#375 - The ketogenic diet, ketosis, and hyperbaric oxygen: metabolic therapies for weight loss, cognitive enhancement, cancer, Alzheimer's disease, brain injuries, and more | Dominic D'Agostino, Ph.D.
In this episode of The Peter Attia Drive, Dominic D'Agostino explores ketosis and its therapeutic applications. He explains how ketosis can be achieved through different methods—including diet, fasting, and supplements—and discusses its role in treating conditions ranging from drug-resistant seizures to aggressive cancers. D'Agostino details the importance of proper electrolyte management when using ketone supplements and shares specific formulations that help maintain this balance.
The discussion extends to ketogenic therapies' potential in treating neurodegenerative conditions like Alzheimer's disease, where ketones may serve as an alternative fuel source for the brain. D'Agostino and Attia also examine hyperbaric oxygen therapy, particularly its applications in treating traumatic brain injuries and concussions, including specific protocols for treatment and emerging research findings in this area.
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1-Page Summary
Nutritional vs. Supplemental Ketosis
In this episode, Dominic D'Agostino explores the various methods of achieving ketosis and their applications in clinical settings. He explains that ketosis can be reached through fasting, diet (typically 60-90% fat), or supplements, with each method raising blood ketone levels. D'Agostino emphasizes that ketogenic diets have shown particular success in managing drug-resistant seizures in children, with about a third of patients experiencing significant improvement.
Ketogenic Diets and Cancer Therapy
D'Agostino discusses the potential of ketogenic diets as a metabolic therapy for cancer, particularly for aggressive cancers like glioblastoma. He highlights ongoing research targeting a specific glucose-ketone index (GKI) of 1-4, combined with various drugs targeting cancer cell metabolism. The approach includes reducing glucose availability and using compounds that inhibit both glycolysis and glutaminolysis in cancer cells.
Neurodegenerative Disease Applications
According to D'Agostino, ketogenic therapies show promise for treating Alzheimer's and other forms of dementia. He explains that glucose hypometabolism is a key characteristic of Alzheimer's, and ketones could serve as an alternative brain fuel source. Currently, 558 registered clinical trials are exploring ketogenic interventions for various neurological conditions, with significant funding being directed toward research in severe psychiatric disorders.
Electrolyte Management in Ketone Supplementation
D'Agostino details the importance of managing electrolyte balance when using ketone supplements. He describes new formulations that combine ketone salts with essential electrolytes (sodium, potassium, calcium, and magnesium) to prevent imbalances. These formulations, including products like Keto Start, help mitigate the diet's natriuretic and diuretic effects.
Hyperbaric Oxygen Therapy Applications
D'Agostino and Peter Attia discuss the promising applications of hyperbaric oxygen therapy (HBOT), particularly for traumatic brain injury and concussion recovery. While not yet FDA-approved for these conditions, emerging research suggests significant improvements in cognitive function, even years after injury. D'Agostino recommends specific protocols, such as two atmospheres of oxygen for 60-90 minutes, five days weekly, for at least 40 sessions in standard cases.
1-Page Summary
Additional Materials
Counterarguments
- While ketogenic diets have been effective for some children with drug-resistant seizures, they may not be suitable for all patients and can have side effects such as nutrient deficiencies, gastrointestinal discomfort, and increased cholesterol levels.
- The potential of ketogenic diets as a metabolic therapy for cancer is still under investigation, and there is not yet a consensus in the medical community about its efficacy. Some cancers may not respond to carbohydrate restriction, and the diet could potentially affect the immune system or normal cells negatively.
- The use of ketogenic diets for neurodegenerative diseases like Alzheimer's is promising but still experimental. More research is needed to understand the long-term effects and potential risks of sustained ketosis in these populations.
- While there are many registered clinical trials investigating ketogenic interventions for neurological conditions, the presence of trials does not necessarily indicate effectiveness, and results must be carefully analyzed upon completion.
- Managing electrolyte balance with ketone supplements is important, but it is also essential to consider the overall nutritional adequacy of the diet and the potential for long-term health implications of supplement use.
- Hyperbaric oxygen therapy (HBOT) may show promise in some studies, but without FDA approval and more widespread, rigorous clinical trials, it remains an experimental treatment. It may not be effective or safe for all individuals with brain injuries or concussions.
