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#19 – Dave Feldman: stress testing the lipid energy model — Whalespan

Content›Video›#19 – Dave Feldman: stress t…

#19 – Dave Feldman: stress testing the lipid energy model

Peter Attia3h 11m · 2020-01-01

Support Rate

62%

210 of 341 claims supported

Support rate

210 of 341 claims supported

210 supported131 partial / not

Claims from this content

267

◐Partially SupportedThe podcast content is not a substitute for professional medical advice, diagnosis, or treatment, and users should not delay seeking medical advice for any conditions.✓Well SupportedAtherosclerosis is caused by the inflammatory response to oxidized cholesterol accumulation in macrophages within the artery wall.✓Well SupportedPatients should demand ApoB or LDL particle count testing if their doctor does not perform it, as it is crucial for understanding lipid-related risk.✓Well SupportedRaising HDL particle count may be a more relevant metric for improving reverse cholesterol transport and clinical outcomes than just HDL cholesterol.✓Well Supported

More from Peter Attia

Peter Attia on Zone 2 Cardio

Peter Attia on Rapamycin (with Matt Kaeberlein)

Attia walks back the clinic protocol: too aggressive for healthy adults

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Bookmarking — the dossier-vs-overview split is the right call. Most of the time I want overview; sometimes I want receipts.

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Non-HDL cholesterol is generally more predictive of cardiovascular risk than LDL cholesterol.

✓Well SupportedAs insulin resistance increases, LDL particle number rises disproportionately to LDL cholesterol, with VLDL contributing.

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

◐Partially SupportedPeter Attia maintains an up-to-date and active list of companies he invests in or advises on his website.

◐Partially SupportedContent from the podcast is not a substitute for professional medical advice, diagnosis, or treatment, and users should seek professional help for medical conditions.

✓Well SupportedFasting can increase serum LDL, potentially indicating LDL's role in substance transport.

◐Partially SupportedLarge VLDL particle number is a marker of insulin resistance, not a therapeutic target.

✓Well SupportedThe term 'hyper responder' was coined to describe individuals whose LDL cholesterol, including particle count, increases significantly on low-carb diets.

✓Well SupportedStatins reduce LDL particles by upregulating LDL receptors on hepatocytes, increasing the catabolism of apoB-containing lipoproteins.

◐Partially SupportedRemnant cholesterol might be a more valuable metric for all-cause mortality than LDL-C alone.

◐Partially SupportedFamilial hypercholesterolemia (FH) is a genetic condition caused by over 2,000 polymorphisms affecting LDL receptors or other pathways, leading to very high serum LDL.

✓Well SupportedTo establish LDL as causal, one must ensure atherogenic dyslipidemia does not affect LDL levels and no other factor causes both LDL and the outcome.

✓Well SupportedCanadian guidelines measure apo-b for ldl risk, while US guidelines favor ldl cholesterol.

✓Well SupportedApoB-containing lipoproteins deliver lipids for growth or repair, and excessive deposition without removal leads to atherosclerosis.

✓Well SupportedThe presence of ApoC3 on VLDL and LDL particles indicates a pathologic remnant, increasing their residence time.

✕Not SupportedHDL cholesterol measures the concentration of cholesterol within HDL particles, not their functionality, making it a crude and incorrect metric.

✓Well SupportedIndividuals with a high percentage of ApoE on their LDL particles likely have reduced risk of heart disease due to enhanced clearance.

✓Well SupportedReplacing saturated fat with monounsaturated fat may resolve high cholesterol without significantly altering total fat consumption or ketosis.

✓Well SupportedLDL is the primary driver for apob particles entering the artery wall, making LDL cholesterol and non-HDL cholesterol key metrics.

✓Well SupportedThe ox LDL assay measures the burden of oxidation within LDL particles.

◐Partially SupportedInsulin sensitivity below 5, preferably below 3, makes LDL particle number, LDL size, and related metrics less significant.

◐Partially SupportedInhibiting PCSK9 prevents LDL receptor degradation, increasing LDL receptor upregulation and enhancing LDL clearance from circulation.

◐Partially SupportedPeter Attia shares updates on his activities, interesting papers he has read, and longevity science, performance, and sleep-related content via a weekly email newsletter.

◐Partially SupportedIn lean mass hyper-responders on a low-carb diet, 5% to 30% may experience a rise in LDL and total cholesterol.

✓Well SupportedHemoglobin A1C thresholds for diabetes classification are typically >65 for diabetic, 57-64 for pre-diabetic, and <57 for normal.

