MUFFINS MAKE YOU SMALL
“Drink me.”
So Alice drank the potion and found herself ten inches tall, now able to pass through the door and cavort with the Mad Hatter and Cheshire Cat.
To LDL particles, that bran muffin or ten-grain bagel you had this morning is just like Alice’s “Drink me” potion: It makes them small. Starting at, say, 29 nm in diameter, bran muffins and other wheat products will cause LDL particles to shrink to 23 or 24 nm.2
Just as Alice was able to walk through the tiny door once she had shrunk to ten inches, so the reduced size of LDL particles allows them to begin a series of unique misadventures that normal-size LDL particles cannot enjoy.
Like humans, LDL particles present a varied range of personality types. Large LDL particles are the phlegmatic civil servant who puts in his time and collects his paycheck, all in anticipation of a comfortable state-supported retirement. Small LDLs are the frenetic, anti-social, cocaine-crazed particles that fail to obey the normal rules, causing indiscriminate damage just for laughs. In fact, if you could design an evil-doing particle perfectly suited to form gruel-like atherosclerotic plaque in the walls of arteries, it would be small LDL particles.
Large LDL particles are taken up by the liver LDL receptor for disposal, adhering to the normal physiologic route for LDL particle metabolism. Small LDL particles, in contrast, are poorly recognized by the liver LDL receptor, allowing them to linger much longer in the bloodstream. As a result, small LDL particles have more time to cause atherosclerotic plaque, lasting an average of five days compared to the one to three days of large LDL.3 Even if large LDL particles are produced at the same rate as small LDL, the small will substantially outnumber the large by virtue of increased longevity. Small LDL particles are also taken up by inflammatory white blood cells (macrophages) that reside in the walls of arteries, a process that rapidly grows atherosclerotic plaque.
You’ve heard about the benefit of antioxidants? Oxidation is part of the process of aging, leaving a wake of oxidatively modified proteins and other structures that can lead to cancer, heart disease, and diabetes. When exposed to an oxidizing environment, small LDL particles are 25 percent more likely to oxidize than large LDL particles. When oxidized, LDL particles are more likely to cause atherosclerosis.4
The glycation phenomenon shows itself with small LDL particles as well. Compared to large particles, small LDL particles are eightfold more susceptible to endogenous glycation; glycated small LDL particles, like oxidized LDL, are more potent contributors to atherosclerotic plaque.5 The action of carbohydrates is therefore twofold: Small LDL particles are formed when there are plentiful carbohydrates in the diet; carbohydrates also increase blood glucose that glycates small LDL. Foods that increase blood glucose the most therefore translate into both greater quantities of oxidation-prone small LDL and increased glycation of small LDL particles.
So heart disease and stroke are not about high cholesterol. They are caused by oxidation, glycation, inflammation, small LDL particles…yes, the processes initiated, then worsened, by carbohydrates, especially the amylopectin A of wheat.
As much as your doctor squawks about statin drugs, heart disease risk is not really about cholesterol. It’s about the particles that cause atherosclerosis. Today, you and I are able to directly quantify and characterize lipoproteins, relegating cholesterol to join frontal lobotomies in the outdated medical practice garbage dump in the sky.
One crucial group of particles that you should be aware of, the granddaddy of them all, is very low-density lipoproteins, or VLDL. The liver packages various proteins and fats together as VLDL particles, so called because abundant fats make the particle lower in density than water, i.e, very low density (thus accounting for the way olive oil floats above vinegar in salad dressing). VLDL particles are then released, the first lipoproteins to enter the bloodstream.
Large and small LDL particles share the same parents, namely VLDL particles. A series of changes in the bloodstream determines whether VLDL will be converted to big or small LDL particles. The composition of diet has a very powerful influence over the fate of VLDL particles, determining what proportion will be big LDL versus what proportion will be small LDL. You may not be able to choose the members of your own family, but you can readily influence what offspring VLDL particles will have and thereby whether or not atherosclerosis develops.
