Tag /

Ketosis

Episodes

rhonda
Premium

Q&A #37 with Dr. Rhonda Patrick (7/09/2022)

Posted on July 9th 2022 (almost 3 years)

Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.

rhonda
Premium

Q&A #36 with Dr. Rhonda Patrick (6/04/2022)

Posted on June 4th 2022 (about 3 years)

Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.

ketosis

Dr. Dominic D'Agostino on Developing a Well-Designed Ketogenic Diet and Harnessing its Benefits

Posted on April 28th 2022 (about 3 years)

Dr. Dominic D'Agostino discusses how ketones affect exercise performance, reduce inflammation, and improve neurological health.

Topic Pages

  • Beta-hydroxybutyrate

    During ketosis, hepatic fatty-acid β-oxidation generates acetoacetate, subsequently reduced to β-hydroxybutyrate, elevating circulating ketone concentrations.

  • Butyrate

    Butyrate is β-oxidized to acetyl-CoA, fueling hepatic mitochondrial ketogenesis and elevating circulating β-hydroxybutyrate during ketosis.

News & Publications

  • Ketogenic diet raises brain blood flow by 22% and increases brain-derived neurotrophic factor by 47%, highlighting its potential to support cognitive function even in people without cognitive impairment. pubmed.ncbi.nlm.nih.gov
    Brain Diet Ketosis Memory BDNF Ketogenic Diet

    Glucose has long been considered the brain’s primary fuel, but ketone bodies may offer critical support, especially during periods of low carbohydrate availability. A recent study found that a ketogenic diet boosted levels of brain-derived neurotrophic factor (BDNF)—a key protein that supports brain health—by 47%, highlighting the diet’s potential to support brain health even in people without cognitive impairment.

    Researchers recruited 11 healthy but overweight adults to participate in a randomized, crossover study. Each participant followed two different diets: a ketogenic diet high in fat and low in carbohydrates, and a standard balanced diet. Each diet lasted three weeks and ended with brain imaging scans (using MRI and PET) and blood tests to measure brain blood flow and BDNF levels.

    They found that the ketogenic diet markedly increased ketone levels in the blood compared to the standard diet. Brain blood flow rose by 22% after eating the ketogenic diet, and BDNF levels increased by 47%. Researchers also found a strong link between ketone levels in the blood and higher brain blood flow.

    This was a small study, but the findings suggest that a ketogenic diet enhances brain blood flow and boosts vital brain-supporting proteins, even in people without memory loss. This opens up new possibilities for using ketogenic nutrition as a strategy to preserve cognitive function and support long-term brain health. Learn how to plan the optimal ketogenic diet in this clip featuring Dr. Dominic D'Agostino.

    Read more
  • Beta-hydroxybutyrate, a ketone used by the brain during fasting or exercise, may help counteract toxic protein buildup in aging and Alzheimer's disease. pmc.ncbi.nlm.nih.gov
    Brain Alzheimer's Diet Ketosis Dementia Protein Ketogenic Diet

    Protein misfolding in the brain is a central player in both aging and Alzheimer’s disease, driving toxic protein buildup and brain cell dysfunction. However, evidence indicates that ketones—a critical brain fuel produced during fasting or exercise—may help reduce or prevent this damage. A recent cell study found that beta-hydroxybutyrate, a type of ketone, helps protect the brain by targeting toxic proteins for disposal.

    Researchers delivered beta-hydroxybutyrate to brain cells collected from mice and monkeys via an exogenous ketone ester. They examined the cells for changes in protein solubility and pathways involved in protein breakdown. They also studied beta-hydroxybutyrate’s effects on pathological proteins, such as amyloid-beta, in a nematode model of Alzheimer’s disease.

    They found that beta-hydroxybutyrate made pathological proteins insoluble, preventing their toxic spread while promoting their clearance through autophagy, the cell’s natural recycling process. This effect was specific to pathological proteins and wasn’t the result of changes in acidity or random chemical interactions. Beta-hydroxybutyrate also reduced amyloid-beta toxicity in nematodes.

    These findings suggest that a ketone ester of beta-hydroxybutyrate counteracts the toxic buildup of proteins in aging and Alzheimer’s disease. Further research is needed to translate these results to humans. Learn more about how ketone ester supplementation may improve brain health in this episode featuring Dr. Mark Mattson.

