Tag /

Metabolism

Episodes

metabolism

How to Improve Metabolic Health with HIIT, Circadian-Timed Eating, & Sleep

Posted on October 7th 2024 (8 months)

Dr. Rhonda Patrick explains how HIIT, circadian-timed eating, and quality sleep improve metabolic health and reduce chronic disease risk.

exercise

Dr. Layne Norton on Building Muscle – Insights on Diet, Training, and Supplements

Posted on August 26th 2024 (10 months)

Dr. Layne Norton and I discuss fat loss, resistance training, seed oils, the carnivore diet, artificial sweeteners, and much more.

aging

Dr. Peter Attia on Mastering Longevity – Insights on Cancer Prevention, Heart Disease, and Aging

Posted on December 27th 2023 (over 1 year)

Dr. Peter Attia presents practical steps we can implement to improve our health, emphasizing the importance of each aspect while providing actionable advice.

Topic Pages

  • Creatine

    Creatine buffers cellular energy metabolism by creatine kinase–mediated reversible phosphorylation to phosphocreatine, rapidly regenerating ATP from ADP.

  • Depression

    Metabolic dysregulation, including insulin resistance and mitochondrial dysfunction, impairs monoamine synthesis and augments neuroinflammation, mechanistically driving depressive pathology.

  • Hydrolyzed collagen

    Hydrolyzed collagen peptides enter systemic circulation, undergo amino-acid metabolism via transamination and oxidation, supplying substrates for collagen resynthesis and gluconeogenesis.

  • NAD+

    NAD+ functions as an electron-accepting cofactor in metabolic dehydrogenase reactions, coupling substrate oxidation to ATP synthesis.

  • Resveratrol

    Resveratrol activates SIRT1 and AMPK, enhancing mitochondrial biogenesis and fatty-acid oxidation, thereby improving cellular metabolic efficiency.

  • Time-restricted eating

    Time-restricted eating synchronizes nutrient availability with circadian clocks, enhancing insulin signaling, mitochondrial oxidative metabolism, lipolysis, and overall metabolic homeostasis.

  • Ultra-processed Foods (UPFs)

    Ultra-processed foods, rich in rapidly digestible carbohydrates and additives, dysregulate insulin signaling and gut microbiota, impairing metabolic homeostasis.

News & Publications

  • Common dietary emulsifiers found in processed foods can disrupt glucose regulation and alter the gut microbiota, potentially driving metabolic and immune dysfunction. www.nature.com
    Gut Microbiome Metabolism

    The additives that make processed foods creamy, smooth, and long-lasting might come with a hidden cost. A recent study in mice found that common dietary emulsifiers disrupt glucose regulation and alter the gut microbiota, potentially contributing to metabolic disorders and immune dysfunction.

    Researchers fed mice diets containing four commonly used emulsifiers: lecithin, sucrose esters, carboxymethylcellulose, and mono- and diglycerides. Then, they analyzed how the compounds affected the gut’s protective mucus barrier and microbial diversity.

    They found that sucrose esters and carboxymethylcellulose elevated the animals' blood glucose and lipids, disrupted glucose regulation, and altered gut microbiota. Similarly, mono- and diglycerides impaired glucose and lipid metabolism, but they also raised markers of inflammation and increased bacterial encroachment into the gut mucus layer, potentially impairing immune function.

    These findings suggest that dietary emulsifiers promote metabolic dysfunction by altering the gut microbiota and disrupting glucose and lipid regulation. Notably, the amounts of emulsifiers in the animals' diets represented a much higher proportion of dietary intake than what humans typically consume, as emulsifiers in processed foods are usually in smaller amounts. Still, long-term consumption could increase exposure through a diet high in processed foods containing emulsifiers.

    Emulsifiers are common in processed foods, including ice cream, baked goods, margarine, salad dressings, and sauces. They help stabilize mixtures of oil and liquids, improving texture and shelf life. Their use reflects the broader role of food additives, which enhance flavor, preserve freshness, and improve processed food products' visual and textural appeal—often at the expense of health. Learn more about the harms of processed foods in Aliquot #111: Why ultra-processed foods and their additives are harmful.

    Read more
  • Long-term intervention with calorie restriction and high-intensity interval training doubles insulin sensitivity and greatly improves liver function in people with a form of fatty liver disease. pubmed.ncbi.nlm.nih.gov
    Exercise Obesity Metabolism Insulin Resistance Fatty Liver

    Metabolic dysfunction-associated steatohepatitis (MASH) is a form of fatty liver disease that promotes inflammation and damage over time. Closely connected to conditions like obesity and insulin resistance, MASH affects nearly one-third of people worldwide. A recent study found that a long-term intervention combining calorie restriction and high-intensity interval training (HIIT) in people with MASH improved liver function, doubling insulin sensitivity.

    Researchers assigned people with MASH to either a treatment group (16 participants) that received lifestyle counseling and exercise training or a control group (eight participants) that continued with standard medical care. The treatment group engaged in supervised HIIT three times a week while reducing caloric intake. The researchers assessed the participants' liver fat, measured blood biochemistries, and evaluated insulin sensitivity before and after the intervention.

    They found that the treatment group experienced notable reductions in body weight, fat mass, and liver injury. Their cardiorespiratory fitness improved considerably, and they exhibited a twofold increase in peripheral insulin sensitivity compared to the control group. Both groups saw reductions in total energy intake and liver fat.

    These findings suggest that combining caloric restriction with regular high-intensity exercise can yield marked improvements in liver health and insulin sensitivity, likely by redistributing excess nutrients to skeletal muscle. Learn more about calorie restriction in this clip featuring Dr. David Sinclair, and HIIT in this clip featuring Dr. Martin Gibala.

    Read more
  • Exposure to benzyl butyl phthalate, a common plastic additive in everyday items, was found to cause extensive reproductive cell disruption and DNA damage. journals.plos.org
    Metabolism Inflammation DNA Damage Pollution Environment Genome

    The risks of everyday plastics may go beyond environmental concerns, affecting our reproductive health on a cellular level. Benzyl butyl phthalate (BBP), a common plastic additive found in toys, cleaning products, food packaging, and cosmetics, has been linked to reproductive and developmental impairments. A recent study in worms found that BPP induced abnormalities in chromosome segregation and increased cell death in reproductive cells.

    Researchers exposed C. elegans, a type of roundworm, to four different concentrations of BBP: 1, 10, 100, and 500 micromolar. Then, they measured the chemical’s effects on the worms' chromosomes and cell structure while tracking its metabolism into two primary byproducts: monobutyl phthalate and monobenzyl phthalate.

    They found that exposure to 10 micromolar BBP induced considerable cellular disruption, increasing germ cell apoptosis, abnormalities in chromosome structure, and elevated levels of DNA damage throughout the reproductive tissues. The compound also triggered increased oxidative stress and affected critical genes involved in cell cycle progression and oxidative metabolism.

    These findings suggest that BBP exposure profoundly affects reproductive health by impairing the cellular processes necessary for healthy chromosome segregation and genomic stability. A person’s phthalate burden may contribute to poor metabolic function, inflammation, and cognitive dysfunction. Learn how sauna use induces substantial sweat losses, promoting the excretion of toxic compounds like BBP.

    Read more
  • Fasting-based dietary strategies, including intermittent fasting and time-restricted eating, show slight superiority over calorie restriction for promoting weight loss and improving insulin sensitivity. www.mdpi.com
    Diet Obesity Metabolism Fasting Time-Restricted Eating Weight Loss

    With millions worldwide affected by obesity-linked conditions like diabetes and cardiovascular disease, understanding which dietary methods are most effective has become crucial. A recent review and meta-analysis found that fasting-based strategies are slightly more effective for promoting weight loss and improving insulin sensitivity than calorie restriction.

    Researchers reviewed 10 randomized controlled trials involving more than 600 participants to compare the effects of fasting-based and calorie-restricted diets on weight loss and metabolic health. Fasting-based strategies included intermittent fasting, time-restricted eating, and alternate-day fasting, while continuous calorie restriction involved reducing daily caloric intake by 20% to 40% without meal timing changes.

    They found that both methods effectively reduced body weight, with participants losing around 5.5 to 6.5 kilograms (roughly 12 to 14 pounds) after six months. Fasting-based approaches had a slight edge in short-term weight and fat loss—about 1 kilogram (2.2 pounds) more than calorie restriction—but both approaches had similar effects on lean body mass, waist and hip circumference, blood pressure, lipid levels, and glucose metabolism. Notably, fasting-based methods also lowered fasting insulin levels and improved insulin sensitivity.

    These findings suggest that while both methods support weight loss, fasting-based diets may offer additional short-term metabolic benefits. Learn more about fasting-based diets and calorie restriction from these great resources:

    What type of fasting is best? Caloric restriction vs. periodic fasting and the importance of re-feeding after a fast The link between sirtuins, calorie restriction, fasting, and the insulin pathway Topic article: Fasting

    Read more
  • Early exposure to a common pollutant changes the gut microbiome, potentially influencing metabolic health. ehp.niehs.nih.gov
    Microbiome Metabolism Hormones Inflammation Pollution

    Persistent organic pollutants are pervasive environmental toxicants that threaten human health. These compounds break down slowly and are often called “forever chemicals.” Surprisingly, the concern isn’t just that these chemicals affect health but rather the mechanisms by which they do so. A recent study in mice found that exposure to persistent organic pollutants altered the animals' gut microbiome composition, skewing it toward a less beneficial profile.

    Researchers exposed young mice to the persistent organic pollutant tetrachlorodibenzofuran (TCDF), a widely distributed byproduct of various chemical processes. They analyzed the animals' gut microbial composition and assessed the physiological and metabolic effects of the exposure.

    They found that mice exposed to TCDF had lower quantities of short-chain fatty acids, indole-3-lactic acid (an anti-inflammatory compound), and hunger-modulating hormones. Exposed mice also had fewer Akkermansia muciniphila, a type of bacteria that modulates metabolism.

    These findings suggest that early life exposure to persistent organic pollutants alters the gut microbiome in mice, adversely affecting metabolism. Learn about the importance of early life establishment of the gut microbiome in this episode featuring Dr. Eran Elinav.

    Read more
  • Aging isn't linear—it may occur in two distinct bursts in our mid-40s and again around age 60. www.nature.com
    Aging Metabolism Immune System Cardiovascular

    We often think of aging as a steady, downhill slope, but a new study suggests aging happens in two distinct bursts—in our mid-40s and again around age 60—when massive shifts in crucial molecules involved in metabolism and other critical processes occur. These shifts may explain why our disease risk and other hallmarks of aging tend to spike at these pivotal times in our lives.

    The study involved 108 adults aged 25 to 75 years living in the U.S. Researchers assessed changes in 135,000 molecular markers in the participants' blood, feces, and bodily fluids for up to seven years, yielding more than 246 billion data points.

    They found that molecular changes occurred in two massive bursts rather than gradually, with changes in cardiovascular health, lipids, and alcohol metabolism appearing around 44 years of age, followed by shifts in crucial biological processes such as immune regulation and carbohydrate metabolism around 60 years.