✓Well SupportedThe liver is an essential organ with no extracorporeal support systems.

✓Well SupportedEstimating VLDL cholesterol by subtracting LDL cholesterol from non-HDL cholesterol is a method that does not always agree with other estimation methods.

✓Well SupportedA zero coronary artery calcium score indicates a very small risk of a coronary event in the next 15 years.

✓Well SupportedElevated ADMA/SDMA may impair nitric oxide synthase, reducing nitric oxide production and leading to vasodilation.

✓Well SupportedThe half-life of an LDL particle is about one day in non-pathologic states, but can be longer in pathologic states like ApoE4.

✓Well SupportedSmaller denser LDL particles are associated with increased cardiovascular risk.

◐Partially SupportedHypofunctioning ApoE2 alleles are associated with net longevity benefits, particularly in cardiac health and neurodegeneration.

◐Partially SupportedHigh LDL triglyceride levels are associated with high LDL particle count and the presence of small LDL particles.

◐Partially SupportedThe liver is the primary organ capable of degrading cholesterol.

✓Well SupportedHigh-sensitivity C-reactive protein (hs-CRP) and fibrinogen are easily obtainable inflammatory markers.

✓Well SupportedIf LDL is absent, atherosclerosis does not develop, regardless of how LDL is lowered.

◐Partially SupportedIndividuals with significantly elevated LDL cholesterol due to ketogenic or low-carbohydrate diets must make personal decisions about managing their lipids.

◐Partially SupportedStatins may slightly increase diabetes risk in susceptible individuals but do not cause Alzheimer's disease.

◐Partially SupportedDirect LDL cholesterol measurement technically includes Lp(a) cholesterol but does not allow inference of Lp(a) levels without direct testing.

◐Partially SupportedIntense exercise resulted in minimal net change in cholesterol within LDL particles.

◐Partially SupportedNot all cases of Familial Hypercholesterolemia involve receptor deficiencies, and some genetic causes lead to fewer LDL receptors.

◐Partially SupportedInformation related to Peter Attia's podcast can be found at petertiamd.com/podcast.

✓Well SupportedNon-HDL cholesterol may be more relevant than LDL cholesterol for individuals on a low-carb diet with higher triglyceride levels.

✓Well SupportedIndividuals in the Kitav or Semane populations may have LDL particle counts equal to or higher than Americans but exhibit no heart disease.

✓Well SupportedDietary cholesterol has virtually no impact on serum lipoproteins because consumed esterified cholesterol cannot enter the gut.

◐Partially SupportedAn apolipoprotein E3 (ApoE3) assay is an ideal clinical assay for identifying problematic remnant lipoproteins like VLDL.

✓Well SupportedThe majority of cholesterol in the body is synthesized internally, with dietary cholesterol playing a trivial role in circulating cholesterol pools.

◐Partially SupportedVLDL and IDL are created to replete lipid stores in tissues, including adipocytes.

◐Partially SupportedConsuming around 90 net carbs per day for three days may increase liver glycogen stores and lead to a drop in LDL-C.

✓Well SupportedLipoproteins originating from the liver are essential for transporting triglycerides and cholesterol to tissues.

✓Well SupportedIndividuals with abetalipoproteinemia, characterized by low LDL levels, exhibit minimal atherosclerosis.

◐Partially SupportedIn individuals with consistently high LDL cholesterol (e.g., over 300 mg/dL), the cholesterol is likely being recycled rather than newly synthesized.

◐Partially SupportedDefective LDL clearance can be inferred if triglyceride burden, cholesterol synthesis, and absorption decrease while LDL particle number increases.

◐Partially SupportedLDL clearance is regulated at the liver level and is not as static as previously believed, with variability influenced by factors beyond genetics.

◐Partially SupportedThe difference in atherogenicity, residence time, and total ApoB load is driven by the LDL particle, not the VLDL particle.

✓Well SupportedIndividuals with familial hypercholesterolemia and lifelong LDL levels of 400-600 mg/dL can have zero atherosclerosis, suggesting LDL is not the sole cause.

◐Partially SupportedChylomicrons, which carry triglycerides, are cleared from circulation within minutes to two hours after a meal.

◐Partially SupportedRemnants are a smaller part of a lipoprotein class, and all known lipoprotein classes, including Lp(a), have remnants.

✓Well SupportedHigh LDL should be considered in the context of high HDL and low triglycerides.