    Read more
  • A ketogenic diet restores long-term potentiation, a crucial mechanism for learning and memory, to healthy levels in mice prone to Alzheimer's-like symptoms, implicating ketone bodies as potential therapeutic agents. www.ucdavis.edu
    Alzheimer's Diet Aging Ketosis Memory Dementia Ketogenic Diet

    A ketogenic diet – a high-fat, low-carbohydrate dietary pattern – offers potential benefits in various health contexts, including weight management and seizure control. Some evidence suggests that the ketogenic diet is beneficial in preventing or treating neurodegenerative diseases, such as Alzheimer’s and dementia. A recent study in older mice found that a ketogenic diet improves memory functions and increases lifespan.

    Researchers compared the effects of a seven-month ketogenic diet to a standard diet in mice prone to developing Alzheimer’s-like symptoms. They examined the hippocampal region of the animals' brains, a crucial area for memory and learning, to gauge the diet’s effects on synaptic plasticity – the brain’s ability to form and reorganize synaptic connections, especially in response to learning or new experiences.

    They found that mice on the ketogenic diet experienced restoration of their long-term potentiation – a measure of synaptic strength and a fundamental mechanism for learning and memory – to levels comparable to healthy mice. They attributed this restoration to the marked elevation of beta-hydroxybutyrate (BHB), a ketone body produced during the ketogenic diet. They also found that the diet triggered enhancements in several key pathways and molecules associated with synaptic plasticity, including notable increases in specific enzymes and brain-derived neurotrophic factor (BDNF), particularly in female mice.

    BDNF is crucial for cognitive functions, providing support for neuronal survival, growth, and differentiation and enhancing learning and memory by strengthening and creating synaptic pathways. Elevated BDNF levels correlate with better cognitive performance, whereas its deficiency is linked to various mental and neurodegenerative disorders, highlighting its significance in brain health. Learn more about BDNF in our overview article.

    These findings suggest that a ketogenic diet ameliorates memory impairments and bolsters neuronal health in an Alzheimer’s mouse model, primarily through the action of BHB and its enhancement of synaptic plasticity. Learn more about beta-hydroxybutyrate in our overview article.

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

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

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

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

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

    Read more
  • Ketone supplements marginally hinder high-intensity cycling performance, echoing earlier research. www.sciencedaily.com
    Exercise Performance Ketosis

    Ketones are molecules produced by the liver during the breakdown of fatty acids. Supplemental ketones – referred to as endogenous ketones – are popular among many athletes due to their purported beneficial effects on performance. A new study shows that endogenous ketone supplementation impairs athletic performance in endurance athletes.

    Researchers asked 23 well-trained adult cyclists to consume a ketone supplement (providing 0.35 grams of ketones per kilogram body weight) or a placebo 30 minutes before completing a 20-minute cycling trial on an exercise bike. The participants repeated the cycling trial a week later with the opposite beverage.

    The researchers found that the participants' power output after taking the ketone supplement was 2.4 percent lower than after taking the placebo, regardless of the order in which they performed the two treatments. The cyclists' average heart rate during the trial was lower after taking the ketone ester, but other factors, such as peak heart rate, glucose levels, and perceived exertion, were similar between the two situations. Out of the 22 participants, 11 felt their perceived exertion was greater after taking the ketone ester, seven felt the same in both situations, and four felt less exertion after taking the ketone ester than when taking the placebo.

    Although this was a small study, these findings suggest that exogenous ketone supplementation impairs performance in endurance athletes in a setting of short-duration, high-intensity training. However, some evidence suggests that ketone supplementation enhances performance in extreme settings in which hypoxia may be a factor, such as mountain climbing. Learn more in this clip featuring ketone expert Dr. Dominic D'Agostino.

    Coming soon: an interview with Dr. Martin Gibala, one of the investigators involved in this study.

    Read more
  • Strict 12-week keto without calorie counting: participants lost >5% percent body fat, 44% of their visceral fat, and 48% better insulin sensitivity www.sciencedaily.com
    Diet Obesity Ketosis Insulin Resistance Metabolic Syndrome Visceral Fat Ketogenic Diet

    This is a Jeff Volek study and used hard biomarkers, checking ketones daily.

    From the article:

    In the study, which appears in the journal Military Medicine, participants on the keto diet lost an average of almost 17 pounds and were able, with support of counselors, to maintain ketosis for 12 weeks. As a group, they lost more than 5 percent of their body fat, almost 44 percent of their belly, or visceral, fat and had a 48 percent improvement in insulin sensitivity – a marker that predicts risk of diabetes.