    These findings suggest that the progression of aging and related diseases is marked by distinct phases at specific ages. Some lifestyle behaviors can delay the changes that drive aging. Learn more about these powerful habits in this episode featuring Dr. Rhonda Patrick.

    Read more
  • Genetics plays a key role in the body's response to exercise. scitechdaily.com
    Exercise Obesity Metabolism Diabetes Genetics

    Many factors influence the extent to which exercise promotes weight loss, including exercise intensity, dietary habits, and overall lifestyle. Evidence suggests genetic differences play a role, too. A recent study found that mice with certain variants of PGC1-alpha—a key regulator of metabolism—consume less oxygen and burn less fat during workouts and are more likely to gain weight despite increased activity.

    Researchers analyzed gene expression in mice to determine the distribution of the three variants of PGC1-alpha: A, B, and C. Then, they assessed the animals' muscle growth, fat burning, and oxygen consumption during rest, short-term exercise, and long-term exercise. They performed the same assessments on 20 men, half of whom had type 2 diabetes.

    They found that although the three variants have similar functions, the A variant is widely distributed throughout the body, but the B and C variants are primarily found in brown adipose tissue, skeletal muscle, and the heart. They found that mice lacking the B and C variants had a diminished response to exercise, consuming less oxygen and burning less fat. These mice gained weight, developed high insulin levels, and were intolerant of cold temperatures. Men who had higher expression of the B and C variants consumed more oxygen and had less body fat, even among those with type 2 diabetes.

    These findings suggest that variants of PGC1-alpha influence the body’s response to exercise and highlight potential strategies for treating obesity.

    Read more
  • Moderate to high nighttime light exposure increases type 2 diabetes risk by up to 53 percent, comparable to genetic factors. t.co
    Metabolism Diabetes Circadian Rhythm Insulin Blue Light

    Circadian rhythms regulate metabolic processes, including glucose metabolism and insulin sensitivity. Disruptions in circadian rhythms can lead to metabolic impairments, increasing the risk of obesity, type 2 diabetes, and metabolic syndrome. A recent study found that personal light exposure patterns predict the risk of developing type 2 diabetes.

    Researchers assessed the light exposure patterns of more than 84,000 UK Biobank participants. Participants wore light sensors for one week to record their day and night light exposure. The researchers tracked the incidence of type 2 diabetes among the participants over an average follow-up period of nearly eight years.

    They found that diabetes risk increased as night light exposure increased. Compared to low light exposure, the risk of diabetes increased by - 29 percent with moderate light exposure. - 39 percent with high-moderate light exposure. - 53 percent with high light exposure. The increased risk associated with night light exposure was comparable to the difference between people with low and moderate genetic risk for diabetes.

    These findings suggest that nighttime light exposure is a risk factor for developing type 2 diabetes, comparable to genetic risk factors. Interestingly, low solar angle light – as in the early morning or late evening – resets the body’s circadian rhythms, improving metabolic health and mood. Learn more about low solar angle light exposure in this episode featuring Dr. Andrew Huberman.

    Read more
  • Plant-based meat substitutes show little effect on cardiometabolic health in people at risk for type 2 diabetes. www.sciencedirect.com
    Diet Metabolism Diabetes Cholesterol Vegetarian

    Plant-based meat substitutes are made from non-meat sources, such as legumes or wheat gluten. They typically mimic the sensory profile of meat products and are popular among those wishing to reduce their animal protein intake for ethical or health reasons. A recent study found that plant-based meat substitutes did not benefit cardiometabolic health in people at risk for type 2 diabetes.

    The study involved 82 adults at risk for type 2 diabetes. Half of the participants ate an animal-based diet, while the others swapped out their usual animal-based foods for plant-based meat substitutes. Researchers assessed their blood lipids (triglycerides, LDL, HDL, and total cholesterol), glycemic control, insulin sensitivity, and blood pressure before and after the eight-week intervention.

    They found that participants who ate the plant-based meat substitutes had higher fiber, sodium, and potassium intake than those who ate animal meat. Their blood lipids showed little improvement, but their diastolic blood pressure decreased, and their insulin sensitivity increased. However, those who ate the animal meat diet had better glycemic control than those on the plant-based diet.

    These findings suggest that plant-based meat substitutes don’t improve cardiometabolic health in people at risk for type 2 diabetes. However, robust evidence demonstrates that high-intensity interval training (HIIT) profoundly affects cardiometabolic health. Learn more in this episode featuring Dr. Martin Gibala.

    Read more
  • Apple cider vinegar promotes weight loss and improves metabolism in young people with overweight or obesity. nutrition.bmj.com
    Diet Obesity Metabolism Weight Loss Polyphenol

    Obesity and overweight are growing global public health concerns, especially among young people. Evidence suggests that apple cider vinegar supports weight loss and improves metabolic health. A recent study found that young people who took apple cider vinegar for 12 weeks lost more weight and exhibited better metabolic parameters than those who took a placebo.

    The study involved 120 teens and young adults with overweight or obesity. Participants received 5, 10, or 15 milliliters (5 milliliters = 1 teaspoon) of apple cider vinegar or a placebo diluted in water daily for 12 weeks. They didn’t make any changes to their diets or activity levels. Researchers measured the participants' anthropometrics (weight, body mass index, waist/hip circumferences, and body fat ratio) and blood glucose, triglyceride, and cholesterol levels at the beginning of the study and again at four-week intervals.

    They found that participants who took apple cider vinegar lost weight in a dose- and time-dependent manner, with those taking higher doses manifesting the greatest weight loss, which increased as the study progressed. All anthropometric measures improved, too, as did blood glucose, triglyceride, and cholesterol levels. None of the participants taking the vinegar experienced any adverse or ill effects.

    These findings suggest that apple cider vinegar promotes weight loss and improves metabolic parameters in young people with overweight or obesity. The investigators noted that these effects occurred without changes to the participants' diets or activity levels, suggesting the effects arose from the vinegar itself. Apple cider vinegar is made by fermenting apple juice. It is rich in vitamins, minerals, amino acids, and polyphenols such as flavonoids, which may confer some of apple cider vinegar’s benefits. Learn about the health benefits of other polyphenols in our overview article.

    Read more
  • Strawberry consumption enhances memory and mood in middle-aged adults, potentially reducing dementia risk. www.uc.edu
    Brain Diet Aging Metabolism Dementia Polyphenol

    With age, cognitive and metabolic dysfunction increases, often coinciding. However, evidence suggests that consuming berries improves cognitive and metabolic health. A recent study found that strawberry consumption improved memory and mood in overweight people with mild cognitive decline.

    Researchers recruited 34 overweight middle-aged adults with insulin resistance who reported mild cognitive decline. Half of the participants consumed a strawberry powder supplement daily for 12 weeks, while the other half consumed a placebo. Both groups abstained from all berry consumption throughout the study. The researchers assessed the participants' cognitive and metabolic functions and moods before and after the intervention.

    They found that those who consumed the strawberry powder exhibited better memory function and fewer symptoms of depression than those who consumed the placebo. However, they did not show any improvements in metabolic function.

    These findings suggest that strawberry supplementation improves cognitive function in middle-aged adults, potentially reducing the risk of dementia, but has little effect on metabolic function. The study’s authors attributed the lack of metabolic response to the relatively low dose and the study’s short duration.

    Strawberries are rich in anthocyanins, a class of polyphenolic compounds that exert potent antidiabetic, anticancer, anti-inflammatory, and anti-obesity effects in humans. Anthocyanins lend their characteristic blue, red, or purple hues to strawberries, blueberries, and other fruits and vegetables. Learn about other polyphenols in our overview article.

    Read more
  • Morning exercise outperforms afternoon workouts in enhancing cardiometabolic health in people with metabolic syndrome. physoc.onlinelibrary.wiley.com
    Exercise Metabolism Diabetes Insulin Metabolic Syndrome Cardiovascular

    The idea that exercise benefits metabolic health is widely accepted. But whether the benefits of exercise are greater depending on when one exercises – morning versus afternoon – is a matter of considerable debate. A recent study shows that morning exercise reduces blood pressure, fasting insulin, and insulin resistance better than afternoon exercise in people with metabolic syndrome.

    Metabolic syndrome is a constellation of conditions characterized by abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoproteins. Having metabolic syndrome increases a person’s risk of cardiovascular disease and type 2 diabetes. Roughly one-third of adults between the ages of 20 and 60 have metabolic syndrome.

    The study involved 139 adults with metabolic syndrome who agreed to participate in three supervised high-intensity interval training sessions every week for 16 weeks. About a third of the participants performed their exercise in the morning, a third did so in the afternoon, and a third didn’t engage in any exercise. Researchers measured the participants' body composition, cardiorespiratory fitness, maximal fat oxidation, blood pressure, and blood metabolites before and after the intervention.

    They found that both exercise groups demonstrated greater body fat loss, reduced waist circumference (nearly an inch), and lower diastolic blood pressure than those who didn’t exercise. However, when comparing the morning exercise group to the afternoon group, they found that morning exercise was more effective at reducing systolic blood pressure (4 percent drop vs. 1 percent), lowering fasting insulin (12 percent drop vs. 5 percent), and decreasing insulin resistance (14 percent drop vs. 4 percent).

    These findings suggest that morning exercise boosts cardiometabolic health better than afternoon exercise. The investigators posited that these effects may be related to circadian rhythms, which influence the body’s response to exercise and dietary intake.

    Finding the time or motivation to exercise in the morning may be challenging for many. Fortunately, most experts agree that some exercise is better than none, as long as it’s not too close to bedtime. Learn more in this clip featuring Dr. Rhonda Patrick.

    Read more
  • Vegan diets linked to cardiovascular and metabolic benefits, with marked improvements in body weight, LDL cholesterol, and fasting insulin. www.ncbi.nlm.nih.gov
    Diet Metabolism Insulin Vegetarian Cardiovascular

    Plant-based dietary patterns are typically higher in fiber, vitamins, minerals, and phytonutrients than other dietary patterns. Consequently, they may confer health benefits that reduce the risk of cardiovascular and metabolic disorders. A recent study found that a vegan diet reduced body weight, LDL (“bad”) cholesterol, and fasting insulin in healthy adults.

    To negate any genetic influences that diet might have on cardiometabolic fitness, researchers recruited 22 pairs of female twins to participate in the study. Within each twin pair, one twin followed a healthy vegan diet for eight weeks, and the other followed a healthy omnivorous diet. The researchers measured the twins' cardiometabolic markers before and after the intervention.

    They found that compared to twins who ate an omnivorous diet, twins who followed a vegan diet experienced reduced body weight, LDL cholesterol, and fasting insulin. Participants following a vegan diet had a lower protein, dietary cholesterol, and vitamin B12 intake and a higher vegetable and dietary iron intake than those on the omnivorous diet. They also reported lower satisfaction with their dietary options.

    The findings from this small study suggest that following a vegan diet confers cardiometabolic benefits in healthy young women, aligning with previous research demonstrating that vegan diets reduce the risk of cardiometabolic disease. They also underscore the considerable influence that diet has on cardiometabolic health. Learn how to avoid dietary deficiencies when following a vegan diet in this clip featuring Rich Roll.