◐Partially SupportedMeasuring changes in desmosterol levels can indicate an individual's cholesterol synthetic function.

◐Partially SupportedFamilial Hypercholesterolemia (FH) is a phenotype with at least 2,000 known variations.

✓Well SupportedAn LDL particle count of 2 x 10^16 causes atherosclerosis, whereas 1 x 10^16 does not.

✓Well SupportedLean mass hyper-responders with high LDL may experience regression of atherosclerosis.

✓Well SupportedIndividuals on low-carb diets typically have Lp(a)-PLA2 levels around 200-250, which is not associated with significant increased risk of high Lp(a).

◐Partially SupportedThe remnant cholesterol value of 13 mg/dL is not significantly different from what would be calculated using the triglyceride-by-five formula.

◐Partially SupportedUpregulation of cholesterol synthesis from saturated fat, possibly linked to regulatory pathways involving ketones or saturated fat, may explain a phenotype of very high LDL particle number, high cholesterol synthesis, and high cholesterol absorption in lean/fit individuals.

◐Partially SupportedMeasuring LDL triglycerides would be the best lipid metric for assessing cardiovascular risk.

◐Partially SupportedIn high-risk patients on statins with very low desmosterol or lathosterol levels, avoiding further suppression of cholesterol synthesis is suggested due to alternative lipid-lowering options.

◐Partially SupportedA highly fat-adapted individual running is in negative fat flux, with zero de novo lipogenesis and lipolysis exceeding esterification.

◐Partially SupportedA study of people with high HDL, low triglycerides, and high LDL is valuable for assessing cardiovascular disease and all-cause mortality risk.

◐Partially SupportedThe cardiovascular benefit of elevated bilirubin follows an inverted U-shaped curve.

✓Well SupportedThe lipid hypothesis posits that LDL cholesterol is harmful and directly injures the endothelium, and is linked to the saturated fat versus polyunsaturated fat debate.

◐Partially SupportedPhytosterols, plant-based sterols that cannot be synthesized by the body, provide insight into cholesterol recirculation.

◐Partially SupportedLDL cholesterol is a necessary but not sufficient cause of atherosclerosis, requiring endothelial dysfunction and inflammation as co-factors.

◐Partially SupportedA small interfering RNA (siRNA) therapy targeting ApoC3 is in clinical trials to impair ApoC3 function.

◐Partially SupportedCurrent clinical methods cannot reliably differentiate between LDL particles originating from VLDL catabolism versus those directly secreted from the liver in LDL form.

◐Partially SupportedDuring a fasted run for a fat-adapted individual, adipocytes release free fatty acids to albumin, which transports some to muscles for beta-oxidation and some back to the liver for conversion to beta-hydroxybutyrate or packaging into VLDL/IDL.

✓Well SupportedFocus should be on insulin sensitivity and reversing insulin resistance, rather than solely on apob particles, if LDL is not directly injurious to the endothelium.

◐Partially SupportedSevere lipid perturbations observed in some individuals on a ketogenic diet may be due to pre-existing genetic predispositions interacting with the diet.

◐Partially SupportedApolipoprotein C3 (ApoC3) increases the residence time of lipoproteins like VLDL and LDL.

✕Not SupportedPCSK9 gain-of-function mutations are excellent proxies for the key features of lean mass hyper-responders and should not be ignored in lipid models.

✓Well SupportedMeasuring ApoB provides an almost exact particle count of lipoproteins.

◐Partially SupportedHigh LDL cholesterol or LDL particle levels may offer a survival advantage during infection.

✓Well SupportedRemoving LDL prevents atherosclerosis, but LDL is necessary but not sufficient for causation.

◐Partially SupportedAtherosclerosis progression involves changes that occur long before significant luminal narrowing is present.

◐Partially SupportedA week-long fast, even in a ketogenic state, may not increase LDL-P as predicted by some models.

◐Partially SupportedThe FOURIER and ODYSSEY OUTCOMES trials showed that PCSK9 inhibitors (evolocumab and alirocumab) reduce major adverse cardiovascular events.

◐Partially SupportedPolyunsaturated fats are likely not as detrimental as historically believed, but are likely not as beneficial as monounsaturated fats.

◐Partially SupportedLongevity encompasses both increasing lifespan and improving healthspan.

◐Partially SupportedThe ApoE2 allele is associated with protective benefits for longevity, particularly in neurodegeneration and cardiovascular health.

