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Fasting

Fasting featured article

Fasting – the voluntary abstinence from food and drink – is an ancient tradition long believed to be vital to humans' physical and spiritual health. Practiced for millennia by various cultures and religious groups, fasting is now widely appreciated for its beneficial effects on human metabolism and healthspan.

A growing body of evidence suggests that in the absence of ready supplies of glucose and fats from meals, fasting flips a metabolic "switch," liberating fat stores via fatty acid oxidation and ketone production while prioritizing the safeguarding of lean muscle mass and function. As such, fasting provides a mechanism that not only improves overall body composition but also triggers the activation of biochemical processes and signaling pathways that optimize human performance and physiological function, possibly slowing the processes of aging and disease.

Fasting also stimulates hormesis, a compensatory defense response following exposure to a mild stressor...

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Q&A #67 with Dr. Rhonda Patrick (2/8/25)

Posted on February 18th 2025 (4 months)

Dr. Rhonda Patrick discusses microdosing nicotine, GlyNac benefits, intermittent fasting and hair loss, and cold & flu relief.

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Does Time-Restricted Eating Have Benefits Independent of Calorie Restriction?

Posted on January 16th 2025 (6 months)

In this clip, Drs. Rhonda Patrick and Layne Norton discuss the benefits, limits, and longevity impacts of time-restricted eating and calorie restriction.

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Q&A #56 with Dr. Rhonda Patrick (2/10/24)

Posted on February 16th 2024 (over 1 year)

Dr. Rhonda Patrick explores creatine, dairy's effect on polyphenols, eggs' health impact, and new weight loss drugs like Ozempic in her latest Q&A.

Topic Pages

  • Beta-hydroxybutyrate

    During prolonged fasting, hepatic fatty-acid β-oxidation drives ketogenesis, elevating circulating beta-hydroxybutyrate for peripheral energy.

  • Brain-derived neurotrophic factor (BDNF)

    Fasting elevates hippocampal BDNF via ketone-induced HDAC inhibition and energy-stress CREB activation, enhancing synaptic plasticity.

  • Butyrate

    Fasting reconfigures gut microbial ecology, increasing butyrogenic Clostridia, thereby raising colonic butyrate that activates epithelial AMPK-mediated metabolic signaling.

  • Fasting

    Fasting induces metabolic switch to fatty-acid oxidation and ketogenesis via reduced insulin and increased AMP-activated protein-kinase activity.

  • FOXO

    Fasting lowers insulin/IGF signaling, reducing Akt-mediated FOXO phosphorylation, promoting nuclear translocation and transcription of autophagy and stress-resilience genes.

  • Myocardial infarction (Heart attack)

    Fasting triggers metabolic switching, ameliorates insulin resistance, dyslipidemia and inflammation, thereby attenuating endothelial dysfunction and atherothrombosis underlying myocardial infarction.

  • Sirtuins

    Fasting elevates cellular NAD+/NADH ratio, activating sirtuin deacetylases that remodel metabolic and stress-response gene expression.

  • Time-restricted eating

    Time-restricted eating applies daily fasting intervals that activate fasting-induced metabolic switches while synchronizing nutrient signaling with circadian clocks.

News & Publications

  • Intermittent fasting three nonconsecutive days per week coupled with regular exercise promotes more weight loss than daily calorie restriction. www.acpjournals.org
    Diet Obesity Fasting Weight Loss

    Diets that require daily calorie cutting are hard to adhere to, and most people gain the weight back within a year. Intermittent fasting, which involves eating very little on some days and freely on others, might offer a more sustainable alternative. A recent study found that fasting three nonconsecutive days per week promoted more weight loss than daily calorie restriction as part of a comprehensive weight loss program.

    Researchers assigned 165 adults aged 18 to 60 with a body mass index between 27 and 46 to one of two diet plans. One group followed a 4:3 intermittent fasting schedule, eating freely on four days of the week and cutting calories by 80% on three nonconsecutive days each week. The second group followed a daily calorie restriction (about 34% less than baseline needs) to match the same total weekly calorie reduction. Both groups also participated in a year-long behavioral weight loss program that included group support and a goal of 300 minutes of moderate exercise weekly.

    After 12 months, participants in the intermittent fasting group lost roughly 6.4 pounds more, on average, than those in the daily calorie restriction group. Just over three-fourths of participants completed the study. The difference in weight loss between the two groups was small but statistically meaningful.

    These findings suggest that intermittent fasting offers a modest advantage over daily calorie restriction for people trying to lose weight, especially when paired with regular exercise and behavioral support. Learn more about the health benefits of intermittent fasting in this clip featuring Dr. Mark Mattson.

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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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  • Mild intermittent fasting can have a surprisingly negative effect on immunity: skipping breakfast led to a 90% drop in white blood cell count. www.sciencetimes.com
    Diet Fasting Immune System

    Skipping breakfast may impair immune function.

    Skipping breakfast adversely affects immune health, a new study in mice shows. Mice that skipped breakfast experienced a 90 percent drop in white blood cell numbers and demonstrated impaired immune function.

    Researchers investigated the effects of fasting on immune health in two groups of mice. One group of mice ate breakfast upon waking, while the other group fasted, skipping breakfast. The researchers measured white blood cell numbers immediately after both groups of mice woke up and at four and eight hours after waking. Then they infected the mice with a type of bacteria that commonly causes pneumonia to see how their immune systems responded.

    They found that after just four hours, the white blood cell numbers in the blood of fasting mice decreased by 90 percent, having accumulated in the bone marrow. Upon refeeding, the number of white blood cells in circulation increased markedly, and most of these cells were older and exhibited pro-inflammatory characteristics. After exposure to the pneumonia-causing bacteria, the mice that fasted were more likely to die (and died sooner) than the mice that didn’t fast.

    These findings suggest that skipping breakfast during fasting impairs immunity. They also align with evidence that an earlier eating window when practicing time-restricted eating (which involves a long overnight fast) is more beneficial](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634676/) than a later one. Learn more about time-restricted eating in this episode featuring Dr. Satchin Panda.](https://www.foundmyfitness.com/episodes/satchin-panda-3)

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  • Dawn-to-dusk fasting reduces disease risk and improves metabolic health in people with metabolic syndrome. medicalxpress.com
    Fasting Metabolic Syndrome Weight Loss

    One month of dawn-to-dusk fasting decreases proteins that drive atherosclerosis, heart disease, and cancer in people who have metabolic syndrome, a recent study has found. People who fasted also lost weight and saw improvements in their metabolic and cardiovascular health.

    The study involved 14 people who had metabolic syndrome – a constellation of health conditions that increases a person’s risk of heart disease, stroke, and type 2 diabetes. Participants fasted (no food or drink) from dawn to dusk for more than 14 hours every day for four weeks. They ate a pre-fast meal (breakfast) before beginning their fast and a post-fast meal (dinner) after ending their fast each day. Researchers analyzed the proteomes (the collective set of proteins) of the participants' peripheral blood mononuclear cells, a type of immune cell.

