What does one eat if they are wheat free, low carb, and low saturated fat? Can anyone give a sample day for this plan?

Have you tried T4/T3 adjustments with apo E4?

How can one find out if one has Apo E4?

Is it possible to have the same reactions to fats such as large increase in LDL, mostly large with little small LDL?  At one point i was 100% small LDL; restrcting carbs and increasing fats of all kind(good ones only) my NMR was 2098 LDL of which 200 were small were small.  HDL was 69 and TRGs 62.  Only way to get these numbers down is to be on statin and zetia.  Thought i was an ApoE 4, but test showed i am ApoE 3/3.
Perhaps i am a hyper-absorber of fats- maybe as bad as ApoE4?   With statin and zetia i can reduce the numbers to LDL total of 640 and <90 small.    So maybe the high fat diet is not so great even for those who are not ApoE4.
Thanks for your thoughts.

I'm getting my ApoE status tested soon.  I've been quite liberal with the healthy fats (olive, avocado, pastured eggs) and include saturated coconut oil and dark chocolate.  I also have high LDL particles - about 1500, but only 139 are small without statins.  I would love to find out I am 3/3 because I've already restricted grains and a variety of foods that I tested as allergic too including nuts.  I asked Dr. D on the forum if having <10% small particles was good news, but he was still worried about the total LDL.  I guess we will see how worried I should really be shortly.  BTW, I've got high Lp(a) at 26mg/dl, so I really don't need another strike against me in my plaque battle.

Lost a nice technical ApoE explanation  I spent a lot of my time on to "server error" .
I'll just lurk from now on.

Mighto:
Please stay here and enlighten us with your comments. Glitches can happen. I made it a habit a long time ago to just copy my text (Ctrl.A, Ctrl. C, on WINDOWS) before sending it. It is easy and takes no time. Text is preserved and you can try again.
I for one am enjoying your musings tremendously.
Cheers, Renfrew

What Renfrew said. I've run into this problem on blogger regularly where it decides to log me off while posting a comment. Now I always save any longish comment before posting. Better safe?

Digging into my 23andMe data, it reports back on APOE e4 status

You can find this as part of the https://www.23andme.com/you/journal/alzheimers/overview , or just check the rs7412 & rs429358 SNP's directly.

I am an APOE 3,4, and here’s what I eat on week days.
Breakfast.
Steamed raw vegetables (eggplant, zucchini, bell peppers, mushrooms, Mexican or yellow squash). Add yellow mustard and dry spices.
Natto twice a week (1 box Mito natto, throw away their soy sauce and mustard packages).
Frozen blueberries (1/8 cup), 3 tbsp flaxseed meal, 1 cup unsweetened almond milk - all microwaved for 2 min. Add ground cinnamon.
Half-ounce piece of part skim milk mozzarella cheese.
Coffee.
Lunch.
Frozen vegetables (California blend – cauliflower, broccoli, carrots) microwaved (reheat). Add a boiled egg, 1/4 avocado, yellow mustard.
Dinner.
Cooked or baked vegetables (cauliflower, bok choy, green cabbage, rapini).  
Sautéed or baked fish (tilapia, salmon, perch, trout), chicken breast, or ground turkey meat balls. Add yellow mustard, horseradish, and dry spices.
Generous amount of raw vegetables (green lettuce, pickles, tomatoes, bell peppers) with hummus.
Decaf tea with a 1/10 serving piece of 90% dark chocolate, half-ounce mozzarella cheese, and some almonds or sunflower seeds.

My daily fruit serving includes a cup of frozen dark berries (blueberries, raspberries, blackberries) from the Costco Three Berry bag.

back incollege i did a report on cancer and ottowarburg and i remember this gene being incredibly linked to cancer risk....any truth to that?

Hi, Steve--
There are indeed genetic predispositions outside of apo E4 that can provide for this response, e.g., apo B receptor variants. What is not known is when you've crossed a threshold of mostly or purely large LDL that is undesirable. Despite $2 billion spent on statin drug-related research, we still have no answer on this question.

Hi, Buck--
Similar issue as the question posed above by Steve: We just don't know what an "allowable" quantity of mostly or purely large LDL particles are. For a working value, I've been trying to keep NMR-derived LDL particle number 1500 nmol/L or less when LDL is purely large, but I have no endpoint data to justify this.

Great program, Gene, given your pattern. And I am impressed at your courage to eat natto!

Hi, Mallary--

Hardly my area, but I believe that the relationship between apo E4 and cancer in various sites is complex and modulated somewhat differently than in other apo E genotypes. Some discussion:
http://aje.oxfordjournals.org/content/170/11/1415.long

Hi, Simon--

The full diet is articulated in detail, including scientific rationale, in several reports on the Track Your Plaque website; link above. Chapter 9 of the New Track Your Plaque Guide is also devoted to this.

As you see, I will be putting out recipes here and on the Track Your Plaque website in coming months.

even 1 reconstructed paragraph just  lost to "server error"

ApoE joins with ApoB and is carried in VLDL and chylomicrons; it is ApoE that binds to tissue cell LDL receptors to start normal uptake. Inside the ApoB with lipids breaks off and heads into tissue cell lysosome.
Meanwhile ApoE and the LDL receptor head back to that cell's membrane, with ApoE carrying some cholesterol out of that cell to build into an HDL molecule for recycling.

I have the worst of both worlds, I think, as I am E2/E4.  Dr. Davis, do you have a specific program for patients with this genotype?

