Disease Engineering

Imagine you contract pneumonia.

You have a fever of 103, you’re coughing up thick, yellow sputum, breathing is getting difficult. You hobble to the doctor, who then fails to prescribe you antibiotics. You get some kind of explanation about unnecessary exposure to antibiotics to avoid creating resistant organisms, yadda yadda. So you make do with some Tylenol®, cough syrup, and resign yourself to a few lousy days of suffering.

Five days into your illness, you’ve not shown up for work, you’re having trouble breathing, and you’re getting delirious. An emergency trip to the hospital follows, where a bronchoscopy is performed (an imaging scope threaded down your airway) and organisms recovered for diagnosis. You’re put on a ventilator through a tube in your throat to support your breathing and treated with intravenous antibiotics. Delayed treatment permits infection to escape into the fluid around your lungs, creating an “empyema,” an extension of the infection that requires insertion of a tube into your chest through an incision to drain the infection. You require feeding through a tube in your nose, since the ventilator prevents you from eating through your mouth. After 10 days, several healing incisions, and a hospital bill totaling $75,000, you’re discharged only to be face eights weeks of rehabilitation because of the extreme toll your illness extracted. Your doctor also advises you that, given the damage incurred to your lungs and airways, you will be prone to more lung infections in the future, and similar situations could recur whenever a cold or virus comes long.

A disease treatable by taking a two week, $20 course of oral antibiotics at home has been converted into a lengthy hospital stay that generated extravagant professional fees, testing, and costly supportive care. You’ve lost several weeks of income. You’re weak and demoralized, frightened that the next flu or virus could mean another trip to the hospital.

Such a scenario would be unimaginable with a common infection like pneumonia, or it would be grounds for filing a malpractice lawsuit. But, as horrific as it sounds in another sphere of healthcare, it is, in effect, analogous to how heart disease is managed in current medical practice.

First, you’re permitted to develop the condition. It may require years of ignoring the telltale signs, it may require your unwitting participation in unhealthy lifestyle choices. Palliative treatments that slow, but don't stop, the progression of disease are prescribed like cholesterol drugs. The process then eventuates in some catastrophe like heart attack or similar unstable heart situation, at which point you no longer have a choice but to submit to major heart procedures. That’s when you receive your heart catheterization, coronary stents, bypass, defibrillators, etc. and you're proudly declared a "success" of medical technology.

Of course, none of these procedural treatments cures the disease, no more than a Band Aid® heals the gash in your leg. The conditions that were present that created your heart disease continue, allowing a progressive disease to worsen. At some point, you will need to return to the hospital for yet more procedures when trouble recurs, which it inevitably does.

A coronary bypass operation costs, on average $85, 653 (AHA 2008 Update; based on 2004 data). That doesn't include the $25,433 cost for the heart catheterization performed by a cardiologist to provide the surgical roadmap of your coronary arteries. If there are any complications of your procedure, then your hospital bill may total a substantially higher figure.

$85, 653 is just the upfront financial pay-off. Over the long run, your life is actually worth far more to the cardiovascular healthcare system because no heart procedure yields a permanent fix. In fact, repeated reliance on the system is the rule.

In fact, over 90% of people who enter the American cardiovascular healthcare system do so through a revolving door of multiple procedures over several years. It is truly a rare person, for instance, who undergoes a coronary bypass operation, never to be seen again the wards of the hospital because he remains healthy and free of catastrophe. A much more familiar scenario is the man or woman who undergoes two or three heart catheterizations, receives 3,4, or 6 stents, followed a few years later by a heart bypass, pacemaker, defibrillator, as well as the tests performed for catastrophe management, such as nuclear stress test, echocardiogram, laboratory blood analysis, and consultation with several specialists. Re-do bypass surgeries--a 2nd, 3rd, or 4th bypass--now comprise 25% of all bypass procedures.

The total revenue opportunity is many-fold higher than the initial 80-some thousand dollars, but instead totals hundreds of thousands of dollars per person.

What motivation can there possibly be to 1) identify coronary disease early, when in its asymptomatic stage, then 2) identify its causes, then 3) correct the causes, and finally 4) shut off the disease? You and I can accomplish this with a few hundred dollars of cost, perhaps a few thousand over many years (to cover costs of fish oil, vitamin D, niacin, and whatever else it takes to stop the expression of the disease). Nobody therefore profits substantially from your prevention effort--except you.