    They found that proteins that drive atherosclerosis, heart disease, and cancer were decreased, but proteins that suppress cancer and inflammation were increased. Interestingly, they found that levels of apolipoprotein B, a protein associated with the development of atherosclerotic heart disease, were markedly lower after a month of fasting, and these lower levels persisted even one week after the fasting period ended. In addition, the participants lost weight, and their insulin resistance and blood pressure improved.

    Evidence suggests that fasting flips a metabolic “switch,” liberating fat stores via fatty acid oxidation and ketone production while safeguarding lean muscle mass and function. Consequently, fasting improves overall body composition but also triggers the activation of biochemical processes and signaling pathways that optimize human performance and physiological function, possibly slowing the processes of aging and disease. Learn more about fasting in our overview article.

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  • The fasting-mimicking diet promotes anticancer immunity in cancer patients. aacrjournals.org
    Cancer Diet Fasting

    The fasting-mimicking diet – a short-term, low-protein, low-carbohydrate diet – improves metabolism and increases immune cell populations that target cancer, according to a 2021 study. Participants who followed the five-day dietary protocol found it easy to adhere to and experienced few ill effects other than fatigue.

    The study involved 101 cancer patients who followed a fasting-mimicking diet that provided up to 600 calories on the first day and up to 300 calories on the remaining days. They repeated the dietary protocol every three to four weeks – up to eight times in all. The patients followed their normal diets between the fasting-mimicking periods but were encouraged to adhere to healthy lifestyles.

    The study’s investigators found that the fasting-mimicking diet reduced the patients' glucose by 18 percent, insulin by 50 percent, and IGF-1 (a growth factor involved in cancer development) by 30 percent. These changes remained stable over the duration of the study. They also found that levels of immunosuppressive cells decreased, but CD8+ T cells – the primary drivers of anti-tumor immunity – increased.

    Research shows that the fasting-mimicking diet creates a hostile microenvironment for cancer cells, sensitizing them to chemotherapy drugs and promoting cell death while preserving healthy cells. This sensitization exploits cancer cells' inability to adapt to extreme environments – a critical aspect of treating certain types of aggressive cancers and preventing their recurrence.

    These findings suggest that the fasting-mimicking diet is a safe and useful adjunct to chemotherapy. Learn about other benefits of the fasting-mimicking diet in this video featuring its creator, Dr. Valter Longo.

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  • System-wide Benefits of Intermeal Fasting by Autophagy www.cell.com
    Fasting Autophagy

    Eating twice a day, without restricting calories, may prevent metabolic syndrome.

    Metabolic syndrome is a constellation of medical conditions that includes high blood pressure, high blood glucose, unhealthy cholesterol levels, and excess abdominal fat. Having metabolic syndrome increases a person’s risk of heart disease, stroke, and diabetes. Findings from a 2017 study suggest that eating two meals per day, without caloric restriction, induces inter-meal autophagy, potentially preventing metabolic syndrome.

    Calorie restriction is the practice of long-term reduced dietary intake, typically characterized by a 20 to 50 percent decrease in caloric intake below habitual levels, without malnutrition or deprivation of essential nutrients. Evidence indicates that calorie restriction induces autophagy; however, adherence to the practice is challenging and often not sustainable.

    Autophagy is a highly conserved adaptive response to stress that involves the sequestration and subsequent destruction of protein aggregates, pathogens, and damaged or dysfunctional cellular components. The primary goal of autophagy is to allow cells to adapt to changing conditions and external stressors, including nutrient scarcity.

    The investigators examined the effects of different dietary patterns on autophagy in mice. They fed one group of mice two distinct meals per day (morning and evening), with each meal providing an equal number of calories. They fed another group of mice the same number of calories, but the mice were allowed to eat anytime during a 24-hour period. They monitored the animals' bodyweight and body composition and measured markers of autophagy and metabolic function.

    They found that the two groups of mice weighed about the same at the end of the 16-month intervention, but mice that ate two distinct meals per day had less bodyfat and more muscle mass than those that ate freely all day. Mice that ate twice daily also exhibited increased expression of autophagy-related genes; browning of white adipose tissue (a phenomenon associated with improved metabolic function in mice); increased the expression of M2 macrophages, which exert anti-inflammatory properties; and improved aspects of metabolism.

    These findings suggest that eating just two meals per day, without restricting total calories, induces autophagy between meals and improves aspects of metabolism. Watch this episode in which Dr. Guido Kroemer describe the effects of calorie restriction on autophagy.

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  • β-Hydroxybutyrate, the body's major source of energy during exercise or fasting, blocks histone deacetylases that otherwise promote oxidative stress www.sciencedaily.com
    Exercise Aging Ketosis Fasting Oxidative Stress HDAC Inhibitor

    From the article:

    “Over the years, studies have found that restricting calories slows aging and increases longevity – however the mechanism of this effect has remained elusive” Dr. Verdin said. Dr. Verdin, the paper’s senior author, directs the Center for HIV & Aging at Gladstone and is also a professor at the University of California, San Francisco, with which Gladstone is affiliated. “Here, we find that βOHB – the body’s major source of energy during exercise or fasting – blocks a class of enzymes that would otherwise promote oxidative stress, thus protecting cells from aging.”

    […]

    Normally HDACs keep a pair of genes, called Foxo3a and Mt2, switched off. But increased levels of βOHB block the HDACs from doing so, which by default activates the two genes. Once activated, these genes kick-start a process that helps cells resist oxidative stress. This discovery not only identifies a novel signaling role for βOHB, but it could also represent a way to slow the detrimental effects of aging in all cells of the body.

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  • Intermittent fasting improves cardiometabolic health. www.sciencedaily.com
    Fasting

    Cardiometabolic syndrome is a constellation of disorders that includes insulin resistance, impaired glucose tolerance, abnormal blood lipids, high blood pressure, and obesity. People who have cardiometabolic syndrome are more likely to die from heart disease or experience a heart attack or stroke than those without the syndrome. Findings presented in a recent review suggest that intermittent fasting improves aspects of cardiometabolic health in people who have obesity.

    Intermittent fasting, an umbrella term that describes periods of fasting between meals, elicits physiological responses similar to those induced by exercise. Intermittent fasting is not a diet that determines what a person eats; rather, it is an eating pattern that determines when they eat. A growing body of evidence suggests that intermittent fasting extends healthspan and lifespan.

    The authors of the study reviewed data from 33 studies investigating the health effects of various patterns of intermittent fasting. These patterns included alternate-day fasting, time-restricted eating, and 5:2 intermittent fasting.

    They found strong evidence that people who practiced intermittent fasting lost 1 to 8 percent of their body weight and decreased their dietary intake by as much as 30 percent (comparable to that achieved with caloric restriction) compared to their baseline, regardless of type of pattern they followed. Those who practiced intermittent fasting also experienced reductions in blood pressure, insulin resistance, oxidative stress, LDL, and triglycerides. Weaker evidence indicated that intermittent fasting improved appetite regulation and gut microbial diversity. The authors concluded that intermittent fasting is safe for most people.