- The recommended protocols for HBOT provided by D'Agostino are specific and may not be universally applicable or beneficial for all patients or conditions. Individual responses to HBOT can vary, and more research is needed to establish standardized treatment guidelines.
Actionables
- You can track your personal glucose-ketone index (GKI) by using a dual glucose and ketone meter to monitor how dietary changes affect your metabolic state. Start by measuring your baseline levels of glucose and ketones in the morning before eating. As you experiment with a ketogenic diet or fasting, continue to measure and record these levels daily to see how they change and aim for a GKI within the therapeutic range mentioned in the research.
- Enhance your understanding of electrolyte management by creating a daily log to track your intake of sodium, potassium, calcium, and magnesium when experimenting with ketone supplements. Use a nutrition tracking app to ensure you're meeting the recommended daily allowances for these electrolytes, adjusting your diet or supplement intake accordingly to maintain balance.
- Explore alternative brain health strategies by engaging in cognitive exercises that complement a ketogenic diet for brain health. Incorporate activities like brain teasers, puzzles, language learning, or musical instrument practice into your routine to potentially synergize with the metabolic benefits of ketones for cognitive function.
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Nutritional vs. Supplemental Ketosis
On the podcast, Dominic D'Agostino explains the differences and applications between achieving ketosis through diet or supplements, and its implications in clinical settings and personal health.
Achieving Ketosis Through Ketogenic Diets Elevates Blood Ketone Levels
Ketosis can be attained via fasting, diet, or supplements, leading to elevated blood levels of ketone bodies like beta-hydroxybutyrate or acetylacetate. A typical ketogenic diet is high in fat, with initial protocols recommending 90% fat, while modified versions propose around 60-70%. Notably, D’Agostino emphasizes the importance of protein intake, especially for pediatric epilepsy patients, where insufficient protein can affect growth adversely.
Ketosis Manages Drug-Resistant Seizures In Children, May Have Broader Applications
D’Agostino shares that ketogenic diets regulate seizures, particularly in instances where medications fail. Early evidence showed fasting could control seizures, influencing the development of ketogenic diets. A clinical report from 1921 detailed striking effects on epilepsy, given the absence of alternative treatments. Today, about a third of drug-resistant patients can see substantial, even complete, seizure control with ketogenic diets, with a smaller percentage potentially cured following the regimen.
Ketosis Supplementation: Elevating Ketones With Salts, Esters, and Precursors
Transitioning to a ketogenic diet may prove challenging initially, hence why electrolytes and ketone salts can help ease this shift. Current supplements in the market can raise ketone levels in the blood similarly to dietary changes, comprising of esters, salts, and precursors, each with their distinct effects on metabolism and [restricted term].
Exogenous Ketones: Esters, Salts, Precursors' Effects on [restricted term], Ketone Levels, Side Effects
Supplement types vary, with esters known for quick, high ketone spikes, potentially stimulating [restricted term], while salts provide a more sustained rise without such effect. Furthermore, there is potential for select ketone molecules to closely replicate the beneficial redox balance seen in dietary ketosis, targeting a one-to-one ratio of beta-hydroxybutyrate to acetoacetate.
Salts have evolved into products like the packet of Keto Start, providing six to 10 grams of pure beta-hydroxybutyrate without electrolytes. Conversely, salts bound to electrolytes, similar to those in Element, can help mediate the transition effects. Intere ...
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Nutritional vs. Supplemental Ketosis
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Clarifications
- Beta-hydroxybutyrate (BHB) and acetoacetate (AcAc) are the two primary ketone bodies produced during ketosis. Acetoacetate is the first ketone formed in the liver, which can then be converted into BHB, the more stable and abundant ketone circulating in the blood. BHB serves as the main energy source for tissues like the brain and muscles during low glucose availability. The ratio of BHB to AcAc reflects the body's redox state and metabolic balance during ketosis.
- Redox balance refers to the equilibrium between oxidized and reduced molecules in cells, crucial for energy production and metabolic health. In ketosis, beta-hydroxybutyrate (reduced form) and acetoacetate (oxidized form) interconvert, reflecting cellular redox state. A one-to-one ratio mimics natural metabolic conditions, supporting optimal mitochondrial function and minimizing oxidative stress. Maintaining this balance helps ensure ketones provide efficient energy without disrupting cellular processes.
