The Mediterranean Zone (22 page)

There is a small percentage of obese individuals (5 to 8 percent) who are actually quite healthy regardless of their level of obesity. They are termed
“metabolically healthy obese.” My definition of metabolically healthy obese is based on the Edmonton Obesity Scoring System (EOSS). This is a much more rigid definition of
healthy
than usually used by researchers. More important, those obese individuals who are truly healthy by the EOSS definition remain healthy for many years. On the other hand, if you are obese and have even one indicator of adverse health (high blood pressure, elevated lipid levels, or elevated blood glucose), then you will see a statistically significant decrease in your eventual health over an extended period of time. The truly “metabolically healthy” have lots of healthy fat cells. While they may not look good in a swimsuit, they are able to store excess fat safely and not have it spread like cancer to other organs in their bodies.

So how do you explain the common theme in diet books that eating carbohydrates makes you fat? After all, the amount of glucose entering the fat cells facilitated by insulin is very limited. Is it possible that eating a lot of carbohydrates can be converted into circulating fat? The answer is yes, through a process known as lipogenesis, which takes place in the liver. As you might expect, certain gene transcription factors play an important role in this process. In particular, it is the carbohydrate response element binding protein (ChREBP), which is activated by glucose, that is the key player. The higher the carbohydrate content of your diet, the more glucose will enter into your liver. Higher levels of glucose activate ChREBP, which when coupled with increased insulin stimulates the synthesis of key enzymes needed to convert carbohydrates to fatty acids. The increased amounts of fatty acids are then reassembled in the liver into lipoproteins that can enter the bloodstream. If levels of these newly synthesized lipoproteins rise too rapidly, insulin will go into action to transfer those fatty acids for safe storage in the fat cells as described above. This is why the current Mediterranean diet has little effect on weight loss. It is simply too high in carbohydrates (especially high-glycemic carbohydrates) to reduce the secretion of insulin and activation of ChREBP.

The obvious solution is to reduce insulin levels, keeping in mind you need some insulin, but not too much, to run a smoothly functioning metabolism. The worst way to manage insulin levels is to simply eat protein with very little fat or carbohydrate. The first step of protein metabolism is its conversion to urea. But without adequate levels of fats or carbohydrates to aid the continued metabolism of urea to less toxic products, it builds up
in the blood, leading to a condition known as rabbit starvation. (Early Arctic explorers who ate only very lean meat, such as rabbits, suffered from this condition.) Anytime the protein levels of the diet exceed more than 40 percent of total calories, the possibility the rapid buildup of urea in the blood will exist. Slightly less dangerous, but definitely not optimal, is the replacement of much of the carbohydrate in the diet with fat as in ketogenic diets such as the Atkins diet. Yes, you will reduce insulin levels, but now what are you going to do with all that extra fat in the blood? If you don’t have enough insulin to drive that fat into fat cells, then the excess fat will go all the wrong places (lipotoxicity), usually starting with the liver. The more desirable approach is to reduce the levels of both fat
and
carbohydrate by restricting calories, yet keeping the amounts of carbohydrates and fat relatively balanced so the liver maintains flexibility in the production of the different sets of enzymes necessary for the efficient metabolic processing of both nutrients. Furthermore, by reducing the absolute levels of both circulating carbohydrates and fat, you keep your fat metabolism running with the efficiency of a Swiss bank. To be even more effective, you want to add EPA and DHA to your diet as they not only inhibit ChREBP activity (decreasing lipogenesis) but also activate another gene transcription factor (PPAR-α) that drives fatty acids away from storage and toward oxidation. This is one time you can say, “It takes fat to burn fat,” as long as that fat is rich in EPA and DHA. Of course, calorie restriction is only possible to maintain on a lifetime basis if you are never hungry, but more on that later in this appendix.

