Plaquology

Plaquology: A new term.

Plaquology: def: (plaque-: atherosclerotic plaque; -ology: study of.) The study of atherosclerotic plaque, originating in the early 21st century during the time period when the material underlying atherosclerosis gained recognition as a measure superior to "risk factors" for cardiovascular disease. Previous to the plaque concept, blood measures of cholesterol and adverse lifestyle habits, such as smoking and sedentary lifestyle, alone had been used to predict potential for cardiovascular events. With acceptance of the concept of plaque measurement, the concept of risk factors was abandoned.


Look it up in the current Oxford Dictionary of the English Language, or Webster's Dictionary, and I'm afraid that you still won't find plaquology . . . but you should.

I'm currently rewriting many parts of the Track Your Plaque book. The rewriting process has caused me to review just how much we've learned these past few years. One of the phenomena that fascinates me is that we now have non-medical people--teachers, software people, engineers, bankers, bed and breakfast owners, retired businesspeople, etc.--all discussing the finer points of coronary atherosclerotic plaque--plaquology--what constitutes plaque, what triggers plaque inflammation, how to quantify potential for plaque rupture or plaque quiescence, what effect various treatments have on plaque composition and behavior, etc.

We now have a legion of Plaquologists!

I'm very proud of our Plaquologists. Having devoted themselves to the study of plaque, their level of knowledge now exceeds that of 99% of practicing physicians, including my colleagues, the cardiologists. While cardiologists spend their day squashing/cutting/vaporizing plaque, they are no more experts in plaquology than a carpenter is an expert in trees. More often than not, cardiologists view plaque as just something that gets in their way, rather than the quantifiable, modifiable, reversible material that we can exert control over.

One of the software tools currently in the works for the Track Your Plaque website is a certification process. Members will be able to gain a "certification" in various topics relevant to plaquology, such as plaque quantification, lipoprotein testing, and nutritional supplements.

How about a Doctor of Plaquology?

Thyroid perspective update

Since the publication of the extraordinary HUNT Study relating the entire spectrum of thyroid function and heart issues, I have been vigorously and systematically examining thyroid function in numerous patients.

While there's no news in relating flagrant low thyroid function with triggering heart disease in several forms, the cut-off between low thyroid and normal thyroid has been a matter of dispute for decades.

In the early 20th century, low thyroid function wasn't diagnosed until someone gained 40 lbs, displayed extravagant amounts of edema (water retention) in the legs and huge bags under the eyes, hair fell out in clumps, and often eventually proved fatal. At autopsy, these unfortunates also showed advanced and extensive quantities of coronary atherosclerotic plaque.

Low thyroid is usually diagnosed on the basis of the blood test, thyroid stimulating hormone, or TSH. TSH is a pituitary gland hormone responsible for stimulation of thyroid function. When thyroid function flags, the pituitary increases TSH release. Thus, a high TSH signals lower thyroid hormone levels.

The difficulty is in distinguishing normal thyroid function from low thyroid function judged by TSH levels. As the years have passed, in fact, the cut-off for "normal" TSH has drifted lower and lower.

The HUNT Study, I believe, clinches the argument: A TSH of 1.5 or lower, perhaps even 1.0 or lower, is desirable to eliminate the excess cardiovascular risk provided by an underactive thyroid, not to mention feel better: more energetic, clearer thinking, greater well-being.

Having now applied this renewed appreciation for thyroid, I have come to believe that:

--Low thyroid function, even subtle levels, are rampant and far more common than ever previously thought. In my office practice, the case could be made that several people per day are marginally or mildly hypothyroid (low in thyroid).
--Restoration of optimal thyroid levels facilitates correction of lipid measures, especially LDL cholesterol and, to a lesser degree, lipoprotein patterns dependent on the insulin axis such as triglycerides and small LDL. It's a lot happier way to correct lipids than statins.

I don't discount the value of feeling better. People who feel better--more energetic, more upbeat, clearer thinking--tend to do better in health overall. If thyroid restoration is a part of that equation, then greater attention should be paid to this facet of health on our way to optimal heart health.

Though I sometimes feel like an endocrinologist dispensing desiccated thyroid (rarely the synthetic T4), I believe that this has been a previously neglected and important part of our effort to achieve coronary plaque stabilization and reversal.

Accidental Health


"I shall never have smallpox for I have had cowpox; I shall never
have an ugly pockmarked face."

Such was the idle comment made by a milkmaid to Edward Jenner in 1768 when Jenner was 19, a remark that later prompted his investigations into using isolates of cowpox injected into humans as the first vaccination against the devastations of the European epidemic of smallpox.

(A caricature of Jenner administering cowpox vaccine to people, causing them to sprout bovine appendages. Image courtesy Wikipedia and the Library of Congress.)

When I look back, something similar has happened here.

Although the Track Your Plaque program is intended to stop and reverse coronary plaque using the only available means of tracking coronary plaque, i.e., heart scans, an unintended panel of benefits follow:

--People lose weight, often dramatically
--People gain greater energy
--Thinking is clearer, emotions more stable
--Sleep is deeper
--Bone density increases
--Physical strength and coordination improve
--Winter blues dissipate
--Blood sugar drops dramatically
--Blood pressure drops

Cholesterol (lipid) panels also settle to values that most physicians deem impossible or impractical, given our target of 60:60:60, i.e., LDL 60 mg/dl or less, HDL 60 mg/dl or higher, triglycerides 60 mg/dl or less. And medications are not always necessary to achieve these values. (When I show these values to my colleagues, they declare them flukes, unobtainable only in select people with high doses of medications.)

I didn’t set out to find the next weight loss solution, nor the key to boundless energy. My goal was "simpler": create a program of heart health. I am, after all, a cardiologist.

I was so intently focused on achieving incremental improvements over the steps leading to heart disease prevention that I failed to recognize the profound phenomena that accompanied it: people were quicker, smarter, thinner, and healthier.

In other words, I believe that we have inadvertently created a program of super health and performance.

Ironically, most people don't want to talk about heart disease, let alone reversal of heart disease. They do want to talk about getting thinner, feeling more energetic, living longer, better cholesterol values, etc.

Perhaps there's a lesson in this.

Livin' La Vida Low Carb interview


I recently provided an interview for Livin' La Vida Low Carb's irrepressible Jimmy Moore.

Jimmy runs a fun set of blogs, webcasts, and the like to broadcast this message of reducing carbohydrates in the diet. He credits his 210 lb weight loss to a strict low-carbohydrate and exercise program.

For the interview, just go to The Livin' the Vida Low Carb Show, Episode 185, or click here.

And click here for Part 2


For more of Jimmy Moore's spin on the entire low-carbohydrate diet experience, he maintains several popular blogs, including Carb Wire and The Livin' La Vida Low-Carb Blog.

Wheat withdrawal: How common?

In response to the recent Heart Scan Blog poll,

Have you experienced fatigue and mental fogginess with stopping wheat, i.e., "wheat withdrawal"?

the 104 respondents said:


Yes, I have experienced it: 26 (25%)

No, I stopped wheat and did not experience it: 65 (62%)

I'm not sure: 3 (2%)

I haven't tried it but plan to: 7 (6%)

I haven't tried it and don't plan to: 3 (2%)



So 25% of respondents reported experiencing the fatigue and mental fogginess of wheat withdrawal. This is similar to what I observe in my practice.

I counsel many patients to consider the elimination of wheat, as well as cornstarch products, in an effort to regain control over:

--Weight
--Appetite
--Low HDL
--High triglycerides
--Small LDL
--High blood sugar
--High blood pressure

All of these issues respond--often dramatically--to elimination of wheat and cornstarch.

Why would there be undesirable effects of eliminating wheat?

One clear issue is that elimination of wheat and other sugar-equivalents deprives your body of glucose. Your body then needs to resort to fatty acid metabolism to generate energy. Apparently, some people are inefficient at this conversion, having subsisted on carbohydrates for the last few decades of their lives. However, as fatty acid metabolism kicks in, energy generation improves. That is my (over-)simplified way of reasoning it through.

However, are there other explanations behind the mental fogginess, drop in energy, and overwhelming sleepiness? Some readers of this blog have suggested that, since opioid-like sequences (i.e., amino acide sequences that activate opiate receptors) are present in wheat, perhaps withdrawal from wheat represents a lesser form of opiate withdrawal. I find this a fascinating possibility, though I know of no literature devoted to establishing a cause-effect relationship.

