Zone Diet: Reducing Diet-induced Inflammation
When people hear the word diet, the first thought that springs into mind is a short period of time filled with hunger and deprivation so they can fit into a swimsuit and then go back to their old eating habits.

Actually, the word diet comes from the ancient Greek root that means “way of life.” Diet is a life-long dietary pattern for some hopefully noble purpose like enjoying a longer healthspan. Diet also generally means discipline, but only if the longer-term purpose is worth it. The goal of the Zone Diet is to reduce the intensity of diet-induced inflammation by attenuating the hormonal factors that increase the intensity of the inflammatory response. That results in a longer healthspan.

Controlling diet-induced inflammation significantly reduces the amplification of existing unresolved cellular inflammation, thus reducing the likelihood of the development of chronic disease. This is why the Zone Diet is the necessary first step of optimizing your Resolution Response. Without a consistent dietary strategy to reduce diet-induced inflammation, you are entrusting your future to genetic good luck (it sometimes happens) or abdicating your future to the drug companies to manage symptoms of some future chronic disease. Unfortunately, drugs will become increasingly more expensive (even those that are generic) as well as making it more likely that you will become a walking polypharmacy taking even more drugs to counteract the side effects of the original drugs.

Molecular Basis of the Zone Diet
The Zone Diet is primarily based on hormonal control theory. The body works best on the concept of homeostasis. Think of this concept as a biological thermostat keeping the levels of hormones in the blood within certain operating limits (i.e., a zone). The Zone Diet was developed to keep these hormones in such a zone if you are willing to treat your diet as if it were a drug taken at the right dose and at the right time.

In the 1990s the diet debate centered on eliminating so-called “evil” foods. For some like Dean Ornish, it was fat. For others, like Robert Atkins, it was carbs. Neither one understood the impact of the diet on the hormonal balance that affected the generation of pro-inflammatory eicosanoids that caused inflammation, which in turn results in insulin resistance.

In reality, both were partially right and partially wrong. Ornish was partially correct that the wrong types of fat (omega-6 fats and palmitic acid) were very pro-inflammatory. But that was no excuse to throw the baby out with the bathwater by eliminating almost all fat and all animal protein because it also contained fat.

Likewise, Atkins was partially correct that consuming too many carbohydrates (especially high glycemic ones like grains and starches) relative to protein would disturb the protein-to-carbohydrate ratio necessary to stabilize blood glucose levels. But by removing most of the dietary carbohydrates, Atkins had also removed the fermentable fiber and polyphenols needed for gut health thereby increasing the likelihood of gut-derived inflammation caused by a leaky gut. At the same time, he was advocating all the benefits of ketosis by eating more fat (especially butter) unaware of the pro-inflammatory properties of saturated fatty acids such as palmitic acid, which is the primary saturated fatty acid in butter. The Atkins diet also perturbs the protein-to-carbohydrate ratio to induce ketosis. One hormonal result consequence of ketosis is to induce the production of excess cortisol that would break down muscle to convert it into glucose for maintaining brain function. The increase in cortisol not only increases insulin resistance but also depresses the immune system.

The Zone Diet was ideally suited to moderate the hormonal extremes advocated by either Ornish or Atkins as shown below.

You need some carbohydrates, but not too much to maintain a balance of insulin. You also need some protein at every meal, but not too much to maintain glucagon levels that help maintain blood glucose levels. Finally, you also need some non-inflammatory fat at each meal, but not too much, to help release one of the satiety hormones (CKK) from the gut to help maintain satiety as well as provide taste.

However, the ultimate controlling factor for insulin levels in the blood is not the levels of carbohydrate in an individual meal, but the degree of insulin resistance a person currently has. That is determined by their levels of cellular inflammation in insulin-sensitive tissues like the muscle, liver, fat cells, and hypothalamus in the brain. It is insulin resistance that keeps blood insulin levels constantly elevated. This is known as hyperinsulinemia. This same insulin resistance also makes it difficult for the hypothalamus in the brain to correctly receive satiety signals that tell you to stop eating. It is not insulin per se that makes you fat and keeps you fat, but insulin resistance that makes you fat and keeps you fat. Thus, the primary goal of the Zone Diet is to first reduce insulin resistance, and then followed to prevent it from returning. To accomplish both goals you have to maintain a relatively constant protein-to-glycemic load ratio at each meal while restricting calories without hunger or fatigue.

