apoB Archives - Parts 4-9, The straight dope on cholesterol « The Eating Academy | Peter Attia, M.D

apoB Archives « The Eating Academy | Peter Attia, M.D. The Eating Academy | Peter Attia, M.D.

The straight dope on cholesterol – Part IV

Previously, in Part I, Part II and Part III of this series, we addressed these 5 concepts:
     #1 — What is cholesterol?
     #2 — What is the relationship between the cholesterol we eat and the cholesterol in our body?
     #3 — Is cholesterol bad?
     #4 – How does cholesterol move around our body?
     #5 – How do we measure cholesterol?
In this post we’ll continue to build out the story with the next concept:

The straight dope on cholesterol – Part V

In Part I, Part II, Part III and Part IV of this series, we addressed these 6 concepts:
     #1 — What is cholesterol?
     #2 — What is the relationship between the cholesterol we eat and the cholesterol in our body?
     #3 — Is cholesterol bad?
     #4 – How does cholesterol move around our body?
     #5 – How do we measure cholesterol?
     #6 – How does cholesterol actually cause problems?
In this post we’ll ...
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23
MAY

224

Categories: Cholesterol, Nutrition & Health

Tags: apoA, apoB, atherosclerosis, cholesterol, HDL, heart disease, inflammation, LDL, LDL-P, lp(a), NMR, pattern A, pattern B, statin

The straight dope on cholesterol – Part VI

Previously, in Part I, Part II, Part III, Part IV and Part V of this series, we addressed these 7 concepts:
     #1 — What is cholesterol?
     #2 — What is the relationship between the cholesterol we eat and the cholesterol in our body?
     #3 — Is cholesterol bad?
     #4 – How does cholesterol move around our body?
     #5 – How do we measure cholesterol?
     #6 – How does cholesterol actually ...
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30
MAY

273

Categories: Cholesterol, Nutrition & Health

Tags: apoA, apoB, atherosclerosis, cholesterol, HDL, heart disease, inflammation, LDL, LDL-P, lp(a), NMR, pattern A, pattern B, statin

The straight dope on cholesterol – Part VII

Previously, in Part I, Part II, Part III, Part IV, Part V ,and Part VI of this series, we addressed these 8 concepts:
     #1 — What is cholesterol?
     #2 — What is the relationship between the cholesterol we eat and the cholesterol in our body?
     #3 — Is cholesterol bad?
     #4 – How does cholesterol move around our body?
     #5 – How do we measure cholesterol?
     
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13
JUN

201

Categories: Cholesterol, Nutrition & Health

Tags: apoAI, apoB, CETP, dalcetrapib, good cholesterol, HDL, HDL-C, HDL-P, Jim Otvos, mendelian, mendelian randomisation. statin, niacin, randomization, RCT, Tom Dayspring, torcetrapib

The straight dope on cholesterol – Part VIII

Last week the Journal of the American Medical Association (JAMA) published an article titled Lipid-Related Markers and Cardiovascular Disease Prediction, which you can download here.  This is quite timely as we are in the midst of our series on cholesterol and heart disease risk factors.
I was planning to write a post on my interpretation of this report, as I know many of you have questions about it, when I was reminded of one of my favorite principles ...
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26
JUN

56

Categories: Cholesterol, Nutrition & Health

Tags: apoA, apoA-I, apoB, cholesterol, HDL, HDL-P, JAMA, LDL, LDL-P, lp(a), Lp-PLA2

The straight dope on cholesterol – Part IX

Previously, across 8 parts of this series we’ve laid the groundwork to ask perhaps the most important question of all:

What should you eat to have the greatest chance of delaying the arrival of cardiovascular disease?

Before we get there, since this series has been longer and more detailed than any of us may have wanted, it is probably worth reviewing the summary points from the previous posts in this series (or you can just skip this and jump to the ...
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12
JUL

236

Categories: Cholesterol, Nutrition & Health

Tags: apoB, cardiovascular disease, cholesterol, HDL, heart disease, LDL, LDL-P, low carb, saturated fat, statins, sugar, TG, triglycerides

lipids library - blogs posts & podcasts by Jimmy Moore (Livin' La Vida Low Carb)

lipids « Jimmy Moore's Livin' La Vida Low Carb Blog

The LLVLC Show (Episode 635): Encore Week 2013 – Dr. Thomas Dayspring

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In Episode 635 of “The Livin’ La Vida Low-Carb Show with Jimmy Moore,” we are so pleased that you voted for noted lipidologist Dr. Thomas Dayspring to return for a brand [...]