- Reductive stress occurs when there is an excess of reducing equivalents like NADH relative to their oxidized form NAD⁺, disrupting cellular redox balance. This imbalance can impair metabolic processes that depend on NAD⁺, such as energy production and detoxification. Elevated ketone levels can increase NADH, leading to reductive stress if not properly managed. Maintaining NAD⁺/NADH balance is crucial for healthy cellular function and avoiding metabolic dysfunction.
- Energy toxicity from ketone over-supplementation occurs when excessive ketone levels disrupt normal cellular energy balance. This can lead to increased production of reactive oxygen species and metabolic stress. The body may respond by raising [restricted term] or acidifying the blood to counteract the imbalance. Such stress impairs cellular function and can cause symptoms like fatigue or discomfort.
- Ketone esters are compounds where ketones are chemically bonded to an alcohol, allowing rapid absorption and conversion to ketones in the liver. Ketone salts consist of ketone bodies bound to minerals like sodium or potassium, providing a slower, steadier ketone release. Precursors are substances metabolized by the body into ketones, such as 1,3-butanediol, which the liver converts into beta-hydroxybutyrate. Metabolically, esters raise ketone levels quickly but may stimulate [restricted term], salts provide sustained ketones with less [restricted term] impact, and precursors rely on liver metabolism for ketone production.
- 1,3-butanediol is processed by the liver using enzymes similar to those that break down ethanol (alcohol). This metabolic pathway can stress the liver, causing elevated liver enzyme levels, which are markers of liver strain or damage. Unlike ethanol, 1,3-butanediol does not cause intoxication but still requires careful dosing to avoid liver overload. Monitoring liver enzymes helps ensure safe use of 1,3-butanediol in ketogenic supplementation.
- Ketogenic diets require a high fat percentage to shift the body's primary fuel source from glucose to ketones, produced by fat breakdown. Protein is limited because excess protein can be converted into glucose through gluconeogenesis, which may prevent or reduce ketosis. Adequate protein is essential for maintaining muscle mass and supporting growth, especially in children. Balancing fat and protein ensures sustained ketosis while meeting nutritional needs.
- Ketogenic diets control drug-resistant seizures by altering brain metabolism to use ketones instead of glucose for energy, stabilizing neuronal activity. This metabolic shift reduces neuronal excitability and neurotransmitter imbalances that trigger seizures. The diet also influences mitochondrial function and reduces oxidative stress, contributing to seizure control. These effects collectively improve seizure threshold in patients unresponsive to medication.
- Electrolytes like sodium, potassium, and magnesium regulate fluid balance and nerve function, which can be disrupted during the initial phase of ketosis. When carb intake drops, [restricted term] levels fall, causing kidneys to excrete more sodium and water, leading to electrolyte loss. This loss can cause symptoms like fatigue, cramps, and dizziness, often called the "keto flu." Supplementing electrolytes helps maintain balance, easing these transition symptoms and supporting overall metabolic function.
- Alpha GPC (L-alpha glycerylphosphorylcholine) is a natural choline compound that supports brain health by increasing acetylcholine, a neurotransmitter important for memory and learning. When combined with ketogenic products, it may enhance cog ...
Counterarguments
- While ketogenic diets are effective for some in managing drug-resistant seizures, they may not be suitable or effective for all patients, and long-term adherence can be challenging.
- The high-fat content of ketogenic diets may raise concerns about cardiovascular health, although research is mixed and suggests that the type of fats consumed is important.
- Adequate protein intake is important, but too much protein can also interfere with the maintenance of ketosis, requiring careful balance.
- The use of exogenous ketones is a relatively new area of research, and long-term safety and efficacy data are still lacking.
- Exogenous ketones may not provide all the benefits of a ketogenic diet, as they do not require the body to mobilize and oxidize its own fat stores.
- The cognitive benefits of combining alpha GPC with ketogenic products are an area of emerging research, and more robust, long-term studies are needed to confirm these effects.
- The claim that modern ketone salts no longer cause gastrointestinal side effects may not apply to all individuals, as sensitivity can vary.
- The idea that fasting sharpens focus is anecdotal and may not be a universal experience; some individuals may experience decreased cognitive function ...
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Ketogenic Diets and Exogenous Ketones For Cancer Therapy
Ketogenic diets are being explored as a potential metabolic therapy for cancer, especially for aggressive cancers like glioblastoma. Research suggests that a specific glucose-ketone index (GKI) and therapies targeting cancer cell metabolism may extend survival.
