#845: How to Use Ketosis for Enhanced Mood, Cognition, and Long-Term Brain Protection — A Practical and Tactical Guide with Dr. Dominic D'Agostino (Plus: Deconstructing Tim’s Latest Keto Experiment)
In this episode of The Tim Ferriss Show, Tim Ferriss and Dr. Dominic D'Agostino explore the science and practical applications of ketosis. They discuss how ketosis affects mental performance, mood, and sleep patterns, while examining its potential role in treating various neurological and psychiatric conditions. The conversation covers successful implementation strategies for a ketogenic diet, including the role of intermittent fasting and optimal macronutrient ratios.
The experts delve into the concept of "metabolic memory" and explain how the body adapts to repeated periods of ketosis. They also evaluate the benefits and risks of exogenous ketone supplements, providing context for their use in different scenarios. From weight management to potential therapeutic applications in conditions like depression and neurodegenerative diseases, this discussion offers insights into ketosis's wide-ranging effects on physical and mental health.
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1-Page Summary
Benefits of Ketosis (Cognitive/Mental and Physical)
Tim Ferriss and Dominic D'Agostino discuss the wide-ranging benefits of ketosis, from cognitive enhancement to physical health improvements. Ferriss reports experiencing increased mental sharpness, mood stabilization, and reduced sleep needs while in ketosis. D'Agostino explains that ketosis elevates GABA, a calming neurotransmitter that reduces anxiety, and promotes weight loss through improved metabolic health.
Practical Strategies For Implementing a Ketogenic Diet
The experts share key strategies for successfully implementing a ketogenic diet. They emphasize the importance of intermittent fasting to facilitate the transition into ketosis, with Ferriss noting that fasting for at least 16 hours depletes liver glycogen. D'Agostino introduces the concept of cycling between strict ketosis and "protein veggie" days to optimize body composition. For maintaining ketosis, they recommend keeping carbs under 20g daily, with moderate protein and high fat intake.
Therapeutic Applications of Ketosis for Various Health Conditions
According to D'Agostino, ketosis shows promise in treating various neurological and psychiatric conditions, including depression, bipolar disorder, and schizophrenia. He discusses its potential in preventing neurodegenerative diseases like Alzheimer's by improving metabolism and reducing inflammation. Additionally, ketosis is being explored as an adjunct therapy for certain cancers, with D'Agostino noting its ability to enhance the immune response and potentially slow tumor growth.
Pros and Cons of Exogenous Ketone Supplements
While exogenous ketone supplements can quickly boost ketone levels, D'Agostino warns about potential risks, particularly with 1,3-butanediol formulations that can cause liver damage. He and Ferriss discuss ways to mitigate negative effects, such as combining ketones with MCT oil to prevent rapid spikes and crashes in ketone levels.
Metabolic Memory and Long-Term Effects of Ketosis
D'Agostino introduces the concept of "metabolic memory," suggesting that the body becomes more efficient at transitioning into ketosis with repeated exposure. He compares this to muscle memory and notes that the benefits of ketosis may extend beyond the active period of the diet, with some effects potentially lasting for months after returning to normal eating patterns.
1-Page Summary
Additional Materials
Counterarguments
- While ketosis may enhance cognitive function for some, individual responses can vary, and some people may experience negative effects such as brain fog or decreased mental performance, especially during the initial transition period.
- The claim that ketosis elevates GABA levels and reduces anxiety is not universally supported; some individuals may experience increased anxiety or mood swings on a ketogenic diet.
- Ketosis can promote weight loss, but it is not inherently superior to other dietary approaches for weight management; calorie balance is still the primary factor in weight loss.
- Intermittent fasting can aid in the transition to ketosis, but it may not be suitable for everyone, and some individuals may experience negative side effects such as fatigue, irritability, or disordered eating patterns.
- The strategy of cycling between strict ketosis and "protein veggie" days may not be optimal for everyone, and long-term adherence to such a regimen can be challenging.
- A daily carbohydrate intake of fewer than 20 grams may be too restrictive and difficult to maintain for some individuals, potentially leading to nutrient deficiencies or decreased quality of life.
- While there is some evidence supporting the therapeutic potential of ketosis for certain conditions, more research is needed to fully understand its efficacy and safety, especially for long-term use.
- The role of ketosis in cancer therapy is still under investigation, and it should not be considered a standalone treatment; it is important to follow evidence-based medical advice for cancer care.
- Exogenous ketone supplements may not be necessary for achieving ketosis and can be expensive; a well-formulated ketogenic diet may be sufficient for most individuals.