THE BRIEF, WONDROUS LIFE OF LDL PARTICLES
At the risk of sounding tedious, let me tell you a few things about these lipoproteins in your bloodstream. This will all make sense in just a few paragraphs. At the end of it, you will know more about this topic than 98 percent of physicians.
“Parent” lipoproteins of LDL particles, VLDL, enter the bloodstream after release from the liver, eager to spawn their LDL offspring. On release from the liver, VLDL particles are richly packed with triglycerides, the currency of energy in multiple metabolic processes. Depending on diet, more or less VLDLs are produced by the liver. VLDL particles vary in triglyceride content. In a standard cholesterol panel, excessive VLDL will be reflected by higher levels of triglycerides, a common abnormality.
VLDL is an unusually social being, the lipoprotein life of the party, interacting freely with other lipoproteins passing its way. As VLDL particles bloated with triglycerides circulate in the bloodstream, they give triglycerides to both LDL and HDL (high-density lipoproteins) in return for a cholesterol molecule. Triglyceride-enriched LDL particles are then processed through another reaction that removes triglycerides provided by VLDL.
LDL particles begin large, 25.5 nm or greater in diameter, and receive triglycerides from VLDL in exchange for cholesterol. They then lose triglycerides. The result: LDL particles become both triglyceride-depleted and cholesterol-enriched and several nanometers smaller in size.6, 7
It doesn’t take much in the way of excess triglycerides from VLDL to begin the cascade toward creating small LDL. At a triglyceride level of 133 mg/dl or greater, within the “normal” cutoff of 150 mg/dl, 80 percent of people develop small LDL particles.8 A broad survey of Americans, age twenty and older, found that 33 percent have triglyceride levels of 150 mg/dl and higher—more than sufficient to create small LDL; that number increases to 42 percent in those sixty and older.9 In people with coronary heart disease, the proportion who have small LDL particles overshadows that of all other disorders; small LDL is, by far, the most frequent pattern expressed.10
That’s just triglycerides and VLDL present in the usual fasting blood sample. If you factor in the increase in triglycerides that typically follows a meal (the “postprandial” period), increases that typically send triglyceride levels up two- to fourfold for several hours, small LDL particles are triggered to an even greater degree.11 This is likely a good part of the reason why non-fasting triglycerides, i.e., triglycerides measured without fasting, are proving to be an impressive predictor of heart attack, with as much as five- to seventeenfold increased risk for heart attack with higher levels of non-fasting triglycerides.12
VLDL is therefore the crucial lipoprotein starting point that begins the cascade of events leading to small LDL particles. Anything that increases liver production of VLDL particles and/or increases the triglyceride content of VLDL particles will ignite the process. Any foods that increase triglycerides and VLDL during the several hours after eating—i.e., in the postprandial period—will also cascade into increased small LDL.
NUTRITIONAL ALCHEMY: CONVERTING BREAD TO TRIGLYCERIDES
So what sets the entire process in motion, causing increased VLDL/triglycerides that, in turn, trigger the formation of small LDL particles that cause atherosclerotic plaque?
Simple: carbohydrates. Chief among the carbohydrates? The amylopectin A of wheat and grains, of course.
TO LIPITOR OR NOT: THE ROLE OF WHEAT
As noted earlier, wheat consumption increases small LDL particles; eliminating wheat reduces or eliminates s
mall LDL particles. But it may not look that way at first.
Here’s where it gets kind of confusing—confusing enough to stump your doctor and open the door for the drug industry to persuade him/her of such things as “cholesterol must be reduced with a statin agent,” just as the tobacco industry once convinced the medical establishment that deep breathing encouraged by smoking cigarettes was good for lung health.
The standard lipid panel that your doctor relies on to crudely gauge risk for heart disease uses a calculated LDL cholesterol value—not a measured value. All you need to calculate LDL cholesterol is a calculator to sum up LDL cholesterol from the following equation (called the Friedewald calculation):
LDL cholesterol = total cholesterol – HDL cholesterol – (triglycerides ÷ 5)
The three values on the right side of the equation—total cholesterol, HDL cholesterol, and triglycerides—are indeed measured. Only LDL cholesterol is calculated.