    […]

    The ketogenic diets in the study included no caloric restrictions, just guidance about what to eat and what to avoid. Carbs were restricted to about 30 to 50 grams daily, with an emphasis on nuts and non-starchy vegetables.

    […]

    Keto diet participants had near-daily check-ins during which they reported blood ketone measurements from a self-administered finger-prick test and received feedback, usually through text messages, from the research team. Ketosis was defined as a blood concentration of ketones, chemicals made in the liver, between 0.5 and 5.0 mM (millimolar).

    Read more
  • Ketogenic diet and β-Hydroxybutyrate may improve disorders of epigenetic machinery via HDAC inhibition, reducing intellectual disability www.sciencedaily.com
    Brain Epigenetics Ketosis Intelligence HDAC Inhibitor Ketogenic Diet

    Ketogenic diet and beta-hydroxybutyrate improve gene transcription and reduce intellectual disability in Kabuki syndrome.

    Kabuki syndrome is a debilitating inherited disorder caused by mutations in two genes involved in the regulation of chromatin remodeling, one of the first steps in DNA transcription. Ketones such as beta-hydroxybutyrate have been shown to enhance DNA transcription and gene expression. Findings from one group of researchers show that a ketogenic diet can alleviate some of the neurological deficits of Kabuki syndrome and improve memory.

    Kabuki syndrome is named for the facial features common to people with the disorder, which looked similar to Kabuki theatre makeup to the Japanese scientists who first researched the disease. In addition to distinctive facial features, the syndrome causes a wide range of health problems such as heart defects, difficulty eating, weak muscle tone, immune deficiency, and intellectual disability. This wide range of severe health issues is explained by the fundamental importance of chromatin remodeling to the body’s functioning, which is impaired in those with Kabuki syndrome.

    Chromatin is the name for the coiled structure DNA forms within the cells of plants and animals, which looks a bit like a tangled telephone cord. This coiled structure prevents DNA from being opened and transcribed (the first step in gene expression and DNA replication) randomly. Chromatin is wrapped around histone proteins that open or close the chromatin, based on whether the histone has a chemical tag called an acetyl group attached or not. As DNA accumulates epigenetic changes over the lifespan, histones become resistant to acetylation, chromatin is harder to open, and gene expression slows. Histone deacetylase (HDAC) inhibitors, such as the ketone beta-hydroxybutyrate (BHB), are compounds that help release histones, open chromatin, prevent loss of gene expression with aging, and may even lengthen lifespan.

    The researchers used a strain of mice that have the same DNA mutations that cause Kabuki syndrome in humans and fed them either a normal diet or a ketogenic diet for two weeks. The researchers fed a third group of mice a normal diet and gave them three daily injections of BHB for two weeks. To assess memory and cognitive performance, mice completed a water maze, a sensitive measure of hippocampal function, which is closely related to memory. The researchers measured changes in gene expression, HDAC activity, and neurogenesis.

    Compared to a normal chow diet, a ketogenic diet increased the concentration of serum BHB, normalized acetylated histone levels, and increased the expression of several genes that are downregulated in Kabuki syndrome. These changes in gene expression enhanced multiple markers of neurogenesis and improved performance during the water maze test. Mice eating a normal diet that received daily BHB injections achieved similar serum BHB levels as mice eating a ketogenic diet and experienced the same gains in neurogenesis.

    This comprehensive study provides insight into the potential of ketogenic diets and supplemental BHB to improve deficits in gene expression in mice with a debilitating genetic disorder. Future research is needed in order to translate these insights into clinically useful information for humans.

    Read more
  • β-Hydroxybutyrate may be a substitute for butyrate in protecting from colon cancer: BHB activates a natural receptor involved in killing cancer cells www.sciencedaily.com
    Nutrition Cancer Diet Ketosis Fiber Butyrate HDAC Inhibitor

    Currently selected for this coming member’s digest by team member Melisa B.

    From the article:

    Researchers report in the April issue of Cancer Research that the GPR109A receptor is activated by butyrate, a metabolite produced by fiber-eating bacteria in the colon. The receptor puts a double-whammy on cancer by sending signals that trigger cell death, or apoptosis, and shutting down a protein that causes inflammation, a precursor to cancer.

    […]

    That got the German research team to search for alternative activators of the receptor, resulting in identification of beta-hydroxybutyrate as a natural receptor activator. The same study showed butyrate also could activate the receptor but with much less potency. That got Dr. Ganapathy thinking about a place where butyrate levels were already high – the colon – which led to his discovery that the receptor was also on colon cells.