- The concept of "metabolic memory" is an emerging area of research, and more evidence is needed to confirm its existence and long-term implications.
- The persistence of ketosis benefits after discontinuing the diet is not guaranteed, and some individuals may revert to their previous metabolic state or experience weight regain.
Actionables
- You can track your cognitive performance by using a daily journal to note changes in mental clarity, mood, and sleep patterns as you follow a ketogenic diet. Start by rating your mental sharpness, mood stability, and sleep quality on a scale from 1 to 10 each day. After a few weeks, review your entries to identify any trends or improvements that may correlate with your dietary habits.
- Create a personalized intermittent fasting schedule by using a calendar app to plan your eating and fasting windows, aiming for at least a 16-hour fast daily. Set reminders for when to start and end your eating window, and use the app to monitor your progress over time, adjusting as needed based on your body's response and your lifestyle.
- Experiment with a "protein veggie" day once a week, where you focus on consuming high-protein, low-carb vegetables, to see how it affects your body composition. Keep a food diary on these days to ensure you're meeting your nutritional goals and to observe how your body responds in terms of energy levels, hunger, and overall well-being.
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Benefits of Ketosis (Cognitive/Mental and Physical)
Ketosis not only assists in weight management but also enhances cognitive performance and mood stability, as discussed by experts like Tim Ferriss and Dominic D'Agostino.
Ketosis Provides Mood Stabilization and Cognitive Enhancement
Tim Ferriss talks about the mood-stabilizing and cognitive enhancement effects of ketosis, based on his personal experience. He notes an increase in mental sharpness, verbal acuity, and a faster ability to process thoughts. Furthermore, he has observed complete mood stabilization and reports feeling calm, stable, and sharp.
Dominic D'Agostino highlights ketosis's potential mental health benefits by explaining that being in a state of ketosis can lead to a quieter mind. He notes that ketosis elevates GABA, a calming neurotransmitter that helps reduce glutamate levels and anxiety. This effect on the brain is compared to the quieting effect produced by alcohol and benzodiazepines.
Ketosis Reduces Anxiety By Elevating the Brain-Stabilizing Neurotransmitter GABA
D'Agostino specifically mentions that ketosis elevates GABA, which reduces anxiety by stabilizing the brain. This shift in brain chemistry can have profound effects on a person's overall sense of well-being and mental clarity.
Ketosis Reduces Sleep Need and Prevents Energy Slumps
Ferriss has found that his sleep needs decrease while in ketosis; he requires only about six to six and a half hours of sleep instead of the usual eight to nine hours. He wakes up feeling alert and ready to start the day without the typical caffeine dependence or an hour-long "booting up" period.
Ferriss also shares that he does not experience the common afternoon energy dips associated with a carbohydrate-rich diet. He suggests his cognitive symptoms disappear within three to four days on a strict ketogenic diet, indicating enhanced cognitive functioning.
Ketosis Promotes Weight Loss and Improves Metabolic Health
D'Agostino discusses weight loss as one ...
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Benefits of Ketosis (Cognitive/Mental and Physical)
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Clarifications
- Ketosis is a metabolic state where the body uses fat, instead of carbohydrates, as its primary energy source. This occurs when carbohydrate intake is very low, causing the liver to convert fat into molecules called ketones. Ketones then serve as an alternative fuel for the brain and muscles. Entering ketosis typically requires reducing carbs to about 20-50 grams per day for several days.
- Ketones are molecules produced by the liver from fat when carbohydrate intake is very low. They serve as an alternative energy source for the brain and body during periods of fasting or low-carb diets. Ketones help preserve muscle by providing fuel when glucose is scarce. This metabolic shift from glucose to ketones is the basis of ketosis.
- GABA (gamma-aminobutyric acid) is the brain's primary inhibitory neurotransmitter, which means it reduces neuronal activity and promotes calmness. Glutamate is the main excitatory neurotransmitter, responsible for stimulating brain activity and promoting learning and memory. An imbalance, with too much glutamate or too little GABA, can lead to anxiety, excitability, or neurological disorders. Ketosis may help restore balance by increasing GABA and reducing glutamate, leading to a calmer, more stable brain state.
- Ketosis increases the production of ketone bodies, which influence brain metabolism and neurotransmitter balance. These ketones enhance the synthesis of GABA, an inhibitory neurotransmitter that calms neural activity. Simultaneously, ketosis reduces glutamate, an excitatory neurotransmitter, by shifting brain energy use and altering enzyme activity involved in neurotransmitter cycling. This balance helps stabilize brain function and reduce anxiety.