So, Gene, I'm curious.  It looks like you have an extremely low intake of protein.  How are your labs and what kind of activity do you do during the day?

Eggs, natto, fish, poultry, and nuts are all rich in proteins, correct? I increase my portions of fish and poultry when I go to gym. I also add canned fish on these days like tuna in water or sardines in mustard sauce. I used to consume large amounts of tofu, but stopped recently based on some negative information I learned from a TYP member forum.
Every weekday I typically walk to and from the train station, 25 min each way. I work out two or three days a week following the slow burn routine; I do cardiovascular, too. I also ride my bike for 2 hrs every weekend.
I am a software engineer, so I spend most of my business hours in front of a computer.
Before I learned about my APOE 4, I used lots of olive and canola oil and was a vegetarian, but had already reduced carbs. My labs were pretty bad and actually much worse than when I ate lots of bread and oatmeal every day. In mid-December 2010, I started eating as described above plus taking niacin (500 mg) and Crestor (10mg). I was already taking the standard TYP supplements – vitamin D3, fish oil, iodine. At the end of March 2011, my NMR was the best I had ever had: LDL-P 568, LDL-C 70, HDL-C 55, Trig 24, HDL-P 29.5, Small LDL-P 293, LDL size 20.4, HDL size 9.7, Large VLDL-P 0.7, insulin resistance 16. I don’t have genetic lp(a). I know the results can be better, so I am looking forward to my next NMR due in the fall.

I'm confused. When you say 1 in 4 have this gene are you saying it's a *problem* in 25% of everyone? As in one-quarter of us should be eating like Gene K (above)? Or is a case where the gene isn't always active or something?

I recently wrote about Alzheimer's on my blog and this question came up in the comment section.  I think about APoE4 completely differently than you do and here is why.  APoE4 confered humans the ability to migrate out of the sahara and north and south to live in climates with less solar radiation.  It allowed us to live with lower vitamin D levels.  Moreover, its presence alone means nothing unless it is accompanied with the epigenetic triggers that make it dangerous.  Dr Davis you and I both know the disease you treat (heart disease) and the one I treat (Cerebrovascular disease) are the same disease just found in different organs.  SO i think we have a lot in common in what we do but how we think about thi sissue is different.  Here is my take.  I posted this answer on another forum and I think it needs to be discussed here.

I think the ApoE4 story is an interesting one and one I briefly touched upon in my AD blog.......I will revisit it.......but ultimately I dont think it is that important if you live an optimal life from 20-60. ApoE4 means much if you make poor epigenetic choices. I think people who come here do do what the rest of America does.

The other reason I think it means little is the epidemiology of ApoE4 in those over 80 yrs old. It does not have any major impact on healthy aging once you get to old age. That tells me that the epigenetic signals need also be present for it to matter.

ApoE4 is like dynamite.......and high insulin and high PUFA consumption and lowered total brain cholesterol (due to altered lipid uptake) are the major lit matches. If they exist by themselves they are harmless......but if they are brought together you are going to get heart disease and AD early and get taken out.

Dr Kruse

So everyone who is eating or planning to eat a high fat diet should get tested for E4, or are there some things that indicate it's probably unnecessary?

Dr Kruse -

It's pretty scary for me to think that maybe I am not supposed to be eating very much saturated fat. If it's true that is unbelievably lame. This is why I'm thinking I need to check to see if I am ApoE4. (How do I test for that?) If I am, then it may explain why, even on a Paleo diet, my LDL is mostly small dense. Are you suggesting that if I keep PUFA very low, like cut out my only remaining source (almonds/pecans), that this could be a key to producing more pattern A LDL? (By the way... I have chosen to eliminate all nuts and nut butters, regardless).

-Jack Kronk

Thanks so much for the thoughts - I am an E4/E4 eating a Paleo 2.0 diet.  As I understand it, high-protein is not a healthy diet, so low-fat & low-carb is not a good idea.  Fat is the healthiest macronutrient, so I'd love your opinion on which types of fat are best for E4s.

It sounds like you have concerns about saturated fat, and of course I avoid n-6 PUFAs and get lots of n-3s from grass-fed animals & fish oil.  What about coconut oil?  Olive oil?

What sort of HDL/LDL/etc  numbers would you look for in an E4/E4 as warning signs?  As health signs?

BTW, I blog occasionally on APOE4 at primale4.wordpress.com, am going to quote your post there.

Thanks for that, Gene.  I may need to go your route with my profile.  I'm following TYP pretty religiously and am having my 6-mo labs this month, so hopefully they will be improved from last time.

Jack as I mentioned to you on my blog I think you clearly need context.  I think your epigentics are telling you something.  But here is what I cant tell you and neither can anyone else.......without testing!  You need to be tested to get that context.  I think your diet you posted gave many clues......but even I did not jump to the easy conclusion.  I think your real underlying issue is multifactorial but your VAP strongly points to a leaky gut as a source of the sdLDL.  I think the bananas and cream are problems too.  Your O6/O3 ratio maybe bad and yes......you may have a bad set of allele's for ApoE4......but guess what!  Your HS CRP was very very low.  This tells me that your match is not lit.  So you may only be carrying a stick of dynamite.  Again......carrying dynamite is not going to blow you up.  This is why you need testing to get more context.