Then what if nobody told you that heart disease could be managed this way? That's what I mean by "disease engineering."

Dr. Steven Gundry on The Livin' La Vida Low-Carb Show

I stumbled on a great interview with cardiothoracic surgeon, Dr. Steven Gundry, on Jimmy Moore's Livin' La Vida Low-Carb Show. (Or, cut and paste: http://www.thelivinlowcarbshow.com/dr-steven-gundry-part-1-episode-179/)

Dr. Gundry has some fun ways of looking at eating and health. I found his comments on the activation of genes (discussed at a very light, non-scientific level) useful. He argues that when humans consume sugar-containing foods, the signal received by the body is that winter is approaching and it's time to build up fat stores in anticipation of the food shortages of cold weather. He finds parallels for this phenomenon in other species. Of course, for humans, winter (in the form of extended calorie deprivation) never comes. In fact, you might argue that, given our excessive reliance on grains, corn, and sugars, that we are, in effect, always in anticipation of a winter that never comes.

I've not read Dr. Gundry's books, but I found this light interview a lot of fun.

Does fish oil ADD to statin therapy?

Yet another patient came to my office today saying, "My primary doctor said that I should stop taking fish oil. He say's that I don't need it because I take Crestor."

The woman was in tears, confused and frightened over a potential disagreement between her doctors.

Is this true? If someone takes a statin drug, like Crestor, Lipitor, Zocor (simvastatin), pravachol, or lovastatin, they don't need to take anything else because the statin drug is so powerful that it eliminates risk?

No. Not even close to the truth.

First of all, let's accept that virtually the entire body of statin drug literature--hundreds of studies, billions of dollars spent--was paid for by the drug industry. It's no news that studies paid for by the sponsor are likely to favor the sponsor. Imagine Ford sponsored a study of Ford vs. GM cars vs. Toyota, paying $10 million to fund the effort. Guess who is likely to come out on top? "Studies show that Ford makes the best car in America." (Sorry, I don't mean to pick specifically on Ford. It's just a widely-recognized brand.)

So that means that the statin literature likely overestimates the benefit of statin drugs. Even so, it's clear from the hundreds of studies performed that the best we can hope for by taking statin drugs is a reduction of heart attack and death from heart attack of 30-35%--best case. That doesn't sound like elimination of risk to me.

What are the incremental benefits of adding omega-3 fatty acids from fish oil added to statins? The best data originate with the JELIS Trial (Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis), in which 19,000 Japanese participants (who already have a high omega-3 intake from diet, usually ranging from 1800-3000 mg per day) experienced a 19% reduction (relative reduction) in cardiovascular events.

GISSI Prevenzione demonstrated a 28% reduction in heart attack, 45% reduction in death from heart attack with fish oil.

Omega-3 fatty acids from fish oil also:

--Reduce triglycerides dramatically
--Accelerate after-eating clearance of digestive by-products, i.e., they correct post-prandial abnormalities
--Modify the character (fragmentation potential, structural strength) of plaque
--Raise HDL modestly

If you buy your fish oil from Sam's Club, Costco, or other discounter, a healthy dose of fish oil might cost you $3 per month. Compare that to the $120 per month average cost of a statin agent. Why is there even a discussion over this?

Sadly, the doctor on Main Street, U.S.A, is the unwitting puppet of the pharmaceutical industry. The pretty drug company representative with nice legs and a cute smile promises lunch, dinner and . . who knows what else? Wink. The fifty-something, hairline-receding doctor can't resist. "Of course I'll prescribe your drug!"

Don't kid yourself: The drug industry knows precisely how to manipulate the behaviors of the deliverers of their products.

So, do statin drugs make omega-3 fatty acids from fish oil irrelevant? Absolutely not.

It's all about trying to inch closer and closer--not to reduction--but to elimination of risk for heart disease.

HDL: “H” is for “happy”

What role do emotions play in HDL cholesterol?

I’ve often observed a peculiar phenomenon: People who come to the office or hospital in the midst of a difficult emotional situation-e.g., stress at home, financial struggles, hospitalization (usually an unhappy occasion)- can show dramatic drops in HDL cholesterol. Not uncommonly, HDL drops 20 or more mg/dl.