    Butyrate plays other protective roles in colon cancer. In 2004, MCG researchers identified a gene, SLC5A8, that transports butyrate inside cells where it inhibits the enzyme HDAC, which gets upregulated in cancer to produce the uncontrolled cell growth that is a disease hallmark.

    “If you block HDAC, you can kill the cancer cell,” Dr. Ganapathy says.

    Read more
  • 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.

    Read more
  • D-beta-hydroxybutyrate supplementation restored impaired brain function and protected against neurodegeneration in mouse model of Parkinson's disease www.sciencedaily.com
    Nutrition Brain Parkinson's Aging Ketosis Neurodegeneration

    From the article:

    Infusion of D-beta-hydroxybutyrate (D-beta-HB) to mice suffering from Parkinson disease restored impaired brain function and protected against neurodegeneration and motor skill abnormalities.

    […]

    Przedborski and colleagues administered the neurotoxin MPTP to mice, which caused dopaminergic neurodegeneration and deficits in the mitochondrial electron transport chain reminiscent of Parkinson disease. Using this model of disease, the authors showed that the infusion of the ketone body D-beta-HB restored mitochondrial respiration and protected against MPTP-induced neurodegeneration and motor deficits. The study supports a critical role for mitochondrial defect in Parkinson disease.

    Read more
  • Beta-hydroxybutyrate produced from a ketogenic diet may improve gout symptoms (animal study) www.sciencedaily.com
    Nutrition Diet Ketosis Inflammation Arthritis NLRP3 Ketogenic Diet

    Beta-hydroxybutyrate reduces symptoms of gout.

    Gout is a painful, debilitating disease that affects more than 8 million people living in the United States. The condition arises when uric acid crystals form in and around the joints, causing inflammation, pain, and impaired mobility. Evidence from a 2017 study suggests that beta-hydroxybutyrate inhibits the activity of the NLRP3 inflammasome, reducing symptoms of gout.

    Beta-hydroxybutyrate is a type of ketone body. It forms in the liver via the breakdown of fatty acids and can be used to produce energy in the mitochondria. Beta-hydroxybutyrate also acts as a signaling molecule that alters gene expression via a wide range of molecular pathways. Ketogenic diets induce beta-hydroxybutyrate production.

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. The NLRP3 inflammasome, in particular, triggers the release of the proinflammatory proteins interleukin (IL)-1 beta and IL-18 and drives pyroptosis, a form of cell death that is triggered by proinflammatory signals and closely linked with inflammation.

    The study involved rats that are prone to developing gout. The investigators fed one group of the rats a normal diet and fed another group a ketogenic diet. After one week, they measured ketones present in the animals' urine. They found that the ketogenic diet induced production of beta-hydroxybutyrate, which in turn protected the animals against uric acid-induced elevations in IL-1 beta. Examination of the animals' joints revealed that the rats that ate the ketogenic diet had less joint inflammation than those fed a normal diet.

    Next, the investigators assessed the effects of beta-hydroxybutyrate on neutrophils, a type of immune cell, from both young and old humans. They found that the compound inhibited the NLRP3 inflammasome-induced IL-1 beta secretion in both young and old neutrophils, suggesting that the ketone plays a role in activating the inflammasome in neutrophils, regardless of age.

    These findings suggest that beta-hydroxybutyrate inhibits the activity of the NLRP3 inflammasome, reducing the symptoms of gout. Researchers do not know if these results translate to humans, however. Learn more about the health effects of beta-hydroxybutyrate in our overview article.

    Read more
  • Salt may increase blood pressure partly through reducing the production of ketone beta-hydroxybutyrate www.sciencedaily.com
    Exercise Gut Diet Microbiome Ketosis Heart Disease Blood Pressure

    From the article:

    “Our team found that high salt consumption lowered levels of circulating beta hydroxybutyrate. When we put beta hydroxybutyrate back in the system, normal blood pressure is restored,” said Dr. Bina Joe, Distinguished University Professor and chair of UT’s Department of Physiology and Pharmacology and director of the Center for Hypertension and Precision Medicine. “We have an opportunity to control salt-sensitive hypertension without exercising.”