We send our ApoE4 patients to an nearby academic lab for testing.  One is likely available in your community because cardiologist and neurologist are ordering this test quite often now.  I think your PUFA content of your diet and of your tissues is critical.  In fact for AD the PUFA content is a major factor.  I believe it is a huge factor for CAD disease as well.  Wheat, Carbs, and PUFA's all drive sdLDL production.  Its not just one part of the diet that does it.  Moreover, the more leaky the gut the more sdLDL one will have as I laid out in my VAP blog that I dedicated to yourself.  I think your case is quite representative to many thousands of people and I am glad we are talking about it here because Dr Davis is a cardiologist and is coming at this issue from a different angle than I am.  I think however when the story plays out.......we will be in the same neighborhood because human biochemistry pathways are constant.  The fuels and hormone status and the situations in our guts are the covariables that make this issue more confusing.  I think people need to know why Apoe4 is important.  It conferred an adaptive advantage to move away from the equator to lower solar radiation and lower vitamin D levels.  This adaptation is seen in many american african americans.  The other interesting finding is that the liver of these patients makes more cholesterol to try to raise the D level and pregnenolone level to offset the deficit.  It never does.  But when this set of circumstance is mixed with a high carb low fat SAD (PUFA rich) it destroys the heart, vessels and brain.  This is what we see today in many parts of the world.  Their diet is now completely mismatched for the original adaptation.  I think if you tweek the diet when you know the epigenetic variables you can easily over come an Apoe4 positive test if youre willing to change.   But you need to test!

Hi, Tim--
Very rare, as you likely know.
I believe that you simply deal with this on a practical level, i.e., deal with the small LDL and insulin resistance issues and postprandial abnormalities from apo E2 as you ordinarily would. Then deal with the LDL-accumulating aftermath from the apo E4 component.

Thanks for the insightful thoughts, Dr. Kruse.
I'm not sure how your approach folds into mine, though fascinating. I do agree that apo E4 is made much worse by the means you cite, i.e., polyunsaturates, carbohydrates that trigger small LDL. This is why, despite the LDL-accumulating effect of apo E4, I focus first on reducing the small LDL component, in effect an anti-inflammatory, glycation-reducing, oxidating-reducing approach, followed only then by dealing with any large LDL-increasing aftermath.
What is not clear to  me is how atherogenic the large LDL is at higher levels in the setting of apo E4. As you know, one of the greatest concerns in apo E4 is that its effects may not be confined to lipid effects, but may extend into non-lipid effects. But that is such poorly charted territory.

Hi, Patri--
The formal data on the various fat fractions and apo E4 are, unfortunately, very skimpy.
Saturated fat clearly increases whatever LDL dominant form there is. However, other forms of fat, even omega-3 fatty acids, also increase apo E4. This become a problem, for instance, when we try to use high-dose omega-3 fatty acids to reduce Lp(a) in the presence of apo E4.
As I commented above in response to Dr. Kruse's comments, as a practical matter I believe it is best to address the worst fraction of LDL particles first, i.e., take dietary steps to reduce small LDL particles, meaning reduce carbohydrate triggers of small LDL. Then deal with the large LDL that emerge by varying fat intake and gauging effect.
Odd thing: Even among apo E4 people, fat intake yields variable LDL-increasing effects, quite variable sometimes.
Also, recall that health extends beyond LDL. So there may be benefits to monounsaturates or omega-3 polyunsaturates, say, that extend to issues like brain and liver health.

Hi Melinda,
Please copy and post this in previous thread for ApoE4 … .
Continuation about ApoE4:
% of ApoE4 messes dynamic inside tissue cell so that ApoB turns to use Scavenger Receptors to try to start cascade which gets signal transducer (Specificity Protein 1) to up-regulate the cell membrane transporter protein ( ABCA1, ATP binding cassette transporter A1) that puts excess cholesterol out from that cell. I believe this is where Doc Davis’ stated ApoB irregularities add to the problem with ApoE4 (since normal human ApoE3 works all by itself to get that signal transducer to bind to ABCA1 to work shucking cholesterol) . When cholesterol gets to build up inside the cell the large LDL can acetylate and form excessive “droplets” in that cell’s cytoplasm; while the small LDL can oxidize from CuSO4- and load up inside that cell’s lysosome.

Meanwhile % of ApoE4 doesn’t just dock with tissue cell LDL receptors and so the macrophage scavenger receptors pick up too much cholesterol laden ApoB/ApoE lipo-protein carrier molecules. Once in the macrophage the same problem of oxidized LDL piling up in lysosome and acetylated LDL burdening cytoplasm occurs; and for that matter, in macrophages, it is down to ApoB to get the signal transducer going if any cholesterol is to be put out by cell membrane transporter protein ABCA1. This is the recipe for risky pro-atherogenic “foam cell” formation; while the individual genetics of ApoE, ApoB, assorted receptor types, signal transducer and transport protein all make it hard to predict how ApoE4 plays out.

Dr. Kruse broaches ApoE4 in alzheimers and this is in large part because ApoE4 causes the brain neurons to get less than optimal cholesterol from the brain’s astrocytes. It is ApoA1 working in HDL complex that controls the astrocyte cholesterol balance and when there is inflammation there is a risk of ApoA1 mis-folding to foster amyloid aggregations. Low intact ApoA1 and ApoE4 together increase the risk factor for cognitive problems and dementia several fold.

