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Metabolism

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Aliquot #148: The Hype and Reality of Nicotinamide Riboside

Posted on July 9th 2026 (19 days)

Nicotinamide adenine dinucleotide, or NAD, is in every cell of your body and plays a central role in energy metabolism, mitochondrial...

exercise

The Best Type of Exercise for Longevity

Posted on November 28th 2025 (8 months)

Dr. Rhonda Patrick and exercise physiologist Brady Holmer discuss a new study which challenges the current exercise guidelines.

blood sugar

Take THIS Supplement Before Meals to Instantly Lower Blood Sugar

Posted on October 1st 2025 (10 months)

In this clip, Dr. Ben Bikman highlights berberine, apple cider vinegar, and ketones—supplements that lower glucose spikes and support metabolic...

Topic Pages

  • Coffee

    Caffeine in coffee antagonizes adenosine receptors, elevating catecholamines, thereby increasing thermogenesis, lipolysis, and basal metabolic rate.

  • Creatine

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

  • Day–night patterns of light exposure

    Light-driven circadian clock entrains metabolic gene expression, modulating glucose homeostasis, lipid oxidation, and energy expenditure across day–night cycles.

  • 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.

  • Rapamycin

    Rapamycin inhibits mTORC1, thereby downregulating anabolic metabolism while promoting autophagy and oxidative metabolic adaptations.

  • 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

  • Lifestyle changes, but not metformin, were linked to a lower burden of chronic disease over time in adults with prediabetes. doi.org
    Diabetes Diet Exercise Metabolism Metformin Weight Loss

    Lifestyle changes and metformin can delay or even prevent type 2 diabetes in people with prediabetes, but it remains unclear whether they also reduce the long-term risk of developing other chronic diseases. Researchers tested this possibility by tracking the long-term health of people who had participated in an earlier clinical trial.

    The original trial randomly assigned 3,234 adults with prediabetes to intensive lifestyle support, metformin, or placebo. During the roughly three-year trial, the lifestyle program aimed for at least 7% weight loss through lower calorie and fat intake and at least 150 minutes of physical activity per week, while metformin was prescribed at 850 mg twice daily as tolerated. After the trial ended, all participants were offered the lifestyle program in group classes over six months. They were then invited to join a follow-up study, which continued tracking their health. During this follow-up, all participants were offered one lifestyle session every three months, while those originally assigned to the lifestyle group were offered two additional sessions each year. These follow-up lifestyle sessions continued for about 12 years. Participants originally assigned to metformin typically had about 18 years of recorded metformin use, although the duration varied widely. The current analysis examined Medicare records from 1,173 participants over roughly 21 years from the start of the original trial, with about 10 years of records available per person. Researchers used the records to determine whether participants developed at least two of 15 chronic conditions and how many conditions they developed overall.

    • Lifestyle support was linked to a slower accumulation of chronic conditions. Compared with the placebo group, the rate of developing at least two chronic conditions was 21% lower, and 25% lower for at least three conditions.
    • The lifestyle group also developed fewer conditions overall. Participants in this group had about 10% fewer chronic conditions on average than those in the placebo group.
    • Costly combinations of chronic conditions were less common with lifestyle support. Compared with placebo, the rate of developing a condition pair associated with especially high Medicare spending was about 43% lower.
    • The lifestyle findings extended beyond diabetes prevention. The association remained when diabetes was left out of the condition count, suggesting that delayed diabetes alone did not explain the pattern. However, participants who developed diabetes were still more likely to accumulate other chronic conditions later.
    • Metformin did not show the same broad benefit. Compared with placebo, it was not clearly linked to a lower rate of developing two or three chronic conditions, fewer conditions overall, or fewer condition pairs associated with especially high Medicare spending. One exception was a lower risk of developing three conditions when diabetes was excluded.

    Many chronic diseases share underlying drivers, including excess body fat, poor metabolic control, and declining physical function. Unlike metformin, the lifestyle program addressed all three. Improvements across these areas could benefit several organ systems at the same time, reducing the likelihood that multiple conditions develop in the same person. Taking medications can also improve metabolic control and delay diabetes, but metformin may not produce the same coordinated changes. The observation that the lifestyle association remained after diabetes was removed supports this interpretation: delayed diabetes was likely one contributor, but not the full explanation.

    A key limitation is that the analysis included only participants who were still alive, enrolled in Medicare, and willing to share their records, limiting how broadly the findings apply. Still, the findings underscore the limits of pharmaceutical treatment alone and the importance of lifestyle changes for long-term health. In episode #96, I explain how high-intensity interval training (HIIT), circadian-timed eating, and quality sleep improve metabolic health and reduce chronic disease risk.

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  • Cutting sleep by 80 minutes per night increased body weight and waist circumference in adults with cardiometabolic risk factors. doi.org
    Metabolism Sleep Weight Loss

    Sleep disorders can promote weight gain, but the effect of the mild sleep loss many people experience in daily life is less certain. A new study tested whether restricting sleep by a little over an hour could change body weight and composition.

    The analysis pooled data from two randomized trials involving 95 adults who normally slept at least seven hours and had elevated risk for heart and metabolic disease. In both trials, participants followed two six-week sleep schedules in a random order: one with their usual sleep and one with bedtime delayed by 1.5 hours. Wrist sensors confirmed that the shorter sleep period reduced nightly sleep by about 78 minutes, to just over six hours. Researchers measured body weight and waist size, used magnetic resonance imaging (MRI) scans to estimate body fat and muscle distribution, tracked physical activity, and measured morning fasting levels of hormones related to appetite regulation and energy stores. In 34 participants, they also estimated energy (calorie) expenditure using the doubly labeled water technique, in which participants drank water containing traceable forms of hydrogen and oxygen.

    • Short sleep modestly increased weight without a clear shift in body composition. After six weeks, participants were about 1 pound (0.45 kg) heavier and had waists about 0.5 cm larger under shorter sleep, but MRI scans did not show a clear shift in body fat or skeletal muscle proportions.
    • Changes in physical activity were limited to sedentary time. Participants spent about 17 more minutes per day sedentary, while their moderate-to-vigorous physical activity was nearly identical under both sleep conditions.
    • Total daily energy expenditure remained unchanged. Estimated energy use averaged about 2,439 kilocalories (kcal) per day during the shorter sleep period and 2,415 kcal during the adequate sleep period.
    • Hormones involved in appetite regulation showed no consistent response. Leptin (a hormone that also reflects energy stored in body fat) was modestly higher with shorter sleep, but two other appetite-related hormones, GLP-1 and ghrelin, did not clearly change.

    One possible explanation for this result is that more waking hours can create more opportunities to consume meals and snacks, while more sedentary time may offset some of the extra energy required to stay awake. Together, these shifts could create a small daily calorie surplus that accumulates over time, allowing weight to rise without a clear change in total daily calorie use. The hormone findings did not point to a separate appetite-driven mechanism. Of the three appetite-related hormones measured, only leptin increased, a change that may reflect the modest weight gain rather than a broader shift in appetite signaling.

    A key limitation is the study's relatively short duration and lack of calorie intake measurements, which make it difficult to clearly explain the observed weight difference or determine whether it would persist under these sleep conditions over time. Still, the results suggest that even a small loss of sleep may be enough to shift weight over a matter of weeks. Aliquot #104 explores the science of optimizing sleep.

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  • Regular sleep timing may be just as important as sleep duration for long-term health. doi.org
    Cancer Cardiovascular Metabolism Mortality Sleep

    Getting enough sleep is a central part of sleep advice, but the day-to-day consistency of sleep and wake times may also matter for long-term health. To test that idea, a study examined whether sleep regularity is linked to the risk of premature death.

    The study analyzed data from more than 60,000 UK Biobank participants who were about 63 years old on average and wore an activity tracker for one week. Using those records, researchers calculated a sleep regularity score, estimating how often participants were asleep or awake at similar times from one day to the next, and compared it with average sleep length. They then linked those sleep measures to death records for up to nearly 8 years.

    • Sleep regularity was a stronger predictor of death rates from any cause over the study period than average sleep length.
    • Compared with the least-regular sleepers, the groups with more regular sleep patterns had about 20% to 30% lower rates of death from any cause during follow-up, after the researchers accounted for demographic, lifestyle, social, and health factors.
    • The two most regular sleep groups also had about 23% to 24% lower rates of death from cancer and about 31% to 38% lower rates of death from cardiovascular, diabetes-related, and other metabolic causes.
    • As a practical anchor, the researchers noted that the most regular sleepers usually fell asleep and woke within about one-hour windows, compared with about three-hour windows in the least-regular group.

    Sleep timing may matter because it helps organize many of the body's daily rhythms, not just sleep itself. When bedtimes and wake times shift from day to day, the timing of light exposure, meals, physical activity, and rest often shifts with them. These cues help synchronize the body's 24-hour rhythms across many organs and tissues, including rhythms involved in blood pressure, blood sugar control, inflammation, hormone signaling, and cellular repair. Irregular timing could therefore create a kind of repeated internal mismatch, where different systems are receiving less consistent signals that help coordinate the body's daily functions.