    Read more
  • Long-term nutritional ketosis improves metabolism and reduces inflammatory markers in women. www.mdpi.com
    Diet Metabolism Ketosis Inflammation Insulin Ketogenic Diet

    Nutritional ketosis is a powerful tool for managing weight and moderating inflammation. However, most studies on ketosis have been conducted in men and have only assessed short-term effects. A recent study found that nutritional ketosis reduces blood glucose, insulin, and inflammatory markers in healthy women practicing long-term ketosis.

    Researchers asked ten healthy young women who had been maintaining nutritional ketosis for more than a year to alter their dietary habits to suppress ketosis. The study involved three one-week phases: nutritional ketosis, suppressed ketosis, and return to nutritional ketosis. The researchers measured the women’s ketone levels daily; at the end of each phase, they took their women’s body measurements and assessed their metabolic and inflammatory biomarkers.

    They found that when the women suppressed ketosis, their insulin, IGF-1, glucose, and pro-inflammatory markers increased. However, when they returned to ketosis, those markers returned to baseline levels.

    These findings suggest that nutritional ketosis maintains healthy metabolism and suppresses inflammation without altering metabolic flexibility. Other evidence demonstrates that a ketogenic diet promotes weight loss and reduces cancer risk. Learn how to design the optimal ketogenic diet in this episode featuring Dr. Dominic D'Agostino

    Read more
  • Vitamin D increases muscle strength and mass without altering body weight in mice. www.biorxiv.org
    Vitamin D Obesity Aging Metabolism Hormones Muscle

    Vitamin D, best known for maintaining calcium balance and bone health, is critical in many physiological processes, including blood pressure regulation, immune function, and cell growth. Evidence now suggests vitamin D also influences body composition and muscle strength. A recent study in mice showed that high vitamin D intake increased muscle strength and mass without altering body weight.

    Researchers fed mice one of three diets, providing low, normal, and high doses of vitamin D for four weeks to achieve deficient, insufficient, and sufficient vitamin D concentrations, respectively. At the end of the fourth week, they assessed the animals' grip strength (a measure of muscle function) and body composition.

    They found that compared to low or normal vitamin D intake, high intake increased grip strength and lean mass and decreased fat mass without altering the animals' weights. High intake also impaired myostatin production and increased the animals' leptin sensitivity and energy expenditure without altering their activity levels.

    Leptin is a satiety hormone that signals the brain to balance energy. When body fat increases or decreases, blood concentrations of leptin change accordingly. Higher leptin levels signal the brain to reduce hunger and boost energy use. However, in obesity, the body becomes less responsive to leptin, dulling its effects on appetite and energy expenditure.

    These findings suggest that vitamin D influences body composition and metabolism by preferentially allocating calories toward muscle development and overall growth rather than fat storage. They also highlight the intricate relationship between obesity and vitamin D status. Learn more about vitamin D in our comprehensive overview article.

    Read more
  • Resistance training counters the potential harms of a high-protein diet in mice. www.sciencedaily.com
    Exercise Diet Metabolism Protein

    A high-protein diet may increase the risk of heart disease, diabetes, and increased body fat, especially in sedentary people. However, a new study in mice demonstrates that resistance training may counter these effects. Mice that ate a high-protein diet and performed resistance exercises gained muscle – not fat – and were more metabolically healthy than sedentary mice on the same diet.

    Researchers fed one group of mice a low-protein diet (7 percent of total calories) and another a high-protein diet (36 percent of total calories). Half of each group performed resistance exercises three times weekly for three months, while the other half remained sedentary. The researchers then compared various parameters, such as body composition, weight, and metabolic indicators, across the different groups.

    They found that the sedentary mice that ate a high-protein diet gained more fat than those on a low-protein diet. However, mice that ate a high-protein diet but engaged in resistance-based training gained muscle mass but not excess body fat. Interestingly, the high-protein-fed mice gained strength faster but, by the study’s end, did not outperform the low-protein group.

    These findings suggest that resistance training can offset the harmful effects associated with a high-protein diet.

    Current recommendations for protein intake for healthy adults – 0.8 grams per kilogram (0.36 grams per pound) of body weight per day – are likely too low for building and maintaining muscle mass. Doubling the recommended amount, ensuring a daily intake of 1.6 to 1.8 grams per kilogram (0.7 to 0.8 grams per pound) of body weight, will pay the greatest dividends for promoting muscle protein synthesis for non-novices. Learn more about the importance of dietary protein in this episode featuring Dr. Stuart Philips.

    Read more
  • A new study reveals genetic influence on omega-3 metabolism in Hispanic Americans. www.sciencedaily.com
    Metabolism Omega-3 Genetics

    Omega-3 fatty acids are essential in human health, influencing multiple organ systems and physiological responses. However, a person’s omega-3 status varies depending on several factors, including their genetic makeup. A new study shows that genetic differences influence how Hispanic Americans metabolize omega-3s.

    Researchers conducted a genome-wide association study, a type of observational study that searches the genome for minor variations in people’s DNA within a particular population. Their analysis included more than 1,400 Hispanic Americans and more than 2,200 African Americans.

    They found that the two groups shared many genetic similarities regarding omega-3 metabolism with European Americans. However, they also identified distinct differences, some influencing how Hispanic Americans metabolize omega-3s. Most of these differences occurred in the FADS region on chromosome 11. FADS (fatty acid desaturase) is a gene that encodes a family of enzymes that convert saturated fatty acids into unsaturated and polyunsaturated fatty acids.

    These findings provide a better understanding of the genetics underlying omega-3 fatty acid metabolism in diverse genetic groups and underscore the importance of considering ancestry in genetic studies. Learn more about how genetic differences influence nutritional status in this episode featuring Dr. Rhonda Patrick.

    Read more
  • Research identifies a possible ceiling for the mitochondrial benefits of intense exercise. www.sciencedirect.com
    Exercise Metabolism Mitochondria

    Mitochondrial function and whole-body maximal oxygen uptake – a surrogate measure of metabolic function and health – are closely linked. Exercise boosts mitochondrial function, but some evidence suggests there is an upper limit to exercise’s benefits. A new study demonstrates that the benefits of exercise on mitochondrial function peak, after which the benefits plateau or even drop.

    The study involved 11 healthy adults enrolled in a four-week high-intensity interval training (HIIT) program. The exercise load and duration gradually increased over the first three weeks of training (scaling up to 154 minutes per week) and then decreased for the final week to allow recovery. Researchers measured the participants' glucose tolerance and collected muscle biopsies throughout the intervention. They also assessed continuous blood glucose profiles in world-class endurance athletes.

    They found that after the week with the highest exercise load, the participants' mitochondrial function had declined markedly, impairing their glucose tolerance and insulin secretion. Interestingly, the impaired mitochondrial function coincided with the loss of cellular Nrf2, a protein involved in the body’s antioxidant defense response. In addition, they found that the endurance athletes had worse glucose control than a matched control group.

    The findings from this small study suggest an upper limit to the mitochondrial benefits of HIIT exists, potentially impeding performance and harming health. However, it’s noteworthy that the participants tolerated 90 minutes of HIIT per week and didn’t experience impairments until reaching 152 minutes. One of the unique advantages of HIIT is that a shorter routine can have robust beneficial effects comparable to those of endurance training. Learn more about HIIT in this episode featuring Dr. Martin Gibala.

    Read more
  • High-intensity exercise mitigates sleep-induced metabolic disruptions, offering a potential defense against type 2 diabetes. www.sciencedirect.com
    Exercise Metabolism Sleep Diabetes Circadian Rhythm Mitochondria

    Poor sleep negatively affects metabolism, impairing glucose tolerance and increasing the risk of developing type 2 diabetes. Findings from a recent study indicate that HIIT compensates for the harmful effects of sleep loss on glucose tolerance.

    Researchers assigned 24 healthy young men to one of three five-night sleep protocols: normal sleep (eight hours nightly), sleep restriction (four hours nightly), and sleep restriction with HIIT. Researchers collected muscle biopsies to assess muscle protein synthesis before and after the intervention.

    They found that the group with sleep restriction experienced marked reductions in glucose tolerance, mitochondrial respiratory function, and sarcoplasmic protein synthesis. They also experienced altered diurnal skin temperature rhythms. However, sleep-restricted participants who engaged in HIIT did not experience these disturbances.

    The sarcoplasm is the cytoplasm of muscle cells. Sarcoplasmic protein synthesis is crucial for muscle growth, repair, and maintenance, contributing to overall muscle health and function.

    This study was small, but the findings suggest that sleep restriction impairs metabolic function, circadian rhythmicity, and muscle protein synthesis. However, engaging in HIIT during periods of sleep restriction helps counter these effects. Learn more about the benefits of HIIT in this episode featuring Dr. Martin Gibala.

    Read more
  • Longevity study reveals key blood markers increase chances of living to 100 and beyond. www.sciencealert.com
    Aging Metabolism Inflammation Genetics Blood Test

    By the year 2050, the number of centenarians – people who are 100 years or older – is expected to increase fivefold. Many factors promote centenarians' extraordinary longevity and likely involve the interaction of both lifestyle and genetic variables. A recent study has found that the blood of centenarians differs from their younger counterparts.

    The study followed more than 44,000 people from their mid-60s to late 90s until they died. Of these, 1224 of them lived to 100 years old. Using blood samples collected earlier in the participants' lives, researchers assessed 12 blood-related biomarkers previously associated with aging or early death, including those associated with inflammation and indicators of malnutrition, anemia, and liver, kidney, and metabolic function.

    They found that higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, and several enzymes involved in metabolism increased the likelihood of reaching 100 years. Notably, centenarians exhibited strikingly consistent biomarker profiles, even from age 65 and beyond, displaying more favorable values than their shorter-lived counterparts.

    Centenarians often carry genetic variants called single-nucleotide polymorphisms associated with longevity. They tend to develop disease much later in life than people of average age span, a phenomenon called “compression of morbidity,” and have longer telomere lengths than adults two to three decades younger. The highest concentrations of centenarians worldwide live in Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica; Ikaria, Greece; and Loma Linda, California.

    The findings from this study demonstrate that biomarkers related to various genetic or lifestyle influences may contribute to greater longevity. Inflammation also plays a role in longevity. Learn more in this clip featuring Dr. Valter Longo.

    Read more
  • Strength training raises resting metabolic rate by 9 percent in men, countering age-associated energy expenditure decreases. pubmed.ncbi.nlm.nih.gov
    Exercise Aging Metabolism

    As people age, their total energy expenditure (total calories burned in a day) decreases primarily due to declines in resting metabolic rate and the energy expenditure of physical activity, driving increases in body fat. Strength training increases fat-free mass (muscle mass), offering a promising intervention to offset these declines. A 2001 study found that strength training increased resting metabolic rate in men, regardless of age, by 9 percent.

    The study involved young and older men and women participating in a supervised strength training program three days a week for 24 weeks. Participants maintained their usual diet and body weight throughout the study period. Researchers assessed the participants' resting metabolic rate and energy expenditure of physical activity before and after the intervention.

