How to avoid Alzheimer's disease! ApoE4 on keto/carnivore? Tommy Wood, MD, PhD

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Paul Saladino1h 40m · 2019-08-13

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188

Claims Supported

138

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138 of 188 claims supported

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Well SupportedThe APOE4 genotype is the major genetic risk factor for Alzheimer's disease, with risk increasing in a dose-dependent manner.Well SupportedMetabolic dysfunction, specifically insulin resistance, is the primary event leading to atherosclerosis, not LDL directly injuring the endothelium.Well SupportedIn the third trimester, babies' serum ketone levels are significantly higher than their mothers', indicating the body shunts ketones to the fetus for brain development.Well SupportedAs insulin resistance increases, LDL particle number rises disproportionately to LDL cholesterol, with VLDL contributing.Well Supported

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Carriers of two copies of APOE4 have a 12-fold increased chance of developing Alzheimer's disease, while carriers of one copy have a two to four-fold increased chance.

Well SupportedApolipoprotein B (ApoB) is the primary marker for atherogenic particles, while Apolipoprotein A (ApoA) is associated with HDL.

Well SupportedThe speaker aims for at least one gram of protein per pound of body weight daily, currently consuming 1.1-1.3 grams per pound.

Partially SupportedStatin use may impair cholesterol synthesis in the brain, potentially impacting cognition.

Well SupportedStatins inhibit HMG-CoA reductase in the liver, which is part of the mevalonate pathway involved in Coenzyme Q10 synthesis.

Well SupportedMonitoring desmosterol may be important to avoid excessive inhibition of cholesterol synthesis in the brain for patients prone to dementia requiring a statin.

Well SupportedThe APOE4 allele emerged relatively recently in human evolution, suggesting that for the majority of human history, individuals possessed the APOE2 or APOE3 alleles.

Well SupportedThe apoE4 isoform historically offered advantages, including protection against infections.

Not SupportedFocusing solely on LDL cholesterol as the sole indicator of cardiovascular risk is a poor predictor.

Well SupportedLipoproteins are spherical molecules used to transport cholesterol and triglycerides through the circulation.

Well SupportedKetones can be utilized by the brain as a fuel source, and research supports their benefits for the brain.

Partially SupportedInsulin resistance or metabolic dysfunction may play a significant role in the accumulation of LDL in arterial walls.

Well SupportedWhen limiting carbohydrates, the body may use LDL lipoprotein particles for energy, potentially leading to higher LDL cholesterol.

Well SupportedBrain lipoproteins are recognized by neurons via LDL receptors, LRP, or scavenger receptors, allowing cholesterol uptake.

Well SupportedA significant majority of obese or overweight Americans likely have some degree of insulin resistance.

Well SupportedAlzheimer's disease can be viewed as 'brain diabetes' where insulin resistance hinders neuronal glucose utilization.

Well SupportedIndividuals who are very insulin resistant may not tolerate carbohydrates well, suggesting a need to limit them until insulin sensitivity improves.

Well SupportedThe E4/E4 genotype increases Alzheimer's risk by 16 times compared to E3/E3, and E3/4 increases risk by about 4.5 times.

Well SupportedBrain insulin resistance, associated with Alzheimer's disease, is linked to IGF-1 resistance, IRS-1 downregulation, and cognitive decline.

Well SupportedIn the Semai population, APOE4 is associated with improved cognitive function in metabolically healthy individuals facing high parasite and pathogen load.

Well SupportedInsulin resistance increases the expression of the APO C3 gene, which is associated with longevity.

Well SupportedIndividuals with ApoE 3/4 or 4/4 genotypes may have difficulty clearing LDL particles from circulation.

Well SupportedInflammation can trigger insulin resistance as an evolutionary mechanism to shift resources to the immune system.

Well SupportedIncreasing insulin sensitivity is the primary goal in managing insulin resistance, achievable through diet and exercise.

