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Tag: Fasting

  • Regular intake of sugary drinks, fruit juices tied to higher Type 2 diabetes risk in boys

    Regular intake of sugary drinks, fruit juices tied to higher Type 2 diabetes risk in boys

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    A small, long-term study of almost 500 children in Massachusetts has found that regularly drinking sugary drinks and 100% fruit juices during childhood and adolescence may be linked to a higher risk of developing Type 2 diabetes among boys than girls, according to preliminary research to be presented at the American Heart Association’s Epidemiology and Prevention│Lifestyle and Cardiometabolic Scientific Sessions 2024, March 18- 21, in Chicago. The meeting offers the latest science on population-based health and wellness and implications for lifestyle.

    While these findings are preliminary, they support the existing evidence about the potential relationship between beverages with added sugar and long-term risk of Type 2 diabetes in children. Pediatricians and other health care professionals should caution young patients and their parents about sugary drinks and fruit juices when discussing healthy eating habits.”


    Soren Harnois-Leblanc, Ph.D., lead investigator, registered dietitian and postdoctoral researcher in the department of population medicine at Harvard Pilgrim Health Care Institute and Harvard Medical School

    According to a 2022 American Heart Association fact sheet about sugary drinks, nearly two-thirds of children and adolescents in the U.S. consume at least one sugary drink, such as soda, lemonade or an energy drink, each day. It also notes that in addition to weight gain, eating too many foods with added sugars, especially from sugary drinks, raises the risk of developing heart disease, high blood pressure, Type 2 diabetes and tooth decay.

    Using data from Project Viva, an ongoing long-term study of women and their children in eastern Massachusetts that began in 1999, researchers explored whether drinking sugary drinks, 100% fruit juices and eating fresh fruits were associated with markers for developing Type 2 diabetes. Researchers calculated the average consumption of sugary drinks, 100% fruit juices, and fresh fruits over childhood and adolescence based on dietary records and assessed their potential associations to three markers of Type 2 diabetes: insulin resistance, fasting blood glucose level and HbA1c levels. These markers were measured by a single blood test while fasting in late adolescence (approximately age 17).

    The analysis found:

    • Each daily serving of sugary drinks (approx. 8 ounces) during childhood and adolescence among boys was associated with a 34% increase in insulin resistance; a 5.6 milligrams per deciliter (mg/dl) increase in fasting glucose levels; and a 0.12% increase in HbA1c levels in late adolescence.

    • Drinking 100% fruit juice throughout childhood and adolescence was linked to a 0.07% increase in HbA1c levels in late adolescence per daily serving of 100% fruit juice among the boys in the study, with only a slight increase in girls of 0.02%.

    • Eating fresh fruit during childhood and adolescence did not appear to have a positive or negative effect on the risk of developing Type 2 diabetes among the boys or girls in the study, according to Harnois-Leblanc.

    The associations between regularly drinking sugar-sweetened beverage and insulin resistance, fasting blood glucose levels and elevated HbA1c levels among boys persisted when other health, family and social factors were considered. These factors included socioeconomic status; child’s and mother’s body mass index; mother’s age at time of child’s birth; maternal and paternal history of Type 1 or Type 2 diabetes; overall diet quality and other lifestyle behaviors.

    “Although several aspects of biology and behaviors differ between boys and girls, I would have expected to also find an association between sugar-sweetened beverages and fruit juice intake and the increases in insulin resistance, glycemia and HbA1c levels in late-adolescent girls. I was also surprised that eating whole fruits did not reduce the levels of these markers of Type 2 diabetes,” Harnois-Leblanc said.

    “The next steps are to use more advanced statistical tools to enable us to better understand the potential causal role of sugary drinks and fruit juices, and to examine whether the relationships may also differ among children by race and/or ethnicity.”

    Study background and details:

    • Researchers analyzed data of children of the 2,128 pregnant women who had children while enrolled in Project Viva. 972 of the children met criteria for inclusion in this study (parent-completed questionnaires at the child’s age-3 examination and no personal or parental history of Type 1 or Type 2 diabetes, assessed separately from parental history of Type 2 diabetes). Of the 972 children, 455 had a fasting blood sample collected at a research visit in late adolescence, Harnois-Leblanc noted.

    • 240 of the children in the study were girls and 215 were boys.

    • Project Viva is a long-term study of women and their children in eastern Massachusetts that began enrollment in 1999. The study is focused on improving maternal and child health by examining the potential impact of various life and health factors during and after pregnancy on the mother’s health and their children’s health, including a review of diet and nutrition. Children were followed from birth to late adolescence, up to age 20 at most recent follow-up.

    • Researchers evaluated the frequency of drinking sugary drinks, fruit juices and eating fresh fruit (based on standard serving sizes) from questionnaires completed by the parent at the child’s age of approximately 3, 8 and 13 years old; and measured fasting blood glucose, insulin and HbA1c levels in late adolescence (average age of 17.4 years).

    The study had several limitations. Although it found an association between regularly drinking sugary drinks and fruit juices and the development of markers for Type 2 diabetes, it could not prove that the drinks caused Type 2 diabetes. Additionally, the relatively small number of study participants may have affected the strength of the association found between sugary drinks and fruit juices and the increased risk of developing Type 2 diabetes.

