Metabolical: The Lure and the Lies of Processed Food, Nutrition, and Modern Medicine

by Robert H. Lustig

A high protein composition of your diet activates mTOR, thereby promoting cell division, development of lean body mass, insulin sensitivity, and bone and cardiovascular health. Conversely, caloric deprivation (see Chapter 14) leads to lowering of ATP levels, which reduces mTOR, making growth an impossibility.

While cell metabolism has everything to do with energy, it has nothing to do with calories.

Each of these three enzymes can exist in one of two states—on or off. Therefore any cell’s metabolic status can be described by one of a total of 2 x 2 x 2, or 8 different combinations of these three enzymes. I want to state that this is a hypothesis, not proven—but this is a new way to think about the role of diet and nutrition, and it fits the available scientific data of nutrients and their effects on growth, burning, and disease.

Rule #1: Don’t take “busy” for an answer.

You must never use or accept the word normal from your doctor, yourself, or anyone else. I mean, what does normal actually mean? Normal for who? At what age? And in what circumstance? This term must disappear from your lexicon. And it should disappear from the entire medical lexicon. Rule #2: Don’t take “normal” for an answer.

BMI is a good measurement for populations (because populations regress to the mean), but not for people (because each of us is an “n of 1”). The real issue is insulin. If you look at the degree of insulin sensitivity at any given BMI, there’s a huge spread, meaning at any given weight, some will be healthy, and some won’t. What determines this isn’t the subcutaneous fat, but the liver (and secondarily, muscle) fat. You can’t determine these factors by looking at a patient’s BMI.

So these people are thought to be normal, thus the widening of the normal range. But just because you haven’t been diagnosed as “sick” doesn’t mean you aren’t.

The medical literature argues that 88 percent of Americans have some level of metabolic dysfunction that’s likely gone unrecognized, whether it’s fatty liver, high blood pressure, high blood uric acid (the cause of gout), high blood lipids, or high blood glucose. All of these are due in some measure to insulin resistance, which is due to metabolic dysfunction.

What would they advise if they did? If 88 percent of people have a problem, maybe it would be smart to assume you do, until such time as your doctor proves you don’t?

#3: Don’t take paternalism for an answer.

All in all, there are four pieces of data you have to diagnose yourself: family history, vital signs, waist circumference, and the standard fasting lab panel done at your doctor’s office. Rule #4: Get the numbers.

Virtually every chronic disease is polygenic, which means that multiple genes are involved in risk; and by most scientists’ estimations, genetics accounts for a maximum of 50 percent of the risk, and usually less. No one gene is going to answer all questions (now with 23andMe, your genetic risk profile can be assessed, but for chronic diseases it’s pretty useless).

The good news is that for chronic disease, genetics only explains about 15 percent of the variance in risk. The other 85 percent is environmental, which means there’s plenty you can do to mitigate your risk for diabetes, cancer, heart disease, dementia, and virtually every other chronic disease.

Vital signs. In general, your vital signs are always normal or you wouldn’t be walking around or reading this book. If

If you’re at the doctor’s office, you’re likely already anxious. Your pulse rate may be 5 to 10 beats per minute higher, and your systolic blood pressure 5 points higher than your baseline, just from fear and activation of the sympathetic nervous system, which is your body’s fight-or-flight mechanism. However, if your blood pressure rises at the doctor’s office above 130/90 on the first measurement and then goes down on the second, this is often referred to as white-coat hypertension, and is usually passed off by your doctor as benign.

The question is whether you can obtain your baseline vital signs at home and away from the doctor’s office—and, most important, while you’re sleeping. You can buy a finger blood pressure cuff at your local pharmacy to check your blood pressure at home, both before you go to sleep and immediately upon waking but before you get out of bed.

for about 20 percent of the public, that’s absolutely true—they’re exquisitely salt-sensitive and consistently need their dietary salt restricted. But most people with functioning kidneys should be able get rid of their excess salt just fine. So why aren’t they? Because we’re dealing with a population-level epidemic of insulin resistance.

Waist circumference. Waist circumference is a sign of either visceral (belly) fat, liver fat, or both. All the diseases of metabolic syndrome are associated with increased waist circumference—even in normal weight people—and so waist circumference is much more sensitive for disease risk than is BMI; in fact, waist circumference is increasing faster than BMI in the population, because it’s the visceral fat that’s going up more than the subcutaneous fat.