    These findings suggest that intermittent fasting is a safe dietary pattern that helps people lose weight and improves cardiometabolic health in people with obesity. Learn more about the beneficial health effects of intermittent fasting in this episode featuring Dr. Mark Mattson.

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  • Time-restricted eating improves athletic performance. www.mdpi.com
    Exercise Fasting Fat Muscle Time-Restricted Eating

    Time-restricted eating involves restricting the timing of food intake to certain hours of the day (typically within an 8- to 12-hour time window) without an overt attempt to reduce caloric intake. Increasing the amount of time spent fasting each day has been used to treat metabolic diseases such as type 2 diabetes and high cholesterol, increase muscle mass, decrease fat mass, and improve exercise performance. Findings of a recent report demonstrate the beneficial effects of time-restricted eating on exercise performance in power athletes.

    Increasing muscle mass and decreasing fat mass is an important goal for many athletes because increasing their strength-to-mass ratio improves performance. While time-restricted eating is one strategy to improve body composition, previous research has shown that other types of intermittent fasting (e.g., religious fasting during Ramadan) decrease power output and endurance. Another study involving intermittent fasting with caloric restriction found similar deficits in athletic performance. The effects of long-term time-restricted eating without caloric restriction are unknown.

    The researchers recruited healthy young males who were currently practicing a power-sport at least three times per week and had been practicing for at least three years. Twelve participants (average age, 22 years) completed four weeks of time-restricted eating and four weeks of a standard meal pattern in random order with two weeks of wash-out in between. During the time-restricted eating period, participants consumed all of their food within an eight-hour window. The researchers measured body composition using X-ray and athletic performance using the Wingate test, a cycling challenge that measures power and total work.

    Time-restricted eating produced a significant increase in total work (a measure of force over a set distance) and average power output (a measure of work over time). These improvements translated to a one second reduction in sprinting time. The participants achieved this change after four weeks of time-restricted eating, but not after one week. Time-restricted eating did not improve peak power, endurance, or body composition.

    Time-restricted eating, along with regular training, improved exercise performance in athletes. Given that the difference between the current and former 400 meter running world records is only 15 hundredths of one second, the one second decrease in sprinting time produced by time-restricted eating is meaningful.

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  • Time-restricted feeding reduces weight gain and cholesterol in male mice. www.sciencedaily.com
    Cholesterol Fasting Fat Muscle Sugar Time-Restricted Eating Weight Loss Lipopolysaccharide

    A Western diet pattern, characterized by a low intake of fruits and vegetables and a high intake of sugar and processed foods, promotes the development of obesity and metabolic disease. Time restricted eating has been shown to decrease weight and improve metabolic health in humans. However, factors such as age and sex modulate both susceptibilty to obesity and likelihood of responding to weight-loss treatments. Authors of a new report found that male mice experienced greater metabolic benefit from time-restricted feeding than females.

    Time-restricted eating, the practice of limiting food intake to an 8- or 12-hour window, is an emerging therapy for the treatment and prevention of metabolic diseases. Much of the research about time-restricted eating in humans is based on research of time-restricted feeding in mice, which has elucidated many of the cellular mechanisms related to [time-restricted eating’s benefits.](​​https://journals.physiology.org/doi/full/10.1152/ajpregu.00775.2005) These two terms distinguish which population, humans or non-human animals, is practicing time-restricted food intake.

    The prevalence of obesity is on the rise in the industrialized world, a problem compounded by an increasing average age in the same populations. The accumulation of extra fat throughout life puts a person at greater risk of metabolic disease as they age. Females are more likely to gain and retain fat mass than males; however, pre-menopausal females tend to have lower rates of type 2 diabetes and cardiovascular disease due to the protective effects of estrogen. Previous research in humans has demonstrated weight loss and improved metabolic health with time-restricted eating; however, additional research is needed to understand the sex- and age-dependent effects of time-restricted eating.

    The researchers used male and female mice of two ages: three months old (equivalent to 20-year-old humans) and 12 months old (equivalent to 42 year-old-humans). They fed mice a chow diet representative of a Western diet pattern with 17 percent of calories from sugar (human equivalent of about 25 ounces of soda per day) and 45 percent of calories from fat including lard and soybean oil. Current dietary guidelines recommend limiting solid fats such as lard). Half of the mice had 24-hour access to food while the other half only had restricted access, limited to just nine hours per day. Mice continued their diet for a total of 12 to 13 weeks. After 10 weeks, the researchers measured changes in the animals' body weight, glucose sensitivity, serum cholesterol, fatty liver, muscle performance, and immune response when challenged with bacterial endotoxin.

    Although mice in the time-restricted feeding group consumed the same amount of food as mice with constant access to food, time-restricted feeding resulted in 15 percent less weight gain in young male mice and 23 percent less weight gain in older male mice. Time-restricted feeding did not significantly prevent weight gain in female mice. Male mice also experienced a greater reduction in serum cholesterol with time-restricted feeding compared to females. Both older male and female mice had lower rates of insulin resistance and fatty liver while on time-restricted feeding. This protection was likely due to changes in gene expression that increased glucose uptake by and decreased glucose output from the liver. In young male mice, time-restricted feeding preserved muscle mass, function, and performance, but not in young females. Finally, when challenged with bacterial endotoxin, older mice practicing time-restricted feeding were significantly more likely to survive septic shock than mice with 24-hour access to food, demonstrating better health and resilience.

    Time-restricted feeding improved survival of septic shock and provided protection against insulin resistance and fatty liver in both sexes; however, male mice experienced greater reductions in body weight and serum cholesterol and maintained greater muscle mass and performance compared to female mice. The authors noted that their research is of particular interest considering the increased risk of severe COVID-19 illness in those with poor metabolic health.

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  • A very-low-calorie diet increases harmful gut bacteria. www.sciencedaily.com
    Obesity Microbiome Fasting Antibiotics

    The gut microbiota is composed of the community of bacteria, archaea, fungi, and viruses that live in the human intestine and is unique to each individual. Diet can modulate the structure and function of the gut microbiota in ways that either increase or decrease disease risk. Findings of a new report detail the effects of a very-low-calorie diet on the gut microbiota, weight loss, and infection risk.

    Following the absorption of most macronutrients (carbohydrates, fats, and proteins) and micronutrients (vitamins and minerals) present in food in the small intestine, undigested food travels to the large intestine where microbes metabolize any remaining nutrients. The amount and type of food consumed in the diet directly affect the amount and type of microbes that can flourish in the large intestine. Consuming a wide variety of foods in the diet supports a wide variety of microbes, while restricting certain foods or restricting caloric intake may reduce the abundance and diversity of the microbiota, a risk factor for disease.

    The authors of the report recruited 80 females who had completed menopause and who had overweight or obesity. They randomized participants to complete a medically supervised weight-loss program or to maintain a stable weight for 16 weeks. Participants in the weight-loss program consumed a very-low-calorie diet (800 calories per day) for eight weeks, followed by four weeks of a conventional low-calorie diet and four weeks of a weight maintenance diet. The researchers sequenced DNA from the participants' gut microbiota to determine the number and type of microbes present. Finally, they collected gut microbiota samples from the baseline and 12-week timepoints from the participants who lost the most weight during the weight loss program. They transplanted these samples into germ-free mice, which lack a microbiota.

