What Causes Cardiovascular Disease? | Lipid Series Part 1 | Dr. Thomas Dayspring | The Proof Ep 251

Introduction

In this episode, Dr. Thomas Dayspring discusses the lipid transport system and how it relates to atherosclerotic cardiovascular disease.

Lipid Transport System

• If the April beam measurement in the blood exceeds a certain level, there are more apob particles circulating than the liver is clearing.

• As that number goes up, the particles are not being cleared by the liver and instead crash into arteries.

• The APO B particle carrying cholesterol passes through the endothelial lining of every artery in our body and ends up in the artery wall.

• This process is step one of atherogenesis.

About Dr. Thomas Dayspring

Dr. Thomas Dayspring's background and expertise are discussed.

Background

• Dr. Thomas Dayspring is an expert in understanding lipids' role in atherosclerotic cardiovascular disease.

• He is certified in Internal Medicine and clinical lipidology.

• He has written textbooks on lipids, published peer-reviewed papers, and illustrated some of the finest lipid images.

Importance of Understanding Lipids

The importance of understanding lipids is discussed.

Understanding Lipids

• It's important to understand how our body transports fats and cholesterol to prevent fatty plaque from building up inside artery walls.

• Atherosclerotic cardiovascular disease is statistically speaking, the most likely reason our life will be cut short globally.

• Studying this complex area of science can help us optimize our lipids as early as possible to prevent heart attacks or strokes.

Thanking Dr. Thomas Dayspring

Peter Attia thanks Dr. Thomas Dayspring for his work and contributions to the field.

Thanking Dr. Thomas Dayspring

• Peter Attia thanks Dr. Thomas Dayspring for his work in preventative cardiology and his ability to explain complex lipidology concepts.

• Dr. Dayspring's illustrations are particularly helpful in understanding these concepts.

• The conversation is a part of a mini-series that will delve into assessing risk and interventions to lower the risk of atherosclerotic cardiovascular disease.

Conclusion

In this episode, Dr. Thomas Dayspring discusses the lipid transport system and its relation to atherosclerotic cardiovascular disease. Understanding how our body transports fats and cholesterol can help us optimize our lipids as early as possible to prevent heart attacks or strokes.

Introduction

In this section, the speaker introduces the goals of the conversation and shares a personal story that inspired his passion for cardiovascular disease prevention.

Goals of the Conversation

• The first goal is to explain how the cardiovascular system works.

• The second goal is to discuss how this system can go awry and increase the risk of atherosclerosis.

• The third goal is to have fun.

Personal Story

• When the speaker was 15 years old, he witnessed his father experiencing chest pain while driving home from a weekend trip.

• His father downplayed it as indigestion or heartburn, but later had to be airlifted to a hospital due to high cholesterol and blood pressure.

• This experience inspired the speaker's passion for understanding and preventing cardiovascular disease.

Understanding Cardiovascular Disease

In this section, the speaker discusses his belief that we could be doing more to prevent cardiovascular disease through lifestyle changes.

Importance of Prevention

• The speaker believes that there is a lot of information available about preventing cardiovascular disease, but we are not doing enough with it.

• He emphasizes that prevention is key because not everyone will be as lucky as his father in surviving an episode of heart disease.

Medications for Prevention

• The speaker mentions medications such as anti-hypertensives and statins that may come up during their conversation about preventing cardiovascular disease.

Introduction to Atherosclerotic Heart Disease

In this section, the speaker talks about his experience as a physician in the 1970s and how heart disease was a major issue at that time. He also discusses how lipidology has made significant progress in treating atherosclerotic heart disease.

The Prevalence of Heart Disease in the 1970s

• The coronary care unit was an exciting place to be due to the high number of acute heart disease cases.

• Many patients with acute coronary syndromes died within hours or days of being admitted to the hospital.

• Witnessing people having heart attacks is not fun, especially when there is little that can be done as a physician.

Progress in Treating Atherosclerotic Heart Disease

• Blood pressure pills were one of the first treatments for heart disease.

• Lipidology has made massive inroads in treating atherosclerotic heart disease.

• Early detection and treatment of risk factors can eliminate atherosclerotic disease as morbidity and mortality.

Understanding Atherosclerosis and Risk Factors

In this section, the speaker provides an overview of atherosclerosis and its impact on cardiovascular health. He also discusses some key risk factors that contribute to the development of this condition.

What is Atherosclerosis?

