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Ketogenic Diet

Episodes

Posted on November 12th 2022 (over 2 years)

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

Posted on May 23rd 2022 (almost 3 years)

In this clip, Dr. Dominic D'Agostino explains the rationale behind the development and use of exogenous ketones.

Posted on May 21st 2022 (almost 3 years)

Dr. Morgan Levine, describes the importance of this step in making her epigenetic clock PhenoAge and that of her postdoctoral mentor GrimAge more accurate in their ability to detect biological age and epigenetic age acceleration.

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News & Publications

  • 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.

  • Roughly 60% of the human brain is made up of fat, which plays a crucial role in the structure and function of brain cells. In Alzheimer’s, fat metabolism in the brain becomes altered, influencing disease progression. A recent study found that a modified Mediterranean ketogenic diet boosted healthy fats in the brain and lowered Alzheimer’s-associated markers.

    The study included 20 adults with prediabetes who were at risk for developing Alzheimer’s. Participants followed the modified Mediterranean ketogenic diet or the American Heart Association diet for six weeks. After a six-week break, they switched to the opposite diet for another six weeks. Before and after each diet intervention, participants underwent cognitive testing, and the researchers evaluated their blood lipids and Alzheimer’s markers, including amyloid-beta and tau.

    They found that the modified Mediterranean ketogenic diet caused notable changes in blood lipids, increasing molecules linked to fat breakdown and energy use (such as free fatty acids and acylcarnitines) while lowering triglycerides. It also boosted healthy lipid types (plasmalogens) and reduced harmful ones (deoxyceramides). These alterations in blood lipids correlated with improved Alzheimer’s biomarkers and cognitive measures. The American Heart Association diet had little or no effect on blood lipids or cognitive function.

    The traditional ketogenic diet is high in fat and low in carbohydrates. The modified Mediterranean-ketogenic diet is rich in fish, lean meats, and fiber-rich green leafy vegetables, nuts, and berries. About 5% to 10% of its calories come from carbohydrates, 60% to 65% from fat, and 30% from protein. In the American Heart Association diet, about 55% to 65% of calories come from carbohydrates, 15% to 20% from fat, and 20% to 30% from protein.

    The findings from this small intervention study suggest that a modified Mediterranean ketogenic diet protects against Alzheimer’s disease. Learn more about the ketogenic diet and Alzheimer’s disease in this clip featuring Dr. Dale Bredesen.

  • Redefining the causes of obesity. www.sciencedaily.com

    Obesity is a complex, multifactorial disease influenced by genetic, molecular, environmental, and behavioral factors. Characterized as having excessive body fat, obesity affects more than 650 million people worldwide and markedly increases a person’s risk for many chronic diseases, including cardiovascular disease, type 2 diabetes, cancer, and depression, among others. The authors of a recent report challenge the prevailing theory regarding the root causes of obesity.

    A widely espoused concept in bodyweight management is the “eat less, exercise more” model, based on the principle that the number of calories consumed must be equivalent to (or less than) the number of calories expended. This model is supported by evidence suggesting that consuming high-fat foods drives overconsumption of calories due the foods' high caloric levels, poor ability to provide satisfaction and fullness, and high “pleasure factor.” However, this concept, which forms the basis for national dietary guidelines, public health messaging, and dietary counseling, is inherently flawed, because it fails to take into consideration the biological mechanisms that promote weight gain. Ultimately it places blame on people with obesity and promotes stigmatization.

    In recent decades, scientists have proposed a new model for explaining the root causes of obesity. In this model, body fat accumulation arises from hormonal responses to the consumption of high-glycemic load carbohydrates, ultimately driving a vicious cycle of body fat accumulation, hunger, and food intake. Commonly referred to as the “carbohydrate-insulin” model of obesity, this new paradigm reverses causation and provides a starting point for developing testable hypotheses.

    The concepts presented in this report suggest that what a person eats, rather than how much, plays key roles in body weight management. The authors of the report posited that if the carbohydrate-insulin model is accurate, dietary modifications that limit carbohydrate intake, such as a ketogenic diet, may alter hormonal responses and promote fat oxidation and weight loss. Learn more about the health benefits of the ketogenic diet in this clip featuring Dr. Dominic D'Agostino.

    Link to full publication.

