He’s 76, Jacked, and Smarter Than Ever — Here’s His Secret – TFP [#013] | Ben Bocchicchio PhD
Gemini Video Summary:
Based on the transcript provided featuring Dr. Ben Bocchicchio and Dave Feldman, here is the analysis and summary.
Video Analysis: Dr. Ben Bocchicchio on Slow Resistance Training & Metabolic Health
A. Executive Summary
Dr. Ben Bocchicchio, a veteran exercise physiologist and pioneer of “Slow Training,” argues that metabolic health and longevity are best optimized through high-intensity, low-force resistance training. He contends that traditional weightlifting relies heavily on momentum (acceleration), which reduces muscle tension and increases joint risk. By deliberately slowing movement speed, individuals can maximize muscle fiber recruitment and metabolic signaling while minimizing force (F=ma), effectively creating a “safe emergency” that stimulates adaptation without injury.
Bocchicchio challenges current longevity orthodoxy regarding Zone 2 cardio, asserting that proper resistance training is superior for stimulating V02 max and mitochondrial efficiency. He advocates for a “behaviorally palatable” protocol consisting of two 15-minute sessions per week, driven by the Pareto principle. The discussion extends to nutrition, where Bocchicchio supports a low-carb, high-protein approach to manage insulin resistance, viewing muscle tissue not just as a mechanical mover, but as the body’s primary endocrine organ for longevity signaling (myokines).
B. Bullet Summary
Muscle as an Endocrine Organ: The skeletal muscle system is the body’s most potent mechanism for delivering physiological signals; it is not merely for locomotion but dictates metabolic capacity.
The Physics of Safety: Injury is caused by Force ($F=ma$). By reducing acceleration ($a$) via slow movement, one reduces Force, thereby protecting joints while maintaining high muscle tension.
Strength Curves vs. Resistance Curves: Traditional free weights have linear resistance that rarely matches the body’s rotational strength curves; slow training maximizes tension throughout the entire range of motion.
Definition of Intensity: True high intensity is defined by muscle fiber recruitment patterns and metabolite production, not merely by heart rate or perceived exertion.
Failure is Necessary: To trigger upward adaptation (hypertrophy and strength), one must reach momentary muscular failure to signal a biological need for growth.
The “Fresh Muscle” HIIT Protocol: Bocchicchio critiques treadmill HIIT because fatigue limits intensity in later intervals. He proposes rotating muscle groups (legs, then back, then chest) to allow each group to be worked at maximum intensity while fresh.
Longevity Correlation: Citing Ruiz et al. (2006), Bocchicchio notes that muscle strength is a stronger correlate to longevity and cancer prevention than many other biomarkers.
15-Minutes, Twice Weekly: A protocol of brief, infrequent, but maximal effort leverages the Pareto principle, providing the majority of benefits with high adherence rates.
V02 Max Debate: Bocchicchio argues that high-intensity resistance training improves oxygen utilization (V02 max) more efficiently than long-duration “base” cardio, challenging the “wide base, high peak” endurance philosophy.
Insulin Resistance: Acknowledges the “unfairness” of genetics; some must strictly limit carbohydrates to manage insulin, while others do not.
Behavioral Palatability: The sustainability of a health intervention is as critical as its efficacy; short duration protocols reduce friction and increase long-term adherence.
Neuroprotective Effects: High-intensity resistance training upregulates BDNF (Brain-Derived Neurotrophic Factor) and VEGF (Vascular Endothelial Growth Factor), linking muscle mass to cognitive preservation.
Homeostasis as Vacillating Equilibrium: Health is not a flat line; it is the ability of the body to effectively manage energy anabolism and catabolism within a safe range.
D. Claims & Evidence Table
Claim Made
Evidence Provided
Assessment
Slower movement reduces injury risk.
Physics ($Force = Mass \times Acceleration$). Reducing acceleration lowers peak force on joints.
Cites Ruiz & Blair (2006, BMJ), noting top-tier strength correlates to 40% lower cancer mortality.