Take Agnes’s case. Agnes had to go to the hospital for an elective procedure, one she’d been dreading for months. Previously, Agnes had been proud of the fact that she’d incrased HDL from 42 mg/dl range all the way up to 71 mg/dl. She accomplished this dramatic increase by eliminating wheat and cornstarch from her diet (which helped her lose 24 lbs), taking vitamin D and omega-3 fatty acids from fish oil, exercise, 2 oz of dark chocolate per day, and a glass of red wine with dinner.

Although I wouldn’t have bothered checking a cholesterol panel for such a procedure, the hospital had a checklist that included a cholesterol panel regardless of necessity. (Such checklists are common in hospitals, meant to ensure that certain basic issues are not overlooked.)

Agnes’ HDL: 29 mg/dl-a 42 mg drop.

Agnes will recover and her HDL will rebound, but the same effect can occur with other stressful situations, such as death in the family, financial worries, marital stress, etc., as well as physical illness.

Interestingly, the opposite may also hold true: Low HDL may increase risk for depression and stress. A study from Finland of 124 depressed persons, for instance, showed a 240% increased likelihood of depression in those with lower HDL cholesterols.

In other words, there seems to be a curious interdependence between HDL and emotions.

Why? Does it represent the indirect effect of adrenaline, cortisol, or other “stress hormones”? Do factors that relate to low HDL, such as unhealthy diet full of carbohydrates and physical inactivity, also tend to cultivate depression?

It certainly seems to be a chicken-egg situation, with one often leading to the other.

Moral of the story: Maintaining a sense of optimism and engaging in activities that bring you satisfaction and enjoyment can help raise HDL, as can strategies such as those followed by Agnes. Avoiding unnecessarily stressful situations can help. HDL is important, since higher levels are associated with much reduced risk for heart disease . . . and perhaps depression.

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.

Apo E4 and sterols: Lethal combination?

Phytosterols, or just "sterols" to its friends and neighbors, are a group of cholesterol-like compounds that are abundant in the plant world. Lately, however, sterols have proliferated in the processed food supply, thanks to the observation that sterols reduce LDL cholesterol when ingested by humans.

This must mean that sterols are good for you.

Uh oh. Wait a minute: There is a rare disease called sitosterolemia in which there is unimpeded intestinal absorption of all sterols ingested through diet. They must have really low LDL cholesterols! Nope. They develop coronary disease--heart attacks, angina, etc.--in their late teens and 20s. In other words, if sterols gain access to your bloodstream, they are bad. Very bad.

Conventional thinking is that only a modest quantity of dietary sterols gain access to the bloodstream. But there are two potentially fatal flaws in this overly simplistic line of thinking:

1) What happens when you load up your diet with "heart healthy" sterols, such as those in "heart healthy" margarines, mayonnaise, and yogurt, effectively increasing sterol intake 10-fold?

2) What happens in people with the genetic pattern, apo E4, that is carried by 25% of the general population that permits much greater intestinal absorption of sterols?

My prediction: Despite the fact that sterols reduce LDL, they may, in certain genetically-susceptible people, such as those with apo E4, increase risk for heart disease: heart unhealthy.

Here are two studies that suggest that greater sterol absorption in people without sitosterolemia are at higher risk for heart disease:

Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

Glucomania

As I suggested in a previous Heart Scan Blog post, a glucose meter is your best tool to:

1) Lose weight
2) Cure diabetes
3) Reduce or eliminate small LDL particles
4) Achieve anti-aging or age-slowing effects


But it means getting hold of a glucose meter and applying it in a very different way.

Diabetics typically check fasting morning glucose and again several times during the day to assess medication effects. But you and I can measure blood glucose to assess the immediate effects of food choices--two very different approaches.

The concept is simple: Check a blood glucose just prior to a food or meal of interest, then one hour after finishing.

Let's take two hypothetical breakfasts. First, oatmeal, a so-called "low-glycemic index" food. Slow-cooked, stone ground oatmeal with skim milk, a handful of walnuts, just a few blueberries.

Blood glucose just prior: 95 mg/dl
Blood glucose one hour after finish: 175 mg/dl

I made those numbers up, but this is a fairly typical response for many adults. (This is why "low-glycemic index" is an absurd notion.) This kind of response causes 1) glycation, the adverse effects of glucose modification of proteins that leads to cataracts, kidney disease, cartilage damage and arthritis, atherosclerosis, skin wrinkles, etc., 2) high insulin response that cascades into fat deposition, especially visceral fat ("wheat belly"), and 3) glucotoxicity, i.e., direct damage to the pancreas that can, over years, lead to diabetes.