Unfortunately, this elegant system starts to run amok when there is increased
cellular inflammation in the fat cells. If you are eating a high-glycemic load diet coupled with high levels of omega-6 fatty acids, AA levels will start building up in the blood. AA along with the other fatty acids in the blood will be taken up by the fat cells through the action of insulin. But as the levels of AA begin to increase in the fat cells, so does cellular inflammation. Now otherwise healthy fat cells start becoming sick fat cells. One of the first consequences of the increase in cellular inflammation is the partial inhibition of a key enzyme (insulin-sensitive lipase) that releases stored fat as insulin levels drop. The release of stored fat, instead of being inhibited by insulin, is being continually released back into the bloodstream because the insulin signaling is being disrupted by the growing cellular inflammation in the fat cell. If your uptake mechanism for removing newly released fatty acids from the fat cells into the blood is saturated (as it will be by eating a high-fat diet), then these constantly released fatty acids from the fat cells begin to get deposited in other organs such as the liver and the muscles cells. As the levels of fat increase inside these organs, their ability to respond to insulin’s signal to take up glucose from the blood also becomes compromised. Now you get insulin resistance in these cells (especially if the fat being released from the fat cells is rich in AA), and glucose levels start to increase in the blood. Since excess blood glucose is also toxic to the body, the pancreas starts pumping more insulin into the bloodstream to try to bring down blood sugar levels. As insulin levels rise in the blood due to insulin resistance, a vicious cycle begins that causes accelerated storage of fat in the fat cells coupled with a growing lipotoxicity in other organs throughout the body. Obviously, this explanation is a little more complicated than making simple blanket statements that carbohydrates make you fat.

The obvious answer is that we eat more calories than we burn. Yes, calories do count. Any excess calories have to go somewhere. Excess carbs can be initially stored in the liver and the muscles, but those storage sites have a limited capacity. However, the excess carbohydrates can be converted to fat via lipogenesis, which takes place in the liver. Excess protein can only be stored in the muscle, but that is an even more limited process that requires consistent weight training to release growth hormone from the pituitary gland. Consumption of excess protein without the presence of growth hormone will simply be metabolized into glucose (via neo-glucogenesis) or fat. On the other hand, excess dietary fat can be indefinitely stored in our fat cells since these cells have the ability to expand dramatically. So if you eat more calories than the body needs to maintain its metabolism, it is quite likely that, with the help of insulin, these extra calories will end up in your fat cells.

But the question is
why
are people eating more calories today? I believe the answer is simple: We are hungrier because the biological Internet that
tells the brain we have more than sufficient calories to maintain our metabolism has been disrupted. As you might expect, the suspect is increased cellular inflammation.

According to the USDA, Americans were eating 474 more calories per day in 2010 than in 1970. That alone is sufficient to explain the increase in obesity. What is more ominous is that more than 90 percent of those increased calories come from added fats and oils (48 percent), grains (38 percent), and sugar and sweeteners (7 percent). Those numbers suggest that if you are looking for a likely suspect for increased obesity, grains and fats are the most likely suspects, not the much smaller increase in the consumption of sugar and sweeteners over the past forty years. Grains (including whole grains) are high-glycemic load carbohydrates that are 100 percent composed of glucose. As they rapidly enter the bloodstream (often faster than sugar), increased insulin secretion is a guaranteed consequence. Many of the added fats are rich in omega-6 fatty acids. With these two food ingredients, you have a surefire metabolic prescription to increase cellular inflammation through the increased production of AA. So why would increased cellular inflammation make you hungry? To understand that, it is necessary to explore the complex science of how our hormones actually control hunger.

Let’s start with insulin. If you consume too many high-glycemic load carbohydrates, then blood glucose levels rapidly rise. Because blood glucose is toxic at high levels, the body responds by secreting insulin to drive excess blood glucose into your fat, muscle, and liver cells.

If the rise in blood glucose is too rapid, then there is often an over-secretion of insulin, and then blood glucose levels drop too low, leading to hypoglycemia. This is what happens when you eat a big meal of pasta at noon, and two hours later you have a difficult time keeping your eyes open. To address the low blood glucose problem caused by consuming high-glycemic load carbohydrates, the brain implores you to begin searching for any high-glycemic food (candy bar, chips, or ideally a sugar-laden soda) that can quickly restore the low blood glucose levels. The use of these foods becomes a way of self-medicating to elevate low blood glucose levels. This may explain why the most popular spot in a hospital at the end of a work shift is the vending machine.