Partially SupportedAlzheimer's disease is often referred to as 'type 3 diabetes' due to brain insulin resistance.

Well SupportedThe desiccated brain supplement from Ancestral Supplements contains sphingomyelin, which plays a central role in the myelin sheath and cell signaling.

Well SupportedAn estimated 85% of the population may have metabolic disease.

Well SupportedOligodendrocytes are major cholesterol producers in the brain, synthesizing cholesterol primarily for myelin sheath formation, and do not supply cholesterol to neurons.

Well SupportedA high LDL cholesterol level may not always be detrimental, particularly for individuals who are insulin sensitive.

Well SupportedThe ApoE2/2 genotype, which is rare, is associated with approximately a 20% risk reduction for Alzheimer's disease.

Well SupportedInsulin resistance is a cellular response to impaired energy metabolism, indicating cells cannot process energy efficiently and are signaling for reduced energy intake.

Not SupportedThere is insufficient solid data directly indicting LDL and apob-containing particles as the cause of endothelial injury leading to atherosclerosis.

Well SupportedLipophilic statins are more likely to cross the blood-brain barrier and suppress cholesterol production, increasing dementia risk.

Partially SupportedInsulin resistance can affect LDL metabolism and raise total cholesterol through a mechanism different from how ketogenic or carnivore diets raise LDL.

Partially SupportedIn individuals without markers of insulin resistance, LDL cholesterol does not correlate with cardiovascular disease.

Well SupportedApoC3 is increased in states of insulin resistance and may cause LDL particles to be retained in the subendothelial space.

Partially SupportedPopulations worldwide consume large amounts of carbohydrates without developing insulin resistance, suggesting that carbohydrate intake alone is not the sole cause.

Partially SupportedLovastatin, the statin found in red yeast rice, is a mycotoxin that inhibits HMG-CoA reductase.

Well SupportedAPOE4 is considered more concerning clinically in individuals of Asian or Caucasian descent compared to those of Latin or African descent.

Partially SupportedKetone production machinery also makes cholesterol, leading to direct LDL secretion.

Partially SupportedInsulin resistance decreases the brain's ability to signal with insulin, potentially causing molecular mechanisms and mitochondrial dysfunction.

Partially SupportedSimvastatin has been largely removed from the market due to pharmacokinetic issues and a high potential for drug-drug interactions, unlike atorvastatin and rosuvastatin.

Well SupportedApolipoproteins bind to lipids, forming lipoproteins and directing their metabolic pathway.

Not SupportedLipophilic statins that cross the blood-brain barrier may increase dementia risk by inhibiting cholesterol production in the brain.

Partially SupportedIndividuals with apoE4 can follow ketogenic or carnivore diets because their ancestors did so for the majority of human evolution.

Well SupportedFasting glucose levels above 150 mg/dL clearly indicate a problem, but values between 105-150 mg/dL are less informative regarding insulin sensitivity.

Partially SupportedFactors contributing to insulin resistance include excessive energy intake, damaged mitochondria, oxidative stress, and inflammation.

Partially SupportedAmyloid beta proteins may have a microbial and antibacterial role.

Well SupportedSerum insulin levels can indicate insulin resistance, even in lean individuals.

Partially SupportedHigh coenzyme Q levels are observed in individuals consuming nose-to-tail diets.

Partially SupportedConsuming desiccated organ supplements, such as brain, can provide nerve trophic factors and growth factors beneficial for mental performance.

Partially SupportedImpaired immune and repair processes in insulin resistance may lead to LDL accumulation in arteries.

Well SupportedUnhealthy eating, stress, poor sleep, and inadequate exercise can trigger symptoms of genetic predispositions like insulin resistance.

Partially SupportedAchieving metabolic health, characterized by insulin sensitivity and absence of metabolic dysfunction, is crucial for reducing overall disease risk.

Partially SupportedInsulin has an anabolic or trophic role in the brain.