    Participants in the weight-loss program lost an average of 14 percent of their body weight (about 27 pounds) after 12 weeks. A very-low-calorie diet reduced the abundance and diversity of microbes in the gut, but these changes were reversed when participants returned to a normal diet. Microbiota samples from the participants in the very-low-calorie diet intervention were enriched in Clostridioides difficile, a gastrointestinal pathogen (commonly referred to as “C. diff.”). This increase was associated with a reduction in the production of bile acids, which aid in dietary fat digestion and are protective against gastrointestinal pathogens. Mice that received a microbiota transplant from the very-low-calorie diet timepoint lost significantly more body weight due to changes in microbiota structure and reduced nutrient absorption, compared to mice that received a microbiota transplant from baseline.

    This research highlights the importance of diet in the interplay between pathogenic and beneficial microbes in the gut microbiota.

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  • Intermittent fasting improves long term memory retention in mice. www.sciencedaily.com
    Fasting Memory Ketogenic Diet

    Intermittent fasting is a broad term that describes periods of fasting between meals, lasting several hours to days. Intermittent fasting increases ketone production because it uses stored fat as an energy source. It also activates genetic pathways associated with enhanced healthspan and longevity. Caloric restriction, which typically involves a 10 to 40 percent reduction in total caloric intake, activates similar pathways. Findings from a new study suggest that intermittent fasting is more effective than caloric restriction in activating klotho, a longevity gene, to improve long-term memory retention in mice.

    The klotho gene provides the instructions for making the klotho protein in mammals, including mice and humans. Klotho is produced primarily in the kidneys, but some is produced in the brain, where it appears to play a role in cognition and in neurogenesis, the process of forming new neurons. Neurogenesis is the basis for memory, but it declines with age, leading to cognitive decline.

    The authors of the study assigned mice to one of three feeding regimens: intermittent feeding every other day (approximately 10 percent fewer calories over a one-week period); 10 percent calorie restriction; or eating freely. After the mice had followed their respective feeding regimens for three months, the authors of the study subjected them to behavioral studies (to assess spatial learning and memory, conducted at 24 hours and ten days post regimen) or gene expression studies.

    The memory assessment conducted at 10 days post regimen revealed that the mice in the intermittent feeding group performed 25 percent better than those in the caloric restriction group and 30 percent better than those that ate freely. The mice in the intermittent feeding group also exhibited more signs of hippocampal neurogenesis and upregulation of the klotho gene. Further analysis revealed that adult hippocampal neurogenesis is dependent upon klotho activity.

    These findings demonstrate that the longevity gene klotho is necessary for neurogenesis and that intermittent feeding may be beneficial in promoting memory retention in humans. A ketogenic diet also improves memory in mice. Learn more in this episode featuring aging expert Dr. Eric Verdin.

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  • Intermittent fasting improves gut microbiota composition and markers of metabolic health. academic.oup.com
    Microbiome Fasting

    Intermittent fasting, a dietary practice in which individuals repeatedly, voluntarily, and heavily restrict food intake for approximately 16 to 24 hours, is a popular dietary intervention for weight loss and increased glucose tolerance. Some of the beneficial effects of intermittent fasting arise from its ability to modulate the gut microbiota, the community of microbes that live in the gastrointestinal tract. Findings of a recent report demonstrate the effect of intermittent fasting on microbiota structure and function in adults observing the Islamic faith-associated month of Ramadan.

    There are many health benefits attributed to intermittent fasting with the American Heart Association claiming that intermittent fasting may produce weight loss, reduce insulin resistance, and lower the risk for cardiometabolic diseases; however, the mechanisms that drive these benefits in humans are unclear. Experiments in mouse models have suggested that intermittent fasting produces changes in circadian biology and remodeling of the gut microbiota, but further research in humans is needed.

    The investigators recruited two cohorts of participants. The first cohort consisted of healthy young adult males (average age, 19 years) who expressed intention to fast during the month of Ramadan according to Islamic law, which dictates 30 days of fasting from dawn to sunset (approximately 16 hours in this study). These participants provided stool samples for microbiome analysis and blood for the measurement of metabolic makers before the start of Ramadan, 15 days into the month, and at the end of the month. The second cohort consisted of healthy middle-aged adults (average age, 40 years). Some participants in this cohort practiced Ramandan fasting and some did not. Participants in this cohort also provided stool samples for microbiome analysis and blood samples for the measurement of metabolic markers. The researchers collected this data at the beginning and end of the month of Ramadan and 30 days afterward.

    The researchers found that microbiota diversity increased among participants practicing Ramadan-associated intermittent fasting compared to non-fasting participants. This diversity was specifically associated with increased abundance of the bacterial families Lachnospiraceae and Ruminococcaceae. Lachnospiraceae is capable of producing the short-chain fatty acid butyrate, which is a known promoter of metabolic health. Increased abundance of Lachnospiraceae was associated with beneficial changes in liver enzymes. Microbiota composition returned to normal 30 days following the end of Ramadan.

    The authors concluded that intermittent fasting alters the composition of the gut microbiota. Specifically, fasting increased the abundance of the butyrate-producing Lachnospiraceae family, which may explain some of the beneficial physiological effects of intermittent fasting.

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  • Fasting "jump starts" dietary strategies to improve symptoms of metabolic syndrome. www.sciencedaily.com
    Microbiome Fasting Blood Pressure

    Metabolic syndrome is a constellation of conditions that includes high blood pressure, high blood glucose, excess abdominal fat, and abnormal cholesterol levels. People with metabolic syndrome are at higher risk for developing heart disease, stroke, and type 2 diabetes. Findings from a new study suggest that fasting “jump starts” dietary strategies to improve symptoms of metabolic syndrome.

    The “Western diet,” also known as the Standard American Diet, is rich in processed foods, red meat, high-fat dairy products, and added sugars. It plays contributing roles in the development of metabolic syndrome. Conversely, the DASH diet – Dietary Approaches to Stop Hypertension – is rich in fruits, vegetables, whole grains, nuts, legumes, low-fat dairy products, and dietary fiber, and low in red meat and sugar-sweetened beverages. It is one of the most commonly prescribed and successful dietary patterns for managing high blood pressure and other aspects of metabolic syndrome.

    Gut health also plays a role in development of metabolic syndrome. In fact, an imbalance in the number of harmful versus helpful microbes in the gut, a condition known as dysbiosis, drives many disease states. Fasting and caloric restriction induce changes in the gut microbiota to promote health.

    The three-month intervention study included 71 adults between the ages of 50 and 70 years who had high blood pressure and metabolic syndrome. Half of the participants followed a modified DASH diet alone, while the other half followed a combined fasting and modified DASH diet. The modified DASH diet was a plant-based dietary program that was low in sodium, fat, and sugar. The combined fasting/DASH diet started with two calorie-restricted vegan days (no more than 1,200 calories per day), followed by a five-day liquid fast that included vegetable juices and vegetable broth (300 to 500 calories per day). Upon completion of the fast, the participants followed the modified DASH plan. Both groups received approximately 50 hours of nutrition counseling, cooking lessons, and lifestyle coaching on exercise and stress management.