- Alcohol and benzodiazepines both enhance the activity of GABA, a neurotransmitter that calms brain activity. This results in reduced anxiety, sedation, and a feeling of relaxation. Ketosis similarly increases GABA levels, promoting a calmer, quieter mind without the impairing effects of these substances. Unlike alcohol and benzodiazepines, ketosis does this naturally through metabolic changes rather than drug intake.
- A diuretic effect means the body increases urine production, leading to more water and salt being expelled. This reduces fluid volume in the bloodstream, which can lower blood pressure. It also causes rapid initial weight loss due to water loss, not fat loss. Prolonged diuretic effects require maintaining electrolyte balance to avoid dehydration.
- When the body loses water and sodium, the total fluid circulating in the bloodstream decreases. This reduction in fluid volume lowers the overall blood volume. Lower blood volume means less pressure exerted on blood vessel walls, resulting in decreased blood pressure. This mechanism helps explain why diuretic effects can reduce blood pressure.
- [restricted term] is a hormone that helps cells absorb glucose from the blood for energy. [restricted term] resistance occurs when cells become less responsive to [restricted term], causing higher blood sugar and [restricted term] levels. This condition stresses the body and can lead to metabolic disorders like type 2 diabetes. Improving [restricted term] sensitivity through diet or lifestyle supports better metabolic health and energy regulation.
- A ketogenic diet typically consists of about 70-80% of calories from fat, 10-20% from protein, and 5-10% from carbohydrates. This low carbohydrate intake forces the body to use ...
Counterarguments
- While ketosis may improve cognitive function for some, individual responses to a ketogenic diet can vary, and some people may experience negative effects such as brain fog or decreased mental performance, especially during the initial adaptation phase.
- The mood-stabilizing effects of ketosis are not universally experienced, and some individuals may find that the diet exacerbates mood disorders or emotional instability.
- The comparison of ketosis's effect on GABA to that of alcohol and benzodiazepines may be misleading, as these substances can have addictive properties and negative health effects that are not associated with a ketogenic diet.
- The reduction in sleep needs reported by some individuals in ketosis may not apply to everyone, and long-term sleep reduction could potentially have negative health consequences.
- The claim that ketosis prevents afternoon energy slumps is anecdotal and may not reflect the experience of all individuals on a ketogenic diet.
- The rapid initial weight loss associated with ketosis is largely due to water loss and may not represent true fat loss; sustainable weight loss requires a long-term commitment to healthy eating and lifestyle habits.
- The diuretic effect of ketosis leading to reduced blood volume and lower blood pressure could be a concern for individuals with normal or low blood pressure, potentially leading to hypotension.
- Lowering [restricted term] levels through ketosis can be beneficial for those with [restricte ...
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Practical Strategies For Implementing a Ketogenic Diet
Tim Ferriss, Dominic D'Agostino, and other experts share strategies for transitioning to and optimizing a ketogenic diet, emphasizing the importance of fasting, macronutrient composition, and cycling ketosis with higher-carb periods.
Fasting Facilitates Transition to Ketosis
Intermittent Fasting Depletes Liver Glycogen, Enabling Fat and Ketone Burning
Intermittent fasting is a powerful tool for transitioning into ketosis, as Tim Ferriss has found through his daily practice for the past six months. He mentions that fasting honed his [restricted term] sensitivity and metabolic health. According to Dr. Rhonda Patrick and Mark Matson's research, fasting for at least 16 hours depletes glycogen from the liver, leading to a metabolic switch and increased mental sharpness. Ferriss notes that, despite initial challenges like irritability and fogginess, his transition to a ketogenic diet was smooth, avoiding the typical "keto flu" symptoms.
D'Agostino explains that during a caloric deficit from fasting, blood ketone levels might appear low, while breath ketone levels may max out the meters, indicating high ketone disposal uptake into tissues.
Cycling Ketosis With Higher-Carb Periods Optimizes Composition
Higher-Protein, Lower-Fat "Protein Veggie" Days Boost Fat Loss and Preserve Muscle
Dominic D'Agostino introduces the concept of "protein veggie" days within a ketogenic diet by reducing fat intake and significantly increasing protein intake. This approach can boost fat loss and preserve muscle. After two days of protein veggie days with reduced fat, D'Agostino feels leaner, attributing the alteration in body composition to the body's trained fat metabolism from ketosis. He pairs higher protein intake with recovery from heavy workouts, and during these days, his calorie intake might be a little lower but focuses on vibrant vegetables.