Strong. Supported by extensive epidemiological data (e.g., The CODE Study, PURE study).
Resistance training is superior to Zone 2 for V02 Max.
Arguments based on mitochondrial demand and muscle signaling; anecdotal success.
Speculative/Debated. Mainstream consensus suggests concurrent training is optimal; Zone 2 is specifically efficient for mitochondrial density/clearance.
15 minutes, 2x/week is sufficient for optimal health.
50 years of clinical practice; adherence data; observation of client results (including the host).
Strong for General Pop. Highly effective for health span/maintenance; elite performance likely requires higher volume.
HIIT on treadmills is suboptimal due to localized fatigue.
Logical argument: tired legs in later intervals cannot generate max intensity to tax the cardiovascular system fully.
Strong. Metabolically logical; “peripheral fatigue” often limits “central” adaptation in standard HIIT.
Diet and Exercise are the two strongest metabolic levers.
Physiological role of insulin sensitivity and glucose disposal via muscle contraction.
Strong. Fundamental law of bioenergetics and endocrinology.
E. Actionable Insights
Adopt Slow Cadence: When lifting, utilize a super-slow cadence (e.g., 10 seconds up, 10 seconds down) to eliminate momentum and maximize tension.
Target Failure safely: Push to the point where concentric movement is impossible. Safety is ensured by the low speed—if you fail, you simply stop, rather than dropping a fast-moving weight.
Circuit-Based HIIT: Instead of resting between sets of the same exercise, move immediately to a different muscle group (e.g., Squat $\rightarrow$ Chest Press $\rightarrow$ Row). This keeps heart rate high while allowing specific muscles to recover for max output.
Frequency Cap: Limit high-intensity resistance sessions to twice a week to allow for full neurological and muscular recovery/supercompensation.
Prioritize Protein: Maintain high protein intake to support the anabolic signal sent by the resistance training, particularly important as age increases to combat sarcopenia.
Reframe “Exercise”: Distinguish between “Activity” (walking, golf, daily movement) which should be daily, and “Exercise” (high-intensity stimulus) which should be infrequent and brief.
Monitor Function, Not Just Aesthetics: Use strength markers and metabolic panels (A1C, Insulin) as success metrics rather than just scale weight.
H. Technical Deep-Dive
1. Mechanics: Momentum vs. Tension
Bocchicchio’s protocol addresses the discrepancy between External Load (weight on the bar) and Internal Tension (force experienced by muscle fibers).
Standard Lift: $Force_{muscle} \approx Mass_{weight} \times (Gravity + Acceleration)$.
At the start of a fast lift, acceleration is high, creating a force spike (risk).
In the middle, momentum takes over, and muscle tension drops (inefficiency).
This enforces Constant Tension, causing rapid occlusion of blood flow, accumulation of metabolites (lactate, H+ ions), and consequent recruitment of high-threshold Motor Units (Type IIb fibers) according to Henneman’s Size Principle, without requiring heavy external loads.
2. Metabolic Signaling (The Myokine Theory)
The transcript emphasizes muscle as a secretory organ. Intense contraction stimulates the release of myokines (interleukins like IL-6, though not explicitly named in the text, this is the mechanism).
Neuro-Cross Talk: The mention of BDNF (Brain-Derived Neurotrophic Factor) suggests that the lactate produced during this glycolytic work crosses the blood-brain barrier, where it facilitates neuroplasticity and astrocyte health.
3. V02 Max and Peripheral Adaptations
Bocchicchio argues V02 max (central adaptation) is driven by peripheral demand. By maximizing the oxygen extraction capability of the muscle (a-vO2 difference) through extreme fatigue, the heart is forced to increase stroke volume to compensate. He argues this can be achieved without the repetitive impact stress of running.
I. Fact-Check Important Claims
Claim:Muscle strength is the primary correlate to longevity.