6-Month Lipid Panel Update On My Nutritional Ketosis N=1 Experiment

Ever since I began my n=1 experiment of the concept of “nutritional ketosis” in May 2012 that has resulted in a 50+ pound weight loss so far while consuming lots of healthy high-fat foods to raise my level of blood ketones, people have been asking me about what’s been happening with my lipid panel. [...]

ATLCX (Episode 29): Dr. Thomas Dayspring | Cholesterol Testing: What Matters Most?

TRY THESE DELICIOUS NEW PRE-MADE PALEO MEALS USE COUPON CODE “LLVLC” FOR 10% OFF YOUR ORDER NOTICE OF DISCLOSURE: http://cmp.ly/3
In Episode 29 of “Jimmy Moore Presents: Ask The Low-Carb Experts,” we’re very excited to bring to you one of the world’s leading lipidologists and experts on just about everything you could ever want [...]

The LLVLC Show (Episode 585): Lipidologist Dr. Thomas Dayspring Explains The Truth About Cholesterol

LISTEN TO JIMMY MOORE’S OTHER PODCASTS:
In Episode 585 of “The Livin’ La Vida Low-Carb Show with Jimmy Moore,” we welcome the Director of Cardiovascular Education at the Richmond, VA-based Foundation for Health Improvement and Technology (FHIT) and lipid expert Dr. Thomas Dayspring. It’s not often we are privileged to have someone quite [...]

Specialty Health Low-Carb Video Series With Gary Taubes And Dr. Thomas Dayspring

I’m always happy to find quality information online that helps continue the education about the tremendous benefits of high-fat, low-carb diets on your health. From insulin resistance, heart disease, obesity, saturated fat, sugar, calories, alcohol, fruits and veggies, cholesterol and more, these are the things that are most important in debating what to do about [...]

Ask The Low-Carb Experts (Episode 6): ‘All Things Lipids (Cholesterol 101)’ | Chris Masterjohn

TRY LIFESHOTZ–A SUGAR-FREE NUTRITION DRINK SUPPLEMENT: NOTICE OF DISCLOSURE: http://cmp.ly/3
In Episode 6 of “Jimmy Moore Presents: Ask The Low-Carb Experts,” we have Chris Masterjohn from Cholesterol-And-Health.com who is a blogger and doctoral candidate in Nutritional Sciences at the University of Connecticut where he will be graduating this Spring. He is the author of [...]

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Apo-lipoprotein E - Wikipedia

Apolipoprotein E - Wikipedia

Apolipoprotein E (ApoE) is a class of apolipoprotein found in the chylomicron and Intermediate-density lipoprotein (IDLs) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.^[1] In peripheral tissues, ApoE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism in an isoform-dependent manner. In the central nervous system, ApoE is mainly produced by astrocytes, and transports cholesterol to neurons via ApoE receptors, which are members of the low density lipoprotein receptor gene family.

Contents 1 Function 2 Gene 3 Polymorphisms 4 Alzheimer disease 5 Interactive pathway map 6 References 7 Further reading 8 External links

Function

APOE ^[2] is 299 amino acids long and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood. It is synthesized principally in the liver, but has also been found in other tissues such as the brain, kidneys, and spleen. In the nervous system, non-neuronal cell types, most notably astroglia and microglia, are the primary producers of APOE, while neurons preferentially express the receptors for APOE. There are seven currently identified mammalian receptors for APOE which belong to the evolutionarily conserved low density lipoprotein receptor gene family.
APOE was initially recognized for its importance in lipoprotein metabolism and cardiovascular disease. Defects in APOE result in familial dysbetalipoproteinemia aka type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron, VLDL and LDL remnants^{[citation needed]}. More recently, it has been studied for its role in several biological processes not directly related to lipoprotein transport, including Alzheimer's disease (AD), immunoregulation, and cognition.
In the field of immune regulation, a growing number of studies point to APOE's interaction with many immunological processes, including suppressing T cell proliferation, macrophage functioning regulation, lipid antigen presentation facilitation (by CD1) ^[3] to natural killer T cell as well as modulation of inflammation and oxidation.^[4]

