Metabolism
Episodes
Dr. Rhonda Patrick explains how HIIT, circadian-timed eating, and quality sleep improve metabolic health and reduce chronic disease risk.
Dr. Layne Norton and I discuss fat loss, resistance training, seed oils, the carnivore diet, artificial sweeteners, and much more.
Dr. Peter Attia presents practical steps we can implement to improve our health, emphasizing the importance of each aspect while providing actionable advice.
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Dr. Rhonda Patrick explains how HIIT, circadian-timed eating, and quality sleep improve metabolic health and reduce chronic disease risk.
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Exercise Nutrition Obesity Metabolism Muscle Polyunsaturated Fat Saturated Fat Time-Restricted Eating Protein Weight Loss Strength SupplementsDr. Layne Norton and I discuss fat loss, resistance training, seed oils, the carnivore diet, artificial sweeteners, and much more.
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Dr. Peter Attia presents practical steps we can implement to improve our health, emphasizing the importance of each aspect while providing actionable advice.
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Dr. Rhonda Patrick describes strategies you can apply immediately to enhance your health and prevent chronic disease.
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Dr. Stuart Phillips discusses how exercise and nutrition influence skeletal muscle-protein turnover and muscle maintenance throughout the lifespan.
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In this clip, Dr. Dominic D'Agostino gives his thoughts on eating an all-meat diet and weighs in on whether it is optimal to eat a diet devoid of fiber.
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In this clip, Dr. Dominic D'Agostino discusses the implications of adding a ketogenic diet to cancer treatment protocols.
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In this clip, Dr. Dominic D'Agostino describes how nutritional ketosis may support the treatment of neurodegenerative and other brain disorders.
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In this clip, Dr. Dominic D'Agostino describes animal research that explores the mechanisms by which the ketogenic diet may benefit the brain.
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In this clip, Dr. Dominic D'Agostino discusses how ketones affect exercise performance.
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In this clip, Dr. Dominic D'Agostino describes strategies to incorporate other fasting modalities into a ketogenic lifestyle diet.
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In this clip, Dr. Dominic D'Agostino discusses how ketones produced during fasting and ketosis protect against muscle loss.
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In this clip, Dr. Dominic D'Agostino discusses the supplements he thinks pair well with a ketogenic diet.
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In this clip, Dr. Dominic D'Agostino outlines the advantages and disadvantages of various ways of quantifying ketosis.
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In this clip, Dr. Dominic D'Agostino discusses the applicability of a ketogenic diet for people with an APOE4 gene variant.
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In this clip, Dr. Dominic D'Agostino describes how breath acetone concentration is a non-invasive tool for measuring fat loss.
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In this clip, Dr. Dominic D'Agostino outlines strategies to initiate a ketogenic diet and mitigate its side effects.
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In this clip, Dr. Dominic D'Agostino details the macronutrient ratios that make up the broad spectrum of ketogenic diets.
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In this clip, Dr. Patrick explains how intense exercise beneficially alters tryptophan and kynurenine metabolism in a way that may benefit depression.
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In this clip, Dr. Ronald Krauss discusses the role of inflammation in lipoprotein metabolism.
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In response to cold-water immersion, the body increases circulation of norepinephrine. This physiological response sets off a cascade of adaptive effects that affect metabolism, the brain, and genetic expression.
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Dr. Eran Elinav discusses the complex interactions between humans and their resident gut microbiomes.
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In this clip, Dr. Satchin Panda describes how circadian rhythms regulate processes including eating behaviors, problem-solving ability, and mood.
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In this clip, Dr. Satchin Panda describes the relationship between melatonin and insulin and how this might determine the best time to eat.
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Dr. Michael Snyder discusses personalized medicine and the use of technologies that monitor metabolism and other health markers.
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In this clip, Dr. Roger Seheult and Dr. Rhonda Patrick discuss how to assess vitamin D requirements and its toxicity potential.
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In this clip, Dr. Giselle Petzinger highlights some of the risk factors for Parkinson's disease, and discusses how this is likely a multifaceted problem.
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In this clip, Dr. Rhonda Patrick goes over harmful substances that can get into breastmilk and negatively affect an infant’s health.
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In this clip, Dr. Rhonda Patrick describes the relationship between metformin and cancer incidence and the relevance for those with type 2 diabetes.
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In this clip, Dr. Dominic D'Agostino describes how gluconeogenesis fills an important role during ketosis to maintain a basal level of glucose.
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In this clip, Dr. Ray Cronise emphasizes the importance of diet to improve healthspan rather than employing tricks to boost metabolic rate.
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In this clip, Dr. Peter Attia and Dr. Rhonda Patrick examine the use of various fuel sources in brain metabolism.
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Dr. Jed Fahey describes some of the factors that influence the conversion of myrosinase-driven conversion of glucoraphanin to sulforaphane.
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In this clip, Dr. David Sinclair describes the role of NAD+ in the regulation of the body's circadian clock and sirtuin production.