Notice from the diagram that describes the Zone Diet that the shape of protein-to-glycemic load ratio is a bell-shaped curve simply because not everyone is genetically the same. But on the other hand, they aren’t that genetically different either.

Problems with Diet Studies
One of the reasons there is so much confusion with diet studies is they are often poorly controlled. Well-controlled diet studies require that you that provide all the food to the subjects so that they don’t have to think. Such studies are difficult to do as well as being very costly. As a result, very few are ever done. Most diet studies just give their subjects some simple written instructions with limited education and hope that they will follow them. Such an approach rarely works for any long-term studies because people tend to revert to their old dietary habits even trying to follow four different diets over a two-year period as shown by Harvard in 2009.

Even more confusing results come from epidemiological studies of populations that make dietary assumptions that best fit the gathered data. In reality, epidemiological studies are only useful in generating a hypothesis to be clinically tested. It’s much easier to take the mass of data from epidemiological studies and put into the computer and see what comes out. Consider this to be the “wisdom of the crowd.” As an example, epidemiological studies were done at Harvard that indicated women who took birth control pills appeared to live longer. On the basis of those studies, over $260 M was spent on a 10-year study to confirm their hypothesis. Unfortunately, the clinical trial based on their positive epidemiological studies found those who were using birth control pills had higher levels of cancer.

However, the worse trials may be meta-analysis diet studies that take a lot of different studies with different protocols and try to analyze the resulting mix. It’s like making scientific sausage.

Even well-controlled diet studies are far more complex than drug studies as you have four variables to control: protein, carbohydrate, fat, and calories. At least two of these diet variables must be held constant to compare the impact of the other two dietary variables. As an example, you can keep the total calories and protein intake constant, and then compare the effects of varying the fat and carbohydrate intakes. And then you need to do it again for the next two variables, and again and again, until you have conducted eight separate long-term studies. Furthermore, you have to supply much, if not all the food, to ensure compliance.

My first book, The Zone, put many nutritional academics’ elegant epidemiological constructs in doubt, and thus created a firestorm within the scientific community. But unlike most popular book authors who haven’t done any academic research, I had a solid publication record and strong patent portfolio. In other words, I knew a thing or two about research.

Soon after The Zone was published, David Ludwig at Harvard Medical School asked me to give a talk at the department of pediatric endocrinology because he had read the book and found the scientific concepts behind the Zone interesting, although highly controversial.

After my lecture they were intrigued, because if I was right, then everyone else in nutrition might be wrong. So, David and a group of those Harvard researchers wrote a government grant to do a study to determine if my predictions of the effect of the Zone Diet on hormone responses might be correct. The proposed grant to the government was promptly turned down because the concept was considered too outlandish by the reviewers. Undaunted, they reached into their internal slush funds and did the study themselves. It was a well-crafted and very clever study. Their subjects were obese adolescents brought to Harvard on three separate occasions over a two-month period to test the effect of three different meal combinations on their hormonal responses. On each visit, the child was provided a Zone meal for dinner and stayed overnight in the metabolic ward. They were awakened at 6 a.m. the next day and had catheters put into their arms to monitor their blood levels to determine how each meal affected their hormones. Then they received one of three different meals on each visit for breakfast. All of the meals contained the same number of calories (about 400), but had different ratios of protein-to-carbohydrate. One of them was a Zone meal consisting of an egg white omelet with some low-fat cheese and a bowl of slow-cooked oatmeal. On the other two other visits, they were given meals that were higher in carbohydrates and lower in protein than the Zone meal, but with different glycemic loads. Then they measured the hormone levels in the blood of each child for the next five hours. The results confirmed the predictions I had made earlier at my seminar about the hormonal effects of the protein-to-the glycemic load ratio of the meal. Five hours after eating each test breakfast meal, the catheters were removed from their arms and then the children were given the same meal for lunch that they had for breakfast on that particular visit. Then they brought the children into a conference room with TVs and comic books where they sat for the next five hours. The room’s conference table was covered with foods like sandwiches, doughnuts, chips, and the children were told they could help themselves to any of these food items if they got hungry. When the Harvard researchers tallied up the resulting food intake, they found those who had consumed two Zone meals back-to-back consumed 46 percent fewer calories compared to when they had eaten the two high-glycemic load meals with less protein but same number of calories. The children simply were not hungry after eating the two consecutive Zone meals. After that study, the glycemic load became a hot topic at Harvard. Later they performed a similar study with obese adults and found that the Zone Diet reduced inflammation nine times more effectively than the then-standard diet currently being recommended by the USDA.