Diabetics with ApoE4 have that % of ApoE4 as an additional limitation; however, irregardless of the ApoE iso-form diabetic dementia risk arises from their glucose loads impairing kidney tubules, and thus fostering the uremic environment that stymies ApoA1 bio-synthesis. The normal role of ApoA1 is to bind to the transport protein which secures cholesterol into a safe bond with HDL; so low ApoA1 from any factor will challenge the brain neuron over time. I suggest there are individuals whose age impaired kidneys contribute to senile dementia from impairing ApoA1 levels being made and also possibly speeding up the normal 4-6 days kidney elimination of ApoA1 ; and so Patri’s comment on limitation of high protein intake is relevant due to it’s demand on aging kidneys.

Reply

The above comment was written by Might-o'chondri-Al.  He asked me to post it in this thread as he is having trouble posting here.

Ok I will test! But I have been asking around how to test and still don't know how? Is this something that I would just ask my doctor about? Maybe I go to the same lab that did my VAP? Since I got my results 3 weeks ago, I have made the following changes: zero bananas, reduced my cream intake by about 70% or so, lowered my overall fruit intake signigicantly, added 2 teaspoons of red palm oil daily, decreased caffeine intake (and now I am doing no coffee in August). I have also decided to eliminate all nuts and nut butters as of 2 days ago. Now my only real source of PUFA left in my diet is bacon, occassional chicken, and avocado. It's weird too, because on SAD, I was probably getting 10 times the PUFA, at least. I cooked in canola, ate loads of grain bread and corn products like tortillas. Maybe adding the saturated fats makes everything more amplified. The only thing now that I am VERY reluctant to give up is starches like potatoes and white rice. If I do, I will surely be VLC again, as I don't eat breads and very little fruit now, and rarely ever indulge in sweets. This means, by default, that most of my calories would then be sat and mono fats. Isn't that not good if I am ApoE4? What a mess! Dr Davis is right about being between a rock and a hard place. Jeez!

"high protein is not a healthy diet". you mean specifically for ApoE4 folks? I haven't been tested for it yet, but I suspect I may be ApoE4. I take whey protein daily and eat lots of eggs and beef. I do this on purpose because I do weight training 5x per week and am building muscle. Could it be true that people who are ApoE4 are not supposed to build much muscle? (logically speaking, due to the restriction on protein)

Is server cooperating now ?

ApoE4 degrades more readily than ApoE 3 or ApoE2; ApoE4 protein fragments that get into a tissue cell's cytosol can have bad effect on that cell's mitochondrial membrane lipid binding . This decreases the mitochondrial efficiency  when they try to perform glycolysis for generating energy.

ApoE4 degradation in a cell cytosol can  decrease the level at which that cell advances it's bio-genesis of  robust mitochondria; this is due to how ApoE4 fragments depresses PPAR gamma expression & PPAR gamma is what promotes making good mitochondria. (Specificly in the case of human fat tissue PPAR gamma is what regulates transcription of pre-adipocytes differentiation into true adipocytes. Hence Avandia & glitazone drugs that target the receptor of PPAR gamma do short out adipocyte differentiation;  and yet risk the side effect of increasing heart disease due to mitochondrial impairment.)

In Alzheimers the form of ApoE makes a difference; and the brain amyloids react to insulin differently with different ApoE iso-forms. The ratio of insulin in cerebro-spinal fluid as compared to insulin in plasma changes with different genotypes of ApoE.   Alzheimer patients tend to have lowered glucose utilization in their brains with  less insulin and insulin-like growth factor receptors, despite the Alzheimer brain harboring fewer insulin degrading enzymes. Which engenders a paradox whereby diabetic brain neuro-pathy experimentally improves with administration of nasal insulin; and similarly,  individuals  with ApoE4  receiving nasal insulin improved their cognitive function, with the boost being higher in ApoE4 carriers than folks with any other alleles of ApoE.

Higher amounts of Alzheimer amyloid  formed tangles are seen in Type 2 diabetics and in those with ApoE4; leading to the conclusion that "normal" ApoE3 fortuitously forms a complex with brain amyloids.
Apparently ApoE iso-forms other that ApoE4 can more readily bring an amyloid to where the molecule LRP-1 (lipo-protein related protein 1) can move that amyloid out across the brain blood barrier .

Hi Melinda,
Thanks for repost, looks like Doctor D hammered his server into shape again.

With regards to the large LDL content.  Again I am not a cardiologist, but a neurosurgeon.  The heart and brain work on the same principles of biochemistry.  And since these two organ take up much of the CO in the body they share much in common.  It is also why when we see neolithic disease affect the heart their is also a similar effect in the brain.  The Apoe4 story is one such case.  But so is the large LDL story.  Cardiology CW today believes that LDL matters.  In neurosurgery today its clear in neurodegenerative disorders we are lacking LDL and cholesterol more often than not.  This is incongruent to biochemistry.  Dr davis has said here in this thread the jury is out on large LDL in his field.  I am submitting that LDL matter little in any field.  Why?  If it did the body would have a specific detailed regulatory control method in place to deal with it and it does not.  In nature, with the consumption of organic, unprocessed parent essential fats rather than adulterated oils (PUFA's) and transfats, LDL cholesterol is supposed to be made up of significant amounts of properly functioning “parent” omega-6, linoleic acid (LA), and is not supposed to be harmful. It is the natural transporter of parent omega-6 and parent omega-3 into the cells. It is thus not critical to lower LDL cholesterol, nor is the absolute LDL number as important, if the diet contains sufficient unadulterated parent essential fats. These are unadultered PUFA's of both the omega 6 and 3 variety for clarity sake.  Also take note that the body has no natural “cholesterol sensor” in the bloodstream—it would if its levels had to be maintained within exact limits; such as, sodium, calcium, and glucose levels are monitored in many systems. For example, glucose levels are maintained to an amazingly tight 0.1% in each of us!  So Nature implemented biological mechanisms if required. There is no need for a cholesterol sensor because the absolute number is irrelevant.  That was my advice to Jack Kronk three weeks ago when he posted his VAP numbers and when I blogged about his numbers.  I understand that Dr Davis may not want to go out on a limb as I have here.  But I dont view it as a limb when the biology and biochemistry support my beliefs fully that LDL cholesterol levels are completely irrelevant to heart disease propagation.  This is why I advocate copious amounts of coconut oil to patients with heart disease and all neurodegenerative disorders including brain tumors and seizure patients.  In fact, my literature is loaded with thousands of papers supporting my belief made here.  I think its long over do that cardiologists start reading "other pathways" of data to reach conclusions that their own field muddies.  As a neurosurgeon, I read Dr Davis literature quite a lot and in comparing the two it is clear that our two fields are on a collision course from two different paths.  I got extreme clarity reading circulation over the last thirty years that cholesterol has nothing to do with heart disease.  Dr Davis has reach conclusions that are quite different from most of his fellow cardiologist as well.  I applaud him.  I just think he is still caught in the lipid hypothesis nightmare and that is the only reason he is not traveling down the road with me in unison.  Since he is a fine doc and one who clearly is ahead of his peers......i'll gladly wait for him on that road because we need him to alter what ails his branch of medicine to get to where we both need to be going for all patients.