◐Partially SupportedPCSK9 overexpression accounts for 3-5% of Familial Hypercholesterolemia patients and was the initial discovery pathway for PCSK9.

◐Partially SupportedIncreased LDL-P after consuming saturated fatty acids may be due to increased cholesterol production, decreased hepatic clearance, or both.

◐Partially SupportedWeight training may lower LDL-C levels due to increased receptor-mediated endocytosis of LDL by muscle cells.

◐Partially SupportedA zero calcium score with a normal lipid panel (excluding triglycerides) indicates less concern about cardiovascular risk.

✓Well SupportedFor individuals with hyper-response to saturated fat, isocalorically shifting to a high monounsaturated fat diet can resolve elevated apob levels in about half of cases.

✕Not SupportedA standard lipid panel provides limited information for cardiovascular risk assessment and requires interpretation in the context of other values.

◐Partially SupportedDave Feldman is skeptical of the LDL-is-causal paradigm for heart disease.

◐Partially SupportedThe benefit of elevated bilirubin is subject to an inverted U-shaped curve, where very high levels negate any antioxidative advantages and lead to harm.

✕Not SupportedDividing triglyceride levels by five to estimate VLDL cholesterol is not recommended.

◐Partially SupportedLDL particles may originate from VLDL particles and are not primarily for energy delivery.

◐Partially SupportedLDL particles carry significantly more cholesterol molecules than HDL particles.

◐Partially SupportedDave Feldman's personal lipid profile includes triglycerides of 74 mg/dL, HDL of 87 mg/dL, and LDL of 216 mg/dL on a non-keto diet.

◐Partially SupportedLDL cholesterol should not be interpreted as a pure risk factor for cardiovascular disease but in the context of overall metabolic health.

◐Partially SupportedLean mass hyper-responders are typically fit, thin, feel well, have good health markers including low inflammation, and may not necessarily be at higher risk for atherosclerosis.

◐Partially SupportedSaturated fat may be converted into cholesterol more readily than ketones.

◐Partially SupportedAll-cause mortality is generally not affected by LDL lowering and may decrease as LDL levels increase.

◐Partially SupportedHigher LDL particles may be driven by increased cholesterol synthesis rather than solely by absorption.

◐Partially SupportedThe recycling of LDL cholesterol is driven by the demand for the originating cargo, which is delivered by VLDL particles.

◐Partially SupportedProblems in immunological roles, potentially induced by lipolysis, can occur on the support side of LDL.

◐Partially SupportedNon-fasted remnant cholesterol may increase as insulin sensitivity improves.

◐Partially SupportedDefective LDL receptors on endothelial cells could lead to dysfunction.

✕Not SupportedSome peers of Dave Feldman may be deluded by confirmation bias and unwilling to acknowledge potential harm from low-carbohydrate diets.

◐Partially SupportedThe lifetime exposure problem is a significant challenge in atherosclerosis research, as drug studies are typically short-term compared to the long development of atherosclerosis.

◐Partially SupportedAn individual with extremely high LDL-P on a ketogenic diet prioritized feeling well over potential long-term cardiovascular risk.

◐Partially SupportedPeter Attia hypothesizes 'lipid malabsorption' where genes affecting LDL-C may also impact cellular lipid uptake, potentially causing endothelial cell dysfunction and atherosclerosis.

◐Partially SupportedHigher levels of phytosterols indicate greater absorption of sterols, as they cannot be synthesized by the body.

◐Partially SupportedHigh LDL-P caused by a ketogenic diet is critical information for individuals at higher cardiovascular risk.

◐Partially SupportedMany in the low-carb community reject mainstream nutritional guidance due to flawed past guidance like the food pyramid.

◐Partially SupportedIncreases in LDL particle number and total cholesterol may not be causal, as individuals increasing dietary or exogenous cholesterol consumption often also increase dietary fat consumption.

◐Partially SupportedFor individuals with extremely high LDL-P on a ketogenic diet, reducing saturated fat is hypothesized to be more impactful than exiting ketosis.

◐Partially SupportedThe long-term relevance of observed LDL-C drops is questioned if effects are transient and require extreme dietary conditions.

◐Partially SupportedIndecision regarding health choices is a decision in itself and requires active consideration.

◐Partially SupportedResistance training may impact the overall lowering of LDL cholesterol numbers.

◐Partially SupportedApolipoprotein C3 (ApoC3) levels correlate with insulin levels, suggesting longer lipoprotein residence times in individuals with type 2 diabetes and hyperinsulinemia.