Verdict:Verified. The 2008 study “Association between muscular strength and mortality in men” (Ruiz et al.) and subsequent meta-analyses consistently show grip strength and leg strength are independent predictors of all-cause mortality, often outperforming blood pressure or BMI.
Citation: Ruiz, J. R., et al. (2008). British Medical Journal.
Claim:High Intensity Resistance Training (HIRT) increases BDNF.
Verdict:Verified. Evidence suggests that lactate, released during intense muscle contraction, acts as a signaling molecule to increase BDNF expression in the hippocampus.
Citation: El Hayek, L., et al. (2019). Nature Metabolism.
Claim:Zone 2 is unnecessary if doing HIRT.
Verdict:Controversial/Nuanced. While HIRT improves cardiovascular markers, Zone 2 (low intensity, steady state) specifically targets fat oxidation efficiency and mitochondrial density in Type I fibers via different pathways (calcium signaling vs. AMPK). Most longevity researchers (e.g., Attia, San Millán) argue both are required for optimal mitochondrial flexibility. Bocchicchio’s stance is a minority view in the current longevity biotech consensus, though practical for time-constrained individuals.
Claim:Walking speed correlates to cognitive efficiency.
Verdict:Supported. Gait speed is a well-established geriatric vital sign. Slower gait speed is predictive of cognitive decline and dementia.
Citation: Dumurgier, J., et al. (2009). Archives of Internal Medicine.
Claim:Nautilus Cams were designed based on geriatric strength curves.
Verdict:Plausible/Anecdotal. Arthur Jones (Nautilus founder) was known for measuring torque curves in various populations to design the “nautilus” spiral cam. This aligns with Jones’s historical design philosophy of matching resistance to the human strength curve.
Lactic Acidosis, Black Mold & B1: What If It’s All Connected? – TFP [#014] | Darren Schmidt
Guest Dr. Darren Schmidt (DC, nutrition-focused clinician) makes the case for the role of B1 deficiency, discusses environmental toxic exposures, explores mitochondrial dysfunction, and examines lactic acidosis as a framework for understanding complex disease patterns. We also discuss metabolic pathways, autonomic issues, and how clinical observations can challenge conventional assumptions.
Gemini Video Summary:
Dr. Darren Schmidt and Dave Feldman investigate the root causes of chronic disease, proposing a model that moves beyond standard risk factors like cholesterol concentration. Schmidt argues that the majority of chronic illnesses stem from three primary vectors: malnutrition, infection, and toxicity, which manifest physiologically as lactic acidosis and mitochondrial dysfunction. Drawing heavily on his own near-fatal exposures to parathion, black mold, and a residential gas leak, Schmidt illustrates how environmental toxins can induce symptoms mimicking heart failure and hypoxia, often missed by standard allopathic diagnostics.
A central theme is the endemic deficiency of Vitamin B1 (Thiamine), which Schmidt identifies as a critical rate-limiter for mitochondrial respiration and autonomic nervous system function. The discussion highlights the clinical utility of the MVX (Metabolomic Vulnerability Index) blood test, which aggregates markers like GlycA, amino acids, and citrate to predict all-cause mortality and guide “concierge” interventions. Feldman and Schmidt largely align on the failure of the standard lipid hypothesis, positing that LDL cholesterol and apolipoprotein B (ApoB) function primarily as part of the innate immune response (opsonins) and antioxidant defense, rather than being independent drivers of atherosclerosis in metabolically healthy individuals.
B. Bullet Summary
Lactic Acidosis as Mechanism: Chronic disease is fundamentally a state of lactic acidosis where the body cannot efficiently convert fuel to energy due to a lack of oxygen or mitochondrial cofactors, leading to cellular suffocation.
B1 is Critical: Thiamine (Vitamin B1) is the essential nutrient for the Pyruvate Dehydrogenase Complex; deficiency mimics hypoxia (“air hunger”), causes neuropathy, and disrupts the autonomic nervous system.