    The study was observational, so it cannot determine whether irregular sleep timing contributed to higher death rates or simply reflected underlying health problems that increased the likelihood of both irregular sleep and earlier death. Nevertheless, the findings suggest that steady sleep and wake windows deserve attention alongside getting enough sleep each night. In episode #107, Dr. Michael Grandner and I explore treatment options for insomnia and science-backed strategies for better sleep.

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  • Nighttime may be an important window for treatment and lifestyle decisions in fatty liver disease. doi.org
    Circadian Rhythm Fatty Liver Metabolism

    Metabolic dysfunction-associated steatotic liver disease (MASLD) involves fat accumulation in the liver, but less is known about whether the underlying metabolic defects vary across the day. Researchers tested whether day–night differences in how the body handles sugar and fat could help explain why fat builds up in the liver.

    The study included 24 overweight adults: 12 with MASLD and 12 controls without MASLD. Participants did not have diabetes, and each completed separate daytime and nighttime testing visits after 12 hours of fasting. Researchers measured insulin sensitivity using the gold-standard hyperinsulinemic–euglycemic clamp and also assessed sugar production and use as well as fat metabolism. Insulin is a hormone that, in insulin-sensitive individuals, effectively helps move sugar (glucose) from the blood into cells and reduces the body's own sugar production. Insulin resistance impairs this process, resulting in higher blood sugar and increased fat release into the bloodstream.

    • Controls showed lower de novo lipogenesis (the liver's production of new fat from non-fat sources) at night, while MASLD participants kept this pathway elevated.
    • In MASLD, but not in controls, the liver produced more glucose at night than during the day under low-dose insulin infusion.
    • The body cleared less sugar from the blood at night in both groups, while MASLD participants consistently had about 40% to 60% lower glucose clearance than controls overall, indicating reduced uptake into skeletal muscle.
    • During low-dose insulin infusion, MASLD participants showed a greater nighttime rise in free fatty acids in the blood than controls, and this was linked to higher liver fat levels measured by an ultrasound-based test.
    • At night, insulin levels were lower only in MASLD, even though participants received the same insulin infusion as during their daytime test. This was not a sign of better insulin sensitivity: the body was still responding poorly to insulin, while its own insulin secretion dropped by more than 66% and insulin was removed from the blood faster.
    • Eleven MASLD patients participated in a 12-week lifestyle and weight-loss program. They lost about 6.3% of their body weight and showed improvements in body composition, liver markers, and liver fat. Even so, many nighttime metabolic differences persisted.

    Rather than pointing to a single defect, the findings suggest a nighttime imbalance in how the body handles fuel in MASLD. Normally, insulin helps coordinate how the liver, muscles, and body fat manage sugar and fat during fasting. That coordination appeared weaker at night in MASLD. The researchers also analyzed proteins in the blood and in small samples of fat and muscle tissue to look for underlying biological signals. These patterns pointed to differences in how the body processes fat for energy and how muscles use fuel. However, this was just an additional exploratory analysis that does not prove that these processes are causing the observed effects.

    Overall, the results indicate that nighttime may be an important window for treatment in MASLD, including when people eat, exercise, or take medications, with large evening meals potentially placing greater metabolic stress. Further studies need to confirm the results and are also needed to test whether changing the timing of these lifestyle behaviors improves outcomes. In Q&A #76, I explain how choline and creatine may help protect against fatty liver disease.

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  • A 6-hour eating window led to weight loss and improved hormonal markers in overweight or obese women with polycystic ovary syndrome. doi.org
    Hormones Insulin Resistance Metabolism Time-Restricted Eating

    Polycystic ovary syndrome (PCOS) affects about 1 in 5 women of reproductive age and is often difficult to treat, particularly when it comes to weight loss and hormone balance. In a new randomized trial, researchers tested whether time-restricted eating (TRE) could improve body weight and metabolic health in PCOS patients without requiring calorie counting.

    The study included 76 overweight or obese women aged 18 to 45 with PCOS. For 6 months, one group ate only between 1 p.m. and 7 p.m., one group followed a diet meant to reduce daily calorie intake by 25%, and a control group kept its usual diet while eating across more than 10 hours per day.

    When compared directly with each other, both diets had similar effects, although some outcomes appeared more pronounced for one diet than the other relative to the control group:

    • Body weight fell by about 3.5% with TRE and 3.8% with calorie restriction (CR) from the start of the study, while it increased by 0.9% in the control group.
    • Both intervention groups also reduced fat mass and waist circumference, while lean mass (mostly muscle and other nonfat tissue) changed little.
    • Visceral fat (the deeper abdominal fat stored around internal organs) showed a clearer decrease in the CR group, although this effect was not consistent across all analyses the researchers performed.
    • Total testosterone dropped in both intervention groups. However, TRE had a more pronounced effect on the free androgen index, a measure that estimates how much biologically active androgen is available to body tissues.
    • Both diet strategies lowered fasting insulin and HOMA-IR, a commonly used estimate of insulin resistance.
    • TRE also reduced HbA1c, a marker that reflects average blood sugar over about three months, while CR more clearly lowered fasting glucose and improved QUICKI, an estimate of insulin sensitivity.
    • Common PCOS-related symptoms and risk factors, including irregular cycles, excess hair growth, acne, oily skin, elevated blood pressure, and abnormal blood lipid levels, did not differ clearly between groups. In a follow-up analysis, participants who lost at least 5% of their body weight had slightly more regular menstrual cycles.

    These findings fit with a central biological pattern seen in PCOS. Excess body fat, especially visceral fat, can worsen insulin resistance. In turn, high insulin levels can stimulate the ovaries to produce more androgens, such as testosterone, and can reduce production of sex hormone-binding globulin, a blood protein that binds testosterone and limits how much of it is active. Elevated androgen levels can disrupt ovulation and contribute to common PCOS symptoms. Both diets improved insulin- and androgen-related measures, suggesting better hormonal regulation. However, these improvements did not translate into clear changes in clinical symptoms. This may be because the weight loss was only modest, and prior studies suggest that at least 5% weight loss may be needed to improve PCOS symptoms.

    The study lasted only 6 months and food intake was self-reported. However, for women with PCOS who find daily calorie tracking difficult to maintain, a fixed eating window may offer a simpler option worth considering. In this clip, I discuss with Dr. Layne Norton the benefits, limits, and longevity impacts of time-restricted eating and calorie restriction.

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  • Garlic-derived compounds may extend lifespan and support healthy aging by improving metabolism. doi.org
    Aging Metabolism

    Hydrogen sulfide is a small signaling molecule that the body produces using sulfur-containing compounds. It helps cells respond to stress, generate energy, and regulate how proteins function. Researchers wanted to know whether increasing production of this molecule over time could promote healthy aging.

    The study included a long-term lifespan experiment in healthy male mice starting at 20 weeks of age. Their diet was supplemented with a garlic-derived mixture of diallyl sulfur compounds (molecules with two small carbon-containing "arms" linked by sulfur atoms). To isolate the role of individual components, separate 18-week experiments tested two purified compounds, diallyl disulfide (DAD) and diallyl trisulfide (DAT), under both the standard and a high-fat diet. The researchers also measured plasma protein persulfidation (a hydrogen sulfide–dependent modification that can change how proteins function) in blood samples from 288 humans with multiple chronic health conditions.

    • In the mice, a single oral dose of the garlic-derived diallyl sulfur mixture briefly increased the blood's capacity to generate hydrogen sulfide.
    • Median survival increased from 787 days in untreated mice to 877 days in those receiving the garlic-derived compounds.
    • Treated mice also performed better on tests of grip strength, hanging endurance, coordination, and several forms of memory later in life.
    • DAD and DAT improved insulin sensitivity and physical performance under both diets, with DAD showing stronger improvements in blood sugar control after a glucose drink among mice on the high-fat diet.
    • DAD and DAT shifted liver fat toward smaller droplets compared with untreated mice under both diets. However, the clearest difference was seen under the high-fat diet, which is known to promote liver fat accumulation and larger fat droplets.
    • At the molecular level, the treatments were linked to reduced activity in inflammation-related pathways, lower mTOR signaling (a central metabolic control pathway), and in standard-diet mice, increased protein persulfidation in the liver.
    • In humans, higher plasma protein persulfidation was linked to stronger grip strength and lower triglyceride levels.

    In the liver, storing fat in smaller droplets makes it easier for the body to manage and use it, whereas large fat droplets tend to build up and disrupt normal metabolism, contributing to metabolic stress and poorer blood sugar control over time. At the same time, the liver showed lower activity in inflammation-related pathways and reduced mTOR signaling. mTOR signaling promotes cell growth and energy storage in nutrient-rich conditions, but constant high activity has been linked to shorter lifespan in animal studies, while more balanced activity is associated with better metabolic health. The observed increase in protein persulfidation offers a possible explanation for these changes, as it can directly alter how proteins involved in metabolism and stress responses function.