• Atherosclerosis is the buildup of fatty plaque in artery walls, which can occur in several arteries throughout the body.

• It is one of the most common causes of cardiovascular disease, leading to many afflictions that affect the heart and blood vessels.

Key Risk Factors for Atherosclerosis

• High cholesterol levels, high blood pressure, smoking, and diabetes are some of the top risk factors for atherosclerosis.

• Early detection and treatment of these risk factors can significantly reduce the likelihood of developing atherosclerotic disease.

Assessing Risk for Atherosclerotic Heart Disease

In this section, the speaker discusses how to assess an individual's risk for developing atherosclerotic heart disease. He also talks about some key diagnostic tools that can be used to evaluate cardiovascular health.

Assessing Risk for Atherosclerotic Heart Disease

• Periodic evaluation with diagnostic tools can help identify individuals at risk for atherosclerotic heart disease.

• Identifying treatable risk factors early in life and treating them appropriately can eliminate atherosclerotic disease as morbidity and mortality.

Key Diagnostic Tools

• Biomarker signs and imaging signs are two important diagnostic tools used to evaluate cardiovascular health.

• These tools can help identify early signs of atherosclerosis and other cardiovascular diseases.

Lipids and Cardiovascular Risk Factors

In this section, the speaker discusses risk factors and markers for cardiovascular disease, including high blood pressure, lipid disturbances, male gender, and age. The focus of the conversation is on lipids as a major risk factor when there are disturbances.

Understanding Lipids

• A lipid is an organic molecule that is not soluble in water.

• Lipids include sterols (such as cholesterol) and fatty acids (which are part of lipids like phospholipids or triglycerides).

• Cholesterol is crucial for cell membranes, hormone production, and bile acid synthesis.

• Plasma is used to transport lipids in the body but it cannot carry them directly due to their insolubility in water.

Relationship between Lipids and Cardiovascular Disease

• High blood pressure and lipid disturbances are major risk factors for cardiovascular disease.

• Male gender and age are also significant risk factors.

• Evolution has given every cell in the body the ability to synthesize cholesterol because it is so crucial. However, transporting lipids through plasma presents a challenge.

Importance of Risk Assessment

• To do the best risk assessment for cardiovascular disease, both risk factors and markers must be considered.

• Blood tests can provide information about biomarkers that help assess risk.

• Age is a major risk factor that cannot be controlled but other factors like high blood pressure and lipid disturbances can be treated with serious interventions.

Lipoproteins and the Lipid Transportation System

This section discusses how lipids are transported in the body through lipoproteins, which are made up of lipids and proteins. The intestine and liver are the only organs that can produce lipoproteins, which transport lipids to cells that need them or eliminate excess lipids from cells.

Lipid Carrying Molecules

• Lipoproteins consist of lipids and proteins.

• The intestine and liver are the only organs that can produce lipoproteins.

• Lipoproteins transport various lipid components to cells that need them or eliminate excess lipids from cells.

Function of Lipoproteins

• Cells upregulate a receptor to internalize the content of a lipoprotein if they need a lipid.

• Cells pump out excess cholesterol into a lipid carrying vehicle called a lipoprotein.

• Lipoproteins take triglycerides in a forward direction from the intestinal liver to various cells or in a reverse direction from cells back to the liver.

• A lipoprotein carrying triglycerides could stop at adipocytes, fat cells, where it would store some of the triglycerides until needed again.

• A lipoprotein could bring cholesterol not triglycerides to steroidogenic organs such as adrenal cortex or gonads for hormone synthesis.

Phospholipids

• Phospholipids are crucial for constructing cell membranes in the body.

Lipoproteins and their Synthesis

In this section, the speaker discusses the synthesis of lipoproteins in the intestine and liver. They also differentiate between two classes of lipoproteins.

Two Locations for Lipoprotein Synthesis

• Lipoproteins are synthesized in two locations: the intestine and liver.

• There are two classes of lipoproteins: those made in the liver or intestine (chylomicrons, VLDL, IDL, LDL), and those that self-create themselves in plasma (HDL).

Differentiating Between Lipoprotein Classes

• Chylomicrons, VLDL, IDL, and LDL have one major structural protein called APO lipoprotein B.

• HDL particles are differentiated from other lipoproteins by their protein structure which is APO A1.

Absorption of Fats and Cholesterol

In this section, the speaker explains how fats and cholesterol are absorbed into the body through digestion.