There have been more than thirty published studies on the Zone Diet where it has been compared to either high-carbohydrate diets or ketogenic diets. Each study came to the same conclusion that the Zone Diet is superior in hormonal control, blood sugar control, blood lipid control, appetite control, fat loss, and most importantly, the reduction of cellular inflammation.

Zone Diet: Calorie Restriction Without Hunger or Fatigue
One of the problems the nutritional community had with the concept of the Zone Diet is they apparently never completely read any of my books. When they saw my recommendation that 30 percent of the calories on the Zone Diet should come from low-fat protein, their immediate response was that the Zone Diet was a high-protein, ketogenic diet that would damage the kidneys and immediately stopped reading the book. If they continued reading just a little further, they would have seen that on the Zone Diet you were actually consuming more carbohydrates than protein, so it couldn’t be considered at high-protein diet nor could it generate ketosis. Furthermore, they didn’t realize that the Zone Diet was also a calorie-restricted diet so that the absolute amount of protein was no more than what Americans were currently eating but spread out more evenly through the day like the intravenous delivery of a cancer drug.

Calorie-restriction is not a new concept, but it usually entails constant hunger and fatigue. What was unique about the Zone Diet was the potential that calorie restriction could be practiced for a lifetime without hunger or mental fatigue because of the hormonal effects generated by the balance of the protein-to-the glycemic load would stabilize blood sugar levels between meals.

History of calorie restriction
The oldest form of calorie restriction is fasting. It was mentioned by Hippocrates and practiced by many religious sects. Fasting is the most extreme version of calorie-restriction because it forces the body to cannibalize itself. Initially, fasting has some beneficial actions such as activating the gene transcription factor AMP kinase, that controls our metabolism to provide the energy needed for the repair of damaged tissue. One of the first consequences of initial fasting is that the activation of AMP kinase accelerates a process called autophagy in which your cell’s damaged molecules are recycled into new materials required for cellular repair. It’s like taking out the garbage. But after all the garbage is cleaned up, if you continue fasting, your body starts digesting protein from healthy tissue to supply glucose for the brain. This happens through a process known as neo-glucogenesis mediated by increasing the levels of the hormone cortisol. Initially during neo-glucogenesis, you lose non-essential protein such as the hair and facial muscle. Eventually, the process extends to digesting essential muscle tissue like the heart. (This is why you can’t fast for more than 50 days—eventually you will die of heart failure.)

Dying due to complete fasting is not a desired outcome for achieving optimal health. Perhaps a less severe method of calorie reduction other than fasting might work. The goal of calorie restriction is to consume the least number of calories while supplying adequate essential nutrients we need to survive including protein, essential fats, as well as vitamins and minerals.

The first recorded evidence of the long-term benefits of a calorie-restricted diet came from Luigi Cornaro, a 15^th century Venetian nobleman. By his late 30s Luigi Cornaro was near death due to his lavish lifestyle of excess food, drink, and the good life. He started a rigorous calorie-restriction program consuming only about twelve ounces of food per day consisting of coarse grain bread, meat broth with a little protein and an egg yolk, vegetable soups, and about three glasses of unaged (new) wine. It worked. He wrote his first diet book (Discourses on the Temperate Life) at age 83 and managed to write two more books on calorie restriction and longevity before dying at 102.

Now we can fast forward to 1935 when Clive McCay demonstrated that restricting calories (but not nutrition) in rats resulted in a significant increase in their lifespans. His experiments have been repeated in a large number of species, including monkeys that are the most genetically similar to humans. Although the increase in lifespan is not as great as with less evolved organisms, the increase in healthspan is significant because of the delay in the development of a wide variety of chronic diseases.

What about humans? Here the clinical data is much more limited. Much of it comes from the CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) trials in which either overweight or normal-weight individuals were asked to reduce their calorie intake by 25 percent over a two-year period. By the end of two years, only about half that calorie restriction goal (about a 12 percent reduction in calories) was actually reached. While they lost body fat (as well as muscle mass), interestingly their levels of insulin-like growth factor (IGF-1) did not decrease. This is the opposite effect found in all the animal experiments suggesting that humans are probably metabolically different than rats.