    The authors of the study measured the participants' blood pressure and other markers of metabolic health, including body weight. They also measured immune cells and assessed the microbial makeup of the participants' gut microbiota.

    Blood pressure (and the need for blood pressure medications) and bodyweight decreased among the participants following the fasting/DASH diet. The gut microbial composition of the participants following the fasting/DASH diet changed markedly during fasting, adopting a profile that was rich in microbes involved in short-chain fatty acid production, mucin degradation, and nutrient utilization. These changes in microbial composition reverted partially upon completion of the three-month DASH diet. The fasting/DASH diet also induced changes in immune cell populations, which were reversed when the participants ended their fast. Notably, fasting reduced the number of proinflammatory immune cells, whereas regulatory T cells increased. The participants who followed the DASH diet alone did not experience changes in their gut microbiota or immune cell populations.

    These findings suggest that combining periodic fasting with a modified DASH diet improves blood pressure, body weight, and metabolic health in adults with metabolic syndrome better than the DASH diet alone. The participants in this study were of Caucasian-European background, potentially limiting the application of its findings. Further study is needed in a more heterogenous population.

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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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  • A pilot study to investigate the immune modulatory effects of fasting in steroid-naïve mild asthmatics www.ncbi.nlm.nih.gov
    Inflammation Fasting Allergies Asthma NLRP3

    A fasting mimetic diet blunts inflammation and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on: the NLRP3 inflammasome; Th2 cell activation and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study where pulmonary function testing (PFT) and peripheral blood mononuclear cells (PBMCs) extraction was performed 24 hours after fasting, with repeated PFT-testing and blood draw 2.5 hours after refeeding. PFT’s were not changed by a prolonged fast. However, steroid-naïve mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics co-cultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production, and reduced CD4+ T cell Th2 activation compared to refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naïve asthmatics, as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient-level dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study, as well as the potential development of caloric restriction interventions for the treatment of asthma.

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  • Every other day fasting in mice protected brain from neurotoxic injury, prior work showing enhanced BDNF www.sciencedaily.com
    Brain Fasting BDNF

    From the article:

    Mice on these three diets were given a neurotoxin called kainate, which damages nerve cells in a brain region called the hippocampus that is critical for learning and memory. (In humans, nerve cells in the hippocampus are destroyed by Alzheimer’s disease). Dr. Mattson’s team found that nerve cells of the meal-skipping mice were more resistant to neurotoxin injury or death than nerve cells of the mice on either of the other diets.

    […]

    Previous studies by Dr. Mattson and his colleagues suggested that nerve cells in the brains of rodents on a meal-skipping diet are more resistant to dysfunction and death in experimental models of stroke and other neurological disorders including Parkinson’s, Alzheimer’s and Huntington’s diseases. Dr. Mattson also has found that meal-skipping diets can stimulate brain cells in mice to produce a protein called brain-derived neurotrophic factor (BDNF) that promotes the survival and growth of nerve cells.

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  • A fasting-mimicking diet improved effectiveness and reduced toxicity of neoadjuvant chemotherapy in breast cancer patients. www.nature.com
    Diet Breast Cancer Fasting

    Chemotherapeutic agents, powerful drugs used in cancer treatment, kill cancer cells but can also damage healthy cells. Chemotherapy administered to shrink a tumor prior to surgery is known as neoadjuvant chemotherapy. Findings from a recent study suggest that following a fasting-mimicking diet before neoadjuvant chemotherapy impacts both the toxicity and efficacy of the treatment.

    A large body of evidence indicates that prolonged fasting can reduce the risk of chronic diseases by improving overall metabolic health. A fasting-mimicking diet, or FMD, is designed to achieve effects similar to a multiple day water-only fast while being easier to follow.

    Previous preclinical research has demonstrated that prolonged fasting sensitizes cancer cells to chemotherapy while protecting healthy cells. Studies in animal models indicate that during prolonged fasting, healthy cells shift to a resting metabolism that protects them from nutrient scarcity; however, cancer cells are unable to do this. The current study investigated whether the fasting-mimicking diet influenced the toxicity or effectiveness of chemotherapy in women with early-stage breast cancer.

    The authors of the randomized controlled study assigned 131 women with stage II/III breast cancer to receive either an FMD or their regular diet three days before and throughout neoadjuvant chemotherapy. Both groups of women experienced similar side effects, despite the fact that only those on the regular diet were given dexamethasone — a drug to lessen side effects. The authors suggest that these findings might eliminate the need for drugs to manage side effects. Researchers observed that women on the FMD were more likely to experience a 90 to 100 percent tumor cell loss as compared to women on a regular diet. Furthermore, patients on the FMD had less DNA damage in T-lymphocytes from chemotherapy than those on the regular diet.

    These findings suggest that an FMD can curb damage to normal cells while increasing a cancer cell’s vulnerability to chemotherapy in women with breast cancer. Further clinical trials will determine if fasting or an FMD in conjunction with standard of care will be helpful in the treatment of other cancers.

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  • Intermittent fasting from dawn to sunset for 30 consecutive days is associated with many health improvements. www.sciencedirect.com
    Fasting

    Time-restricted eating is a form of daily fasting wherein the time of the day during which a person eats is limited or compressed. Findings from a recent study suggest that time-restricted eating aligns eating and fasting cycles to the body’s innate 24-hour circadian system, altering the body’s production of proteins and reducing the risk of developing chronic conditions such as cancer, diabetes, and cognitive decline.

    Circadian rhythms are the body’s 24-hour cycles of biological, hormonal, and behavioral patterns. They modulate a wide array of physiological processes, including the body’s production of hormones that regulate sleep, hunger, metabolism, and others, ultimately influencing body weight, performance, and susceptibility to disease. The timing of food intake strongly influences circadian rhythms.

    The authors of the study conducted a proteomic signature study – a type of analysis that identifies and quantifies the proteins present in a cell, tissue, or organism. The study involved 14 healthy adult men and women (average age, 32 years) who fasted for 14 or more hours every day from dawn to dusk for a month. The participants provided blood samples at three time points in the study: before and after the 30-day fasting period and one week after the fasting period had ended.

    The proteomic analysis revealed that the 30-day daytime fast influenced the production of proteins that protect against chronic conditions such as cancer, metabolic syndrome, inflammation, and Alzheimer’s disease, among others. These findings suggest that intermittent fasting might be beneficial in preventing or reducing the risk of developing chronic diseases.

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  • Diet-induced thermogenesis is higher after breakfast than after dinner. academic.oup.com
    Obesity Fasting Protein Dairy

    Eating increases the body’s metabolic rate, a phenomenon referred to as diet-induced thermogenesis (also known as the “thermic effect” of food). Diet-induced thermogenesis begins about an hour after eating, peaks about two hours later, and then maintains a steady level for several more hours. Approximately 5 to 15 percent of a person’s daily energy expenditure– an estimate of how many calories a person burns per day – is due to diet-induced thermogenesis.