Digestion Process

• After eating a meal containing fats and cholesterol, they enter the small intestine where they get packaged into chylomicrons.

• Bile acids secreted by the liver help transport these lipids to the brush border of the small intestine where they can be absorbed.

Intestinal Absorption of Lipids

This section discusses the process of lipid absorption in the intestine and how it is transported throughout the body.

Receptors for Lipid Absorption

• The intestine has receptors that recognize fatty acids, fatty acid transport proteins, and sterols.

• The major receptor for recognizing sterols is called Neiman pick C1 like one (NPC1L1).

Synthesis of Organic Lipid Molecules

• Primitive organic lipid molecules such as fatty acids, cholesterol, phytosterols, and partially hydrolyzed phospholipids are absorbed by the intestine.

• These lipids are then synthesized into triglycerides, cholesterol ester, lysophospholipid, and phospholipids with two fatty acid legs.

Formation and Transport of Chylomicrons

• The enterocyte forms a chylomicron by attaching all these lipids to Apo B protein.

• Chylomicrons are released into the lymphatic system before entering the bloodstream through the thoracic duct.

• Chylomicrons deliver their lipid load to various tissues in need of energy such as skeletal muscles and cardiac muscle.

Hydrolysis of Triglycerides

• Triglycerides from chylomicrons are hydrolyzed by lipoprotein lipase when they reach muscular beds that require energy.

• Fatty acids break away from their glycerol backbone and are pulled into muscles where they undergo beta oxidation to create ATP.

Remnant Chylomicron

• As chylomicrons lose their triglycerides, they become smaller and release surface phospholipids.

• The remaining cholesterol is not taken up by muscles and is instead synthesized de novo.

Lipoprotein Transport System

This section discusses the lipoprotein transport system and how it works.

Delivery of Energy

• Chylomicrons have a short half-life in minutes, while VLDL has a half-life of 6-8 hours.

• Phospholipids shed by chylomicrons and VLDL are grabbed by phospholipid transfer protein and used to mature HDL particles.

• Lipoproteins work together to help each other build up empty.

Delivery of Triglycerides and Cholesterol

• VLDL delivers triglycerides to muscles after being secreted by the liver.

• Once they shrink, they either become an IDL or are rapidly returned to the liver.

• IDL is cleared at the liver with hepatic lipase causing further apolysis, shrinking it into LDL.

• LDL receptors prefer to clear particles with apoe and apob on it so all of a sudden LDL particles have an immensely longer plasma residence time than do kylos for sure vleels idls.

LDL and Reverse Cholesterol Transport

This section discusses the role of LDL in supplying cholesterol to peripheral tissues, the mechanism by which HDL extracts cholesterol from cells, and how reverse cholesterol transport occurs.

LDL's Role in Supplying Cholesterol

• The adrenal cortex can upregulate LDL receptors to supply it with cholesterol when overworking.

• Gonads virtually never express LDL receptors as they synthesize a ton of cholesterol or extract it from HDL particles.

• An individual can have an LDL cholesterol of 10 without gonadal or adrenal cortical dysfunction because LDL doesn't supply those organs with their cholesterol.

Why Do LDLS Hang Around for So Long?

• APO A1 extracts unneeded cholesterol from any cells and forms bigger HDL particles.

• CETP is a lipid transfer protein that allows HDL to transfer its internal fluids to an LDL particle.

• One molecule of cholesterol goes from the HDL to the LDL, but in return, the LDL sends a molecule of triglyceride to the HDL.

• If this happens frequently, small HDLs are created that can go back and fill up at cells.

Reverse Cholesterol Transport

• Direct reverse cholesterol transport is when HDL brings back excess cholesterol directly to the liver.

• Indirect reverse cholesterol transport is when an HDL gives its excess cholesterol to an LDL particle that returns it to the liver via its receptors.

• Total reverse cholesterol transport is direct plus indirect.

• Serum HDL levels provide no insight into total reverse cholesterol transport.

Lipoprotein Origin and Function

This section discusses the origin and function of lipoproteins in the body.

Enterocytes and Chylomicron Lipoproteins

• Enterocytes separate food from the lymphatic system.

• Chylomicron lipoproteins package up fats and cholesterol from food or liver.

• Receptors like Neiman Peak C1 N1 affect chylomicrons.