    The study has important limitations. Results from animal studies cannot be directly translated to humans, and the observations in humans do not prove that these compounds caused the health differences. Even so, if controlled clinical trials confirm similar effects in people, these findings could point to a role for sulfur-containing compounds in supporting metabolic health and healthy aging. To learn more about how garlic affects metabolism, see Q&A #78, where I explore its effects on cholesterol levels.

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  • Prediabetes may be reversible without weight loss through changes in body fat distribution. doi.org
    Diabetes Metabolism Visceral Fat

    Prediabetes, a condition in which markers of blood sugar regulation are higher than normal but not yet in the diabetic range, is typically treated by focusing on weight loss. However, many people struggle to lose weight or keep it off. A new study examined whether people with prediabetes could return to normal blood sugar levels without losing weight, and whether this change affected their future risk of type 2 diabetes.

    The researchers analyzed data from a previous large German lifestyle intervention study, focusing on 234 adults with overweight or obesity (BMI around 30) who maintained or even gained a small amount of weight over one year. Participants underwent detailed metabolic testing, including oral glucose tolerance tests (OGTT, which tracks blood sugar and insulin levels over two hours after consuming a glucose drink) and MRI scans to track fat distribution, and were followed for up to 10 years to monitor whether they developed type 2 diabetes.

    • About 22% of the participants who did not lose weight still returned to normal blood sugar levels after one year, showing that remission can occur without weight loss.
    • Within this group, those who returned to normal blood sugar regulation had a 71% lower risk of developing type 2 diabetes over up to 10 years of follow-up.
    • Participants who improved their blood sugar regulation showed better insulin sensitivity, meaning their bodies responded more effectively to insulin. Measures of how much insulin the body releases and how well the insulin-producing cells (called beta cells) work also moved in a healthier direction, but these changes were not strong enough to draw firm conclusions.
    • Body weight, total body fat, muscle mass, fitness, diet adherence, physical activity, and circulating inflammatory markers showed similar patterns over time in participants who returned to normal blood sugar regulation and those who did not, suggesting that these factors alone did not explain the difference.
    • Participants who improved their blood sugar regulation tended to store fat in a healthier way, with a higher proportion of subcutaneous fat (fat under the skin) compared to visceral fat (fat stored around internal organs), rather than clear differences in individual fat depots.

    These results point to a weight-independent effect related to how fat is distributed in the body. Visceral fat is closely linked to metabolic dysfunction because it is more biologically active and releases fatty acids and inflammatory signals to key metabolic organs such as the liver. This can promote insulin resistance, increase blood sugar production, and strain the pancreas over time. In contrast, subcutaneous fat is better at safely storing excess energy and releases fewer harmful signals, making it less likely to interfere with normal blood sugar control.

    The study was a post hoc analysis, meaning the subgroup was defined after the trial, which limits how confidently cause and effect can be established. In addition, key measures of insulin function were based on indirect calculations rather than gold-standard methods such as the hyperinsulinemic-euglycemic clamp. Overall, the findings suggest that strategies to prevent type 2 diabetes may need to focus not only on weight loss, but also on how the body stores fat. In episode #96, I explain how HIIT, circadian-timed eating, and quality sleep improve metabolic health and reduce chronic disease risk.

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  • Losing visceral fat is linked to slower brain shrinkage and better cognition over time. doi.org
    Brain Metabolism Visceral Fat

    A growing body of research suggests that obesity may be associated with accelerated brain aging, but where fat is stored may be even more important than how much you have. To explore this, researchers followed people for several years to see whether reducing visceral fat, the deep abdominal fat around organs, was tied to better brain health later in life.

    The study included 533 adults, most of them men with an average age of about 61, who had previously participated in clinical trials testing how different diets and lifestyle strategies affect body weight and fat distribution. Those trials lasted about 18 to 24 months. Between 5 and 16 years later, the participants underwent detailed testing, including brain and abdominal MRI scans to assess brain structure and fat distribution, along with standard tests of memory and thinking.

    • Participants with more visceral fat generally had lower scores on a test of overall thinking ability, particularly among those with higher brain volume measures.
    • When the researchers looked at participants with fat measurements taken at three time points (at the start and end of the original trials, and later during this new study), lower long-term exposure to visceral fat was linked to better cognitive and memory scores later in life.
    • Participants who lost more visceral fat during the original intervention period tended to have larger total brain volume and gray matter volume (gray matter contains most of the brain's nerve cells and is essential for processing information). In a smaller group with repeated brain scans, those with lower visceral fat showed a slower decline in gray matter and hippocampal measures (the hippocampus is a key memory center in the brain) over time.

    The researchers also looked at how visceral fat might affect the brain. Measures of blood sugar control were most strongly linked to later brain changes. In particular, fasting glucose and HbA1c stood out more than cholesterol or common markers of inflammation. This suggests glucose regulation may be an important pathway linking visceral fat to brain health. Visceral fat is strongly associated with insulin resistance, a condition in which the body's cells respond poorly to insulin, leading to higher blood sugar levels over time. Over the long term, these changes can damage blood vessels and reduce blood flow to the brain. Other processes, such as inflammation and weakening of the blood-brain barrier (the system that controls what enters the brain) may also play a role.

    Because participants were not randomly assigned after the original trials ended, the study cannot prove that visceral fat loss directly caused the brain benefits. Even so, these findings suggest that where fat is stored may matter more for brain health than body weight alone. In this clip, Dr. Ben Bikman explains the primary causes of insulin resistance and how to reverse it in as little as 90 days.

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  • Hourly 3-minute movement breaks improved blood sugar control in sedentary office workers. doi.org
    Blood Pressure Blood Sugar Cholesterol Exercise Metabolism

    Long hours of sitting in office jobs contribute to metabolic dysfunction, but practical and evidence-based strategies to counter this within daily routines remain limited. In a new randomized trial, researchers tested whether brief bodyweight exercises built into each work hour could improve metabolic health over 12 weeks.

    The study enrolled 86 adults aged 25–55 from three desk-based workplaces who sat more than six hours per day and reported fewer than 150 minutes per week of moderate-to-vigorous physical activity (MVPA). Researchers focused on fasting blood glucose, blood glucose two hours after a standardized glucose drink, and HOMA-IR, an estimate of insulin resistance. One group of participants continued their usual routines, while the other group was instructed to perform seven 3-minute exercise sessions during the 9 AM–5 PM workday using simple movements: marching in place, desk or wall push-ups, squats, heel raises, arm circles with shoulder rolls, and torso twists.

    • Participants reported more energy, less afternoon fatigue, and better productivity.
    • Fasting blood glucose fell by 5.6 mg/dL relative to the control group, 2-hour glucose fell by 10.4 mg/dL, and HOMA-IR decreased by 0.42. HDL cholesterol increased by more than 3 mg/dL, while total cholesterol and LDL cholesterol did not clearly differ between groups.
    • Waist circumference decreased by 2.1 cm relative to control, BMI dropped by 0.4 kg/m², body fat fell by 0.9 percentage points, and systolic blood pressure decreased by 4 mmHg.
    • Among participants with prediabetes, 56% in the intervention group returned to normal glucose levels, compared with 13% of controls.

    Repeated bouts of muscle contraction, particularly in large postural and leg muscles, can stimulate glucose uptake through insulin-independent pathways. This process involves activation of AMP-activated protein kinase (AMPK), a cellular energy sensor that responds to increased energy demand, and promotes translocation of GLUT4, the main glucose transporter that moves glucose from the bloodstream into muscle cells. Spreading the breaks across the day likely enhanced the metabolic benefits by placing some physical activity sessions after meals, when blood glucose rises and regulation is more demanding.

    The study was small and short-term, and did not include dietary tracking, but it points to a simple, low-cost and low-effort strategy that fits into typical workdays. In this clip, Brady Holmer and I discuss how incorporating short bursts of vigorous activity throughout the day can meaningfully impact long-term health and lifespan.

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  • Activity in a specific brain circuit after exercise may drive endurance gains, not just muscle and cardiovascular changes. doi.org
    Brain Exercise Metabolism Neurons

    Most explanations for how exercise training improves endurance focus on changes in muscles and other organs outside the brain. A new study asked whether the brain also helps drive those training adaptations.

    The researchers studied adult mice and combined repeated exercise with brain activity recordings, muscle gene analyses, and techniques that allowed them to selectively silence or activate specific neurons. They focused on steroidogenic factor 1 (SF1) neurons in the ventromedial hypothalamus (VMH), a brain region involved in regulating energy use and metabolism. They compared normal training with conditions where SF1 neurons were prevented from sending signals, or where SF1 neuron activity was increased after exercise sessions.

