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Authors: Mark Sisson

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Once you understand the process, it’s instructive to take a step back and realize how important exercise is to creating insulin sensitivity (along with low-insulin eating, of course). If you frequently empty your liver and muscle cells of glycogen with brief, intense workouts (you burn a little bit of glucose during the long, slow stuff, too), you become adept at not only burning calories but replenishing: accepting nutrients transported by insulin into your liver and muscle instead of just having them go straight to fat. If you are sedentary and eating a moderate or high-carbohydrate diet, there is no selection pressure (to borrow an apropos term from our evolution discussions) to be insulin sensitive. My foolproof prevention plan—or, dare I say, cure (you read my disclaimer legalese, right?)—for those with type 2 diabetes, obesity, and heart disease, no matter how overwhelming their genetic predisposition is to these conditions, is to exercise according to the
Primal Blueprint
laws and moderate insulin production with your diet.

It’s interesting to note that levels of growth hormone and other important health-enhancing hormones are also adversely affected by insulin resistance. The pituitary gland makes growth hormone, which is then sent to the liver to signal the production of insulin-like growth factors (IGFs). Many of our cells have surface receptors for IGFs. Because of its similar structure, insulin binds to IGF receptors and prevents growth hormone-stimulated IGFs from doing their job. The thyroid gland produces a hormone called T4, which is converted in the liver to T3, the primary hormone that controls energy metabolism. When your liver becomes insulin resistant, conversion of T4 to T3 declines
drastically. This leads to a decrease in metabolic rate, increased fat storage, and diminished energy levels and brain function.

High insulin levels over long periods of time also hamper sex hormone synthesis, causing levels of testosterone, DHEA, and other sex hormones to decline steeply as we age. Hormone levels naturally decline over time, but this flagship premise of the multi-billion-dollar antiaging industry is greatly exacerbated by insulin resistance as opposed to the mere passing of the seasons. Remember, if Grok was lucky, he could enjoy dramatically better health and physical fitness into his 70s than most of today’s baby boomers. Sex hormones are supposed to be transported through the bloodstream by globulin (a blood protein) to act upon target organs and tissues. When excessive insulin is present, these hormones stay bound to globulin instead of getting dropped off at the target cells (e.g., the adrenal glands, sex organs, and brain are all strongly impacted by sex hormones) and doing their thing. Even an expensive antiaging hormone regimen cannot override this undesirable sex hormone-binding-to-globulin condition caused by excessive insulin.

Clearly, the ideal strategy is to assimilate your dietary nutrients using only the insulin you need to restock muscle and liver glycogen stores, rebuild muscle and other tissue with amino acids, and, finally, transport fatty acids to assist with a variety of essential metabolic functions (including energy storage). By maintaining an optimal balance between insulin and glucagon, you become like an ATM machine, always open for deposits and withdrawals based on your daily energy needs. Clearly, insulin is absolutely essential to life. It’s just that chronic overproduction of insulin (also known as hyperinsulinemia) turns a good thing into a bad thing. It’s as simple as this: when you eat the
Primal Blueprint
–style foods that fit your genes, you’ll be able to fit into your jeans!

But a Little Bit Won’t Hurt, Right?

If these clinical details about the long-term damage from a high insulin-producing diet are not sufficient to get you to change your breakfast order today, consider the short-term unpleasant effects of high-carbohydrate (and particularly high-sugar), insulin-producing meals and snacks (on otherwise healthy, nondiabetic folks). In short (sing along now), it’s “high-low, high-low, toward insulin resistance you go!”

Ingesting a high-carbohydrate food or meal (sugary foods and beverages, desserts, processed grains, etc.) generates an immediate increase in blood glucose levels, which has the short-term effect of elevating your mood, energy level, and alertness (remember, your brain prefers glucose as fuel). In a matter of minutes, however, your pancreas (in a valiant effort to reduce the amount of toxic glucose in your bloodstream and store it someplace useful) is prompted to secrete a large amount of insulin. Depending on the type and amount of carbs you consumed and your degree of insulin sensitivity, this insulin
rush can eventually cause your blood glucose levels to decline so much that your glucose-dependent brain is now low on fuel. As a result, you may soon feel sluggish, foggy, and cranky and have trouble focusing. While this explains the familiar post-lunch afternoon blues, extensive data also suggest a strong link between attention deficit/hyperactivity disorder (ADHD) and processed carbohydrate consumption/insulin production.