    “Diet and cardiometabolic health are complex, with many factors varying over time and interacting in different ways, and this study represents one small piece of this puzzle,” Harnois-Leblanc said.

    American Heart Association nutrition committee member Penny M. Kris-Etherton, Ph.D., R.D., FAHA, said, “This study has shown that greater sugar sweetened beverage intake, including fruit juice, throughout childhood and adolescents is associated with higher markers of diabetes risk in late adolescents in boys but not girls. It is striking that many measures of Type 2 diabetes risk were increased in boys at such an early age.”

    Kris-Etherton, an emeritus professor of nutritional sciences at Penn State University, was also a co-author of the Association’s 2018 science advisory on low-calorie sweetened beverages and cardiometabolic health.

    “Importantly, although fruit intake did not appear to be protective, it nonetheless was not associated with increased Type 2 diabetes risk,” she said. “These findings support the current dietary recommendations of the Association, and many organizations, to limit or eliminate drinking sugar sweetened beverages and instead consume whole fruits, which are high in so many nutrients especially the shortfall nutrients in the average American diet.” (Shortfall nutrients are the vitamins and nutrients that people are missing each day from the foods they eat; long-term deficiencies in some vitamins and nutrients have been linked to adverse health outcomes.)

    The health care resource called Know Diabetes by Heart, developed by the American Heart Association and the American Diabetes Association, provides information about preventing heart disease and stroke while living with Type 2 diabetes. The initiative aims to raise awareness and understanding of the link between Type 2 diabetes and cardiovascular disease, provide resources and support to help people better manage their risk for heart disease and stroke, support health care professionals by sharing the latest clinical guidelines and science and engage health systems to improve quality of care for people with Type 2 diabetes.

    Source:

    American Heart Association

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  • Mediterranean diet’s aromatic herbs lower blood sugar

    Mediterranean diet’s aromatic herbs lower blood sugar

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    In a recent study published in the journal Nutrients, researchers from Spain investigated the influence of aromatic herbs and spices in the Mediterranean diet (MedDiet) on the glycemic profiles of patients with type 2 diabetes mellitus (T2DM). They found that black cumin, cinnamon, ginger, curcumin, and saffron significantly lowered fasting blood glucose levels. Further, they found that black cumin and ginger significantly improved glycated hemoglobin (HbA1c) levels in T2DM patients, while cinnamon and ginger significantly lowered insulin concentration.

    Review: Changes in food preferences and ingestive behaviors after glucagon-like peptide-1 analog treatment: techniques and opportunities. Image Credit: aboikis / ShutterstocReview: Changes in food preferences and ingestive behaviors after glucagon-like peptide-1 analog treatment: techniques and opportunities. Image Credit: aboikis / Shutterstock

    Background

    T2DM is a critical healthcare concern, affecting 460 million people globally. Its prevalence has surged in the past four decades, contributing to three or more comorbidities in 60% of patients ten years after diagnosis and causing 6.7 million annual deaths. Various risk factors, including genetics, metabolism, and the environment, influence the disease. While non-modifiable factors like ethnicity and family history play a role, addressing the modifiable risk factors such as lack of physical activity, obesity, and an unhealthy diet can potentially prevent T2DM. Dietary guidance is essential for improving patients’ lifespan and quality of life.

    MedDiet emphasizes high consumption of extra-virgin olive oil, low-glycemic-index carbohydrates, and moderate fish, poultry, and dairy intake. Additionally, it limits the intake of red meat and alcohol. Evidence suggests that MedDiet can positively impact metabolic syndrome and T2DM, as demonstrated by lowered diabetes risk and improved glycemic profiles. The diet incorporates various aromatic herbs and spices, such as black cumin, clove, parsley, saffron, thyme, ginger, black pepper, rosemary, turmeric, basil, oregano, and cinnamon, known for potential health benefits, including antitumor, antioxidative, anti-inflammatory, and cholesterol-lowering properties. Therefore, researchers in the present study aimed to examine the effect of all these aromatic spices and herbs on the glycemic profiles of T2DM subjects.

    About the study

    For the present systematic review and meta-analysis, databases including Web of Science, PubMed, and Scopus to identify peer-reviewed articles and interventional studies. Case studies, commentaries, letters, conference papers, narrative reviews, and studies not conducted in humans or those involving children were excluded. The systematic review included 77 studies, while the meta-analysis included 45 studies (3050 participants).

    The studies involved varying dosages of the spices and herbs and assessed their effect on glycemic profiles. The primary outcomes included fasting glucose, insulin, and HbA1c alterations, while secondary outcomes included variations in body weight and body mass index (BMI). Statistical analysis involved the determination of changes in means and standard deviation and the use of Cochrane Q and Higgins I2 tests. The risk of publication bias was assessed using Egger plots. The quality of the included trials was assessed using the methodology described by Kmet et al.

    Results and discussion

    Cinnamon supplementation significantly reduced fasting glucose in six out of eleven studies. The meta-analysis indicated a reduction of 18.67 mg/dL compared to placebo, but the difference was not statistically significant in considering predictive value. Curcumin supplementation in seven studies showed a significant reduction in fasting glucose (p < 0.001) compared to placebo, with a significant difference including predictive value. Ginger supplementation in ten studies demonstrated a reduction in fasting glucose (17.12 mg/dL, p = 0.0004) compared to placebo, with no significant difference, including predictive value. Black cumin supplementation in eight studies resulted in a significant reduction in fasting glucose (p = 0.0001) compared to placebo, with no significant difference in considering predictive value. Using saffron supplementation resulted in substantially lowering glucose, an effect more pronounced when combined with physical activity. Overall, black cumin demonstrated the most substantial reduction in fasting glucose, followed by cinnamon and ginger.