Macronutrient Composition Is Key For Maintaining Ketosis
Under 20G Carbs, Moderate Protein, High Fat For Ketosis
To achieve and maintain strict ketosis, Ferriss aims for moderate protein and at least 50% of calories from fat, with carbohydrate intake limited to under 20 grams per day. He cautions that consuming protein in liquid form can cause a quick rise in amino acids, which could halt ketosis. Slowing the absorption process is key, and this can be achieved with meals high in fat, fi ...
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Practical Strategies For Implementing a Ketogenic Diet
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Counterarguments
- Intermittent fasting may not be suitable for everyone, and some individuals may experience negative side effects such as hormonal imbalances, increased stress levels, or disordered eating patterns.
- The "keto flu" may not be avoidable for all individuals, as the severity and occurrence of symptoms can vary widely based on personal health status and genetic factors.
- The claim that fasting for at least 16 hours improves [restricted term] sensitivity and metabolic health is not universally applicable, as individual responses to fasting can differ.
- Breath ketone meters may not always provide an accurate measure of ketone uptake by tissues, as they can be influenced by various factors such as hydration levels and the presence of certain compounds in the breath.
- Cycling higher-carb periods into a ketogenic diet may not be optimal for maintaining a state of ketosis or achieving certain health goals, and some individuals may find it disrupts their metabolic adaptation.
- The concept of "protein veggie" days may not be necessary for everyone on a ketogenic diet, and some may find that consistently maintaining a standard ketogenic macronutrient ratio works better for their goals.
- The recommendation to limit carbohydrates to under 20 grams per day for strict ketosis may be too restrictive for some individuals, and higher carbohydrate intake may still allow for ketosis depending on the person's metabolic flexibility and activity level.
- The suggestion that consuming protein in liquid form may halt ketosis is not universally accepted, as the impact on ketosis can vary depending on the overall dietary ...
Actionables
- You can track your macronutrient intake using a personalized food diary app to ensure you're staying within the recommended ranges for a ketogenic diet. By logging everything you eat, you can monitor your carbohydrate intake to stay under 20 grams per day, balance your protein consumption, and adjust your fat intake to make up at least 50% of your calories. This helps you maintain strict ketosis and manage your diet more effectively.
- Create a "keto transition kit" for yourself that includes a variety of high-fat, moderate-protein snacks, electrolyte supplements, and a breath ketone meter. This kit will support you during the initial phase of intermittent fasting and transitioning to ketosis, helping you avoid the "keto flu" and monitor your ketone levels to ensure you're on the right track.
- Experiment with a weekly meal rotation that includes standard ketogenic days, "protein veggie" days, and controlled ...
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Therapeutic Applications of Ketosis for Various Health Conditions
Ketosis, a metabolic state where the body burns fat for energy, is gaining attention for its potential therapeutic applications in various health conditions, including neurological disorders, neurodegenerative diseases, and certain cancers.
Ketosis May Benefit Neurological Disorders and Psychiatric Conditions
D'Agostino discusses the broad application of ketosis for metabolic psychiatry and points out its potential to help with major depression, bipolar disorder, schizophrenia, anxiety disorders, and anorexia nervosa. The ketogenic diet has been recognized to quiet the brain and control seizures across various forms, making its anti-seizure effects promising for conditions like epilepsy, depression, bipolar disorder, and schizophrenia.
Ketosis' Calming, Anti-Seizure Effects Promising For Epilepsy, Depression, Bipolar, Schizophrenia
After contracting Lyme disease and experiencing "pseudo dementia," Ferriss entered strict ketosis, resulting in the disappearance of cognitive symptoms within a few days. By maintaining nutritional ketosis for several weeks, Ferriss notes the complete remission of cognitive and joint pain symptoms.
Ketosis May Help Prevent Neurodegenerative Diseases
D'Agostino discusses the impact of ketosis on age-related chronic diseases like Alzheimer's and indicates that ketosis affects biomarkers known to drive such diseases. He emphasizes the importance of [restricted term] and inflammation regulation and ensuring no deficiencies in vital nutrients, linking metabolic health to brain health, which can delay or prevent Alzheimer's.
Ketosis May Delay Alzheimer's By Improving Metabolism, Lowering Inflammation, and Boosting Brain Energy
Ferriss, with his family's history of neurodegenerative diseases, shows a personal interest in exploring the efficacy of a ketogenic diet to potentially delay something like Alzheimer's. D'Agostino endorses using a continuous glucose monitor for insights on food impacts, noting the benefits of beta-hydroxybutyrate for brain energy and blood flow, which can alleviate issues like vascular dementia.