    The effects may be microbiome mediated. Read the following excerpt from discussion in a Cell spotlight:

    Changes in the microbiota, specifically a decrease in Lactobacillus spp., in rats fed a high-salt diet have also been implicated in drivingthe progression of hypertension. The authors found that Lactobacillus spp. and Proteobacteria were reduced and Prevotella spp. were increased by a high-salt diet. The changes in the microbiota were associated with a decrease in gluconeogenesis and ketone metabolism, which was not restored by supplementation with 1,3-butanediol. Interestingly, after 1,3butanediol treatment, Proteobacteria and Prevotella shifted back toward the low-salt relative abundance and also correlated with an increase in protective Akkermansia levels.

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

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

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

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

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

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

    Read more
  • A ketogenic diet may be beneficial for people with brain tumors. www.sciencedaily.com
    Cancer Ketosis Ketogenic Diet

    Glioma is a collective term for tumors that arise from the glial cells in the brain. Astrocytoma, the most common form of glioma, arises from star-shaped cells in the brain called astrocytes. The the survival rate for glioma, including astrocytoma, is low. Findings from a recent study suggest that a ketogenic diet is beneficial for people with astrocytoma.

    Ketogenic diets are low in carbohydrates and high in proteins and fats. They cause the body to oxidize fats to produce ketones for energy. For many years, ketogenic diets have been used in the clinical setting to reduce seizures in children. They are currently being investigated for the treatment of cancer because evidence suggests that cancer cells cannot use ketones for energy.

    The eight-week intervention study involved 25 people with astrocytoma whose disease was stable following chemotherapy. Participants followed a weekly dietary protocol consisting of five days of a ketogenic diet (consuming 20 grams or less of carbohydrates per day) and two non-consecutive days of fasting (consuming less than 20 percent of their estimated caloric needs). Participants kept food diaries and provided weekly blood and urine for measuring ketones, insulin, glucose, hemoglobin A1c (a measure of long-term blood glucose control), and IGF-1. They underwent brain scans at the beginning and end of the intervention.

    About half of the participants adhered to the dietary intervention, which was well-tolerated and elicited few adverse events. Despite the relatively low compliance, all the participants had ketones in their urine, with 80 percent achieving moderate levels. Participants' hemoglobin A1c, insulin, and fat body mass decreased, but their lean body mass increased. No changes were noted in glucose or IGF-1 levels. The brain scans showed that ketone concentrations increased in the brain (including the tumor tissue) and correlated with ketone levels in the urine.

    These findings demonstrate that a ketogenic diet is safe for people with astrocytoma and may be beneficial as adjunctive therapy. Learn more about how a ketogenic diet, combined with fasting and the standard of care treatment, may help treat aggressive cancers in this clip featuring Dr. Valter Longo.

    Read more
  • A ketogenic diet improves immunity and reduces excessive inflammation. elifesciences.org
    Ketosis COVID-19 Ketogenic Diet

    A Western dietary pattern, characterized by a low intake of fruits and vegetables and a high intake of red and processed meats and added sugars, promotes chronic diseases, including obesity. It also increases low-grade inflammation by directly reprogramming immune cells to become pro-inflammatory. Authors of a recent report investigated the impact of a ketogenic diet on immunity.

    Glucose is the primary energy source for most cells in the body. However, when a person fasts or restricts carbohydrate intake, the body produces ketones from dietary and body fat for energy. One such ketone is beta-hydroxybutyrate, which has been shown to ameliorate low-grade inflammation and related diseases in mice. Whether consuming a very low carbohydrate diet alters immunity in humans is unclear.

    The investigators recruited 44 healthy adults to complete a three-week ketogenic diet that provided less than 30 grams of carbohydrates per day (the amount in about two slices of sandwich bread). Participants gave blood samples before and after the diet period for measurement of immune cells, including antibody-producing T cells. The researchers exposed white blood cells from the pre-diet and post-diet timepoints to varying concentrations of beta-hydroxybutyrate for 48 hours, stimulated them to produce an immune response, and measured the effect.

    When exposed to beta-hydroxybutyrate, pre-diet white blood cells associated with the innate immune system (the driver of chronic low-grade inflammation) did not alter their behavior; however, antibody-producing white blood cells associated with the adaptive immune system became more active. CD4+ and CD8+ T cells exposed to the highest concentration of beta-hydroxybutyrate (10 millimolar), comparable to the maximum circulating level in humans, produced more cytokines used to fight infection. Regulatory T cells, which prevent autoimmunity and excessive inflammation, also increased their activity, including the mitochondrial metabolism of ketones. Participants lost a significant amount of weight over the three-week ketogenic diet period, and their post-diet T cells showed the same metabolic and immunological responses as those in the in vitro experiment.