    They found that strength training increased the participants' resting metabolic rate by 7 percent, regardless of age. However, they observed a gender-related difference, with men experiencing a 9 percent increase in resting metabolic rate, while women did not experience a notable increase. This effect persisted even after adjusting for fat-free mass.

    These findings suggest that strength training increases resting metabolic rate, an effect influenced by gender but not age. Learn more about the benefits of strength training in this episode featuring Dr. Brad Schoenfeld.

    Read more
  • Just 30 minutes of reduced-exertion high-intensity training weekly improved sedentary people's aerobic capacity and metabolic health. link.springer.com
    Exercise Metabolism Diabetes Aerobic

    Type 2 diabetes is a metabolic disorder characterized by skeletal muscle insulin resistance. High-intensity interval training (HIIT) improves skeletal muscle insulin sensitivity, but the demanding nature of traditional HIIT sessions can be daunting for people unaccustomed to regular physical activity. A 2012 study found that reduced-exertion high-intensity interval training (REHIT) improved aerobic capacity and metabolic health in people who were sedentary – a risk factor for developing type 2 diabetes.

    The study involved 29 sedentary young adults. Half the participants engaged in three 10-minute REHIT sessions weekly for six weeks. Each session consisted of low-intensity cycling and one or two brief “all-out” sprints lasting between 10 and 20 seconds. The other half of the participants remained sedentary. Researchers assessed the participant’s aerobic capacity (measured as VO2 peak) and insulin sensitivity before and after their respective interventions.

    Ten of the 15 REHIT participants completed all 18 sessions, indicating high compliance. Aerobic capacity increased by 15 percent in males and 12 percent in females. Insulin sensitivity improved by 28 percent in males but not in females. Participants rated their perceived exertion as “hard” or “somewhat hard.”

    Encouraging regular, balanced exercise that includes cardiorespiratory, strength, and flexibility training can optimize health benefits. However, addressing barriers, such as lack of time or access to formal exercise equipment, is crucial to have widespread effects. The findings in this small study suggest that brief, reduced-exertion high-intensity training improves aerobic capacity and metabolic health in sedentary people despite a low time commitment (just 30 minutes per week) and relatively low effort. Learn more about REHIT and how it differs from HIIT and SIT in this clip featuring Dr. Martin Gibala.

    Read more
  • Genes involved in muscle function, energy production and utilization, and oxygen delivery play critical roles in how exercise boosts VO2 max. bmcgenomics.biomedcentral.com
    Exercise Metabolism Genetics Muscle Aerobic

    VO2 max – the maximum rate of oxygen a person can consume during exercise – is a robust predictor of a person’s risk for chronic diseases and death. Exercise increases VO2 max, but how well a person responds to exercise training varies considerably and may be influenced by genetics. A 2017 systematic review identified nearly 100 genes that likely influence a person’s VO2 max response to exercise training.

    Researchers reviewed 35 studies investigating genetic variants in the context of supervised aerobic exercise interventions aimed at improving VO2 max. The studies were based on DNA samples from more than 4,200 people of varied genetic makeup.

    The researchers' analysis identified 97 genes that might influence a person’s VO2 max response to exercise training by modulating muscle function and efficiency, electrolyte balance, lipid metabolism, oxidative phosphorylation, energy production, and oxygen delivery. They found that people who responded more favorably to exercise training tended to have more positive response alleles – genetic variants associated with a more favorable or beneficial response to exercise training – in those genes.

    These findings highlight the influence of specific genetic variants on a person’s response to exercise training and their effect on VO2 max improvements. However, the authors cautioned that while most of the articles reviewed in their analysis primarily investigated a single or a limited number of candidate genes or markers, exercise-related traits are intricate and influenced by multiple genes working in concert. Learn how Tabata, a type of HIIT, increases VO2 max in this clip featuring Dr. Martin Gibala.

    Read more
  • Time-efficient sprint interval training matches traditional exercise for cardiometabolic health. www.ncbi.nlm.nih.gov
    Exercise Metabolism Aerobic Cardiovascular

    Traditional moderate-intensity continuous exercise training (MICT) promotes cardiometabolic health but requires a considerable time commitment, a factor many people often cite as a reason for not exercising. Evidence suggests sprint interval training (SIT) offers similar benefits for insulin sensitivity and heart health as MICT. A 2016 study found that 12 weeks of SIT improved cardiometabolic health as effectively as MICT – with one-fifth of the time commitment.

    SIT typically involves short bursts of high-intensity exercise followed by low-intensity recovery periods. It is sometimes described as a “sprint from danger” pace, equating to one’s top running speed, executed for five to ten seconds.

    The study involved 27 young, sedentary men who engaged in SIT, MICT, or no exercise (a control group) for 12 weeks. Those who engaged in SIT performed three 20-second high-intensity intermittent exercise sets within a 10-minute cycling session, while those who engaged in MICT performed 50 minutes of continuous cycling exercise at a moderate intensity. Both groups underwent muscle biopsies and body composition analyses before and after the interventions.

    SIT and MICT improved peak oxygen uptake by 19 percent, indicating improved cardiorespiratory fitness. In addition, both groups demonstrated enhanced insulin sensitivity and increased levels of citrate synthase, a marker of muscle mitochondria content.

    Although this was a small study, its findings suggest that SIT can be an effective and time-efficient strategy to improve cardiometabolic health among sedentary people. The findings also underscore the importance of considering alternative exercise strategies that may be more feasible for people with limited time for workouts. Learn more about SIT in this clip featuring Dr. Martin Gibala.

    Read more
  • Findings suggest restricting eating to an eight-hour window enables similar weight loss as cutting calories by 25 percent. www.latimes.com
    Diet Metabolism Time-Restricted Eating Weight Loss

    Traditional weight-loss programs typically emphasize calorie restriction – often cited as the primary reason participants drop out. But time-restricted eating is a weight loss strategy that limits one’s daily eating window to a specific period without focusing on restricting calories. A new study found that time-restricted eating was as effective as calorie restriction for weight loss.

    The study included 90 adults with obesity who followed one of three dietary patterns for a year: time restriction, calorie restriction, and no restriction (a control group). The time-restricted group ate during an eight-hour window, from noon to 8:00 p.m., without limiting calories. The calorie-restricted group cut their calories by 25 percent. The control group ate during a 10-hour (or more) window and did not change their diets. Researchers assessed the participants' body weights, metabolic markers, and caloric intake throughout the study.

    They found that the time-restricted and calorie-restricted groups experienced considerable weight loss compared to the control group by the end of the year. The time-restricted group lost more than 10 pounds (~4.8 percent of their body weight), while the calorie-restricted group lost nearly 12 pounds (~5.3 percent). There was no statistically significant difference in weight loss between the two groups. Notably, the control group averaged a 2.4-pound weight gain over the year.

    These findings suggest that time-restricted eating is as effective for weight loss as calorie restriction. In this study, the eating window began around noon – often described as a “late” window. However, some evidence indicates that an early eating window is more beneficial than a later one. Learn more about time-restricted eating in this episode featuring Dr. Satchin Panda.

    Read more
  • Older women and those with obesity clear alcohol from their systems 52 percent faster, according to new research. www.technologynetworks.com
    Obesity Aging Metabolism Alcohol

    The effects of alcohol vary between people, largely due to differences in alcohol absorption rates and metabolism in the gut. A new study has found that older women and those with obesity clear alcohol from their systems 52 percent faster than younger women and those with healthy weights.

    Researchers analyzed the findings of three studies that investigated alcohol clearance rates in 143 women. They used a computer-assisted alcohol infusion system to model the self-administration of alcohol. They also measured the women’s body fat via DEXA or bioelectrical impedance.

    They found that women with obesity, particularly those who were older, cleared alcohol 52 percent faster than women with a healthy weight. They also found that age and lean body mass explained 72 percent of the differences in the alcohol elimination rate among women.

    These findings suggest that women with obesity eliminate alcohol faster than leaner women, likely due to the increase in fat-free mass that often accompanies obesity, especially in older women. Drinking alcohol increases a person’s risk for many chronic diseases, but exercise can help reduce alcohol cravings. Learn more in this short video featuring Dr. Rhonda Patrick.

    Read more
  • Artificial intelligence tool shows 96 percent accuracy in early Parkinson's disease diagnosis. parkinsonsnewstoday.com
    Parkinson's Metabolism Polyphenol

    Early diagnosis of Parkinson’s disease is important because many commonly used treatments for the condition are more effective when administered early on. New research suggests that a new artificial intelligence tool can help diagnose Parkinson’s disease well before symptoms manifest, with 96 percent accuracy.

    Researchers used machine learning to analyze metabolites – byproducts of metabolism – in the blood of 78 people, half of whom had Parkinson’s disease.

    They found that the machine learning tool was approximately 96 percent accurate when differentiating between healthy people and those with Parkinson’s disease, based on their blood metabolites. They also found that people with Parkinson’s disease were more likely to have high levels of a poly-fluoroalkyl substance in their blood and low levels of triterpenoids, cholestane steroids, and diacylglycerol.

    Polyfluoroalkyl substances, also known as PFAS, are man-made chemicals used in food packaging, household products, and drinking water. PFAS are not excreted in bodily fluids like sweat or urine; rather, they persist in the body for indefinite periods and are often referred to as “forever chemicals.” Triterpenoids, cholestane, and diacylglycerol are plant-based bioactive dietary compounds that exert antioxidant and neuroprotective effects.

    These findings suggest that machine learning is a useful tool in detecting Parkinson’s disease early based on metabolites in blood. They also highlight possible interventions to reduce the risk of developing the disease, such as reducing exposure to PFAS and including plant-based bioactive compounds in the diet. Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.

    Read more
  • Supplemental vitamin K2 improves diabetes markers and glycemic control. pubmed.ncbi.nlm.nih.gov
    Metabolism Diabetes Insulin Resistance Vitamin K Insulin

    Vitamin K2 – a form of vitamin K produced in the gut – plays important roles in blood clotting, bone mass maintenance, and blood vessel contractility. But new research shows that supplemental vitamin K2 also improves diabetes markers. People with type 2 diabetes who took supplemental vitamin K2 had better markers of glycemic control than those who took a placebo.

    Researchers performed a three-part study in humans and mice. First, they conducted a randomized controlled trial involving 60 adults who had type 2 diabetes. Half of the participants took vitamin K2 every day for six months, while the other half took a placebo. Then the researchers transplanted gut microbes from vitamin K2-supplemented mice into obese mice. Finally, they analyzed the gut microbial composition and their metabolites in both humans and mice.

    They found that the participants who received supplemental vitamin K2 experienced marked reductions in levels of fasting blood glucose (13.4 percent), insulin (28.3 percent), and HbA1c (7.4 percent), indicating improved glycemic control. Similarly, the mice demonstrated improved glucose tolerance after receiving the gut microbe transplants. Lastly, the researchers found that certain metabolites that play roles in glucose metabolism, including bile acids and short-chain fatty acids, increased in the feces of both groups. Furthermore, they identified a specific type of bacteria that was responsible for producing these metabolites.