  • Hyperglycemia, which occurs when glucose levels in the blood rise to dangerous levels, is a hallmark of diseases such as metabolic syndrome and type 2 diabetes. The effects of hyperglycemia are well documented and include cellular damage, inflammation, and pro-cancer effects; however, few studies have elucidated the cellular mechanisms of hyperglycemia. Findings of a new report suggest mitochondrial damage explains the connection between hyperglycemia and disease.

    Glucose is consumed in the diet from simple sugars and starches. Glucose transport proteins, which move glucose from the bloodstream into cells, are expressed in the heart, skeletal muscle, adipose tissue, and brain among others. TXNIP is a protein that binds to glucose transporters, preventing the movement of glucose into cells. Mice who do not produce the TXNIP protein, called knockouts, experience uncontrolled glucose transport into cells. Glucose metabolism produces damaging compounds called reactive oxygen species, which attack the delicate lipid membranes in mitochondria, the cell structures that produce energy.

    Brown adipose tissue is particularly vulnerable to the effects of hyperglycemia. This fatty tissue produces heat in response to cold temperatures, while white adipose tissue is mainly for energy storage. Brown adipose tissue appears brown because it has a higher density of mitochondria, which may make these cells more susceptible to damage from hyperglycemia, especially in cold temperatures.

    The investigators compared normal mice with those that did not express the TXNIP protein in their brown adipose tissue. After exposing both groups of animals to cold temperatures (40°F, 4°C) for four hours, the researchers measured their body temperatures using a thermal camera and performed an in vitro study to examine the cellular integrity of mitochondria and their ability to produce energy from multiple common fuel sources.

    These experiments revealed that TXNIP knockout mice had lower body temperatures after cold exposure than normal mice, suggesting that their brown adipose tissue was less effective at producing heat under stress conditions. Their mitochondria also showed signs of membrane damage and reduced concentration of polyunsaturated fats, which indicated that they were significantly more stressed due to reactive oxygen species produced during cold exposure compared to mitochondria in normal mice. TXNIP knockout mice had lower expression of genes related to energy metabolism and heat production.

    Interestingly, the researchers found that severely restricting the TXNIP-deficient animals’ glucose intake by feeding them a ketogenic diet for five weeks mitigated the stress-induced deficit in mitochondrial function and reversed the detrimental changes to the polyunsaturated fat content of their mitochondrial membranes.

    These findings indicate that excess sugar intake creates mitochondrial dysfunction, which contributes to poor health. A ketogenic diet reversed the effects of hyperglycemia on mitochondrial function.

  • 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.

  • 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.

  • Obesity affects more than 650 million people worldwide. Although low-carbohydrate and low-fat diets are effective at helping people lose weight, the health benefits and sustainability of the two dietary approaches are matters of controversy. A recent trial weighed the benefits of low-fat versus low-carbohydrate diets.

    The causes of obesity and overweight are not fully known. Some scientists have suggested that consuming high-glycemic carbohydrates increases insulin levels, ultimately driving a vicious cycle of body fat accumulation, hunger, and food intake, commonly referred to as the “carbohydrate-insulin” model of obesity. Others have suggested that consuming high-fat foods drives overconsumption of calories due the foods' high caloric levels, poor ability to provide satisfaction and fullness, and high “pleasure factor.”

    The four-week crossover trial involved 20 healthy men and women (average age, 30 years). Half of the participants ate an animal-based, ketogenic, low-carbohydrate diet that provided about 10 percent of its calories from carbohydrates and about 75 percent from fat and high calorie foods. The other half ate a plant-based, low-fat diet that provided about 10 percent of its calories from fat and about 75 percent from carbohydrates and low-calorie foods. After two weeks on their respective diets, participants switched diets and adhered to the new diet for another two weeks. All meals were prepared and served in an in-patient metabolic ward to ensure compliance. The study investigators monitored the participants' weight, vital signs, blood ketones, energy expenditure, activity, and other measures throughout the study.

    Although both diets promoted weight loss, participants on the low-carbohydrate diet lost more weight (1.5 pounds) and faster, but the difference was not statistically or clinically significant. The participants who ate the low-fat diet had higher glucose and insulin levels compared to those who ate the low-carbohydrate diet. They didn’t report any differences in hunger, fullness, or satisfaction with their meals. When eating the low-fat diet, participants ate about 690 fewer calories per day than when eating the low-carbohydrate diet over the two-week period.

    These findings suggest that whereas eating a low-carbohydrate diet is beneficial in reducing glucose and insulin levels, the low-fat diet reduces appetite, a finding that contradicts the carbohydrate-insulin model of obesity.