Ketogenic Diets and Therapies Combining Ketosis With Anti-Cancer Drugs May Extend Survival In Aggressive Cancers Like Glioblastoma
The episode with Dominic D'Agostino focuses on the prospects for ketogenic diets as metabolic therapy for cancer. D'Agostino highlights the potential applications of 1,3-butanediol, which has a glucose-lowering effect and has been shown to suppress growth in metastatic cancer when mixed with a standard diet, inducing ketosis.
A review called "Ketone Metabolic Therapy Framework for Glioblastoma" with 49 authors, including oncologists and basic science researchers, is being conducted to make metabolic therapy part of the standard care for cancers where standard treatments are less effective. Glioblastoma is the primary focus, but the findings may be applicable to other cancers exhibiting the Warburg effect.
Clinical trials ongoing reveal that achieving and maintaining a GKI of 1-4 is part of a comprehensive, calculated metabolic-based intervention that may include diet, glycolytic drugs, and anti-glutamine drugs, highlighting the benefits of combining these with different drugs to potentially extend survival. The discussions consider ketone metabolic therapy with CAR-T therapy for lymphoma and the possibility that pancreatic cancer may be better suited for demonstrating the effectiveness of ketogenic diets.
Glucose-Ketone Index of 1-4 as Adjuvant Cancer Therapy
A glucose ketone index (GKI) of 1-4, which compares the millimolar concentration of glucose to ketones in the blood, is targeted. Unlike the standard American diet, which results in a GKI of 50, therapy aims for a GKI of between 1 and 4, preparing the body for other treatments. Various drugs targeting glucose metabolism are being considered. One such drug is ...
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Ketogenic Diets and Exogenous Ketones For Cancer Therapy
Additional Materials
Clarifications
- A ketogenic diet is very low in carbohydrates, moderate in protein, and high in fats. This macronutrient ratio forces the body to use fat as its primary energy source instead of glucose. When fat is broken down, the liver produces molecules called ketones, which can be used for energy by many tissues, including the brain. This metabolic state is called ketosis.
- The glucose-ketone index (GKI) is a ratio that measures the balance between blood glucose and ketone levels, reflecting metabolic state. A low GKI indicates higher ketone levels relative to glucose, suggesting a state of ketosis, which may starve cancer cells reliant on glucose. This index helps monitor and guide metabolic therapies aiming to shift energy sources from glucose to ketones. It is used to optimize treatment effectiveness by maintaining a metabolic environment unfavorable to cancer growth.
- The Warburg effect describes how cancer cells prefer to produce energy by fermenting glucose into lactate even when oxygen is available, unlike normal cells that use oxygen for energy. This metabolic shift supports rapid cell growth and survival in tumors. It creates a unique vulnerability in cancer cells that therapies can target by disrupting their altered glucose metabolism. Understanding this effect helps explain why ketogenic diets, which lower glucose availability, may hinder cancer growth.
- 1,3-Butanediol is a type of alcohol that the body can convert into ketone bodies, which serve as an alternative energy source to glucose. It helps induce ketosis by raising blood ketone levels without requiring carbohydrate restriction. This compound can lower blood glucose by shifting metabolism toward fat and ketone utilization. It is being studied for its potential to support metabolic therapies in conditions like cancer.
- Glycolytic drugs inhibit enzymes involved in glycolysis, the process cancer cells rely on for energy, starving them of fuel. Anti-glutamine drugs block glutaminolysis, another metabolic pathway cancer cells use to grow and survive. By targeting both pathways, these drugs create a metabolic crisis that can lead to cancer cell death. This dual approach exploits cancer cells' dependence on altered metabolism compared to normal cells.
- [restricted term] reduces glucose production in the liver and improves [restricted term] sensitivity, lowering blood sugar levels. Hexokinase inhibitors block the enzyme hexokinase, which cancer cells use to start breaking down glucose for energy. SGLT2 inhibitors prevent glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine. Together, these drugs reduce glucose availability to cancer cells, stressing their metabolism.
- Autophagy is a natural process where cells break down and recycle their own components to survive stress or nutrient shortage. In cancer therapy, inducing autophagy can lead to cancer cell death by exhausting their energy and resources. This process helps remove damaged parts of the cell, preventing cancer growth and promoting cell death. Targeting autophagy can make cancer cells more vulnerable to treatments.