The problem is that this equation was developed by making several assumptions. For this equation to work and yield reliable LDL cholesterol values, for instance, HDL must be 40 mg/dl or greater, triglycerides 100 mg/dl or less. Any deviation from these values and the calculated LDL value will be thrown off.13, 14 Diabetes, in particular, wildly throws off the accuracy of the calculation; 50 percent inaccuracy is not uncommon: 200 mg/dl might really be 100, 100 mg/dl might really be 150. Genetic variants can also throw the calculation off (e.g., apo E variants), as does any change in diet. In other words, relying on calculated LDL cholesterol is like asking a four-year-old about the anticipated movements of the stock market—the answer may be cute, but hardly accurate.
Another problem: If LDL particles are small, calculated LDL will markedly underestimate real LDL. Conversely, if LDL particles are large, calculated LDL will overestimate real LDL (meaning the people at lowest risk are the most likely to have statin drugs forced on them).
To make the situation even more confusing, if you shift LDL particles from undesirably small to healthfully large by some change in diet—a good thing—the calculated LDL value will often appear to go up, while the real value is actually going down. While you achieved a genuinely beneficial change by reducing small LDL, your doctor tries to persuade you to take a statin drug for the appearance of high LDL cholesterol. (That’s why I call LDL cholesterol “fictitious LDL,” a criticism that has not stopped the ever-enterprising pharmaceutical industry from deriving billions of dollars in annual sales of statin drugs. Maybe you benefit, but you probably don’t; calculated LDL cholesterol can’t tell you, even though that is the FDA-approved indication: high calculated LDL cholesterol.) LDL cholesterol is a virtually worthless value, a bogeyman of cardiovascular health, yet the basis for prevailing medical practice and billions of dollars of drug company revenues, not to mention the explosion of foods and supplements purported to “reduce cholesterol.”
The only way for you and your doctor to truly know where you stand is to actually measure LDL particles in some way, such as LDL particle number (by a laboratory method called lipoprotein analysis via nuclear magnetic resonance, NMR, or electrophoresis) or apoprotein B. (Because there is one apoprotein B molecule per LDL particle, apoprotein B provides a virtual LDL particle count.) It’s not that tough, but it requires a health practitioner willing to invest the extra bit of education to understand these issues and turn away the drug sales rep dropping by the office—probably the same practitioner who recognizes that wheat and grains cause heart disease and do not prevent it.
For years, these simple facts eluded nutrition scientists. After all, dietary fats, maligned and feared, are composed of triglycerides. Logically, increased intake of fatty foods, such as greasy meats and butter, should increase blood levels of triglycerides. This proved true—but only transiently and to a small degree.
More recently, it has become clear that, while increased intake of fats does indeed deliver greater quantities of triglycerides into the liver and bloodstream, it also shuts down the body’s own production of triglycerides. Because the body is able to produce large quantities of triglycerides that handily overwhelm the modest amount taken in during a meal, the net effect of high fat intake is little or no change in triglyceride levels.15
Foods high in carbohydrates, on the other hand, contain virtually no triglycerides. Two slices of whole grain bread, an onion bagel, or sourdough pretzel contain negligible triglycerides (i.e., fats). But carbohydrates possess the unique capacity to stimulate insulin, which in turn triggers fatty acid synthesis in the liver, a process that floods the bloodstream with triglycerides.16 Depending on genetic susceptibility to the effect, carbohydrates can send triglycerides into the hundreds or even thousands of mg/dl range. The body is so efficient at producing triglycerides that high levels, e.g., 300 mg/dl, 500 mg/dl, even 1,000 mg/dl or more, can be sustained twenty-four hours a day, seven days a week for years—provided the flow of carbohydrates continues.
In fact, the recent discovery of the process of de novo lipogenesis, the liver alchemy that converts sugars into triglycerides, has revolutionized the way nutritional scientists view food and its effects on lipoproteins and metabolism. One of the crucial phenomena required to begin this metabolic cascade is high levels of insulin in the bloodstream.17, 18 High insulin levels stimulate the machinery for de novo lipogenesis in the liver, efficiently transforming carbohydrates into triglycerides, which are then packaged into VLDL particles.