Fasting lab tests. There’s a boatload of information to be gleaned from fasting lab tests, but it often takes an experienced clinician who’s up-to-date in their medical knowledge and expertise to know how to order and interpret them properly. Here’s the list of the tests you need to make sure your doctor orders: lipid profile (LDL-C, HDL-C, TG), homocysteine (Hcy) level, alanine aminotransferase and aspartate aminotransferase (ALT and AST), uric acid, fasting insulin, fasting glucose, and hemoglobin A1c

The serum triglyceride (TG), when unloaded of its fat at the adipose tissue, becomes the small dense LDL. Therefore, the TG:HDL (high-density lipoprotein) ratio—the real ratio of bad to good cholesterol—is the best biomarker of small dense LDL, the best biomarker of cardiovascular disease, and the best surrogate marker of insulin resistance and metabolic syndrome.

The second thing to look at is the HDL. If it’s over 60, it almost doesn’t matter what the other fractions are, as this is a sign of good cardiovascular health. If the HDL is under 40 (men) or under 50 (women), then your predisposition for heart disease is much higher.

there is yet another dietary pathway to heart disease, and it has nothing to do with LDL or triglycerides. If you have a family history of heart disease, tell your doctor to look at your diet and epigenetics by drawing a serum homocysteine (Hcy) level. This is a lab test that is not routinely ordered because it’s not correlated with genetics and heart disease, only with diet and heart disease. Hcy is an amino acid associated with heart disease, but it does not come from eating protein. Hcy should be completely cleared from the bloodstream and eradicated or it will build up in the blood vessel and cause inflammation.

Fifth, you can also assess diet and mitochondrial function by measuring uric acid, which rises with sugar consumption. High uric acid levels lead to gout and hypertension, and also generate liver fat. Uric acid is a by-product of liver carbohydrate metabolism, especially when it metabolizes sugar. This prevents the mitochondria from metabolizing pyruvic acid to carbon dioxide, which forces the liver to turn excess energy into liver fat. Levels above 5.5 indicate mitochondrial dysfunction and insulin resistance.

Every practitioner gets a fasting glucose on all their adult patients, looking for type 2 diabetes. Yet this is the single worst parameter to measure, because it’s the last thing to change. Once the fasting glucose rises over 100 mg/dl (signifying glucose intolerance; 126 means diabetes), metabolic syndrome is in full force, and there are no options for prevention anymore; now you’re in full-fledged treatment mode. But in fact, a fasting blood glucose of 90 is already questionable. The same is true for hemoglobin A1c (HbA1c), the blood test that assesses glucose control over the preceding three months. By everyone’s estimation, under 5.5 percent is normal, while over 6.5 percent is frank type 2 diabetes.

So, irrespective of the fasting glucose, you want to have a simultaneous fasting insulin level, which tells you how hard the pancreas is working. A fasting insulin of greater than 15 microunits/ml usually means significant insulin resistance, and risk for metabolic disease. From the glucose and insulin levels together, you can calculate an index called the homeostatic model assessment of insulin resistance (HOMA-IR = glucose x insulin ÷ 405), which assesses your risk for diabetes. A HOMA-IR of less than 2.8 is excellent, 4.3 is average, and anything higher means trouble.

Chronic disease has many definitions—but perhaps the best one is: how well your mitochondria perform at baseline and in response to the stress of living and eating. If your mitochondria are fresh, fit, and functional, it doesn’t matter how much you weigh. If your mitochondria are dull, dilapidated, and under duress, it also doesn’t matter how much you weigh. But there’s no simple blood test for mitochondria,

Your waist circumference is a key. If it’s high, expect that there is some metabolic problem, and that you will have to change your diet to improve your insulin resistance.

If your waist circumference is high and your blood pressure is also high, assume the problem is sugar, not salt. If your blood pressure is high and your waist circumference is low, the problem might be salt or stress.

Fresh, fit, and functional mitochondria burn glucose and ketones to completion (see Chapter 8), and generate few oxygen radicals. They don’t nee...

Mitochondria are inhibited by uric acid, low folate, and fructose, which both cause mitochondria to be overwhelmed in order to divert energy to fatty acid and triglyceride production. Signs of poor mitochondrial function are high uric acid and high homocysteine. Signs of liver fat are high ALT and high fasting insul...

As stated in Chapter 2, obesity is a red herring. It’s a symptom of the disease, not the cause.