    Vitamin K is a fat-soluble vitamin. The body has limited vitamin K storage capacity, so the body recycles it in a vitamin K redox cycle and reuses it multiple times. Naturally occurring forms of vitamin K include phylloquinone (vitamin K1) and a family of molecules called menaquinones (vitamin K2). Vitamin K1 is synthesized by plants and is the major form found in the diet. Vitamin K2 molecules are synthesized by the gut microbiota and found in fermented foods and some animal products (especially liver).

    These findings suggest that vitamin K2 participates in maintaining glycemic control in people with type 2 diabetes. They also underscore the role of the gut microbiota in this process. Learn about other roles for the gut microbiota in this episode featuring Dr. Eran Elinav.

    Read more
  • Maternal omega-3 potentiates fetal brown fat via synergistic action of miRNA production and histone modifications, possibly a lifelong benefit www.sciencedirect.com
    Metabolism Omega-3 Development Metabolic Syndrome Brown Fat

    Omega-3 supplementation during pregnancy promotes brown fat formation in offspring.

    A new study in mice showed that omega-3 fatty acid consumption during pregnancy and lactation promoted the formation of brown fat in offspring. Omega-3s also increased energy expenditure and cold resistance.

    Researchers fed female mice either a diet rich in omega-3 fatty acids or a diet devoid of omega-3s throughout their pregnancies and lactation. They measured their offspring’s brown fat and energy expenditure and assessed their capacity to maintain their core body temperature in cold temperatures.

    They found that the mice whose mothers ate a diet rich in omega-3s had higher concentrations of brown fat than those whose mothers did not consume omega-3s. In addition, they had higher energy expenditure and were more efficient at maintaining their core body temperature in cold temperatures. Genetic analysis revealed that the increase in brown fat synthesis was mediated via epigenetic mechanisms. You can learn more about epigenetic mechanisms in our article here.

    Brown fat, also known as brown adipose tissue, is found in all mammals and is particularly abundant in newborns. Unlike white fat, brown fat is metabolically active tissue that is rich in mitochondria. It helps maintain body temperature during cold exposure, during which its uptake of glucose is eightfold higher than that of muscle tissues, driving increases in energy expenditure.

    Cold exposure increases brown fat activity in humans, possibly benefitting whole-body glucose utilization and insulin sensitivity. Learn more about the effects of cold exposure in our overview article.

    Read more
  • Time-restricted eating activates genes involved in metabolism and autophagy. www.sciencedaily.com
    Metabolism Genetics Autophagy Time-Restricted Eating

    Time-restricted eating influences the activation of roughly 70 percent of all genes in mice, a new study shows. Mice that ate on a time-restricted schedule had fewer active genes involved in inflammation and oxidative stress and more active genes involved in metabolism and autophagy – a cellular defense mechanism.

    Researchers fed two groups of mice a Western-style diet, which is high in fat and sugars, for seven weeks. One group was allowed to eat whenever they chose to, but the other group was allowed to eat only during a nine-hour window each day. At the end of the seven-week intervention, the researchers analyzed gene activity in the animals' tissues at different times of the day.

    They found that time-restricted eating altered the activity of more than 80 percent of genes involved in protein synthesis, folding, and maintenance. They also found that time-restricted eating altered amino acid, fat, and glucose metabolism and re-aligned the circadian rhythms of the animals' organs.

    These findings suggest that time-restricted eating influences gene activity in mice. If the findings translate to humans, they could have far-reaching implications for chronic metabolic disorders, neurodegenerative diseases, cancer, and other diseases. Learn more about the health benefits of time-restricted eating in this episode featuring Dr. Satchin Panda, the senior investigator for this study.

    Read more
  • Early-life obesity increases the risk of macular degeneration later in life. www.sciencedaily.com
    Obesity Metabolism Inflammation Immune System Eyes

    Obesity in early life induces changes in immune cells that may increase the risk of macular degeneration later in life, a study in mice has found. These changes linger even after weight loss and the restoration of normal metabolism.

    Researchers fed mice a diet that promoted weight gain early in life. Then they studied the effects of having excess body fat on the animals' adipose tissue macrophages – a type of immune cell found in fat. Later, they put the mice on a diet that promoted weight loss.

    They found that having excess body fat induced epigenetic changes in the macrophages that, in turn, induced an inflammatory response. This pro-inflammatory response persisted even after the mice lost weight. They also found that the macrophages could migrate from the fatty tissue to other parts of the body, including the eyes, where they could contribute to the onset of macular degeneration.

    Macular degeneration is the leading cause of blindness worldwide. Having excess body fat is the second leading risk factor for macular degeneration. In fact, a person’s risk of developing macular degeneration increases by 75 percent with each 0.1 increase in their waist-to-hip ratio – a measure of abdominal obesity.

    Read more
  • Hot water baths before bedtime reduce the risk of hypertension. www.eurekalert.org
    Aging Metabolism Heat Stress Blood Pressure

    Older adults who regularly bathed in hot springs in the evening were less likely to have hypertension, a new study has found. Having hypertension markedly increased the likelihood of having other chronic diseases, however.

    Researchers gathered information about the hot spring bathing habits and overall health of more than 10,000 older adults. The participants lived near Beppu, Japan, an area known for its many hot springs.

    They found that older adults who regularly bathed in hot springs in the evening were approximately 15 percent less likely to have hypertension. Older adults who didn’t frequent the hot springs were roughly 50 percent more likely to have type 2 diabetes, heart arrhythmia, stroke, gout, or abnormal blood lipids.

    Evidence suggests that chronic mental stress promotes hypertension. Research has shown that bathing in hot springs improves mental health and reduces stress. Other research has shown that hot water bathing before bedtime promotes faster sleep onset and better sleep quality, which could reduce the risk of developing hypertension.

    Exercise, hot baths, and sauna use may have similar effects on promoting sleep and reducing blood pressure. Learn more about the effects of sauna use on hypertension in this clip featuring Dr. Jari Laukkanen.

    Read more
  • Silencing of estrogen receptor α in a brain area of the hypothalamus led to metabolic syndrome in mice. (2007) www.sciencedaily.com
    Brain Metabolism Hormones Fat Estrogen Blood Sugar Metabolic Syndrome Weight Loss Visceral Fat

    From the article:

    Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.

    To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.

    Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.

    When estrogen levels in the VMN dipped, the animals' metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.

    The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.

    View full publication

    Read more
  • Honey may benefit cardiometabolic health. www.sciencedaily.com
    Diet Metabolism Cardiovascular

    Consuming honey improves blood glucose and cholesterol levels, a recent analysis shows. Raw, unprocessed honey from a single floral source provides the greatest health benefits.

    Researchers reviewed the findings of 18 studies that investigated the effects of honey consumption on various cardiometabolic risk factors, including body fat, glucose levels, blood lipids, blood pressure, inflammatory markers, and others. They also noted the effects of processing and sourcing on honey’s effects.

    They found that honey lowered fasting blood glucose, LDL (“bad”) cholesterol, and triglycerides and increased HDL (“good”) cholesterol and some markers of inflammation. Raw honey – which is unprocessed – had the greatest beneficial effects, especially if it was from a single source, particularly black locust or clover.

    Honey is a complex mixture of sugars, enzymes, proteins, minerals, vitamins, and other bioactive substances that exert antioxidant, antibacterial, and antiseptic effects in humans. Evidence suggests that honey benefits cardiovascular, metabolic, neurologic, and gastrointestinal health.

    These findings demonstrate that, despite its naturally high sugar content, honey differs from other natural sweeteners and may benefit cardiometabolic health. Refined sugar, on the other hand, has profound, negative effects on the human body. Learn more in this episode featuring Dr. Rhonda Patrick.

    Read more
  • Estradiol may act as a regulator of muscle energy metabolism and muscle cell viability: loss of estrogen in menopause may promote sarcopenia www.sciencedaily.com
    Metabolism Hormones Estrogen Muscle Apoptosis

    From the article:

    The effects of estrogen on skeletal muscles are not yet well known. The study from the University of Jyväskylä discovered that estrogen acts as an upstream regulator for the energy metabolism and viability of muscle cells.

    […]

    “These findings help to understand why menopausal women’s muscles get smaller and their muscle strength diminishes,” Dr. Laakkonen explains. Skeletal muscle is important for whole-body metabolism. Therefore, these results are important when fighting against the elevated risk of metabolic diseases associated to aging.

    In total 24 pre- and postmenopausal women participated in this muscle research on middle-aged women.

    From the publication:

    The major canonical pathways found to be differentially regulated included mitochondrial dysfunction, oxidative phosphorylation, glycolysis, and TCA-cycle, strong indicators for affected energy metabolism. The major biological processes predicted to be affected were related to cell death, apoptosis, and cell survival, as well as contractility of the muscle and glycolysis. Furthermore, E2 [17β-estradiol] was predicted to be an upstream regulator of these processes, which we confirmed by exposing myotubes to E2 in vitro.

    View full publication

    Read more
  • Estrogen-sensitive brain circuit may help women control obesity by stimulating physical activity and thermogenesis, animal study suggests. (2022) www.sciencedaily.com
    Brain Obesity Metabolism Hormones Estrogen Thermogenesis

    From the article:

    The team reveals in the journal Science Advances an estrogen-activated neurocircuit that stimulates thermogenesis, or body heat production, and physical activity in animal models. The circuit begins in neurons located in a region of the hypothalamus called the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH). These neurons interact with estrogen via estrogen receptor-alpha (ER-alpha) and respond to the hormone by connecting to and communicating with serotonin-producing neurons located in another brain region called dorsal raphe nucleus (DRN).

    The circuit not only responds to estrogen, but also to changes in ambient temperature and in the nutritional status of the animal. Interestingly, the circuit seems to be functional in males but, at this point, its physiological relevance is not clear.

    […]

    “For example, the circuit can be activated when it’s cold, stimulating thermogenesis and physical activity, which would help the animal stay warm,” Xu said. “The circuit can be inhibited when the animal is hungry, which would shut down thermogenesis and physical activity, saving energy to adapt to the lack of nutrients.”

    View full publication

    Read more
  • Estrogens may act on distinct hypothalamic neurons to regulate energy homeostasis and reproduction, mouse study suggests. (2011) www.sciencedaily.com
    Brain Obesity Metabolism Hormones Estrogen Neuron Metabolic Syndrome

    From the article:

    “When women approach menopause, they gain weight in fat and their energy expenditure goes down,” says Deborah Clegg of the University of Texas Southwestern Medical Center. Estrogen levels decline and women grow increasingly susceptible to obesity and metabolic syndrome.

    Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone’s influence on metabolism, Clegg suspected receptors in the brain.

    […]

    The researchers showed female mice lacking ERα [estrogen receptor-α (ERα)] in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERα from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERα receptors in those same neurons also led to various problems in ovulation and fertility.

    View full publication

    Read more
  • Mouse study suggests that interleukin-6 (IL-6) may regulate body weight by increasing substances in the brain that trigger weight loss. (2012) www.sciencedaily.com
    Brain Metabolism Satiety Weight Loss IL-6

    From the article:

    The results show that the cells that are affected by interleukin-6 produce substances that not only affect our sense of hunger and fullness but also control the body’s ability to burn fat. “Interleukin-6 increases levels of substances in the brain that trigger weight loss, which could explain why high levels of this molecule lead to weight loss,” says doctoral student Erik Schéle, who is presenting the results in his thesis.