The early twenty-first century will go down in history as the Age of Carbohydrate Consumption. Today, half or more of all calories consumed by Americans come from carbohydrates.19 Such a dietary pattern means that de novo lipogenesis can proceed to such extreme degrees that the excess fat created infiltrates and accumulates in the liver. That’s why so-called non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatosis (NAS)—“fatty liver”—have reached such epidemic proportions that gastroenterologists have their own convenient abbreviations for them. NAFLD and NAS lead to liver cirrhosis, an irreversible disease similar to that experienced by alcoholics, thus the non-alcoholic disclaimer.20
Ducks and geese are also capable of packing their livers full of fat, an adaptation that allows them to fly long distances without sustenance, drawing on stored liver fat for energy during annual migration. For fowl, it’s part of an evolutionary adaptation. Farmers take advantage of this fact when they produce geese and duck livers full of fat: Feed the birds carbohydrates from grains, yielding foie gras and the fatty pâté you spread on whole wheat crackers. But for humans, fatty liver is a perverse, unphysiologic consequence from being told to consume more carbohydrates, a process that can lead to cirrhosis and liver failure. Unless you’re dining with Hannibal Lecter, you don’t want a foie gras–like liver in your abdomen.
This makes sense: Carbohydrates are the foods that encourage fat storage, a means of preserving the bounty from times of plenty. If you were a primitive human, satiated from your meal of freshly killed boar topped off with some wild berries and fruit, you would store excess carbohydrate calories in case you failed to catch another boar or other prey in the coming days or weeks. Insulin helps store the excess energy as fat, transforming it into triglycerides that pack the liver and spill over into the bloodstream, energy stores to be drawn from when the hunt fails. But in our bountiful modern times, the flow of calories, especially those from carbohydrates such as grains, never stops, but flows endlessly. Today, every day is a day of plenty.
The situation is worsened when excess visceral fat accumulates. Visceral fat acts as a triglyceride repository, but one that causes a constant flow of triglycerides into and out of fat cells, triglycerides that enter the bloodstream.21 This results in liver exposure to higher blood levels of triglycerides, which further drives VLDL production.
Diabetes provides a convenient testing ground for the effects of high-carbohydrate eating, such as a diet rich in “healthy whole grains.” The majority of adult (type 2) diabetes is brou
ght on by excessive carbohydrate consumption; high blood sugars and diabetes itself are reversed in many, if not most, cases by reduction of carbohydrates.22
Diabetes is associated with a characteristic “lipid triad” of low HDL, high triglycerides, and small LDL, the very same pattern created by excessive carbohydrate consumption.23
Dietary fats therefore make only a modest contribution to VLDL production, while carbohydrates make a much larger contribution. This is why low-fat diets rich in “healthy whole grains” have become notorious for increasing triglyceride levels, a fact often glossed over as harmless by advocates of such diets. (My personal low-fat adventure many years ago, in which I restricted intake of all fats, animal and otherwise, to less than 10 percent of calories—a very strict diet, à la Ornish and others—gave me a triglyceride level of 350 mg/dl due to the plentiful “healthy whole grains” I substituted for the reduced fats and meats.) Low-fat diets typically send triglycerides up to the 150, 200, or 300 mg/dl range. In genetically susceptible people who struggle with triglyceride metabolism, low-fat diets can cause triglycerides to skyrocket to the thousands of mg/dl range, sufficient to cause fatty liver NAFLD and NAS, as well as damage to the pancreas.
Low-fat diets are not benign. The high-carbohydrate, plentiful whole grain intake that unavoidably results when fat calories are reduced triggers higher blood glucose, higher insulin, greater deposition of visceral fat, fatty liver, and more VLDL and triglycerides in the bloodstream, which then cascades into greater proportions of small LDL particles. Terrible dietary advice is then dealt with by prescribing drugs for diabetes and high cholesterol. Yes, this is the prevailing non-sensical standard in modern healthcare, little better than bloodletting or prescribing heroin for a cough.
Wheat Belly (Revised and Expanded Edition) Page 18