The ingestion of lots of carbohydrates, followed by the secretion of lots of insulin causing low blood glucose levels is perceived as a stressful event by the hypothalamic-pituitary-adrenal (HPA) axis. This homeostasis-monitoring part of your endocrine system triggers the fight-or-flight response, causing your adrenal glands to release epinephrine (commonly called “adrenaline”) and cortisol into your bloodstream. Cortisol breaks down precious muscle tissue into amino acids, some of which are sent to the liver and converted into glucose through gluconeogenesis. The ensuing liver-generated blood glucose rush gives you the boost your brain thinks you need—at the expense of your muscle tissue! Depending on your individual sensitivity to glucose and insulin, the stress response to this seesaw process may now make you feel amped, jittery, edgy, and hyper, and you may have a racing heartbeat.

After some time passes and the stress response subsides, you can experience a post-stressful-event-combined-with-sugar-crash condition affectionately known as burnout. This physical, mental, and emotional lull prompts a strong craving for another quick high from sugar, and the cycle repeats. Over time, your continued abuse of the stress response system can overwork your pancreas and adrenal glands, paving the way for health problems like chronic fatigue, inflammation, and weight gain.

Besides the unsettling energy swings and added stress, sugar also seriously hampers immune function. We know that excessive and/or prolonged production of cortisol is a potent immune suppressor (the fight-or-flight mechanism diverts resources to provide an immediate energy boost). Research also shows that sugar itself can impair the function of immunity-related phagocytes (immune system cells that remove bacteria or viruses from the bloodstream) for at least five hours after ingestion. This impairment happens through a process known as competitive inhibition, when excess glucose prevents the all-important antioxidant vitamin C from being transported inside certain immune cells. Because both molecules use the same mechanism and entry point to gain access to the inside of the immune cells, the presence of excessive glucose can overwhelm the transporter site and block vitamin C from entering. With your guard summarily down, oxidative stress on your body increases as free radicals are allowed to run wild. Furthermore, your blood thickens as a response to these immune stressors, which is why heart attacks (in people predisposed to them) tend to occur after a meal.

Over time, the continued abuse of the insulin system leads to the serious health problems detailed previously in this chapter. Note that the chain of events described here happens routinely in a normal, healthy person who overdoes carbohydrate or sugar intake. Experiencing these high-low, high-low cycles from sugar ingestion is no fun, but it does mean you still have some sensitivity to the negative effects of sugar ingestion and insulin production. If you
don’t
experience significant noticeable symptoms from eating lots of carbohydrates (particularly sugar), you are likely well on your way, or have already developed, the extremely problematic condition of insulin resistance. The analogy of a smoker feeling minimal to no immediate ill effects from his or her habit is relevant here. I’d argue that a vast majority of the population is somewhere on this continuum, far outside of the healthy ideal of a diet that moderates carb intake and insulin production in line with our genetic requirements for health.

Naturally, grain or sugar products will jack up blood glucose levels quickly and produce a greater insulin response than consuming a similar amount of calories from vegetables and fruits or combining a few carbs with slower burning protein or fat calories. While it’s obviously preferable to mute the immediate insulin spike, your diet’s total insulin load is still a serious concern. If you are routinely eating 150 to 300 grams (or more) of carbs per day, you will likely gain weight insidiously (unless you exercise like crazy) and still increase your risk of developing other associated health problems, including the “oxidation and inflammation” syndrome that is the major culprit behind heart disease, which I’ll detail in the next section, about cholesterol.

It’s Not About Cholesterol…Really, It’s Not!