    It is known that our normally low levels of interleukin-6 in the brain increase dramatically during an infection, typically accompanied by reduced hunger and fatigue.

    “Our previous findings would indicate that interleukin-6 can play a key role in regulating the metabolism of healthy individuals too,” says Erik Schéle.

    “This is clearly substantiated by our finding that mice which lack interleukin-6 get fat, and that the metabolism of rats injected with interleukin-6 directly into the brain increases.”

    View full publication

    Read more
  • Dysregulated tryptophan metabolism contributes to abdominal aortic aneurysm formation in mice. (2017) www.eurekalert.org
    Metabolism Cardiovascular Aneurysm

    From the article:

    “Our data found a previously undescribed causative role for 3-hydroxyanthranilic acid (3-HAA), a product of tryptophan metabolism, in abdominal aortic aneurysm formation,” said Dr. Ming-Hui Zou, director of the Center for Molecular and Translational Medicine at Georgia State and a Georgia Research Alliance Eminent Scholar in Molecular Medicine. “We believe agents that alter tryptophan metabolism may have therapeutic potential for preventing or treating abdominal aortic aneurysm. Our findings suggest that reducing 3-HAA may be a new target for treating cardiovascular diseases.”

    The kynurenine pathway is the major route for the metabolism of tryptophan, and other studies have found this pathway plays a key role in the increased prevalence of cardiovascular disease. The researchers sought to identify the role of the kynurenine pathway and its products in angiotensin II (AngII)-induced abdominal aortic aneurysm. AngII is a hormone that increases blood pressure by constricting the blood vessels and is the principal mediator for the development and progression of abdominal aortic aneurysm.

    The researchers generated mice with genetic deficiencies by crossbreeding, and then infused the mice with AngII.

    The study is the first to show that genetic deletion of indoleamine 2,3-dioxygenase (IDO) or the decrease in the gene expression of kynureninase (KNU) in the body restrained AngII-induced abdominal aortic aneurysm in mice deficient in apolipoprotein e.

    In addition, the researchers made the discovery that 3-HAA was responsible for AngII-induced abdominal aortic aneurysm in the body.

    View publication

    Read more
  • Obese when compared to those with normal body fat had much higher inflammation: 53% higher CRP, 30% higher TNF-a, 17% higher WBC count, 42% higher IL6 linkinghub.elsevier.com
    Obesity Aging Metabolism Inflammation Immune System Metabolic Syndrome IL-6

    Strong link between accumulated visceral fat and chronic inflammation.

    A person’s waist-to-hip ratio compares their waist measurement to that of their hips. A high ratio can be an indicator of excess fat accumulation around the waist, often referred to as visceral fat. Findings from a 2005 study suggest that visceral fat is associated with markers of inflammation.

    Visceral fat is stored in the abdominal cavity near the liver, pancreas, and intestines. The accumulation of visceral fat is linked to increased risk of cardiovascular disease and other chronic diseases. Many factors drive visceral fat accumulation, including poor sleep, an obesogenic diet, and sugar-sweetened beverage intake, among others.

    The study involved more than 3,000 healthy males and females (18 to 89 years old) living in Greece. The investigators calculated the participants' body mass index (BMI) and measured their waist and hip circumferences. Participants provided blood samples for the assessment of inflammatory biomarkers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), amyloid A (an apolipoprotein secreted in the acute stage of inflammation), white blood cells, and interleukin-6 (IL-6).

    The investigators found that approximately 36 percent of the males and 43 percent of the females had excess visceral fat. Approximately 20 percent of the males and 15 percent of the females had obesity. Participants with greater visceral fat had 53 percent higher CRP, 30 percent higher TNF-alpha), 26 percent amyloid A, 17 percent higher white blood cell counts, and 42 percent higher IL-6, compared to participants with normal fat distribution. The relationship between visceral fat and inflammatory markers was stronger than that between obesity and inflammation, even when considering the participants' age, income, education, and other potential confounding factors.

    These findings suggest that visceral fat and inflammatory processes are linked. The investigators posited that excess accumulation of visceral fat may increase the risk for cardiovascular disease by driving inflammation.

    Read more
  • Compounds produced during ketosis may slow prostate cancer growth. www.biorxiv.org
    Cancer Metabolism Ketosis Prostate Carbohydrates Ketogenic Diet

    Prostate cancer is a leading cause of cancer death among men in the United States. While some prostate cancers respond well to local treatment, many cases require systemic treatments, such as chemotherapy or hormone therapies, which can have many side effects. Because having overweight or obesity increases the risk of death from prostate cancer](https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.22443), newer and alternative therapies that slow cancer growth and help patients lose weight are needed. Findings of a new report show that a low carb diet generates ketones and other metabolic compounds associated with slower prostate cancer growth.

    Low carbohydrate and ketogenic diets are popular with adults looking to lose weight, but they also have therapeutic power for a growing list of diseases such as epilepsy, [diabetes](​​https://www.magonlinelibrary.com/doi/full/10.12968/pnur.2020.31.4.176), Parkinson’s disease, and some cancers. In addition to the metabolic benefits of weight loss, many anticancer compounds are produced during ketosis such as beta-hydroxybutyrate, a short-chain fatty acid with documented antioxidant and anti-inflammatory effects. Additional research is needed to characterize the wide range of molecules generated on a low carb diet and explore their relationship to prostate cancer growth.

    The investigators recruited participants who had recurrent prostate cancer and a BMI in the overweight or obese range (greater than 24). They assigned participants to consume a low carbohydrate diet (less than 20 grams of carbohydrates per day) for six months or continue their habitual diet. Participants provided a blood sample to measure metabolic and cancer biomarkers at multiple time points.

    The investigators found increased concentrations of multiple ketone bodies in the blood and increased expression of genes for ketone production, indicating participants succeeded in maintaining ketosis. A low carbohydrate diet altered serum concentrations of multiple amino acids, such as glycine, alanine, and asymmetric dimethylarginine, and increased the expression of genes involved in the synthesis of malate, citrate, and branched-chain amino acids. The researchers found a relationship between increased concentrations of ketosis-related compounds and prostate specific antigen (PSA) double time (a marker of prostate cancer growth rate), indicating that cancer growth was reduced as ketosis intensified.

    These results show that metabolites produced in response to a ketogenic diet may contribute to the beneficial effects of a low carb diet for patients with prostate cancer.

    Read more
  • Metabolic adaptation “cancels out” some of the calorie-burning effects of exercise. www.sciencedirect.com
    Exercise Obesity Metabolism

    Traditionally, governments and public health authorities have placed a high emphasis on recommending physical activity as a means of combating weight gain and obesity. Yet, randomized controlled trials have found exercise alone to have a relatively modest effect on body weight, yielding weight loss averages in the order of 4 to 11 pounds (2 to 5 kilograms) in people with overweight and obesity. Some researchers have posited that metabolic adaptation causes the body to compensate for energy burned during exercise by reducing the baseline metabolic rate and ultimately “canceling out” some of the exercise-induced calorie deficit. Findings from a recent study indicate that much of the effort of exercise is lost to energy compensation, especially among people with excess bodyweight.

    The researchers’ analysis revolved around energy expenditure data collected in a cohort of more than 1,700 healthy adults, excluding those involved in competitive sports training or were pregnant or breastfeeding. They focused on three measures: baseline energy expenditure (i.e., the energy required to fuel basic functions such as respiration, tissue repair, and immune defense, minus any physical activity), total energy expenditure (i.e., total calories burned over the same period of time), and physical activity expenditure (inferred by subtracting baseline from total energy expenditure).

    Looking at the relationships between the three types of energy expenditure, the researchers corroborated what many smaller studies have suggested. That is, the more energy a person used during physical activity, the more their baseline metabolism slowed down to avoid a calorie deficit. The result of this adaptation is that total energy expenditure is approximately 28 percent lower on active days than might be expected given the number of calories burned during physical activity.

    This metabolic compensation was independent of the participants' sex or age. However, it was significantly affected by fat mass and body mass index (BMI), as individuals in the 90th percentile of BMI recouped approximately 49 percent of calories burned through physical activity by lowering their baseline metabolism.

    These findings suggest that exercise may be a considerably less effective weight loss tool for people with overweight or obesity. They also raise interesting questions about causality, such as whether people who have overweight are better metabolic “compensators” because of their high level of adiposity (which may have hormonal and signaling properties conducive to this form of adaptation) or whether they become overweight because they start out life by being better “compensators” and are more likely exceed their baseline metabolic needs with food. The possibility of innate differences in compensation receives some support from evidence for significant ethnic disparities in baseline metabolism. It is worth mentioning that exercise benefits human health independently of potential weight loss, through effects such as improved endothelial cell function, neurogenesis, glucose regulation, and inflammation.

    Read more
  • Less blue-light exposure at night improves metabolism. www.sciencedaily.com
    Metabolism Blue Light

    Inorganic light-emitting diodes – better known as LEDs – are ubiquitous in the modern era. Found in cell phones, televisions, computer screens, and a host of other electronic devices, LEDs emit short-wave, high-energy blue light, which has been linked to a wide range of harmful effects on health and sleep. Findings from a recent study suggest that organic LEDs (OLEDs), which produce less light in the blue-wave spectrum, have fewer harmful effects on human metabolism.

    Light exposure is one of the primary regulators of the body’s circadian rhythms and plays key roles in sleep quantity and quality. For example, evidence indicates that afternoon exposure to blue light impairs the release of melatonin – the “sleepiness hormone” – in a dose-dependent manner. Similarly, use of LED-lit devices in the evening interferes with sleep by promoting alertness.

    The cross-over study involved ten healthy males (average age, 25 years) who did not have sleep disorders. The participants were exposed to either LED, OLED, or dim light for four hours prior to going to sleep. The study investigators assessed the participants' sleep quality via polysomnography as well as the participants' self-assessment. The participants ate breakfast one hour after waking up, and the authors measured the participants' energy expenditure, fat oxidation, core body temperature, and melatonin levels for four hours (continuously) in a room with regular lighting. Each of the participants underwent all three lighting scenarios.

    The investigators found that after OLED exposure, the participants' energy expenditure and core body temperature during sleep were lower than after LED exposure, but their fat oxidation was higher. In addition, the increase in fat oxidation following OLED exposure was associated with higher melatonin levels. Sleep quality did not differ markedly between the different lighting scenarios.

    These findings suggest that evening OLED exposure elicits fewer harmful health effects than LED exposure, likely because OLEDs emit less blue light. Learn more about the effects of blue light in this clip featuring sleep expert Dr. Matthew Walker.

    Read more
  • Eating protein at breakfast is best for growing muscle mass. pubmed.ncbi.nlm.nih.gov
    Microbiome Metabolism

    Dietary protein is essential for the growth of skeletal muscle, a process called hypertrophy. Circadian rhythms – the body’s 24-hour cycles of biological, hormonal, and behavioral patterns – modulate a wide array of nutritional and metabolic processes, including amino acid absorption and utilization. However, it is unclear how circadian rhythms affect muscle hypertrophy. A report published this month suggests that distributing dietary protein equally across meals is best for maintaining muscle mass.