Gene

The protein, ApoE, is mapped to chromosome 19 in a cluster with Apolipoprotein C1 and the Apolipoprotein C2. The APOE gene consists of four exons and three introns, totaling 3597 base pairs. ApoE is transcriptionally activated by the liver X receptor (an important regulator of cholesterol, fatty acid, and glucose homeostasis) and peroxisome proliferator-activated receptorγ, nuclear receptors that form heterodimers with Retinoid X receptors.^[5] In melanocytic cells APOE gene expression may be regulated by MITF.^[6]

Polymorphisms

ApoE is polymorphic^[7][8] with three major isoforms: ApoE2 (cys112, cys158), ApoE3 (cys112, arg158), and ApoE4 (arg112, arg158).^[9] Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158,^[10][11][12] these differences alter apoE structure and function. These have physiological consequences:

• E2 (rs7412) is found in approximately 7 percent of the population.^[13] This variant of the apoprotein binds poorly to cell surface receptors while E3 and E4 bind well.^[14] E2 is associated with both increased and decreased risk for atherosclerosis. Individuals with an E2/E2 combination may clear dietary fat slowly and be at greater risk for early vascular disease and the genetic disorder type III hyperlipoproteinemia—94.4% of such patients are E2/E2, while only ∼2% of E2/E2 develop the disease, so other environmental and genetic factors are likely to be involved (such as cholesterol in the diet and age).^[15][16][17] E2 has also been implicated in Parkinson's disease^[18]
• E3 (rs429358) is found in approximately 79 percent of the population.^[13] It is considered the "neutral" Apo E genotype.
• E4 is found in approximately 14 percent of the population.^[13] E4 has been implicated in atherosclerosis, Alzheimer's disease,^[19][20] impaired cognitive function,^[21][22] reduced hippocampal volume,^[22] faster disease progression in Multiple Sclerosis,^[23] unfavorable outcome after traumatic brain injury,^[24] ischemic cerebrovascular disease,^[25] sleep apnea,^[26][27] and reduced neurite outgrowth.^[28]

Alzheimer disease

The E4 variant is the largest known genetic risk factor for late-onset sporadic Alzheimer disease (AD) in a variety of ethnic groups. Caucasian and Japanese carriers of 2 E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, as compared to those not carrying any E4 alleles. While the exact mechanism of how E4 causes such dramatic effects remains to be fully determined, evidence has been presented suggesting an interaction with amyloid.^[29] Alzheimer disease is characterized by build-ups of aggregates of the peptide beta-amyloid. Apolipoprotein E enhances proteolytic break-down of this peptide, both within and between cells. The isoform ApoE-ε4 is not as effective as the others at catalyzing these reactions, resulting in increased vulnerability to AD in individuals with that gene variation.^[30]
The pivotal role of ApoE in AD was first identified through linkage analysis by Margaret Pericak-Vance^[31] while working in the Roses lab at Duke University^[32] Linkage studies were followed by association analysis confirming the role of the ApoE4 allele as a strong genetic risk factor for AD.^[19][20]
Although 40-65% of AD patients have at least one copy of the 4 allele, ApoE4 is not a determinant of the disease - at least a third of patients with AD are ApoE4 negative and some ApoE4 homozygotes never develop the disease. Yet those with two e4 alleles have up to 20 times the risk of developing AD.^{[citation needed]} There is also evidence that the ApoE2 allele may serve a protective role in AD.^[33] Thus, the genotype most at risk for Alzheimer disease and at an earlier age is ApoE 4,4. The ApoE 3,4 genotype is at increased risk, though not to the degree that those homozygous for ApoE 4 are. The genotype ApoE 3,3 is considered at normal risk for Alzheimer disease. The genotype ApoE 2,3 is considered at lower risk for Alzheimer disease. Interestingly, people with both a copy of the 2 allele and the 4 allele, ApoE 2,4, are at normal risk, similar to the ApoE 3,3 genotype.
The connection between neuron failure in Alzheimer disease and depleted myelin cholesterol (via ApoE deficiency) has also been described in Cholesterol Depletion and consequently is a known adverse drug reaction to statin therapy.^{[34][35][36][37][38]}