• Chylomicrons enter circulation, provide energy to muscle cells, dump off triglycerides, become smaller, and turn into chylomicron remnants that go back to the liver.

Liver Synthesis of VLDLs and LDLs

• The liver synthesizes VLDL molecules that deliver triglycerides to tissues.

• As they dump off triglycerides, they become smaller and take on a new name as IDL molecules.

• They can then become LDL molecules whose primary role is to bring cholesterol back to the liver or take it off HDL particles.

Purpose of Cholesterol in Lipoproteins

• Cholesterol is put in lipoproteins to make them spherical and create volume for other lipids.

• It helps shape and create volume in lipoproteins but is not put there to be delivered somewhere.

Cholesterol Production and Lipoprotein Proteins

This section discusses the importance of cholesterol production within the gonads or adrenal cortex, how organs synthesize de novo cholesterol, and the role of lipoprotein proteins in wrapping around these particles.

Cholesterol Production and Lipoprotein Proteins

• High serum blood cholesterol requires great cholesterol production within the gonads or adrenal cortex.

• Organs synthesize de novo cholesterol using acetate or citrate as an initial building block.

• Lipoprotein proteins wrap around chylomicrons, VLDL, IDL, LDL, and HDL. ApoB is present in all except HDL which has ApoA1.

Beta Lipoprotein Family and Particle Concentration

This section discusses the differences between beta lipoproteins and HDL particles. It also explains how particle concentration influences atherogenesis.

Beta Lipoprotein Family and Particle Concentration

• The beta lipoprotein family contains ApoB particles with one molecule per particle while HDL contains one to four molecules of their structural protein ApoA1.

• Particle number drives APO B particle carrying cholesterol into artery walls causing atherogenesis.

• When this system is working well at physiological norms levels, LDL particles are finding their way back to the liver instead of depositing as plaque in artery walls.

Physiological Norm Levels

This section explains what happens when apob particle concentration exceeds a certain level.

Physiological Norm Levels

• When apob particle measurement in the blood exceeds a certain level, there are more particles circulating than the liver is clearing.

• As the number of particles increases, they are not being cleared by the liver and instead crash into nearby artery walls causing atherogenesis.

• Most people get other lipid concentrations tested but measuring ApoB is by far the best metric for cardiovascular risk assessments.

Atherosclerosis in Children

This section discusses how children's cholesterol levels differ from adults and how it affects their risk of developing atherosclerosis.

Atherosclerosis in Children

• Children have physiologic levels of ApoB particles with measurements ranging from 20 to 50 milligrams per deciliter.

• Infants have very little circulating cholesterol in their bodies yet their brains develop normally for several years.

• Very few people with physiologic numbers of ApoB particles ever get atherogenesis or atherosclerosis.

APO B and Atherosclerosis

In this section, Dr. Brewer discusses the relationship between APO B and atherosclerosis, as well as the importance of measuring APO B early in life to prevent atherogenesis.

Importance of Measuring APO B Early in Life

• Measuring APO B early in life can help identify individuals who are at risk for developing atherosclerosis.

• Starting a better lifestyle in young people with high levels of APO B can halt atherogenesis before it begins.

• Many 18 to 22-year-olds have significant non-clinical (symptomless) atherosclerosis due to high levels of APO B.

• Cholesterol cannot enter artery walls without an APO B particle dumping it there.

Threshold Levels for APO B

• The concentration of APO B in young humans is around 40 to 50 milligrams per deciliter.

• The threshold level for developing atherosclerotic plaque depends on other risk factors present, such as smoking or diabetes.

• In general, people should aim to be in the bottom 20th percentile population cut point for their age group, which is around 80 milligrams per deciliter.

• People with super high levels of APO B (above the 80th percentile, around 115-120 milligrams per deciliter), are most commonly at risk for developing atherosclerotic heart disease.

Exceptions to the Rule

• While high levels of APO B are the biggest risk factor for atherosclerosis, there may be protective factors that prevent it from occurring in a small minority of people.

• However, there is no data to support the idea that having high levels of APO B is safe in the long term.

Atherosclerosis and the Role of ApoB

This section discusses how ApoB particles get stuck in the arterial wall, leading to atherosclerosis.

ApoB Particles and Connective Tissue Molecules

• ApoB particles can get stuck in the intimate, which is the outer connective tissue area of the arterial wall.

• The ApoB protein on the surface of the particle has great affinity for connective tissue molecules.