Whatever the mechanism, I find it very peculiar that this food widely touted by the USDA, American Heart Association, and other agencies actually triggers a withdrawal syndrome in approximately 25% of people. Spinach does not trigger withdrawal. Nor does flaxseed, olive oil, almonds, and countless other healthy foods.

Then why would whole wheat grains be lumped with other healthy foods?

Treat the patient, not the test

"Treat the patient, not the test."

That is a common "pearl" of medical wisdom often passed on during medical training.

It refers to the fact that we should always view any laboratory or imaging test in the context of the live, human patient and not just treat any unexpected value that doesn't seem to make sense.

I raise this issue because it recently came up on a discussion on the Track Your Plaque Forum. A Member with a high heart scan score of around 1100 was advised by his doctor that it should be ignored, because he'd prefer to treat the patient, not the test. The patient is apparently slender, physically active, and entirely without symptoms, with favorable cholesterol values as well. The high heart scan score didn't seem to jive with the appearance of the patient, as viewed by this doctor.

This common phrase is meant to impart wisdom. It is a reminder that we treat real people, not just a jumble of laboratory values.

But the unspoken part of the equation is that judgment needs to be applied. A well looking person who shows an unexpected rise in white blood cell count could just have a screwy result, or could have leukemia. Liver tests (AST, ALT) that top 400 could represent a fluke, or dehydration incurred during a long workout, or hepatitis from a long ago blood transfusion.

Yes, treat the patient. But don't be an idiot and entirely dismiss the signficance of an unexpected laboratory or imaging test. A heart scan score of 1100 should be as readily dismissed as discovering a white blood cell count of 90,000 (normal is less than 12,000), or a 5 cm mass in the lung. The absence of symptoms or the failure of conventional risk factors to suggest causation is insufficient reason to dismiss the concrete findings of a test.

In this particular person, dismissing the significance of the heart scan finding by suggesting that the doctor should treat the patient, not the test, is tantamount to:

--Colossal ignorance
--Malpractice
--A certain sentencing of the hapless patient to future major heart procedures, heart attack or death (20-25% likelihood every year, or a virtual certainty over the next 5 years).

There is an ounce of wisdom in this old medical pearl. But there's also plenty of room for a knuckleheaded doctor to misconstrue and abuse its meaning for the sake of covering up his/her ignorance, laziness, or lack of caring.

Does high cholesterol cause heart disease?

How often does someone develop coronary heart disease from high cholesterol alone?

Believe drug industry propaganda and you'd think that everyone does. Physicians have bought into this concept also, driving the $27 billion annual sales in statin cholesterol drugs.

In my experience, I can count the number of people who develop coronary disease from high cholesterol alone on one hand. It happens--but rarely.

That's not to say that cholesterol is not an issue. That rant populates many of the kook websites and conversations on the internet that argue that high cholesterol is a surrogate for some other health issue, or that it is part of a medical conspiracy.

The problem with conventional measurement of cholesterol is that it ignores the particle size issue: whether particles are large or small. Small LDL are flagrant causes of coronary atherosclerotic plaque. Large LDL is a rather meager cause. Simple cholesterol measurement also ignores the presence of other factors that lead to heart disease, like lipoprotein(a) and vitamin D deficiency.

Conventional total and LDL cholesterol do not distinguish between large and small particles, nor reveal the presence of other hidden patterns. An LDL cholesterol of 150 mg/dl, for instance, may contain 100% large LDL--a relatively good situation that by itself is unlikely to cause heart disease, or it might contain 100% small LDL--a very bad situation that is likely to cause heart disease. Just knowing that LDL is 150 mg/dl tells you almost nothing. In 2008, most people have some mixture of the two, particularly with the proliferation of "healthy whole grains" in the American diet, foods that trigger formation of small LDL.

The imprecision and uncertainty of conventional total and LDL cholesterol has provided ammunition for some to discount the entire cholesterol concept. And they are right to a degree: cholesterol by itself is indeed a lousy predictor of heart disease. But small LDL is a very reliable predictor of potential for heart disease. Dismissing the entire concept because the standard measurement stinks is not right, either.

It is therefore an unfortunate oversimplification to say that high cholesterol causes heart disease or that it doesn't. It can--but not always, depending on size and other factors. In my view, it is therefore irreponsible to treat total or LDL cholesterol without knowledge of particle size. I've seen this play out many times: Someone with an LDL cholesterol of 150 mg/dl but all large still gets prescribed a statin drug by his/her doctor. Or someone with an LDL of 100 mg/dl--generally "favorable" by most standards--is not treated but it is all small and the person is truly at high risk. (Also, knowledge that all LDL particles are small does not mean that statins are the preferred agent. In my view, they are not.)

Are humans meant to be omnivores?

Are humans meant to be omnivores?

Does the ideal human diet include animal products like meat, fish, cheese, eggs, and dairy products?

Or should the ideal diet be devoid of all animal products?a vegetarian diet?

Though the argument is distorted by modern food processing methods (e.g., factory farming, long-term administration of antibiotics), convenience foods, and pseudo-foods crafted by food manufacturers, there are, obviously, proponents of both extremes.

The Atkins’ diet, for instance, advocates unrestricted intake of animal products, regardless of production methods or curing (sausage and bacon). At the opposite extreme are diets like Ornish (Dr. Dean Ornish’s Program for Reversal of Heart Disease) and the experiences of Dr. Colin Campbell, articulated in his studies and book, The China Study, in which he lambasts animal products, including dairy, as triggers for cancer and heart disease.

So which end of the spectrum is correct? Or ideal?

For the sake of argument, let's put aside philosophical questions (like not wanting eat animal products because of aversion to killing any living being) or ethical concerns (inhumane treatment of farm animals, cruel slaughtering practices, etc.). Does the inclusion of animal products provide advantage? Disadvantage?

The traditional argument against animal products has been saturated fat. If we accept that we’ve demoted the saturated fat question to a place far down the list of importance (though this is yet another argument to discuss another time), several questions emerge:

• If humans were meant to be vegetarian, why do omega-3 fatty acids (mostly from wild game and fish) yield such substantial health benefits, including dramatic reduction in sudden death from heart disease?

• Why would vitamin K2 (from meats and milk, as well as fermented foods like natto and cheese), obtainable in only the tiniest amounts on a vegetarian diet, provide such significant benefits on bone and cardiovascular health?

• Why would vitamin B12 (from meats) be necessary to maintain a normal blood count, prevent anemia, keep homocysteine at bay, and lead to profound neurologic dysfunction when deficient?


Omega-3 fatty acids and vitamins K2 and B12 cannot be obtained in satisfactory quantities from a pure vegetarian diet. The consequences of deficiency are not measured in decades, but in a few years. The conclusion is unavoidable: Evolutionarily, humans are meant to consume at least some foods from animal sources.

That's not to say that we should gorge ourselves on animal products. Gout (excessive uric acid) and kidney stones are among the unhealthy consequences of excessive quantities of meats in our diets.

It pains me to say this, since I’ve always favored a vegetarian lifestyle, mostly because of philosophical concerns, as well as worries about the safety of our factory farm-raised livestock and rampant inhumane practices.

But, stepping back and objectively examining what nutritional approach appears to stack the odds in favor of optimal health, I believe that only one conclusion is possible: Humans are meant to be omnivorous, meant to consume some quantity of animal products in addition to vegetables, fruits, nuts, and other non-animal products.

The question is how much?

Are you wheat-free?

According to the recent Heart Scan Blog poll, Are you wheat-free?, the 173 respondents said:

Yes, I am free of wheat products.
87 (50%)

No, I include wheat products in my diet.
73 (42%)

I'm not sure.
1 (0%)

I think you're nuts.
12 (6%)


That's kind of what I expected.

There are people who have eliminated wheat and experienced nothing except a feeling of deprivation. These people are in the minority. Though the poll was not set up to reflect this (i.e., asked who tried it and experienced no perceptible benefit), in my experience, this applies to about 20% of people. Little happens with elimination of wheat beyond modest weight loss. Those are the people who generally think I'm nuts.

Or, these people may have been brainwashed by "official" agencies like the USDA, the American Diabetes Association, and American Heart Association and the constant marketing of (high markup) grain products like Cheerios and Shredded Wheat . Some people are really uncomfortable going against the "grain" of popular public opinion.

Then there are the people who try to eliminate wheat and fail. They can't deal with the overwhelming fatigue, mental fog, and moodiness that comes with withdrawal from wheat, the phenomenon of converting from a sugar-burning metabolism to a fat-burning metabolism. Although wheat withdrawal usually runs its course in 2-5 days, some people find it intolerable. (That would be another fun poll to run: Have you experienced wheat-withdrawal?) Occasionally, the withdrawal is replaced by endless cravings, a phenomenon that applies to only about 10% of people. These are the true "wheat addicts." These are the people who eliminate wheat, lose 40 lbs, then regain it when they have one cracker and the floodgates of impulse control crumble.