    • Exercise activated VMH SF1 neurons, and activity in this brain circuit after a workout was necessary for normal endurance gains and some metabolic adaptations to training.
    • When communication between SF1 neurons and other cells was blocked, exercise performance declined, the usual training-related changes in muscle gene activity were largely eliminated, and improvements in endurance were prevented. The mice also shifted to using carbohydrates earlier during exercise, indicating altered fuel use.
    • Increasing the activity of these neurons after workouts enhanced later endurance, suggesting "exercise mimetic" potential, meaning it reproduced some of the effects of exercise.
    • Over time, training made these neurons easier to activate, and this increase occurred alongside better endurance.

    Together, the findings support a body-to-brain-to-body model of training adaptation. The VMH acts as a central regulator of energy balance, integrating signals about the body's fuel state and coordinating hormonal and autonomic responses, such as glucose release from the liver. Repeated activation of SF1 neurons during recovery may create plasticity, the brain's ability to strengthen circuits through experience. These changes may let the brain keep a kind of record of past workouts and influence metabolic responses during future workouts. Those signals may also help enable training-related muscle gene programs and shift fuel use patterns. Training adaptations may therefore depend in part on this learned brain response, not on muscle and cardiovascular changes alone.

    Future research will need to determine whether similar mechanisms operate in humans and whether targeting post-exercise brain activity could help enhance or preserve training benefits in clinical populations.

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  • Blood-flow restriction training, but not conventional strength training, improved mitochondrial function and reduced visceral fat in adults with type 2 diabetes. doi.org
    Diabetes Exercise Metabolism Strength

    Strength training is a cornerstone of type 2 diabetes care, yet heavy lifting is not feasible for all patients. Researchers recently tested whether a modified approach, called blood-flow restriction training (BFRT), could deliver similar strength and metabolic benefits using much lighter weights.

    The randomized study involved 20 inactive adults with type 2 diabetes who trained three times per week for 12 weeks. One group performed BFRT using about 30% of their one-repetition maximum (1RM, the heaviest weight a person can lift once). During each set, inflatable cuffs placed around the upper legs partially reduced blood flow. The comparison group performed conventional resistance training at about 70% of their 1RM without cuffs.

    • Both training programs increased thigh muscle size and leg strength to a similar degree, even though the BFRT group used much lighter weights.
    • Only the BFRT group showed clear improvements in skeletal muscle mitochondrial respiration, which reflects how effectively mitochondria generate cellular energy (ATP). The activity of citrate synthase, an enzyme used as a marker of mitochondrial content, also increased only in this group.
    • Only the BFRT group improved mitochondrial respiration in fat tissue and reduced visceral fat, the fat stored deep in the abdomen around internal organs and strongly linked to insulin resistance and cardiovascular disease risk. In contrast, subcutaneous fat tissue volume decreased only after conventional strength training. Subcutaneous fat tissue lies just under the skin and is generally considered metabolically less harmful than visceral fat.
    • Both groups experienced lower resting heart rate and lower diastolic blood pressure. Body mass index decreased modestly in both groups.
    • Conventional training produced clearer improvements in aerobic fitness and blood triglyceride levels.
    • Neither program clearly enhanced insulin sensitivity, reduced liver fat, or meaningfully altered key insulin signaling proteins in skeletal muscle.

    Restricting blood flow during light exercise creates temporary local oxygen and energy stress, which makes the muscles respond as if they were lifting heavier loads. This stress may help explain the observed increases in AMPK and PGC-1α, key regulatory proteins of mitochondrial biogenesis, the process by which cells build new mitochondria. The training also increased signals linked to angiogenesis, the formation of new blood vessels, which may improve oxygen delivery to muscle and contribute to the observed improvements in mitochondrial function.

    The findings suggest that people with type 2 diabetes can achieve important muscle and metabolic benefits without lifting heavy weights. Larger studies are needed to confirm whether this approach is effective and practical for broader clinical populations. In this clip, Dr. Brad Schoenfeld describes how blood flow restriction is used, its advantages, and its possible drawbacks.

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  • Parkinson's disease is linked to body fat loss and a shift in how the body produces and uses energy. doi.org
    Biomarkers Metabolism Mitochondria Parkinson's

    Unintentional weight loss is common in Parkinson's disease, yet doctors still do not fully understand why it happens. Researchers in Japan examined whether changes in the body's energy chemistry could help explain this pattern.

    The study included 91 people with Parkinson's disease and 47 healthy adults. Researchers estimated body composition using bioelectrical impedance analysis, a method that passes a small electrical current through the body. They also analyzed fasting blood samples to examine molecules involved in how the body produces and uses energy.

    • People with Parkinson's disease weighed less than controls, mainly because they had less body fat. Muscle mass was not clearly different between groups.
    • Blood levels of lactic acid and succinic acid were lower in Parkinson's disease. These molecules are part of glycolysis and the Krebs cycle, two linked processes cells use to extract energy from glucose.
    • Ketone bodies, specifically acetoacetic acid and 3-hydroxybutyric acid, were higher in Parkinson's disease. Ketone bodies are fuel molecules produced from the breakdown of fat.
    • Within the Parkinson's disease group, higher ketone levels were associated with lower body mass index (BMI).
    • Markers of amino acid breakdown, including 2-hydroxybutyric acid and 2-oxobutyric acid, were also elevated in Parkinson's disease patients, suggesting that protein-derived fuels may contribute more to energy supply in Parkinson's disease.
    • The phospholipid phosphatidylcholine (40:2), a fat molecule found in cell membranes, was higher in Parkinson's disease and increased with more advanced disease stages.

    These findings suggest a potential shift in how the body produces and uses energy. Signals of altered carbohydrate metabolism suggest that the body may rely less on glucose for energy. In response, the body may rely more on fat and amino acids as energy sources. This pattern may reflect impaired mitochondrial function, although reduced calorie intake, increased energy expenditure, or medication effects could also contribute. At the same time, higher levels of phosphatidylcholine indicate broader changes in how lipids are handled as the disease advances. Phosphatidylcholine contains fatty acids that can influence membrane stability, oxidative stress, and the clumping of proteins such as alpha-synuclein (a hallmark of Parkinson's disease).

    Future long-term studies that ideally use more precise body composition analysis methods could determine whether these metabolic changes occur early and predict weight loss. If confirmed, blood-based metabolic markers might help clinicians identify patients at higher risk of nutritional decline and guide targeted dietary or metabolic therapies. In Aliquot #114 and Aliquot #115, I discuss supplements and lifestyle factors that boost mitochondrial function and production.

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  • Berry-derived anthocyanins reverse impaired glucose tolerance in adults with prediabetes. doi.org
    Diabetes Metabolism Polyphenol

    Prediabetes affects hundreds of millions of people worldwide, and growing evidence suggests that its different subtypes do not respond uniformly to the same interventions. In a new study, researchers focused on impaired glucose tolerance, a common form of prediabetes marked by high blood sugar after meals, and tested whether a supplement rich in anthocyanins (polyphenols found in berries and other deeply colored fruits) could help the body handle sugar more effectively.

    A total of 68 Chinese adults aged 30 to 60 with isolated impaired glucose tolerance took part in this randomized, double-blind, placebo-controlled trial for 12 weeks. Participants received standard lifestyle guidance and were randomly assigned to take either anthocyanin capsules (160 mg per day) or a placebo. The researchers measured how well participants processed glucose using an oral glucose tolerance test (OGTT), which tracks blood sugar and insulin levels after a glucose drink. They examined insulin sensitivity, meaning how effectively the body responds to insulin, and beta-cell function, which reflects how well the pancreas releases insulin.

    • More than half of participants taking anthocyanins returned to normal glucose tolerance, compared with less than one-third of those taking placebo.
    • Insulin sensitivity improved more in the anthocyanin group, measured by the Matsuda index, a calculation that reflects how well the body uses insulin during the OGTT.
    • Insulin levels one and two hours after the glucose drink dropped more in the anthocyanin group, suggesting the body needed less insulin to manage blood sugar.
    • The study's main beta-cell function measure, the oral disposition index, did not clearly differ between groups.
    • Overall blood sugar exposure after the glucose drink declined with anthocyanins but changed little with placebo.
    • Levels of advanced glycation end products (AGEs) in the skin fell in the anthocyanin group. These compounds form when sugars bind to proteins and are considered markers of long-term metabolic stress.

    The findings indicate that improved insulin sensitivity, rather than increased insulin secretion, explains the remission of impaired glucose tolerance. A central mechanistic signal was the reduction in skin AGEs, which correlated modestly with improvements in overall glycemic exposure and insulin sensitivity, supporting a biologically meaningful link. This is consistent with evidence that AGEs can impair insulin's effectiveness by chemically binding to insulin itself and to insulin receptors. Anthocyanins may reduce AGE burden by neutralizing reactive sugar byproducts and limiting AGE-driven inflammation.

