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Written By: Dr. Barry Sears Creator of the Zone Diet

Written by Dr. Barry Sears
on April 12, 2022

To make science reproducible, you must have definitions. The more rigorous the description, the more likely the science behind it can be replicated and valuable in the future. Unfortunately, the term “anti-inflammatory diet” is one of those non-scientific definitions. To define an anti-inflammatory diet, you first need to dive into the background on the source of most of the body’s chronic low-level inflammation.

What Causes Chronic Low-Level Inflammation?

Much of the chronic low-level inflammation that is the underlying cause of many chronic diseases is diet-induced. The reason goes back to evolutionary times in which nutrient storage and the immune system were intimately connected in a single organ described as a “fat body” (1). After millions of years of evolution, this once integrated system is now controlled by separate systems (immune system, intracellular metabolism, and adipose tissue), yet they maintain constant cross-communication. Consequently, inflammation in any one of these systems will create inflammation in the others. The diet is how all three are linked together for better or worse.

The Problem with Excess Calories

Excess calorie intake tends to create inflammation because it creates metabolic stress. The easiest way to determine if you are consuming unnecessary calories is the physical appearance of excess body fat. Regardless of what you might hear, the only way you lose excess body fat is to reduce calorie intake. That’s also the primary way to reduce inflammation. Therefore, any definition of an anti-inflammatory diet must include being defined as a calorie-restricted diet. The molecular reason you must restrict calories is that there is a very intricate relationship between excess fat stores and metabolism mediated by the master regulator of metabolism known as AMP-activated protein kinase (AMPK). Calorie restriction activates AMPK, whereas excess calorie intake inhibits AMPK. The inhibition of AMPK leads to insulin resistance, which is the first step in developing many chronic disease conditions such as diabetes, heart disease, and neurological diseases such as Alzheimer’s. The reason is that AMPK is a complex enzyme that acts as an energy sensor in every cell in the body that regulates metabolism, including immuno-metabolism (the ability of metabolism to control your immune system) and oxidation of stored body fat (2).

How the Diet Inhibits AMPK

Two dietary factors inhibit AMPK activity. The first is excess calories, and the other is excess glucose (3). You develop excess body fat due to consuming excessive amounts of calories, glucose, or both as they are dietary inhibitors of AMPK. If AMPK is inhibited, its ability to control fat oxidation is also inhibited. Therefore, if you have excess body fat, it simply means AMPK is being inhibited in every organ in the body. The result is inflammation increases as AMPK is no longer inhibiting NF-κB, which is the genetic master switch of inflammation in every cell (4,5)

You Need Some Stored Body Fat, But How Much?

At the same time, stored body fat is essential to provide the reserve energy to keep the body functioning. So what’s the right level of body fat? To be considered metabolically fit, the average male should have a body fat percentage between 14 to 17 percent body fat and the average female between 22 and 25 percent body. This definition is vastly different from recommended body mass indexes of less than 25 for both sexes. For example, the average male with a BMI of 25 has 28 percent body and the average female with a BMI of 25 has about 33 percent body fat (6). How can you quickly tell if you have body fat of those percentages? When you can see one of your six abdominal muscles. If you see more than one abdominal muscle, then consider adding more monounsaturated fat to your existing diet to ensure you have adequate levels of stored fat needed for recovery from injuries or to maintain your metabolism.

There’s More to An Anti-Inflammatory Diet Than Simply Reducing Calories

Reducing calories is only the first step of defining an anti-inflammatory diet. You also must have the correct balance of macronutrients to increase satiety, so you aren’t hungry as you reduce total calorie intake. Moreover, an appropriate macronutrient balance is required to maintain stable blood sugar levels for the brain (so you don’t develop hypoglycemia) and increase satiety signals to the brain from the gut, so you aren’t hungry between meals. This increased satiety is essential since it’s only without hunger that it is possible to practice continuous calorie restriction.

What’s the Right Macronutrient Balance?

First, you must have adequate protein at every meal (about 25 grams). That protein level at every meal should be balanced with about 35 grams of absorbable low-glycemic carbohydrates (primary non-starchy vegetables with limited amounts of fruits) rich in fermentable fiber. This combination is necessary to maintain an adequate hormonal balance and maintain stable blood glucose levels. Finally, each meal has a low total fat content (about 12 grams) but primarily monounsaturated fat. Each meal would contain between 400 and 500 calories. This results in a calorie-restricted, protein-adequate, moderate carbohydrate, low-fat diet rich in fiber but without hunger or fatigue (4,5). The common name of such a calorie-restricted anti-inflammatory diet is the Zone Diet.

What is the Difference Between the Zone and the Zone Diet?

The Zone is defined as the physiological state in which you consistently maintain the metabolic balance necessary to reduce, resolve, and repair the inflammatory damage caused by diet-induced inflammation (4,5). To reach the Zone, in addition to following the Zone Diet, you need adequate omega-3 fatty acids to make resolvins to reduce inflammatory stress and activate AMPK and sufficient intake of polyphenols to activate AMPK optimally. However, without following the calorie-restricted anti-inflammatory Zone diet to prevent the intake of excess calories and glucose, you will constantly be inhibiting optimal AMPK activity regardless of the levels of omega-3 fatty acids and polyphenols you are consuming. That lack of dietary control will take you out of the Zone and compromise your ability to control chronic low-level inflammation in every organ in your body.

Science Supports the Zone Diet

More than 40 clinical studies published since 1998 have used that definition of a calorie-restricted anti-inflammatory diet and validated the Zone Diet (7-48). They have consistently demonstrated the effectiveness of such a diet, especially in treating type 2 diabetes, a chronic disease characterized by chronic low-level inflammation

The Real Goal of Medicine

The goal of medicine should be to avoid developing any type of chronic disease for as long as possible. The foundation for reaching that goal is following an anti-inflammatory diet for a lifetime. The result is to extend your healthspan, defined as longevity minus years of disability (49). It all starts with your ability to control diet-induced inflammation. Using a highly defined anti-inflammatory diet, like the Zone Diet, is a great starting point.



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