Next day, let's try a breakfast of 3-egg omelet made with green peppers, sundried tomatoes, and olive oil.

Blood glucose just prior: 95 mg/dl
Blood glucose one hour after finish: 93 mg/dl

This is a meal of virtually zero-glycemic index. This kind of response triggers none of the effects experienced following the oatmeal. Repeated over time and you fail to trigger glycation, you stop provoking insulin, and visceral fat mobilizes rather than accumulates: you lose weight, particularly around the middle.

We therefore aim to keep the one-hour blood glucose 100 mg/dl or less. If you start with a high fasting blood glucose of, say, 118 mg/dl, then we aim to keep the one-hour after-eating blood glucose no higher than the pre-meal.

It works. Plain and simple.

This makes the primary care docs crazy: "How dare you check your blood sugar! You're not diabetic." In truth, blood glucose meters are relatively simple devices to use. The test strips and lancets will cost a few bucks. (The meters themselves are either low-cost or free, just like Gillette sometimes sends you a beautiful new razor for free but expects you to buy the blades). These are direct-to-consumer products. While a prescription written by your doctor for a glucose meter and supplies helps insurance cover the costs, you can easily get these devices without a prescription. Some stores, like Target, keep their devices out on the shelves with the shampoo and bath soap.

Warning: Anyone taking diabetes drugs will have to consult with their doctors about the safety of such an approach. Because this approach can actually cure diabetes in some people, if you are taking some diabetes drugs, especially glyburide, glipidize, and glimepiride, you can experience dangerously low blood sugars, just as any non-diabetic taking these drugs would.

Diarrhea, runny noses, and rage: Poll results

Here are the results of the week-long poll asking the question:

Have you experienced a wheat re-exposure syndrome?
Yes, undesirable gastrointestinal effects 223 (41%)

Yes, asthma or sinus problems 51 (9%)

Yes, joint pains and/or swelling 85 (15%)

Yes, emotional or other nervous system effects 59 (10%)
No, nothing, nada  107 (19%)

No. Wheat is sacred and you're all nuts  13 (2%)


There are several interesting observations to make from this informal poll. First, as I have observed, the most common wheat re-exposure syndrome is gastrointestinal, usually involving cramps, diarrhea, and lame explanations to your dinner partner.

Second most common: joint pains and/or swelling.

Third: asthma or sinus congestion.

The incidence of emotional or nervous system effects surprised me a bit. I didn't expect 10% of people to share this effect. This is an effect I also experience personally, along with the gastrointestinal consequences.

To be sure, this is a skewed poll, since many people likely come to this blog in the first place because of such issues. But I was nonetheless impressed with the relatively modest proportion of people who did not share such a re-exposure syndrome: only 19%.

Beyond the interesting numbers provided by readers, a good many also provided some fascinating and graphic comments. Here's a sample:




Sassy said:

Reflux -- starts a day later and goes for up to a week. And Bloat:2-5 inches on my waistline in a day, lasting up to three. Miserable. And why, having experienced this once, have I done it often enough to verify the connection with certainty? I am working on that one.



Anonymous said:
Wheat increased hunger with even with only a small amount. Crackers in soup was enough to set it off.

Also, when I was trying to get off wheat, I noticed that 2 eggs and 2 bacon and I could go 5 hours before hunger, or 2 eggs and 2 bacon and toast was good for three hours before hunger. That was the final step to giving up wheat. Now three years and 59 Kg [130 lbs!] loss later, there is no doubt in my mind that wheat is evil, and I do not regard it as suitable for human food. I speculate that it increases ghrelin or cortisol.

Anna said:
For me, in the two years since I began eating Gluten-Free (Low Carb for 6 years), the few times I've had re-exposure to wheat, I've experienced fast onset and intense abdominal pain (known exposure during the daytime) and heartburn, indigestion, intense nausea, and disrupted sleep (exposures during evening meal not discovered until the next day).