    Further, only ginger and black cumin exhibited a significant improvement in HbA1c, and cinnamon and ginger significantly decreased insulin levels. Among the analyzed aromatic herbs and spices in the MedDiet, ginger stood out as the sole contributor to significant decreases in all three examined outcomes: HbA1c, fasting glucose, and insulin level.

    The quality of studies selected for the review (mean score 0.54) was lower than the quality of studies selected for the meta-analysis (mean score 0.68). Despite the large scale of the study, the findings are limited by the lack of consideration of body weight and lifestyle changes affecting fasting glucose levels, alongside challenges posed by varying study quality, inadequate statistical analyses, and the absence of standardized herb dosage information.

    Conclusion

    In conclusion, the present study could identify the potential therapeutic benefits of various aromatic herbs and spices in MedDiet for diabetes management. Further research is needed to determine optimal dosages and assess the impact of active components of the herbs and spices, facilitating their application in targeted interventions for glycemic control in T2DM patients.

    Journal reference:

    • Effect of Aromatic Herbs and Spices Present in the Mediterranean Diet on the Glycemic Profile in Type 2 Diabetes Subjects: A Systematic Review and Meta-Analysis. Garza MC et al., Nutrients, 16(6):756 (2024), DOI: 10.3390/nu16060756, https://www.mdpi.com/2072-6643/16/6/756

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  • Increased adherence to DASH diet related to decreased probabilities of metabolic disease conditions among adolescents, particularly overweight girls

    Increased adherence to DASH diet related to decreased probabilities of metabolic disease conditions among adolescents, particularly overweight girls

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    In a recent study published in Scientific Reports, researchers evaluated the relationship between Dietary Approaches to Stop Hypertension (DASH) and metabolic health status among Iranian overweight and obese adolescents.

    Study: Association of priori-defined DASH dietary pattern with metabolic health status among Iranian adolescents with overweight and obesity. Image Credit: monticello/Shutterstock.com
    Study: Association of priori-defined DASH dietary pattern with metabolic health status among Iranian adolescents with overweight and obesity. Image Credit: monticello/Shutterstock.com

    Background

    Adolescent overweight and obesity are global health concerns associated with metabolic conditions such as hypertension, blood lipid abnormalities, impaired glucose metabolism, and insulin resistance. These diseases increase the risk of cardiovascular disease, type 2 diabetes, and early death—lifestyle variables such as food and physical exercise influence metabolic health.

     Recent studies report favorable relationships between high vegetable and fruit intake and low sugary beverages and fats, implying a link between healthy diets and metabolically healthy overweight or obesity. The DASH diet, which contains more vegetables, fruits, whole grains, legumes, seeds, and low-fat-type dairy foods, has been researched in adolescents, but disputed findings call for more research.

    About the study

    In the present cross-sectional study, researchers explored the metabolic impact of DASH diets among overweight and obese adolescents.

    The team surveyed 203 adolescents aged 12 to 18 years with overweight or obesity status, as determined by body mass index (BMI) values using the Quetelet formula. Eligible students did not follow weight-loss diets, had no endocrinal or genetic disease, and did not use vitamin or mineral supplements or medications that could alter their metabolic profiles. 

    The researchers obtained dietary intake data using standardized food frequency questionnaires (FFQs). They also collected data on anthropometric parameters such as circulating insulin, blood pressure, lipid profile, and fasting blood sugar. The team characterized DASH scores based on eight components, i.e., higher intake of low-fat dairy foods, whole grains, seeds, nuts, vegetables, fruits, and legumes, and lower consumption of sodium, sweetened beverages, and processed and red meats.

    The team obtained blood samples from all participants for biochemical analysis. They measured insulin levels by enzyme-linked immunosorbent assays (ELISA) and ascertained metabolic health status based on insulin resistance, determined using the International Diabetes Federation (IDF) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) criteria.

    The researchers assessed physical activity levels using the Physical Activity Questionnaire for Adolescents (PAQ-A) and total calorie intake using the United States Department of Agriculture (USDA) food composition database. They used multivariate logistic regression to calculate the odds ratios (ORs) for the association between DASH diets and metabolic health, adjusting for age, gender, physical activity, socioeconomic status, and total calorie intake.

    Results

    The mean values for age and BMI of the study participants were 14 years and 27 kg/m2, respectively. Among participants, 79 (42 girls and 37 boys, 39%) suffered from metabolically unhealthy overweight or obesity (MUO) by the IDF definition, and 62 (32 girls and 35 boys, 33%) were MUO following the IDF and HOMA-IR guidelines. Using the IDF definition, MUO prevalence in the DASH diet’s highest tertile was lower compared to the lowest statistical tertile (10 vs. 67%). Using HOMA-IR guidelines yielded similar findings (10 vs. 61%).