✕Not SupportedExcluding genetic studies when investigating the relationship between lipid profiles and cardiovascular disease limits the available data.

◐Partially SupportedIndividuals with a family history of type 2 diabetes should proactively address it.

◐Partially SupportedA fasting glucose of 103 mg/dL warrants monitoring and proactive measures to prevent type 2 diabetes.

◐Partially SupportedDave Feldman proposes that lean mass hyper-responders on ketogenic or low-carbohydrate diets may have a different genesis of heart disease than the standard LDL causal paradigm.

◐Partially SupportedDiabetic ketoacidosis is associated with very elevated levels of LDL cholesterol and triglycerides.

✕Not SupportedDave Feldman's model does not adequately explain why VLDL production would drive increased LDL concentration, as insulin-sensitive individuals typically have lower triglyceride export from the liver.

◐Partially SupportedDave Feldman's LDL-P increased from 920 nmol/L to 1380 nmol/L after one week of a ketogenic diet.

◐Partially SupportedVLDL particle number is approximately 80 in insulin-sensitive individuals, 84 in insulin-resistant non-diabetics, and 100 in type 2 diabetics.

◐Partially SupportedA hemoglobin A1c of 6.1% indicates pre-diabetes or diabetes, and acting on this information is a decision.

◐Partially SupportedPeter Attia is seeking studies on the link between high LDL, high HDL, and low triglycerides with cardiovascular disease in individuals without genetic predisposition or specific drugs.

◐Partially SupportedNon-hepatic receptor-mediated endocytosis of LDL is primarily valuable for tissues requiring cholesterol for hormone synthesis.

◐Partially SupportedPopulation-level data can obscure individual variations, such as individuals with very high LDL who do not develop atherosclerosis.

◐Partially SupportedLDL may function as a source of raw material, such as cholesterol, for muscle cell membrane repair.

◐Partially SupportedLowering LDL in patients with established cardiovascular disease may not fully mitigate risk but probabilistically moves them in a better direction.

◐Partially SupportedHDL particles carry immunoglobulins and other proteins that play a role in immune function.

◐Partially SupportedInjecting LPS into a person leads to a higher HDL cholesterol level.

◐Partially SupportedIt is important to identify patients for whom LDL lowering is causing unacceptable harm elsewhere, such as impaired cholesterol synthesis.

◐Partially SupportedIn patients with triglycerides below 130 mg/dL, 38% of LDL particles were de novo secreted by the liver, while 62% originated from IDL or VLDL.

◐Partially SupportedA ketogenic diet can lead to LDL-P exceeding 3500 nmol/L in young individuals.

◐Partially SupportedHDL particles may have a more important immunological role than LDL particles.

◐Partially SupportedLDL cholesterol generally decreases under caloric deprivation.

◐Partially SupportedAssessing lipid and lipoprotein numbers should include baseline measurements of triglycerides, desmosterol, sitostanol/sitosterol, and LDL particle number.

◐Partially SupportedElevated bilirubin levels above a threshold of 10 are toxic and lead to significant illness.

◐Partially SupportedThe 'keto gains' community has fewer reported cases of pronounced LDL-C increases compared to runners or individuals doing yoga.

◐Partially SupportedUnderstanding genetic alterations is important for individuals susceptible to certain metabolic phenotypes.

◐Partially SupportedNot all free fatty acids released during lipolysis are oxidized; some are re-uptaken by fat cells if the hormonal milieu permits.

◐Partially SupportedElevated cholesterol levels in individuals with high ketones can be corrected by addressing metabolic deficits with IV fluids, glucose, insulin, potassium, and normalizing electrolyte and fluid balance.

◐Partially SupportedThe liver functions as the body's 'energo-stat', detecting circulating energy currencies like ATP ratios to regulate energy balance.

◐Partially SupportedReducing triglycerides may be achieved by increasing liver glycogen stores, which could lead to less VLDL and subsequently less LDL secretion.

◐Partially SupportedThe speaker will be convinced if LDL-P is shown to be atherogenic independent of remnant lipoproteins, high HDL, or low triglycerides.

◐Partially SupportedPerturbing lipid metabolism can have unintended effects that need to be evaluated for relevance to atherosclerosis.

◐Partially SupportedCIMT and CAC are tests used to gauge advanced arterial disease, distinct from biomarkers like LDL cholesterol.

◐Partially SupportedA regression analysis on triglycerides, HDL, and LDL-P would be valuable for understanding the lipid energy model.