    Although larger and longer trials are needed, these findings suggest that anthocyanin supplementation may represent a targeted, nutrition-based strategy for managing impaired glucose tolerance. In Q&A #61, I discussed strategies for diagnosing prediabetes and managing it through lifestyle changes.

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  • Genetic evidence ties higher blood caffeine levels to lower body fat and reduced type 2 diabetes risk. dx.doi.org
    Caffeine Coffee Metabolism

    Caffeine is a widely consumed psychoactive substance, but its long-term metabolic effects are often hard to isolate because coffee, tea, and soft drink habits correlate with many other health-related behaviors. To address that problem, researchers used human genetics to ask whether long-term differences in blood caffeine levels relate to adiposity and cardiometabolic disease.

    The researchers applied a method called Mendelian randomization, which uses naturally occurring genetic differences to explore cause-and-effect relationships. Because inherited genetic variants are fixed at conception, they create natural groups that are largely not shaped by later habits or environmental factors. In this study, the researchers focused on two genetic variants near the CYP1A2 and AHR genes, which are involved in regulating how caffeine is metabolized in the body. The team then linked these caffeine-related differences to large genetic datasets containing information on body mass index (BMI, a weight-to-height measure), body fat, type 2 diabetes, and major cardiovascular diseases.

    • People with genetic variants linked to higher predicted blood caffeine tended to have lower BMI.
    • Higher genetically inferred blood caffeine levels were associated with lower whole-body fat mass, while lean mass, which includes muscle and organs, showed no meaningful change.
    • Individuals with genetically predicted higher caffeine levels had a lower risk of type 2 diabetes.
    • When the researchers examined possible pathways, they estimated that about 43% of the lower diabetes risk could be attributed to reductions in BMI.
    • No strong links were found between higher predicted blood caffeine levels and major cardiovascular diseases, including ischemic heart disease, atrial fibrillation, heart failure, or stroke.
    • The same genetic variants linked to higher caffeine levels were also associated with drinking less coffee and tea, likely because people who metabolize caffeine more slowly tend to consume less of it to achieve the same stimulant effects.

    Slower caffeine breakdown keeps circulating levels elevated for longer periods, which may increase energy expenditure through caffeine-induced thermogenesis and fat oxidation. Experimental work suggests caffeine enhances mitochondrial activity, increases sympathetic nervous system signaling, and shifts brown fat tissue toward a more metabolically active state. Caffeine has also been shown to increase satiety and reduce energy intake in some settings. Over years, even small increases in daily energy expenditure and decreases in energy intake could meaningfully alter fat accumulation and downstream insulin signaling.

    Because this genetic analysis reflects lifelong caffeine exposure rather than a specific intake level, it cannot indicate an effective dose, and its reliance on only two variants from mostly European datasets further limits precision. Even with these constraints, the study provides causal evidence linking sustained caffeine exposure to metabolic benefits. In episode #103, I synthesize extensive research to illuminate how the timing, brewing methods, and additives to coffee influence its health benefits and risks.

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  • Ultra-processed foods impaired metabolism and reproductive health in men, even without excess calories. doi.org
    Diet Inflammation Metabolism Obesity Ultra-Processed Foods Reproductive Health

    Modern diets are often dominated by ultra-processed foods (UPFs), yet scientists still debate whether their harm arises mainly from their tendency to drive excess calorie intake or also from other aspects of industrial processing. To test this, researchers at the University of Copenhagen conducted a tightly controlled crossover study in healthy men.

    The study enrolled 43 men aged 20 to 35, each randomized to two 3-week diet phases with a 12-week break between them. Both meal plans were matched for calories and macronutrients, but differed sharply in composition: the ultra-processed version supplied about 77% of calories from UPFs, while the minimally processed plan contained less than 1%. One study arm received adequate calories based on estimated energy expenditure and the other received 500 calories per day in excess.

    Results showed that processing level, not just calories, shaped health outcomes:

    • Men gained about 1.3 to 1.4 kilograms more (mostly from increased fat mass) on the ultra-processed diet than on the minimally processed diet, in both the adequate- and excess-calorie groups.

    Adequate-calorie group:

    • Total cholesterol and the LDL-to-HDL ratio were higher on the ultra-processed diet than on the minimally processed diet — both signs of worse lipid balance.
    • The signaling molecule interleukin-4 (IL-4) increased on the ultra-processed diet. IL-4 is a cytokine with a dual role in immunity, promoting both allergic responses and supporting anti-inflammatory and tissue-repair processes.

    Excess-calorie group:

    • Diastolic blood pressure was higher on the ultra-processed diet than on the minimally processed diet.
    • Growth differentiation factor-15 (GDF-15) decreased on the ultra-processed diet. GDF-15 is a mitochondrial stress signal that promotes energy expenditure and appetite suppression.
    • Follicle-stimulating hormone (a hormone essential for sperm development) was lower on the ultra-processed diet, yet sperm concentration did not change.

    Because calories and macronutrients were matched and estimated intake was similar within arms, the findings indicate effects attributable to processing level itself. The researchers suggest several explanations, including that the processing may increase the usable energy of foods or influence hormones that regulate appetite and metabolism. Packaging chemicals and additives might also contribute through subtle endocrine effects.

    The study was brief, so some effects may not have had time to fully manifest, and it also depended on participants strictly adhering to the prescribed diets. Additionally, the findings published so far are not the main outcome the study was originally designed to test, but rather exploratory health measures the researchers chose to examine as well — so they should be viewed as early signals rather than firm conclusions. However, the pattern suggests that reducing heavily processed foods could benefit both metabolic and reproductive health. In this clip, I explain how ultra-processed foods impact appetite, inflammation, and long-term disease risk.

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  • Combining vitamin D supplementation with regular exercise shows a significant reduction in insulin resistance and improved lipid regulation, potentially offering an innovative approach to managing type 2 diabetes and related metabolic disorders. doi.org
    Cholesterol Diabetes Exercise Insulin Resistance Metabolism Vitamin D Triglycerides

    Despite ongoing prevention efforts, type 2 diabetes and related metabolic disorders affect millions worldwide, but the strategic combination of two common lifestyle approaches may offer new potential for disease management. Researchers tested whether combining vitamin D supplementation with structured exercise improves blood sugar control, lipid levels, and vitamin D status more than either approach on its own.

    This work pooled 18 randomized controlled trials in adults, totaling 1,104 participants drawn from groups with varying health conditions. Interventions paired vitamin D supplementation, with doses from 400 to 8,000 international units per day or 50,000 international units per week, with aerobic, resistance, or interval training delivered for 4 weeks to 18 months. The study looked at how the combination stacked up against exercise alone, vitamin D alone, and no intervention, as well as how each single approach compared with doing nothing.

    Combining vitamin D supplementation with regular exercise outperformed the control group and often exceeded single interventions across several metabolic outcomes:

    • The combined intervention lowered fasting insulin more than control, exercise alone, and vitamin D alone.
    • Insulin resistance fell with the combined strategy versus control and vitamin D alone; both single interventions also beat control.
    • Fasting glucose decreased with the combined approach compared with control.
    • The combined strategy reduced triglycerides and raised HDL cholesterol compared with vitamin D alone.
    • Serum 25-hydroxyvitamin D, the circulating form of vitamin D used to assess vitamin D status, increased with the combined approach versus control and exercise alone, but not versus vitamin D alone.
    • As a single intervention, vitamin D lowered LDL cholesterol compared with control.

    The improvements seen with the combined approach may reflect how exercise and vitamin D influence overlapping pathways. Exercise can increase the activity of 1α-hydroxylase in muscle, the enzyme that converts vitamin D into its active form, and it may also enhance the expression of the vitamin D receptor, which improves the ability of cells to respond to vitamin D signaling. When supplementation raises circulating 25-hydroxyvitamin D, more substrate becomes available for this activation. Stronger vitamin D signaling helps reduce inflammation and regulate glucose metabolism, in part by supporting insulin production and efficiency. Acting together, these processes provide a plausible explanation for the observed improvements in insulin resistance and lipid regulation beyond the well-established effects of exercise on metabolic health.

    Conclusion:
    Taken together, combining vitamin D supplementation with structured exercise may improve metabolic health compared with either approach alone, with the clearest advantages seen for fasting insulin and partial benefits in insulin resistance and lipid outcomes. While the results are promising, several cautions apply, including small trial sizes, uneven reporting, medication use that could confound effects, limited ability to analyze dose and training frequency, and high heterogeneity for some outcomes. However, since both strategies are generally safe, accessible, and inexpensive, the study highlights the importance of maintaining sufficient vitamin D levels and engaging in regular exercise. More importantly, the findings reinforce the need to approach metabolic health from multiple angles rather than relying on a single lifestyle change, with the potential for combined strategies to produce synergistic benefits over time. Learn more about how to improve metabolic health in episode #96.