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In this clip, Dr. David Sinclair describes how sirtuins, caloric restriction, fasting, and the insulin-IGF-1 pathway converge to modulate aging and lifespan.
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In this clip, Dr. Roland Griffiths and Dr. Rhonda Patrick discuss the sociocultural aspects of hallucinogenic substance use.
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Dr. Valter Longo defines the different fasting modalities, and compares and contrasts the variations of each in duration and degree of restrictiveness.
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Dr. Valter Longo discusses how the fasting-mimicking diet is one of the few dietary interventions that can increase relative lean body mass.
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Dr. Eric Verdin explains how nicotinamide adenine dinucleotide levels diminish with age along with the ongoing research to understand the reasons why.
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Dr. Guido Kroemer describes how fasting associated with sickness behavior is critical to surviving infection.
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Dr. Guido Kroemer describes the anti-diabetes and anti-obesity effects of exercise-induced autophagy.
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Dr. Satchin Panda explains the role of the suprachiasmatic nucleus – the body's master clock – and how it affects metabolism.
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Dr. Satchin Panda describes CLOCK's varied response to light and food and how those responses affect metabolism.
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Dr. Satchin Panda describes his take on what "healthy" means from a circadian perspective and how time-restricted eating plays a part.
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Dr. Satchin Panda discusses the controversy surrounding consumption of black coffee or tea while practicing time-restricted eating.
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Dr. Dale Bredesen describes the risks associated with APOE4 and identifies strategies for mitigating that risk.
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Dr. Ruth Patterson discusses how skipping breakfast and eating late into the evening may contribute to worse metabolic health.
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In this clip, Dr. Ruth Patterson discusses how eating in accordance with the body's natural circadian rhythm may reduce the risk of breast cancer.
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Dr. Elissa Epel describes how pre-pregnancy parental health impacts offspring.
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Dr. Rhonda Patrick and Dr. Elissa Epel discuss how obesity affects genes in sperm DNA involved in metabolic health and cognitive function.
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Several studies have established causation showing that sleep duration is a major determinant of insulin sensitivity.
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Epigenetics Vitamin D Nutrition Exercise Aging Metabolism Sleep Diabetes Telomeres DNA Damage Stem Cells Stress Melatonin Vitamin E Genetics 23andMe Heat Stress Autophagy Autism Folate Sauna AntioxidantOur genes influence the way we absorb and metabolize micronutrients. Nutrigenomics looks at the influence genetic variation has over micronutrient absorption/metabolism and the biological consequences of this dynamic relationship.
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Dr. Satchin Panda discusses the practical aspects of implementing fasting, time-restricted eating, shift work strategies, and more.
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Nutrition Vitamin D Metabolism Diabetes Telomeres Omega-3 Inflammation Depression DNA Damage Stem Cells Micronutrients Mitochondria Autophagy Autism Schizophrenia Resveratrol Sulforaphane Insulin Blue LightDr. Rhonda Patrick makes her fifth appearance on the Joe Rogan Experience.
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Fasting Metabolism Breast Cancer Insulin Resistance Podcast Inflammation Video Insulin Time-Restricted EatingDr. Ruth Patterson discusses the role of fasting in the prevention and survivorship of breast cancer.
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Dr. George Brooks discusses the metabolic pathway known as the “lactate shuttle" and its role in the recovery from traumatic brain injury.
Topic Pages
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Creatine
Creatine is a naturally occurring compound best known for its widespread use as a dietary supplement to enhance physical performance.
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Depression
Depression – a neuropsychiatric disorder affecting 322 million people worldwide – is characterized by negative mood and metabolic, hormonal, and immune disturbances.
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Hydrolyzed collagen
Hydrolyzed collagen, a mixture of peptides derived from collagen, may improve skin aging, decrease arthritis-induced pain, increase bone mineral density, and reduce hypertension.
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NAD+
NAD+ is a cofactor that plays an essential role in metabolism, DNA repair, and immunity. Its depletion accelerates aging.
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Resveratrol
Resveratrol is a polyphenolic compound produced in plants that demonstrates anti-inflammatory and anti-aging properties in humans.
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Time-restricted eating
Time-restricted eating is a form of daily fasting wherein a person eats only during a limited time window, typically 8- to 12-hours.
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Ultra-processed Foods (UPFs)
UPFs are formulations of mostly cheap industrial sources of dietary energy (calories) and nutrients plus additives that have negative effects on human health.
News & Publications
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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.
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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.
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Supplemental vitamin K2 improves diabetes markers and glycemic control. pubmed.ncbi.nlm.nih.gov
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.
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Time-restricted eating activates genes involved in metabolism and autophagy. www.sciencedaily.com
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.
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Hot water baths before bedtime reduce the risk of hypertension. www.eurekalert.org
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.
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Dysregulated tryptophan metabolism contributes to abdominal aortic aneurysm formation in mice. (2017) www.eurekalert.org
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.
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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
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.
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Afternoon exercise improves insulin tolerance more than morning exercise. www.ncbi.nlm.nih.gov
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.
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Fasting activates multiple metabolic pathways. www.nature.com
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.