Beating the Heart Association diet is child's play



In response to the Heart Scan Blog post, Post-Traumatic Grain Disorder, Anne commented:


While on the American Heart Association diet my lipids peaked in 2003. I even tried the Ornish diet for a short time, but found it impossible.

Total Cholesterol: 201
Triglycerides: 263
HDL: 62
LDL: 86

After I stopped eating gluten (I am very sensitive), my lipid panel improved slightly. This past year I started eating to keep my blood sugar under control by eliminating sugars and other grains. Now this is my most recent lab:

Total Cholesterol: 162
Triglycerides: 80
HDL: 71
LDL: 75


Isn't that great? This is precisely what I see in practice: Elimination of wheat and sugars yields dramatic effects on basic lipids, especially reductions in triglycerides of up to several hundred milligrams, increased HDL, reduced LDL.

Beneath the surface, the effects are even more dramatic: reductions or elimination of small LDL particles, reduction or elimination of triglyceride-containing lipoproteins, elimination of the marker for abnormal post-prandial (after-eating) lipoproteins, IDL, reduced c-reactive protein. Add weight loss from abdominal fat stores and reduced blood pressure.

In fact, I would go so far as to speculate that, if the entire nation were to follow Anne's lead and eliminate wheat and sugars, "need" for 30% of all prescription medications would disappear. The incidence of diabetes would be slashed, the U.S. would no longer lead the world in obesity.

Anne and I are not the first to make this observation. It has also been made in several studies, such as:

The Duke University study of low-carbohydrate diets in type II diabetics. In this study, 50% of low-carb participants became non-diabetic: They were cured.

One of the many studies conducted by University of Connecticut's Dr. Jeff Volek, demonstrating dramatic improvement in glucose, insulin (reduced 50%) and insulin responses, and lipids.

Dr. Ron Krauss' early studies that hinted at this effect, even though the "high-fat" diet wasn't really low-carbohydrate.

If wheat and sugar elimination has been shown to achieve all these fabulous benefits, why hasn't the American Heart Association spoken in favor of this dietary approach and other- low-carbohydrate diets ? Why does the American Heart Association maintain its "Check-Mark" stamp of approval on Cocoa Puffs and Count Chocula cereals?

Victim of Post-Traumatic Grain Disorder

Heart Scan Blog reader, Mike, shared his story with me. He was kind enough to allow me to reprint it here (edited slightly for brevity).



Dr. Davis,

I was much intrigued to stumble onto your blog. Heart disease, nutrition, and wellness are critically important to me, because I’m a type 2 diabetic. I’m 53 and was diagnosed as diabetic about 5 years ago, though I suspect I was either diabetic or pre-diabetic 5 years before that. Even in a metropolitan area it's next-to-impossible to find doctors sympathetic to any approach beyond the standard get-the-A1c-below 6.5, get LDL <100, get your weight and blood pressure normal, and take metformin and statins.

I’m about 5’10-and-a-half and when I was young I had to stuff myself to keep weight on; it was an effort to get to 150 pounds, and as a young man, 165 was the holy grail for me. I always felt I’d look better with an extra 10-15 pounds.
I ate whatever I wanted, mostly junk, I guess, in my younger years.

When I hit about age 35, I put on 30 pounds seemingly overnight. As I moved toward middle age I became concerned with the issue of heart health, and around that time Dr. Ornish came out with his stuff. I was impressed that he’d done a
study that supposedly showed measurable decrease in atherosclerotic plaque, and had published the results of his research in peer-reviewed journals. It looked to me as though he had the evidence; who could argue with that? I tried his plan on and off, but as so many people note, an almost-vegan diet is really tough. It was for me, and I could never do it for any length of time. But given that the “evidence” said that I should, I kept trying, and kept beating up on myself when I failed. And I kept gaining weight. I got to almost 200 pounds by the time I was 40 and have a strong suspicion that that’s what caused my blood sugar to go awry, but my doctor at the time never checked my blood sugar, and as a relatively young and healthy man, I never went in very often.