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  • Single course oral fecal microbiota transplant in adolescents with obesity linked to lower body fat and metabolic risk four years later. doi.org
    Cholesterol Inflammation Metabolic Syndrome Metabolism Microbiome Weight Loss

    Adolescent obesity often persists into adulthood and raises cardiometabolic risks, but altering the gut microbiome may help shift long-term health trajectories. Researchers tested whether taking capsules containing gut microbes from healthy donors during adolescence could leave durable clinical and microbiome changes years later.

    Researchers followed up on a previous trial where adolescents received either gut microbiota from healthy lean adults or a placebo. About four years later, 55 participants returned for assessment. The team measured body composition, metabolic markers, and gut microbial and viral profiles using DNA sequencing.

    At the four year visit, several cardiometabolic and body composition measures favored the transplant group:

    • Waist circumference was 10 cm lower in the fecal transplant group.
    • Total body fat percentage was 4.8 points lower.
    • A metabolic syndrome severity score was lower.
    • The inflammation marker hs-CRP was 68 percent lower.
    • HDL cholesterol was 0.16 mmol per liter higher.

    These health differences were accompanied by lasting shifts in the gut microbiome. Adolescents who received donor microbes had a more diverse and markedly reshaped gut microbiome compared with placebo. Signatures of donor bacteria could still be detected years later, and participants who took up more donor strains soon after treatment tended to retain more of them long term. The gut bacteriophages – viruses that infect bacteria – also showed lasting donor patterns. Some of these microbial and viral differences were linked with healthier metabolic scores and weight change, although these links cannot prove cause and effect.

    Conclusion:
    A single course of oral fecal microbiota transplant during adolescence was followed by lower central adiposity and body fat, lower systemic inflammation, and a better composite metabolic risk score about four years later, while BMI remained similar. However, it's important to mention that BMI is a limited measure because it doesn't distinguish between fat and lean mass and can therefore miss meaningful shifts in fat distribution. The gut microbiome continued to show donor traits, which might help explain the observed health effects. However, the study has limitations: it was unblinded, had high dropout rates, didn't track medication or lifestyle changes continuously, and used a statistical approach that may increase false positives. Overall, the results are promising, but they warrant cautious interpretation and further confirmation. Learn more about the microbiome in episode #70 featuring Dr. Eran Elinav.

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  • Boosting glycogen breakdown in neurons with tau-related damage improves symptoms of neurodegeneration, a potential strategy for Alzheimer's and related diseases. www.nature.com
    Alzheimer's Blood Sugar Brain Dementia Metabolism

    Neurodegenerative diseases like Alzheimer's disease and frontotemporal lobar degeneration are characterized by the abnormal buildup of tau, a protein that damages brain cells and drives cognitive decline. A recent study found that tau-related disorders in both fruit flies and humans are closely linked to neuronal accumulation of glycogen—the stored form of glucose—and that breaking down this glycogen substantially reduces tau-related brain damage.

    In this study, researchers used fruit flies genetically engineered to produce a harmful form of human tau protein, as well as neurons derived from human stem cells taken from people with frontotemporal lobar degeneration. They tested how diet and enzymes involved in glycogen breakdown affected brain cell health, analyzed molecular changes through metabolomics and genomics, and examined how tau protein interacts with glycogen inside cells.

    They found that both fruit flies and human neurons with tau-related damage had unusually high levels of glycogen. When they boosted the activity of an enzyme called glycogen phosphorylase, which breaks down glycogen, symptoms of tauopathy improved dramatically: The fruit flies showed fewer signs of neurodegeneration, and human neurons became healthier. Dietary restriction had similar effects by naturally increasing glycogen breakdown, redirecting glucose metabolism away from energy production and toward a stress-reducing pathway called the pentose phosphate pathway.

    These findings suggest that tau-related brain diseases worsen when glycogen builds up in neurons, and that breaking down this excess sugar protects brain cells. By interrupting what appears to be a vicious cycle between glycogen and tau accumulation, this approach could offer a powerful new direction for treating Alzheimer's disease, frontotemporal lobar degeneration, and related conditions. Intermittent fasting promotes the breakdown of glycogen, likely contributing to its brain-protective effects. Learn more in this clip featuring Dr. Mark Mattson.

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  • Individual responses to carbohydrate intake vary widely due to metabolic health factors, with insulin-resistant individuals experiencing greater blood sugar spikes from foods such as rice and potatoes. www.nature.com
    Carbohydrates Diet Insulin Resistance Metabolism

    Not everyone handles carbohydrate intake the same way. In fact, the spike in blood sugar that follows a meal—called the postprandial glycemic response—can vary widely between individuals, even when they eat the same food. A recent study found that individual responses to carbohydrate-rich meals, such as rice or potatoes, depended strongly on a person's underlying metabolic health, with people who were more insulin resistant showing much greater blood sugar spikes.

    Researchers measured blood glucose levels continuously in 55 participants (using continuous glucose monitors) as they ate seven standardized carbohydrate meals, including bread, rice, potatoes, and grapes. They also tested whether "preloading" a carbohydrate-rich meal with fat, protein, or fiber could blunt blood sugar spikes. Participants underwent intensive metabolic testing and provided blood and stool samples so the researchers could analyze insulin resistance, beta cell function, blood lipids, proteins, and gut microbes.

    The study revealed striking differences between individuals in their responses to different carbohydrate meals. Rice triggered the highest average blood sugar spike, but the size of that spike varied by person. For example, people who responded most strongly to potatoes were 25% more likely to be insulin resistant and have weaker beta cell function, while those who spiked after grapes were more insulin sensitive. Those who spiked in response to rice were more likely to be Asian; those who spiked in response to bread tended to have higher blood pressure. Preloading with fat, fiber, or protein worked better for people with good insulin sensitivity.

    Molecular analyses revealed that insulin-resistant participants had higher levels of triglycerides linked to poor metabolic health, while those with elevated blood pressure showed distinct patterns in circulating metabolites. The gut microbiome also differed between high and low responders, with microbial pathways involved in carbohydrate metabolism more active in those with larger blood sugar spikes.

    These findings suggest that a one-size-fits-all approach to managing blood sugar may fall short. Understanding a person's unique metabolic profile—as well as their microbiome—may be essential for preventing or managing conditions like type 2 diabetes and cardiovascular disease. Learn more about the gut microbiome's role in regulating blood glucose and cholesterol in this clip featuring Dr. Michael Snyder, the lead investigator on this study.

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  • 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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  • 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.

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  • 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.

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  • 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

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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

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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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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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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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  • 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.

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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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  • 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.

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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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  • 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.

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  • 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.

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  • 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.

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  • 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.”

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  • 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.

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  • 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.”

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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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  • Researchers discover fundamental roles of glucosamine in brain www.sciencedaily.com
    Brain Metabolism

    Glucosamine plays important roles in brain function.

    Glucosamine is a type of sugar found in the muscles, cartilage, and other soft tissues of the body. It is commonly marketed as a dietary supplement used for joint pain and stiffness. Evidence from a 2021 study suggests that glucosamine is prevalent in brain glycogen, where it plays important roles in glycosylation.

    Glycogen is a multi-branched polysaccharide that serves as the stored form of glucose in the human body. Most of the body’s glycogen stores are found in the muscles and liver, but some glycogen is found in the brain, primarily in the astrocytes, a type of cell involved in neurogenesis and blood-brain barrier maintenance. In diseases in which glycogen storage is impaired, glycogen-like cellular aggregates called polyglucosan bodies can form in the brain, altering brain function and driving dementia.

    Glycosylation is a biochemical process in which glucose is added to an amino acid. It plays important roles in determining the structure, function, and stability of proteins. Glycosylation influences neurological function, and disturbed glycosylation is implicated in the pathogenesis of many neurological disorders, including cognitive decline.

    The investigators conducted a multi-part study. First, they determined the overall composition of the sugars in the glycogen of liver, muscle, and brain tissue of mice using gas chromatography and mass spectrometry. They found that liver glycogen contained just 0.1 percent glucosamine, and muscle glycogen contained approximately 1 percent of the sugar. However, brain glycogen contained 25 percent glucosamine.

    Then, using a special form of mass spectrometry (called “MALDI TW IMS”), they quantified and tracked the movement of the glucosamine in the brains of healthy mice and mice that had glycogen storage diseases. They found that the mice with the glycogen storage diseases had impaired glucosamine movement, abundant polyglucosan bodies, and evidence of impaired cell metabolism and glycosylation.

    These findings suggest that glucosamine in brain glycogen is essential for brain health. They also may help identify strategies for treating glycosylation disorders, which cause severe neurological symptoms, including dementia.

