Then & Now: Calorie Restriction and the Impact on Disease

Reduce your risk of chronic disease by making simple changes to your diet. Starting with Hippocrates 2,500 years ago, to Luigi Carnaro 400 years ago, to Dr. Barry Sears today, data continues to prove that a calorie restricted diet can reduce your risk of chronic disease. Discover how you can benefit from history repeating itself.

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More than 400 years ago, Luigi Cornaro demonstrated that calorie restriction increases your health span. The story began in the year 1507, when Cornaro, a Venetian nobleman, was near death at age 40 due to a poor dietary lifestyle. At that point, he started a rigorous calorie-restriction program. Starting at age 83, Cornaro wrote three widely-read diet books. When Cornaro died at age 99, his death was due simply to old age, not from any chronic disease.

Calorie Restriction is Not Malnutrition

Calorie restriction is not the same as starvation. It usually consists of a 30% reduction in normal caloric intake without sacrificing any nutrition. A recent study set out to validate the impact of calorie restriction on species closest to humans.1 The researchers used rhesus monkeys which share 93% of the same genes as us and live for about 30 years. So essentially you can assume these findings from monkeys should be applicable to humans. Virtually all the earlier work on calorie restriction had been done in worms and mice which are not quite the same as humans in terms of genes or lifetime.

What was impressive about this study, was that it was a 30-year experiment to determine the long-term consequences of caloric restriction versus normal intake. When the calorie restriction was started after the monkeys had reached maturity, they didn’t live that much longer than those fed a normal diet. They did however have significantly lower levels of cancer, heart disease, and insulin resistance than controls consuming a normal laboratory diet. The authors state that there are clear parallels between humans and rhesus monkeys and that it is quite probable that the healthy effects of calorie restriction seen in monkeys will also be visible in humans.

The Advantages of a Calorie-Restricted Diet

To understand the real advantage of a calorie-restricted diet requires an understanding of the link between diet and inflammation. A calorie-restricted diet is also an anti-inflammatory diet. This means that chronic diseases with a strong inflammatory linkage such as obesity, diabetes, Alzheimer’s, heart disease, and cancer to name just a few, can either be prevented or significantly managed following such an eating plan.

One would think following an anti-inflammatory diet should be the goal of health care reform. This could be our answer to continually rising healthcare costs, especially since the majority of those costs come when we are plagued chronic disease in our last years of life? Today health care “reform” generally increases the size of your deductible before your health insurance actually kicks in. The best strategy to overcome such “reform” is simply to not to get sick in the first place. That is the promise of calorie restriction. The proof it works was demonstrated in the above mentioned 30-year rhesus monkey study.

Of course, calorie restriction in free living humans is only possible if you are never hungry or fatigued. The Zone Diet was built upon this concept. That makes the Zone Diet a lifelong dietary program to treat heart disease and diabetes by reducing inflammation. The caloric ratio of the macronutrients (carbohydrates to protein to fat) is approximately 40–30–30. This balance allows for stabilization of blood sugar to prevent hunger and fatigue.

The Zone is also nutritionally superior (if not greatly exceeding standard diet) if the carbohydrates consumed are primarily non-starchy vegetables. These will be exceptionally rich in essential nutrients including polyphenols and fermentable fiber (i.e., prebiotics) necessary for gut health.

If you take the 30% calorie restriction in the rhesus monkey study and applied it to humans, that would mean an average adult male would consume 1,500 calories per day and an average female 1,200 calories per day. It doesn’t sound like a lot a calories, but without the correct balance of macronutrients, those decreased calorie levels would likely generate constant hunger and fatigue.

Obviously, this would make it difficult to live the rest of your life regardless of the health benefits. I put forward the balance of macronutrients necessary for controlling hunger and fatigue in my first book, The Zone.2 A decade later, those same recommendations were the foundation of the new dietary guidelines of the Joslin Diabetes Center at Harvard Medical School for treating obesity and diabetes.3 This year, Joslin published their 5-year study on diabetic patients following such a dietary program.4 The results were exceptionally encouraging for all diabetics. And if they are good for diabetics, then they will be extraordinary for non-diabetics.

How to Combat Hunger on a Calorie Restricted Eating Plan

Your first thought might be: How can I comply with this monkey food business, I’ll surely die. I guarantee you that the monkeys didn’t die following a calorie-restricted diet and neither will you. How? First, the carbohydrate intake on the Zone Diet is limited to about 40% of total calories. This ensures that the brain gets its daily need for glucose, which is about 130 grams of glucose.

The Zone Diet contains 100 to 150 grams of carbohydrates (400 to 600 calories), split over three meals and one or two snacks, which easily supplies that level of glucose for optimal brain function. However, if these carbohydrates were mostly composed of non-starchy vegetables then to consume 400 to 600 calories of carbohydrates would require you to eat approximately 4 pounds per day. Although this represents only about 50 – 67% of the total amount of carbohydrates in our typical American diet, you can see it may be difficult to consume the required amounts for the Zone Diet because of the very low glycemic index of the carbohydrates.