I’ve had bouts of PSVT [paroxysmal supraventricular tachycardia, a rapid heart rhythm] every now and again since I was 12 or so. I used to convert the rhythm with Valsalva, but as I moved into my forties, occasionally my blood pressure would be elevated and it made me nervous to do the procedure because it was my understanding that it spikes your blood pressure when you do it. So I began going to the ER to have the rhythm converted, which they do quite easily with adenosine. On one of my infrequent runs to the ER to get a bout of PSVT converted, they discovered my blood glucose was 500 mg/dL, and I’d never experienced any symptoms! They put me in the hospital and gave me a shot of insulin, got it town to 80 mg/dL easily,
diagnosed me as diabetic, and put me on 500 mg. metformin a day.

I was able to get my A1c down to 7, then down to 6.6, and about that time I read a number of Dr. Agatston’s books, and began following the diet, and pretty quickly got my A1c down to 6.2, and my weight down, easily, to 158. That was fine with my doctor; he acted as though I was in good shape with those numbers. Soon I ran into Dr. Bernstein’s material, and came face to face with a body of research that suggested I needed to get the A1c down to below 5! That was both discouraging and inspiring, and frankly it’s been difficult for me to eat as lo-carb as I appear to need to, so I swing back and forth between 6.2 and 6.6. I know I need to work harder, be more diligent in my carb control, and I see with my meter that if I eat low-carb I have great postprandial and fasting blood sugars, but since I don’t particularly get any support or encouragement from
either my doctor or my wife for being so “radical,” it’s hard to pass the carbs by.

One thing that always confused me was that though I saw on my meter that BG [blood glucose] readings were better with a lo-carb diet, and though I saw the preliminary research suggesting that lo-carb could be beneficial in controlling CVD, I didn’t understand why Ornish had peer-reviewed research demonstrating reversal of atherosclerosis on a very-lowfat diet. How could two opposing approaches both help? I wondered if it were possible that one diet is good for diabetes, and the
other good for heart health. That would mean diabetics are screwed, because they always seem to end up with heart disease.

From time to time I’d look for material that explained this seeming contradiction. I was determined to try to stay lo-carb, simply because I saw how much better my blood sugars are when I eat lo-carb; but it’s hard in the face of this or that website that tells you about all the dangers of a lo-carb diet and that touts the lo-fat approach. That tends to be the conventional wisdom anyway.

Finally in one of those searches I came across your material, and saw you offer what was at last an explanation of what Ornish had discovered--it wasn’t a reversal of atherosclerotic plaques he was seeing; it was that his diet was improving endothelial dysfunction in people who had had high fat intakes.

Odd as it may seem to you, that little factlet has been enough to allow me to discard entirely the lingering ghost of a suspicion that I ought to be eating very-lowfat. In fact, I was very excited to see your claim that your approach can reverse atherosclerotic plaque.

It would be nice to find a doctor who’d be supportive of your approach. My doctor isn’t much interested in diet or
nutrition. He just wants my weight in the acceptable range, my blood pressure good, and my LDL 100 or below (which I know isn’t low enough). He’s not particularly interested in getting a detailed lipid report. I hope I can talk him into ordering one so that it’s more likely I can get it covered by my insurance.

I very much appreciated the links you gave to Jenny’s diabetes websites, and I’ve resolved to get even better control of my BG by being more diligent with my diet. I’m planning on joining your site, reading your book, and following your advice. I just have this sort of deflating feeling that it would have been better if I’d stumbled upon this before I had diabetes. Still, it’s nice to have a site that offers to laypeople the best knowledge available concerning how to take care of their heart.



Mike is yet another "victim" of the "eat healthy whole grains" national insanity, the Post-Traumatic Grain Disorder, or PTGD. The low-fat dietary mistake has left many victims in its wake, having to deal with the aftermath of corrupt high-carbohydrate diets: diabetes, heart disease, and obesity.