    Individuals in the uppermost tertile of the DASH diet were more physically active, with higher HDL-c levels and lower blood pressure, fasting blood sugar, insulin, triglyceride, and HOMA-IR levels, compared to those in the lowest tertile. Confounder adjustment showed that individuals in the highest vs. lowest DASH tertile had 91% and 92% lower MUO odds using the IDF/IR (OR, 0.09) and IDF definition (OR, 0.08), respectively.

    The highest vs. lowest DASH adherence was associated with decreased odds of hyperglycemia, hypertriglyceridemia, insulin resistance, and low HDL cholesterolemia, with odds ratios of 0.1, 0.3, 0.1, and 0.3, respectively. Subgroup analysis by BMI and sex indicated that the association was more robust among females (OR, 0.02) than males (OR, 0.09). The DASH diet likely improves metabolic health by lowering inflammation because of its high fiber, antioxidants, potassium, magnesium, and low salt content.

    Conclusions

    Overall, the study findings showed that increased adherence to the DASH diet was related to decreased probabilities of metabolic disease conditions among Iranian adolescents, particularly overweight girls. The study also found that adhering to the DASH diet reduced the risk of hypertriglyceridemia, hyperglycemia, insulin resistance, and low HDL cholesterol. Further research, including prospective surveys, could validate the study findings.

    The inverse association observed between the DASH dietary pattern and the MUO category in the current study indicates that adolescents must increase the intake of health-associated DASH components, including fruits, vegetables, legumes, low-fat-type dairy foods, whole grains, seeds, and nuts while limiting the consumption of unhealthy foods such as processed and red meats, sweetened beverages, and salt to improve dietary quality and decrease the metabolic disease burden.

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  • Study reveals the body’s molecular response to prolonged fasting

    Study reveals the body’s molecular response to prolonged fasting

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    New findings reveal that the body undergoes significant, systematic changes across multiple organs during prolonged periods of fasting. The results demonstrate evidence of health benefits beyond weight loss, but also show that any potentially health-altering changes appear to occur only after three days without food. 

    The study, published today in Nature Metabolism, advances our understanding of what’s happening across the body after prolonged periods without food. 

    By identifying the potential health benefits from fasting and their underlying molecular basis, researchers from Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and the Norwegian School of Sports Sciences provide a road map for future research that could lead to therapeutic interventions – including for people that may benefit from fasting but cannot undergo prolonged fasting or fasting-mimicking, such as ketogenic, diets. 

    Over millennia, humans have developed the ability to survive without food for prolonged periods of time. Fasting is practiced by millions of people throughout the world for different medical and cultural purposes, including health benefits and weight loss. Since ancient times, it has been used to treat diseases such as epilepsy and rheumatoid arthritis. 

    During fasting, the body changes its source and type of energy, switching from consumed calories to using its own fat stores. However, beyond this change in fuel sources, little is known about how the body responds to prolonged periods without food and any health impacts – beneficial or adverse – this may have. New techniques allowing researchers to measure thousands of proteins circulating in our blood provide the opportunity to systematically study molecular adaptions to fasting in humans in great detail. 

    Researchers followed 12 healthy volunteers taking part in a seven-day water-only fast. The volunteers were monitored closely on a daily basis to record changes in the levels of around 3,000 proteins in their blood before, during, and after the fast. By identifying which proteins are involved in the body’s response, the researchers could then predict potential health outcomes of prolonged fasting by integrating genetic information from large-scale studies. 

    As expected, the researchers observed the body switching energy sources – from glucose to fat stored in the body – within the first two or three days of fasting. The volunteers lost an average of 5.7 kg of both fat mass and lean mass. After three days of eating after fasting, the weight stayed off – the loss of lean was almost completely reversed, but the fat mass stayed off. 

    For the first time, the researchers observed the body undergoing distinct changes in protein levels after about three days of fasting – indicating a whole-body response to complete calorie restriction. Overall, one in three of the proteins measured changed significantly during fasting across all major organs. These changes were consistent across the volunteers, but there were signatures distinctive to fasting that went beyond weight loss, such as changes in proteins that make up the supportive structure for neurons in the brain. 

    For the first time, we’re able to see what’s happening on a molecular level across the body when we fast. Fasting, when done safely, is an effective weight loss intervention. Popular diets that incorporate fasting – such as intermittent fasting – claim to have health benefits beyond weight loss. Our results provide evidence for the health benefits of fasting beyond weight loss, but these were only visible after three days of total caloric restriction – later than we previously thought.” 


    Claudia Langenberg, Director of Queen Mary’s Precision Health University Research Institute (PHURI)

    Maik Pietzner, Health Data Chair of PHURI and co-lead of the Computational Medicine Group at Berlin Institute of Health at Charité, said: 

    “Our findings have provided a basis for some age-old knowledge as to why fasting is used for certain conditions. While fasting may be beneficial for treating some conditions, often times, fasting won’t be an option to patients suffering from ill health. We hope that these findings can provide information about why fasting is beneficial in certain cases, which can then be used to develop treatments that patients are able to do.” 

    Source:

    Queen Mary University of London

    Journal reference:

    Pietzner, M., et al. (2024). Systemic proteome adaptions to 7-day complete caloric restriction in humans. Nature Metabolism. doi.org/10.1038/s42255-024-01008-9.