- CAR-T therapy is a type of immunotherapy where a patient’s T cells are genetically modified to better recognize and attack cancer cells. It is primarily used for certain blood cancers like lymphoma. Combining CAR-T with ketone metabolic therapy may enhance treatment by weakening cancer cells metabolically while boosting immune attack. This dual approach aims to improve overall effectiveness against tumors.
- Glutamine is a key nutrient that can ...
Counterarguments
- The efficacy of ketogenic diets for cancer therapy is not conclusively proven, and more rigorous clinical trials are needed to establish their role in cancer treatment.
- The optimal glucose-ketone index (GKI) for cancer therapy is not universally agreed upon, and individual responses to such dietary interventions can vary significantly.
- While ketogenic diets may show promise in some studies, they may not be suitable or safe for all cancer patients, particularly those with other health conditions or nutritional deficiencies.
- The long-term effects of ketogenic diets and exogenous ketones on cancer progression and overall health are not well understood.
- Some cancer cells may adapt to use ketones for energy, potentially diminishing the effectiveness of ketogenic diets as a therapeutic strategy.
- The combination of ketogenic diets with anti-cancer drugs may not provide additional benefits over standard care in some cases, and potential drug-diet interactions need to be carefully considered.
- The use of 1,3-butanediol and other exogenous ketones may have side effects or health risks that have not been fully explored.
- The focus on metabolic therapy may divert attention and resources from other promising research areas in cancer treatment.
- The application of a ketogenic diet or metabolic therapy may be challenging to implement in a clinical setting due to dietary compliance, patient preferences, and the need for close monitoring.
- The role of [restr ...
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Ketogenic Diets and Exogenous Ketones in Cancer Therapy Trials Face Slow Progress Due to Design and Funding Challenges
Trials examining ketogenic diets and cancer therapy face obstacles due to various research and logistical challenges.
Dominic D'Agostino notes the slow progress in clinical trials for cancer therapy involving ketogenic diets and exogenous ketones, pointing out the necessity to convince policymakers and funding agencies such as the NIH and the DOD of the potential benefits of ketogenic metabolic therapy. He emphasizes the challenges in trial design, including the necessity of knowledgeable oncologists and dietitians, creating appropriate inclusion-exclusion criteria, and addressing patient heterogeneity.
There's ...
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Ketogenic Diets and Exogenous Ketones in Cancer Therapy Trials Face Slow Progress Due to Design and Funding Challenges
Additional Materials
Clarifications
- Ketogenic diets are high-fat, low-carbohydrate eating plans that shift the body's energy source from glucose to ketones. Exogenous ketones are supplements that raise ketone levels in the blood without dietary changes. In cancer therapy, these approaches aim to starve cancer cells of glucose, which many tumors rely on for growth. This metabolic shift may slow tumor progression and enhance treatment effectiveness.
- The NIH is the primary U.S. government agency that funds medical research to improve health and save lives. The DOD also funds medical research, especially projects with potential military or veteran health benefits. Both organizations provide grants that support clinical trials and innovative therapies. Their funding decisions significantly influence which medical studies can proceed.
- Ketogenic metabolic therapy is a treatment approach that uses a high-fat, low-carbohydrate diet to shift the body's energy source from glucose to ketones. This metabolic change aims to starve cancer cells, which often rely heavily on glucose for growth. The therapy may also include supplements called exogenous ketones to increase ketone levels in the blood. It is being studied as a potential complementary strategy alongside conventional cancer treatments.
- In clinical trials, inclusion-exclusion criteria are rules that determine who can or cannot participate, ensuring the study group is appropriate and results are reliable. Patient heterogeneity refers to differences among patients, such as age, genetics, or disease stage, which can affect how they respond to treatment. Managing these factors is crucial to accurately assess the therapy’s effectiveness and safety. Poorly designed criteria or ignoring patient variability can lead to inconclusive or misleading trial outcomes.
- Knowledgeable oncologists are needed to properly assess cancer progression and treatment effects within the trial. Dietitians ensure patients follow the ketogenic diet correctly, maintaining nutritional balance and safety. Both experts help tailor the intervention to ind ...