My husband wants to think he's fine with wheat (though I know that he has at least one gene that predisposes to celiac), but IMO, he isn't. He eats no wheat at home because that's the default, and he's OK with that. But if he goes out to dinner at a restaurant that serves "good" artisan bread, he will indulge in a few bites (he does restrict his carb intake, so it's still a limited amount). More often than not, he will sleep fitfully on those nights, snore more, and wake in the night with indigestion. He wants to bury his head in the sand and will only acknowledge the discomfort being due to eating too many carbs, not the wheat itself. I notice he sleeps fine if he eats a small amount of potato or rice. Go figure.

Our 12 yo son has been eating GF for two years also. About 6 months into GF, he unknowingly ate wheat a number of times (licorice candy laces at a friend's house), which resulted in outbreaks of canker sores in his mouth each time. He also exhibits mood and behavior changes when he eats wheat, which is what prompted me to test him for gluten intolerance in the first place.

Mark said:
If I go for 3-4 days without wheat, grains or sugar and then go out and binge on a pizza and ice cream or something like that I become explosive within 20 minutes to an hour. It's like a wheat and sugar rage.(I'm not saying this is an excuse for rage, I'm saying it has happened to me and I believe partly do to re-exposure) It seems the combination of the wheat plus sugar can be the worst.

I get red rashes around my neck sometimes right away and sometimes up to a day or later and sometimes get bad diarrhea. 
I think it can be almost dangerous to cut things like gluten and sugar suddenly out of the diet without being very serious about keeping them out. I have found it very hard to cut out wheat without binging on it later after 4 or 5 days. I don't believe that my symptoms are just psychological either.

I was also diagnosed with ADHD as a young kid and then rediagnosed with adult ADHD by 3 different doctors. I also have bouts of mania at times too. I am considering trying to go completely gluten/refined carbohydrate free to see if it helps with the symptoms and gives me some relief.

I have never been tested for celiac or gluten intolerance but I would like to be. I think it would help explain to my girlfriend, family and friends why I can't go out and eat pizza or have a beer or ice cream. Right now they all think I'm a hypochondriac. At times I have experienced an intense fatigue the next day like I can't wake up and also sharp pains in my body and headaches.

Anonymous said:
I ditched wheat a year ago after my wife was diagnosed celiac. I immediately experienced a number of health improvements (blood lipids, sleep, allergies, etc.).

Fast forward: We all suffered some inadvertent wheat exposure yesterday via some chocolate covered Brazil nuts (of all things). This accidental A-B-A experimental design resulted in the following:

1. My celiac wife experienced what she calls "the flip" within an hour of exposure (i.e., intense GI distress).
2. My five-year old son went to bed with some wicked reflux.
3. I woke up with some twinges in my lower back and an ache in my football-weary left shoulder. I was also complaining to my wife about fuzzy-headedness that refused to respond to caffeine or hydration. I could only describe it as "carb flu"...

And then I read your post!

Anne said:
Depression, agitation and brain fog if I get glutened. Some times this comes with abdominal pain and a rash on my back - I think it is dose dependent. Cross contamination with wheat is a big issue when eating out. Needless to say, I eat out infrequently and then try to stick with the restaurants that are the most aware of gluten issues.

Terrence said:
Several weeks ago, I started Robb Wolf's 30 day challenge.

The first two weeks were brutal - calling it a withdrawal flu was a massive understatement. So, I thought I would try some wheat and see what happened (could not be worse, I thought). Well, it was.

I still felt extremely crappy, but I was now MASSIVELY GASSY - AMAZINGLY GASSY, for about 48 hours - flatulence on wheels, in spades. I did not go out at all in those 48 hours - when the gas came on, it went out, LONG, and QUICKLY and LOUDLY.

I am easing back into wheat and grain free. I am gluten free today and tomorrow (Sunday and Monday). I expect to try a small amount of wheat on Thursday, then maybe a little more the following Thursday.

Donald said:
I have limited wheat consumption severely over the last 8 months. I have lost 120 pounds, no longer have bouts of illness, asthma, depression, or low energy. I also take vitamin D and other supplements that have helped (many are from your blog recommendations).

Last week I ate a small piece of cake and dessert pizza. Shortly thereafter I started sneezing, had a scratchy throat, and runny nose. I called off sick the next day for fear of being contagious. My symptoms subsided quickly and I am now attributing them to the processed flour eaten at my work luncheon. I think it was an allergic reaction since I recall having much more severe symptoms fairly regularly in my wheat eating days. Those were attributed to an "allergy" of unknown origin back then.