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  • Understanding obesity’s effects on liver metabolism

    Understanding obesity’s effects on liver metabolism

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    Your liver plays a vital role in your metabolism, the biological process which converts food into energy. We know that being overweight can negatively affect metabolic activity, but not exactly how. To better understand this, researchers compared the livers of mice which were a typical weight with mice which were obese. They were surprised to find that biological regulation of metabolic activity, after a period of feasting and fasting, was reversed between them. In typical mice, allosteric regulation (the process which controls metabolism) was inhibited during feeding and activated when fasting. However, in obese mice, allosteric regulation increased during feeding and decreased when fasting. Investigating the reasons behind this reversed biological behavior could help health professionals understand how obesity affects the body and the development of disease.

    The World Obesity Federation (WOF) estimates that by 2035, over 4 billion people will be overweight or living with obesity. This may lead to a rise in obesity-related health conditions, such as heart disease, nonalcoholic fatty liver disease and Type 2 diabetes. Identifying the causes and effects of obesity, which is now understood to be a complex disease, is key for physicians looking to provide support and help people stay healthy.

    One known way that obesity can affect health is by impacting metabolism, the process by which our bodies take in, store and use energy from our food. Certain organs play key roles in this process, notably the liver. Not only is food processed there to provide energy, but it is one of the places where useful products at the end of the metabolic process are stored until we need them. To better understand the effects of obesity on the liver, researchers compared the livers of typical mice and obese mice after periods of feeding and fasting.

    The team carried out trans-omics analysis, an approach where they gathered data on five sets of biological processes (multi-omics). They then combined these layers of data with information from biological databases to create a trans-omic network. This gave them an overview of how the different layers interacted. “

    We constructed a trans-omic network of metabolic reactions in the livers of mice that could feed freely. We then compared this with data we had previously gathered from mice that had fasted for 16 hours. While enzyme and allosteric regulation which controls metabolism was suppressed in typical mice during feeding, we were surprised to find that the reverse occurred in obese mice and that this activity increased.”

    Professor Shinya Kuroda, Graduate School of Science, University of Tokyo

    When we eat, our liver builds up stores of energy which is then released as needed, a system known as metabolic homeostasis. However, the researchers saw that in obese mice this equilibrium became dysregulated, i.e., normal function was disrupted, indicating a potential breakdown of the system. This could lead to metabolic disorders such as tiredness, lack of energy and decreased appetite. By contrast, they saw that transcriptional regulation, a process which regulates metabolism and controls cell activity at a genetic level, did not change much between feeding and fasting. This means that, compared to allosteric regulation, it is more stable and less affected by what we eat.

    The team noted that what they observed may not only be evidence of disruption within the liver alone, but a change to broader metabolic cycles throughout the body. “Obesity is a metabolic disease, so to understand it, it is important to construct a trans-omic network with metabolome (the complete set of small-molecule chemicals) at its center,” said Kuroda. “We are interested not only in the liver, but also how the products of metabolic reactions circulate between liver and muscle through the blood in obese mice, which is what we will be working on now.”

    Source:

    Journal reference:

    Bai, Y., et al. (2024) Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity. iScience. doi.org/10.1016/j.isci.2024.109121.

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  • Insights into gut plasticity mechanisms unveiled through fruit fly research

    Insights into gut plasticity mechanisms unveiled through fruit fly research

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    One of the most striking examples of gut plasticity can be observed in animals that are exposed to prolonged periods of fasting, such as hibernating animals or phyton snakes that goes for months without eating, where the gut shrinks with as much as 50%, but recovers in size following a few days of re-feeding. Importantly, the capacity of the gut to undergo resizing is broadly conserved. Hence, in humans, an increase in gut size is observed during pregnancy, which facilitates the uptake of nutrients to support the growth of the fetus.

    The Colombani Andersen lab at the section of Cell & Neurobiology, Department of Biology, University of Copenhagen uses the fruit fly, Drosophila, to study the mechanisms that regulate gut plasticity. The results have just been published in the scientific journal Nature Communications.

    Taking advantage of the broad genetic toolbox available in the fruit fly, we have investigated the mechanisms underpinning nutrient-dependent gut resizing.”


    Dr. Ditte S. Andersen

    The results show that nutrient deprivation results in an accumulation of progenitor cells that fail to differentiate into the mature cells causing the gut to shrink. Upon refeeding these stalled progenitor cells readily differentiate into mature cells to promote regrowth of the gut.

    Ditte S. Andersen continues: – “We have identified activins as critical regulators of this process. In nutrient restrictive conditions, activin signaling is strongly repressed, while it is reactivated and required for progenitor maturation and gut resizing in response to refeeding. Activin-dependent resizing of the gut is physiologically important as inhibition of activin signaling reduces survival of flies to intermittent fasting”.

    Regulators of organ plasticity are essential for host adaptation to an ever-changing environment, however, the same signals are often deregulated in cancers. Indeed, mutations affecting activin signaling are frequent in cancer cells in a variety of tissues. Our study provides a starting point for investigating the link between aberrant activin signaling and the development of colorectal cancers and sets the stage for exploring the efficiency of anti-activin therapeutic ­strategies in treating colorectal cancers.

    Source:

    University of Copenhagen – Faculty of Science

    Journal reference:

    Christensen, C. F., et al. (2024). Drosophila activins adapt gut size to food intake and promote regenerative growth. Nature Communications. doi.org/10.1038/s41467-023-44553-9.