◐Partially SupportedHigh cholesterol levels, such as LDL-P above 3500, may not always correlate with increased cardiovascular risk.

◐Partially SupportedA properly functioning lipid energy system, indicated by LDL-C, ApoB, and triglycerides, is more important than individual marker levels.

◐Partially SupportedAtherosclerosis can develop for a significant period without detectable signs, potentially up to 60% occlusion before luminal narrowing becomes apparent.

◐Partially SupportedApproximately 2,000 known genetic mutations result in a phenotype of high LDL, high HDL, and low triglycerides, which should be considered in lipid models.

◐Partially SupportedThe expansion of LDL particle number is the critical factor in cardiovascular disease risk, not necessarily the increase in VLDL particle number.

◐Partially SupportedLDL particle number (LDL-P) can vary over a three-day period.

◐Partially SupportedBilirubin may possess antioxidative properties, contributing to cardiovascular protection.

◐Partially SupportedLP PLA2 levels above 600 are concerning.

◐Partially SupportedThere is currently no reliable method to determine remnant cholesterol levels.

◐Partially SupportedStopping smoking improves cardiovascular outcomes.

◐Partially SupportedWeight loss signifies that lipolysis exceeds fat re-entry into fat cells.

✕Not SupportedDismissing LDL's relevance and promoting statin conspiracy theories is a dangerous problem within the low-carb community.

◐Partially SupportedCorrecting metabolic deficits in diabetic ketoacidosis with IV fluids, glucose, and insulin normalizes glucose, fluid balance, electrolytes, and cholesterol.

✕Not SupportedRemnant cholesterol levels are generally low and track well with triglycerides, and are not clinically relevant outside of specific pathologic states.

✕Not SupportedComparing non-HDL cholesterol or remnant cholesterol as predictors of cardiovascular disease to LDL cholesterol is like comparing rubbing two stones to rubbing two logs for fire when a Zippo lighter is available.

✕Not SupportedThere is no evidence that PCSK9 hyper-functioning patients experience toxic endothelial reactions due to impaired cholesterol uptake.

✕Not SupportedTriglycerides are not sufficient to understand lipid metabolism.

✕Not SupportedDave Feldman's lipid energy model fails to account for the increased mass of cholesterol and number of LDL particles observed in certain phenotypes.

✕Not SupportedThere is no known cardiovascular reason to have high LDL cholesterol.

✕Not SupportedHigh HDL-C and low triglycerides do not negate the importance of LDL-C levels for cardiovascular health.

✕Not SupportedHDL-C alone provides no understanding of lipid metabolism.

◐Partially SupportedIf cholesterol metabolism were purely about energy, individuals would have more cholesterol-depleted particles rather than making more cholesterol.

◐Partially SupportedDriving LDL cholesterol to zero may not be the optimal strategy because it might come at other costs, despite reducing atherosclerosis risk.

◐Partially SupportedApoC3-targeting drugs may offer limited benefit to insulin-sensitive individuals.

◐Partially SupportedInsulin resistance is associated with high triglycerides and VLDL, which are associated with cardiovascular disease.

◐Partially SupportedIn lean mass hyper-responders, ldl cholesterol and ldl particle number are concordant.

◐Partially SupportedA sterol panel is essential for a comprehensive assessment of lipid metabolism in addition to advanced lipid panels.

◐Partially SupportedProperly functioning lipid metabolism is indicated by LDL-C, HDL-C, and triglycerides.

◐Partially SupportedLipoprotein concentration and residence time influence the amount of lipoproteins entering the artery wall.

◐Partially SupportedMeasuring LDL particle number before starting a low-carb diet is recommended to understand potential changes.

◐Partially SupportedIncreased cholesterol synthesis is distinct from cholesterol passively carried by LDL particles.

◐Partially SupportedLipoproteins require a complex system for selective uptake of components by cells.

◐Partially SupportedLDL particles can carry up to 1,500 molecules of cholesterol.

◐Partially SupportedInjecting lipopolysaccharides (LPS) can induce higher fatty acid synthesis and lipolysis in the liver, increasing triglycerides.

✕Not SupportedIncreasing polyunsaturated fat intake carries a risk of increasing lipid peroxidation.

◐Partially SupportedSwapping fat for carbs in a ketogenic shake for two days, followed by a high-fat diet for five days, resulted in an immediate and sustained drop in LDL-C.