    The authors concluded that a very low carbohydrate diet or ketogenic diet is a clinical tool for improving T cell-mediated immunity. They suggested that nutrition and dietary interventions should be used more in modern medicine.

    Read more
  • Beta-hydroxybutyrate, a ketone, increases brain-derived neurotrophic factor expression: relevance for neurodegenerative disease www.sciencedaily.com
    Exercise Brain Alzheimer's Diet Ketosis BDNF HDAC Inhibitor

    β-hydroxybutyrate production consequent to exercise induces within the muscle the activities of a key promoter involved in the production of brain-derived neurotrophic factor.

    From the article:

    Studies have shown that BDNF levels in the brains of people with Alzheimer’s or Huntington’s disease are, on average, half that of people without either brain-damaging disease.

    Among the key findings of the current study was that a ketone, a chemical naturally produced in the liver called beta-hydroxybutyrate (DBHB), triggers biological reactions that activate the BDNF gene to produce more of its protein. DBHB has long been known to build up in the body and brain with exercise. Ketones are “by-product” chemicals made when animals break down fat as an alternative energy source after having drained more readily available sugar stores during exercise.

    Specifically, Chao says, the researchers found that DBHB prevents other proteins in the brain known as histone deacetylase complexes, or HDACs, from suppressing BDNF production by altering the environment of the BDNF gene.

    Read more
  • Brain aging emerges in the late 40's but dietary ketosis increases overall brain activity and stabilizes functional networks. news.stonybrook.edu
    Brain Aging Ketosis Insulin Time-Restricted Eating Carbohydrates Ketogenic Diet

    Insulin resistance and poor blood glucose control – defining characteristics of type 2 diabetes – drive changes associated with brain aging and cognitive decline. A growing body of evidence suggests that dementia is the manifestation of insulin resistance and altered metabolism in the brain. A recent study suggests that dietary patterns that promote ketosis improve brain metabolism and function.

    Ketosis is a metabolic state that results in the body’s production and use of ketones (byproducts of fatty acid metabolism). It occurs under conditions of fasting, starvation, and low carbohydrate intake. Ketones induce physiological and metabolic responses to promote brain health.

    The study had multiple components. First, the authors of the study investigated the time course of human brain aging. Using functional MRI (fMRI) data from more than 900 people between the ages of 18 and 88 years, they determined that neural network stability is a biomarker of brain aging, and the loss of network stability manifests as early as the fifth decade of life (average age, 47 years). They found that the greatest changes in the brain occur around the age of 60 years.

    Then they performed fMRI scans on 12 young adults (average age, 28 years) to assess how different energy sources – glucose versus ketones – alter brain function. Each participant underwent three scans under different dietary conditions: a normal diet without fasting, a normal diet with overnight fasting, or a ketogenic diet for one week. They performed fMRI scans on 30 young adults (average age 29 years) 30 minutes after they took an oral bolus of either glucose or ketones or after following their normal diet with overnight fasting. The authors of the study measured the participants' blood glucose and ketone levels before and after each of the scans.

    The fMRI scans revealed that ketones increased overall brain activity and stabilized functional networks, but glucose had the opposite effect, regardless of whether the ketones were produced endogenously or supplied from exogenous sources. These findings suggest that dietary interventions that increase ketone production may be useful in mitigating the harmful effects of glucose on the brain.

    Certain dietary patterns promote ketosis. For example, the Ketoflex 12/3 diet, a form of time-restrictive eating that limits the period during which a person eats to a 12-hour window at least three hours before bedtime, promotes the production of ketones. Watch this clip in which Dr. Dale Bredesen describes this novel dietary protocol and how it improves cognitive function.

    Read more
  • Mice fed a high-fat, low-carbohydrate diet were better able to combat the flu virus and had better survival rates than mice fed a normal diet. www.sciencedaily.com
    Ketosis Immune System Protein Carbohydrates Weight Loss Ketogenic Diet

    More than 20,000 people die every year in the United States from influenza-related complications. Findings from a new study demonstrate that a ketogenic diet confers protection against the influenza virus and improves survival rates in mice.

    A ketogenic diet is a high fat, moderate protein, low carbohydrate eating pattern that causes the body to oxidize fat to produce ketones for energy. The ketogenic diet has been used in the clinical setting to reduce seizures in children and is being investigated for the treatment of traumatic brain injury, Alzheimer’s disease, weight loss, and cancer.