Big Pharma and your helpful friends at the FDA, the AMA, and other reputed health agencies have done a great job of vilifying cholesterol and saturated fat as the major causes of atherosclerosis and heart disease via the well-accepted lipid hypothesis of heart disease. You know their story by now. Your arteries are like pipes. Cholesterol is the fatty, sticky gunk that clogs them up if you eat too many high-cholesterol animal products (meat, eggs) or saturated fats in general. According to Conventional Wisdom, you should eat a low-fat, low-cholesterol, high complex-carbohydrate diet. If your diet or genetic “bad luck” results in a total cholesterol level over 200, you simply take cholesterol-lowering statin medicines to safely reduce your risk.

In recent years, many elements of Conventional Wisdom about cholesterol have been called into question. While there is significant dispute and uncertainty on the issue among respected experts, there is compelling evidence that freely dispensing powerful statin medications to reduce all forms of cholesterol offers only minimal protection from heart disease and stroke. Furthermore, it’s almost universally agreed that lifestyle modifications (such as losing weight, reducing intake of processed carbs and fats,
consuming omega-3 oils, exercising, and managing stress levels) can do a much better job than statins in eliminating the major heart disease risk factors.

Because I highly respect the valiant battle medical professionals are fighting with today’s heart disease pandemic (after all, they often have little or nothing to do with patients until they show up on the appointment calendar with clogged pipes), I’d like to assert here that this is not a “Mark versus your doctor” battle of the egos. Rather, I believe this is an unbiased interpretation of cutting-edge data that extends beyond the narrow and dated “eating fat drives cholesterol drives heart disease” paradigm that most of us, including physicians, are familiar with.

This discussion will give you a deeper understanding of exactly what causes heart disease (
hint
: it’s inflammation and oxidation, driven primarily by poor food choices, excessive insulin production and all forms of stress in excess, including overexercising) and help you do a better job minimizing heart disease risk than just following the party line of “Don’t eat cholesterol—and take drugs if your numbers are high.” If you are already familiar with the basics of blood chemistry and a firm believer in the concept that cholesterol is
not
an efficient marker for heart disease, you may want to skip ahead to the sidebar “How to Sneeze at Heart Disease.” Otherwise, fasten your seat belt and hang on for the ride; it could save your life.


Using total cholesterol level—or even your LDL cholesterol value—as a heart disease risk factor is like saying, ‘Going to the beach is dangerous.’ It’s irrelevant in the absence of further context, such as Metabolic Syndrome and other accomplices to heart disease
.

Among the most notable research refuting the cholesterol story is the highly respected Framingham Heart Study. The study (which I reference often at
MarksDailyApple.com
) has followed the dietary habits of 15,000 participants (residents of Framingham, Massachusetts) over three generations. It is widely regarded as the longest (it began in 1948 and is still going strong!), most comprehensive epidemiological (study of health and illness factors on a population) assessment in medical history. It has led to the publication of more than 1,200 research articles in leading journals. Study director Dr. William Castelli summarized the issue unequivocally when he said, “Serum cholesterol is not a strong risk factor for coronary heart disease.” Among the study’s highlights are these:


There is no correlation
between dietary cholesterol intake and blood cholesterol levels.


Framingham residents who ate the most
cholesterol, saturated fat, and total calories actually
weighed the least
and were the most physically active.

Luckily for us, over the past decade, hundreds of bright, clear-thinking researchers have reexamined this data, conducted new research, and written extensively on how and why the Conventional Wisdom lipid hypothesis of heart disease is deeply flawed. (Google the term
cholesterol skeptics
and you’ll discover an organized group called the International Network of Cholesterol Skeptics, populated by dozens of leading M.D.’s and Ph.D.’s in the field from across the globe.) Their research now shows that atherosclerosis is caused mainly by the excessive oxidation (and the ensuing inflammation) of a certain type of cholesterol that constitutes a small fraction of the mostly good stuff flowing through your bloodstream.

Ironically, in many cases, it appears that this oxidation might be made worse by consuming the very (cholesterol-free) polyunsaturated fats in vegetable and grain oils that the medical establishment led us to believe were healthier than animal fats! The millions who use statin drugs daily incur a significant expense and endure disappointing side effects. For nearly all users, there is little or no demonstrable reduction in heart disease risk.

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