    Circadian clocks located in the brain and other organs are driven by changes in the expression of genes such as Circadian locomotor output cycles kaput, commonly referred to as “Clock.” Mice that do not express the Clock gene do not experience day-night variations in metabolism, disrupting amino acid absorption by skeletal muscle. Amino acids are required for activation of genes such as the mammalian target of rapamycin (mTOR), which promotes autophagy, a system of disassembly and recycling of unnecessary or dysfunctional cellular components that is essential for hypertrophy.

    The investigators conducted a set of experiments in mice and an observational study in humans. They fed mice two meals per day containing either 11.5 percent or 8.5 percent protein for two weeks. Mice consumed these meals in three patterns of protein distribution: high protein at breakfast and low protein at dinner; equal protein at both meals; or low protein at breakfast and high protein at dinner. In a second experiment, the researchers fed mice branched chain amino acids, which are used in high concentrations by the body for building muscle, at breakfast or dinner. In both experiments, the researchers performed muscle overloading, which puts stress on muscles to encourage hypertrophy, similar to weight lifting in humans. They measured changes in muscle strength, muscle gene expression, plasma amino acid concentrations, plasma growth factor concentrations, and autophagy.

    All mice gained muscle mass in response to muscle overload; however, mice that consumed a high-protein breakfast and low-protein dinner had greater gains in muscle mass and rate of hypertrophy than mice that consumed a low-protein breakfast and high-protein dinner. Likewise, mice that consumed a branched chain amino acid supplement in the morning gained more muscle mass and had a higher rate of hypertrophy than mice that consumed the supplement at night. Mice that do not express the Clock gene did not experience gains in muscle mass or hypertrophy with early protein or branched chain amino acid intake, suggesting these gains were circadian-related.

    The researchers found that branched chain amino acid concentrations increased following a high-protein meal regardless of time, so these gains in hypertrophy were not due to circadian fluctuations in plasma amino acid concentrations. Likewise, insulin-like growth factor concentrations increased following a high-protein meal regardless of time and likely did not affect the rate of hypertrophy. However, the activation of autophagy in overloaded muscle was greater in mice that consumed a high-protein breakfast compared to a high-protein dinner, potentially contributing to a higher rate of hypertrophy.

    Next, researchers recruited 60 women who completed a questionnaire about their consumption of protein foods at breakfast, lunch, and dinner. The researchers classified participants as early protein consumers or late protein consumers based on their answers and measured the participants' body composition, physical activity, and grip strength.

    Muscle mass tended to be higher in participants who consumed protein earlier in the day, but this relationship was not statistically significant. Early protein consumers also had significantly greater grip strength and higher skeletal muscle index, which is the ratio of muscle mass in a person’s arms and legs to their height. These relationships remained significant even after taking diet and activity into account. Finally, skeletal muscle index increased as the percent of daily protein eaten at breakfast increased, meaning the more protein that was consumed in the morning, the greater the increase in skeletal muscle index.

    These results indicate that circadian genes drive day-night variation in muscle metabolism and protein utilization. Early protein consumption is more beneficial for growing and maintaining muscle than late protein consumption.

    Read more
  • Milk chocolate exerts differential health effects, depending on the timing of consumption. www.the-scientist.com
    Metabolism

    A wide range of beneficial health effects have been ascribed to consumption of chocolate, especially dark chocolate, which is rich in bioactive compounds that exert antioxidant, anti-inflammatory, and cardioprotective properties. Consumption of milk chocolate, however, is widely associated with harmful effects (such as weight gain) due to its high caloric content. Findings from a recent study suggest that milk chocolate exerts differential health effects, depending on the timing of consumption.

    A growing body of evidence suggests that the timing of food intake plays important roles in metabolic regulation and circadian rhythmicity. For example, eating a large, carbohydrate-rich meal late in the evening impairs glucose tolerance and insulin secretion, contributing to the risk of developing type 2 diabetes.

    The study involved 19 Caucasian postmenopausal females with normal weight or overweight (average age, 52 years; average body mass index, 25). The participants followed their typical dietary pattern for the duration of the study, with three interventions in random order: 100 grams of milk chocolate (roughly the amount in a standard size candy bar – 542 calories) with breakfast for two weeks, within an hour of waking up; 100 grams of milk chocolate for two weeks, within an hour before bedtime; and no chocolate for two weeks. A one-week washout period separated each intervention. They completed questionnaires that assessed their hunger and appetite for sweets at various timepoints throughout the study. The study investigators assessed the participants' anthropometric measures, including body mass index, total body fat, and waist circumference. They also assessed the composition and function of the participants' gut microbiota and measured their blood glucose levels, body temperature, and sleep quality.

    The study investigators found that consuming 100 grams of milk chocolate in the morning or evening did not cause the women to gain weight. The women reported that they felt less hunger and less desire to eat sweets. When they ate milk chocolate in the morning, they consumed about 300 fewer calories during the rest of the day; their fat burning increased; their fasting blood glucose and waist circumference decreased; and their sleep quality was impaired. When they ate milk chocolate in the evening, they consumed about 150 fewer calories during the rest of the day; their physical activity, heat dissipation after meals, and carbohydrate metabolism increased; and their sleep quality improved. Both timings of chocolate consumption altered the composition and function of the gut microbiota.

    These findings demonstrate that the timing of milk chocolate consumption has varied effects on metabolism, dietary intake, and sleep function, potentially influencing overall health. Learn how food timing influences cancer risk in this clip featuring Dr. Ruth Patterson.

    Read more
  • Afternoon exercise improves insulin tolerance more than morning exercise. www.ncbi.nlm.nih.gov
    Exercise Metabolism

    The circadian rhythm is controlled by a central clock in the brain and by peripheral clocks in skeletal muscle, adipose tissue, and other organs. Together, these clocks coordinate the expression of genes related to a variety of metabolic processes with daily light, eating, and activity cycles. New research suggests that exercising in the afternoon maximizes metabolic benefits due to circadian-driven cycles.

    While light is the main driver of the central circadian clock in the brain, peripheral clocks are responsive to a number of environmental signals such as eating and exercise. When these activities are out of sync with normal light/dark cycles, as seen with shift work, metabolic dysfunction occurs. Previous research in humans has reported severely impaired glucose and insulin regulation with circadian disruption.

    The investigators recruited a group of 32 males (average age, 58 years) who had type 2 diabetes or were at risk for developing type 2 diabetes. Participants completed 12 weeks of combined aerobic and resistance training in the morning (8 a.m. to 10 a.m.) or afternoon (3 p.m. to 6 p.m.). The researchers measured insulin tolerance, body composition, and exercise performance before and after the intervention.

    Participants who exercised in the afternoon improved their insulin sensitivity by 34 percent, while insulin sensitivity in the morning group improved only 3 percent. The afternoon group also experienced a significantly greater reduction in fasting glucose levels, fat mass, percent body fat, and exercise performance. Although it wasn’t statistically significant, afternoon exercise also tended to improve glucose output from the liver, another marker of metabolic health.

    The authors concluded that exercising in the afternoon improved insulin tolerance, body composition, and exercise performance to a greater extent than morning exercise in those with metabolic dysfunction. The authors speculated that circadian cycles in skeletal muscle or cycles in body hormone levels may be the cause of this effect, although further research is needed to fully understand the impact of exercise timing on metabolism.

    Link to full study. Learn more about the importance of circadian rhythms in this episode featuring expert Satchin Panda.

    Read more
  • Fasting activates multiple metabolic pathways. www.nature.com
    Metabolism Fasting

    Fasting – the voluntary abstinence from food and drink – triggers the activation of a vast array of biochemical processes and signaling pathways that optimize human performance and physiological function, possibly slowing the processes of aging and disease. A recent study found that fasting induced profound, diverse increases in the metabolites present in blood.

    Metabolites are substances produced in an organism, cell, biological fluid, or tissue during metabolism. The collection of these metabolites in their entirety is referred to as the metabolome. Metabolomics is an emerging field of study involving the identification and quantification of the metabolome at a specific time point to create a metabolic profile that provides information about the body’s physiological state. Previous research has identified 126 distinct metabolites in human blood.

    The authors of the study drew blood samples from four healthy, young (average age, xx years) non-obese volunteers at three intervals (10, 34, and 58 hours) during a period of fasting. They analyzed the participants' metabolomic profiles in whole blood, plasma, and red blood cells and identified changes (increases or decreases) in the metabolites. Their analysis revealed that the participants' blood glucose levels remained within the normal range (70 to 80 mg/dL) and ATP levels were consistent throughout the fasting period. Levels of most of the previously identified metabolites remained unchanged during the fast, but 44 metabolites increased, and two decreased.

    Those that increased included butyrate, branched-chain amino acids, carnitines, organic acids, coenzymes, pyrimidines, purines, antioxidants, and molecules associated with the pentose phosphate pathway. These compounds support multiple metabolic pathways and biological processes, including gluconeogenesis (the production of glucose from ketones, glycerol, and amino acids), protein synthesis, and mitochondrial activity, among others. The compounds that decreased were aspartate (an amino acid) and gluconate (a glucose derivative).

    These findings suggest that fasting induces a metabolically active state in healthy, young adults. However, this was a very small study, so larger studies are needed to confirm the findings.

    Read more
  • Vitamin C part of crucial pathway that eliminates toxic byproducts of fat metabolism www.sciencedaily.com
    Metabolism Vitamin C DNA Damage Fat

    From the article:

    “It’s true that vitamin C does react with oxidized lipids to form potential genotoxins,” said Balz Frei, professor and director of the Linus Pauling Institute, and co-author on this study. “But the process does not stop there. We found in human studies that the remaining vitamin C in the body continues to react with these toxins to form conjugates - different types of molecules with a covalent bond - that appear to be harmless.”

    In human tests, the OSU scientists found in blood plasma extraordinarily high levels of these conjugates, which show this protective effect of vitamin C against toxic lipids.

    “Prior to this, we never knew what indicators to look for that would demonstrate the protective role of vitamin C against oxidized lipids,” Stevens said. “Now that we see them, it becomes very clear how vitamin C can provide a protective role against these oxidized lipids and the toxins derived from them. And this isn’t just test tube chemistry, this is the way our bodies work.

    Read more
  • A small study found that 4 nights of sleep restriction (5hrs sleep/night) resulted in decreased satiety after a calorically dense meal. www.sciencedaily.com
    Metabolism Sleep Satiety

    A small study found that 4 nights of sleep restriction (5hrs sleep/night) resulted in decreased satiety after a calorically dense meal and altered lipid metabolism in healthy people. Catch up sleep one night only helped a little.

    This was a very small study that needs to be repeated. The preliminary results found that four consecutive nights of 5 hours of sleep per night changed lipid metabolism in healthy individuals. Lipids were cleared from the bloodstream faster after a meal but they were stored in adipose tissue. This could partially explain why people did not feel satiated after a calorically dense meal.