Partially SupportedFactors such as chronic stress, sleep deprivation, nutrient insufficiency, hyperglycemia, glucose swings, toxic metal exposure, and infections are associated with Alzheimer's disease and amyloid beta accumulation.

Partially SupportedBefore LDL retention occurs in the subendothelial space, there is an expansion of the extracellular matrix and smooth muscle cells within the intima.

Well SupportedTriglyceride content in lipoproteins influences their plasma residence time and potential for atherogenicity.

Partially SupportedIncreasing cholesterol levels are associated with increasing risk of Alzheimer's disease in individuals without the APOE4 allele.

Partially SupportedThe APOE4 genotype is problematic primarily in metabolically unhealthy individuals.

Partially SupportedIndividuals with a low triglyceride to HDL ratio or a coronary artery calcium score of zero or less than 100 may not benefit from statin therapy.

Partially SupportedAncestral Supplements' organ meat capsules are freeze-dried, low-temperature dehydrated, and encapsulated in gelatin from New Zealand cows.

Partially SupportedKetones serve as a transport mechanism for fat energy and cholesterol synthesis in the brain, bypassing the blood-brain barrier.

Partially SupportedInsulin resistance can originate in fat cells, muscle cells, or organs like the liver.

Well SupportedThe APOE4 protein's single amino acid substitution alters its conformation and impairs its function as a cholesterol acceptor and transporter.

Partially SupportedStatins were originally derived from monacolins, such as monacolin K from red yeast rice, which has led to recalls due to adverse effects.

Partially SupportedA healthy endothelium may negate the need to focus on lowering LDL particle levels, especially in populations without widespread insulin resistance.

Well SupportedIndividuals with ApoE4 are advised to reduce saturated fat intake.

Partially SupportedIn metabolically unhealthy individuals, LDL levels are strongly associated with cardiovascular disease.

Partially SupportedAn increased cerebrospinal fluid to serum insulin ratio in diabetes suggests rising insulin levels similar to the periphery.

Well SupportedAPOE4 carriers who experience traumatic brain injury have significantly worse outcomes compared to non-carriers with TBI.

Not SupportedFailed attempts to treat Alzheimer's by targeting amyloid beta antibodies suggest amyloid is not the sole problem.

Partially SupportedAdipose tissue functions as an endocrine organ, releasing hormones called adipokines and cytokines.

Partially SupportedApolipoprotein B (ApoB) interacts with the LDL receptor.

Partially SupportedElevated LDL may be a consequence of the mechanism driving it, rather than the elevated LDL itself, in predicting future cardiovascular events.

Partially SupportedUnrefined saturated fats, such as tallow, are not problematic and are consumed in a natural form.

Partially SupportedApolipoproteins are proteins inserted into lipoprotein particles like LDL, VLDL, HDL, and chylomicrons.

Partially SupportedApoE plays a role in cholesterol transport and immune modulation, potentially offering benefits in individuals with high infection burden.

Partially SupportedNeurons require trophic factors like insulin for survival, and resistance to these factors can lead to neuronal death.

Partially SupportedLoss of cholinergic neurons in the basal forebrain correlates with symptom severity in neurological conditions.

Partially SupportedDale Bredesen suggests avoiding large amounts of refined saturated fats for individuals with the apoE4 allele.

Partially SupportedInsulin can cross the blood-brain barrier and play a role in brain health.

Partially SupportedLiquid fats may affect the gut differently than solid fats, potentially increasing the translocation of endotoxins across the gut lining.

Not SupportedInsulin resistance is a central factor binding together various health problems, but its root causes are often overlooked in favor of simply reducing carbohydrate intake.

Not SupportedFat tissue acts as a buffer for metabolic disease and is protective; reducing or eliminating fat cells increases the risk of diabetes.

Partially SupportedPoor sleep quality, nutrient quality, omega-3 fatty acid intake, and hyperglycemia interact with ApoE4 to increase Alzheimer's disease risk.