    A few factors influence the degree of diet-induced thermogenesis, including meal size, macronutrient content (protein versus fat, for example) and environmental temperature. Age and physical activity may also play roles in diet-induced thermogenesis. Findings from a new study suggest that circadian variations in energy expenditure influence diet-induced thermogenesis.

    The randomized, cross-over, laboratory study involved 16 healthy, normal-weight men. Each of the men ate three meals per day in the laboratory for three days and maintained a regular sleep pattern. The authors of the study conducted indirect calorimetry tests to determine the participants' energy expenditure and collected participants' blood samples before and after meals to gauge glucose tolerance. The participants rated their feelings of hunger on a Likert scale.

    Meals consisted of a high-calorie breakfast and low-calorie dinner or the converse – a low-calorie breakfast and a high-calorie dinner. The high-calorie meals provided 69 percent of the participants' calorie needs and the low-calorie meals provided 11 percent. All lunches were identical and provided 20 percent of the participants' calorie needs.

    The indirect calorimetry tests revealed that the participants' diet-induced thermogenesis after breakfast was generally 2.5 times higher than after dinner. The participants' glucose levels were, on average, lower after breakfast than after dinner. Glucose levels were 17 percent higher after eating the low-calorie dinner compared with levels after eating the low-calorie breakfast. The participants reported having greater feelings of hunger, especially for sweet foods, on days when they ate the low-calorie breakfast.

    These findings highlight the role of circadian variation in metabolism and underscore the need for modifying food intake to exploit this variation.

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

    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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  • Fasting reduces the numbers of circulating monocytes in healthy humans and mice without compromising immune function. www.mountsinai.org
    Fasting Time-Restricted Eating

    Fasting and other forms of caloric restriction are associated with reduced risk of many chronic diseases. Monocytes, white blood cells that play key roles in the body’s immune response, can contribute to the pathogenesis of chronic inflammatory diseases. Findings from a new study demonstrate that fasting reduces the number of circulating monocytes without compromising immune function.

    The authors of the study analyzed blood samples from 12 healthy adults taken at the beginning of the study (baseline), three hours after they ate, and 19 hours after commencing a fast. All the samples were taken at the same time of day (3pm). After fasting, the participants' blood levels of monocytes were markedly lower than after eating. Fasting did not lower blood levels of monocytes below the normal range in people whose baseline levels were already low.

    The study was replicated in mice, with a fasting protocol suitable for rodents. The outcome was similar, with monocytes drastically reduced. A longer fast in the mice yielded even more favorable reductions in monocytes in various tissues as well as reductions in several types of leukocytes, including eosinophils, natural killer cells, and T cells.

    These findings illuminate the role of dietary intake in the regulation of the body’s immune and inflammatory responses and suggest that fasting and other forms of caloric restriction may be viable strategies to reduce inflammation in chronic disease states.

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  • Exercise mitigates muscle mass losses during severe energy deficit by inhibiting the induction of autophagy. www.mdpi.com
    Exercise Fasting Protein

    Severe energy deficit, such as would occur during dieting or prolonged hospitalization, promotes skeletal muscle losses. A recent study demonstrated that exercise mitigates some of these losses by inhibiting the induction of autophagy.

    Autophagy is a highly conserved cellular defense mechanism that sequesters protein aggregates, pathogens, and damaged or dysfunctional organelles into vesicles called autophagosomes and then delivers them for destruction. The primary goal of autophagy is to allow the cell to adapt to changing conditions and external stressors, including energy deficit.

    The study involved 15 overweight or obese men between the ages of 30 and 50 years. In the first phase of the study, the participants ate a very low-calorie diet consisting solely of sucrose or whey protein and engaged in endurance exercise consisting of 45 minutes of arm exercises and eight hours of walking for four days. This diet/exercise protocol created an energy deficit of approximately 5,500 calories per day. In the second phase, they ate a control diet and engaged in limited exercise for three days.

    At the end of each phase, participants provided muscle biopsies for analysis, which revealed that severe energy deficit induced autophagy in skeletal muscle, but endurance exercised inhibited this induction, especially in the lower extremities. Interestingly, dietary intake of protein had little effect in preserving muscle mass.

    The authors of the study proposed that exercise may sensitize the skeletal muscle to the anabolic signals that inhibit autophagy induction during energy deficit. These findings underscore the importance of exercise during dietary restriction, especially during prolonged hospital stays, to prevent or reduce skeletal muscle losses.

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  • Time-restricted eating may help reduce weight and prevent diabetes and heart disease in people with metabolic syndrome. www.sciencedaily.com
    Fasting Triglycerides Time-Restricted Eating Blood Pressure Dairy Metabolic Syndrome

    More than a third of adults living in the United States have metabolic syndrome, a constellation of conditions that includes abdominal (central) obesity, high blood pressure, high fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. People who have metabolic syndrome are at increased risk of developing diabetes and heart disease. A new study suggests that time-restricted eating may reduce this risk.

    Time-restricted eating is a form of daily fasting that aligns 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.

    This study involved 19 adults (average age, 59 years) who had metabolic syndrome. Most of the participants were obese, took a statin or antihypertensive drug, and had poor blood glucose control. They followed a time-restricted eating pattern that allowed them to eat during a 10-hour daytime window with a 14-hour overnight fast for 12 weeks. No overt attempt to change physical activity or diet quality or quantity was required.

    At the end of the study, participants exhibited reduced waist circumference and body fat, lowered blood pressure, and improvements in lipid profiles and blood glucose control. These findings suggest that time-restricted eating may have potential as an adjunct to current therapies to treat metabolic syndrome.

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  • Study demonstrates that exercising before eating breakfast burns more fat, improves insulin sensitivity, & increases glucose uptake into muscle. www.sciencedaily.com
    Exercise Fasting Insulin Time-Restricted Eating Carbohydrates

    Exercise promotes the uptake of glucose into muscle cells and increases insulin sensitivity. Other physical adaptations occur during exercise, as well, including increased muscle mass, decreased fat mass, and improved mitochondrial function. Previous research has demonstrated that training in the fasted state promotes greater glucose tolerance and insulin sensitivity and induces higher fatty acid oxidation compared to training in the fed state. A recent study bolsters these findings, demonstrating that exercising before eating breakfast may enhance some of the beneficial effects of exercise.

    The six-week, single-blind, randomized, controlled trial involved 30 overweight or obese men who engaged in moderate-intensity cycling either before or after eating a high-carbohydrate, mixed-macronutrient breakfast. The men exercised for three, 30-minute sessions the first week and progressed to three, 50-minute sessions over the remaining weeks.

    The men who exercised before eating had nearly 2-fold higher whole-body lipid utilization rates as well as decreased carbohydrate utilization compared to the men who exercised after eating. The effects were sustained throughout the entire six-week study period. These findings suggest that exercising before eating breakfast burns more fat, improves insulin sensitivity, and increases glucose uptake into muscle tissue compared to exercising after eating breakfast. Exercising after eating may blunt these effects, however.

