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.

No more Lovaza

That's it: I will NEVER ever write another prescription for Lovaza.

I actually very rarely write a prescription for Lovaza, i.e., prescription fish oil. But this was the last straw.

I advised a patient that we've had good success using high-doses of fish oil to reduce lipoprotein(a), Lp(a). 6000 mg per day of the omega-3 component (EPA + DHA) from fish oil reduces Lp(a) in 60% of people after one year. (Recall that Lp(a) is the most aggressive known lipid-related cause of heart disease.)

The two preparations I generally suggest are either the very affordable Sam's Club Members Mark Triple-Strength Fish Oil with 900 mg EPA + DHA per capsule: 7 capsules per day. Another great product (my personal favorite because of its extreme purity--it doesn't even smell like fish oil): Pharmax Finest Pure Fish Oil with 1800 mg EPA + DHA per teaspoon: 3 to 3 1/2 teaspoons per day.

Both preparations work great and are quite affordable, given the high dose. For the Sam's Club preparation, it will cost around $30 per month, while the Pharmax liquid will run around $49 per month.

Well, the woman's husband insisted on a prescription for Lovaza. One Lovaza capsule contains 784 mg EPA + DHA per capsule: 7 to 8 capsules per day.

Here are some prices for Lovaza from online pharmacy discounters:
Prescription Giant: $78.99 for 30 capsules ($2.63 per capsule)
Planet Drugs Direct: $135 for 100 capsules ($1.35 per capsule)

These are lower than the prices I obtained in past by calling local pharmacies in my area, quite a bit lower, in fact.

Filling the Lovaza prescription at Prescription Giant will therefore cost $552.93 to $631.92 per month; at Planet Drugs Direct it will cost $283.50 to $324.00 per month. At local pharmacies, a similar 7 to 9 capsules Lovaza per day will cost upwards of $800 to $900 per month.

The patient's husband insisted on the Lovaza prescription because he knew that his insurance would cover it. When I pointed out that this was a large cost that would have to be borne by others in their healthcare premiums, he said that didn't matter to him.

I hesitated, but ended up writing the prescription for 7 Lovaza capsules per day. As soon as I handed to him, I regretted it. In fact, I am embarassed and angry at myself for having given in.

So I vowed: I will NEVER EVER write another prescription for Lovaza.

I do not believe that we should spread the excessive profiteering of the pharmaceutical industry around on the backs of people who pay their healthcare insurance premiums, just so that a few people, like this selfish couple, can save a few dollars a month.

This is your brain on wheat II

In the original Heart Scan Blog post, This is your brain on wheat, I discussed how opioid peptides (i.e., small proteins that act like opiates such as heroine or morphine) that result from digestion of wheat cause unique effects on the human brain, particularly addictive behaviors. I also briefly reviewed how elimination of wheat has been shown to reduce auditory hallucinations and other psychotic behaviors in a subset of people with paranoid schizophrenia.

These two phenomena, addictions and schizophrenia, are most likely the result of exorphins that cross the blood-brain barrier. Exorphins--exogenous morphine-like compounds--can be blocked by opiate-blocking drugs like naloxone and naltrexone. Naloxone is used in hospitals to reverse morphine or heroine overdoses; naltrexone is being repackaged into a weight loss drug, since blocking wheat-derived exorphins reduces appetite. (Yes: The USDA tells us to eat more wheat, the drug industry sells us the antidote.)

There's another way that wheat can affect the brain and nervous system: immune-activated damage.

This is similar to the effect seen in celiac. There's even overlap with some of the antibody markers used to diagnose celiac, like the anti-gliadin antibodies and the anti-endomysium antibodies.

The most common immune neurological syndrome consequent to wheat consumption is cerebellar ataxia, a condition in which an immune response causes damage to the Purkinje cells of the cerebellum, the portion of the brain responsible for balance and coordination. This results in stumbling, incoordination, incontinence, and eventually leads to reliance on a cane or walker and wearing a diaper. Average age of onset: 53 years. A shrunken, atrophied cerebellum can be seen on an MRI of the brain.

Problem: Most people with central nervous system damage caused by wheat do not have any intestinal symptoms, like diarrhea and abdominal pain, the sort of symptoms usually associated with celiac disease. It means the first sign of wheat-induced brain damage may be bumping into walls and wetting your pants.