We should all hope and pray that "low-fat, eat healthy whole grains" goes the way of Detroit gas guzzlers and sub-prime mortgages.

Drug industry "Deep Throat"

A Heart Scan Blog reader brought the following letter from a former pharmaceutical sales representative to congress to my attention.

Interesting excerpts:

As a former drug representative for Eli Lilly, I spent 20 months increasing the market share of my company’s drugs. I was recruited fresh from college with an eager desire to employ my degree in molecular biology and biochemistry. Shortly after my hiring, it became clearly apparent that a drug sale had much more to do with establishing personal relationships than it did with understanding the latest science. However, any doubts I held regarding the effectiveness of such methods were dispelled by the results of my persuasiveness and the financial rewards I received for my efforts. The latter also helped me rationalize the many ethically dubious situations I routinely encountered in my work. Upon my departure from the industry, I began working for the public’s health. Seven years later, as a result of my experiences and education I am more convinced than ever that the goals of the pharmaceutical industry often stand in direct conflict with the practice of ethical and responsible medicine. Nothing in my recent research causes me to believe that my experiences were anything but typical of the training and practice of the majority of drug reps plying their trade today.


“There’s a big bucket of money sitting in every [doctor’s] office.” – Michael Zubillaga, Astra Zeneca Regional Sales Director, Oncology


The majority of drug reps entering the work force today are young and attractive. The ranks of reps are replete with sexual icons: former cheerleaders, ex-military, models, athletes. Of course, as a sales job, the reps must be eloquent and convincing. Depending on the population, certain ethnicities are preferred either to make the rep distinct among other reps or to provide them with a cultural advantage in connecting with their clients. Noticeably lacking among most new reps is any significant scientific understanding. My personal case illustrates this point rather vividly: In my training class for Eli Lilly's elite neuroscience division, selling two products that constituted over 50% of the company's profits at the time, none of my 21 classmates nor our two trainers had any college level scientific education. In fact, that first day of training, I taught my class and my instructors the very basic but crucial process by which two nerve cells communicate with one another. It is very likely that the majority of my class couldn't explain the difference between a neuron and a neutron prior to sales school. While it's certainly a bonus to have a scientifically educated representative, it is far from a primary recruitment criterion. Youth is a much higher criterion for the sales position.

Sales representative trainers are almost always veteran sales representatives and consequently, much of the training they offer is implicit in the anecdotes they give. This informal training parallels the standard training offered by the industry and in many ways compliments it. It is tacitly accepted by management and perceived as the "real" training by many veteran sale representatives. Among the more dubious "unofficial" lessons a new rep learns are: how to manipulate an expense report to exceed the spending limit for important clients, how to use free samples to leverage sales, how to use friendship to foster an implied "quid pro quo" relationship, the importance of sexual tension, and how to maneuver yourself to becoming a necessity to an office or clinic.

The most troubling aspect of pharmaceutical sales is systematic befriending of our clients. In addition to the psychological profiling mentioned above, drug reps are taught to constantly be on the lookout for personal effects that will help us connect to our doctors. When entering an office for the first time, we nonchalantly survey it for clues to ingratiate ourselves with our client. Similarly, conversations are intentionally steered into the realm of personal details such as religion, family, or hobbies to acquire similar information. As a matter of training, we collect this data subtly. In the course of a conversation with clients, we may glean facts about their prescribing preferences, the dates of their children’s birthdays, where they were born, or what music they enjoy. Training encourages us to commit these details to memory just long enough to return to our cars and instantly type up a “call report” listing the details of our conversation. On a daily basis, we connect our computers to a central database that uploads the information we’ve acquired, allowing us to share it with our partner drug reps and company marketers. Subsequently, drug reps interweave pieces of conversation specifically tailored to appeal to their client drawn from personal information that wasn’t necessarily shared with them. For example, Dr. Jones will be nothing but grateful when I supply him with a cake celebrating his children’s birthday when, in fact, he told my partner (and not me) the birthdates several months prior in a personal conversation.