John said:
I suffered from Ankylosing Spondylitis, Iritis, Plantar Fasciits, etc for a number of years. I restricted carbs, especially wheat and I've been symptom free for the past two years now.

Lori said:
I found wheat to be one of the worst things for giving me gas bloating and acid reflux, and I'd had sinus and nasal congestion my whole life. When I ate that cookie, it just re-introduced old problems. I can occasionally eat a gluten-free, grainy goody at my party place without any side effects. I also have a little sprouted rice protein powder every day.

Another odd thing about wheat: it was hard for me to stop eating it once I started. I could go through a whole box of cookies in one sitting, even though I wasn't a binge eater. But I can have a couple of gluten-free cookies and stop.

Paul said:
Except for one slip up this recently past holiday season, I've been sugar-grain-starch free since July 2008. Mental fog was the most noticable re-exposure symptom I had.

My mom has had the worst acid-reflux for 40-plus years. It had become so bad that she was on three medications just to deal with the symptoms. After much training and coaxing, I finally got across to her 
how to totally get off wheat. Not at all to my surprise, after being wheat free for a few weeks, she lost weight and her acid reflux was GONE!

But she had been addicted to wheat for so long, she relapsed, and the reflux fire soon returned. Wheat must be akin to heroin with some people. Even though they know it's very bad for them, they can't help themselves.

Onschedule said:
Re-exposure often leads to diarrhea for me, or such a heavy feeling of tiredness that all I can do is lay down and pass out. A local pizzeria makes a darn good pie, but since I started practicing wheat-avoidance, I can't keep my eyes open after eating there. I can't say for sure that it's the wheat causing it, but definitely something in the crust. Diarrhea, on the other hand, is definitely triggered by the wheat for me.

My mom complained of gastric reflux for years, but never filled the prescriptions that her doctors would give her. I suggested wheat-avoidance- gastric reflux disappeared within 3 days and hasn't returned (has been 6 months now). I've already commented elsewhere on this blog about how much weight and bloating she has lost...

Steve said:
Interesting that I should sit down, turn on my computer and find your poll. Having gone several weeks, maybe months, avoiding gluten, I took my daughter and her boyfriend out to eat because my wife has been working late at the office lately. Although I was thinking I would just eat my steak and chicken, I succumbed to the temptation of eating about a dozen greasy, breaded shrimp that my daughter and her boyfriend ordered. It's 1:39am and I still do not feel sleepy. My left nostril is completely blocked, my stomach feels bloated, really, really full and I've been burping. In your poll I checked sinus problems but could have chose gastrointestinal or nervous problems just as well. 


A few weeks ago my daughter brought home a pizza and, once again, despite my knowing that I shouldn't, I ate a couple of pieces. I was sick for two days. The pain in what I think was my transverse colon was so bad I thought I might have to go to ther emergency room. Before I ate the pizza I had never gone grain-free that long before. I did this after reading Robb Wolf's book. 


I AM CONVINCED. No more wheat for me! Please, Lord, give me strength.

LV said:
What don't I experience! I typically avoid wheat (and gluten for that matter) as I'm pretty sure it makes me sick, but when I slip (or someone else slips me some) I end up with massive amounts of joint swelling and tenderness, diarhea, cramping, gas, bloating and brain fog. I'm absolutely miserable. Just that alone is enough to keep me off gluten. I have RA, so if I have repeated exposures I'll have a flare which SUCKS!

The perfect Frankengrain

Pretend I'm a mad food scientist. I'd like to create a food that:

1) Wreaks gastrointestinal havoc and cause intractable diarrhea, cramps, and anemia.
2) Kills some people who consume it after a long, painful course of illness.
3) Damages the brain and nervous system such that some people wet their pants, lose balance, and lose the ability to feel their feet and legs.
4) Brings out the mania of bipolar illness.
5) Amplifies auditory hallucinations in people with paranoid schizophrenia.
6) Makes people diabetic by increasing blood sugars.
7) Worsens arthritis, such as osteoarthritis and rheumatoid arthritis.
8) Triggers addictive eating behavior.
9) Punishes you with a withdrawal process if you try to remove it from your diet.

I will develop a strain that is exceptionally hardy and tolerates diverse conditions so that it can grow in just about any climate. It should also be an exceptionally high yield crop, so that I can sell it cheaply to the masses.