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  • Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat

    Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat

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    A recent Nature Communications study performed analyses of blood samples obtained from a randomized clinical trial. It showed that three cycles of fasting-mimicking diet (FMD) in adults were associated with lower pre-diabetes markers, lower hepatic fat, and a higher lymphoid-to-myeloid ratio, which is an indicator of the aging of the immune system. 

    Study: Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Image Credit: Kmpzzz/Shutterstock.com
    Study: Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Image Credit: Kmpzzz/Shutterstock.com

    Background

    Metabolic syndromes are characterized by the co-occurrence of three symptoms from within: abdominal obesity, dyslipidemia, insulin resistance, and elevated CRP levels. Research has shown that obesity accelerates liver aging and acts on other molecular hallmarks of aging. Another feature of aging is immunosenescence, which is the altered function and composition of the immune system. 

    Dysfunction in different types of cells stemming from aging is at the center of many diseases, including cancer, cardiovascular disease, and so on. This suggests that intervening in the aging process could lead to the prevention or amelioration of human diseases. This has indeed been noted in animal models where slowing down cellular deterioration led to new or functional intra-cellular components.

    Everyday nutrition has been seen to play a crucial role in speeding up the aging process in rodents, and this could possibly be true in humans as well. Besides the nutrient content, the number of hours for which meals are consumed influences lifespan and health. In this regard, time-restricted eating (TRE), periodic water-only fasting (PF), and intermittent fasting (IF) have gained popularity recently. 

    About the study

    A fasting-mimicking diet (FMD) is a low-calorie, plant-based, and low-protein dietary intervention that lasts for 5-days. FMD followed by a normal diet has been seen to have positive effects on both cellular healthspan and function. The hypothesis tested here was that FMD cycles reduce biological age by improving the levels of various markers of aging.

    For this study, blood samples were obtained from a randomized control trial, followed by recording cellular and metabolic measurements. Insights were also provided on lymphoid/myeloid ratios, blood markers, and visceral and hepatic fat, which are secondary outcome measures and biomarkers associated with age-related diseases and aging generally. 

    The biological age of participants was studied before and after they completed 3FMD cycles.

    It is also important to note that the biological age and the chronological age may differ because aging is a heterogeneous process. Biological age is based on many multisystem biomarkers, which helps us understand the rate and level of organismal aging. 

    Study findings

    A calorie reduction of 15–20% below the normal levels was seen to have significant effects on the risk factors for multiple diseases. Preliminary findings showed that alternate-day fasting and caloric restriction (CR) are effective at reducing the risks related to aging. However, chronic CR is quite a severe intervention that could, in principle, reverse the benefits by reducing lean body mass and weight. 

    The cohort comprised individuals who were healthier than the average American person. In this cohort, 3 FMD cycles were followed by a reduction in median biological age of 2.5 years. Furthermore, reductions in 20-year risk for cause-specific and all-cause mortality were noted.

    The findings assume that the associations between mortality and biological age mirror the effect of change in biological age, but this fact is yet to be proven. Nevertheless, the results documented here offer early evidence of the potential health benefits of FMD, even in a cohort of relatively healthier individuals.

    The benefits of FMD were most noted in individuals who were relatively more unhealthy at baseline. In terms of mechanisms, FMD lowered the hepatic fat fraction and visceral fat in study participants with non-alcoholic fatty liver disease and obesity. In this way, FMD cycles act to prevent diabetes and metabolic syndrome. Another explanation could be the importance of shared mechanisms, e.g., general rejuvenating effects in organs and cells, which lower systemic inflammation.

    Conclusions

    In sum, it was suggested that sustained FMD or similar dietary interventions may lead to improvements in population health by extending life expectancy, slowing the rate of aging, and reducing the risks of disease-specific mortality. More specifically, 3 FMD cycles each year could lead to a less than one year gain in biological age for every year increase in chronological age. 

    A key limitation of the study centers around the small sample size and lack of heterogeneity in health status at baseline. Characteristics that study participants did not capture could change the impact of FMD on biological age, thereby making the current estimates inaccurate. Furthermore, extrapolation of the 3–6 months effects of the FMD to lifelong intervention should be interpreted with caution. This is because the effects may cease to persist if participants return to their pre-intervention lifestyles.  

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  • Fasting-mimicking diet reduces biological age and disease risks, study shows

    Fasting-mimicking diet reduces biological age and disease risks, study shows

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    Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new USC Leonard Davis School of Gerontology-led study.

    The study, which appears in Nature Communications on Feb. 20, adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD).

    The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast. The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study.

    This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age.”


    Valter Longo, Professor, USC Leonard Davis School

    Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects. They can:

    • Promote stem cell regeneration

    • Lessen chemotherapy side effects

    • Reduce the signs of dementia in mice

    In addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans.

    The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now.

    Lower disease risks & more youthful cells

    The study analyzed the diet’s effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients who were randomized to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days.

    The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids. Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet.

    An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results. Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome. In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio – an indicator of a more youthful immune system.

    Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age – a measure of how well one’s cells and tissues are functioning, as opposed to chronological age – by 2.5 years on average.

    “This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function,” Longo said.

    The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD’s potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said.

    “Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age,” Longo said.