Ketosis as an Adjunct Therapy for Certain Cancers
D'Agostino mentions ketosis stimulates the adaptive immune response, which is significant for the body to target and neutralize foreign threats. This enhancement of the immune response is under research in conjunction with cancer therapies. Ferriss elaborates on the advantage of depriving glucose-sensitive cancers throug ...
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Therapeutic Applications of Ketosis for Various Health Conditions
Additional Materials
Clarifications
- Ketosis is a natural metabolic state where the body uses fat instead of carbohydrates for energy. When carbohydrate intake is very low, the liver converts fat into molecules called ketones, which serve as an alternative fuel. This process helps maintain energy levels, especially for the brain, which normally relies on glucose. Ketosis typically occurs during fasting, prolonged exercise, or a ketogenic diet.
- The ketogenic diet is a high-fat, very low-carbohydrate eating plan that forces the body to use fat instead of glucose for energy. By drastically reducing carbohydrate intake, the liver converts fat into ketone bodies, which serve as an alternative fuel source. This metabolic shift is called ketosis. The diet typically includes foods like meat, fish, eggs, dairy, oils, nuts, and low-carb vegetables.
- "Pseudo dementia" refers to cognitive impairment that mimics dementia but is caused by reversible conditions like depression or infections. In Lyme disease, inflammation and infection can lead to symptoms such as memory loss and confusion resembling dementia. Unlike true dementia, pseudo dementia symptoms can improve with treatment of the underlying cause. Thus, Lyme disease-related pseudo dementia is a temporary cognitive dysfunction linked to infection rather than permanent brain degeneration.
- Beta-hydroxybutyrate (BHB) is a primary ketone body produced during ketosis that serves as an efficient alternative fuel for the brain when glucose is low. It crosses the blood-brain barrier easily, providing neurons with energy and supporting cognitive function. BHB also has signaling roles that promote blood vessel dilation, improving cerebral blood flow. Additionally, it reduces oxidative stress and inflammation, protecting brain cells and enhancing overall brain health.
- The adaptive immune response is the body's targeted defense system that learns to recognize and remember specific pathogens for stronger future attacks. Ketosis may enhance this response by providing energy-efficient fuel (ketone bodies) that supports immune cell function and reduces inflammation. This improved environment helps immune cells respond more effectively to threats like infections or cancer cells. Thus, ketosis can potentially boost the body's ability to fight diseases through a more robust adaptive immunity.
- Glucose-sensitive cancers rely heavily on glucose for energy and rapid growth. These cancers often exhibit increased glycolysis, known as the Warburg effect, even in the presence of oxygen. Depriving them of glucose can starve cancer cells, slowing tumor growth and making treatments more effective. Ketosis reduces blood glucose levels, limiting fuel availability for these cancer cells.
- Highly glycolytic cancers rely heavily on glucose for energy through a process called glycolysis, even when oxygen is available. This metabolic trait makes them vulnerable to therapies that reduce glucose availability, such as ketogenic diets. By limiting glucose, these diets may slow tumor growth and improve treatment outcomes. Targeting cancer metabolism is a growing area of research in oncology.
- The Glucose Ketone Index (GKI) is a ratio that compares blood glucose levels to ketone levels, providing a measure of metabolic state. It helps determine how deeply a person is in ketosis, which is important for optimizing therapeutic effects. Lower GKI values indicate higher ketosis and are associated with better outcomes in conditions like epilepsy and cancer. Monitoring GKI guides dietary and treatment adjustments to maintain effective ketosis.
- Continuous glucose monitoring (CGM) uses a small sensor inserted under the skin to measure blood sugar levels in real time throughout the day. It helps track how different foods and activities affect glucose, enabling better metabolic control. In ketosis, stable low glucose levels indicate effective fat-burning and ketone production, which supports brain energy and reduces inflammation. Monitoring glucose helps optimize diet and maintain metabolic states beneficial for brain health.
- [restricted term] helps regulate blood sugar and supports brain cell function. ...
Counterarguments
- While ketosis has shown potential benefits for neurological disorders, it is not universally effective for all individuals, and some may not respond to the diet or may experience adverse effects.
- The long-term sustainability of the ketogenic diet is a concern, as it is a restrictive diet that may be difficult for individuals to adhere to over time.