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  • Divergent effects of resistance and endurance exercise on plasma bile acids, FGF19, and FGF21 in humans pubmed.ncbi.nlm.nih.gov
    Exercise Metabolism Hormones FGF21

    Endurance and resistance training are associated with distinct hormonal signatures Exercise is widely accepted to be beneficial to our health. Research finds it to have a positive dose-dependent impact on factors varying from cognitive function and bone strength to all-cause mortality and metabolic health. But does the specific mode of exercise make a difference? A 2018 study suggests that resistance and endurance exercise engage largely distinct hormonal responses in the body. It also highlights endurance training as a particularly useful tool for engaging biochemical signals that can help combat substance addiction.

    To compare resistance and endurance training, researchers recruited ten healthy young men (average age 24 years) to participate in a cross-over study. This meant that each participant engaged in both forms of exercise, with half randomly selected to first perform a one-hour endurance training session before “crossing over” to one resistance training session after a 6-to-12-day rest period. The other half of the participants followed the reverse order.

    Training sessions were individually tailored to ensure equivalent levels of physiological stress across participants. For instance, resistance training sessions required participants to complete five sets of 10 reps for each exercise, at resistance levels corresponding to 90 percent of their 10 rep maximum capacity. The endurance training sessions were designed to make participants work at 70% of their VO2max(i.e. maximum oxygen uptake capacity). Importantly, participants exercised 10 hours after receiving controlled meals to prevent nutritional factors from interfering with hormone levels in their blood, which was drawn immediately before and at several timepoints after exercise.

    The experiment revealed some surprising insights into the hormonal pathways engaged by the two forms of exercise. Shortly after resistance training, participants had lower plasma levels of fibroblast growth factor 19 (FGF19) – a protein secreted by the small intestine and implicated fighting metabolic disease by stimulating the formation of metabolically active brown fatty tissue and increasing sensitivity to the satiety hormone leptin. The drop in FGF19 shortly after resistance exercise is somewhat counterintuitive given robust links between strength training and metabolic health. It raises questions about a potential long-term rebound increase following recovery, which our team looks forward to seeing explored in future studies.

    Endurance exercise engaged a distinct biochemical pathway. It caused a near-triple increase in the pancreatic hormone glucagon, which stimulates the release of glucose and fatty acids into the blood. This glucagon spike was followed by an increase in plasma fibroblast growth factor 21 (FGF21) – a metabolic regulator implicated in processes ranging from fatty acid oxidation and ketone body production to the regulation of appetite for addictive substances like alcohol. The findings suggest that endurance and resistance training are associated with distinct hormonal and metabolic benefits, and that endurance exercise in particular may be a helpful strategy in combating addiction.

    Link to full study

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  • 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.

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  • 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.

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  • 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.

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  • 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.

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  • Milk chocolate exerts differential health effects, depending on the timing of consumption. www.the-scientist.com
    Metabolism Microbiome Sleep Circadian Rhythm Dairy Blood Sugar

    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.

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  • The effect of acute sleep deprivation on skeletal muscle protein synthesis and the hormonal environment www.ncbi.nlm.nih.gov
    Sleep Metabolism Hormones Cortisol Testosterone Muscle Protein

    Poor sleeping habits impair normal cognitive and metabolic function and are associated with worse mental and physical health outcomes in the short- and long-term. Sleep loss may also interfere with protein synthesis, driving skeletal muscle losses, a risk factor for obesity, type 2 diabetes, and frailty. Authors of a recent report measured the effects of sleep deprivation on muscle protein synthesis.

    Skeletal muscle is metabolically active. Having more muscle mass promotes insulin sensitivity and reduces the risk of developing type 2 diabetes. Previous research in rats has shown that sleep deprivation reduces the activity of enzymes that build muscle, such as testosterone and insulin-like growth factor (IGF)-1, and increases the activity of enzymes that break down muscle, such as cortisol. The same shift in hormones may occur in humans deprived of sleep.

    Thirteen young adults (average age, 21 years) completed two testing days in random order in which they experienced one night of sleep deprivation and one night of normal sleep. On one day, participants consumed a standardized meal at home at 7 p.m., reported to the laboratory at 9 p.m., and were not permitted to sleep until 7 a.m. During the night, participants were allowed to engage in quiet activities and eat low-protein fruits and vegetables as snacks. On the other day, participants consumed a standardized meal at home at 7 p.m., then slept at home between 10 p.m. and 7 a.m.. On both days, researchers collected blood samples and muscle tissue samples, following a standardized breakfast meal.

    One night of sleep deprivation reduced muscle protein synthesis by 18 percent. This was accompanied by a significant 24 percent reduction in serum testosterone levels in male participants and a significant 21 percent increase in cortisol levels in all participants. There was no difference in plasma insulin or IGF-1 levels and no difference in markers of muscle protein degradation.

    The authors concluded that just one night of sleep deprivation interferes with muscle protein synthesis. Chronic sleep deprivation may cause loss of muscle mass due to long-term suppression of muscle-building enzymes.

    The good news is exercise is known to counter at least some of the negative effects that sleep loss has on metabolism. For example, high-intensity interval training before a night of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids caused by lost sleep in healthy males.

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  • Added sugars decrease metabolic health, survival, competitive ability, and reproduction in mice at human-relevant doses. www.sciencedaily.com
    Sugar Metabolism Cholesterol Mortality Blood Sugar Sugar-Sweetened Beverages Reproductive Health

    Average sugar consumption in the United States has increased 50 percent since the 1970s, due in part to the use of high fructose corn syrup in beverages and other processed foods. The mechanisms by which added sugars lead to metabolic diseases such as obesity, type 2 diabetes, cardiovascular disease, and fatty liver disease have been explored in research using mouse models; however, the dose of sugar used in these animal studies is usually much larger than what is normally consumed by people. Authors of this report investigated the effects of human-relevant doses of added sugars on health and behavior in mice.

    Mouse models are a useful tool in research because mice can be kept in environments where their exposure to light, food, socialization, and other environmental inputs is completely controlled, minimizing variation between mice when exposed to a dietary intervention. However, these highly controlled environments, combined with large doses of experimental foods, often limit the generalizability of mouse research for human health. Organismal performance assays, which use seminatural conditions to put experimental animals in direct competition with each other, more accurately measure survival, competitive ability, and reproduction (common measures of evolutionary fitness) in response to environmental exposures.

    The investigators fed one group of mice a diet containing 25 percent of calories from a 1:1 mixture of fructose and glucose, the same ratio of sugars found in beverages and processed foods containing high fructose corn syrup. They fed a second group of mice a control diet in which the added sugars were replaced with cornstarch and fiber. Both groups of mice consumed their respective diets and lived in controlled environments for 26 weeks before entering the organismal performance assay, upon which all mice consumed the high-sugar diet. The researchers observed mice as they competed for territory, resources, and mates for 26 to 32 weeks.

    Female mice fed a high sugar diet prior to entering the organismal performance assay were twice as likely to die than female mice fed a normal diet. Male mice fed a high sugar diet controlled 26 percent less territory and produced 25 percent less offspring compared to mice fed a normal diet prior to entering the organismal performance assay. A high-sugar diet increased fasting cholesterol levels and decreased glucose tolerance.

    The authors concluded that a high sugar diet decreased survival, competitive ability, and reproduction in mice and led to metabolic dysfunction. This study was the first to use organismal performance assays in combination with an environmental intervention and the first to demonstrate the negative health effects of added sugars in mice at human-relevant doses.

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  • Short bouts of high-intensity interval training promote cardiometabolic health. www.sciencedaily.com
    Exercise Metabolism Insulin Cardiovascular

    Exercise training provides a wide range of physiological benefits that help maintain cardiovascular health. Although most people acknowledge the benefits of exercise, many people do not exercise, often due to the time commitment involved in regular training. A recent review describes the cardiovascular benefits associated with short-duration high-intensity interval training.

    High-intensity interval training, often referred to as HIIT, is a popular form of exercise involving short bursts of intense aerobic exercise interspersed with periods of rest or lower-intensity exercise. A classic example of HIIT is combining sprints (high-intensity) with jogging (low-intensity). During a typical HIIT session, exercisers typically achieve 80 to 100 percent of their VO2max (a measure of respiratory function) or maximum heart rate. Most HIIT workouts are brief, lasting just 15 to 30 minutes.

    An abundance of research has demonstrated that short bouts of HIIT improves cardiorespiratory fitness, metabolic function, and body composition, among other effects, even in the absence of clinically significant weight loss. The mechanisms that drive these effects are thought to be related to improvements in muscle tissues' oxidative capacity, enhanced insulin response, and improvements in heart function (specifically, left ventricle ejection fraction) and vascular compliance (an indicator of blood vessel elasticity and storage capacity).

    Short bouts of HIIT elicit many of the same health benefits that longer bouts of HIIT or traditional forms of exercise (sometimes to a greater extent) and are considered safe, even for inactive people. The authors of the review posit that such types of activity offer a means to improve cardiometabolic health in inactive people, requiring little time commitment and modest effort.