Dr. Kruse,

What is your response to the fact that people with familial hypercholesterolemia (FH) have an exaggerated risk of CVD versus those who are not lacking ldl receptors? Why do so many of them have cardiac events in their 20's and 30's? Surely, you would not relegate this phenomenon to increased consumption of PUFA's and/or higher insulin?

There are five major classes of FH due to LDLR mutations.  FH is a collection of genetic defects.  Many believe that the end result of these defects (IE high LDL or cholesterol) cause the diseases associated with it.  I do not.  Why?  When these people live past their 6th decade they have extremely low levels of neurodegeneration.  I believe the cause of the early on set  CAD is tied to secondary effects of what the primary genetic disease does to the liver to alter its function.  If one looks at FH patients and their VAP results one sees a pattern of chronic gut inflammation that is the real source of the atherosclerosis that causes higher incidences we see in FH.   These patients all have altered gut biofilms and some of the lowest levels of Vit K2 and vit D.  They also have extremely low DHEA S and pregnenolone levels are pointing to a chronic inflammation......due not to the high cholesterol level but to an altered gut axis.  Read my blog on this here.    http://jackkruse.com/your-vap-brain-love-not-war/   My views on this topic are radically different because even with severe LDL lowering treatments the disease patterns these people face remain unchanged.  Why?  because their gut remains the source of the inflammation that damages their arteries for their entire life.  We need to focus our efforts on the gut side of the equation and not the LDL side.  Ironically Dr Davis has done this with his assault on wheat.  Wheat drives sdLDL via what mechanism?  It screws up the liver and increases gut permeability to cause issues.  His current ideas and mine are very close.......but no one is tying this together.  I think my VAP post on the gut provides you the link.

Genetic high total cholesterol is related to the over 50 amino acid variations of PCSK9 (pro-protein conertase subtilisn/kexin 9,  which comprises 692 amino acids). Individuals producing an excess of PCSK9 more extensively degrade their cholesterol receptors with surface defects; and so don't readily take up LDL out of circulation, which lets blood levels of LDL rise higher. Conversely, those making sparse PCSK9 can't degrade their LDL receptors, which pull lots of cholesterol into a tissue cell where it can pile up over time in that cell's lysosome; and blood levels of LDL seem to drop.


PCSK9's worst version is D3744; where total cholesterol trends to 4 times normal and risk of death is estimated to be even +/- 10 years sooner than even other problematic PCSK9 genetic variations that affect maybe 1 in 500 westerners and account for +/- 5% of all pre-mature coronary heart disease. As regards the "older" age survival ability of those with familial high cholesterol  this may be due to the way over time plaque holds less lipid content and acquires more collagen with calcium infiltration. In other words younger plaque is less stable and more likely to burst free and be perilous.

If fretting about plaque be aware that the average duration of carotid plaque is +/- 9.6 years; according to Carbon 14 dating from autopsies. Plaque may even form multiple times during one's life and the statistically dangerous symptoms take 5 - 15 years to manifest. Increased levels of circulating plasma insulin accelerate the rate that plaque forms; and also adds to a plaques instability (ie: potential to rupture) due to insulin's interaction with genes involved in the immune response;  like how those with insulin resistance make more pro-inflammatory cytokines. This bolsters Doc Davis' insistance to control glucose, since the down stream result is a more stable plaque.

Noteably, there is the so called "protective cytokine" TGF beta which can allay plaque rupture. This is hard to predict for individuals because we have no way to assess who has what types of TGF beta receptors around , since normal and then plaque ridden blood vessels can harbor different TGF beta receptors. TGF  is considered a vital player inside vascular smooth muscle cells because it forms part of the interactive sequence that stops the smooth muscle cells from altering; and it bears mentioning that excess cholesterol can inhibit some TGF beta pathways.

For those who asked (Jack Kronk, Peggy, et.al.) about where and how one can get tested for ApoE it's simple:   Virtually any large commercial lab in the U.S. can do the test, e.g., Labcorp, Quest, etc.   Also, Atherotech (VAP) and Berkeley Heart Labs will do the test as well.   Since it's a genetic test, it's only run once during a person's lifetime.  The test can run anywhere from around $100 on up, depending on which lab runs it for you.