Then there are the majority, 50% in the poll, though more like 70% in my face-to-face experience. Why is my experience skewed? Well, the people I deal with every day come because of coronary disease in some form (abnormal heart scan score, for instance) or because of lipid or lipoprotein abnormalities. So my experienced is skewed towards people who are likely to have something abnormal, such as high triglycerides or small LDL particles, both of which are created by including wheat in the diet.

This last group also shows unexpected effects of wheat elimination: substantial weight loss, dramatic reductions in blood sugar and triglycerides, increase in HDL, reductions in small LDL, reduction in c-reactive protein and other inflammatory measures. Appetite shrinks considerably. Not uncommonly, improved well-being, reduction in bowel complaints like cramping or "irritable bowel syndrome" is experienced, some rashes clear, occasionally arthritis will improve. See below for some of the testimonials to this experience.

When I first set out to advise people to eliminate wheat, I did it because I reasoned that it would be a quick and simple way to get people to reduce blood sugars and help correct the ubiquitous metabolic syndrome that afflicts nearly 50 million Americans now. And it did indeed accomplish that simple goal. But I did not expect all the other benefits to develop, the dramatic weight loss, improved well-being, reduction in hunger, etc.

I view wheat elimination as an easy-to-remember, digestible way to obtain enormous health benefits in a coronary plaque-control program, one that works for most--but not all--people. And I relate this experience not to sell you something, but to simply relate what I see as the truth, a way that is contrary to conventional advice yet works enormously well.



Unsolicited testimonials of people who have successfully been wheat-free:

Barbara W said:

It's true! We've done it. My husband and I stopped eating all grains and sugar in February. At this point, we really don't miss them any more. It was a huge change, but it's worth the effort. I've lost over 20 pounds (10 to go)and my husband has lost 45 pounds (20 to go). On top of it, our body shapes have changed drastically. It is really amazing. I've got my waist back (and a whole wardrobe of clothes) - I'm thrilled.

I'm also very happy to be eating foods that I always loved like eggs, avocados, and meats - without feeling guilty that they're not good for me.

With the extremely hot weather this week in our area, we thought we'd "treat" ourselves to small ice cream cones. To our surprise, it wasn't that much of a treat. Didn't even taste as good as we'd anticipated. I know I would have been much more satisfied with a snack of smoked salmon with fresh dill, capers, chopped onion and drizzled with lemon juice.

Aside from weight changes, we both feel so much better in general - feel much more alert and move around with much greater flexibility, sleep well, never have any indigestion. We're really enjoying this. It's like feeling younger.

It's not a diet for us. This will be the way we eat from now on. Actually, we think our food has become more interesting and varied since giving up all the "white stuff". I guess we felt compelled to get a little more creative.

Eating out (or at other peoples' places) has probably been the hardest part of this adjustment. But now we're getting pretty comfortable saying what we won't eat. I'm starting to enjoy the reactions it produces.


Weight loss, increased energy, less abdominal bloating, better sleep--I've seen it many times, as well.


Dotslady said:

I was a victim of the '80s lowfat diet craze - doc told me I was obese, gave me the Standard American Diet and said to watch my fat (I'm not a big meat eater, didn't like mayo ... couldn't figure out where my fat was coming from! maybe the fries - I will admit I liked fries). I looked to the USDA food pyramid and to increase my fiber for the constipation I was experiencing. Bread with 3 grams of fiber wasn't good enough; I turned to Kashi cereals for 11 years. My constipation turned to steattorrhea and a celiac disease diagnosis! *No gut pains!* My PCP sent me to the gastroenterologist for a colonscopy because my ferritin was a 5 (20 is low range). Good thing I googled around and asked him to do an endoscopy or I'd be a zombie by now.

My symptoms were depression & anxiety, eczema, GERD, hypothyroidism, mild dizziness, tripping, Alzheimer's-like memory problems, insomnia, heart palpitations, fibromyalgia, worsening eyesight, mild cardiomyopathy, to name a few.

After six months gluten-free, I asked my gastroenterologist about feeling full early ... he said he didn't know what I was talking about! *shrug*

But *I* knew -- it was the gluten/starches! My satiety level has totally changed, and for the first time in my life I feel NORMAL!



Feeling satisfied with less is a prominent effect in my experience, too. You need to eat less, you're driven to snack less, less likely to give in to those evil little bedtime or middle-of-the-night impulses that make you feel ashamed and guilty.



An anonymous (female) commenter said:

My life changed when I cut not only all wheat, but all grains from my diet.

For the first time in my life, I was no longer hungry -no hunger pangs between meals; no overwhelming desire to snack. Now I eat at mealtimes without even thinking about food in between.

I've dropped 70 pounds, effortlessly, come off high blood pressure meds and control my blood sugar without medication.

I don't know whether it was just the elimination of grain, especially wheat, or whether it was a combination of grain elimnation along with a number of other changes, but I do know that mere reduction of grain consumption still left me hungry. It wasn't until I elimnated it that the overwhelming redution in appetite kicked in.

As a former wheat-addicted vegetarian, who thought she was eating healthily according to all the expert advice out there at the time, I can only shake my head at how mistaken I was.




Stan said:

It's worth it and you won't look back!

Many things will improve, not just weight reduction: you will think clearer, your reflexes will improve, your breathing rate will go down, your blood pressure will normalize. You will never or rarely have a fever or viral infections like cold or flu. You will become more resistant to cold temperature and you will rarely feel tired, ever!



Ortcloud said:

Whenever I go out to breakfast I look around and I am in shock at what people eat for breakfast. Big stack of pancakes, fruit, fruit juice syrup, just like you said. This is not breakfast, this is dessert ! It has the same sugar and nutrition as a birthday cake, would anyone think cake is ok for breakfast ? No, but that is exactly the equivalent of what they are eating. Somehow we have been duped to think this is ok. For me, I typically eat an omelette when I go out, low carb and no sugar. I dont eat wheat but invariably it comes with the meal and I try to tell the waitress no thanks, they are stunned. They try to push some other type of wheat or sugar product on me instead, finally I have to tell them I dont eat wheat and they are doubly stunned. They cant comprehend it. We have a long way to go in terms of re-education.

Yes. Don't be surprised at the incomprehension, the rolled eyes, even the anger that can sometimes result. Imagine that told you that the food you've come to rely on and love is killing you!



Anne said:

I was overweight by only about 15lbs and I was having pitting edema in my legs and shortness of breath. My cardiologist and I were discussing the possible need of an angiogram. I was three years out from heart bypass surgery.

Before we could schedule the procedure, I tested positive for gluten sensitivity through www.enterolab.com. I eliminated not only wheat but also barley and rye and oats(very contaminated with wheat) from my diet. Within a few weeks my edema was gone, my energy was up and I was no longer short of breath. I lost about 10 lbs. The main reason I gave up gluten was to see if I could stop the progression of my peripheral neuropathy. Getting off wheat and other gluten grains has given me back my life. I have been gluten free for 4 years and feel younger than I have in many years.

There are many gluten free processed foods, but I have found I feel my best when I stick with whole foods.



Ann has a different reason (gluten enteropathy, or celiac disease) for wanting to be wheat-free. But I've seen similar improvements that go beyond just relief of the symptoms attributable to the inflammatory intestinal effects of gluten elimination.



Wccaguy said:

I have relatively successfully cut carbs and grains from my diet thus far.

Because I've got some weight to lose, I have tried to keep the carb count low and I've lost 15 pounds since then.

I have also been very surprised at the significant reduction in my appetite. I've read about the experience of others with regard to appetite reduction and couldn't really imagine that it could happen for me too. But it has.

A few weeks ago, I attended a party catered by one of my favorite italian restaurants and got myself offtrack for two days. Then it took me a couple of days to get back on track because my appetite returned.

Check out Jimmy Moore's website for lots of ideas about variations of foods to try. The latest thing I picked up from Jimmy is the good old-fashioned hard boiled egg. Two or three eggs with some spicy hot sauce for breakfast and a handful of almonds mid-morning plus a couple glasses of water and I'm good for the morning no problem.

I find myself thinking about lunch not because I'm really hungry but out of habit.

The cool thing too now is that the more I do this, the more I'm just not tempted much to do anything but this diet.