• These particles can be bound to proteoglycans in the arterial wall and remain there forever.

Macrophages and Foam Cells

• For atherosclerosis to develop, an ApoB cholesterol-containing particle has to be ingested by a macrophage that is in the arterial wall connective tissue.

• Some retained ApoB particles are substrates for receptors on macrophages that they will internalize.

• If a macrophage keeps internalizing huge numbers of these particles, it becomes super cholesterol engorged and turns into a foam cell.

• Foam cells are collections of cholesterol that form plaque in the artery wall.

Endothelial Dysfunction and Inflammation

• Transcytosis of ApoB particles can occur with perfectly healthy endothelial cells.

• Inflammation of endothelium occurs when macrophages start ingesting these particles and secreting pro-inflammatory cytokines chemokines.

• Many human conditions like collagen diseases, insulin resistance, diabetes have subtle elevations of C-reactive protein, which can lead to endothelial dysfunction and inflammation.

• Risk factors like high blood pressure and smoking also play a role in the quality of the endothelium.

APOB and Inflammation

This section discusses the relationship between APOB and inflammation, as well as the impact of elevated levels of LDL cholesterol on atherosclerosis.

APOB and Inflammation

• Insulin resistance and diabetes are pro-inflammatory states.

• Movement and flux of APOB-containing lipoproteins from circulation into the intima is inevitable, but other risk factors can exacerbate this process.

• Elevated levels of LDL cholesterol can lead to a pro-inflammatory state, which contributes to atherosclerosis.

• Even if there is no inflammation present initially, once an APOB particle enters the macrophage it will cause inflammation.

Transcytosis and Foam Cells

This section discusses transcytosis, foam cells, and how they contribute to atherosclerosis.

Transcytosis

• Most APOB-containing lipoproteins that pass through the endothelium get caught there or rot away without contributing to atherosclerosis.

• There is no quantitative data on how many particles undergo transcytosis versus become retained in the intima.

Foam Cells

• Something has to happen to differentiate retained APOB particles that become substrates for macrophage endocytosis versus those that do not. Oxidation may be one factor but there is little human data supporting this theory.

The Role of Phospholipids in LDL Particle Aggregation

In this section, the speaker discusses how phospholipids on LDL particles can be rearranged by enzymes called mutases, leading to the formation of aggregated LDL particles that are more attractive to macrophage receptors.

Phospholipid Rearrangement and Aggregation

• Phospholipids on retained April B LDL particles can be oxidized or rearranged by mutases.

• Certain phospholipids become attractive targets for macrophage receptors, leading to aggregation of multiple LDL particles.

• Aggregated LDL particles bind together and undergo some degree of oxidation.

• Macrophages internalize hundreds of aggregated LDL particles instead of just one, leading to foam cell formation and fatty plaque buildup.

The Importance of Reducing APO B Containing Lipoproteins

In this section, the speaker emphasizes the importance of reducing APO B containing lipoproteins such as VLDLs, IDLs, and mainly LDLS in circulation over time to prevent retention and modification being taken up by macrophages.

Concentration Reduction is Key

• To stop the process of retention and modification being taken up by macrophages, we need to reduce the concentration of APO B containing lipoproteins such as VLDLs, IDLs, and mainly LDLS in circulation over time.

• Large concentrations of APO B containing lipoproteins lead to endothelial dysfunction and damage.

• Large concentrations of LDLS are responsible for the majority of invasion into the artery wall.

• Reducing LDL particle concentration is achievable with various therapeutic maneuvers.

The Role of Oxidized LDL in Bloodstream

In this section, the speaker questions whether oxidized LDL floating in the bloodstream is of any consequence and discusses how people often say that if you don't consume certain oils, you don't have to worry about oxidation of LDL.

Questions About Oxidized LDL

• The speaker questions whether oxidized LDL floating in the bloodstream is of any consequence.

• People often say that if you don't consume certain oils, you don't have to worry about oxidation of LDL.

Oxidized LDL

In this section, the speaker discusses the use of oxidized LDL as a biomarker and its relationship to atherosclerotic disease.

Uselessness of Oxidized LDL as a Biomarker

• The measurement of minimally oxidized LDL in the bloodstream is a useless metric for measuring oxidized LDL.

• Standard oxidized LDL tests that laboratories offer are not useful and are just a way for labs to make money.

• The oxidation of LDL particles occurs in the intima, not in circulation.