Now, if my evil scheme goes as planned, I will then persuade the USDA that not only is my food harmless, but it is good for health. If they really take the bait, they might even endorse it, create a diet program around it.

Dag nabit! Such a plan has already been implemented. Another evil food scientist already beat me to the punch. The food is called wheat.

Diabetes: A study in aging

Diabetics experience long-term health difficulties, including atherosclerosis/heart attacks, peripheral vascular disease, hypertension, cataracts, kidney disease, neuropathies, male erectile dysfunction, osteoarthritis, and colorectal cancer. They also die, on average, 10 years earlier than non-diabetics.

In effect, diabetics compress their lives into a shorter period of time. They experience all the "complications" of aging at a younger age. People without diabetes, of course, can develop atherosclerosis, cataracts, kidney disease, etc., but they tend to do so later in life compared to diabetics.

One index of the rate of aging (but not chronologic age itself) is hemoglobin A1c, or HbA1c, a "moving average" of glycated hemoglobin, i.e., glucose-modified hemoglobin. Blood glucose glycates hemoglobin linearly and irreversibly; measuring HbA1c thereby provides an index of the last 60 or so days average blood glucose.

To put HbA1c values into perspective:

Average HbA1c of hunter-gatherers: 4.5%
Average HbA1c for Americans: 5.6%
American Diabetes Association definition of diabetes: 6.5% or greater
American Diabetes Association definition of adequate control of diabetes: 7.0% or less

Why do diabetics age faster? There are likely several reasons. One important reason is glycation, as indexed by HbA1c. Glycated proteins in the lens of the eye causes cataracts. Glycated proteins in cartilage leads to arthritis. Glycated LDL particles (apo B) leads to atherosclerosis. Glycated nerve cells causes neuropathy. And so on.

If glycation underlies many of the phenomena of aging, then we might surmise that:

1) The less you glycate, the slower you age.
2) The more you glycate, the faster you age.

Therefore, the higher the HbA1c, the faster you are aging.

What foods increase HbA1c? Carbohydrates. That bowl of slow-cooked, stone ground oatmeal? A one-hour after-eating blood sugar of 170 mg/dl is common. Your doctor says that's okay because it's below 200 mg/dl and you don't "need" medication yet.

Fish oil: The natural triglyceride form is better

If you have a choice, the triglyceride form of fish oil is preferable. The triglyceride form, i.e., 3 omega-3 fatty acids on a glycerol "backbone," is the form found in the body of fish that protects them from cold temperatures (i.e., they remain liquid at low ambient temperatures).

Most fish oils on the market are the ethyl ester form. This means that the omega-3 fatty acids have been removed from the glycerol backbone; the fatty acids are then reacted with ethanol to form the ethyl ester.

If the form is not specified on your fish oil bottle, it is likely ethyl ester, since the triglyceride form is more costly to process and most manufacturers therefore boast about it. Also, prescription Lovaza--nearly 20 times more costly than the most expensive fish oil triglyceride liquid on a milligram for milligram basis--is the ethyl ester form. That's not even factoring in reduced absorption of ethyl esters compared to triglyceride forms. Remember: FDA approval is not necessarily a stamp of superiority. It just means somebody had the money and ambition to pursue FDA approval. Period.

Taking any kind of fish oil, provided it is not overly oxidized (and thereby yields a smelly fish odor), is better than taking none at all. All fish oil will reduce triglycerides, accelerate clearance of postprandial (after-eating) lipoprotein byproducts of a meal (via activation of lipoprotein lipase), enhance endothelial responsiveness, reduce small LDL particles, and provide a physical stabilizing effect on atherosclerotic plaque.

But if you desire enhanced absorption and potentially lower dose to achieve equivalent RBC omega-3 levels, then triglyceride forms are better.

Here are cut-and-pasted abstracts of two of the studies comparing forms of fish oil.

Bioavailability of marine n-3 fatty acid formulations.

Dyerberg J, Madsen P, Moller JM et al. 
Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.
(Full text of the Dyerberg et al study made available at the Nordic Naturals website here.)



Eur J Clin Nutr 2010 Nov 10. 

Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.

Neubronner J, Schuchardt JP, Kressel G et al. 
Institute of Food Science and Human Nutrition, Leibniz Universität Hannover, Am Kleinen Felde 30, Hannover, Germany.