No more canned foods

If you haven't already caught the news, it's time to eliminate canned foods and exposure to plastics that contain the chemical, bisphenol A (BPA). A worrisome and unexpected association with heart disease and diabetes has been found.

This issue has been debated for some years ever since scientists at the NIH detected BPA in the blood samples of 93-95% of Americans, with consumer protection advocates calling for more research or even the outright banning of BPA , while industry representatives have argued that the data fail to conclusively prove adverse health effects.

Well, the argument has been tilted heavily in favor of increased consumer protection with the publication of a study in the Journal of the American Medical Association by Dr. Iain Lang and associates at the University of Exeter, UK, and the University of Iowa. Their study, released Sept. 17, 2008, Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults, persuasively demonstrated a 40% increased incidence of coronary heart disease, heart attack, and diabetes with increasing exposure to BPA (as judged by urine levels) among the nearly 1500 adults aged 18-74 years. People with coronary heart disease had double the blood level of BPA compared to those without.

In addition, higher urine levels of BPA were associated with abnormalities of two liver tests, GGT and alkaline phosphatase.

Interestingly, although much of the debate over adverse health effects of BPA have centered around concern over cancer and reproductive risks, an association with cancer did not hold. (No analysis for reproductive issues was conducted in these adults, since most of the concern is for children exposed through polycarbonate baby bottle use. Some BPA critics have raised questions like low birth weight developing from exposure.) No relationship to thyroid disease was identified, also.

The editorial accompanying the study added some sharp commentary:

"Subsequent to an unexpected observation in 1997, numerous laboratory animal studies have identified low-dose drug-like effects of BPA at levels less than the dose used by the US Food and Drug Administration and the Environmental Protection Agency to estimate the current human acceptable daily intake dose (ADI) deemed safe for humans. These studies have shown adverse effects of BPA on the brain, reproductive system, and--most relevant to the findings of Lang et al--metabolic processes, including alterations in insulin homeostasis and liver enzymes. . . For example, when adults rats were fed a 0.2 microgram/kg per day dose of BPA for 1 month (a dose 250 times lower than the current ADI), BPA significantly decreased the activities of antioxidant enzymes and increased lipid peroxidation, thereby increasing oxidative stress. When adult mice were administered a 10 microgram/kg dose of BPA once a day for 2 days ( a dose 5 times lower than the ADI), BPA stimulated pancreatic beta cells to release insulin."

This study, piled on top of the worrisome literature that precede it, are enough for me: No more tin cans (which are lined with BPA), no more hard plastics labeled with recycling code #7 or #3, no more polycarbonate water bottles (the hard ones, often brightly colored). Microwaveable-safe may also mean human-unsafe, as highlighted by this damning assurance from the Tupperware people that BPA is not a health hazard.

The National Toxicology Program also issued these advice in response to the Lang study to reduce BPA exposure (reported by the Washington Post) :

· Don't microwave polycarbonate plastic food containers. Polycarbonate may break down from overuse at high temperatures and release BPA. (Manufacturers are not required to disclose whether an item contains BPA, but polycarbonate containers that do usually have a No. 7 on the bottom.)

· Reduce use of canned foods, especially acidic foods such as tomatoes that can accelerate leaching of BPA from plastic can linings. Opt for soups, vegetables and other items packaged in cardboard "brick" cartons, made of safer layers of aluminum and polyethylene plastic (labeled No. 2).

· Switch to glass, porcelain or stainless-steel containers, particularly for hot food or liquids.

· Use baby bottles that are BPA-free; in the past year, most major manufacturers have developed bottles made without BPA.
Small LDL particles and increased HbA1c--An evil duo

Small LDL particles and increased HbA1c--An evil duo

Small LDL particles are triggered by consumption of carbohydrates. Eat more "healthy whole grains," for instance, and small LDL particles skyrocket.

Increased hemoglobin A1c, HbA1c, a reflection of the last 60-90 days' blood sugars, is likewise a reflection of carbohydrate consumption. The greater the carbohydrate consumption and/or carbohydrate intolerance, the greater the HbA1c. Most regard a HbA1c of 6.5% or greater diabetes; values of 5.7-6.4% pre-diabetes. However, note that any value of 5.0% or more signifies that the process of glycation is occurring at a faster than normal rate. Recall that endogenous glycation, i.e., glucose modification of proteins, ensues whenever blood sugars increase over the normal range of 90 mg/dl (equivalent to HbA1c of 4.7-5.0%). Glycation is the fundamental process that leads to cataracts, arthritis, and atherosclerosis.

Put the two together--increased quantity of small LDL particles along with HbA1c of 5.0% or higher--and you have a powerful formula for heart disease and coronary plaque growth. This is because small LDL particles are not just smaller; they also have a unique conformation that exposes a (lysine residue-bearing) portion of the apoprotein B molecule contained within that makes small LDL particles uniquely glycation-prone. Compared to large LDL particles, small LDL particles are 8-fold more prone to glycation.

So glycated small LDL particles are present when HbA1c is increased above 5.0%. Small, glycated LDL particles are poorly recognized by the liver receptor that ordinarily picks up and disposes LDL particles, unlike large LDL particles, meaning small LDL particles "live" much longer in the bloodstream, providing more opportunityt to do its evil handiwork. Curiously, small LDL particles are avidly taken up by inflammatory white blood cells that can live in the walls of arteries, where they are oxidized--"glycoxidized"--and add to coronary atherosclerotic plaque.

The key is therefore to tackle both small LDL particles and HbA1c.

Comments (53) -

  • Linda

    10/30/2011 4:00:13 PM |

    What do you consider to be ideal cholesterol readings? I am about to visit a new doctor, a D.O., and I am sure she is going to insist on blood tests for cholesterol plus stress testing, etc. My thyroid TSH was 2.70, but she is already showing reluctance to prescribe any thyroid meds. It is going to be a battle.

  • John Lorscheider

    10/30/2011 4:32:57 PM |

    And it is not just about the wheat either.  It’s all carbs.  Fructose, oats, rice, pasta, potatoes and certain fruits, etc. all drive up HbA1c and small LDL.  Just for a reality check I bought a can of and made a bowl of “properly prepared” Scottish oatmeal yesterday according to Nourishing Traditions.  Those are the minimally processed chewy steel cut oats soaked with warm water and kefir overnight and served with butter and cream.  Yeah, they were good alright, but my fasting BG was 88 and one-hour PP was 158.  A fast 5-mile run and it was back down to 84.  The container is in the garbage can now.  This morning was two pasture raised eggs and bacon with ½ cup of blueberries and Greek yogurt.  Fasting BG 89 and one-hour PP was 88.  My HbA1c went from 5.8 to 5.1 in less than a year and hope to get below 5.0 soon.  The stubborn small LDL percentage dropped during same time period but still have a way to go in that regard.

  • Buddy

    10/30/2011 8:12:20 PM |

    I'm not completely sold on HbA1C < 6.0% being a useful metric for anything but populations.  The problem is that the current HbA1C tests do not control for erythrocyte age and I see wide variations among piers on simialr  grain free lowish carb healthy diets.

    There has been much more research on this effect as it pertains to diabetics that have falsely low HbA1c:  http://www.ncbi.nlm.nih.gov/pubmed/9773739
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581997/

    There is some evidence out there that it works the other way as well, and it makes intuitive sense that the lower inflammation and oxidation associated  with a healthy diet would increase erythrocyte longevity.

    Of course observational studies about any topic (small LDL or HbA1c) are always to be taken with a grain of salt.

  • Rosanne

    10/30/2011 8:30:42 PM |

    I wonder if you have ever experienced with any of you patients  what is going on with my husband?  He has very few small LDL particles, at least according to a VAP test - he is type A with lots of large, fluffy LDL.  But his HbA1c is 6.1.  His fasting glucose is 80, 1 hour post-prandial it's 1685, triglycerides are 60.  This is all on a grain-free, very low-carb Paleo diet.  Do you have any clue what is causing the HbA1c to be elevated?  Could it be anything besides carbs?  He gets lots of exercise and is very fit and lean.  

    Some have suggested that too much protein can also cause elevated HbA1c, due to gluconeogenisis causing higher levels of glucose.  But why would the body make more glucose than it needs?  And why would that excess glucose not show up in his fasting and post-prandial glucose numbers?

    Is there any other factor, besides blood glucose, that can contribute to elevated HbA1c?  No doctor yet has been able to answer this question for us.

  • Rosanne

    10/30/2011 8:32:55 PM |

    Sorry for the typo, his 1 hour post-prandial glucose is 85.