Controlling Oxidation

• It is speculative whether diet and consumption of antioxidants, vitamin E, and polyphenols can control oxidation.

• Healthy lifestyles may help reduce atherosclerotic disease by reducing inflammation but it is unclear how exactly they do it.

APO B Particle and Inflammation

• High APO B is causal for atherosclerotic disease.

• Reducing cholesterol deposition in the intima by stopping APO B from going into the artery wall will arrest arterial wall inflammation.

• Atherosclerosis doesn't develop in every square inch of an artery throughout your body; there are certain key locations where blood is coming hard.

Differences Between Veins and Arteries

In this section, the speaker discusses why fatty plaque buildup tends to occur more frequently in arteries than veins.

Factors Contributing to Fatty Plaque Buildup

• Blood pressure starts factoring into fatty plaque buildup in arteries.

• Arteries are tortuous, and atherosclerosis doesn't develop in every square inch of an artery throughout your body.

• Fatty plaque buildup tends to occur where blood is coming hard.

Veins vs Arteries and Atherosclerosis

In this section, Dr. Tom Daypring discusses the difference between veins and arteries in terms of thrombotic complications and atherosclerosis. He also talks about the mechanism behind atherosclerosis.

Veins are subject to thrombotic complications not atherosclerosis

• Particles are present in both veins and arteries.

• Veins are subject to thrombotic complications, not atherosclerosis.

• Saphenous veins were used for coronary bypasses but now putting a vein in an arterial milieu can cause development issues.

Mechanism behind Atherosclerosis

• Blood flow and blood kinetics play a role in the development of atherosclerosis.

• Epidemiologic studies show that ApoB is causal in the development of atherosclerosis.

• Randomized controlled clinical trials control for things like ApoB or change it during trials to study its effects.

• Genetic studies look at genes associated with atherosclerosis to determine if certain metrics matter.

Determining Elevated APO B Levels

In this section, Dr. Tom Daypring discusses how someone can determine whether their APO B level or LDL cholesterol level is elevated due to genetics or lifestyle.

Polygenic Risk Score

• The science is moving towards polygenic risk scores that analyze all Snips associated with arthrosclerotic risk or protection.

• An abnormal polygenic risk score indicates genetic abnormalities that increase arthrosclerotic risk.

Understanding Lipid Disorders and Genetics

Dr. Peter Attia discusses how lipid disorders are caused by underlying genetic abnormalities, which interact with environmental factors to increase the risk of developing atherosclerosis.

The Role of Genes in Lipid Disorders

• Lipid disorders have an underlying genetic abnormality that interacts with environmental factors.

• Depending on the genes you have, leading a healthy lifestyle may not be enough to prevent lipid disorders.

• Genes play a significant role in the development of atherosclerosis, and new drugs are being developed to target specific genes involved in this process.

Longevity and Healthspan

• People born with gene mutations that reduce their risk of atherosclerosis may show greater longevity.

• However, longevity is not just about living longer but also living disease-free (healthspan).

• Preventing degenerative diseases such as atherosclerosis can improve healthspan even if it does not guarantee longer life.

Mechanisms Behind Elevated ApoB

• There is an idea that the mechanism by which ApoB is elevated affects the quality or function of those particles and their ability to become retained and modified during atherogenesis.

Familial Hypercholesterolemia and Genetic Analysis

In this section, the speaker discusses how genetic analysis can help diagnose familial hypercholesterolemia (FH) and determine the risk level of patients with high LDL cholesterol levels.

FH Diagnosis and Genetic Analysis

• FH diagnosis requires high LDL cholesterol levels that put patients within the definition of FH.

• Genetic analysis can identify monogenic disturbances that cause high LDL cholesterol levels in some patients.

• Patients with a genetic mutant have a higher risk than those without, but both are at immense risk for cardiovascular disease.

• Modern therapeutic modalities can restore APO B levels to physiological levels, reducing the risk of cardiovascular disease regardless of genetic cause.

Lean Mass Hyper Responder and High Fat Diets

In this section, the speaker discusses lean mass hyper responders (LMHR), their lipid profiles, and how high-fat diets affect their health.

LMHR Diagnosis and Secondary Causes

• LMHR is an absurd term as most people who fall under this category are not lean.

• Rule out secondary causes of hyper beta lipoproteinemia such as severe hypothyroidism, renal disease, liver diseases or certain diets like ketogenic diet before diagnosing LMHR.