The “Gas Leak” Case: Schmidt treated his own severe cardiac and hypoxic symptoms—caused by an undetectable gas leak—using high-dose synthetic B1 (Benfotiamine), which facilitated oxygen transfer despite the environmental toxin.
MVX Blood Test: The MVX test measures physiology rather than disease labels, utilizing nuclear magnetic resonance (NMR) to assess inflammation (GlycA), toxicity (small HDL particles), and malnutrition (BCAAs).
Dietary Malnutrition: High-calorie malnutrition is rampant; high intake of processed carbohydrates depletes B1 stores, which the body can only hold in small quantities (approx. 30mg).
Environmental Blind Spots: Physicians frequently miss environmental causes of heart disease, such as mold toxicity, heavy metals, and low-level carbon monoxide/gas exposure.
Infection and Heart Disease: A significant portion of cardiovascular events may be driven by infections (e.g., periodontal bacteria, Lyme, viral load) rather than lipids alone.
LDL as Immune Defense: LDL particles act as opsonins, tagging pathogens for macrophage removal; high LDL in the context of infection or toxicity is a protective, planned immune response.
Transcytosis vs. Passive Entry: Feldman argues that LDL enters the subendothelial space via transcytosis—an active, planned biological process by endothelial cells—rather than passively “leaking” through.
Macrophage Expansion: Macrophages likely endocytose LDL particles to acquire the phospholipids and cholesterol necessary to expand their size (up to 5x) to fight pathogens.
The “Pyromaniac” Analogy: Feldman compares chronic disease to a pyromaniac’s neighborhood: you need more fire stations (nutrients/LDL) because there are more fires (inflammation/damage), not because the fire stations are the cause.
Detoxification is Key: Healing requires removing the interference (toxins/infections) using binders (zeolite, charcoal, carbon technology) before nutrition can fully restore function.
Satiety Diet: Schmidt advocates for a “High Satiety” diet (high protein, moderate fat, low carb) as the evolutionary baseline for health.
Limits of Keto/Carnivore: While effective elimination diets, long-term adherence can mask underlying nutritional deficiencies (like specific amino acids) if not monitored via testing like MVX.
C. Claims & Evidence Table
Claim Made
Evidence Provided
Assessment
B1 deficiency is a primary driver of “air hunger” and autonomic dysfunction.
Schmidt’s case study of gas leak survival; historical reference to “wet beriberi” symptoms; citation of Lonsdale & Marrs’ work.
Strong Mechanism. Physiological role of B1 in respiration is well-established.
Lactic Acidosis is the “crux” of all chronic disease.
References to Dr. Roy Lee (1930s) and Otto Warburg; clinical observation of recovery when treating acidosis.
Reductionist. While mitochondrial dysfunction is central to metabolic disease, claiming it is the sole crux is a broad generalization.
MVX Score accurately predicts 5-year mortality.
Citations of NIH cohorts (CathGen, Intermountain) and recent UK Biobank study (300k participants).
Strong. Backed by emerging metabolomic research and insurance/actuarial data.
LDL particles are actively transported (transcytosis) into artery walls.
Feldman cites the 2020 EAS consensus paper mechanism section; biological implausibility of passive entry.
Strong. Aligns with current mechanistic understanding of endothelial biology.
Standard “Normal” Lab Ranges are misleading (e.g., Insulin).
Comparison of functional ranges (Insulin < 5) vs. LabCorp ranges (Insulin < 24).
Strong. Consensus in longevity/metabolic health circles supports tighter control of insulin.
Seed oils cause inflammation despite lack of direct RCT proof.
Clinical observation; inference based on oxidation rates of PUFAs; elimination improves MVX scores (N=1).
Speculative/Inferential. Mechanism (oxidation) is plausible, but high-quality human RCT evidence remains debated.
High BCAA levels indicate insulin resistance/liver dysfunction.
Correlation between high circulating BCAAs and inability to utilize protein/defat the liver.
Supported. Elevated BCAAs are a known biomarker for insulin resistance and metabolic syndrome.