The writer's comments ring true: The relentless attention-grab of sales representatives, using clever tactics that include access to detailed records of physician prescribing habits, big smiles and eye-winking, are detailed perfectly.

There's nothing wrong with a business doing its job by marketing its products and services. What is so wrong about this picture is that one side is so well-equipped, heavily funded, with access to extraordinary resources that the other side (physicians) don't have. And the physicians aren't the victims--YOU are.

A middle-aged, receding hairline physician, faced with a 28-year old attractive woman asking all manner of ingratiating questions but knowing full well what she is doing, having strategized for weeks on how to manipulate the behavior of her "mark," is helpless.

Like the mortgage-backed security crisis, we've reached another phenomenon of crisis proportions. Direct-to-consumer drug advertising, drugs for non-conditions and well people, pinpoint marketing of drugs to physicians--it's all gone too far.

Personally, drug representatives are not welcome in my office. This generally prompts puzzled, followed by angry, looks from the representatives, often traveling with a district supervisor hoping to help polish their pitch. If patients didn't request free samples, the reps would not step foot in the office.

Triglyceride Buster-Update

In the last Heart Scan Blog post, I described Daniel's experience reducing his triglycerides from 3100 mg/dl to around 1100 mg/dl with use of omega-3 fatty acids from fish oil, along with modifications in his diet. This was accomplished in the space of around two weeks.

An update: Daniel has continued another 10 days on his fish oil, along with elimination of wheat, cornstarch, and sugars.

Repeat triglyceride: 202 mg/dl. That's 93.5% reduction in the space of three weeks--no drugs involved.

Daniel really did nothing extraordinary. He simply followed the simple advice I provided to take a moderate dose of EPA+DHA from over-the-counter fish oil supplements, along with elimination of the foods that are extravagant triggers of triglycerides.

He's got just a little further to go to achieve the biologically ideal level of less than 60 mg/dl. You can see that it is not really that difficult--provided someone didn't load you down with nonsense about "cutting your fat," or statin or fibrate drugs.

Triglyceride buster

Two weeks ago, Daniel started with a triglyceride level of 3100 mg/dl, a dangerous level that had potential to damage his pancreas. The inflammatory injury incurred could leave him with type I diabetes and inability to digest foods, since the insulin-producing capacity and the enzyme producing capacity of the pancreas are lost.

Daniel added 3600 mg of omega-3s per day. Within 10 days, his triglycerides dropped nearly 2000 mg to just over 1100 mg/dl--still too high, but an incredible start.

The power of omega-3 fatty acids from fish oil to reduce triglycerides is illustrated most graphically by people with a condition called "familial hypertriglyceridemia" that is responsible for triglyceride levels of 500, 1000, even several thousand milligrams. That's what Daniel has. Given appropriate doses of omega-3s, triglycerides drop hundreds, even thousands, of milligrams.

No question: Omega-3 fatty acids from fish oil are the best tool available for reduction of triglycerides. The effect is dose-dependent, i.e., the more you take, the greater the triglyceride reduction.

How omega-3s exerts this effect is unclear, though there is evidence to suggest that omega-3s suppress several nuclear receptors involved in triglyceride (VLDL) production and increase the expression or activity of the enzyme lipoprotein lipase, an enzyme that clears triglycerides from the blood.

I am continually surprised at the number of people with high triglycerides who are still treated with a fibrate drug, like Tricor, or a statin drug, when fish oil--widely available, essentially free of side-effects, with a proven cardiovascular risk-reducing track record--should clearly be the first choice by a long stretch.

Among its many benefits, omega-3 fatty acids from fish oil also:

Reduce matrix metalloproteinases (MMP)--Two fractions of MMPs, MMP-2 and MMP-9, are inflammatory enzymes present in atherosclerotic plaque that are suspected to trigger plaque "rupture." Omega-3s have been shown to reduce both forms of MMP.

Block uptake of lipids in the artery wall--Suggested by a study in mice.