There are three commonalities to all the diseases that we call metabolic syndrome: 1) despite all efforts, these diseases are all increasing in incidence, prevalence, and severity at a faster rate than obesity; 2) they’re all exacerbated by obesity, although not specifically caused by it; and 3) while there are drugs to treat the symptoms of each one (including obesity), there are no drugs to either treat, cure, or prevent the diseases themselves.

every single one of these pathologies can be prevented, mitigated, and in many cases reversed, by changes in diet. And none of these changes in diet have anything to do with calorie restriction. In most cases, reversal can be accomplished just by removing processed food and substituting Real Food

People think processed food is food, because it’s calories and macronutrients, but in fact processed food gets in and poisons those pathways instead.

sugar, the main component of processed food, is the primary driver of four chronic diseases. It’s also a likely candidate for another five, listed in order below. These nine diseases together total about 75 percent of the healthcare burden in the US, and 60 percent globally. Processed food is behind them all, sugar makes them worse, and there’s no drug that prevents or reverses any of them. Below is a comparison of how well drugs versus food work to ameliorate these nine different chronic diseases.

Using a ketogenic diet (see Chapter 14) for two years without caloric restriction, they reversed diabetes in 80 percent of their patients, were able to discontinue insulin in 94 percent of their patients who were injecting, and induced a twenty-nine-pound weight loss as well.

Food can either prevent, cause, or reverse diabetes. Drugs may lower the blood glucose, but they can’t fix the diabetes.

statins lower LDL-C, but don’t reduce risk of heart attack (except in those who’ve already had one).

fish oil, a dietary supplement, reduced incidence of heart attack by 8 percent—as well if not better than statins—because most of us are omega-3 deficient to start with

The first issue is the role of omega-3 fatty acids (see Chapter 19), which act in two ways: by reducing general levels of inflammation, risks for heart disease are lower; and by reducing serum triglyceride levels, there’s less chance of plaque buildup. The second issue is insulin, because insulin increases coronary artery smooth muscle proliferation, making it more likely to get a clot. And the third issue is sugar—the percent of calories in the diet as added sugar predicts risk for dying of a heart attack, exclusive of calories or obesity. Conversely, removing added sugar from the diet removes the atherogenic particles (the small dense LDL), lowers triglycerides, and raises HDL—all protective against heart disease.

NAFLD is now the leading cause of liver transplant in the US. It was unheard of prior to 1980, and now affects 25 percent of the world’s population, and 40 percent of the adult US population.

damage the liver, there are two stages of fatty liver disease both driven at least in part by processed food and drinks. And guess what? Alcohol and soda have the same detrimental effects.

the same processes are going on everywhere, and there’s a strong association between the rotting of your teeth and your liver. Dental caries are associated with NAFLD, whether separately or linked is undetermined, but the instigator of both is sugar.

But sugar is just one reason as to why processed food drives cancer.

The fact of the matter is, diabetics are four times more likely to develop dementia than the general population. Furthermore, both forms (Alzheimer’s disease and vascular dementia) are increased in people with diabetes—because insulin resistance affects the brain.

Autoimmune diseases are a disaster and there are no good medicines available (steroids work, but the treatment is worse than the disease). They’ve been around for centuries, but there’s been a clear uptick in the last fifty years. Why? Two hypotheses have been proffered to explain it: the barrier hypothesis (our skin or lungs are letting in antigens) and the hygiene hypothesis (we don’t eat dirt and are too hygienic). But in fact, in the gut, they’re the same thing; because the gut is the dirtiest place in the world—one hundred trillion bacteria to have to fend off at all times—you don’t need an intestine, you need a fortress. We’ve known for a while that leaky gut is akin to chinks in the walls of that fortress. Antigens, like enemy soldiers, escape through those chinks into the bloodstream, where T cells and antibodies react against them. But in a case of mistaken identity, these immune cells then accidentally identify parts of your body as foreign invaders and generate an immune response to kill them off, a process termed molecular mimicry.

a low-sugar, high-fiber Mediterranean diet has been shown to be efficacious at prevention and treatment of rheumatoid arthritis. Furthermore, introduction of fiber to the diet appears to improve asthma (frequently an autoimmune disease), likely by improving gut function and reducing inflammation.

Insulin resistance has been shown to be a primary cause of clinical depression in humans. Sugar is a specific driver of insulin resistance, and one cause of depression in both rats and humans. So it should be no surprise to anyone that two studies, one in Europe and one in China, showed that ultra-processed food consumption is associated with depression in people.

The foods that drive metabolic syndrome are those that are most clearly associated with the foods that people binge on—refined carbs and sugar. The question is, does the depression drive the food choices, which then drive the metabolic syndrome; or do the food choices drive the metabolic syndrome, which then drives the depression? Which is cause and which is effect?

we do know is that many people can eat their way both out of their metabolic disease and out of the depression by s...