  • Dr. William Davis

    10/30/2011 9:08:02 PM |

    The most common explanation, Rosanne, is that the HbA1c can stay high long after blood sugars have come under control.

    It may be due to the extended longevity of RBCs that occurs in the setting of low-carbohydrate diets that allow a previously high HbA1c to stay high for an extended period.

    There's also the possibility of a hemoglobin variant that allows this.

    I would put more stock in the blood glucose values by fingerstick than the HbA1c.

  • arlene

    10/31/2011 12:42:56 AM |

    Thank you for explaining this.  I just had my blood work done for the first time since quitting wheat and going low carb in April.  Since I've lost a lot of weight, and a lot on my waist, I am very curious to see what my numbers are.  This will help me compare the important stats.  What is an ideal HbA1c?

  • pjnoir

    10/31/2011 7:37:40 PM |

    I can't go near oatmeal, steel cut or any other type.  Its just eggs and avocados for breakfast these days with a lot of Asparagus in the spring with my yolks.  Oatmeal has been banished for good.

  • Bob Sparkes

    10/31/2011 10:46:27 PM |

    Your article discuses how the combination of small LDL particles  and high blood sugar
    results in plaque. Is the article cited below  by University of Washington at St. Louis useful here? The article points out the role of low Vitamin D in plaque formation with LDL  and high blood sugar. Or am I confusing two separate mechanisms in plaque formation.

    http://news.wustl.edu/news/Pages/14489.aspx

  • Dr. William Davis

    11/1/2011 2:01:29 AM |

    Hi, Bob--

    Yes, I believe it is two unrelated mechanisms. However, this is a fascinating finding to tell us why people do so well from a heart standpoint when we correct vitamin D deficiency.

  • learn chinese

    11/1/2011 4:05:55 AM |

    Thank you for explaining the topic. i learn more about Small LDL. great post.

  • Jeanne

    11/1/2011 5:36:29 AM |

    Dr. D,  
    Can this be related to the lysine- arginine balance in the body? Would taking arginine supplements affect the amount of lysine residue causing problems in any way?  Just thinking out loud ...

    Thanks!

    Jeanne

  • Amit

    11/1/2011 8:01:31 AM |

    HI Doctor Davis,

    I know its not the right place, but I could not find your email.

    I read "wheat belly", it was revolutionary for me,  and I am persuaded it can bring much relieve to many ailments.

    I also wrote several posts about this issue on my health blog (in Hebrew)  based on your book and your Blog.

    Thank you for the great service you are offering in your work!

    Amit.
    Israel.

  • Janis

    11/1/2011 2:40:01 PM |

    Hello Dr. Davis,
    I'm new to your blog. Just finished reading Wheat Belly. Excellent book! I also listened to the podcast with Robb Wolf. That's how I heard about you. Not to get off topic (didn't know how else to contact you) and this is probably a silly question, but would like clarification if you could help. I've been purchasing the 85% Lindt chocolate bars until you mentioned that you eat the 90%. I read the label and it said that it is pressed with alkali. You mentioned to avoid this process as it removes the healthful flavonoids. By saying "pressed" is that a different process? The chocolate was very good, but I want to make sure I'm getting the healthful flavonoids, especially when we don't eat too many sweets. Thank you so much for your time.

  • Might-o'chondri-AL

    11/1/2011 6:44:50 PM |

    Hi Dr.,
    I am confused how to  reconcile  HbA1c details  from J Am Coll Nutrition 2005, Vol.24(1):22-29
    "Dietary Carbohydrate and Glycated Protein in the Blood in Non-Diabetic Subjects"
    http://www.jacn.org/content/24/1/22.full
    (and their relevant references no. 10 -  19 & 34-39 )

  • Rosanne

    11/1/2011 7:15:17 PM |

    This has been going on for 2 1/2 years and in fact, the longer he has been low-carb Paleo, the higher the HbA1c has gotten.  When he started, it was 5.5 and has slowly
    crept up to the 6.1 reading.
    Thanks for the mention of the hemoglobin variant, I guess that's must be it.  Can we stop worrying about the HbA1c since his glucose values are so good?

  • STG

    11/1/2011 7:34:13 PM |

    Dr. Davis:
    What do you you think of Jenny Ruhl's advocacy of the 5% club at Blood Sugar 101? Your guidelines appear to be more aligned with Dr. Bernstein's and Dr. Ron Rosedale's? Do you think that all individuals ( including prediabetics, daibetics and glucose intolerant ) should strive for a HbA1c below 5%?

  • Dr. William Davis

    11/2/2011 1:36:45 AM |

    HI, STG--

    That is precisely what I aim for, also: HbA1c of 5.0% or less. At that level, metabolic consequences of blood sugar essentially disappear. This is, of course, at variance with conventional guidelines.

  • Dr. William Davis

    11/2/2011 1:37:19 AM |

    That would be my vote. Ask your doctor, also, about fructosamine, another sugar markers.

  • Dr. William Davis

    11/2/2011 1:39:24 AM |

    Hi, Might--

    Were you referring to their conclusion about polyunsaturates?

  • Dr. William Davis

    11/2/2011 1:42:08 AM |

    My bar says "processed" so, yes, the flavonoid content can be expected to be reduced in this bar. The best way to get a full dose of cocoa flavonoids is in undutched cocoa powder.

    I still think you can enjoy your dark chocolate, but you just might not expect full benefit from this particular bar.

  • Dr. William Davis

    11/2/2011 1:44:08 AM |

    Thank you, Amit!

    What is the wheat situation in Israel? Is it pushed there as much as it is here by official agencies and food companies?

  • Dr. William Davis

    11/2/2011 1:44:43 AM |

    Sorry, Jeanne, I don't believe the answer is known.

  • Might-o'chondri-AL

    11/2/2011 3:35:43 AM |

    Hi Dr. D.,
    Authors in this report say glycated protein & HbA1c do not interact  with blood glucose in same way (ref #17) and that it is glycated albumen rather than glycated hemoglobin that is very senstitve to blood glucose levels (ref # 18,19); especially since 60% HgA1c is genetic (ref #61).
    AGE (advance glycation endproducts) they say is more indicated by fructosamine level from high blood glucose. Although diabetics with high fructosamine also have high HbA1c. whereas for a non-diabetic  high fructosamine does not relate to their HbA1c level (ref#16).
    This impies that (since most obese individuals never will become diabetic &  longevity/cognitive function of the overweight is good) a lot of the risk factor of small LDL with HbA1c depends on genetics/ epigenetics.
    My confusion is if your insistence on HbA1c for non-diabetics is misdirected or just due to it being a common first test people can do.

  • Amit

    11/2/2011 5:15:45 AM |

    Wheat is the most common carbohydrate in Israel. It is eaten almost every meal. I think that the largest source of calories is wheat.

    Regarding Diabetes there is no awareness that whole wheat is especially bad for such patients. Diabetes association (and many more) do recommend whole wheat. Although they are suggesting to avoid eating large quantity of bread at once.

    Wheat is being pushed, though, I don't think that somebody here is pushing wheat deliberately, just coping recommendation from abroad, and using the most cheap and easy carbohydrate.

    Amit.

  • Nora

    11/2/2011 12:10:50 PM |

    I have been on my Wheat Bellies journey for 8  weeks now.  I am trying to follow your suggestions on heart health and I know that you have your plate full right now, but just a request.  Have you ever thought of doing healthy heart retreats?  I would love to have a chance to go away for a long weekend, have all my blood work done right, have it evaluated, talk to a doctor and then maybe have a few cooking classes.  Throw in a few yoga classes or walks for stress reduction and you have a whole picture!!  

    I have high blood pressure that is 'controlled' to some degree with Tekturna (150mg) and Amlodipine (10mg). This morning it was 150/90, so it is often not very controlled. Since 9/1 and going wheat free, I have lost 23 pounds but still have 50 to lose.  My take away from your writings is that plaque is the  main cause of heart disease and that keeping a low blood glucose level is the best strategy, but there is not much about  high blood pressure in your work.  What role does it play and will being a wheat free low carber offer me relief from my high blood pressure?  Or will it stay high since I have a family history of high blood pressure and therefore will probably have to continue on my meds.  While I, of course, am doing everything in my power to lower my blood pressure, is it not really a number I should focus on when trying to control my heart health?

  • Renfrew

    11/2/2011 9:08:47 PM |

    Hi Doc,
    have you seen this? You are prominently featured here:
    http://www.lef.org/news/LefDailyNews.htm?NewsID=11842&Section=Nutrition
    Great summary!

