were more than seventimes more likely to get the diagnosis.

The study, which was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School,  published July 3rd in JAMA Ophthalmology.

“The use of these drugs has exploded throughout industrialized countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, the study’s corresponding author. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

NAION is relatively rare, occurring up to 10 out of 100,000 people in the general population. NAION is the second-leading cause of optic nerve blindness (second only to glaucoma) and it is the most common cause of sudden optic nerve blindness. NAION is thought to be caused by reduced blood flow to the optic nerve head, with the consequence of permanent visual loss in one eye. According to Rizzo, the visual loss caused by NAION is painless and may progresses over many days before stabilizing, and there is relatively little potential for improvement. There are currently no effective treatments for NAION. 

The impetus for the study occurred in the late summer of 2023 when Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend — three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. The physicians observed all three were taking semaglutide.

This anecdotal recognition led the Mass Eye and Ear research team to run a backward-looking analysis of their patient population to see if they could identify a link between this disease and these drugs, which had been surging in popularity.

Semaglutide was developed to treat type 2 diabetes. The drug encourages weight loss, and its use has snowballed since its launch as Ozempic for diabetes in 2017. The drug was also approved for weight management, branded as Wegovy, and released in 2021.

The researchers analyzed the records of more than 17,000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analyzed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

There are several limitations to the study. Mass Eye and Ear sees an unusually high number of people with rare eye diseases, the study population is majority white, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. The researchers also couldn’t determine if the patients actually took their medication or if they started and then stopped taking semaglutide at some point and how this might have impacted their risk.  

Importantly, the study does not prove causality, and the researchers don’t know why or how this association exists, and why there was a difference reported in diabetic and overweight groups.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is preexisting significant visual loss from other causes.”

Authorship: In addition to Rizzo and Zekavat, other Mass General Brigham co-authors include Jimena Tatiana Hathaway, MD, MPH (MEE); Madhura P. Shah, BS (MEE); David B. Hathaway, MD (BWH); Drenushe Krasniqi, BA (MEE); John W. Gittinger Jr, MD (MEE); Dean Cestari, MD (MEE); Robert Mallery, MD (MEE); Bardia Abbasi, MD (MEE); Marc Bouffard, MD (MEE); Bart K. Chwalisz, MD (MEE) and Tais Estrela, MD (MEE).

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New study confirms forever chemicals are absorbed through human skin

New research, published in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) – chemicals which do not break down in nature – can permeate the skin barrier and reach the body’s bloodstream.

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A study of 17 commonly used synthetic ‘forever chemicals’ has shown that these toxic substances can readily be absorbed through human skin. 

New research, published in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) – chemicals which do not break down in nature – can permeate the skin barrier and reach the body’s bloodstream.  

PFAS are used widely in industries and consumer products from school uniforms to personal care products because of their water and stain repellent properties. While some substances have been banned by government regulation, others are still widely used and their toxic effects have not yet been fully investigated. 

PFAS are already known to enter the body through other routes, for example being breathed in or ingested via food or drinking water, and they are known to cause adverse health effects such as a lowered immune response to vaccination, impaired liver function and decreased birth weight.  

It has commonly been thought that PFAS are unable to breach the skin barrier, although recent studies have shown links between the use of personal care products and PFAS concentrations in human blood and breast milk.  The new study is the most comprehensive assessment yet undertaken of the absorption of PFAS into human skin and confirms that most of them can enter the body via this route. 

Lead author of the study, Dr Oddný Ragnarsdóttir carried out the research while studying for her PhD at the University of Birmingham. She explained: “The ability of these chemicals to be absorbed through skin has previously been dismissed because the molecules are ionised. The electrical charge that gives them the ability to repel water and stains was thought to also make them incapable of crossing the skin membrane. 

“Our research shows that this theory does not always hold true and that, in fact, uptake through the skin could be a significant source of exposure to these harmful chemicals.” 

The researchers investigated 17 different PFAS. The compounds selected were among those most widely used, and most widely studied for their toxic effects and other ways through which humans might be exposed to them. Most significantly, they correspond to chemicals regulated by the EU’s Drinking Water Directive.   

In their experiments the team used 3D human skin equivalent models – multilayered laboratory grown tissues that mimic the properties of normal human skin, meaning the study could be carried out without using any animals. They applied samples of each chemical to measure what proportions were absorbed, unabsorbed, or retained within the models. 

Of the 17 PFAS tested, the team found 15 substances showed substantial dermal absorption – at least 5% of the exposure dose. At the exposure doses examined, absorption into the bloodstream of the most regulated PFAS (perfluoro octanoic acid (PFOA)) was 13.5% with a further 38% of the applied dose retained within the skin for potential longer-term uptake into the circulation.  