Not SupportedAddressing upstream factors that cause neuronal stress is more effective than treating the accumulation of amyloid beta.

Partially SupportedIn the Bolivian Tsimane population, LDL was not a significant predictor of coronary artery calcium.

Partially SupportedWhen circulating glucose is decreased, ketones provide precursors for synthesis, not just acting as fuel.

Partially SupportedUnrefined, non-heated, non-rendered fat, including organ meats and suet, is likely beneficial for humans.

Partially SupportedIberian pork fat from White Oak Pastures is a highly palatable fat source.

Partially SupportedGlucose metabolism can lead to increased oxidative stress and excess hydrogen peroxide production.

Partially SupportedApolipoprotein E (ApoE) is a protein composed of approximately 230 amino acids, with polymorphisms at locations 112 and 157 determining ApoE2, ApoE3, or ApoE4 variants.

Partially SupportedImprovements in sanitation, such as clean running water, and modern medicine, particularly in neonatal and pediatric care, have significantly reduced childhood mortality and increased life expectancy.

Partially SupportedLifestyle factors like good sleep, diet, and sun exposure cannot be patented, potentially explaining their limited focus in medical research.

Partially SupportedIn the elderly, higher total cholesterol levels predict an older chronological age but do not correlate with an increased prediction of mortality.

Partially SupportedIncreased LDL particle residence time in circulation may lead to particle modification, increasing cardiovascular disease risk.

Partially SupportedDietary fats can interfere with LDL receptors, increasing LDL residence time in circulation.

Partially SupportedLow Coenzyme Q10 levels are a cause for concern.

Partially SupportedAstrocytes are the primary metabolic regulators of the brain, producing metabolic fuels for neurons and regulating the blood-brain barrier.

Partially SupportedMicroglia are the resident immune cells of the brain, originating from the same lineage as macrophages.

Partially SupportedNeurons require small amounts of trophic factors, such as insulin, for survival signaling.

Partially SupportedGlucose uptake into brain neurons via the GLUT3 transporter is not insulin-dependent.

Partially SupportedAmyloid-beta burden does not correlate with symptom burden in Alzheimer's disease, and removing amyloid beta does not lead to dramatic symptom improvement.

Partially SupportedAmyloid beta plaques in the brain can be associated with viral particles.

Partially SupportedFungal-derived and lipophilic statins are associated with a higher incidence of cognitive decline and dementia.

Partially SupportedStatin therapy does not appear to benefit individuals in good metabolic health who are not insulin resistant.

Partially SupportedThe Blue Zones concept may be a myth due to potentially fraudulent claims of supercentenarians from poor birthdate recording.

Partially SupportedReducing intake of refined saturated fats like butter and MCT oil is advisable when entering ketosis.

Partially SupportedInsulin sensitivity is a direct modulator of circulating cholesterol levels, affecting PCSK9 levels and LDL receptor function, and insulin resistance can lead to elevated cholesterol.

Not SupportedThe overemphasis on LDL in Western medicine overlooks the mechanism by which elevated LDL is achieved, which may be more predictive of cardiovascular risk than the LDL level itself.

Partially SupportedLipoproteins, such as LDL, have known immunologic functions and are not universally toxic.

Partially SupportedFor individuals with APOE4, increased saturated fat intake may lead to higher cholesterol levels.

Partially SupportedThe high odds ratio of 13.4 for APOE4 contributes to fear surrounding this genetic variant.

Partially SupportedRefined saturated fats, unlike unrefined ones, can cause dramatic shifts in endotoxins.

Partially SupportedIn familial hypercholesterolemia, elevated LDL and total cholesterol are associated with increased cardiovascular risk in younger individuals, but may offer protection against infections in older, insulin-sensitive individuals.

Partially SupportedThe total amount of carbohydrates consumed, rather than just the percentage of total calories, is a significant factor in developing insulin resistance, especially when delivered through processed foods.

