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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 (9 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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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
    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.

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  • 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.

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  • 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.

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