Estimated worldwide human allele frequencies of ApoE *[39]
Allele	ε2	ε3	ε4
General Frequency	8.4%	77.9%	13.7%
AD Frequency	3.9%	59.4%	36.7%

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Statin Pathway edit

^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

About LecturePad - Clinical Cardiology, Diabetes and Endocrinology, Lipids and Lipidology and Cardiometabolic Disorders

About LecturePad

By Clinicians For Clinicians

LecturePad is a leading destination for continuous professional development by clinicians for clinicians, focusing on prevention and clinical application in the fields of Clinical Cardiology, Diabetes and Endocrinology, Lipids and Lipidology and Cardiometabolic Disorders.

We have created a truly interactive site, which brings together the very best tools in education and clinician focused practical content designed to assist you in your quest to be your very best when it comes to clinical practice.  Features include:

• Live Case Consult* - Real case studies to help interpret advanced biomarker testing. Ask the expert clinical questions about your cases.
• Live lectures by experts in the field.
• Medical Genius - Challenging competitions and activities for clinicians.
• Lipidaholics Anonymous – A biweekly newsletter by renowned clinical lipidologist Dr. Thomas Dayspring, highlighting case studies, references of the week, and current happenings.
• Clinical Pal - Connect with other clinicians, expand your clinical network, share your knowledge and learn from others, discuss your cases, create your own clinical group or join others.
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Heart Disease / Cholesterol - Chris Kresser articles library

Heart Disease / Cholesterol

For the last half century, the medical establishment has vigorously promoted the notion that high cholesterol is a primary risk factor for coronary heart disease, and that a diet high in saturated fat and cholesterol causes heart disease. These hypotheses are widely accepted as fact by many physicians and the general public alike, despite the overwhelming body of evidence that suggests otherwise.

In the following articles, I review over fifty years of research demonstrating that:

1. High cholesterol is not the primary cause of heart disease.
2. Diets high in saturated fat and cholesterol don’t cause heart disease.
3. Consumption of so-called “heart healthy” vegetable oils is linked to heart disease, cancer and many other conditions.
4. Statin drugs don’t reduce the risk of death for most people, and have dangerous side effects and complications.

I also discuss the latest theories on what causes heart disease and a truly “heart healthy” approach to diet and lifestyle that is supported by both modern science and centuries of traditional wisdom.

Articles

• Study Reveals Doubt on Cholesterol Drug
• Three Eggs a Day Keep the Doctor Away!
• The Truth About Statin Drugs
• Research Alert: Antidepressants & Cholesterol
• Inflammation Worsens Danger of Heart Disease
• More on Statin Side Effects
• More Silly Shenanigans Against Saturated Fat
• Have Some Butter With Your Veggies!
• New Study Puts Final Nail in the “Saturated Fat Causes Heart Disease” Coffin
• Ten Steps to Preventing Heart Disease Naturally
• Why You Should Eat More (not less) Cholesterol
• For a healthy heart, stick to butter

Hacking HDL up for APOE4 - PaleoHacks.com

2 Months ago, I posted a question I'm still hacking on about finding optimum lipid profile for heart/brain health in APOE4 here... http://paleohacks.com/questions/80505/potential-hacks-resolve-heart-brain-dilemma-for-apoe4#axzz1klJhxOz9 I've been doing VAP test at 30 day intervals since this first test. Managed to push up size profile from 25% to 40% 'large and fluffy' LDL in the first month - a good early sign. Then per suggestions elsewhere on PH set out to raise HDL (which was flat at 47) in the second by adding coconut oil (2 tbsp/day), add 5000 IU D3 (for total of 8000 IU), and more fermented food (have come to love sauerkraut). Unfortunately, really no effect after another 30 days (HDL from 47 to 48). Maybe it takes time, but I'm thinking something's still not right as LDL went up from 170 to 200 and size went down a bit (only 35% large and fluffy). Per hints @Quilt and @Grace elsewhere in cyberspace about ultra-sensitivity of APOE4's to dairy, I'm going to remove all dairy this month (I still use lots of butter and occasional cheese). Any other hack suggestions to add to the mix? Also, happy to take suggestions for look for other clues (e.g. hormones, vitamins, minerals)? apoe4 cholesterol brain-gut-axis flag asked Jan 28 2012 at 14:25 Russ 573●1●8

interested mine is similar – Mallory Jan 28 2012 at 16:27

For more Paleo Diet hacks: http://paleohacks.com/questions/93451/hacking-hdl-up-for-apoe4#ixzz2PWnbfTsc
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2 Answers
oldest newest votes