One likely reason the subjects couldn’t achieve the projected level of calorie restriction was they were probably always hungry because of an unbalanced ratio of the protein-to-glycemic load used in those studies. Frankly, who wants to be hungry for two years, let alone the rest of their life? The Zone Diet solves that problem because as I will show you shortly, it is actually difficult to eat all the food on the Zone Diet even when restricting calories. I call it the Zone Paradox.

The Zone Paradox
One of the reasons the nutritional community has such a hard time in understanding the Zone Diet is because its starting point is not the number of calories you need, but the amount of protein required to maintain your muscle mass. You have plenty of calories already stored as excess body fat that can be released for your energy needs, but only if you can reduce the insulin resistance that keeps those fatty acids trapped in your fat cells.

When you lose muscle, you not only lose strength, but also you lose the primary depot in the body to dispose of excess glucose in the blood. The amount of protein you need on a daily basis to maintain your current muscle mass depends on two factors: (1) the amount of muscle mass you have, and (2) how physically active you are. Neither of these factors come from a bathroom scale, but you can easily calculate them using tables I have published in my earlier books or using a simple calculator found at www.zonediet.com/resources/body-fat-calculator.

Not surprisingly males need more protein than females to maintain their higher levels of muscle mass. Also, as you might expect, athletes have more muscle mass than their sedentary peers and require more dietary protein to maintain their higher level of existing muscle mass. Furthermore, they require even additional dietary protein to replace the muscle protein damaged during intense exercise. In other words, the amount of protein you need on a daily basis to maintain your muscle mass is unique to you.

Once you determine the amount of protein you need on a daily basis to maintain your existing muscle mass, then you simply divide that amount of protein evenly at every meal like you would when taking a drug. For most females that will be about 3 ounces of low-fat protein at a meal and for most males that will be about 4 ounces of low-fat protein at each meal (this is essentially the size and thickness of the palm of your hand). In either case, these are not excessive amounts of protein. In fact, this is exactly the same recommendation of every dietician in the world who state that you should never consume more low-fat protein at any meal than you can fit on the palm of your hand. I totally agree. I only add that you should never consume any less low-fat protein than that at any meal otherwise you will not consume enough protein to induce satiety for the next five hours. It should be noted that male or female athletes will need slightly more protein than the average person, but not that much as I will discuss later.

Frankly, I don’t care where the protein comes from as long as it is low-fat protein because your goal is to set the hormonal balance to increase the release of excess stored body fat to be used for energy. This also ensures you are consuming protein that is low in saturated fat, especially palmitic acid that is the most pro-inflammatory of the saturated fats. That low-fat protein could be chicken, fish, very lean red meat, egg whites, dairy, tofu, or plant-based meat substitutes.

Thus, the first step of constructing a Zone meal is based on the amount of protein you need. The next step for making a Zone meal is you have to balance the protein at each meal with the right amount of carbohydrates. That’s about a third more carbohydrates than protein in terms of grams. The types of carbohydrates for the best hormonal response is determined by your current level of insulin resistance. For most individuals that will be about three to four servings of non-starchy vegetables at each meal and adding a little fruit like a half-cup of berries or a very small piece of fruit, such as half a small apple. Both types of carbohydrates are known as low-glycemic carbohydrates because the glucose in them doesn’t enter the blood at a rapid rate. Such a meal will automatically be rich in fermentable fiber and polyphenols that are essential for gut health.

Finally, to complete your Zone meal, you add a dash (that’s a small amount) of monounsaturated fat like olive oil, guacamole or slivered nuts. A dash can be considered a teaspoon of olive oil, a tablespoon of guacamole or 1/3 ounce of nuts. That’s it for a Zone meal. Now just repeat the same template meal after meal and you are following the Zone Diet.

The Zone Diet is a calorie-restricted diet that is protein-adequate, carbohydrate-moderate (but rich in fermentable fiber and polyphenols), and low in fat, It is also very difficult to eat all the food because you would be eating ten servings of vegetables and fruits per day. At the same time, you are stabilizing blood glucose levels for the brain as well as sending satiety signals (by consuming adequate protein at each meal) from the gut to the brain directly via the vagus nerve that tells you to stop eating. Who could argue with that? Apparently every “expert” in nutrition.

Doing the Math
I have come to conclude that one of reasons nutritional science is in such a morass is that no one ever does the simple math for different diets. First, the only way you are going to lose excess body fat is to restrict calories. That can only be achieved if you stabilize blood glucose levels, send the correct satiety signals from the gut to the brain to stop eating, and reduce insulin resistance so that stored fat can easily be released between meals to provide high-octane fuel for your body.