Counterarguments
- While ketogenic diets and exogenous ketones may show promise, it is important to acknowledge that the evidence base is still evolving, and more rigorous research is needed to establish their efficacy and safety in cancer therapy.
- The slow progress in clinical trials could also be attributed to the complexity of cancer as a disease, which may require multifaceted treatment approaches beyond dietary interventions.
- Convincing policymakers and funding agencies requires not just advocacy but also solid preliminary data, which may be lacking for ketogenic metabolic therapy in the context of cancer.
- The challenges in trial design are not unique to ketogenic diet studies but are common in many areas of clinical research, suggesting a need for broader improvements in clinical trial infrastructure.
- The frustration over the progress of trials should be balanced with an understanding of the regulatory and ethical standards that are in place to ensure patient safety and the validity of research findings.
- The heavy investment by pharmaceutical companies in d ...
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Ketogenic Diets and Ketones for Neurodegenerative Disease Therapy
The potential for ketogenic diets and ketone supplements to treat neurodegenerative diseases such as Alzheimer's is under investigation. Dominic D'Agostino discusses the role of brain metabolism and systemic inflammation in neurodegenerative conditions and highlights the ongoing research in this area.
Ketogenic Therapies May Help Alzheimer's and Other Dementia Patients By Improving Brain Metabolism and Reducing Inflammation
Glucose Hypometabolism Marks Alzheimer's; Ketones Offer Alternative Brain Fuel
D'Agostino reveals that a hallmark characteristic of Alzheimer's disease is glucose hypometabolism. In patients with mild cognitive impairment, which can be interpreted as an early stage of dementia, glucose hypometabolism is a ubiquitous characteristic. He suggests that ketones could provide an alternative fuel source for the brain, which is especially beneficial for patients displaying this condition.
Combining Ketosis With Neuroprotective Therapies Investigated
Although not detailed extensively, Dominic D'Agostino shows interest in combining ketosis with other neuroprotective therapies. He talks about the advantages of a comprehensive metabolic-based formula that might incorporate ketones alongside other cofactors and neuroprotective therapies to treat Alzheimer's and other forms of dementia. However, he points out challenges with funding agencies who are reluctant to fund such multi-compound formulas.
Clinical Trials on Ketogenic Diets and Exogenous Ketones' Impact on Cognition and Neurodegeneration Markers Ongoing
D'Agostino touches on the significant research being carried out in the field of ketogenic dietary interventions for neurodegenerative diseases. He mentions 558 registered clinical trials related to ketogenic diets on clinicaltrials.gov. Some of these studies focus on psychiatric disorders and potentially involve cognition or neurodegeneration.
Dominic D'Agostino discusses ongoing studies that are examining the effects of ketones on cognitive deficits in Alzheimer's disease. These studies are identifying patients, such as those with significant glucose hypometabolism, who respond favorably to ketone-based therapies.
He also mentions the Bazuki group funding million-dollar studies across severe psychiatric disorders at various universities, which shows the significant investment and int ...
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Ketogenic Diets and Ketones for Neurodegenerative Disease Therapy
Additional Materials
Counterarguments
- While ketogenic diets may offer an alternative fuel source, it is not yet clear if they can fully replace glucose as the brain's primary energy source, especially in the long term.
- The universality of glucose hypometabolism in patients with mild cognitive impairment may not be absolute; there could be variability in metabolic dysfunction among patients.
- The long-term safety and feasibility of ketogenic diets or ketone supplementation in the elderly or those with neurodegenerative diseases have not been fully established.
- Combining ketosis with other neuroprotective therapies could introduce complexities in determining which therapy is providing benefit and may complicate patient adherence.
- The efficacy of comprehensive metabolic-based formulas that include ketones and other cofactors has not been proven and may vary significantly between individuals.
- The number of registered clinical trials (558) does not necessarily indicate the effectiveness or success of the interventions being studied.
- The positive response to ketone-based therapies in patients with significant glucose hypometabolism may not be generalizable to all patients with Alzheimer's or other neurodegenerative diseases.
- Financial investments in research, such as those by the Bazuki group, do not guarantee successful outcomes or clinical applicability of the ketogenic diets in treating psychiatric or neurodegenera ...