The amount absorbed seemed to correlate with the length of the carbon chain within the molecule. Substances with longer carbon chains showed lower levels of absorption, while compounds with shorter chains that were introduced to replace longer carbon chain PFAS like PFOA, were more easily absorbed. Absorption of perfluoro pentanoic acid for example was four times that of PFOA at 59%. 

Study co-author, Dr Mohamed Abdallah, said “our study provides first insight into significance of the dermal route as pathway of exposure to a wide range of forever chemicals.  Given the large number of existing PFAS, it is important that future studies aim to assess the risk of broad ranges of these toxic chemicals, rather than focusing on one chemical at a time.”  

Study co-author, Professor Stuart Harrad, of the University of Birmingham’s School of Geography, Earth and Environmental Sciences, added: “This study helps us to understand how important exposure to these chemicals via the skin might be and also which chemical structures might be most easily absorbed. This is important because we see a shift in industry towards chemicals with shorter chain lengths because these are believed to be less toxic – however the trade-off might be that we absorb more of them, so we need to know more about the risks involved.” 

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Chronic loneliness may increase stroke risk among older adults

When loneliness was assessed at baseline only, the participants considered lonely had a 25% higher risk of stroke than those not considered lonely. Among the participants who reported loneliness at two time points, those in the “consistently high” group had a 56% higher risk of stroke than those in the “consistently low” group, even after accounting for a broad range of other known risk factors.

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Chronic loneliness may significantly raise older adults’ risk of stroke, according to a new study led by Harvard T.H. Chan School of Public Health. 

“Loneliness is increasingly considered a major public health issue. Our findings further highlight why that is,” said lead author Yenee Soh, research associate in the Department of Social and Behavioral Sciences. “Especially when experienced chronically, our study suggests loneliness may play an important role in stroke incidence, which is already one of the leading causes of long-term disability and mortality worldwide.”

While previous research has linked loneliness to higher risk of developing cardiovascular diseases, few have examined the impact on stroke risk specifically. This study is one of the first to examine the association between loneliness changes and stroke risk over time.

Using 2006-2018 data from the Health and Retirement Study (HRS), the researchers assessed the association between changes in loneliness and stroke incidence over time. During 2006-2008, 12,161 participants—all adults ages 50 and above who never had a stroke—responded to questions on the Revised UCLA Loneliness Scale, from which the researchers created summary loneliness scores. Four years later (2010-2012), 8,936 participants who remained in the study responded to the same questions again. The researchers then placed the participants into one of four groups according to their loneliness scores across the two time points: “consistently low” (those who scored low on the loneliness scale at both baseline and follow-up); “remitting” (those who scored high at baseline and low at follow-up); “recent onset” (those who scored low at baseline and high at follow-up); and “consistently high” (those who scored high at both baseline and follow-up).

Among the participants whose loneliness was measured at baseline only, 1,237 strokes occurred during the follow-up period (2006-2018). Among the participants who provided two assessments of loneliness over time, 601 strokes occurred during the follow-up period (2010-2018). The researchers analyzed each group’s risk of stroke over the follow-up period in the context of their experiences with loneliness, controlling for other health and behavioral risk factors. These included social isolation and depressive symptoms, which are closely related but distinct from loneliness.

The findings showed a link between loneliness and higher risk of stroke and found that chronic loneliness heightened risk the most. When loneliness was assessed at baseline only, the participants considered lonely had a 25% higher risk of stroke than those not considered lonely. Among the participants who reported loneliness at two time points, those in the “consistently high” group had a 56% higher risk of stroke than those in the “consistently low” group, even after accounting for a broad range of other known risk factors. While the baseline analyses suggest loneliness at one time point was associated with higher risk, those who experienced remitting or recent onset loneliness did not show a clear pattern of increased risk of stroke—suggesting that loneliness’ impact on stroke risk occurs over the longer term.

“Repeat assessments of loneliness may help identify those who are chronically lonely and are therefore at a higher risk for stroke. If we fail to address their feelings of loneliness, on a micro and macro scale, there could be profound health consequences,” said Soh. “Importantly, these interventions must specifically target loneliness, which is a subjective perception and should not be conflated with social isolation.”

The authors noted that further research examining both nuanced changes in loneliness over the short-term, as well as loneliness patterns over a longer period of time, may help shed additional light on the loneliness-stroke association. They also noted that more research is needed to understand the potential underlying mechanisms, and that the study findings were limited to middle-aged and older adults and may not be generalizable to younger individuals.

Other Harvard Chan authors included Ichiro Kawachi, Laura Kubzansky, Lisa Berkman, and Henning Tiemeier.

Chronic Loneliness and the Risk of Incident Stroke in Middle and Late Adulthood: A Longitudinal Cohort Study of U.S. Older Adults” was written by Yenee Soh, Ichiro Kawachi, Laura D. Kubzansky, Lisa F. Berkman, Henning Tiemeier, and appeared in eClinicalMedicine.

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