Modify postprandial responses--In the first few hours after eating (the "postprandial" period), a flood of digestive byproducts of a meal are present in the bloodstream. While research exploring postprandial effects is still in its infancy, it is clear that omega-3 fatty acids have the capacity to favorably modify postprandial patterns. One common surrogate measure for postprandial abnormalities is intermediate-density lipoprotein, or IDL, that we obtain in fasting blood through lipoprotein panels like NMR and VAP. With sufficient omega-3s alone, IDL is completely eliminated.

Unfortunately, most of my colleagues, if they even think to use omega-3s, choose to use the prescription form, Lovaza. Indeed, several representatives from AstraZeneca, the pharmaceutical outfit now distributing this miserably overpriced product, frequently barge their way into my office poking fun at our use of nutritional supplements instead of the prescription Lovaza. "But insurance covers it in most cases!" they plead. "And your patients will know that they're getting the real product, not some fake. And they'll have to take fewer capsules!"

I never use Lovaza to reduce triglycerides, even in familial hypertriglyceridemia--the FDA-approved indication for Lovaza--and have not yet seen any failures, only successes.

Newsweek, Time, and other fronts for the drug industry

I used to believe that conventional print media--newspapers, magazines--were unbiased, untouchable flames of truth. Perhaps there was a time when this was true, when the young reporter, eager to change the world, uncovered the story that righted some huge wrong.

Those days are drawing to a close.

Today, the once powerful print media are collapsing due to the competition of the cheaper, broader reach of the internet.

Jogging does NOT cause heart disease


Periodically, I'll come across a knuckleheaded report like this one from Minneapolis:

Marathon Man’s Heart Damaged by Running?


Of course, the obligatory story about how a cardiologist came to the rescue and "saved his life" with a stent follows. In other words, a stent purportedly saved the life of this vigorous man with no symptoms and high capacity for exercise.

Does vigorous exercise, whether it's marathon running, long-distance biking, or triathlons, cause coronary disease? Should all vigorous athletes run to their doctor to see if they, too, need their lives to be "saved."

Let me tell you what's really going on here. People with the genetic pattern lipoprotein(a), or Lp(a), tend to be slender, intelligent and athletic. For genetic reasons, these people gravitate towards endurance sports like long-distance running. Lp(a) is a high-risk factor for coronary disease. It is the abnormality present in the majority of slender, healthy people who are shocked when they receive a high heart scan score or have a heart attack or receive a stent. (I call Lp(a) "the most aggressive known coronary risk factor that nobody's heard about.")

The association between endurance exercise and heart disease is just that: an association. It does not mean that exercise is causal. Having seen coronary plaque detected with heart scans in many runners, virtually all of whom demonstrated increased Lp(a), I believe that Lp(a) is causal.

Unfortunately, the man in the Minneapolis story, now that his life is "saved," will likely be advised to take a statin drug and follow a low-fat diet . . . you know, the diet that increases Lp(a).

Warning: Your pharmacist may be hazardous to your health

Pharmacists can be very helpful resources when it comes to questions about prescription drugs.

The operant word here is drugs.

What they are most definitely not expert on are nutritional supplements. In fact, a day doesn't pass by without having to dispell one falsehood or another conveyed to a patient about a nutritional supplement by a pharmacist.

Among the more common falsehoods told to patients by pharmacists:

"You have to take Niaspan. Sloniacin doesn't work."

Patent nonsense. A few years back, I was the largest prescriber of Niaspan in Wisconsin. Although I am embarassed to admit it, I also spoke for the company, educating fellow physicians on the value of niacin for correction of lipid disorders.

Then I shifted to Sloniacin due to cost--it costs 1/20th the cost of prescription Niaspan. I examined the pharmacokinetic data (pattern of release in the body), the published literature (e.g., the famous HATS Trial), and have used Sloniacin over 1000 times in patients. In my experience, there is no difference: no difference in efficacy, no difference in safety, no difference in side-effects. There is a BIG difference in price.