- The ketogenic diet may lead to nutrient deficiencies if not carefully planned, as it restricts or eliminates certain food groups that are important sources of vitamins and minerals.
- The evidence supporting the use of the ketogenic diet for psychiatric conditions such as major depression, bipolar disorder, and schizophrenia is still emerging, and more rigorous clinical trials are needed to establish its efficacy and safety.
- The claim that strict ketosis can rapidly alleviate cognitive symptoms related to conditions like Lyme disease-induced pseudo dementia is based on anecdotal evidence and may not be generalizable.
- The role of ketosis in cancer treatment is complex and not fully understood; while it may have benefits for certain types of cancer, it is not appropriate for all cancer patients and should be considered on a case-by-case basis.
- The impact of ketosis on the immune system is an area of ongoing research, and its effects may vary depending on the individual and the specific health condition.
- The use of continuous glucose monitoring and the Glucose Ketone Index (GKI) as tools for managing health conditions through ketosis requires further validation in clinica ...
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Pros and Cons of Exogenous Ketone Supplements
Exogenous ketone supplements, utilized by some athletes for rapid ketone level increases, raise concerns due to potential toxicities and poor tolerability.
Exogenous Ketone Supplements Boost Circulating Ketone Levels Rapidly
The podcast discusses exogenous ketones like Keto Start, an exogenous ketone salt-based product. Tim Ferriss reveals he took Keto Start with MCT oil about an hour and a half ago, which is popular among certain athletic populations. Dominic D'Agostino’s ketone Mojo device measures D beta-hydroxybutyrate, and racemic salts contain both D and L forms, with the L form taking longer to metabolize and thus remaining in the blood longer.
Toxic Formulations of 1,3-butanediol Can Cause Liver Damage
D'Agostino warns about the toxic potential of 1,3-butanediol, found in some ketone esters he has patented. Chronic consumption of supplements containing 1,3-butanediol could cause liver damage, characterised by inflammation, sinusoidal dilation, and gaps in the liver. This is because 1,3-butanediol metabolizes to beta-hydroxybutyrate aldehyde via alcohol dehydrogenase and aldehyde dehydrogenase, producing harmful compounds like beta-hydroxybutyrate aldehyde. Despite normal transaminase levels in the blood, direct examination of livers showed necrosis, indicating that liver problems might not be reflected in common blood tests. Older individuals, especially those with diminished detoxification abilities, are particularly susceptible to the toxic effects of 1,3-butanediol.
Pharmacokinetics and Tolerability of Exogenous Ketones
D'Agostino raises concerns about the tolerability and pharmacokinetics of 1,3-butanediol-based exogenous ketones. Rapid ketone spikes and subsequent crashes caused by these supplements could halt endogenous ketone production, triggered by the substantial [restricted term] response. D'Agostino highlights the field is shifting away from 1,3-butanediol-based keytones because of these issues, including uncomfortable side effects such as gastrointestinal distress and "disaster pants." He observes that taking a significant amount of a ketone ester causes a quick ketone rise and drop within two hours, with a corresponding increase in [restricted term].
Ferriss experienced intestinal discomfort and a subjective feeling of tiredness with doses above 11 milliliters, suggesting some ketone supplements could be problematic. Dependency issues, abrupt cessation leading to withdrawal resembling alcohol withdrawal, increasing dizzy spells, and dependency have been documented with 1,3-butanediol consumption.
Combining Ketone ...
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Pros and Cons of Exogenous Ketone Supplements
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Clarifications
- Beta-hydroxybutyrate (BHB) exists as two mirror-image forms called enantiomers: D and L. The D form is the biologically active isomer that cells readily use for energy through normal metabolic pathways. The L form is metabolized more slowly because it is not efficiently processed by the enzymes that handle the D form. As a result, L-BHB remains in the bloodstream longer before being converted or excreted.
- Racemic salts contain equal amounts of two mirror-image forms (enantiomers) of a molecule, called D and L isomers. In ketone supplements, the D form is the biologically active ketone used efficiently for energy. The L form is metabolized more slowly and may linger longer in the bloodstream without providing immediate energy. This mixture affects how quickly and how long ketone levels stay elevated after supplementation.
- 1,3-Butanediol is a synthetic alcohol used as a precursor in some ketone esters to raise blood ketone levels. It is metabolized by the liver into beta-hydroxybutyrate, a primary ketone body used for energy. This conversion provides a sustained release of ketones compared to direct ketone salts. However, its metabolism can produce toxic intermediates affecting liver health.