Export to Sheets
D. Actionable Insights
Test for MVX: If accessible, order the MVX Plus panel to assess metabolic vulnerability, inflammation (GlycA), and nutritional status independent of standard cholesterol metrics.
Inspect Your Environment: Actively test your home for radon, carbon monoxide/gas leaks, and mold (ERMI test), especially if you have resistant fatigue or cardiac symptoms with “normal” lipids.
Supplement B1 (Thiamine): For symptoms of “air hunger,” fatigue, or neuropathy, consider trying Benfotiamine(fat-soluble B1) or TTFD. Start with standard doses and monitor paradoxical reactions (initial worsening).
Prioritize Protein: Adopt a “High Satiety” diet approach: prioritize protein and nutrient density. Aim for 90% of calories from whole unprocessed meats/fats.
Detox Support: If toxicity is suspected (via low small HDL particle count), utilize binders like activated charcoal, zeolite, or bentonite clay to assist excretion.
Monitor Fasting Insulin: Ignore standard lab ranges. Aim for a fasting insulin level below 5 µIU/mL.
Fact-Check Diet Changes: Don’t assume a diet (Keto/Carnivore) is working indefinitely. Re-test blood work (specifically looking for amino acid deficiencies or inflammatory markers) every 6 months.
H. Technical Deep-Dive
1. The Mechanism of Lactic Acidosis and B1 Deficiency Schmidt refers to “Lactic Acidosis” not merely as the acute medical emergency (SEPSIS) but as a chronic metabolic state. The biochemical bottleneck is often the Pyruvate Dehydrogenase Complex (PDC).
Normal Function: Glucose → Pyruvate. The PDC converts Pyruvate into Acetyl-CoA, which enters the Krebs (Citric Acid) Cycle in the mitochondria to produce ATP via oxidative phosphorylation.
The B1 Role: Thiamine Pyrophosphate (TPP), a derivative of B1, is a mandatory cofactor for the E1 subunit of the PDC.
Dysfunction: In B1 deficiency (or hypoxic states like CO poisoning), the PDC is inhibited. Pyruvate cannot enter the mitochondria. instead, it is shunted to Lactate Dehydrogenase (LDH), converting Pyruvate → Lactate.
Result: This results in cytosolic acidosis (buildup of H+ ions) and a failure of efficient ATP production, leading to “cellular suffocation” and autonomic failure.
Getty Images
2. MVX Markers Breakdown The MVX test relies on NMR spectroscopy to quantify specific metabolites:
GlycA (Glycoprotein Acetyls): A composite marker of systemic inflammation, reflecting the glycosylation of acute-phase proteins (Alpha-1 acid glycoprotein, Haptoglobin, etc.). Unlike CRP, which fluctuates rapidly, GlycA provides a stable integration of inflammatory status over time.
Citrate: Elevated plasma citrate suggests a “traffic jam” at the entry of the mitochondria; citrate is not being utilized in the Krebs cycle, indicating mitochondrial dysfunction.
BCAAs (Valine, Leucine, Isoleucine): While essential, chronically elevated plasma BCAAs are strongly associated with insulin resistance. The mechanism involves the downregulation of branched-chain α-ketoacid dehydrogenase (BCKDH) in adipose tissue, preventing BCAA catabolism.
3. LDL Transcytosis & Immune Function Feldman challenges the “gradient-driven” infiltration model of atherosclerosis.
Transcytosis: This is an active, receptor-mediated transport. Endothelial cells express receptors (like SR-BI or ALK1) that bind LDL. The cell invaginates, forming a vesicle that traverses the cytoplasm and releases the LDL into the subendothelial space.
Why? Feldman hypothesizes this is a planned response to deliver lipids to macrophages. Macrophages (M1 phenotype) require massive lipid uptake to synthesize membranes and inflammatory cytokines. LDL serves as a resource packet for this immune expansion.