There's no such thing as a "no-carb" diet

When I tell patients how I advise a wheat-free, cornstarch-free, sugar-free diet on the background of a low-carbohydrate diet, some people ask: "But can I live on a no-carb diet?"

Well, there's no such thing as a "no-carb" diet. Low-carb, yes. No-carb, no.

Here are the carbohydrate contents of various "low-carb" foods:

Gouda cheese--3 oz contains 1.65 grams carbohydrates
Mozzarella cheese--1 cup contains 2.89 grams carbohydrates
Walnuts--4 oz (56 nuts) contains 2.96 grams carbohydrates
Almonds--4 oz contains 1.38 grams carbohydrates
Sour cream--one-half cup contains 3.31 grams carbohydrates
Red wine--3.5 oz glass contains 2.69 grams carbohydrates
Eggplant--1 cup cooked contains 8.33 grams carbohydrates
Green pepper--1 medium-sized raw contains 5.52 grams carbohydrates
Cucumber--1 medium contains 4.34 grams carbohydrates
Tomato--1 medium contains 4.82 grams carbohydrates

(Nutrition data from USDA Nutrient Database)

In other words, foods thought to be "low-carb" actually contain a modest quantity of carbohydrates.

Such modest quantities of carbohydrates may not be enough to trip your blood sugar. But add up all the "low-carb" foods you consume over the course of a day and you can easily achieve 30 grams or more carbohydrates per day even without consuming any higher carbohydrate foods.

Why doesn't your doctor try to CURE diabetes?

Imagine you have breast cancer. You go to your doctor and she says, "As your pain worsens, we'll help you with pain medication. We'll fit you with a special bra to accommodate the tumor as it grows. That's all we're going to do."

"What?" you ask. "You mean just deal with the disease and its complications, but you're not going to help me get rid of it . . . cure it?"

It would be incredibly shocking to receive such advice. Then why is that the sort of advice given when you are diagnosed with diabetes?

Say you go to the doctor. Lab values show a fasting blood sugar of 156 mg/dl, HbA1c (a reflection of your previous 60 days average glucose) of 7.1%. Both values show clear-cut diabetes.

Your doctor advises you to 1) start the drug metformin, then 2) talk to the diabetic teaching nurse or dietitian about an American Diabetes Association (ADA) diet.

The ADA diet prescribed encourages you to increase carbohydrates and cut fats at each meal and maintain a consistent intake so that you don't experience hypoglycemic (low blood sugar) episodes. You follow the diet, which causes you to gain 10-15 lbs per year, increasing your "need" for diabetes medication. You doctor adds Actos, then Januvia, then injections of Byetta.

Three years and 34 lbs later, you are not responding well to the drug combination with blood sugars rarely staying below 200 mg/dl. You've developed protein in your urine ("proteinuria"), lost 30% of your kidney function, and you are starting to lose sensation in your feet. So the doctor replaces some of your medication with several insulin injections per day.

This formula is followed millions of times per year in the U.S. So where along the way did your doctor mention anything about a "cure"?

Adult diabetes is the one chronic disease that nobody cares to cure. Treat it, maintain control over blood sugars, but cure it? Most physicians say it's impossible.

The tragedy is that diabetes is a curable condition. I've seen it happen many times. Physicians dedicated to curing diabetes like low-carb expert, Dr. Mary Vernon, have cured it countless times. Dr. Eric Westman and colleagues have been building the case for the carbohydrate-restricted cure for diabetes with studies such as this. In this last study, of the 8 participants on insulin + medications at the start of the study, 5 no longer required medications at the close of the study--they were essentially non-diabetic.

I tell patients that diabetes, in fact, is a disease you choose to have or not to have--provided you are provided the right diet and tools. Sadly, rarely are diabetics told about the right diet and tools.

That's why Cadbury Schweppes has been a major contributor to the American Diabetes Association, as are other processed food manufacturers and the drug industry, all who stand to profit from maintaining the status quo.

The cure? Eliminate or at least dramatically reduce carbohydrates, the foods that increase blood sugar.

Note: If you have diabetes and you are taking any prescription agents, such as glyburide, glipizide, insulin, and some others, you will need to discuss how to manage your medications if you reduce carbohydrates. The problem is finding a doctor or other resource to help you do this.