◐Partially SupportedIncreased dietary cholesterol consumption can trigger a hyper-synthetic pathway for cholesterol in susceptible individuals.

◐Partially SupportedIt is crucial to specify the type of cholesterol change when discussing cholesterol.

◐Partially SupportedChylomicrons are lipoproteins originating from the gut that primarily carry dietary fat and are hydrolyzed by lipoprotein lipase via apoC-II.

◐Partially SupportedIndividuals on a low-carbohydrate diet who are fat-adapted are likely utilizing both dietary and endogenous triglyceride sources.

◐Partially SupportedDetecting a change in all-cause mortality in drug studies requires significant statistical power.

?Limited ResearchInsulin resistance, ApoB, and LDL-P may not apply to individuals who are ketogenic and fat-adapted.

?Limited ResearchIn individuals on a low-carb diet with high triglycerides, elevated LDL particles may result from increased VLDL transport.

?Limited ResearchPeter Attia is uncertain that individuals with very high LDL cholesterol are absolutely at increased risk for atherosclerosis or that their risk is commensurate with their lipid profile.

◐Partially SupportedDietary fat intake can influence LDL cholesterol levels, potentially moving within a wide range.

◐Partially SupportedProblems with lipid or lipoprotein absorption, unrelated to the total quantity of LDL particles, are a primary concern for malnourishment.

◐Partially SupportedIndividuals who are high synthesizers of cholesterol tend to be low absorbers, suggesting a self-regulating system.

◐Partially SupportedThe LXR gene regulates cholesterol regulation within enterocytes, jettisoning excess through the ABCG5/ABCG8 transporter.

◐Partially SupportedDietary cholesterol plays a trivial role in circulating cholesterol levels because its side chains are not absorbable.

◐Partially SupportedLDL-C levels are at least as sensitive to carbohydrate intake as they are to fat intake.

◐Partially SupportedReducing saturated fat intake to 25 grams per day while maintaining ketosis may help manage cholesterol.

◐Partially SupportedElevated LDL cholesterol in some individuals on high-fat diets may be reversible by eliminating saturated fat.

◐Partially SupportedHyper-responders to dietary changes may be producing more cholesterol due to mass balance principles.

◐Partially SupportedDeficiencies in cholesterol absorption and transport mechanisms can lead to hypercholesterolemia.

◐Partially SupportedChylomicrons primarily deliver fat-based energy, while HDL is not involved in energy delivery.

◐Partially SupportedThe speaker maintained a strict ketogenic diet during the period of the kinetic experiment.

◐Partially SupportedThe liver maintains the lipid supply by continuously putting energy back out.

◐Partially SupportedIn a fasted state, chylomicrons and their remnants should be absent from blood tests.

◐Partially SupportedFamilial Hypercholesterolemia may offer a slight protective advantage in cases of infection and diabetes.

◐Partially SupportedMendelian randomization can be discounted if mutations measured for cholesterol levels also affect other factors driving cardiovascular processes.

◐Partially SupportedReducing blood pressure or smoking will lead to improved cardiovascular outcomes.

◐Partially SupportedIndividuals with Familial Hypercholesterolemia are born with a normal vascular system that becomes destroyed over time.

◐Partially SupportedDysfunctional endothelial cells can contribute to atherosclerosis.

?Limited ResearchThe role of LDL in combating oxidative stress is not sufficiently evidenced.

◐Partially SupportedAtherosclerosis requires uptake of oxidized sterol by a macrophage.

◐Partially SupportedReducing blood pressure, smoking, or lipoproteins improves cardiovascular outcomes.

◐Partially SupportedReducing blood pressure improves cardiovascular outcomes.

◐Partially SupportedTransient increases in HDL cholesterol observed in patients with Systemic Inflammatory Response Syndrome are interpreted as a significant reverse cholesterol transport mechanism delivering cholesterol to adrenal glands.

◐Partially SupportedDave Feldman's personal data showed regression of plaque in carotid arteries while maintaining LDL-C levels over 200 mg/dL and LDL-P levels over 2000 nmol/L.

◐Partially SupportedThe liver regulates cholesterol by secreting it into bile, which is transported into enterocytes where the LXR gene attempts to manage excess.

◐Partially SupportedRemnant cholesterol may help address the problem of why anyone would have high triglycerides, rather than all triglycerides being utilized by tissues or stored in adipocytes.

◐Partially SupportedLipoproteins are lipid-carrying proteins produced by the body in the gut and liver, measured in quintillions, that transport various lipids including triglycerides, cholesterol, and fat-soluble vitamins.