Status:True. This is a classic symptom of “Wet Beriberi” (Shoshin Beriberi). It causes high-output heart failure and pulmonary congestion, leading to severe shortness of breath.
Claim:Gas leaks can be odorless and cause chronic illness.
Status:True. While natural gas is odorized with mercaptan (rotten egg smell), small leaks outdoors or in well-ventilated areas may be sub-threshold for smell but accumulate chronically. Furthermore, Carbon Monoxide (combustion byproduct) is odorless and causes cellular hypoxia.
Claim:American Heart Association (AHA) acknowledged infection/toxins.
Status:Verified context. The AHA has published scientific statements acknowledging that environmental pollutants (like particulate matter and heavy metals) are modifiable risk factors for cardiovascular disease (e.g., AHA Scientific Statement 2023 on “Contaminant Metals”). They also acknowledge the link between periodontal disease/inflammation and heart health.
Claim:Insulin references ranges are too high (up to 24 µIU/mL).
Status:True. Most metabolic health experts consider optimal fasting insulin to be <5−8 µIU/mL. Reference ranges are statistical averages of a largely metabolically unhealthy population, not biological optimals.
Deep Dive on LDL, ApoB, and Cardiovascular Disease – TFP [#011] | Austin Dudzinski
Gemini Video Summary
This dialogue represents a critical examination of the traditional Lipid Hypothesis, specifically within the context of the Lipid Energy Model (LEM) and the Lean Mass Hyper-Responder (LMHR) phenotype. The conversation centers on the preliminary findings of the “Keto CTA” study, which suggests that in metabolically healthy individuals with exceptionally high LDL levels (driven by a ketogenic diet), there is no observed correlation with atherosclerotic plaque progression over one year.
Austin provides a clinical pharmacist’s perspective, critiquing the pharmaceutical standard of care—specifically the aggressive use of exogenous insulin for Type 2 diabetics—favoring instead dietary interventions (deprescribing). The discussion dissects the mechanics of lipidology, challenging the notion that LDL concentration operates principally via passive diffusion. Instead, they argue for a model of transcytosis driven by energy demands. Considerable time is spent auditing major epidemiological studies (e.g., PESA, MESA, Western Denmark Registry) and statin trials (4S, CARDS, ASPEN), arguing that data manipulation and “statistical wizardry” often obscure the primacy of metabolic health over isolated LDL metrics. The core thesis is that metabolic health (insulin sensitivity) is the dominant variable in longevity and cardiovascular risk, and that “cholesterol focus” is often a “disastrous distraction.”
B. Bullet Summary
Insulin Deprescribing: Dietary intervention (Keto) can often remove Type 2 diabetics from high-dose exogenous insulin in under two weeks, reducing costs and hypoglycemia risk.
Fructose-Sodium Connection: Fructose malabsorption may correlate with sodium absorption issues; strict ketogenic dieters may require significantly higher sodium intake (up to 8-12g/day in Austin’s N=1 case) to mitigate “keto flu” symptoms.
The “Triad” Phenotype: Lean Mass Hyper-Responders are defined by High LDL, High HDL, and Low Triglycerides. This profile is distinct from atherogenic dyslipidemia (High LDL, Low HDL, High Trigs).
Keto CTA Study Preliminary Data: In the tracked cohort, high LDL and ApoB levels did not correlate with plaque progression, non-calcified plaque volume, or percent atheroma volume over the study period.
Baseline Calcification Predictive: The strongest predictor of plaque progression was baseline CAC score, supporting the “plaque begets plaque” theory rather than the “LDL begets plaque” theory in this specific context.
Transcytosis vs. Diffusion: Feldman argues that LDL enters the arterial wall via active transcytosis (regulated transport) rather than passive diffusion driven by concentration gradients.
PESA Study Critique: The speakers argue the PESA study overstates LDL risk in “healthy” populations by using inconsistent data visualization (bar graphs with vastly different “n” values) and ignoring the low absolute event rates.