  • marta

    11/4/2011 9:48:08 AM |

    Are you going to translate his books into Spanish some day?
    I'm very interested in reading them. thanks

  • Dr. William Davis

    11/4/2011 12:48:56 PM |

    Hi, Marta--

    There has been interest specifically in Wheat Belly for translations. Spanish is at the top of the list.

    When that happens, I will announce here and elsewhere. Thanks for asking.

  • Dr. William Davis

    11/4/2011 12:50:33 PM |

    Thanks, Renfrew!

    Life Extension has been an important supporter of my efforts and vice versa.

  • Dr. William Davis

    11/4/2011 12:53:43 PM |

    Hi, Nora--

    Excellent suggestion on the heart health retreats. I've thought a lot about it and will likely do it in future. Just not quite sure about the details. One hurdle: Few people want to fly to Milwaukee, so we'd have to find an exotic or interesting, probably warm, place to do it.

    Hypertension is indeed a big issue. It is also among the last things to respond to weight loss and diet, often lagging behind many months after weight loss. So it really pays to be patient while you are on this health journey. Given your family history, you still might be left with hypertension, but at least you will have minimized it.

  • Dr. William Davis

    11/4/2011 12:54:43 PM |

    Thanks, Amit.

    By the way, all anyone has to do is check a fingerstick blood sugar 1-hour after consuming anything wheat to observe the astounding blood sugar consequences of wheat consumption.

  • Dr. William Davis

    11/4/2011 12:58:54 PM |

    Hmmm. I'm sorry if I'm being dense, Might, but I'm still not sure I follow.

    I'm not actually advocating anything except to show how glycated small LDL is a really bad player. When viewed from multiple different directions, small LDL particles are looking worse and worse. In this instance, having any measure of glycation phenomena, whether fructosamine, glycated albumin, or glycated hemoglobin, suggests that small LDL particles are also being glycated and thereby gaining heightened atherogenic potential.

  • Sally

    11/4/2011 2:02:44 PM |

    Dear Dr. Davis,

    I am reading your book Wheat Belly and want to thank you so much for writing this book.

    I've avoided gluten for years.  Arthritis and other annoying symptoms vanished...but I started gaining weight!   My blood sugar starting rising!   I couldn't understand it!  It was horrifying!  Well thanks to you, I realize that gluten free breads, candies, flours,  frozen pizzas, pastas and those gluten free "tv dinners" sold at Whole Foods did nothing to help my waist line or blood sugar.  I am now following the wonderfully easy plan in your book and am confident the weight will come off.

    Thank you for such terrific recipes.  Will you be writing an accompanying Wheat Belly cookbook as well?  I certainly hope so.  Please do!   If not, can you recommend some cookbooks that comply with your eating instructions?

    Thanks again for such a life changing book.  Sally

  • HS4

    11/4/2011 9:09:05 PM |

    There are a few people in Israel trying to enlighten others about the dangers of wheat and other 'modern' carbs.  My sister is one of them, has been trying to think of ways to get some essays to the public.  But what Amit says is correct - a lot of wheat is eaten there, many people buy small breads  rolls daily - it's very fresh, delicious, so it will be a tough thing to stop. Many of the best restaurants in Israel serve Arabic food which always comes with freshly baked loaves of pita.  The 'national snack' is pita stuffed with falafel (fried balls of ground chickpeas, onions, garlic and spices), fresh & pickled vegetablesj, hummus and/or tehina sauce. This is available everywhere and always fresh.  Becasue the food is generally very good in Israel and also very fresh it's hard to avoid wheat, which I've noticed every time I visit.

  • palo

    11/5/2011 5:07:43 PM |

    Dr. Davis, the evidence speaks for itself that consumption of carbohydrates, increase small LDL, suggesting an LC diet of less than 50 grams to mitigate the damage.
    But what about endurance athletes (runners, cyclists, triathletes etc.) that work out one and a half to three hours per day and consume copious amounts of carbohydrate to fuel their long workouts.
    Is the exercise neutralizing the carbohydrates' harmful effects? If so, can you suggest a dosage for certain amount of exercise?

  • Might-o'chondri-AL

    11/6/2011 8:26:57 PM |

    Hi Dr. Davis,
    Non-diabetics just seem to have one feature going for them - their platelets don't respond the same as diabetics. I am inclined to think that albumin in our blood is more relevant than the hemoglobin being glycated . (This is not to criticize your preventative approach , since Type II diabetes can go on to develop &  I like what you are teaching us about small LDL.)

    " One common qualitative change in plasma albumin is nonenzymatic glycosylation, which occurs during states of prolonged hyperglycemia....Platelet aggregation ...is enhanced in the presence of albumin that has been incubated in a medium containing levels of glucose that are higher than would be seen in normal patients but are consistent with those seen in diabetics....(Journal of Parenteral and Enteral Nutrition 18:516-520, 1994)

    Once the glycation of albumin fosters more platelet aggregation in diabetics (& the insulin resistant person!) their platelets show more secretion and adhesion leading to the vascular plaque build up that the insidious small LDL can get into. Yet, for the non-diabetic the +/- 570 insulin receptors on each platelet normally respond differently to their insulin exposure.

    Specifically (in non-diabetics) the insulin actually stymies the platelet from becoming "activated" and probably explains how it is that not everyone who eats carbohydrates suffers cardio-vascular insults. Of course there are non-diabetics with genetic variants that adversely affect their plaque dynamics (ex: defect in insulin receptor signalling, that receptor's Beta subunit, G-protein pathways).

    ( For the techno-nerds: proper insulin receptor response on platelet keeps  platelet cAMP level from dropping & so no endoplasmic reticulum calcium floods out into platelet cell cytosol, platelet granule doesn't secrete ATP, platelet alpha-granule doesn't secrete P-selectin & there isn't mitogen-activated signalling to make thromboxane A2 , etc.  Basically, in the diabetic/insulin resistant these processes go forward uninhibited by normal insulin signalling & their circulating platelets don't keep rolling along suspended in the bloodstream .)

  • Adam

    11/7/2011 5:27:55 PM |

    Omega 3 Fish Oil BAD NEWS for Apoe 4/3!!!  

    Ok Dr. Davis, I really need your advice on this one.   In following TYP, I have been taking 3200 mg day EPA/DHA fish oil 1.4:1 ratio.   Recent testing shows I have gotten my HS Omega 3 Index to 9.5,  and my Omega 6 to Omega 3 ratio to 2:9  so this pretty good.   Now for the bad news....ever since I started taking 3200 mg day fish oil...over a 2 month period my HDL went from 48 to 38, a whopping 20% reduction in the critically important good HDL that I need to remove plaque.  I exercise extensively, and I also take 10mg day crestor (crestor is one of the few statins that's supposed to raise HDL not lower it). Now,  I have heard from several sources that Fish Oil (more than 1000 mg day) supplements are actually BAD for Apoe4/3 people because it lowers HDL.  So now I am confused Dr. Davis.....do I follow your TYP advise and stay on 3200 mg day fish oil in order to keep a close to 10 HS Omega 3 Index....but suffer lower HDL and less plaque removal/reversal....or do I stop the Fish oil in order to raise my HDL  but suffer the risks of little to no fish oil??

    Please advise...

    An extremely confused Apoe 4/3

  • Might-o'chondri-AL

    11/7/2011 11:02:03 PM |

    Hi Adam,
    HDL drop can be due to accelerated small HDL's  breakdown/clearance & if that was mostly lingering small HDL then it didn't have much reverse cholesterol transport function left in it anyway. If total HDL drops but small HDL turnover is  now more optimal &/or if it is a greater % of the large HDL then there is better reverse cholesterol transport dynamic despite the total HDL drop.

    ApoE has 299 distinct amino acid positions & the difference between the 3 types are due to which amino acid is in positions 112 & 158 ( respectively ApoE4 @112=arginine & @158 =arginine, ApoE3 @112=cysteine & @158=arginine, ApoE2 @112=cysteine & @158=cysteine). Because ApoE4 has arginine at position 112 this then orientates facing away from the standard grouping of 4 helix at that N-terminal to more closely cozy up to the alpha-helix of the C-terminal that in ApoE naturally overlays the N-terminal. Thus ApoE4 can uniquely feature a "salt bridge" to that C-terminal that affects how ApoE unfolds/functions when ApoE goes to work.
    ApoE's manner of unfolding at it's N-terminal  is crucial to how it deals with lipids, phospholipids (ex: cell membranes)and  proteoglycans on a cell surface. Fish oil alters cell membrane phospholipid composition and then the proteoglycans there must suitably interact with that EPA enriched type of cell surface. Since each ApoE's C-terminal presents an interface that challenges  how that ApoE  works at any target cell the  peculiar ApoE4 "salt bridge" uniquely conditions the way interactions play out. (And each of the separate 3 classic types of ApoE  can get mutations, mostly at positions 136-150, to complicate degree of LDL receptor interaction, etc.)