High-Fat Diets and APO B Levels

• High-fat diets raise APO B through mostly saturated fat shutting down LDL receptors or inducing cholesterol synthesis.

• As more people adopt ketogenic diets, lipidologists see more cases of raised APO B due to diet than other secondary causes.

• LMHR patients can continue their high-fat diet, but a combination of therapies may be required to control APO B levels.

• Drugs are not very effective in treating LMHR patients due to the complexity of factors involved.

Sterile Regulatory Element Binding Protein and Liver X Receptor

This section discusses the role of nuclear transcription factors, specifically sterile regulatory element binding protein (SREB) and liver X receptor (LXR), in regulating genes that modulate cholesterol homeostasis.

SREB and LXR

• SREB and LXR are nuclear transcription factors that regulate genes involved in cholesterol homeostasis.

• SREB senses saturated fat and shuts down LDL receptors to prevent excess lipids from entering the liver.

• These sensors control genes that modulate cholesterol homeostasis.

Fiber, Dietary Cholesterol, and Microbes

This section discusses how fiber can help lower cholesterol levels in the body by binding to cholesterol in the gut or regulating gut microbes. It also explores why it's difficult to answer whether dietary cholesterol significantly affects blood cholesterol levels.

Fiber

• Fiber can bind to cholesterol in the gut, making it less readily available for absorption or incorporation into biliary salts.

• Fiber may have a regulatory effect on gut microbes that convert free cholesterol to coprostanol, which cannot be absorbed by the body.

Dietary Cholesterol

• The absorption of dietary cholesterol is complex and involves multiple stages.

• Genetic differences can affect how much dietary cholesterol is absorbed by an individual.

• It's difficult to answer whether dietary cholesterol significantly affects blood cholesterol levels because of these complexities.

Absorption of Sterols in the Gut

This section delves deeper into the absorption of sterols in the gut, including how bile ducts produce most of the cholesterol found in our guts, how different enzymes work together to absorb sterols, and how HDL particles can help absorb cholesterol.

Absorption of Sterols

• The absorption of sterols in the gut involves multiple stages, including the production of cholesterol by bile ducts and the absorption of sterile by biliary cells.

• Different enzymes, such as acat, work together to absorb sterols.

• HDL particles can also help absorb cholesterol.

Hyperabsorption of Cholesterol

In this section, the speaker discusses hyperabsorption of cholesterol and how it affects dietary recommendations.

Hyperabsorption of Cholesterol

• Hyperabsorbers of cholesterol should reduce their cholesterol intake in their diet.

• Phytosterol supplements should be avoided by hyperabsorbers as they absorb a sterol that the human body does not want to see.

• High HDL cholesterol is not necessarily an indicator of hyperabsorption, but it could suggest it.

• If someone is a hyper absorber, the drug of choice would be a zetamide, which blocks absorption of cholesterol.

Genetic Studies

• Genetic studies can help determine if someone is a hyper absorber and what type of problem they have.

• Acetamine can be used to block absorption for those who cannot afford genetic tests.

High Density Lipoprotein (HDL)

In this section, the speaker discusses HDL and its role in transporting excess cholesterol from cells or tissues.

Purpose of HDL

• HDL's primary purpose is to transport excess cholesterol from cells or tissues.

• Nuclear transcription factors regulate expression in ABC A1 ABC G5 GA being the lxr especially would down-regulate abca1 if someone has too much cholesterol in their system.

• The nuclear transcription factors sense the cellular milieu and tell genes what to do.

Lab Metrics

• Laboratory metrics are not always helpful in determining cholesterol levels.

• In the next conversation, lab metrics will be discussed in more detail.

Importance of Self-Study in Lipidology

In this section, the speaker emphasizes the importance of self-study in mastering lipidology and provides tips on how to become a better student.

Becoming a Better Student

• Trustworthy and respected people in the field are essential to follow.

• Half of what you learn will be wrong, so be prepared to forget it and learn new things.

• Follow the right people on Twitter, including @DrLipid for readily available information.

• Be careful with internet sources as there are many unreliable sources out there.

Conclusion

In this section, the speakers conclude their discussion by thanking each other and expressing excitement for future conversations.

Final Thoughts

• The podcast would not have happened without cholesterol.

• The upcoming conversations will focus on measuring heart disease risk and interventions.

• Thank you for taking control of your health, and we look forward to seeing you again next week.