In my last lipotropen test, I do not absorb chol not do I make it.  Am I a closed system?  My lp[a] is 41.  I am very puzzled.

Dee

That was from the Boston Heart lab.  I am a AP03/3.

Super interesting!

Do you know what SNP is PCSK9 ?  I'd like to look up it in my 23andme info.
Thanks,
George

Plasma PCSK9 levels correlate with cholesterol in men but not in women
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References and further reading may be available for this article. To view references and further reading you must purchase this article.


Janice Maynea, , , Angela Raymonda, Anna Chaplinb, Marion Cousinsb, Nadine Kaefera, Charles Gyamera-Acheamponga, Nabil G. Seidahc, Majambu Mbikaya, Michel Chrétiena and Teik Chye Ooia, b

aHormones, Growth and Development Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ont., Canada

bClinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ont., Canada

cLaboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Que., Canada

Received 29 June 2007.  Available online 18 July 2007.

Abstract
Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that negatively regulates low density lipoprotein receptor (LDLR) levels. Several single nucleotide polymorphisms (SNPs) in PCSK9 have been linked to autosomal dominant hypercholesterolemia (ADH). Conversely, hypocholesterolemia associates with both ‘loss of function’ nonsense and missense SNPs in PCSK9. We examined the association of plasma PCSK9 with lipoprotein parameters in 182 normolipidemics. For men (n = 98) plasma PCSK9 averaged 6.08 ± 1.96 μg/ml and Spearman analysis revealed significant correlation between it and total cholesterol (TC), LDLC, and TC/high density lipoprotein (HDLC) (r = 0.276, 0.282, and 0.228, respectively). For women (n = 84) plasma PCSK9 averaged 6.46 ± 1.99 μg/ml having no correlation with TC, LDLC or TC/HDLC. The ratio of plasma PCSK9/LDLC increased in men carrying ‘loss of function’ PCSK9 variations. Our results suggest a gender difference in PCSK9 regulation and function with PCSK9 correlated to TC and LDLC in men but not women.

Keywords: Plasma PCSK9; Loss of function; Hypocholesterolemia; Hypercholesterolemia; Single nucleotide polymorphisms

Article Outline
Materials and methods
dI found this on the internet, I'm not sure if this is what you need?  

Dee

All patients with FH need to have their thyroid optimized.  This issue was hashed out at the Ancestral Health Symposium on August fifth at UCLA.  Jack Kronk's VAP is helping many patients learn how to raise their HDL to increase endotoxin clearance from the portal circulation to prevent oxidation of slow moving cholesterol because of A lack of their LDL receptor.  Thyroid optimization can overcome this to a degree but it requires a physician who knows precisely how to do this and not create an unsafe situation.  Their diets has to be a strict low carb moderate protein paleo diet high in coconut oil.

This too can be assessed by looking at thyroid beta receptors......it is associated with down regulation or resistance of this specific thyroid receptor.  A company in Denmark has a clinical trial on going about this specific receptor.  Thyroid hormones bing to both thyroid alpha and beta receptors.  But disease that affect the LDL receptors seem to preferentially knock out the thyroid beta receptor.

I apologize if I sent the wrong ifo.  Didn't read it through.
Dee

Dr K. -

I am inquiring with the my Doc about getting tested for ApoE. I will let you know how that goes.

Regarding hypothyroidism, yah the issue that I'm running into is that "it requires a physician who knows precisely how to do this and not create an unsafe situation".

This is the problem with our medical system in America. I live in San Diego, one of the biggest, most advanced cities on earth, and I am having trouble finding anyone over here that can truly help me with this. My doctor situaiton is pathetic. Sorry to say that, but I'll call a spade a spade. All they want to do is put me on Lipitor and go low fat whole grain. So then I am stuck with doing my own diligent research, and appyling knowledge that I can learn from people who actually know what they are talking about, and right now, for me, that means the internet. Incredible when you think about it.

When you say low carb, do you mean no starch as well, not even potatoes? By the way... the name of this post is "The Exception to Low Carb". So... that's why this is so confusing. Some very knowledgable people think it's best to raise my intake of starches and lower my fats. If my body is creating more LDL (even small dense) because of my saturated fat intake, then it makes sense to replace sat fats with something else. I already get enough protein, so then I am left with carbs. If it has to be carbs, isn't safe starch my only real option? It can't be 'sugar'. It can't be 'fructose', or grain starch, right? Should I eat loads of salads? Or I am on the wrong track completely? Should I look at upping my mono fats in place of saturated, like using mac nut oil for cooking? Or would mono fats be just as problematic?

You see? Honestly, I know this stuff stone cold. I know what *most* people do well with, but if we don't figure out how being pre-disposed to having issues with LDL receptors really changes things, we are going to (deservedly) get hammered by the low-fat whole grain camp when a fair amount of people who thought they had it all figured out are dropping dead from eating fats because they are ApoE and had no idea.

I'm genuinely glad that my example is helping people. No doubt I am. But I'd be alright with feeling like I'm getting somewhere with all this in my personal case as well. At the moment, I can't really say that I feel that way just yet.