However, if you can’t find a convenient source of glucose to quickly restore blood sugar levels, then the brain has an alternative mechanism to do
so: increasing cortisol secretion to break down muscle into glucose via a process known as neo-glucogenesis. This is what happens when you follow ketogenic low-carbohydrate diets such as the Atkins diet. The common party line for advocates of ketogenic diets is that the brain prefers ketones to glucose for energy. I simply don’t buy that argument. Even under total starvation conditions, the brain levels of glucose never drop to less than 40 mg/dl due to neo-glucogenesis. At lower blood glucose levels (such as 25 to 35 mg/dl), the brain goes into lethargy, convulsions, and potentially a coma. If ketones generated by ketogeneic diets were such great sources of energy for the brain, then theoretically blood glucose levels could drop to zero and the brain would be completely happy.

Researchers at Harvard Medical School demonstrated that cortisol levels increased by 18 percent after three months on the Atkins diet. Some of the consequences of increased cortisol levels are (1) you are hungrier (due to increased insulin resistance), (2) sicker (due to depressed immune function), and (3) less mentally sharp (due to destruction of neurons in the hippocampus region of the brain by their continuing exposure to excess cortisol). Three pretty good reasons to maintain adequate levels of blood glucose—not too much so the body secretes more insulin to reduce potentially toxic glucose levels in the blood, but not too little, which would cause the overproduction of cortisol in order to produce enough glucose for the brain.

However, insulin and cortisol are only two of many hormones that are key in the control of hunger and satiety. Some of the other hormones in this complex orchestration of appetite are listed below.

The activation of satiety and hunger neurons is affected by a number of different hormones sending in information from diverse locations throughout the body. This complexity is best illustrated by how insulin works. High levels of insulin in the blood lower blood glucose levels. This
makes you hungry because the brain is now deprived of its primary source of energy. If the brain is hungry, then you will be hungry. However, inside the brain it is a different story. Once insulin enters the brain, it can inhibit the stimulation of the hunger neurons, thus increasing satiety. (This is why if you push insulin levels too low by eating too few calories or not enough carbohydrates, you get hungry again.) What prevents insulin from signaling the brain to stop looking for food is insulin resistance. The same is true for the hormone leptin, which is produced in your fat cells. The more excess body fat you have, the more leptin you generate. Theoretically, if leptin can get to the brain, obese individuals will stop eating. Unfortunately, the same cellular inflammation that generates insulin resistance in the brain also generates leptin resistance. To overcome both insulin resistance and leptin resistance in the central nervous system, you have to reduce cellular inflammation if you want to increase satiety. This is why hunger is really a consequence of increased cellular inflammation, not decreased willpower. Fortunately, both insulin and leptin resistance can be reduced by following the Mediterranean Zone, which balances both hunger and satiety hormones so that you are not hungry for five hours after a meal.

Ultimately, much of the hormonal action that regulates hunger takes place in the brain, specifically at the base of the hypothalamus. Within this part of the hypothalamus are both appetite-stimulating (hunger) and appetite-suppressing (satiety) neurons. Hormones such as neuropeptide Y (NPY) stimulate the hunger neurons, whereas peptide YY (PYY) stimulate the satiety neurons. Depending upon which set of neurons is activated, an integrated signal is sent to another part of the hypothalamus that ultimately determines whether you should eat or not. Sound complicated? Yes, but that is only part of the issue.

Although the digestive system is a great distance from the brain, it also plays a significant role in the control of both hunger and satiety. The hormone ghrelin is activated by the lack of food in the stomach. Its release from the stomach goes directly to the brain to activate the hunger neurons. However, PYY (stimulated by dietary protein) is secreted from the ileum (the lower part of the small intestine) and the upper part of the colon (the large intestine) to inhibit the action of ghrelin secreted by the stomach. This provides a nice on-off system to signal to the brain from different parts of the digestive system as to when to start and stop eating. Obese individuals have reduced levels of PYY, which means they have a reduced
“off” switch when it comes to appetite control. Other gut-based hormones such as GLP-1 and CCK also aid in the satiety mechanism.