Partially SupportedOptimizing metabolic health through diet, sun exposure, movement, and social connections can mitigate risks associated with ApoE4 and LDL particle number.

Partially SupportedFactors like ApoE4, high LDL particle number, endothelial dysfunction, and neuronal stress are associated with increased risk of cardiovascular disease and dementia, particularly in individuals with metabolic disease.

Partially SupportedEstrogen decline around menopause increases Alzheimer's disease risk because estrogen is a trophic factor for neurons.

Partially SupportedAmyloid beta accumulation in the brain is a response to neuronal stress, not necessarily a direct cause of cognitive decline or Alzheimer's disease.

Partially SupportedViral particles, diabetes/insulin resistance, and BMAA are stressors that can lead to neuronal damage and amyloid beta production.

Partially SupportedAccumulation of amyloid beta becomes problematic if the underlying stressor is not removed or if sleep is inadequate, hindering clearance.

Partially SupportedThe homozygous APOE4 allele is associated with a 13.4 odds ratio for negative health outcomes.

Partially SupportedAmyloid beta has protective effects, including anti-inflammatory, antioxidant, and antimicrobial properties.

Partially SupportedThe modern environment creates unique susceptibilities, particularly for individuals with apoE4.

Partially SupportedHigher levels of LDL cholesterol are protective against infections and may contribute to longer lifespan in the elderly.

Partially SupportedInsulin-sensitive fat acts as a buffer for metabolic disease.

Partially SupportedActivating GLUT4 transporters with movement, rather than insulin, is the optimal way to avoid insulin resistance.

Partially SupportedOligodendrocytes form the white matter of the brain, enabling high-speed neural signal transmission.

Partially SupportedNeurons utilize cholesterol for fuel and cell membrane integrity.

Partially SupportedHigher cholesterol levels, particularly total and LDL cholesterol in midlife, are associated with a higher incidence of Alzheimer's disease.

Partially SupportedAPOE4 may be protective of cognition in the absence of insulin resistance and hyperglycemia.

Partially SupportedBMAA, an algal toxin, can cause amyloid accumulation and is linked to Alzheimer's disease in populations consuming fruit bats that eat BMAA-laden fruit.

Partially SupportedThe speaker's carbohydrate sources include sweet potatoes and fruit, while fat sources include eggs, meat, and high-fat dairy.

Partially SupportedMost people will thrive on ketogenic or carnivore diets, regardless of genetic polymorphisms in fatty acid metabolism.

Partially SupportedApoE4 is a significant genetic risk factor for dementia.

Partially SupportedGenetic predispositions may influence an individual's tolerance to carbohydrates before developing insulin resistance.

Partially SupportedAvoiding contagious insulin resistance through a good lifestyle may be more important than having the apoE4 allele for protection against neurological insults.

Partially SupportedPlant toxins may trigger insulin resistance.

Partially SupportedElevated LDL may not be a problem in individuals without pre-existing metabolic disease.

Partially SupportedKetogenic diets, high-fat diets, and carnivore diets are not believed to increase risk for individuals with apoE4, especially when metabolic health is good.

Partially SupportedPerceived health dangers are often overstated when extrapolated from sick populations to healthy ones.

Partially SupportedAlterations in LDL particles increase LDL residence time but require prior metabolic impairments.

Partially SupportedInsulin resistance can influence multiple physiological factors, potentially making them appear as independent risk factors.

Partially SupportedLarge blood glucose swings damage the artery lining, increasing permeability and LDL retention.

Partially SupportedApoE3 on the surface of LDL particles may increase their retention time in the sub-endothelial space.

Partially SupportedHigh insulin levels and elevated homocysteine are associated with changes in the endothelium that increase LDL retention.

Partially SupportedInflammation signals a need to shift resources to the immune system, assuming an infection is present.

Partially SupportedIndigenous populations historically had a mortality rate 150 times higher in children aged 0-10 years compared to Westernized populations.