Patients with apoe4 have a higher rate of AD and AD is associated with a cholesterol deficiency in the brain.  So for me apoe4 is a signal to load with the MCT of coconut oil which has massive benefits to the brain metabolically.  I find it hard to believe this is bad for the heart at any level because CAD tends to mirror CVD across all measures.  I think only cardiologist have this problem with Larger particle LDL because of the faulty lipid hypothesis.  cAD is an inflammatory condition.  It ha little to do with cholesterol itself.  If the cholesterol is oxidized then there are issues but this can be followed by acute phase reactants from the liver like HS CRP.  When it's up HDL tends to be low......and it's low because the liver is being bombard by gut endotoxins and this is a direct measure of the oxidation potential of an overwhelmed portal circulation.  To further the point......thyroid hormone, testosterone, estrogen, and high vitamin D levels all raise liver HDL and this is how they protect against heart disease.  I maintain large LDL confers no risk without inflammation.......and a low HDL is a great way to know if your liver is being overwhelmed in the portal circulation.  This is why vitamin K2 confers a great cardiac benefit.......it comes from a healthy gut biome.  vAP tells you a ton about your portal circulations inflammatory burden.

M-Al, just copy your text prior to the post, or write it in the editor. I don't know which browser you use, but in Chrome if you use "back" on "server error", it will return what you typed in a reply.

Following your diet I took an NMR last summer and this summer.  The small LDL particles went down (835 to 709) but the total particles went up (1800 to 2100).  Should I stick with your diet (low carb, no wheat, D, omega3's), one Walmart glucometer) or go back to rice and beans?

I got quote at $390 for just an ApoE genetic test. Is that normal?

Have you seen any reduction in your LDL following this diet?

I've been eating paleo/primal for about a year, dropped 10 pounds, and brought my triglycerides down from a high of 325 three years ago to 130. Unfortunately, my LDL-p is over 2600 (first time it was checked), and I found out I'm APO e4/e4.

The doctor says e4/e4 should go vegan, which seems about as anti-primal as you can get.

Any suggestions for where to start looking for eating guidelines?

My goodness, how very confusing!!  I'm hypothyroid.  My HDL is 95. My total C is 285. Ny LDL is 186. But my LDL fractions are mostly big and plumb and my small total 23. So, I think I'm ok...buy my doc thinks I should go vegan. I want coconut oil, little red meat.  I evercise 5x week. My heatt stress tests were all 'well within'   So, it sounds as though I need to get the E4 tested   More?

I would be deeply grateful for your advice. I am doing my best to understand how to cope with my aPOE 3/4 status. I have Alzheimer's on both sides of my family, which has killed or is in the process of killing several relatives, including my father and maternal grandmother. Unsurprisingly, I have received much conflicting data.

I am 46. I eat a strict Paleo diet (grass-fed, wild-caught, etc.) except for some resistant starch in the form of parboiled rice and unmodified potato starch. I consume approximately 50-60% fats (majority saturated fats including daily MCT oil), 30-40% protein and 10-20% carbs. I exercise vigorously and non-vigorously -- but not every day. (Incidentally, over three years I naturally increased my testosterone by 38% using this approach, going from the low 3's to 5.3.)

My LDL is 128. My HDL is a distressingly low 33. Triglycerides are 59.

MY NEXT MOVE: Seek out an LDL particle-size test. If that reveals my LDL particles to be of an unhealthy size then I will need to consider a different approach in regard to sat fats. Also, looking  to improve my sleep, which has been my Achilles' heel (consistently get only around six hours). Finally, using super-consistent exercise and increasing oyster intake to boost the HDL.

I would appreciate any guidance.(!)

Best / Mario

Dr. Davis,
Isn't a catheter used for an angiogram?  I thought an angiogram is a necessity before surgery for an aortic abdominal aneurysm?  What are the other alternatives if catheters make so much rubbish?  Just wondering since my mother is considering having surgery for her AAA and needs to have an angiogram first.
Thanks,
Josephine Keliipio
Hawaii

Dr. Davis doesn't answer questions posted to his blog any longer. He announced this some time ago.

I think the point of his little story about being green is to avoid having to have such a procedure done in the first place. I don't believe he is suggesting that you ask the Hospital to recycle all the left over rubbish from such a procedure. At the rate of pay of those people, they'd probably have to charge you a couple of hundred dollars to sort everything out that could be recycled..  

I am only a lay person but I believe there is no alternative (less rubbish producing that is) to the procedure your Mom needs done. Don't worry about the trash and focus on your Mom's outcome instead.

Good luck with your Mom's procedure.

Catheter angiogram is no longer needed to demonstrate arteries, especially arterial anatomy in the abdomen, extremities,head and neck, including, carotids and intracerebral arteries, arteries in the arm or legs. There is now, an alternative, non-invasive. This consist of CT, CTA, or even better, without radiation an MRI,MRA. The only indication for catheter angiogram is if there is plan for angioplasty, or placement of a stent.
No one or nobody should be subjected, to a catheter angiogram, in this day and age.
I hope this helps.

Dr. Davis,

Much obliged for the post.  It provides me with a wonderful counter to claims that a grain-based diet has less of an environmental impact.

Wheat=Heart Disease=Medical Waste

jonathan

Anonymous #2,
Thanks for your comment about angiograms. I am still learning about this procedure and am glad to know that there may be other alternatives. My mom had no plans for a stent or an angioplasty but it seems that angiograms are the standard for elderly patients electing to fix AAAs. Anyway, lots of questions to ask the cardiologist when we see him again in a few weeks. Josephine

Mmmm...stay out of the surgical ICU also, if you can help it. We generated on average 3-4 large cans of waste per room (14) per shift (12hr) per day. Efforts to separate out recyclables were futile. And let's not even get into hand washing. This was in 2000. I hope things have improved.