Furthermore, you never want to consume more than 30 to 40 grams of carbohydrates at any one meal. Any greater amount is going to generate excess insulin, which makes you hungry and fatigued by driving down blood glucose levels. The result is you are constantly hungry, searching for food all the time.

The secret of the Zone Diet is that the glycemic load of a meal is balanced by adequate levels of low-fat protein (25-30 grams) at each meal to help stabilize blood sugar levels and to release satiety hormones (like PYY and GLP-1) from the gut to tell the brain to stop eating.

The Zone Paradox: Fewer Calories Doesn’t Equate to Hunger or Fatigue

Although the Zone Diet is a calorie-restricted diet, you will not be hungry or fatigued. This is the Zone Paradox. It is untrue that the Zone Diet is a high protein diet. Yet, following the Zone Diet guidelines you still get the absolute protein intake of the typical American diet because even though the percentage of protein (30% of total calories) is higher, the total number of calories being consumed daily is restricted. Because of its calorie restriction, it is also a low fat diet in absolute terms. Finally since you always consume more carbohydrates than protein, it is difficult to refer to the Zone Diet as a high-protein, low-carbohydrate diet. It’s simply not correct since you are always consuming more carbohydrates than protein at a meal. Thus, the best description of the Zone Diet it is a calorie-restricted, protein-adequate, carbohydrate-moderate, and low fat dietary plan. Who could argue with that? Obviously not the Joslin Diabetes Center at Harvard.

As Hippocrates said 2,500 years ago, “Let food be your medicine and medicine your food.” Luigi Cornaro demonstrated it works 400 years ago, and today the Zone Diet makes it possible to live better with the least amount of effort if you are willing to balance your meals to live a life without hunger or fatigue.


  1. Mattison JA et al. “Caloric restriction improves health and survival of rhesus monkeys.” Nat Comm 8:1-12 (2017).
  2. Sears B. The Zone. Regan Books. New York, NY (1995).
  3. Giusti J and Pizzotto J-A. “Interpreting the Joslin Diabetes Center and Joslin Clinic clinical and nutrition guidelines for overweight and obese adults with type 2 diabetes.” Curr Dia Rep 6:405-408 (2005).
  4. Hamdy O et al. “Long-term effect of intensive lifestyle intervention on cardiovascular risk factor in patients with diabetes in real-world practice: a 5-year longitudinal study.” BMJ Open Dia Res Care 5:e000259 (2017).

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 45 years to the study of lipids. He has published 40 scientific articles and holds 14 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 14 books, including the New York Times #1 best-seller, The Zone, which have sold more than 6 million copies in the U.S. and have been translated into 22 different languages.


  1. karen e owens

    You are a pioneer in so many areas..This is another example. Following the very systematic zone diet I have prevented diabetes after being diagnosed as pre-diabetic 13 yrs, ago. In running a Nutrition Program/Fair for the needy people of our Milwaukee, i found out your suggestions are in fact reinforced by the Dept of Agriculture and Nutrition Education dept of Wisconsin..Bravo, Dr. Sears!

    • Barry Sears

      Thank you for your kind comment and your own personal results.

      The principles of the Zone Diet (a calorie-restricted, protein-adequate, moderate-carb, low-fat diet with a 40-30-30 ratio of carbs/protein/fat) are identical to those formulated by the Joslin Diabetes Institute at Harvard ten years after the publication of The Zone to manage diabetes. I feel in good company.

  2. Charmaine Mire

    Hello, Dr. Sears, can you please comment on recent diet recommendations by others in the nutrition field that our caloric ratio should be more along the lines of 20/20/60, carbohydrate/protein/ fat. Some even say 70-80% fat is not too much when the fats are “good fats” (fish oil, coconut oil, olive oil, etc.) One reason provided is that the brain needs fat more than glucose, but also for other metabolic functions. Are you familiar with these recommendations and is this newer information or do you disagree with these recommendations? Thank you!

    • Barry Sears

      What is missed in these caloric battles is definiing: (1) the goal of the diet, (2) the absolute amount of nutrients that are required, (3) the total calories consumed, and (4) the balance of those calories. The goal of the Zone Diet is the reduction of chronic inflammation that can be measured in the blood. To achieve that measured clinically. One adequate protein to maintain muscle mass and hormonal control, but that protein has to be evenly throughout the day. That will be between 90 and 110 grams of protein per day. You need a moderate level of carbohydrates to maintain blood glucose for the brain. That will be about 150 grams of carbs per day. Finally you require a low fat diet with between 40 to 50 grams of fat per day. Any more of these nutrients will cause hormonal distortions and accumulation of excess body fat. Also your goal is to consume the least amount of calories without hunger or fatigue. That can be best achieved by a 40-30-30 calorie balance. This is why the Joslin Diabetes Institute at Harvard Medical Schoo recommends both the calorie restriction and macronutrient based of the Zone Diet for treating diabetes.