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  • Time-restricted eating may be linked to greater motivation to engage in voluntary exercise. www.sciencedaily.com
    Exercise Fasting Ghrelin Time-Restricted Eating Dairy Weight Loss

    Limiting food intake and engaging in exercise are highly effective strategies for weight loss. People who are obese are often sedentary, however, due to physical limitations and a lack of motivation to exercise. Compelling findings from a new study in mice suggest that ghrelin, a hormone linked to appetite, may increase motivation to engage in exercise.

    Ghrelin, which is produced primarily in the stomach, stimulates appetite, increases food intake, and promotes fat storage in mice and humans. It is often referred to as the “hunger hormone” and is linked to reward-driven behavior. Previous studies have shown that ghrelin administration increases activity in mice in anticipation of food.

    The current study involved mice that were fed on a time-restricted eating schedule (twice daily) versus mice that were allowed to eat freely throughout the day. Both groups of mice ate roughly the same amount of food each day. The mice that were fed on the time-restricted schedule were more motivated to engage in voluntary exercise and ran on an exercise wheel for longer periods. The increase in the animals' activity corresponded to increases in ghrelin levels. Conversely, inhibiting ghrelin attenuated the animals' motivation to exercise.

    Hunger-related behaviors such as increased activity are essential to animals in the wild or human hunter-gatherers because they must forage and seek out or hunt for food. Tapping into these ancient hormonally-driven behaviors may help resolve modern-day concerns of obesity and lack of exercise. However, a small study in humans demonstrated that time-restricted eating decreased morning levels of ghrelin (and subsequently appetite), so more studies on the effects of time-restricted eating and ghrelin in humans are needed.

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  • Time-restricted eating, a ketogenic diet, and exercise improved cognitive function and markers of metabolism in a woman with ApoE4 and Alzheimer's . www.sciencedirect.com
    Alzheimer's Ketosis Fasting Insulin Triglycerides Time-Restricted Eating Metabolic Syndrome Ketogenic Diet

    Time-restricted eating (TRE), a ketogenic diet, and exercise improved cognitive function and markers of metabolism including triglycerides, VLDL, and HbA1c in a 71-year-old woman with ApoE4 that has mild Alzheimer’s disease and metabolic syndrome (case study).

    This is an interesting proof of principle study showing that implementing a nutrition protocol purposed at raising plasma ketones through fasting (TRE) a ketogenic diet and physical exercises can compensate for insulin resistance and the ApoE4 gene in a mild Alzheimer’s patient experiencing cognitive impairment.

    The APOE4 gene is the largest risk factor for Alzheimer’s disease besides age itself.

    To learn more check out this episode highlight of Dr. Dale Bredesen talking about time-restricted eating and a ketogenic diet in the context of Alzheimer’s disease in people with and without ApoE4.

    Episode: https://youtu.be/PWZbeq6MCKU

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  • Supplements during fasting? Lyme disease, West Nile virus
    Fasting Dairy Supplements

    I know it’s generally said to not take any supplements during fasting, especially prolonged fasting. But I have Lyme, West Nile, and also travel from USA to Germany every 2 months for work (7h time difference). I get sick every time! So my goals are to not get sick when travelling, conquer Lyme and West Nile, and not be dying for a nap at 8 in the morning. I’m fat adapted, do intermittent fasting easily, daily monitoring of blood glucose and ketones. I get into ketosis easily (4.5 on the morning after lots of veggies for dinner, and 85 glucose).

    So for sure I will do prolonged fasting, but I’m nervous about not taking Lyme supplements. I’m doing the Buhner protocol, which involves mixing herbal powders like Japanese knotweed in water, and chugging. Some of this involves tinctures as well.

    So my question is: would taking these powders disrupt the fast? (Yes, I know they would, but would they disrupt it enough to make it better to skip them altogether?)

    My second question is: would tinctures be better? (yes, I know they would, but my question is really about whether even tinctures should be avoided? I know the “official” answer is “avoid them because we don’t know enough yet on how autophagy works,” but I’m curious to find out what anyone might know about this.

    Thanks for any thoughts, Kelly

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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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  • Beta-hydroxybutyrate production from fasting or a ketogenic diet may reduce the production of senescent cells associated with vascular aging www.sciencedaily.com
    Aging Ketosis Heart Disease DNA Damage Fasting Ketogenic Diet

    Fasting or beta-hydroxybutyrate administration reduces cellular senescence.

    Beta-hydroxybutyrate (BHB) is a ketone produced by the body during times of carbohydrate scarcity such as those encountered while practicing a ketogenic diet, fasting, or exercise, which have all demonstrated the ability to extend healthspan and lifespan. However, the precise effects of beta-hydroxybutyrate on the cellular mechanisms of aging are not well understood. Findings of one report show that BHB administration and fasting both reduce senescence in mice.

    Senescence occurs when a damaged cell terminates its normal cycles of growth and reproduction for the purpose of preventing the accumulation of damaged DNA or mitochondria. While senescence plays a vital role in human development and wound healing, the accumulation of senescent cells is associated with diseases of aging such as Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, type 2 diabetes, and glaucoma. Lifestyle habits or drugs that increase beta-hydroxybutyrate may extend healthspan and reduce disease risk by slowing the rate of senescence.

    The researchers conducted an experiment that involved culturing human vascular endothelial (i.e., blood vessel cells) from the umbilical cord and aorta, followed by an experiment with mice. To compare the effects of BHB supplementation and fasting, the researchers fed one group of mice a normal diet, then randomly assigned them to receive an injection of BHB or a placebo after they had fasted for just five hours. Using a second group of mice, the researchers randomly assigned half of the group to fast for 72 hours and the other half to eat normally. In both the cell culture and mice experiments, the researchers measured changes in gene expression and metabolic activity.

    The researchers found that BHB reduced senescence in vascular cells due to increased expression of the transcription factor Oct4, which is a protein that binds to DNA and regulates cell regeneration and stem cell differentiation. Compared to mice who received a placebo injection, mice who received BHB had reduced senescence in vascular cells through the same Oct4 pathway as in cell culture. Mice who fasted also robustly activated Oct4, leading to activation of senescence-associated markers such as mTOR inhibition and AMPK activation, two pathways that modulate lifespan.

    Prior to this study, it was not known whether Oct4 was active in adult cells; however, these results show fasting or BHB administration activates youth-associated DNA factors that reduce senescence in mice and cell culture. Future studies are needed to translate these results into relevant use for humans because humans have very different nutritional needs than mice to cells in culture.

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  • Dietary Restriction Improves Intestinal Cellular Fitness to Enhance Gut Barrier Function and Lifespan in D. Melanogaster papers.ssrn.com
    Diet Aging Fasting

    Loss of gut integrity is linked to various human diseases including inflammatory bowel disease. However, the mechanisms which lead to loss of barrier function remain poorly understood. Using D. melanogaster, we demonstrate that dietary restriction (DR) slows the age-related decline in intestinal integrity by enhancing enterocyte cellular fitness through upregulation of dMyc in the intestinal epithelium. Reduction of dMyc in enterocytes induces cell death through JNK signaling leading to increased gut permeability and reduced lifespan upon DR. Genetic mosaic and epistasis analyses suggest that cell competition, whereby neighboring cells eliminate unfit cells by apoptosis, mediates cell death in enterocytes with reduced levels of dMyc. Reducing enterocyte apoptosis partially rescued the increased gut permeability and shortened lifespan upon loss of dMyc. We propose that dMyc acts as a barometer of enterocyte cell fitness impacting intestinal homeostasis in response to changes in diet and age.