- Alcohol dehydrogenase (ADH) converts alcohols into aldehydes by removing hydrogen atoms. Aldehyde dehydrogenase (ALDH) then oxidizes these aldehydes into acids, which are less toxic and easier to eliminate. This two-step process is crucial for metabolizing substances like ethanol and certain alcohol-based compounds. Accumulation of aldehydes can cause cellular damage and toxicity.
- Beta-hydroxybutyrate aldehyde is a reactive intermediate formed during the metabolism of 1,3-butanediol. It can cause cellular damage by forming harmful adducts with proteins and DNA. This leads to oxidative stress and inflammation, contributing to liver toxicity. Its accumulation disrupts normal liver function and promotes tissue injury.
- Liver inflammation is the swelling and irritation of liver tissue caused by injury or toxins. Sinusoidal dilation refers to the widening of small blood vessels in the liver, which can disrupt normal blood flow. Necrosis means the death of liver cells, leading to loss of tissue function. Gaps in liver tissue indicate areas where cells have died or been damaged, creating spaces that impair liver structure and function.
- Standard blood transaminase tests measure enzymes like ALT and AST released during liver cell injury. However, early or localized liver damage may not cause enough enzyme release to raise blood levels. Some toxic effects cause structural liver changes without widespread cell death, so enzymes remain normal. Direct liver examination or imaging can reveal damage that blood tests miss.
- Endogenous ketone production occurs in the liver when the body breaks down fats for energy during fasting or low carbohydrate intake. [restricted term], a hormone released after eating carbohydrates or protein, signals the body to store energy and inhibits fat breakdown. This suppression reduces the liver's production of ketones, as the body prefers to use glucose for fuel. Therefore, high [restricted term] levels prevent the natural generation of ketones.
- [restricted term] is a hormone that helps regulate blood sugar by promoting glucose uptake and storage. High [restricted term] levels signal the body to stop producing ketones, as it prioritizes using glucose for energy. This inhibits ketosis, the metabolic state where fat is broken down into ketones for fuel. Therefore, [restricted term] spikes can quickly halt the benefits of ketogenic metabolism.
- MCT oil is a fat composed of medium-chain triglycerides, which are absorbed faster than long-chain fats because they go directly to the liver via the portal vein. In the liver, MCTs are rapidly converted into ketones, providing an immediate energy source. MCT oil slows gastric emptying, meaning food and supplements leave the stomach more gradually, leading to steadier nutrient absorption. This slower absorption helps prevent sudden spikes in blood ketone and [restricted term] levels.
- "Disaster pants" is a humorous slang term describing sudden, uncontrollable diarrhea or urgent bowel movements. It often occurs as a side effect of substances that irritate the digestive system or speed up gut motilit ...
Counterarguments
- The efficacy and safety of exogenous ketones can vary widely depending on the individual's health status, metabolism, and existing diet, which is not addressed in the text.
- The text may overemphasize the potential risks of 1,3-butanediol without considering the dosage and frequency of intake that could lead to such adverse effects.
- The claim that older individuals are more susceptible to 1,3-butanediol toxicity might require more nuanced discussion, including the consideration of overall health and concurrent medication use.
- The text does not discuss the potential benefits of exogenous ketones for therapeutic uses, such as in neurological disorders, which could provide a more balanced view of their utility.
- The assertion that the field is moving away from 1,3-butanediol-based ketones may not reflect the entire scope of current research and development in the area of ketone supplementation.
- The suggestion to combine exogenous ketones with MCT oil to mitigate negative effects may not be suitable for all individuals, especially those with certain lipid m ...
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Metabolic Memory and Long-Term Effects of Ketosis
Cycling Ketosis May Have Lasting Benefits
Ferriss and D'Agostino discuss the concept of metabolic memory and how it may contribute to the enduring effects of cycling in and out of ketosis for better health.
Body's "Metabolic Memory" Aids Transition to Fat-burning Post-Ketosis
Dominic D'Agostino introduces the idea of a "metabolic memory," which may aid the transition back to fat-burning after periods off ketosis. He suggests that similar to muscle memory, there is a metabolic version that makes returning to ketosis easier and offers more benefits each time someone engages in ketosis. D'Agostino explains that staying in ketosis enhances metabolic flexibility and the efficiency of fatty acid oxidation enzymes. He likens it to muscle memory; once someone builds up capacity, regaining the ability is quicker the next time around if they take a break. Metabolic memory also involves changes in mitochondrial function and capacity, meaning that even after a break, these mitochondria can rapidly respond upon re-exposure to ketosis.