Unfortunately, most pharmacists get their information on niacin from the Niaspan representative.


"You shouldn't be taking vitamin D supplements. I have prescription vitamin D here."

What the pharmacist means is that you should replace your vitamin D3, or cholecalciferol--the form recognized as vitamin D by the human body--with the plant form of vitamin D, vitamin D2 or ergocalciferol.

Since when is a plant form of a hormone (vitamin D is a potent hormone, not a vitamin; it was misnamed) better than the human form?

I've previously talked about this issue in a blog post called Vitamin D for the pharmaceutically challenged.

The notion that D2 is somehow superior to the real thing, D3, is absurd. I use D3 only in my practice and have checked blood levels thousands of times. As long as the D3 comes as a gelcap, drops, or powder in a capsule, it works great, yielding predictable and substantial increases in blood levels of 25-hydroxy vitamin D. If it comes as prescription D2 (or over-the-counter D2), I have seen many failures: no increase in blood levels of vitamin D or meager increases.

Prescription status is no guarantee of effectiveness.


"Why do you need iodine? You already get enough from food."

The NHANES data over the last 25 years argue otherwise: Iodine deficiency is growing, particularly as people are avoiding iodized salt and the iodine content of processed foods is diminishing. The explosion in goiters in my office also suggest this is no longer a settled issue.

On the positive side, it is exceptionally easy to remedy with an inexpensive iodine supplement. That is, until the pharmacist intervenes and injects his bit of nutritional mis-information.


I'm not bashing pharmacists. In fact, Track Your Plaque's own Dr. BG has a pharmacy background, and she is an absolute genius with nutritonal supplements. But she is a rare exception to the rule: Most pharmacists know virtually nothing about nutritional supplements. You might as well ask your hairdresser.

"Healthy" people are the most iodine deficient

Ironically, the healthiest people are the most likely to be deficient in iodine.

Why?

Healthy people tend to:

--Avoid iodized salt because of public health advice to limit sodium
--Use sea salt to obtain minerals like magnesium--but sea salt contains little iodine
--Limit meat--Carnivores obtain more iodine than vegetarians or vegans. In one study, up to 80% of vegans were iodine-deficient (Krajcovicova-Kudlackova M et al 2003).
--Exercise--Substantial amounts of iodine are lost through sweating. In a study of high school soccer players, 38.5% were severely iodine deficient, compared to 2% of sedentary students (Mao IF et al 2001).


That is indeed what I am seeing in my office, as well: The healthiest, most attentive to healthy eating, and most physically active are the ones showing up with small goiters (enlarged thyroid glands) and increased TSH and low free T4 levels.

Why am I checking thyroid and talking about iodine? Because even the smallest degree of thyroid dysfunction can double, triple, or quadruple your risk for cardiovascular events. See the posts Is normal TSH too high? and Thyroid perspective update.

What kind of iodine do you take?

The results of the latest Heart Scan Blog poll are in.

204 respondents answered the question:


Do you take an iodine supplement?

The responses:

Yes, I take Iodoral, Lugol's, or SSKI
26 (12%)

Yes, I take potassium or sodium iodide
19 (9%)

Yes, I take kelp tablets or powder
64 (31%)

No, I rely on generous use of iodized salt
23 (11%)

No, I don't supplement iodine at all
66 (32%)

Isn't iodine something you put on cuts and scratches?
6 (2%)


I am heartened by the number of respondents taking iodine in some form. After all, iodine is an essential trace mineral. Without it and health suffers, often dramatically.

However, I am concerned by the percentage of people who don't supplement iodine at all: 32%. Interestingly, this is approximately the proportion of people who come to my office who also do not supplement iodine who are now showing goiters, or enlarged thyroid glands due to iodine deficiency. Goiters lead to hypothyroidism (low thyroid hormone levels), followed by hyperactive nodules, not to mention undesirable effects like weight gain, fatigue, hair loss, constipation, intolerance to cold, higher LDL cholesterol and triglycerides, and heart disease.