    Akagi, Kazutaka and Wilson, Kenneth A. and Katewa, Subhash D. and Ortega, Mauricio and Simmons, Jesse and Kapuria, Subir and Sharma, Amit and Jasper, Heinrich and Kapahi, Pankaj, Dietary Restriction Improves Intestinal Cellular Fitness to Enhance Gut Barrier Function and Lifespan in D. Melanogaster (2018). Available at SSRN:

    https://ssrn.com/abstract=3155743 or http://dx.doi.org/10.2139/ssrn.3155743

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  • Intermittent fasting increased gut bacteria diversity, reduced inflammation, demyelination, and axonal damage in multiple sclerosis (MS) animal model. www.cell.com
    Gut Microbiome Fasting Multiple Sclerosis Autoimmunity

    Intermittent fasting (every other day) increased gut bacteria diversity and reduced inflammation, demyelination, and axonal damage in multiple sclerosis (MS) animal model. A small pilot trial in humans with MS showed many similar changes to the gut microbiome and blood adipokines such as leptin. The effects of fasting on immune cells included a reduction of pro-inflammatory IL-17-producing T cells and increased numbers of T regulatory cells which prevent autoimmunity.

    The small pilot trial in humans showed increased bacteria richness in species that have previously been shown to promote T regulatory cell accumulation in the colon.

    Interestingly, this study did what is called a metagenomic analysis and found that the ketone pathway was enhanced in the gut microbiome by intermittent fasting. This is super interesting because bacteria in the gut normally produce short chain fatty acids and ketones from fermentable fiber but suggests that the gut microbiome regulates its own ketone body metabolism during fasting!

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  • Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes www.cell.com
    Insulin Resistance Fasting Insulin Time-Restricted Eating Blood Pressure Weight Loss

    A small randomized controlled clinical trial finds time-restricted eating within a 6-hour window (fasting for 18 hours) without reducing calories or losing weight improves insulin sensitivity, beta cell function, blood pressure, oxidative stress and reduces evening appetite.

    All eating was supervised and approached metabolic ward rigor. The improvements in metabolism were independent of weight loss and the reduction in blood pressure was so significant that it was comparable to the standard of care blood pressure medication (ACE inhibitors).

    The time-restricted eating they started early with the first meal at 8 am and dinner before 3 pm. The importance of time of day for this type of intermittent fasting is still an interesting open question, especially since there’s a lot of advocacy for late eating among 16:8 advocates, however, insulin sensitivity usually declines later in the day (and is exacerbated by the production of melatonin, which has an effect of shutting off insulin secretion). Interestingly, Dr. Satchin Panda has been gathering data via his mobile app (my circadian clock) that suggests an eating window later in the day may be comparable to an early eating window.

    To learn more about time-restricted eating and intermittent fasting check out the two separate podcasts I did with Dr. Satchin Panda. The episodes have summaries, timelines, and transcripts!

    Round 2 episode: https://www.foundmyfitness.com/episodes/satchin-round-2

    Round 1 episode: https://www.foundmyfitness.com/episodes/satchin-panda

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  • Late-night eating increases weight gain, raised insulin, fasting glucose, cholesterol & triglycerides in small trial. www.sciencedaily.com
    Insulin Resistance Fasting Circadian Rhythm Fat Insulin Triglycerides Time-Restricted Eating

    A small clinical trial finds that eating later in the day (12 pm to 11 pm) increased weight gain, raised insulin, fasting glucose, cholesterol, and triglyceride levels compared to eating earlier in the day (8 am to 7 pm).

    In the small study, each of the nine healthy weight adults underwent each of the two conditions: daytime eating (three meals and two snacks between 8 a.m. and 7 p.m.) for eight weeks and delayed eating (the same three meals and two snacks eating from noon to 11 p.m.) for eight weeks after a 2-week washout period. This is a small trial and needs to be repeated but is in line with another study that showed when healthy adults eat meals that are identical for breakfast, lunch, or dinner, the postprandial glucose increase is lowest after breakfast and highest after dinner even though the meals were 100% identical.

    For more on meal timing and time-restricted eating…check out my podcasts with the experts, Dr. Satchin Panda and Dr. Ruth Patterson on youtube and iTunes.

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  • Fasting-like diet kills autoimmune cells & replaced them with healthy cells & improved symptoms in MS patients. www.sciencedaily.com
    Brain Fasting Immune System Multiple Sclerosis Autophagy Dairy Autoimmunity Ketogenic Diet

    This fasting-like diet also promotes regeneration of the myelin in mice with multiple sclerosis. In human patients with multiple sclerosis, the fasting-like diet led to improvements in symptoms if followed by a Mediterranean diet or a ketogenic diet.

    Here is the fasting-like diet that humans were given: Day 1 – pre-fasting followed by Day 2-8 – very low calorie diet. Day 1-prefasting consists of an 800 kcal (about 40% of normal caloric intake similar to mouse Day1 FMD) monodiet (fruit, rice, or potatoes) by preference of individuals. On the following day patients were recommended to use an oral laxative, Natrium Sulfuricum (20-40 g). FMD consisted of 100 ml vegetable broth or vegetable juice with 1tablespoon of linseed oil 3 times daily, plus additional calorie-free liquids. The daily calorie intake was predefined with 200 – 350 kcal (10-18% of normal caloric intake similar to mouse Day 2-3 FMD). Patients were advised to drink 2-3 L of unsweetened fluids each day (water, and herbal teas) and to use an enema if tolerated. After the 7-day fasting period solid foods were stepwise reintroduced for three days, starting with a steamed apple at day 8. After the fasting and refeeding period a normocaloric, plant-based Mediterranean diet was maintained until study end.

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  • Beta-hydroxybutyrate produced from a ketogenic diet, fasting, or high-intensity exercise dampens inflammation via blocking of the NLRP3 inflammasome www.sciencedaily.com
    Exercise Diet Ketosis Inflammation Fasting Immune System NLRP3 Ketogenic Diet

    From the article:

    BHB is a metabolite produced by the body in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet. Dixit said it is well known that fasting and calorie restriction reduces inflammation in the body, but it was unclear how immune cells adapt to reduced availability of glucose and if they can respond to metabolites produced from fat oxidation.

    Working with mice and human immune cells, Dixit and colleagues focused on how macrophages – specialized immune cells that produce inflammation – respond when exposed to ketone bodies and whether that impacts the inflammasone complex.

    The team introduced BHB to mouse models of inflammatory diseases caused by NLP3. They found that this reduced inflammation, and that inflammation was also reduced when the mice were given a ketogenic diet, which elevates the levels of BHB in the bloodstream.

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