LDL pattern B

Here's a Q&A I stumbled on in the Forum of MedHelp, where people obtain answers from presumed health "experts."

Question:

My VAP test results in July 07 identified an LDL Pattern B.
Overall results:
Total 150
HDL 75
LDL 61
Trig 60
HDL-2 17
LP(a) 6.0
LDL Pattern B

Medications:
Lipitor 10mg
Zetia 10mg
Altace 10mg
Atenolol 50mg
Plavix 75mg
Aspirin 81mg

I had several heart attacks which resulted in CABG performed May 2000. I am a 53 year old white male , 6'1", 190 pounds, exercise every day, watch my diet and feel great. Everything looks OK except my LDL Pattern B. Is there any therapy to improve the Patten B?


Answer from CCF, MD:
Your results indicate an LDL pattern B, which generally indicates small atherogenic LDL particles which may cause increased risk for CAD. However, there are several problems with LDL patterning: 1) its unreliability (of LDL pattern testing ), 2) unclear clinical evidence regarding regarding the usefulness of LDL patterns and particle size. The majority of evidence regarding the progression of atherosclerosis is with LDL lowering and to an smaller extent HDL raising.

All available clinical evidence shows that any particles in the VLDL, IDL, or LDL range are atherogenic, and there is no evidence that whether belonging to pattern A or B one is more atherogenic than others.

Subclass studies have proliferated over the last few years, but many of these studies were funded or subsidized either by suppliers of the assays as a method to expand their use and move them into mainstream practice, or by pharmaceutical companies in an attempt to claim some advantage over other therapeutic agents.
Thus, current data on LDL subclasses are at best incomplete and at worst misleading, suffering from publication bias, and now given the recent results of the Ensign et al. study, unreliable.

Your LDL, and HDL are at goal. The Lpa level is still not clearly linked as a modifiable risk factor for CAD, although elevated levels are now know to be linked to stroke.

Continue with your present treatments: aspirin, plavix, ateonol and altace are all essential medications.



Wow. The extent of ignorance that pervades the ranks of my colleagues is frightening.

Contrary to the response, LDL particle size assays are quite reliable and accurate. I've performed many thousands of lipoprotein assays and they yield reproducible and clinically believable results. For example, eliminate wheat, oats, cornstarch, and sugars and small LDL drops from 2400 nmol/L to 893 nmol/L (NMR)--huge drops. If repeated within a short period of time, the second measure will correspond quite closely.

The data are also quite clear: Small LDL particles (i.e., "pattern B") are a potent predictor of cardiovascular events. What we lack are the treatment trials that show that reduction of small LDL results in reduced cardiovascular events. The reason for this is that small LDL research is not well-funded, since there is no prescription drug to treat small LDL, only nutritional means. Niacin (as Niaspan) is as close as it comes for a "drug" to reduce small LDL. But diet is far more effective.

Given the questioner's fairly favorable BMI of 25.1 and his history of aggressive heart disease, it is virtually certain that he has what I call "genetic small LDL," i.e., small LDL that occur on a genetically-determined basis (likely due to variants of the cholesteryl-ester transfer protein, or CETP, or of hepatic lipase and others).

Ignoring this man's small LDL will, without a doubt, consign him to a future of more heart attacks, stents, and bypass. Maybe by that time the data supporting the treatment of small LDL will become available.

What increases blood sugar more than wheat?

Take a look at these glycemic indexes (GI):


White bread 69
Whole wheat bread 72
Sucrose 59
Mars bar 68
White rice 72
Brown rice 66


I've made issue in past of whole wheat's high GI--higher than white bread. Roughly in the same glycemic league as bread are shredded wheat cereal, brown rice, and a Mars candy bar.

With few exceptions, wheat products have among the highest GIs compared to the majority of other foods. For instance:


Kidney beans 29
Chick peas 36
Apple 39
Ice cream 36
Snickers Bar 40


Yes, by the crazy logic of glycemic index, Snickers is a low-glycemic index food.

While I do not believe that low GI makes a food good or desirable, since low GI foods still provoke high blood sugars, small LDL particles, trigger glycation, and other abnormal phenomena, they are clearly less obnoxious than the items in the first list.