  • James Buch

    11/8/2011 3:14:01 PM |

    Dear Doctor Davis,

    I am wondering if you can clarify the "oxidized LDL Cholesterol" concept.  Including, of course the Small LDL as well.

    I began wondering if the oxidation is primarily in the package, the LDL wrap, the signaling protein, or the internal body of cholesterol itself. Of course, all of the above is also a possibility.

    The nature of the oxidation could be a good clue as to how it is especially detrimental to health, and so far, I haven't found much easily available on the mechanisms of the detrimental effects. While it is useful to know the harmful nature of oxidized small LDL, some insight into the mechanism of harmful effects would be welcome and minimize the nagging question of "Why" for me.

  • josef

    11/8/2011 5:07:20 PM |

    This might be of interest:

    A large study called the STRRIDE trial looked at the effects of different intensities and volumes of exercise on LDL particle size in sedentary, overweight men and women over eight months [3].  Group A performed 176 minutes of low intensity exercise (walking) per week.  Group B performed 117 minutes per week at a moderate to high intensity (jogging, cycling, or using an elliptical machine).  Group C exercised about the same amount of weekly time as group A, but at the same intensity as group B.  

    As one would likely guess, group C showed the biggest improvement in changing LDLs from small and dense to large and buoyant.  However, a more telling sign was that group B had a stronger effect than group A, despite exercising an hour less per week.  In other words, intensity is more important for improving LDL particle size than volume of exercise.

    A follow-up of the subjects in this study showed some discouraging and encouraging effects on the particle size changes [4].  The discouraging news was that five days of inactivity following the study almost completely attenuated the particle size benefits from the trial.  However, before you start labeling exercise as futile, consider this: while five days of rest basically brought the exercise groups back to baseline LDL particle sizes, they were still much better off than the sedentary control group, who experienced significant digressions in particle size during the course of this study

  • Might-o'chondri-AL

    11/8/2011 7:18:31 PM |

    Hi James Buch,
    The enzyme hepatic lipase's (HL) lipolytic hydrolysis of the phospho-lipids on the LDL surface changes it so that LDL's load of cholesterol esters can get taken out; this reduces the molecule's volume and thus is then small LDL (smLDL). Men have more HL than women, until they go through  menopause, and this propensity toward smLDL ( that can get oxidized) may explain male's earlier tendency of coronary artery disease. Visceral/central obesity trends to upregulate HL & it seems visceral obesity affects men more than women (of course central obesity in both women & men will raise both  genders'  HL enzyme levels). What decreases HL levels are things like calorie restriction & aerobic exercise (sedentary life increases HL).

    Doc harps on avoiding elevated triglycerides after meals that load triglycerides into VLDL  molecules because the enzyme cholesterol ester transfer proetein (CETP) shunts triglycerides from VLDL (& chylomicrons) over to the standard circulating "big bouyant" (large & fluffy) LDL and fosters transfer of cholesterol out of that LDL; the triglyceride takes up less space and thus get smLDL.
    Central obesity usually correlates with elevated triglycerides and increased HL levels. However, if triglyceride genetics (or epigentics from Doc's diet ,etc.)  in the obese without that usual accompanying high triglycerides then that upregulated HL doesn't cause a lot of that individual's standard "big bouyant" LDL to become smLDL. HL also hydrolysizes triglycerides (and phospho-lipids) of chylomicrons, BetaVLDL, IDL, LDL & HDL. Both CETP & HL enzymes being elevated alone, or together, can provoke smLDL - genetic polymorphisms exist for both enzymes.

    sm LDL has less antioxidants left yet it's surface has higher ratio of poly-unsaturated acids which make it's phospho-lipids more at risk of oxidation. And smLDL has less sialic acid left on it's surface which fosters more poly-anion proteoglycan binding that increases the smLDL molecule's transportability across the endothelial lining into the artery wall .
    Doc harps on need for Magnesium because in real time magnesium is what interrupts the oxidation of smLDL from locking into an altered state & then salvaged plain old smLDL doesn't get to go on to be so damaging.

  • Might-o'chondri-AL

    11/9/2011 3:24:05 AM |

    Continued for J. Buch,
    Oxidized small LDL (oxLDL)  has fragments from it's oxidized PUFA (poly-unsaturated fatty acid) that are reactive aldehydes (ex: malon-di-aldehyde & 4-hydroxynoneal-lysine) which then fragment that smLDL's  lipoprotein ApoB.  That peroxidation of a PUFA acyl chain of  the smLDL phospholipid  leaves a type of carboxyl portion that the beta-2-glyco-protein I (Apo H) binds to using a "reactive" ketone as ligand link. Thus it is the position of the "reactive" ketone (keto-cholesteryl-9-carboxy-nonanoate) on the involved cholesterol molecule's spine that determines the % of glyco-protein bonding that occurs (genetics influences ketone placement on a human cholesterol molecule).

    Magnesium (Mg++) in the very early stage of glycated protein (Doc warns against advanced glycation end products) hooking up with LDL reverses the glyco-protein link to the "reactive" ketone. But if deficient Mg allows time to consolidate that contact then only a physiologiclly abnormally high pH will let Mg re-break that bonding.

    Immunological T cells respond (with age & gender differences)  to try to get oxLDL off the artery wall;  and, if there is too much to handle there is the risk of developing a so-called oxidized LDL-containing Immune Complex (oxLDL-IC). And this oxLDL-IC provokes cytokines that perpetuate the inflammation response. Over time and older age there is  less output of a malon-di-aldehyde oxLDL  immune response; which is possibly what leads to long established plaque having less lipid component and more involvement of collagen. It is relatively younger plaque that is unstable and more likely to rupture; the collagen draws in more Calcium and unfortunately provokes artery hardening problems.

    Now the lipid part from this oxLDL-IC gets into an immunological monocyte cell's endosome  and the ApoB gets into that same monocytes lysosome - sub-compartments inside the cytosol (cell interior). Then the lipid part in the endosome triggers heat shock protein (HSP 70/70B) which wrenches things so that the lysosome can't get to work on the lipid and ApoB prevents the lysosome from doing proper interactions at the inside of that cell's membrane to expel  the burdens. Once oxLDL cholesterol esters bulk  up a macrophage (monocyte) due to increasingly futile lysosome  activity  it becomes the notorious "foam" cell. Eventually that macrophage cell dies and the whole load get's polymerized into plaque.

  • Might-o'chondri-AL

    11/9/2011 8:03:57 PM |

    Hi Dr. Davis - with your indulgence:
    Back to platelets( see above Nov. 7): vascular remodeling with age &/or ROS exposes a bit of phosphatidyl serine  that platelets can "snag" onto as platelets flow along. Key to accomplish platelet snagging is signaling by  the promoter P2gamma12 and normally insulin signaling down inhibits P2gamma12. But, notably for Type II diabetics (and assumedly proportional to an individual's insulin resistance) their insulin doesn't inhibit that snag signal. Type II diabetics also have P2gamma12 upregulated in their platelets. And if anyone is of P2gamma12  haplo-type H2 those individuals will have even more of the receptors for it and therefore an  increased risk of peripheral artery disease. Irregardless of haplo-type, the Type II diabetic's propensity for peripheral artery problems are compounded by  their basal level of excess P2gamma12 .

    Adhesion to the artery then physically involves the platelet surface Glyco-protein Ib & vonWillebrand factor hitched to collagen provoking Integrin 2beta1 (GPVI) so the platelet/collagen sets in place. If the level of promoter P2gamma12 in that challenged site is fortuitously low then the rate of adhesion to the blood vessel is poor. So, predictably, for Type II diabetics the adhesion rate (like platelet secretion & aggregation) is higher than normal. GPVI insult also signals a release of ADP & this ADP (like collagen itself) independently induces aggregation of platelets; the plaque recruits to build itself up to be more fibrous. The plaque matrix serves as nesting for oxLDL & dying macrophage foam cells to polymerize with.