11% of respondents report using lots of iodized salt. This may or may not be sufficient to provide enough iodine to prevent goiter and allow normal thyroid function. The success of this strategy depends to a great extent on how often salt is purchased. Salt that sits on the shelf for more than a month is devoid of iodine, given iodine's volatility.

I am also favorably impressed by the number of people who take "serious" iodine supplements like Lugol's solution, Iodoral, or SSKI. Of course, people who read The Heart Scan Blog tend to be an unusually informed, healthy population. The 12% of people in the poll who take these forms of iodine does clearly not mean that 12% of the general population also takes them. But 12% is more than I would have predicted.

On the Track Your Plaque website, we are awaiting an interview with iodine expert, Dr. Lyn Patrick. I'm hoping for some juicy insights.
The exception to low-carb

The exception to low-carb

I witness spectacular results restricting carbohydrates, both in the office as well as in my online experiences, such as those in Track Your Plaque. Of course, the diet I advocate is not just low-carb; it starts with elimination of wheat (for a long list of reasons). So the diet is wheat-free in the setting of low-carbohydrate.

What does this accomplish? Here's a partial list:

--Weight loss-Specifically, loss of visceral fat, the kind hinted at on the surface as "love handles" or what I call "wheat belly."
--Reduced blood sugar and HbA1c (reflecting prior 60-90 days glucose)
--Marked reduction in small LDL and triglycerides, increased HDL
--Reduced inflammatory measures like c-reactive protein
--Reduced leptin and leptin resistance, increased adiponectin
--Reduced estrogen and prolactin in men, accompanied by shrinkage or loss of enlarged breasts ("man boobs"); reduced estrogen in females accompanied by reduced risk for breast cancer

Pretty impressive. But there's one group of people who can experience unexpected effects with this diet: The 25% of people with apoprotein E4.

Everybody has two genes for apo E; the most common type is apo E 3/3. Around 1 in 4 people have 1, less commonly 2, genes for apo E4.

I hate apo E4. I hate apo E4 because it means I've got to dust off the nonsense I used to tell patients about cutting their fat, cutting their saturated fat. But that's what apo E4 people have to do. But it doesn't end there.

Apo E4 people also typically have plenty of small LDL particles triggered by carbohydrates. Put fats and carbohydrates together and you get an explosion of small LDL particles. Remove fats, small LDL goes down a little bit, if at all. Remove carbohydrates, small LDL goes down but total LDL (mostly large) goes up. The large LDL in apo E4 does seem to be atherogenic (plaque-causing), though the data are fairly skimpy.

So apo E4 creates a nutritional rock and a hard place: To extract full advantage from diet, people with apo E4 have to 1) go wheat-free, low-carb, then 2) not overdo fats, especially saturated fat.

It still gives me the creeps to tell an apo E4 person that they've got to watch their fats, worse than watching Starsky and Hutch reruns.

Comments (60) -

  • Simon

    7/30/2011 10:45:35 PM |

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

  • Paul

    7/30/2011 11:44:42 PM |

    Have you tried T4/T3 adjustments with apo E4?

  • PeggyC

    7/30/2011 11:48:10 PM |

    How can one find out if one has Apo E4?

  • steve

    7/31/2011 12:38:22 AM |

    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.

  • Buckaroo Banzai

    7/31/2011 5:19:21 AM |

    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.

  • Might-o'chondri-AL

    7/31/2011 6:35:43 AM |

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

  • Renfrew

    7/31/2011 12:46:17 PM |

    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

  • Beth@WeightMaven

    7/31/2011 2:17:43 PM |

    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?

  • Jolly

    7/31/2011 2:26:04 PM |

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

    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.

  • Gene K

    7/31/2011 3:39:12 PM |

    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.

  • Gene K

    7/31/2011 3:43:03 PM |

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

  • mallory

    7/31/2011 4:18:37 PM |

    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?