Take a look at this list:

Cornflakes 80
Rice cakes 80
Rice Krispies 82
Rice pasta, 92
Instant potatoes 83
Tapioca 81



Starches that are dried and/or pulverized, such as cornstarch, potato starch, rice starch, and tapioca starch (cassava root) will increase blood sugar even more than wheat. Foods with these starches have GI's of 80-100.

Cornstarch, potato starch, rice starch, and tapioca starch: Sound familiar? These are the main starches used in "gluten-free" foods. A hint of the high GI behavior of these dried starches is seen in the GI for cornflakes of 80.

So remember: Wheat-free is not the same as gluten-free. Gluten-free identifies junk carbohydrates masquerading as healthy because they don't contain one unhealthy ingredient, i.e. wheat.

China fiction?

Dr. Colin Campbell caused a stir with publication of his 2005 book, The China Study. Dr. Campbell, after extensive animal and epidemiologic research conducted in China over 20 years, concluded that a diet high in animal protein, especially casein, was associated with increased cancer, osteoporosis, and heart disease risk.

Richard Nikoley of Free the Animal and Stephan Guyenet of Whole Health Source have been talking about an analysis of the China Study raw data performed by a young woman named Denise Minger.

Denise's analysis is nothing short of brilliant, absolutely "must" reading for anyone interested in nutrition.

Her comments on the relationship of wheat to heart disease:

Why does Campbell indict animal foods in cardiovascular disease (correlation of +1 for animal protein and -11 for fish protein), yet fail to mention that wheat flour has a correlation of +67 with heart attacks and coronary heart disease, and plant protein correlates at +25 with these conditions?

Speaking of wheat, why doesn’t Campbell also note the astronomical correlations wheat flour has with various diseases: +46 with cervix cancer, +54 with hypertensive heart disease, +47 with stroke, +41 with diseases of the blood and blood-forming organs, and the aforementioned +67 with myocardial infarction and coronary heart disease?

Carbohydrate-LDL double whammy

Carbohydrates in the diet trigger formation of small LDL particles. Because carbohydrates, such as products made from wheat, increase triglycerides and triglyceride-containing lipoproteins (chylomicrons, chylomicron remnants, VLDL, and IDL), LDL particles (NOT LDL cholesterol) become triglyceride-enriched. Triglyceride-enriched LDL particles are "remodeled" by the enzyme, hepatic lipase, into triglyceride-depleted, small LDL particles.

The list of reasons why small LDL particles are more atherogenic, i.e., plaque-causing, is long:

--Small LDL particles, being smaller, more readily penetrate the endothelial barrier of the arterial wall.
--Small LDL particles are more adherent to glycosaminoglycans in the artery wall.
--Small LDL particles are poorly taken up by the liver LDL receptor, but enthusiastically taken up by macrophage receptors of the sort in your artery walls.
--Because of their poor liver clearance, small LDL persists in the bloodstream far longer than large LDL.
--Small LDL particles are more oxidation-prone. Oxidized LDL are more likely to trigger inflammatory phenomena and be taken up by macrophages in the artery wall.

Let me add another reason why small LDL particles are more likely to cause plaque: They are more likely to undergo glycation. (More on glycation here.)

Glycation occurs when glucose (sugar) molecules in the blood or tissue modify proteins, usually irreversibly. Small LDL particles are uniquely glycation-prone. (This is likely due to a conformational change of the apoprotein B in the small LDL particle, exposing lysine residues along apo B that become glycated.)

Here's a great demonstration of this phenomenon by Younis et al:


"LDL3" is the small type. Note that small LDL particles are 4-5 times more glycated than large LDL. That's a big difference.

Once glycated, small LDL is especially resistant to being taken up by the liver. Like annoying in-laws, they hang around and hang around and . . . The longer they hang around, they more opportunity they have to contribute to plaque formation.

So, carbohydrates trigger formation of small LDL particles. Once formed, small LDL particles are glycated when blood sugar increases. While LDL can be glycated even when blood sugars are in the normal range (90 mg/dl or less), glycation goes berserk when blood sugars go higher, such as a blood sugar of 155 mg/dl after a bowl of steel-cut oatmeal.