Actionables
- You can explore the potential cognitive benefits of a ketogenic diet by starting a food journal to track your cognitive function alongside your dietary intake. Begin by noting your current eating habits and cognitive performance levels, such as memory recall or focus during tasks. Gradually introduce more ketogenic-friendly foods into your diet, such as avocados, nuts, and fatty fish, while reducing your intake of carbohydrates. Regularly assess any changes in your cognitive abilities to see if there's a correlation with your new diet.
- Consider taking a ketone supplement and monitoring its effects on your mental clarity and energy levels. Purchase a reputable brand of exogenous ketones and start with the recommended dosage. Keep a daily log of your mental performance, noting times of day when you feel more alert or focused. This personal experiment can help you determine if ketone supplementation has a noticeable impact on your cognitive function.
- Engage in a self-guided learning project about the role of glucose and ketones in brain h ...
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Electrolyte Management and Formulations of Ketone Supplements
Ketone supplements, while beneficial in various ways, come with potential risks such as electrolyte imbalances. Researcher D'Agostino discusses the importance of managing these risks, as well as the mitigating effects of electrolyte blends in ketone supplements.
Ketone Supplements May Cause Imbalances, Electrolyte Blends Mitigate
Ketone Salts: Sodium, Potassium, Calcium, Magnesium Beta-Hydroxybutyrate Provide Ketones and Replenish Electrolytes
D'Agostino raises concerns about liver toxicity with 1,3-butanediol and its potential linkage to electrolyte imbalance from large doses over time. To mitigate electrolyte imbalances on a ketogenic diet, D'Agostino points out that consuming ketone electrolytes when starting the diet can help. His conversation indicates a push towards creating balanced formulations that include ketone salts — specifically sodium, potassium, calcium, and magnesium beta-hydroxybutyrate — to replenish electrolytes. He discusses creating a quad salt blend that provides both ketones and needed electrolytes. D'Agostino notes that the ketone salts, due to their ionic bond, act as a natural buffer when consumed in large doses, helping to prevent possible acidic conditions. He highlights that their current formulation does not lead to an excessively high electrolyte load given their absence of chloride, which often concerns additional electrolyte consumption.
D'Agostino mentions products such as Audacious Nutrition's Keto Start, which provides about one gram of electrolytes, including sodium, calcium, magnesium, and potassium. These products offer a viable solution for those initiating the ketogenic diet, aiming to prevent dehydration from the diet's natriuretic and diuretic effects. Furthermore, he addresses concerns over sodium overload from ketone salts and clarifies that the negative effects, including hypertension, are ...
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Electrolyte Management and Formulations of Ketone Supplements
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Counterarguments
- While electrolyte blends in ketone supplements may help mitigate imbalances, it is important to consider individual variability in electrolyte needs and the potential for these blends to still cause imbalances in some people.
- The claim that large doses of 1,3-butanediol may cause liver toxicity needs to be substantiated with more robust clinical evidence to establish a direct causal relationship.
- The assertion that consuming ketone electrolytes when starting a ketogenic diet helps prevent imbalances may not account for the full spectrum of dietary and metabolic factors that can influence electrolyte status.
- The idea that ketone salts act as a natural buffer and prevent acidic conditions might oversimplify the body's complex acid-base balance and the potential for ketone salts to still contribute to acidosis in certain contexts.
- The statement that ketone salt formulations without chloride do not lead to excessively high electrolyte loads does not consider that other electrolytes in excess can also cause health issues.
- The suggestion that negative effects such as hypertension are mostly linked to sodium chloride and not other sodium compounds may not fully acknowledge the role of total sodium intake from all sources in hypertension risk.
- The potential benefits of combining ketone supplements with MCTs for improved ...
Actionables
- You can track your electrolyte intake using a food diary app to ensure balance when using ketone supplements. By logging your daily food and supplement consumption, you can monitor the levels of sodium, potassium, calcium, and magnesium you're getting and adjust your intake accordingly. For example, if you notice you're consuming a lot of sodium but not enough potassium, you can look for foods high in potassium to add to your meals.
- Create a hydration schedule that includes drinking water mixed with a pinch of unflavored electrolyte powder throughout the day. This can help maintain hydration and electrolyte levels without overloading on any particular electrolyte. For instance, you might drink a glass of electrolyte-infused water first thing in the morning, another mid-morning, one with lunch, one in th ...
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Hyperbaric Oxygen Therapy
Dominic D'Agostino and Peter Attia discuss the promising applications of hyperbaric oxygen therapy (HBOT) in treating a range of conditions from traumatic brain injury to cancer, exploring its efficacy and the challenges associated with its use.