Ditto on having to struggle with Doctors to order tests. My Doctor thought that my lipid profile showed I was not in great danger until I showed him the results of my CT scan.He simply refuses to order tests like vit d levels. I have given up trying and simply get the tests myself.

Ditto to having difficulty getting my PCP to run tests. I was low in Vitamin D and got it up by the end of last summer. I asked for a check after last winter and he refused because my vitamin D is now "good". In the summer I was getting some sunlight. I wanted to know if it had dropped during the winter months.

There are online places that offer all the blood tests. I guess that is one alternative when the doctor refuses.

Anne-

You echo a repeated complaint we get: It is a frequent stumbling block  requesting laboratory tests (or other test, for that matter) that are clearly beneficial, but beyond the comprehension of your doctor.

We are searching for solutions. Our collective efforts will, given sufficient time and inventiveness, lead us all to a practical answer.

I think you have hit the nail on the head.  I used to think I was fairly well informed on health and that my doctor was giving me excellent care.  But over a few years I realized I had a lot of "not sick but annoying" health problems.  My *former* primary care doctor (I had seen her for a decade) was willing to prescribe for some of the symptoms but didn't seem interested in the "big picture" and even dismissed my theories.  She missed or dismissed so many things (hyperglycemia, hypothyroidism, relaxed pelvic ligaments), even when I asked about these conditions.  It was a rude awakening for me and I found other doctors who treated me with the appropriate treatments (rather than just Rx for symptoms) or at least listened to my ideas and I am much improved.  Now I am a much more informed patient and I don't hesitate to question, re-question, and learn on my own.  

And while I don't like the idea of "shopping around" for a "puppet" doctor who will just do as I say, I have learned it is a good idea to get additional opinions (even if it means paying out of pocket) or try a new PCP, even within the same network (my HMO lets me see any PCP in the same network).   I made a huge mistake thinking that my former doctor couldn't have been wrong or that a long history with a doctor was better than starting all over with a new PCP.   I now realize that I am part of the team for my healthcare, even the leader sometimes, not just a passive observer.

I think you have hit the nail on the head.  I used to think I was fairly well informed on health and that my doctor was giving me excellent care.  But over a few years I realized I had a lot of "not sick but annoying" health problems.  My *former* primary care doctor (I had seen her for a decade) was willing to prescribe for some of the symptoms but didn't seem interested in the "big picture" and even dismissed my theories.  She missed or dismissed so many things (hyperglycemia, hypothyroidism, relaxed pelvic ligaments), even when I asked about these conditions.  It was a rude awakening for me so I found other doctors who treated me with the appropriate treatments (rather than just Rx for symptoms) or at least listened to my ideas; two years later and I am much improved.  Now I am a much more informed patient and I don't hesitate to question, re-question, and learn on my own.  

And while I don't like the idea of "shopping around" for a "puppet" doctor who will just do as I say, I have learned it is a good idea to get additional opinions (even if it means paying out of pocket) or try a new PCP, even within the same network (I now know my HMO insurance lets me see any PCP in the same network).   I made a huge mistake thinking that my former doctor couldn't have been wrong or overlooking anything or that a long history with a doctor was better than starting all over with a new PCP.  

Now I am part of the team for my healthcare, even the leader sometimes, not just a passive observer.

Awesome, just awesome.Brilliant blog that has helped me ALOT so I am eternally grateful. Phil

I just had a heart scan. 44 year old female with family history of heart disease.  Both parents in 40's with heart attacks/by-pass surgery...My cardiologist ask if I had ever been diagnosed with a hiatal hernia and the scan looked somewhat like the one you show.  It looked like I had one Big Heart!  He told me to follow-up with my PCP.  I did, he is new for me and not sure I see eye-to-eye with him, but he insist a hernia can not show up on a heart scan, I told him, I saw it, I saw the scan, I saw the white circle...I have had GERD for 5-6 years now, nausea almost every morning on top of the reflux in the morning and my family always complain how long it takes me to eat! Guess what, I'm having an upper GI in the morning.  Thanks for this information...I thought maybe I was loosing my mind!

Thank you! Sadly, many physicians are becomming a parody when it comes to "procedures". I've heard a neurolgist (family friend) fret, "I went into the wrong field; I end up spending time examining patients instead of doing procedures and can't make any money! I should have gone into orthopedics." Pitiful. In some practices the push for procedures is as bad or worse than the old "publish or perish" dilema of academia.

Who suffers? The patients. And the clinical skills of the physician.

Well said!

Hi Dr. Davis,

Charlie Rose, just last night, hosted a round table of cardiologists to discuss heart disease.  Hopefully it will be available for viewing on the web.

Among the participants was a President emeritus of the American Association of Cardiology (Steven Nissen).

The discussion was all about quick resuscitation(sp?) and providing "2nd chances" in crisis situations, high cholesterol, blood pressure, etc.

The themes you devote yourself to were essentially undiscussed.  No discussion of nuanced lipid analysis, CT scanning, or advances in understanding of the potential positive impacts of food and supplements.

It is precisely that kind of amorphous discuss of heart disease risk which is so depressing.

I'll see if I can find a link to an archived video to get your feedback.

Here's the link to the Charlie Rose show page that should contain yesterday's discussion of heart disease once the video is put up.  Video #8 is already up.  The Heart Disease video is #9.

href="http://www.pfizer.com/think/think_cr_science.jsp"