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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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  • Exercise improves markers of cardiometabolic health. www.sciencedaily.com
    Exercise Metabolism Insulin Resistance Nitric Oxide Brown Fat Cardiovascular

    Exercise exerts a wide range of beneficial effects on the human body that influence cardiovascular, metabolic, and overall health. The molecular mechanisms that drive these effects are not widely understood, however. Findings from a new study provide insights into the molecular cardiometabolic response to acute exercise.

    The study involved 471 adults (average age, 54 years) enrolled in the Framingham Heart Study, a long-term, ongoing study of cardiovascular disease risk among people living in Framingham, Massachusetts. The authors of the study measured levels of 588 metabolites in blood drawn from the participants before and immediately after ergometric cardiopulmonary exercise testing. They replicated these methods in a second group of 783 participants.

    The authors noted changes in 508 of the metabolites. In particular, they observed changes in metabolites implicated in cardiometabolic risk, including reduced levels of those involved in insulin resistance and increased levels of metabolites associated with lipolysis, nitric oxide bioavailability, and adipose browning – the process by which white adipose tissue converts to brown adipose tissue, increasing energy expenditure and improving glucose and lipid metabolism. These changes were diminished among participants with a higher BMI, suggesting that obesity (or the metabolic disturbances that accompany it) may block the benefits of exercise.

    These findings provide insights into the molecular mechanisms that drive the widespread cardiometabolic benefits of exercise and support public health recommendations to engage in regular physical activity.

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  • Time-restricted eating improves insulin sensitivity in healthy men. academic.oup.com
    Time-Restricted Eating Metabolism Fasting Circadian Rhythm Muscle Insulin Blood Sugar Weight Loss

    Insulin sensitivity refers to how well the body’s cells respond to insulin – a critical aspect of maintaining healthy blood glucose levels. Lifestyle behaviors and dietary modification may help improve insulin sensitivity. Findings from a new study suggest that early time restricted eating improves insulin sensitivity.

    Time-restricted eating is a form of daily fasting that aligns the eating and fasting cycles to the body’s innate 24-hour circadian system. People who practice time-restricted eating typically eat during an 8- to 12-hour daytime window and fast during the remaining 12 to 16 hours. Unlike intermittent fasting, which involves caloric restriction, time-restricted eating permits a person to eat as much as they want during the eating window.

    The intervention study involved 16 healthy young men (average age, 23 years) who were moderately active and had BMIs between 18 and 27. After an overnight fast, the men underwent indirect calorimetry testing to determine their resting metabolic rate – the rate at which the body burns calories when at rest. The men wore continuous glucose monitors and tracked their dietary intake and physical activity.

    After a one-week baseline period, the men’s metabolic response to a liquid test meal containing carbohydrates and protein was assessed. Eight of the men began the time-restricted dietary pattern, in which they consumed all their calories (eating whatever they wanted) during a window between 8 a.m. and 4 p.m. – considered “early” time-restriction. Nine months later, another group of eight men took part in the same process, but they ate whenever they wanted to, but their caloric intake was matched to that of what the men ate during the time-restricted eating period (which was about 400 calories per day lower than usual due to the limited time frame in which they ate). Both interventions lasted two weeks, after which both groups of men underwent metabolic testing again.

    The men who followed the time-restricted eating pattern reduced their overall caloric intake and lost more weight, compared to the men who followed a calorie-restricted diet. Similarly, the men following the time-restricted diet experienced improvements in their whole-body insulin sensitivity as well as skeletal muscle uptake of glucose and branched-chain amino acids. The two groups of men had similar physical activity levels.

    These findings demonstrate that early time-restricted eating improves insulin sensitivity and promotes weight loss in health men and has potential applications for interventions in people who are metabolically compromised. You can read about time-restricted eating in our overview article.

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  • Alpha-lipoic acid supplements promote weight loss in obese people who are otherwise healthy. www.sciencedaily.com
    Obesity Metabolism Antioxidant Weight Loss Supplements

    Obesity is a major contributor to many of the leading causes of death, including cardiovascular disease, stroke, diabetes, and cancer. More than 650 million adults are obese worldwide. Findings from a new study suggest that alpha-lipoic acid promotes weight loss in obese adults.

    Alpha-lipoic acid is a naturally occurring substance present in the human body and in some foods. It is a powerful antioxidant that amplifies the beneficial effects of other antioxidants in the body such as glutathione and coenzyme Q10. Alpha-lipoic acid participates in metabolism by inhibiting fatty acid and triglyceride synthesis and, in turn, promoting fatty acid oxidation, triglyceride clearance from the liver, and fat loss. Dietary sources of alpha-lipoic acid include spinach, broccoli, and organ meats, among others. It is widely available as a dietary supplement.

    The randomized, double-blind, controlled trial involved 81 overweight or obese adults between the ages of 21 and 60 years who had elevated triglycerides but were otherwise healthy. Half of the participants took 600 milligrams of alpha-lipoic acid per day, while the other half took a placebo. The participants were asked to not change their diet or physical activity for the duration of the 24-week study. The authors of the study took anthropometric measures, checked vital signs, and collected blood and urine samples from the participants at the beginning of the trial, at week 12, and at week 24.

    The authors found that the participants who took alpha-lipoic acid did not experience changes in their triglyceride levels, but they did lose body weight. The greatest losses were observed among women and obese participants, who lost as much as 5 percent of body weight. Those who took alpha-lipoic acid also had higher levels of antioxidant enzyme expression, which is associated with reduced inflammation – a key driver in many diseases.

    These findings demonstrate that alpha-lipoic acid reduces body fat in overweight or obese people, independent of dietary or physical activity changes.

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  • Perchlorate, a pollutant in water, harms human health. www.eurekalert.org
    Pollution Metabolism Hormones Pregnancy Development Environment

    Perchlorate, a chemical used to propel rockets and airbags, accumulates in the environment as a pollutant. A new study suggests that perchlorate can enter the water supply and might be more detrimental to human health than previously thought.

    Perchlorate is transported from the blood into the thyroid gland by the sodium/iodide symporter, or NIS, which usually transports iodide and sodium. Iodide, the negatively charged form of iodine, is involved in producing thyroid hormone, which plays an important role in metabolism and development.

    Previous research has demonstrated that sodium and iodide are co-transported by the NIS symporter in a two to one ratio in an energetically favorable reaction. The current study investigated the mechanism by which perchlorate affects the function of this transporter.

    The authors of this cell culture study used radioactive iodine to determine how perchlorate influenced iodide transport across the NIS symporter. Using varying concentrations of perchlorate, they measured how much iodide was transported compared to sodium.

    The authors found that perchlorate inhibited the transport of iodide in two ways. First, it competed with iodide for a receptor site. In a second mechanism, perchlorate altered the shape of the transporter by blocking one of the two sodium binding sites. Normally, iodide is co-transported into thyroid cells with two sodium ions, providing the energy required to drive iodide into the cell. When perchlorate blocks one of the sodium binding sites, a single sodium ion is transported with iodide in a less energetic reaction. This slower iodide transport means that less iodide reaches the thyroid gland leading to lower thyroid hormone production.

    These findings suggest that perchlorate in the environment, even at low levels, can decrease the amount of iodide taken up by the thyroid gland. The resulting reduction in thyroid hormone production can be harmful to health, particularly to sensitive populations, including pregnant women, fetuses, and nursing infants.

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  • 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.

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  • Eating earlier in the day promotes lipid oxidation (fat burning). www.sciencedaily.com
    Fasting Metabolism Circadian Rhythm Fat

    Circadian rhythms, the body’s 24-hour cycles of biological, hormonal, and behavioral patterns, modulate a wide array of physiological processes, including the body’s production of hormones that regulate hunger, metabolism, sleep, and others. A new study suggests that circadian rhythms influence body weight by impairing lipid oxidation – the burning of fat.

    The small study, which was conducted in two sessions, involved six healthy adults between the ages of 51 and 63 years old whose BMIs were between 22.2 and 33.4 (normal to obese). During the first session, the participants received three meals per day: breakfast (700 calories), lunch (600 calories), and dinner (1,000 calories). The second session differed in that instead of receiving breakfast, the participants received a late-night (10 PM) snack (700 calories). The overnight fast was approximately 14 hours, regardless of whether the participants ate breakfast or the late evening snack.

    The authors of the study monitored the participants' metabolism in a whole-room respiratory chamber during the two sessions, which lasted 56 hours each. They found that eating a late-night snack rather than an isocaloric breakfast markedly altered the participants' capacity to burn fat, and this shift in metabolism was driven by circadian rhythm-regulated metabolic patterns. These findings suggest that late-night eating may drive body fat accumulation and subsequent increased risk for metabolic disorders such as type 2 diabetes.

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  • 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.

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  • 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.

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  • 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

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  • 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

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  • 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

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  • 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

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  • 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.

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  • 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.

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  • 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

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  • 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.

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