According to D'Agostino, by following a regimen that suggests a form of cycling—going on ketosis for several weeks and then taking a break—metabolic benefits can be maintained. He even references Dr. Valter Longo's research that indicates five days of fasting can impact cardiometabolic biomarkers for up to three months, hinting at the lasting effect of diet interventions.
Durability of Ketosis Benefits Under Study
Dominic D'Agostino indicates that the benefits derived from ketosis may last beyond the active period of the diet, with ongoing research clarifying these potential long-term impacts. The discussion about the fasting mimicking diet and its influence on cardiometabolic bioma ...
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Metabolic Memory and Long-Term Effects of Ketosis
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Clarifications
- Metabolic memory refers to the body's ability to "remember" previous metabolic states, such as fat-burning during ketosis, through lasting cellular and molecular changes. This includes adaptations in mitochondria, enzyme activity, and gene expression that persist after returning to a normal diet. These changes make it easier and faster for the body to re-enter ketosis and efficiently burn fat again. Essentially, metabolic memory helps maintain improved metabolic flexibility and health benefits over time.
- Ketosis is a metabolic state where the body uses fat, rather than carbohydrates, as its primary energy source. When carbohydrate intake is low, the liver converts fatty acids into molecules called ketone bodies, which can be used by cells for energy. This shift reduces reliance on glucose and increases fat oxidation, the process of breaking down fat for fuel. Mitochondria, the cell's energy producers, adapt to efficiently use ketones, enhancing fat-burning capacity.
- Metabolic flexibility is the body's ability to efficiently switch between burning carbohydrates and fats for energy depending on availability. It is important because it helps maintain stable blood sugar levels and supports energy balance during different dietary or activity conditions. Poor metabolic flexibility is linked to [restricted term] resistance and metabolic diseases like type 2 diabetes. Enhancing metabolic flexibility improves overall metabolic health and endurance.
- Fatty acid oxidation enzymes are proteins that help break down fatty acids into smaller molecules to produce energy. They work primarily in the mitochondria, the cell's energy factories. This process is crucial during ketosis, when the body relies on fat rather than carbohydrates for fuel. Efficient fatty acid oxidation improves the body's ability to use fat as an energy source.
- Mitochondria are the cell's powerhouses, producing energy by burning fuels like fats and sugars. In ketosis, mitochondria increase their ability to efficiently burn fat-derived molecules called ketones for energy. Enhanced mitochondrial function means cells generate energy more effectively, supporting better metabolism and endurance. Improved mitochondrial capacity also helps the body adapt quickly when switching between fuel sources, like from glucose to ketones.
- Dr. Valter Longo is a researcher known for studying fasting and its effects on aging and disease prevention. Cardiometabolic biomarkers are measurable indicators in the body, like blood sugar, cholesterol, and blood pressure, that reflect heart and metabolic health. Longo's research shows that short-term fasting can improve these biomarkers, reducing risks for conditions like diabetes and heart disease. This suggests diet interventions can have lasting positive effects on overall metabolic and cardiovascular health.
- A fasting mimicking diet (FMD) is a low-calorie, low-protein, low-carbohydrate eating plan designed to mimic the effects of fasting while still providing some nutrients. It triggers similar metabolic and cellular responses as water-only fasting, such as reduced inflammation and improved metabolic health. FMD is typically followed for a short period, like five days, to promote health benefits without the challenges of complete fasting. Research by Dr. Valter Longo has shown FMD can improve markers related to aging, metabolism, and disease risk.
- [restricted term] sensitivity refers to how effectively the body's cells respond to [restricted term], a ...
Counterarguments
- The concept of "metabolic memory" is not widely recognized or supported by a large body of scientific evidence, and more research is needed to validate its existence and effects.
- The comparison of metabolic memory to muscle memory is metaphorical and may not accurately reflect the underlying biological processes.
- The long-term effects of cycling in and out of ketosis are not well understood, and there may be potential risks or negative effects associated with frequent transitions between metabolic states.
- The benefits of ketosis may not be universal, and individual responses can vary based on genetics, lifestyle, and other health factors.
- The research by Dr. Valter Longo on fasting may not directly apply to ketosis, as fasting and ketogenic diets are different interventions with distinct physiological effects.
- Some studies suggest that long-term adherence to a ketogenic diet may have adverse effects on cardiovascular health, gut microbiota, and nutrient intake.
- Improved [restricted term] sensitivity and increased energy levels could be the result of multiple factors, not solely attributable to periods of ketosis or fasting.
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