    Source:

    University of Southern California

    Journal reference:

    Brandhorst, S., et al. (2024). Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications. doi.org/10.1038/s41467-024-45260-9.

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  • How does intermittent fasting affect the gut microbiome?

    How does intermittent fasting affect the gut microbiome?

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    In a recent study published in the journal Frontiers in Nutrition, a group of researchers evaluated how various intermittent fasting (IF) regimens impact the composition of the human gut microbiome.

    Study: The impact of intermittent fasting on gut microbiota: a systematic review of human studies. Image Credit: Tatiana Shepeleva / ShutterstockStudy: The impact of intermittent fasting on gut microbiota: a systematic review of human studies. Image Credit: Tatiana Shepeleva / Shutterstock

    Background 

    Fasting, the voluntary avoidance of food and drinks, varies from calorie restriction (CR), which reduces daily calorie intake without causing malnutrition. Fasting is categorized into IF and prolonged fasting (PF), with PF involving water-only consumption for two or more days. IF is popular in various lifestyles, religions, and cultures, encompassing methods like time-restricted eating (TRF), where food intake is limited to 12-18 hours daily, alternate day fasting (ADF), and the 5:2 diet, which alternates between fasting and unrestricted eating days. While TRF may not reduce overall calorie intake, ADF limits calories to about 25% of daily needs on fasting days. Research indicates IF benefits weight loss, blood pressure, anti-inflammatory responses, and metabolic health, partly through modifications in the gut microbiota, impacting glucose metabolism and inflammation. Further research is needed to clarify the specific effects of IF on the human gut microbiome and its implications for health due to the current heterogeneity and limited scope of existing studies.

    About the study 

    The present review explored IF effects on gut microbiota, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)2020 guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO). Initial and follow-up searches across four databases targeted English studies up to 2021, including direct author contacts, to ensure comprehensive IF research coverage.

    The review’s inclusivity spanned various IF modalities, initially focusing on TRF before expanding to ADF and the 5:2 diet in response to the scarcity of TRF-specific research. Exclusions were made for non-human, observational, and non-experimental studies, among others, favoring randomized controlled trials, quasi-experimental studies, and pilot studies without restrictions on participant demographics.

    The selection process involved a thorough screening of titles and abstracts by three independent reviewers, utilizing Rayyan Qatar Computing Research Institute (QCRI) for efficient collaboration and conflict resolution. This initial phase reduced the pool from 1,172 records to 22 potential studies, further narrowed down through consensus after full-text review. The expansion of inclusion criteria and a second search round eventually enriched the review with eight pertinent studies despite the initial limitation to TRF studies.

    Data extraction was evenly distributed among reviewers, focusing on outcomes related to gut microbiota diversity and composition alongside study and participant characteristics without making assumptions about unclear data. The risk of bias was rigorously assessed using Cochrane’s tools, facilitating an unbiased and thorough synthesis of the available evidence on the impact of IF on gut microbiota.

    Study results 

    The present systematic review process precisely outlined the search and selection stages, leading to a critical evaluation of the included studies for risk of bias, utilizing Cochrane’s tools. This appraisal revealed varied levels of bias, highlighting a need for a cautious interpretation of the findings.

    The review delved into the intricacies of IF impacts on gut microbiota, dissecting the methodologies employed across studies to assess microbiota composition and diversity. Through this exploration, it emerged that while several studies observed changes in microbiota richness and diversity, the findings were not uniformly consistent, indicating a complex interplay between IF and gut microbiome dynamics.

    Analyses of gut microbiota richness and diversity across studies on IF showed varied outcomes, indicating IF’s significant but variable impact on the gut microbiome is influenced by demographic and dietary factors. Beta diversity assessments revealed distinct shifts in microbial communities under different IF protocols, highlighting the diet’s personalized effects on gut health. Moreover, the composition of gut microbiota demonstrated both consistent and varied changes in bacterial populations, reflecting the complex influence of IF on the gut ecosystem. This variability suggests IF’s effects are shaped by the specific fasting approach, individual dietary habits, and baseline microbiome characteristics, pointing to an interaction between diet and gut health.

    Additionally, the review illuminated the broader physiological and metabolic implications of IF, including weight loss and dietary changes, across various forms of fasting. While some studies reported significant weight reduction and alterations in energy intake, others highlighted the stability of macronutrient percentages or shifts in food group consumption, painting a complex picture of IF’s influence on diet and body composition.

    The differential findings across TRF, ADF, and 5:2 diet studies not only reflect the diverse methodologies and populations studied but also hint at the potential for IF to induce specific microbiota and metabolic changes, contingent upon the nature and context of the fasting intervention. As revealed through this review, the variations in dietary intake and its subsequent impact on weight and metabolic health emphasize the intricate relationship between fasting practices, nutritional status, and gut microbiome composition.

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  • Ramadan fasting linked to favorable metabolic changes and reduced chronic disease risk

    Ramadan fasting linked to favorable metabolic changes and reduced chronic disease risk

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    In a recent study published in The American Journal of Clinical Nutrition, researchers carried out a metabolomics investigation to elucidate the impacts of Ramadan fasting on health and metabolism. Their study group comprised 72 participants who provided blood shortly before and after Ramadan fasting, based on which researchers generated metabolic scores. Study findings, obtained by comparing participants’ metabolic scores against those maintained by the UK Biobank, reveal that Ramadan fasting significantly reduced the risks of lung, colorectal, and breast cancers.