Early Hyperbaric Oxygen Therapy Promising For Traumatic Brain Injury and Concussion
Efficacy of Hyperbaric Oxygen for Neurological Conditions Undergoing Trials
D'Agostino tr
aces the history of hyperbaric oxygen therapy, from seminal studies over a century ago to its potential as part of a comprehensive cancer treatment plan. The therapy's promise for augmenting standard care, particularly with respect to neurological and cancer conditions, is an ongoing area of interest. D'Agostino points to the research into HBOT's impact on glioblastoma cells. He also mentions funding for research into oxygen toxicity seizures related to diving, which has relevance to hyperbaric therapy's impact on the brain.
Recent developments extend the promise of hyperbaric oxygen therapy even further. Data soon to be released from different study groups suggests that HBOT can improve cognitive function in patients who have suffered a traumatic brain injury years earlier. The Aviv Clinic has seen significant improvements in patients after HBOT, lot only in cognitive function but also in cardiometabolic biomarkers. The Department of Defense has funded a $30 million trial investigating the neuroregenerative potential of HBOT, with results expected within the next year. D'Agostino notes that past studies without sham controls have anecdotal indications of benefits from hyperbaric oxygen therapy for long-ago brain injuries.
To address traumatic brain injury more specifically, D'Agostino recommends a standard protocol involving two atmospheres of oxygen for 60 to 90 minutes, five days a week, for a minimum of 40 treatment sessions. For a more mild protocol potentially suitable for mild concussions, a softer hyperbaric oxygen protocol of about 1.3 atmospheres three times per week over two weeks is suggested, using soft chambers available in some gyms.
D'Agostino also explores the combination of supplemental and dietary ketosis with HBOT, conducting clinical trials to see how they affect the latency to a seizure in a hyperbaric environment. These trials simulate diving conditions and are aimed at understanding how various therapies ca ...
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Hyperbaric Oxygen Therapy
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Counterarguments
- The efficacy of HBOT for conditions like traumatic brain injury and cancer is still under investigation, and more robust, large-scale, placebo-controlled trials are needed to establish its effectiveness.
- While historical studies provide a basis for HBOT, medical practices have evolved, and treatments that were promising in the past may not meet current scientific standards or may have been superseded by more effective therapies.
- The improvement in cognitive function and biomarkers reported by the Aviv Clinic after HBOT treatment may be subject to placebo effects or other confounding factors; independent replication of these results is necessary.
- The anecdotal evidence of benefits from HBOT for old brain injuries without sham controls lacks the rigor of controlled clinical trials and may not be reliable.
- The combination of supplemental and dietary ketosis with HBOT is an experimental approach, and until clinical trial results are available, it remains speculative whether this combination is beneficial.
- FDA limitations on HBOT approval are based on a rigorous evaluation process, and the lack of approval for certain uses suggests that the evidence for these applications may not yet meet the required standards for safety and efficacy.
- The potential benefits of HBOT, even if administered acutely after brain injury, must be weighed against the lack of conclusive evidence and the possibility of unknown long-term effec ...
Actionables
- You can explore the potential of HBOT by consulting with healthcare professionals who specialize in this therapy to understand if it's a suitable option for your specific health needs, especially if you have a history of brain injury or a neurological condition. For instance, if you've experienced a concussion in the past, discussing HBOT with a neurologist could provide insights into whether this therapy could benefit your cognitive function based on the latest research and trials.
- Consider incorporating a ketogenic diet into your routine to potentially enhance brain health, as research is looking into its combined effects with HBOT. Start by gradually reducing your carbohydrate intake and increasing healthy fats, and monitor how you feel. This doesn't require any special skills and can be done with guidance from nutrition resources or a dietitian.
- If you face logistical challenges in accessin ...
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1-Page Summary- Nutritional vs. Supplemental Ketosis
- Ketogenic Diets and Exogenous Ketones For Cancer Therapy
- Ketogenic Diets and Exogenous Ketones in Cancer Therapy Trials Face Slow Progress Due to Design and Funding Challenges
- Ketogenic Diets and Ketones for Neurodegenerative Disease Therapy
- Electrolyte Management and Formulations of Ketone Supplements
- Hyperbaric Oxygen Therapy
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