      I should point out that the brain requires glucose and if there is not enough in the diet, then cortisol will be secreted to break down muscle mass into glucose for maintaining brain function. The brain cannot burn fat, otherwise it would consume itself. Unfortunately, there far too many “experts” without any significant understanding of the published clinical literature that makes for constant dietary confusion.

  3. Joonhong Jang

    Hi Barry, as you know I’ve been trying to introduce the Zone concept and the Zone diet guideline to more doctors, more patients and more general persons here in Korea since 2002 when I published the Korean version of The Zone. However, it’s not easy but very tough to do so. Please encourage me not to give up.

    • Barry Sears

      It’s all about continuing education of physicians on the newest research of the role of diet in treating chronic inflammation. Nothing worth accomplishing is ever easy, but it is easier to maintain persistence when constantly supported by robust science.

  4. Richard Head

    I have been involved with analyzing the effects of diet restriction, helping our bacteria and interval exercise effects on our overall health and how this works. I thing the informationI have collected over the years from valid science journals has great merit and proof. See my blog – Mental decline and what to do for interesting info as to why and how to increase your health. (No sales involved just vital info free to you)

    • Richard Head

      I would like to elaborate on how calorie restriction works. Most studies show you need a long time of NO calories , up to 24 hours. Why? This effect is on the repair system of our cells. We have an amazing pharmacy in our cells and this produces vital repair chemicals when signaled. Our cells are damage each and every day and repair is vital. Most chronic diseases and aging due to failure of repair. The lack of calories for a prolonged time is a stress signal that causes the genes (Sirtuns) to release the cleanup chemicals. So, yes caloric restriction is important but it must be done for a prolonged time to get the effect necessary. I suggest a 2 day a week (eg. Mon and Thurs) with no calories from the dinner the night before to dinner of the day the restriction is done.

  5. Michael J. Douglas

    Hello I first read the Zone book and Mastering the zone back in 1999. I have been a regular customer of some of your products and I have a concern about how much Omega 3 and now you have the new Omega 2’s. So how much is enough? I think the recommendation is 4 per capsules per day. Then the polyphenols are to be taken to help the oxidation of the omega 3’s. I like you first five booKs that were focused on food. Now with your supplements I may have the balance wrong. If I follow the flow chart in Mastering the Zone book and take the supplements as recommended I believe it is too much. Any suggestions on how to get re-balanced and should I be taking Omega 2. The doc I go to said that omega 3 benefit was not conclusive and the I can get the same benefit from 1 baby aspirin a day. I don’t believe that, so I thought I’d ask for your thoughts.

    Thank you and keep up the good work.


    • Denis Sullivan

      Don’t guess, test. Your AA/EPA ratio will tell you how much Omega Rx2 to consume and you do need it. The supplements are just that. They won’t leave you unbalanced. You were right in not believing your doc. His info is out of date! Unlike you, your doc obviously hasn’t read any Zone books. Until he does he knows less than you and the doc should be asking you questions, not the other way around!

    • Barry Sears

      The OmegaRx 2 is more concentrated so you would potentially need less. However, the AA/EPA ratio of the blood will give you far greater precision in determining your optimal level. The goal is try to get the AA/EPA ratio between 1.5 and 3. The Zone Diet remains the foundation for anti-inflammatory nutrition, but higher levels of next generation of omega-3 fatty acids and polyphenols can significantly enhance the anti-inflammatory benefits of the Zone Diet. Relative to your physician, I don’t believe he understands that the hormones (resolvins) needed to resolve inflammation can only be synthesize if there are higher levels of EPA and DHA in the blood s. Resolution of inflammation is a completely different process than the inhibition of inflammation. The AA/EPA ratio will provide the information with great precision to indicate the amount of OmegaRx 2 you need for optimal resolution.

  6. Norma

    Dear D. Barry Sears,

    I came across your post in doing research. I have a chronic disease . Its MIA (Mycobacterium avium-intracellulare infection ), Its now in its advance stages. I can’t stop coughing. My ribs hurt, my chest hurts, and my throat is always sore. Do you have any advise on a good diet to follow in order to get rid of this illness. I feeling really bad. I also have to mention I also have sarcoidosis. Most sarcoid patients get MIA. My doctors having given up on me. I no longer take medication.

    Kindest Regards
    Norma Roldan

    • Barry Sears

      You definitely have unresolved inflammation coming from the infection. Obviously an anti-inflammatory diet like the Zone Diet supplemented with high-dose EPA and DHA to provide the substrates to make the hormones (resolvins) to resolvin ongoing inflammation would be an excellent choice. I would start with 7.5 grams of EPA and DHA, but only if highly refined.


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