2


Are you doing any high intensity exercising? That seems to make a huge difference in my HDL. Sprints, sprints and more sprints.
link|flag
answered Jan 28 2012 at 15:57

Anonymous Chump
6,375●5●20


AC, Actually forgot to mention that indeed is my next hack per plan. Just started doing McGuff/BBS HIIT lifting last week after last test (wanted to see what diet only would do). Good idea to pick up more sprints, too. – Russ Jan 28 2012 at 18:15


0


I thought it might be useful to see some HDL history from an APOE4/3. I don't have any VAP data, but it seems low trigs provide similar info. I have to admit I'm trying to make sense of it all myself.
My best lab numbers so far seem to be at a time when I was eating a CW healthy diet (low fat) with high intensity, shorter duration exercise most days. CRP<0.5. My best guess for the change from mid-60s is diet refinement to less processed foods/wheat.
08/30/12: TC 398, LDL 301, HDL 81, trig 79 (PHD removed multi/selenium supp, tallow for cream)
04/27/12: TC 407, LDL 315, HDL 76, trig 79, TSH 1.76, fT3 2.53 (PHD 1-year; 30% C, 20% P, 50% F)
02/23/11: TC 226, LDL 142, HDL 78, trig 32 (45-50% C, 30-35% P, 20-25% F; oats, brown rice, lean meat)
02/27/07: TC 226, LDL 149, HDL 65, trig 61 (CW healthy diet)
As you've questioned, is better to have good looking lab lipids, or maybe instead reduced inflammation/oxidation?
Do you have any updates?
link|flag
answered Sep 3 at 14:22

MarkES
1,714●2●11

1

Both. Your 400 TC is just too high and so is 301 LDL. What's funny is you had lower trigs with CW higher carb diet. But then I also have lower trigs with a higher carb diet. Let me guess: you were never overweight; always in shape; exercised routinely. You went Paleo already in shape, not out of shape like most people here. If so, you may not gain so much from Paleo: no weight to lose. If you did sub 80 carbs, it may have increased inflammation and CRP in response to glucose preservation and FT3 decrease. I would get carbs to about 40%: eat tubers and white rice. That's Paleo. – Mambo Nov 9 at 5:30

1

I'm E2/E4 and have done enough experiments to know that if I increase SaFA, my LDL goes up by 50 points. Never more than 180 but around 120-160. If I go heavy yams, sweet potatoes, my LDL is between 60-100. Not that big a movement as some other E*/E4s so I'm lucky in that regard. Your results reflect mine but with a bigger jump in LDL and TC. My trigs also don't go down to like 40 like some people on a LC diet; instead it's around 100, whereas if I do 150-200g carbs, trigs go down to 60. Weird? No. Healthy carbs trump processed carbs. – Mambo Nov 9 at 5:34


Mambo, I appreciate the feedback and very helpful to hear about your experience. Your guesses are pretty good and I was already fit before Paleo. Ironically, I was initially looking for dietary changes to improve my lipids and now I'd be happy to reach my pre-Paleo lipids while still eating whole foods. I haven't been sub-80g carbs, instead pretty consistent 150g (30%) carbs from all sources. Which is about 100g (20%) carbs from potatoes, sweet potatoes, white rice. Is your 40%, 150-200g carbs, from all sources or from potatoes and white rice (they have a little fat/protein too)? – MarkES Nov 9 at 13:40


Another thing I've heard regarding trigs is the idea of getting more dietary phospholipids and fewer triglycerides (more fats from food, less from oil). So, I'm also trying that, which also means less calories from SFA (coconut oil). It's much tougher to eat higher fat getting it mainly from whole foods. How about your HDL, does that vary? – MarkES Nov 9 at 13:40


Feel free to shoot me an email - info in my profile. – MarkES Nov 9 at 13:40

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