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Dr. Sears' Blog

Breaking down the latest research on Anti-Inflammatory Nutrition
Written By: Dr. Barry Sears, Ph. D | Creator of the Zone Diet

Written by Dr. Barry Sears
on January 13, 2023

For the past six years, the Mediterranean diet has been voted the Best Diet in America as well as the best diet to manage diabetes. It’s remarkable since no one can define the Mediterranean diet. No one knows how many calories you should consume each day or how many grams of protein or fat should be consumed daily on the Mediterranean diet. There is also no distinction between low-glycemic or high-glycemic carbohydrates, protein-to-carbohydrate balance, etc. It certainly doesn’t give a strong feeling of robust science for the best diet in America as I pointed out in my book, The Mediterranean Zone (1).

            Furthermore, the initial results indicating the breakthrough of the Mediterranean diet published in 2013 had to be retracted and republished because of severe methodological problems in the study (2). Nonetheless, the lack of good science doesn’t prevent the Mediterranean diet from being consistently voted the top diet for general health and diabetes management for the past six years.

            A new study presents much more controlled research that can be used to compare the benefits of the Mediterranean diet to the Zone diet (3). The study was a direct head-on comparison to the Zone diet, so it was a “winner take all.” The study was conducted in a metabolic ward in an Italian hospital where all the food was provided to the subjects. The subjects also had significant insulin resistance (HOMA-IR > 4). Since the subjects were confined to the hospital, their dietary intake was tightly monitored. The control group received a calorie-restricted Mediterranean diet (500 calories less than needed to maintain their current weight) consisting of 55 percent carbohydrates, 20 percent protein, and 25 percent fat. The active group had the same level of calorie restriction but it was composed of 40 percent carbohydrates, 30 percent protein, and 30 percent fat. Although the authors cite this higher protein diet as a “high-protein Mediterranean diet,” it was identical to the Zone diet I described in 1995 (4). Furthermore, it was a crossover study since halfway through the study, the diets the subjects were consuming were switched after ten days to reduce any potential impact of individual metabolic characteristics of the subjects on the results.

The Results

The Zone diet demonstrated superior insulin resistance and hyperinsulinemia reductions compared to the Mediterranean diet.  But there is more. The Zone diet also reduced the variability of blood glucose levels, indicating better hormonal stability between meals than the Mediterranean diet. This result was hardly new since Harvard investigators reported similar results after a single Zone meal compared to an isocaloric meal containing a higher level of carbohydrates and a lower level of protein in 1998 (5). In addition, the Zone diet is the primary dietary program used by the Joslin Diabetes Research Center at Harvard Medical School for treating type 2 diabetes. The reason is that the Zone diet is defined and, more importantly it works (6-9).

            So why don’t you hear more about the Zone diet in the medical research literature? I think the primary reason appears to be that the researchers wish to believe they came up with the idea of the macronutrient balance of the Zone diet all on their own, even though the Zone Diet was granted a U.S. patent for the treatment of hyperinsulinemia and insulin resistance in 2000 (10). Furthermore, since more than six million books on the Zone diet have been sold in the United States since the publication of The Zone in 1995, it is not that no one has ever heard of the Zone diet.

            Another problem is understanding the underlying metabolic problem that causes what is loosely termed “insulin resistance. “ It’s insulin resistance that causes weight gain and diabetes. However, insulin resistance can be best understood as a general term to describe the disruption of your metabolism. Furthermore, insulin resistance is associated with many other chronic disease conditions other than obesity and type 2 diabetes. These other chronic diseases include heart disease and Alzheimer’s. However, the most likely molecular cause of insulin resistance is the inhibition of the master regulator of metabolism known as AMPK (11).

            To optimally activate AMPK, you need a dietary triad consisting of the calorie-restricted Zone diet coupled with adequate intakes of omega-3 fatty acids and polyphenols.  This is the Zone Nutritional System. Each of these nutritional interventions works synergistically with each other to increase AMPK activity.  Any single intervention is good but using all three simultaneously is powerful. The molecular mechanisms of their interactions are complicated, but nutrition is always more complex than simple pharmacology.



  1. Sears B. The Mediterranean Zone. Ballantine Books. New York, NY (2014)
  2. Estruch R et al. “Retraction and Republication: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90 Retraction of Publication.” N Engl J Med. 378:2441-2442. doi: 10.1056/NEJMc1806491. (2018)
  3. Tettamanzi F et al. “A high-protein diet is more effective in improving insulin resistance and glycemic variability compared to a Mediterranean diet: A cross-over controlled inpatient dietary study. Nutrients 13:4380. doi: 10.3390/nu13124380. (2021)
  4. Sears B. The Zone. Regan Books. New York, NY (1995)
  5. Ludwig DS et al. “High glycemic index foods, overeating, and obesity.” Pediatrics 103:E26. doi: 10.1097/00008480-199908000-00005. (1999)
  6. Giusti J and Rizzott J. “Interpreting the Joslin Diabetes Center and Joslin Clinic clinical guideline for overweight and obese adults with type 2 diabetes.” Curr Diab Report 6:405-408. doi: 10.1007/s11892-006-0014-y. (2006)
  7. Hamdy O. “Diabetes weight management in clinical practice—the Why Wait model,” US Endocrinology 4:49–54. doi.org/10.17925/USE.2008.04.2.49. (2008)
  8. Hamdy O. and Carver C. “The Why WAIT program: improving clinical outcomes through weight management in type 2 diabetes.” Curr Diab Rep 8:413-420. doi: doi: 10.1007/s11892-008-0071-5. (2008)
  9. Hamdy O. et al. “Long-term effect of intensive lifestyle intervention on cardiovascular risk factors in patients with diabetes in real-world clinical practice: a 5-year longitudinal study.” BMJ Open Diabetes Res Care 5:e000259. doi: 10.1136/bmjdrc-2016-000259. (2017)
  10. Sears, B. “Method of and nutritional and pharmaceutical compositions for reduction of hyperinsulinemia.” U.S. Patent No. 6,140,304 (2000)
  11. Sears B and Saha A. “Dietary activation of AMP-activated protein kinase (AMPK) to treat insulin resistance.” Evolving Concepts in Insulin Resistance doi: http://dx.doi.org/10.5772/intechopen.103787. (2022)

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