I have already stated that the appropriate protein-to-glycemic load balance for the Zone Diet is about 1/3 more low-glycemic load carbs than low-fat protein at the meal. And if you want about 30 percent of calories as fat in that meal, then the number of calories coming from protein and carbohydrate in a meal would be 70 percent of the rest of the calories (all three macronutrients must equal 100 percent). So, if you want about 1/3 more calories as low-glycemic carbohydrates relative to protein at the meal, then the total carbohydrate-protein-fat composition of a Zone meal is about 40 percent low-glycemic load carbohydrates, 30 percent low-fat protein, and 30 percent fat, but primarily as monounsaturated fat. But caloric percentages are meaningless unless you look at the absolute level of each macronutrient because it is the balance of protein and carbohydrates in grams at each meal that determines the appropriate hormonal responses for the next five hours.

Let’s see what the Zone Diet looks like on a daily basis, remembering that protein and carbohydrates contain four calories per gram and fat contains nine calories per gram.

	Typical Female	Typical Male
Carbohydrates per day	120 grams	150 grams
Protein per day	90 grams	112 grams
Fat per day	40 grams	50 grams

Let’s look at calories per day. If you are consuming 1,200 calories per day (typical for the average female) that would be three meals each consisting of a little less than 400 calories per meal and one Zone snack. At 1,500 calories per day (typical for the average male), that would be three meals consisting of 400 calories per meal plus one or two Zone snacks.

Your brain needs about 130 grams of glucose per day, meaning your carbohydrate intake should be an adequate amount to keep the brain happy with its optimal fuel (which is glucose, not ketones) throughout the day. On the other hand, consuming too much carbohydrate at any meal will cause an over-secretion of insulin leading to a reduction in blood glucose levels within a few hours leading to hypoglycemia causing increased hunger and mental fatigue.

The amounts of protein consumed on the Zone Diet are pretty close to what the average American (female or male) is already eating, but now evenly split throughout the day. Finally, the Zone Diet would qualify as low-fat diet by any standard.

You’d think you would starve on 1,200 calories per day. But let me show you how much food would be required to achieve that calorie level:

 Carbohydrates (120 grams) per day
8 servings (4 cups) of cooked non-starchy vegetables requires about two pounds of raw vegetables.

2 servings (1 cup) of fresh fruit

1 serving of either legumes (3 oz.) or slow-cooked oatmeal (3 oz.)

This amount of carbohydrates would also provide more than 40 grams of total fiber and lot of polyphenols

Protein (90 grams)

3 servings of 3 oz. of low-fat protein at each meal

Fat (40 grams)

2 tablespoons of extra virgin olive oil per day translates into 2 teaspoons per meal

Most women would have a hard time consuming that amount of food even when consumed evenly throughout the day. At 1,500 calories per day for the average male, the amounts of food to be consumed are correspondingly greater. You can find hundreds of Zone meals as well as protein calculator to determine your own unique protein requirements at www.zoneliving.com.

Besides never being hungry or mentally fatigued following the Zone Diet, a recent study published in 2017 indicated there are some significant health benefits for eating ten servings of vegetables and fruits per day like a 33 percent reduction in stroke, a 24 percent reduction in heart disease, a 13 percent reduction in cancer, and finally a 31 percent reduction in all-cause mortality. I am eagerly waiting for any drug to deliver similar performance results.

Summary
The Zone Diet is an anti-inflammatory diet because it reduces the intensity of diet-induced inflammation. This is accomplished by reducing the intake of omega-6 and saturated fatty acids that are pro-inflammatory. It also reduces the activation of the gene transcription factor, NF-kB, which is the genetic master switch that turns on the inflammatory response as well as improving gut health to reduce the entry of bacterial fragments into the blood (explained in the next chapter) and reducing the formation of glycosylated proteins, both of which can activate NF-kB. This is why following the Zone Diet is the obligatory first stage for optimizing your Resolution Response because it is your best dietary tool to reduce the overall intensity of diet-induced inflammation. Mastering this stage of the Zone Pro-Resolution Nutrition system makes it much easier to initiate to the next stages of the Resolution Response which are the resolution of residual cellular inflammation and then repairing the tissue damage caused by that inflammation.