375 - The ketogenic diet, ketosis, and hyperbaric oxygen: weight loss, cognition, cancer, and more

The speaker advocates for a high-protein ketogenic diet as the most effective approach for weight loss, emphasizing that calories still matter, contrary to some popular beliefs. He recommends a protein intake of 20-30% of total calories, which for an active individual like himself (220 lbs) could mean up to 220 grams per day, significantly higher than the RDA. This high protein intake is crucial for satiety and muscle preservation, especially as one ages. Carbohydrate intake should be kept between 50-100 grams per day, but critically, at least one-third of these carbs must come from fiber (e.g., broccoli, avocado, cucumber, asparagus), avoiding highly glycemic options like carrots or bell peppers. The speaker stresses the importance of tracking total calories and macronutrients, as it's easy to overeat calorically dense foods like macadamia nuts or heavy cream on a ketogenic diet. He believes that creating a 10-20% energy deficit through this diet formulation is the primary lever for weight loss, while the ketogenic aspect provides benefits like increased satiety, reduced appetite, and improved metabolic flexibility.

The speaker acknowledges the therapeutic potential of carnivore diets, particularly for individuals suffering from autoimmune disorders. He views it as the 'ultimate elimination diet,' which can help identify and remove dietary triggers. While a strict carnivore diet (meat and water only) might seem nutritionally incomplete, he notes that vitamin C deficiency is surprisingly not observed, especially if nose-to-tail eating (including organ meats) is practiced. Magnesium levels, however, can trend low, suggesting potential supplementation needs. He believes that a fatty carnivore diet, especially when combined with caloric restriction, can induce ketosis, which contributes to its therapeutic effects. The speaker finds the anecdotal evidence from individuals who have seen significant improvements in their conditions, such as vitiligo, to be compelling, even if large-scale clinical trials are lacking.

The speaker strongly recommends using exogenous ketone electrolytes (ketone salts) to facilitate the transition into a ketogenic diet. This practice helps mitigate the unpleasant symptoms of the 'keto flu,' which include brain fog, fatigue, and orthostatic hypotension. These symptoms arise because, in the early stages of carbohydrate restriction, glucose levels drop before the body's endogenous ketone production fully ramps up, creating an 'energetic gap' in the brain. Additionally, carbohydrate restriction has a natriuretic and diuretic effect, leading to the loss of sodium and water, which can cause electrolyte imbalances. Ketone salts address both issues by providing an immediate source of beta-hydroxybutyrate (BHB) for brain energy and replenishing crucial electrolytes. The speaker notes that ketone salts have an advantage over ketone esters in that they do not cause a rapid insulin spike or significant glucose lowering, making them a safer and more stable option for this purpose. He suggests aiming for blood ketone levels of 1-2 mmol/L, as higher levels from supplements can lead to 'energy toxicity' and other issues.

The speaker advocates for situational fasting, rather than making it a default daily practice. He suggests using fasting strategically when specific benefits are desired, such as during inflammatory events (e.g., shingles, herpes simplex flare-ups), for gastrointestinal issues, or when needing heightened cognitive focus for demanding tasks like grant writing or paperwork. His personal experience indicates that fasting for half a day or more in these situations makes him 'sharper.' He believes that for metabolically flexible individuals, this targeted approach can yield more benefits than continuous fasting, as the body can efficiently switch to alternative fuel sources when needed, providing a cognitive boost and reducing inflammation.

The speaker notes that anorexia nervosa is the psychiatric disorder with the highest mortality. While traditional approaches to anorexia typically avoid any form of dietary restriction, new research, including case reports, suggests that a ketogenic diet, particularly when combined with ketamine, can lead to remission. This unexpected efficacy is attributed to the ketogenic diet's profound effects on neuropharmacology, hedonic responses, and mood stabilization, which are critical factors in anorexia. The speaker, initially skeptical, now finds the emerging data promising and compelling, highlighting ongoing studies funded by the Bazooki group.

The speaker acknowledges that the buzz around NAD supplementation has largely died down because existing forms like NR and NMN have not delivered meaningful or measurable benefits in clinical trials. He attributes this failure primarily to delivery problems, specifically the liver's highly efficient metabolism of NAD precursors, which prevents sufficient amounts from reaching systemic circulation and crossing the blood-brain barrier. However, he is involved in research with new, stabilized NAD molecules that are currently in Phase 2 and 3 clinical trials. These novel formulations aim to overcome the liver's 'greediness' and deliver NAD more effectively to target tissues, particularly the brain and muscles. He believes these stabilized forms hold significant potential, especially in contexts of energetic metabolic stress, such as oxygen toxicity, traumatic brain injury, and age-related NAD decline, rather than solely as longevity molecules.

The speaker highlights the emergence of continuous ketone monitors (CKMs) as a significant advancement in tracking ketosis. He specifically mentions Sai Bio as a company producing a remarkably reliable device that looks and functions similarly to a continuous glucose monitor (CGM). This CKM measures beta-hydroxybutyrate (BHB) and has shown good specificity and accuracy, particularly in the first week of use. However, he notes that readings can drop to about half of blood measurements in the second week. A key insight from using CKMs is that during a calorie deficit, blood ketone levels might appear low while breath ketones are high. This is because tissues rapidly utilize ketones from the blood, even as the body continues to produce them and blow off acetone. The speaker also points out that current CKMs, like the Abbott device and Sai Bio, primarily measure the D-enantiomer of BHB, meaning they don't account for the L-enantiomer or other ketone bodies like acetoacetate and acetone, which could lead to an underestimation of total ketone levels.

The speaker discusses the ongoing, large-scale clinical trial at the University of South Florida, funded by the Department of Defense, to rigorously evaluate hyperbaric oxygen therapy (HBOT) for traumatic brain injury (TBI) and PTSD. This $30 million project utilizes six dedicated chambers and employs a sophisticated sham control where subjects experience pressure pulses during compression and decompression but remain at one atmosphere, making it difficult for them to discern if they received active treatment. This addresses a major flaw in previous studies, which often used hyperbaric air as a control, inadvertently providing some therapeutic benefit. The trial aims to provide definitive answers to the efficacy of HBOT for these conditions, which currently lack FDA approval despite anecdotal reports and some suggestive data. The speaker, while peripherally involved, highlights the scientific rigor and the potential for the facility to become a treatment center if benefits are confirmed.