    Study: Metabolomics of Ramadan fasting and associated risk of chronic diseases. Image Credit: Odua Images / ShutterstockStudy: Metabolomics of Ramadan fasting and associated risk of chronic diseases. Image Credit: Odua Images / Shutterstock

    Can depriving your body of food make you healthier?

    Fasting, the intentional abstention from consuming food and sometimes liquids, is practiced for clinical, religious, political, and fitness reasons, the latter of which is rapidly growing in popularity. Reports reveal that globally, many health-conscious individuals are gravitating toward ‘time-restricted fasting,’ an approach that restricts daily eating to a predetermined period each day (usually six to eight hours). Popularized by the term’ intermittent fasting,’ this trend promises general health improvements, weight loss, and fitness benefits.

    Unfortunately, apart from observational evidence for weight loss, comprehensive metabolic and cohort-based studies into the other benefits of time-restricted fasting remain lacking. Ramadan, the Muslim month of fasting, reflection, prayer, and community, shares every trait of time-restricted fasting except its intent (Ramadan is religious fasting). This provides a ‘natural experiment’ to quantify the positive or negative impacts of time-restricted fasting.

    Two previous works have investigated the impacts of Ramadan fasting on health. However, these studies were small-scale (n = 11, 25) and used dated analytical tools focused on overweight and obese individuals not representative of the fitness-oriented. This presents the need for an updated study using the latest metabolomics techniques and a larger, more generalized sample cohort, the results of which will inform the billions of Muslims and health-minded people worldwide.

    About the study

    In the present study, researchers recorded the metabolomics alterations following Ramadan fasting. Their study cohort was the London Ramadan Study (LORANS), an observational cohort comprising 140 Muslims who observe the Ramadan fast. Study data collection included demographic data, medical records, and two blood samples provided a few days before and a few days following initiation of the fast. Additionally, blood pressure and body composition were recorded during routine blood collection.

    Study inclusion criteria comprised age (above 18 years), intended duration of fast (20 days or more), and completed data records. Pregnant women were excluded from the study. Following exclusions due to unmet criteria requirements, 72 participants were included for data analyses, all providing written informed consent to participate in the study.

    Blood samples were processed to separate and isolate the plasma, which in turn was subjected to high-throughput Nuclear Magnetic Resonance (NMR) spectroscopy using the Nightingale platform. The Nightingale platform was chosen due to its ability to identify and quantify 169 lipids and metabolites. It was also selected because the United Kingdom’s (UK) Biobank dataset includes Nightingale platform readings. The UK Biobank is a country-wide large-cohort prospective study comprising 500,000 English citizens representative of the nation.

    Linear mixed-effects models were used to compare NMR readings from blood samples provided before and after fasting, allowing a one-to-one comparison of the metabolite changes arising as outcomes of the fasting process. Additionally, UK Biobank Nightingale platform metabolite readings were used to compute metabolic risk scores for common chronic diseases, including cancers and cardiometabolic disorders. These values were then applied to NMR readings from this study to measure the relative change in chronic disease risk as a consequence of Ramadan (and, by extension, intermittent) fasting.

    Study findings

    Demographic analyses revealed that the mean age of the 72-strong study cohort was 45.7 years, 48.6% (n = 35) of whom were male. Body assessments during blood collection visits showed that, on average, participants lost 1.7 kg and 1.1% of their body fat in the two to three weeks between measurements. Nightingale platform analyses show that of the 169 measured metabolites, 14 were observed to change significantly when comparing blood collections.

    These included one inflammation marker, one amino acid, two glycolysis-related metabolites, two ketone bodies, two triglycerides, and six lipoprotein subclasses. The most significant differences before/after Ramadan were observed for lactate (β = -0.31, P <0.001), acetate (β= -0.22, P <0.001), tyrosine (β= – 0.10, P=0.019) (all inverse) and acetone (β= 0.10, P=0.019) (direct).

    For establishing the metabolic risk scores, baseline characteristics of 117,981 UK Biobank participants were used to establish seven scores, including diabetes (using 46 metabolites), coronary heart disease (16), hypertension (25), renal failure (12), lung cancer (nine), colorectal cancer (two), and breast cancer (one). Applying these scores to present study participants reveals that the relative risk of lung, colorectal, and breast cancers decreased by 9.6%, 2.4%, and 1.1%, respectively. In contrast, the other measured outcomes observed no changes in metabolic risk scores.

    Conclusions

    The present study uses Ramadan fasting as a natural experiment to investigate the effects of time-restricted fasting on people’s health and chronic illness risk. It used cutting-edge, high-throughput NRM spectroscopy via the Nightingale platform to compute chronic disease metabolite risk scores.

    When applied to the 72 included study participants, the metabolic risk scores highlight the beneficial role of Ramadan fasting in reducing the risk of certain cancers such as lung (-9.6%), colorectal (-2.4%), and breast (-1.1%), while having no measurable effects on cardiovascular disease risk.

    Ramadan fasting is associated with short-term favorable changes in the metabolic profile concerning the risk of some chronic diseases. These findings should be further investigated in future, larger studies of longer follow-up with clinical outcomes.

    Journal reference:

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