◐Partially SupportedStratifying a million randomly selected people in the US for high LDL could yield significant data on cardiovascular risk.

◐Partially SupportedMild elevations in liver function tests typically do not indicate a synthetic issue due to the liver's large functional reserve.

◐Partially SupportedDeficiencies in transporters like Niemann-Pick C1-like 1 or ATP-binding cassette transporters can lead to significantly increased cholesterol levels, independent of LDL receptor function.

◐Partially SupportedAtherosclerosis progresses through documented stages, beginning with lipoproteins entering the artery wall via diffusion.

◐Partially SupportedThe body of literature supporting LDL's causal role in atherosclerosis is of a significantly higher quality than that which produced the food pyramid.

◐Partially SupportedThere appears to be a higher proportion of lean and/or fit individuals who are metabolically flexible among participants who submit data to cholesterolcode.com.

◐Partially SupportedA significant drop in LDL-C and LDL-P occurs within three days of consuming large amounts of dietary fat.

◐Partially SupportedBlood tests, including the ox LDL assay, provide probabilities of events occurring in the artery rather than a direct measurement of arterial status.

◐Partially SupportedGenetic, pharmacologic, and mechanistic data collectively provide a high degree of certainty sufficient to guide clinical action in lipid management.

◐Partially SupportedVery low asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels are exceptionally low and unexpected.

◐Partially SupportedThe height of bars in the presented chart represents milligrams per deciliter of cholesterol or triglyceride, not LDL particle number.

◐Partially SupportedThe presented data reflects the net flux of cholesterol and triglycerides in LDL particles, not the movement of individual particles.

◐Partially SupportedHigh LDL-C levels (200+ mg/dL) on four consecutive tests may indicate regression in carotid arteries.

◐Partially SupportedThe secretion level of cholesterol per LDL particle tends to be fairly standard.

◐Partially SupportedLipoproteins play a role in the causality of atherosclerosis, which is influenced by many factors.

◐Partially SupportedCardiovascular studies often show a reduction in coronary mortality without a statistically significant change in all-cause mortality.

◐Partially SupportedMany genes influencing lipid metabolism are unidentified, and FH is a phenotypic diagnosis with diverse genetic causes.

◐Partially SupportedThe burden of proof should be on the lipidology community to demonstrate that LDL is causal for cardiovascular disease.

✕Not SupportedMyocardial infarction should be considered a critical event in emergency medicine protocols.

◐Partially SupportedIn a state of negative fat flux during weight loss on a low-carb diet, de novo lipogenesis is zero, esterification is present, and lipolysis is greater than esterification.

◐Partially SupportedA low-carbohydrate diet can lead to an increase in serum cholesterol, which may be due to increased fat trafficking and co-transport with cholesterol in lipoproteins, rather than solely increased absorption.

◐Partially SupportedA ketogenic diet typically raises HDL cholesterol.

◐Partially SupportedThe low-carb high-fat (LCHF) diet and ketogenic diet are dietary approaches to manage blood glucose levels and potentially avoid type 2 diabetes.

◐Partially SupportedAdopting a low-carb high-fat diet can lead to a significant increase in LDL cholesterol and total cholesterol.

◐Partially SupportedDave Feldman's father saw his type 2 diabetes A1c improve from 8.3 to 5.9 after adopting a low-carb high-fat diet.

◐Partially SupportedDave Feldman's sister is no longer hypertensive after adopting a low-carb high-fat diet.

◐Partially SupportedA low-carb diet can cause cholesterol to rise substantially in some individuals.

◐Partially SupportedStatins inhibit cholesterol synthesis, but most cells can produce sufficient cholesterol for their own needs, except for gonadal and steroidal tissues during high stress.

◐Partially SupportedA patient with a high calcium score and bad CTA was treated as a secondary prevention patient with aggressive lipid-lowering therapy.

◐Partially SupportedLowering LDL cholesterol is unambiguously clear in reducing cardiovascular disease risk.

◐Partially SupportedThe primary purpose of LDL particles is to transport cholesterol back to the liver.

◐Partially SupportedIndividuals can be categorized based on their cholesterol synthesis levels: hyper-synthesizers, normal synthesizers, and low synthesizers.

◐Partially SupportedScientific claims cannot be proven in the absolute sense, only supported or refuted by data.

◐Partially SupportedIncreased cholesterol synthesis is linked to higher organismal growth and increased cell demand.