To lose weight, prick your finger

We know that foods that trigger insulin lead to fat storage. Putting a stop to this process allows you to mobilize fat and lose weight. If you're starting out from scratch, rapid and dramatic weight loss can be experienced, as much as one pound per day.

So how can you stop triggering insulin?

The easiest way is to eliminate, or at least minimize, carbohydrates. My favorite method to restrict carbohydrates is to eliminate wheat and minimize exposure to other carbohydrates, such as oats, cornstarch, and sugars. All these foods, wheat products worst of all, cause blood sugar and insulin to skyrocket.

Another way is to check your blood sugar one hour after completing a meal and keep your after-eating, or "postprandial," blood sugar 100 mg/dl or less. Let's say you are going to eat stone ground oatmeal, for example. Blood sugar prior to eating is, say, 90 mg/dl. One hour after oatmeal it's 168 mg/dl--you know that this is going to trigger insulin and make you fat. Oatmeal should therefore be eliminated.

Keeping blood sugar to 100 mg/dl or less after eating teaches you how to avoid provocation of insulin. A shrinking tummy will follow.

To do this, you will need:

1) A glucose meter--My favorite is the One Touch Ultra Mini ($13.42 at Walmart). It's exceptionally easy to use and requires just a dot of blood. Drawback: Test strips are about $1 each. Accuchek Aviva is another good device. (We've had a lot of problems with Walgreen's brand device.)
2) Test strips--This is the costly part of the proposition. Purchased 25 or 50 at a time, they can cost from $0.50 to $1.00 a piece.
3) Lancets--These are the pins for the fingerstick device that comes with the glucose meter. A box should be just a few dollars.

No prescription is necessary, nor will insurance pay for your costs unless you're diabetic. To conserve test strips, use them only when a new, untested food or food combination is going to be consumed. If you had two scrambled eggs with green peppers, sundried tomatoes, and olive oil yesterday and had a one hour postprandial glucose of 97 mg/dl, no need to check blood sugar again if you are having the same meal again today.

Iodine update

As the iodine experience grows, I've made several unique observations.

Up to several times per day, I see people who are responding in some positive way to iodine supplementation. (See previous Heart Scan Blog posts about iodine: Iodine deficiency is REAL and The healthiest people are the most iodine deficient.)

Among the phenomena I've observed:

1) A free T4 thyroid hormone at the low end of normal, or even in the below normal range, along with a highish TSH (usually >1.5 mIU/L) are the most frequent patterns that signal iodine deficiency. Occasionally, a low free T3 value will also increase, though this is the least frequent development.

2) At a dose of 500 to 1000 mcg iodine per day, it requires anywhere from 3 to 6 months to obtain normalization of thyroid measures.

3) Reversal of small goiters also occurs over about 6 months.

4) Iodine intolerance is uncommon. If it occurs, using a low starting dose, e.g., 100-200 mcg per day, usually works. The dose can be increased gradually over the ensuing months.

5) Perceptible benefits of iodine occur only occasionally. The most common perceptible effects are increased energy and increased warmth, especially of the hands and feet.

6) Some people who have taken thyroid hormones for years will develop reduced need for their medication with iodine supplementation. In other words, their physician was inadvertently treating iodine deficiency with thyroid hormone replacement. Anyone already on any thyroid preparation(s), e.g., Synthroid, levothyroxine, Armour thyroid, Naturethroid, etc., should watch for signs of hyperthyroidism when iodine is added. But having your own thyroid gland make its own thyroid hormones is better and healthier than relying on the prescription agents. Just be sure to monitor your thyroid measures.

7) Iodine toxicity can occur--Two people in my clinic population developed iodine toxicity by taking 6000 mcg iodine per day for 6 or more months. (Both patients did it on their own based on something they read). Iodine toxicity is evidenced by shutting down your thyroid, i.e., marked increase in TSH, e.g., 15 mIU/L.


Most of the people in my clinic obtain their iodine from kelp tablets. Some use potassium iodine (KI) drops. A handful have used the high-potency Iodoral (12.5 mg or 12,500 mcg iodine per tablet); this was also the form that generated the toxic effects in the two females.

All in all, iodine deficiency is actually far more common than I ever suspected. Not everybody is iodine deficient. But a substantial minority of the Midwest population I see certainly are.