    Other studies have shown that sleep restriction also alters hormones that regulate satiety. Several studies have also shown that sleep restriction disrupts glucose metabolism. Many mechanisms may be at play.

    One night of catch up sleep led to some improvements but satiety and lipid metabolism were still disrupted.

    Read more
  • Exercising while fasted induces adaptations to mitochondria in muscle/fat tissue including increased fatty acid metabolism that is blunted by feeding. www.ncbi.nlm.nih.gov
    Exercise Metabolism Fasting Triglycerides Aerobic

    Exercising while fasted induces adaptations to mitochondria in muscle and adipose tissue including increased fatty acid metabolism that is blunted by pre-exercise feeding (meta-analysis of 46 clinical studies).

    Exercising in a fasted state increased the release of fatty acids stored in adipose tissue and the use of them for energy in muscle and adipose tissue (ie. fat burning). It also increased the use of intramuscular triglycerides over glycogen in muscle tissue. Exercise while fasted also caused mitochondria to increase gene activity in genes related to fatty acid metabolism making them more efficient as using fat for energy. These adaptations were blunted by pre-exercise feeding.

    Pre-exercise feeding did enhance performance in long-duration exercise (> 60 minutes) but had no effect on aerobic training shorter than 60 minutes. Pre-exercise feeding also slightly enhanced anaerobic exercise (ie. run until exhaustion) but had no effect on high-intensity interval training.

    Read more
  • Role of dietary transition metals on host microbiota and risk of disease www.gutmicrobiotaforhealth.com
    Nutrition Gut Diet Microbiome Metabolism Immune System Micronutrients Iron Protein

    Transition metals are required cofactors for many proteins that are critical for life, and their concentration within cells is carefully maintained to avoid both deficiency and toxicity. To defend against bacterial pathogens, vertebrate immune proteins sequester metals, in particular zinc, iron, and manganese, as a strategy to limit bacterial acquisition of these necessary nutrients in a process termed “nutritional immunity.” In response, bacteria have evolved elegant strategies to access metals and counteract this host defense. In mammals, metal abundance can drastically shift due to changes in dietary intake or absorption from the intestinal tract, disrupting the balance between host and pathogen in the fight for metals and altering susceptibility to disease. This review describes the current understanding of how dietary metals modulate host-microbe interactions and the subsequent impact on the outcome of disease.

    https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30262-2

    Read more
  • Nutrient-induced Mitochondrial Activation (NiMA): A Novel Lysosome-to-Mitochondria Signaling Pathway Disrupted by Amyloid-β Oligomers papers.ssrn.com
    Nutrition Alzheimer's Metabolism Mitochondria Neuron Insulin Neurons Protein

    The mechanisms of mitochondrial dysfunction in Alzheimer’s Disease (AD) are incompletely understood. We show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-β oligomers, which are precursors of amyloid plaques in AD brain and stimulate mTORC1 protein kinase activity at the plasma membrane, but not at lysosomes, block this nutrient-induced mitochondrial activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in AD brain. NiMA was also disrupted in fibroblasts derived from a patient with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity, and links mitochondrial dysfunction to AD by a mechanism dependent on soluble building blocks of plaques and tangles. https://ssrn.com/abstract=3188445

    Read more
  • Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1 papers.ssrn.com
    Nutrition Metabolism Biomarkers Circadian Rhythm Behavior Autophagy Protein

    The circadian clock coordinates behavioral and circadian cues with the availability and utilization of nutrients. Proteasomal degradation of clock repressors, e.g., cryptochrome (CRY)1 maintains periodicity of the clock. Whether autophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERB, and CRY1 are lysosomal targets, and that α macroautophagy (hereafter autophagy) specifically degrades CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that degradation of CRY1 is time-imprinted to maintenance of blood glucose levels. CRY1 contains several light chain 3 (LC3)-interacting region (LIR) motifs, which facilitate the interaction of cargo proteins to the autophagosome marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1 that exert circadian control over blood glucose levels by regulating CRY1 degradation, revealing CRY1 LIRs as potential targets in regulation of glucose metabolism.

    Toledo, Miriam and Tarabra, Elena and Batista-Gonzalez, Ana and Merlo, Paola and Feng, Daorong and Sarparanta, Jaakko and Botrè, Francesco and Pessin, Jeffrey E. and Singh, Rajat, Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1 (2018). Available at SSRN: https://ssrn.com/abstract=3155564 or http://dx.doi.org/10.2139/ssrn.3155564

    Read more
  • Hair Regeneration by Small Molecules That Activate Autophagy papers.ssrn.com
    Aging Metabolism Autophagy Metformin Autoimmunity

    Hair plays important roles, ranging from the conservation of body heat to the preservation of psychological well-being. Hair loss or alopecia affects millions worldwide and can occur because of aging, hormonal dysfunction, autoimmunity, or as a side effect of cancer treatment. Methods that can be used to regrow hair are highly sought after, but lacking. Here we report that hair regeneration can be stimulated by small molecules that activate autophagy, including the longevity metabolites α-ketoglutarate and α-ketobutyrate, and the prescription drugs rapamycin and metformin which impinge on TOR and AMPK signaling.

    Chai, Min and Jiang, Meisheng and Vergnes, Laurent and Fu, Xudong and de Barros, Stéphanie C. and Jiao, Jing and Herschman, Harvey R. and Crooks, Gay M. and Reue, Karen and Huang, Jing, Hair Regeneration by Small Molecules That Activate Autophagy (2018). Available at SSRN: https://ssrn.com/abstract=3188356 or http://dx.doi.org/10.2139/ssrn.3188356

    Read more
  • Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila | eLife elifesciences.org
    Aging Metabolism Depression

    Abstract: Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging remains to be understood. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila, we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state. We show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis diminishes the pro-lifespan benefits mediated by PRCs-deficiency, transgenic increase of glycolytic genes in wild-type animals extends longevity. Together, we propose that epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging and that stimulation of glycolysis promotes metabolic health and longevity.

    Discussion: Aging is a complex process that can be regulated by a network of multiple mechanisms. It has been well-established that enhancing NAD+ biogenesis promotes healthy lifespan (Anderson et al., 2002; Balan et al., 2008; Mills et al., 2016). As noted, supplementation of NAD+ precursors profoundly elevates energy metabolism by increasing the expression of genes in the TCA cycle as well as glycolysis in C. elegans (Mouchiroud et al., 2013), and promotes glucose metabolism with increased flux through pentose phosphate and glycolytic pathways in mice on a high-fat diet (Mitchell et al., 2018). Therefore, it would be interesting to test whether the life-benefit effects of NAD+ might be through at least in part by the activation of glycolysis. Intriguingly, while declining intracellular NAD+ and thus increased NADH/NAD+ ratio correlate with aging (Zhu et al., 2015), our experiments in Drosophila demonstrate that increased ratios of GSH/(GSH +GSSG) and NADH/NAD+ due to enhanced glycolytic activities may provide a simple but effective way to retard aging. The oxidative phosphorylation, although produces more ATP than glycolysis, can yield intracellular ROS. The accumulation of ROS is the leading proposed cause of decline in cellular function and integrity in aging (Balaban et al., 2005). Thus, modulating H3K27me3 may reprogram bioenergetic decline during aging, which in effect reduces cellular damage and deterioration. Importantly, mammalian glycolytic genes have also been shown as PRCs targets (Brookes et al., 2012). Future investigations, including in-depth comparative analysis of PRCs and glycolytic pathway in the aging process in both flies and humans, may harness common operative mechanisms that modulate metabolic homeostasis and healthy longevity. Given the reversible nature of epigenetic pathways, this study proffers a tempting strategy against age-associated physiological decline and disease.

    Read more
  • Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR. - PubMed - NCBI www.ncbi.nlm.nih.gov
    Cancer Metabolism Stress Circadian Rhythm Autophagy

    Citation: Cell. 2018 Jun 28;174(1):72-87.e32. doi: 10.1016/j.cell.2018.05.009. Epub 2018 May 31.

    Abstract Recent reports indicate that hypoxia influences the circadian clock through the transcriptional activities of hypoxia-inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify to recapitulate the tumor microenvironment. Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation. Acidification of several human and murine cell lines, as well as primary murine T cells, suppresses mechanistic target of rapamycin complex 1 (mTORC1) signaling, a key regulator of translation in response to metabolic status. We find that acid drives peripheral redistribution of normally perinuclear lysosomes away from perinuclear RHEB, thereby inhibiting the activity of lysosome-bound mTOR. Restoring mTORC1 signaling and the translation it governs rescues clock oscillation. Our findings thus reveal a model in which acid produced during the cellular metabolic response to hypoxia suppresses the circadian clock through diminished translation of clock constituents.

    Read more
  • Sulforaphane (found in broccoli sprouts) causes 20% fat loss by changing gut bacteria & increasing mitochondria in fat in mice. www.sciencedaily.com
    Gut Obesity Microbiome Metabolism Inflammation Sulforaphane Fatty Liver NRF2 Endotoxemia Lipopolysaccharide Visceral Fat

    Sulforaphane from broccoli sprouts causes 20% visceral fat loss by changing gut bacteria and increasing mitochondria in fat in mice. The mice fed sulforaphane also lowered fatty liver and reduced blood glucose levels. Sulforaphane reduced inflammation by decreasing a species of bacteria in the gut that is responsible for producing endotoxin, which is a major source of inflammation. Also, sulforaphane increased the levels of UCP1, which is responsible for increasing mitochondrial biogenesis (the generation of new mitochondria) in fat (called browning of fat). The browning of fat increases fat metabolism and can lead to fat loss. There have been human studies showing that sulforaphane decreases inflammatory biomarkers and improves blood glucose levels. It will be interesting to see future studies looking at these two new functions of sulforaphane in humans. For more information check out my video on sulforaphane or my podcast with Dr. Jed Fahey, who discovered broccoli sprouts are the best source of sulforaphane. Sulforaphane video: https://youtu.be/zz4YVJ4aRfg Sulforaphane podcast: https://youtu.be/Q0lBVCpq8jc

    Read more
  • New 20-page report on cryotherapy just released! Cold shock boosts norepinephrine up to 5-fold & increase type of immune cell that kills tumor cells. www.foundmyfitness.com
    Exercise Brain Alzheimer's Aging Metabolism Inflammation Memory Immune System Norepinephrine Protein

    This 20-page report explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. Rhonda discusses how cold exposure increases norepinephrine up to 5-fold in the brain and what the temperature and duration needed to do this are, how norepinephrine has an effect on mood, vigilance, focus, and attention, how cold exposure increases cold shock proteins including one in the brain that repairs damaged synapses and in muscle prevents atrophy, how cold-induced norepinephrine lowers inflammation and pain by decreasing the levels of 3 inflammatory mediators, how chronic cold shock may increase immune cell numbers and particularly a type of immune cell that kills cancer cells, how cold exposure increases metabolic rate, the number of mitochondria, and the burning of fat, what the effects of different cold exposure temperatures and timing are on athletic performance, recovery time, and muscle mass, and the differences between various types of cold shock modalities, including cold water immersion and whole body cryotherapy.

    Read more