    The authors of the study fed a ketogenic diet or regular chow to mice for seven days and then infected them with influenza virus. The mice that ate the ketogenic diet lost less weight, maintained better blood oxygen levels, and had improved survival rates compared to the mice that ate the regular chow. In addition, the mice on the ketogenic diet had higher levels of specialized T-cells in their lungs that enhanced airway cell mucus production to improve lung barrier function.

    Interestingly, the beneficial effects of a high fat diet were only observed with the ketogenic diet. Feeding the mice a high-fat, high-carbohydrate diet or providing exogenous ketones in the diet had no beneficial effects against influenza virus.

    Read more
  • 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

    Read more
  • PPAR-Alpha Agonists
    Diet Ketosis Fat Saturated Fat Dairy Ketogenic Diet

    For the last year and a half, I have been on a ketogenic diet. Admittedly, it was heavy on saturated fat from dairy. Recently discovered that I have hypofunctioning PPAR-alpha genetics. Which now makes perfect sense because I could never get my ketones above 1 mmol, and my LDL skyrocketed (~190 on NMR, 86 when not in ketosis). Obviously, there were negatives to that dietary approach for me, but there were also a lot of positives. Not to mention, I would like to take advantage of the potential for longevity, decreasing cancer risk, etc that the ketogenic diet holds. Since learning this info (on top of the not so stellar labs), I have transitioned to a more Mediterranean diet with an emphasis on PUFA and MUFA. I’ve thought about doing periods of ketosis and fasting every now and then, while using PPAR-alpha agonists (like sesamin) to offset the genetic hypofunctioning. Would really like to get some insight on the safety, efficacy, etc of doing this.

    Read more
  • 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.

    Read more
  • Insulin Sensitivity and Glucose Tolerance Are Altered by Maintenance on a Ketogenic Diet (2010) academic.oup.com
    Ketosis Insulin Carbohydrates Ketogenic Diet

    Low-carbohydrate, ketogenic diets (KD) are frequently implemented in efforts to reduce or maintain body weight, although the metabolic effects of long-term exposure to this type of diet remain controversial. This study assessed the responsivity to peripheral and central insulin, glucose tolerance, and meal-induced effects of consuming a KD in the rat. After 8 wk of consuming chow or KD, caloric intake after peripheral or central insulin and insulin and glucose levels after a glucose challenge were assessed. In a separate group of rats, glucose and insulin responses to either a low- or high-carbohydrate test meal were measured. Finally, rats maintained on KD were switched back to a chow diet, and insulin sensitivity and glucose tolerance were evaluated to determine whether the effects of KD were reversible. Maintenance on KD resulted in decreased sensitivity to peripheral insulin and impaired glucose tolerance. Furthermore, consumption of a high-carbohydrate meal in rats that habitually consumed KD induced significantly greater insulin and glucose levels for an extended period of time, as compared with chow-fed controls. Responsivity to central insulin was heightened in KD rats and associated with increased expression levels of insulin receptor mRNA. Finally, returning to a chow diet rapidly reversed the effects of KD on insulin sensitivity and glucose tolerance. These data suggest that maintenance on KD negatively affects glucose homeostasis, an effect that is rapidly reversed upon cessation of the diet.

    Read more
  • Suppression of insulin with a ketogenic diet improves the efficacy of cancer drugs known as PI3K inhibitors and shrinks tumors in mice. www.nature.com
    Cancer Ketosis Insulin Ketogenic Diet

    Suppression of insulin with a ketogenic diet improves the efficacy of cancer drugs known as PI3K inhibitors and shrinks tumors in several different animal models of cancer.

    Insulin activates the PI3K pathway is usually which then leads to cell proliferation and tumor growth. Drugs inhibiting the PI3K pathway have not been very effective due to an insulin feedback response. A ketogenic diet lowered the insulin response and made the drugs more effective.

    The researchers point out that this study doesn’t suggest a ketogenic diet alone would treat cancer. Their data showed in a leukemia model, the ketogenic diet seemed to make cancer more aggressive in mice who were not also given a PI3K inhibiting drug. However, the combination of a PI3K inhibitor and ketogenic diet showed efficacy in many different cancer types (in mice).

    Talk of a pilot clinical study in humans is underway.

    Read more
  • 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.

    Read more