  • Dr. William Davis

    7/31/2011 4:48:42 PM |

    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.

  • Dr. William Davis

    7/31/2011 4:50:18 PM |

    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.

  • Dr. William Davis

    7/31/2011 4:51:22 PM |

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

  • Dr. William Davis

    7/31/2011 5:06:39 PM |

    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

  • Dr. William Davis

    7/31/2011 5:08:35 PM |

    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.

  • Might-o'chondri-AL

    7/31/2011 7:28:48 PM |

    even 1 reconstructed paragraph just  lost to "server error"

  • Might-o'chondri-AL

    7/31/2011 7:33:54 PM |

    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.

  • Tim Dietz

    7/31/2011 8:32:10 PM |

    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?

  • Tim Dietz

    7/31/2011 8:49:56 PM |

    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?

  • Gene K

    8/1/2011 4:13:05 AM |

    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.

  • TimK

    8/1/2011 7:34:36 AM |

    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?

  • Dr. Jack Kruse

    8/1/2011 12:21:31 PM |

    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

  • Peter Silverman

    8/1/2011 6:24:50 PM |

    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?

  • Jack Kronk

    8/1/2011 8:12:52 PM |

    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

  • Patri Friedman

    8/1/2011 8:58:31 PM |

    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.

  • Tim Dietz

    8/2/2011 1:42:49 AM |

    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.

  • Dr. Jack Kruse

    8/2/2011 3:51:19 AM |

    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.

  • Dr. Jack Kruse

    8/2/2011 4:05:59 AM |

    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!

  • Dr. William Davis

    8/2/2011 11:01:58 AM |

    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.

  • Dr. William Davis

    8/2/2011 11:07:23 AM |

    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.

  • Dr. William Davis

    8/2/2011 11:12:52 AM |

    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.

  • Melinda

    8/2/2011 2:57:02 PM |

    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

  • Melinda

    8/2/2011 3:01:05 PM |

    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.

  • Jack Kronk

    8/2/2011 4:52:20 PM |

    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!

  • Jack Kronk

    8/2/2011 5:01:51 PM |

    "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)

  • Might-o'chondri-AL

    8/2/2011 5:20:02 PM |

    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 .

  • Might-o'chondri-AL

    8/2/2011 5:31:26 PM |

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

  • Dr. Jack Kruse

    8/3/2011 4:57:17 PM |

    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.

  • Davide

    8/4/2011 2:24:29 AM |

    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?

  • Dr. Jack Kruse

    8/4/2011 4:21:16 PM |

    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.

  • Might-o'chondri-AL

    8/4/2011 10:55:40 PM |

    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.

  • jegesq

    8/5/2011 4:28:04 AM |

    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.

  • Dee

    8/5/2011 1:49:05 PM |

    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

  • Dee

    8/5/2011 2:20:34 PM |

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

  • George Zachary

    8/6/2011 12:21:32 AM |

    Super interesting!

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

  • Dee

    8/6/2011 12:29:15 AM |

    Plasma PCSK9 levels correlate with cholesterol in men but not in women
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    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

  • Dr. K

    8/6/2011 8:27:02 PM |

    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.

  • Dr. K

    8/6/2011 10:05:56 PM |

    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.

  • Dee

    8/6/2011 11:28:44 PM |

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

  • Jack Kronk

    8/8/2011 2:28:15 PM |

    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.

  • Dr. K

    8/11/2011 12:38:34 AM |

    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.

  • majkinetor

    8/14/2011 2:59:37 PM |

    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.

  • Peter Silverman

    8/16/2011 5:08:49 PM |

    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?

  • Jack Kronk

    8/24/2011 7:29:11 PM |

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

  • Adriana

    10/5/2011 12:33:30 PM |

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

  • Eric

    7/9/2012 6:43:01 PM |

    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?

  • Gary Mullennix

    5/4/2013 4:38:16 AM |

    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?

  • Mario

    3/9/2014 9:46:46 AM |

    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

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