The “Power of Zero”: In MESA and Western Denmark data, individuals with a CAC of zero have extremely low event rates regardless of LDL levels, suggesting LDL is not an independent driver of risk in the absence of established disease.
Statin Trial Anomalies: Discussion of the CARDS and ASPEN trials suggests that when strictly analyzing diabetic populations, the benefit of statins becomes statistically insignificant or highly variable, contradicting standard guidelines.
Metabolic Health Primacy: A recurring argument is that metabolic syndrome (insulin resistance) is the primary engine of cardiovascular disease, and LDL is often a “passenger” or proxy for that metabolic dysfunction, except in genetic conditions like Monogenic FH.
Risk Stratification: The speakers propose stratification based on metabolic health; high LDL in an insulin-sensitive person is fundamentally different from high LDL in an insulin-resistant person.
Pharmacological Skepticism: Austin critiques the “Run-in Period” in drug trials, noting it weeds out individuals with side effects before the trial begins, artificially inflating tolerability data.
D. Claims & Evidence Table
Claim Made
Evidence Provided
Assessment
High LDL/ApoB does not predict plaque progression in LMHR.
Preliminary data from the “Keto CTA” study (n=100) showing flatline association between LDL levels and plaque volume changes.
Speculative/Emerging. Data is compelling but unpublished (at time of recording) and limited to 1-year duration. Contradicts consensus.
Metabolic health is more predictive of CVD risk than LDL.
Citations of Western Denmark Registry and MESA showing low event rates in CAC=0 populations despite variable LDL, provided metabolic health is intact.
Strong. Supported by growing body of literature emphasizing insulin resistance as a primary CVD driver.
Sodium needs increase significantly on Ketogenic diets.
Austin’s N=1 experiment (salt tablets resolving symptoms); theoretical link to insulin lowering causing natriuresis (sodium excretion).
strong (Physiological). Well-established that low insulin leads to kidney sodium dumping, though specific dosages vary by individual.
Statins show no benefit in pure diabetic populations.
Comparison of CARDS (primary prevention) and ASPEN (mixed) trials; claim that strictly diabetic cohorts show overlapping event lines.
Controversial. Conflicts with major clinical guidelines (ACC/AHA), though the critique regarding “statistical wizardry” in post-hoc analysis is methodologically valid.
LDL enters endothelium via active transport (Transcytosis), not diffusion.
Reference to 2020 EAS paper acknowledging transcytosis; argument that concentration gradient alone cannot force particles through glycocalyx.
Plausible/Technical. The mechanism is scientifically sound, but whether high LDL concentration upregulates transcytosis remains a point of debate.
Epidemiology is often “garbage” for nutrition causal inference.
Reference to “Grilling the Data” paper (red meat analysis) showing results depend entirely on covariate adjustments.
Strong. Broad academic consensus exists on the limitations of nutritional epidemiology and “healthy user bias.”
Export to Sheets
E. Actionable Insights
Prioritize Metabolic Metrics: Shift focus from isolated LDL-C to the Triglyceride/HDL ratio and HOMA-IR (insulin resistance). These are likely stronger gauges of immediate cardiovascular risk.
Verify with Imaging: If LDL is high but metabolic health is optimal, utilize Coronary Artery Calcium (CAC) scans or CT Angiograms (CCTA) to determine actual atherosclerotic burden rather than relying on probabilistic risk calculations.
Sodium Titration on Low Carb: If experiencing fatigue, cramping, or dizziness on a ketogenic diet, consider sodium supplementation. The standard “low sodium” advice may be counterproductive in a low-insulin state.
Contextualize LDL: Recognize that LDL particles carry energy (triglycerides). In lean, low-carb individuals, high LDL may represent high energy trafficking rather than stalled clearance (The Lipid Energy Model).
Question “Relative Risk” in Trials: When reviewing drug efficacy (e.g., PCSK9 inhibitors or statins), look for absolute risk reduction and Number Needed to Treat (NNT), rather than just relative risk, which can be misleadingly high (e.g., 88% relative reduction vs. minimal absolute change).