Abstract

There is a debate currently about whether different chemical forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are absorbed in an identical way. The objective of this study was to investigate the response of the omega-3 index, the percentage of EPA+DHA in red blood cell membranes, to supplementation with two different omega-3 fatty acid (n-3 FA) formulations in humans. The study was conducted as a double-blinded placebo-controlled trial. A total of 150 volunteers was randomly assigned to one of the three groups: (1) fish oil concentrate with EPA+DHA (1.01?g+0.67?g) given as reesterified triacylglycerides (rTAG group); (2) corn oil (placebo group) or (3) fish oil concentrate with EPA+DHA (1.01?g+0.67?g) given as ethyl ester (EE group). Volunteers consumed four gelatine-coated soft capsules daily over a period of six months. The omega-3 index was determined at baseline (t(0)) after three months (t(3)) and at the end of the intervention period (t(6)). The omega-3 index increased significantly in both groups treated with n-3 FAs from baseline to t(3) and t(6) (P < 0.001). The omega-3 index increased to a greater extent in the rTAG group than in the EE group (t(3): 186 versus 161% (P < 0.001); t(6): 197 versus 171% (P < 0.01)). Conclusion: A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.

Diarrhea, asthma, arthritis--What is your wheat re-exposure syndrome?

Have you experienced a wheat re-exposure syndrome?

As I recently discussed, gastrointestinal distress--cramps, gas, diarrhea--is the most common "syndrome" that results from re-exposure to wheat after a period of elimination.

Others experience asthma, sinus congestion and infections, mental "fogginess" and difficulty concentrating, or joint pains and/or overt swelling.

Still others say there is no such thing.

Let's take a poll and find out what readers say.

Marathoners, triathletes, and heart disease

Curious thing: People with lipoprotein(a) gravitate towards elite levels of exercise.

I tell my lipoprotein(a) patients that, if they want to see a lot of other people with lipoprotein(a), go to a marathon or triathlon.

This effect applies more to males than to females, just as the fascination with numbers seems to be confined to men, too. That's why I've posted in past about the "prototypical" lipoprotein(a) male.

I believe this is a big part, perhaps the only, reason why there seems to be a modest increased risk for cardiovascular events despite high exercise levels in marathoners. It has nothing to do with the exercise itself; it has to do with the kind of people who choose to exercise at this level.

The best fish oil

The best fish oils available are the liquid forms. Contrary to many people's expectations, the best liquid fish oils have no fishy odor or taste.

I use a lot of liquid fish oils because of the higher doses we use in the Track Your Plaque program, as well as our strategy of high-dose fish oil to reduce lipoprotein(a). Women, in particular, don't like taking the oodles of capsules required to achieve the higher doses we need. So the ladies really like the liquid forms.

The best liquid fish oils are non-fishy, highly-concentrated, and come in the better absorbed triglyceride form. Many capsules, including prescription Lovaza, are the less well-absorbed ethyl ester form. Several studies, such as this one, have now demonstrated that the naturally-occurring triglyceride form yields higher blood (RBC) levels of omega-3 fatty acids, likely due to more efficient digestion via pancreatic lipase.

While there are many good forms of fish oil and only a few bad, these are the best of the best:

Pharmax
The Pharmax Finest Pure Fish Oil with Essential Oil of Orange contains 1800 mg EPA + DHA per teaspoon. This is the preparation I've been taking.

Nordic Naturals
The Nordic Naturals lemon-flavored ProOmega Liquid contains 2752 mg EPA + DHA per teaspoon, the most concentrated of any fish oil I've seen.

(This list is not exclusive. These are just two brands I've used extensively with good results.)

These highly-concentrated, triglyceride forms are more expensive, due to their concentrated nature. 1 teaspoon Pharmax fish oil, for example, provides an equivalent quantity of omega-3 fatty acids as 6 standard fish oil capsules on a milligram for milligram basis, but more like 8 to 9 capsules when absorption efficiency is factored in. The triglyceride form is also more laborious to manufacture. On our Track Your Plaque Marketplace, our Pharmax 500 ml runs $58.95 list. (500 ml provides 100 teaspoons or 600-capsule equivalent.)

Note that, minus the protection of the capsule, liquid fish oils will oxidize if not refrigerated. So be sure to keep your liquid fish oil in the fridge.