    ROS remodeling agents of the vasculature come from mitochondrial activity and  it appears certain (overlooked) relevant gene pheno-types (and their respective polymorphisms) can be pro-plaque (or preventative) - speaking here in the sense of  a primal influence on plaque risk as well as  tendency of the actual amount of plaque. Sirtuin 5 (Sirt5), a mitochondrial Sirt (there are nuclear Sirt too) binds to Uncoupling Protein 5 (UCP5) and governs that (& other) UCP. Sirt (there are 6 types) remodels chromatin (DNA spooled around a histone ) via histone de-acetylase enzyme; while our UCP (there are 5 types) work in the inner mitochondrial membrane governing the proton electro-chemical gradient that is integral to the chain of oxidative phosphorylation (a way to generate ATP, among other functions).

    Sirt action on DNA includes (among other dynamics) the cellular level encoding of how individual fatty acid metabolism fine tunes -  lipid fatty acids included.Sirt action on DNA includes (among other dynamics) the cellular level encoding of how individual fatty acid metabolism fine tunes -  lipid fatty acids included. Doc's diet/protocol may ( I suggest) sometimes  tweak out favorable health response(s) via induced epigenetics, because of remodeling that is induced in the chromation DNA unit packaging . Sirt's histone de-acetylase working depends on NAD- to drive Sirt and Doc's diet/protocol theoretically seems to be capable of altering NAD flow patterns from his weaning of cells'  mitochondria off of glucose.

    UCP5  rules the inner mitochondrial membrane potential & the rate of oxygen use, which can become relevant to ROS levels. Both UCP5 and Sirt5 are upregulated in hypertension and Type II diabetics; the confluence of having geneticly more UCP5 along with Sirt5 are implicated in increased carotid artery plaque. (Of course nothing is linear in humans so haplo-type T- carrier UCP5 polymorphism rs5977238 benefit with less plaque risk and reduced plaque numbers.) Note: I am skipping over other Sirt & UCP; but will add that lots of pheno-typic UCP1 spins out extra amounts of reactive super oxide to drive down nitric oxide and implicated in accelerated aging of the vasculature.

  • Jack Kronk

    11/10/2011 8:13:40 PM |

    Might/Doc - Does this mean that if you DONT have proper insulin receptor response that all of the things listed in the last paragraph become untrue? (meaning bad?)

    Would this mean that you are implying a low carb diet would be the best solution due to the insulin issues?

    I ask because I cannot raise my HDL for the life of me. It is completely stalled at 40. And my LDL is primarily small dense kind. I have only really had this problem since going "LC Paleo" and adding a ton of sat fat to my diet but then I added back in starches and other carbs and became more moderate carb, while still continuing to eat bacon/eggs/cheese/cream/butter/beef/coconut oil/ghee/nuts etc.

    Now I've got people telling me to go back to LC, and exactly the reverse, people telling me that I need to cut out the fats including dairy and go low sat fat.

  • STG

    11/10/2011 11:18:15 PM |

    Mito....:
    I have viewed your comments at the Hyperlipid and always appreciate your detailed biochemical/physiological explanations per topic. Your grasp of details and mechanisms is amazing! What is your background? Are you a biochemist by trade?

  • Kent

    11/11/2011 4:34:12 PM |

    A retreat is an excellent idea!  It would be a great time of learning and discussions. I vote for Gulf Shores Alabama Smile

  • Might-o'chondri-AL

    11/11/2011 7:02:07 PM |

    HI STG,
    My hope here is that I never hijack Dr. Davis'  blog ( I never personally posted on Hyperlipid blog).  I trust  Doc's readers know he is not responsible for any errors I make. Being semi-retired from consulting on agro-industrial projects in developing countries I feed my mind by keeping up with health science & commenting here about correlations to Doc's work.

  • Might-o'chondri-AL

    11/12/2011 9:33:23 AM |

    Hi J. Kronk,
    Saw your 11 Nov. query &  feel diet advice here is for Doc to offer (not me). Doc discusses ApoE pheno-types he restricts dietary fat for. You "tagged" me where I  was elaborating on platelets' interaction with insulin & how insulin resistance is a game changer (not sure what confusing).

    If one is insulin resistant then the signaling to build-up (anabolism) from insulin is selectively diminished and consequently break-down (catabolism) signals get  into play. Proteo-lysis is protein cleaving and HDL's protein component can be more rapidly subject to proteo-lysis; which I presume (?) is why/how some people degrade their HDL so quickly. Genetic quirks (& gender) also hit HDL levels notably;  yet  if quick enough turnover the "stale" HDL  might be being replaced by more functional HDL. According to the "HATS" study HDL alone is not a predictor of coronary artery disease mortality.

    Niacin usually decreases rate of catabolism of HDL,  it helps secrete more ApoA1 to make into HDL & decreases amount of  smLDL. Niacin isn't perfect since it alters the extent to which HL (hepatic lipase enzyme) can work on a  HDL molecule to morph  it into the kind of HDL that has the maximum reverse cholesterol transport capability. HL is what hydrolyses the triglycerides in HDL - so, basicly if HDL loaded with trigs it has sparser room for scavenging cholesterol.


    One's genetic response to increased levels of circulating palmitate free fatty acid can interfere with insulin signalling in the liver. Whether clinically insulin resistant or due to a genetic quirk (you?),  palmitate can phosphorylate liver insulin receptors in a manner unlike "normal" individuals do in the Akt process (insulin normally should get Akt going to stop liver gluco-neo-genesis - since insulin has glucose to drive into cells ). Essentially "excess" palmitate, in this example, is causing only a partial phosphorylation of Akt & is how researchers can use very high fat diets to induce experimental diabetes .

    I don't hear you being insulin resistant, so address genetics of Protein Phosphatase 2A (PP2A), which  has components involved in it's regulation and is subject to different structure. How PP2A parts interact with distinct parts of the Akt molecule can  impair some interactions,  yet leave other parts of Akt responsive ( to do what Akt  is normally designed to do). Palmitate can raise PP2A levels in the liver by 30%; so basically the more PP2A  around and/or the molecule's genetic tweaks the weaker a key part of  the liver's Akt response is going to be.

    Since palmitate  being in the liver does not stop insulin there from fostering more trigs there are still post-prandial trigs going into the VLDL . In other words the liver insulin resistance and rogue genetics can leave the part of Akt that governs lipo-genesis still responsive to insulin. Doc warns us about trig enriched VLDL & chylomicrons promptly driving  smLDL that doesn't degrade & small particle numbers measure high; he is more adamant about post-prandial trigs but genetic high overnight trigs can occur.

    I don't think coconut oil acts the same way high animal fat sometimes does on Akt . We internally make palmitate when acetyl-CoA acted on by enzyme acetyl CoA carboxylase  to make malonyl-CoA that fatty acid synthase converts to palmitate. I think most of coconut oil's fatty acids are metabolized before getting into that pathway so maybe coconut oil is worth parsing when genetics or insulin resistance drives up smLDL.

  • STG

    11/12/2011 6:16:07 PM |

    Mito..
    Excuse my error about you posting on the Hyperlipid. I guess I have read your posts elsewhere. In any case, your posts are very educational and explain precisely the biochemistry  Thanks for sharing your knowledge!

  • Mark

    8/14/2012 3:24:54 AM |

    Hi Dr. Davis,
    I’m 47 yrs old. I’ve had migraines since I was a teen and I developed Athsma this past January (hate it). During the process of discovery the drs found I have a 50% blockage in one of the 5, non critical, arteries running along the back of my heart. Scared me, to say the least. I’ve always eaten quite healthfully (for what I knew), am thin @ 6′ 1″/155lbs (was 175lbs in Jan.). Had total cholesterol of 200/LDL of 146/HDL of 50. Drs wanted me to do Lipitor. Researched and said, “No, thanks.” Started exercising 5-6 days/wk (lifting + walk/run), taking red yeast rice, fish oils, fish, no meat, no dairy, no eggs, lots of veggies/fruit, etc., but still eat beans, oats (every AM), occasional wraps. After 6 wks my blood work (VAP) was as follows: LDL=86, HDL=43, VLDL=17, TOT. CHOL=146, Trigycerides=66, Non-HDL (LDL+VLDL)=103.

    Seemed GREAT to me! The dr wasn’t impressed. Said my ‘particle size’ was small: LDL1(a)=8.1, LDL2(a)=0, LDL3(b)=39.5, LDL4(b)=24.9. Density Pattern=B.

    I’ve continued but don’t know how to elevate my HDL and reduce the particle size/change the pattern to the more favorable ‘A’. Getting down about this. Working hard but, seems like I can’t find answers that work, anywhere! What might you would work in my situation? Also, Is niacin ANDRed Yeast Rice a bad idea?
    I’ll hang up and listen. Thank you,
    Mark

    PS - I left this post on another page, as well.

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