Diet Quality over Macronutrients: Focus on eliminating the “Standard American Diet” (processed, hyper-palatable combination of fats and carbs). This yields the majority of health benefits regardless of whether the final diet is vegan, Mediterranean, or Carnivore.
H. Technical Deep-Dive
The Lipid Energy Model (LEM) & Transcytosis
The conversation challenges the Response to Retention hypothesis, which posits that LDL particles passively diffuse into the sub-endothelial space driven by concentration gradients, get retained by proteoglycans, oxidize, and trigger atherosclerosis.
The LEM Proposition: Feldman proposes that VLDL (Very Low-Density Lipoprotein) secretion is upregulated in carbohydrate-restricted, lean individuals to traffic triglycerides to peripheral tissues for fuel. As VLDL rapidly offloads triglycerides (hydrolysis via LPL), it shrinks to LDL. Because these individuals have high turnover but low hepatic uptake (potentially due to cellular cholesterol satiety), LDL accumulates. This accumulation is a marker of energy transport, not necessarily pathology.
Transcytosis Mechanism: The speakers highlight that endothelial cells are not passive sieves. Transport of lipoproteins like LDL across the endothelial barrier occurs largely via SR-BI (Scavenger Receptor Class B Type 1) and ALK1 mediated transcytosis—an active, vesicular transport system.
Argument: If transport is active, the endothelial cell regulates entry based on need (cholesterol/lipids for repair or signaling) or injury response. Therefore, high serum concentration of “native” (unmodified) LDL does not inherently force entry into the arterial wall unless the endothelium is inflamed or signaling for repair.
Implication: In the absence of systemic inflammation (low hs-CRP) and endothelial injury (normal blood pressure, low glucose), the rate of LDL transcytosis may remain low despite high luminal LDL concentration, explaining the lack of plaque progression in the Keto CTA cohort.
I. Fact-Check Important Claims
Claim:High LDL does not cause atherosclerosis in metabolically healthy individuals.
Consensus:False/Nuanced. The established medical consensus (EAS, AHA) states LDL is unequivocally causal in atherosclerosis, with risk being a function of cumulative exposure (mg/dL × years).
Correction/Debate: The speakers argue this consensus relies on data from metabolically unhealthy populations or genetic FH. The “Keto CTA” data is novel because it isolates High LDL in a metabolically healthy population. While the speakers’ data is provocative, it currently lacks the multi-decade longitudinal evidence required to overturn the consensus on cumulative exposure.
Claim:Statins do not benefit diabetics (citing CARDS/ASPEN).
Consensus:Misleading. The CARDS trial was terminated early because the advantages of atorvastatin were so pronounced (37% reduction in major cardiovascular events).
Analysis: Austin argues this benefit disappears when adjusting for primary vs. secondary prevention and scrutinizing the data (“statistical wizardry”). However, clinical guidelines strongly recommend statins for diabetics due to their high baseline risk. Discontinuing statins based on this podcast analysis would contradict standard of care.
Claim:Red meat consumption is not causally linked to colorectal cancer.
Consensus:Debated. The IARC classifies processed meat as Group 1 (carcinogenic) and red meat as Group 2A (probably carcinogenic).
Counter-Evidence: The “Grilling the Data” analysis mentioned suggests that these associations are weak and prone to confounding (Healthy User Bias—red meat eaters in observational studies often smoke/drink more). The absolute risk increase in epidemiological studies is often very small (<1.2 hazard ratio), which Bradford Hill criteria would deem weak for causality.
⸻
Next Step: Would you like me to extract the specific physiological mechanisms Austin mentioned regarding fructose malabsorption and sodium transporters to better understand the electrolyte requirements on a ketogenic diet?
The workouts noted seem pretty mild to me, but I suppose they may be beneficial. I go for more variety and different levels of intensity covering lower body one day and upper body the next.
