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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 August 04, 2020

We continually hear about the health reasons why you should lose weight. But what are the molecular reasons? Now we have a clue; increased production of resolvins. Resolvins are a group of molecules derived from omega-3 fatty acids that help resolve inflammation.  In a recent paper, it was demonstrated that losing a moderate amount of weight (about 11 pounds in 12 weeks) resulted in a dramatic increase in certain resolvins (1). As I discuss in my newest book, The Resolution Zone, resolvins are among the key players in the body’s internal Resolution Response that allows you to heal from inflammatory damage, especially diet-induced inflammation (2).

            Not all resolvins increased in that study. The only resolvin that increased was RvE1, which increased by 600 percent! This increase is critical since RvE1 promotes increased bone formation, decreased atherosclerosis, decreased diabetes, decreased neurological problems, and improved tumor clearance in animal models (3-9). The same benefits are also observed in humans who lose weight, suggesting that increased production of RvE1 may be a primary reason for the clinical benefits of weight loss.

            What is the best way to lose weight and keep it off to gain all of these benefits of increased RvE1 production? It remains the Zone diet (10). Here are the basic rules for permanent weight loss by following the Zone diet.

Zone Diet Rules


#1. You have to reduce calories

The only way to lose weight by the diet is to reduce calories. There is no mystical new way. Ketogenic diets have no “metabolic advantage” compared to the Zone diet (11), and intermittent fasting is no better than continuous calorie restriction (12,13). A calorie is a calorie. That is why calorie restriction is the foundation of the Zone diet. However, the secret is to reduce calories without hunger or fatigue, which leads to the next rules for following the Zone diet.

Dr.-Sears-Weight-Loss-and-Resolvins-Blog-02#2 Consume adequate protein at each meal

You will need at least 25 grams of protein at every meal to induce hormonal signals (such as PYY and GLP-1) that come from the gut and go directly to your brain to stop hunger.

Dr.-Sears-Weight-Loss-and-Resolvins-Blog-003#3 Hormonal control in the blood is key

The level of protein at each meal must be balanced by the appropriate glycemic load. This achieves a stable balance of insulin and glucagon in the blood after each meal to stabilize blood sugar levels. The balance of these opposing hormones stabilizes blood glucose levels to prevent hunger and mental fatigue for the next four to five hours. Consistent blood sugar control comes from maintaining the appropriate protein-to-glycemic-load at each meal, which is another critical feature of the Zone diet.

Dr.-Sears-Weight-Loss-and-Resolvins-Blog-04#4 Reduce the glycemic load by eating primarily non-starchy vegetables as your carbohydrates

The easiest way to reduce the glycemic load is to increase your intake of non-starchy vegetables while moderating fruits and significantly reducing your consumption of grains and starches. The reason is that non-starchy vegetables have the highest amount of fermentable fiber with the least amount of carbohydrates. Fermentable fiber is used by the microbes in your gut to generate the formation of short-chain fatty acids that enhance the satiety effects of PYY and GLP-1.


#5 Dramatically reduce your intake of saturated and omega-6 fatty acids

The Zone diet is a diet that is low in total fat. However, the fat it contains is rich in monounsaturated fats (which are non-inflammatory) and highly restricted in saturated fats and omega-6 fats (which are pro-inflammatory).

Zone Diet Tips

Here are some simple dietary tricks to get started and make compliance easier.

#1. Eat your protein first before you consume your carbohydrates

It takes more time for protein to enter the blood than does carbohydrates. By eating your protein at a meal first you will achieve a better hormonal balance (14,15).

#2 Calorie density per meal is important

Consuming too many calories, even if they are perfectly balanced, can cause inflammation in the hypothalamus, which disrupts the appetite control center in the brain (16). The Zone diet recommends about 400 calories per meal to prevent such hypothalamic inflammation caused by consuming too many calories in a meal.

#3 Time restriction for eating should be based on your circadian rhythms, not your watch.

A recent study indicates that the more calories consumed at night induced more fat accumulation compared to the same number of calories consumed during daylight hours (17). Furthermore, the same study demonstrated the importance of eating breakfast to be in alignment with the circadian regulation of your metabolic pathways.  This spreading of your calorie intake to be in alignment with circadian rhythms also relates to calorie density. The more you restrict your feeding duration, the higher the calorie density during that shortened eating period, and thus the higher likelihood of hypothalamic inflammation (16). A good rule to follow is to eat within one hour after waking up and stop eating no later than 12 hours after waking up. This timing might be considered to be a “12-12” feeding cycle to minimize fat accumulation and prevent hypothalamic inflammation since you are reducing the calorie density through your eating window.


Many of the clinical benefits of weight loss may be attributed to increased resolvin production. The most clinically-validated way to achieve and maintain weight loss is the Zone diet as long as you follow the rules. Of course, if you follow the Zone diet to reduce inflammation, you also want to take omega-3 fatty acids to resolve inflammation and add adequate levels of polyphenols to repair the damage caused by inflammation. The combination of the Zone Diet coupled with high-purity omega-3 fatty acids and polyphenol supplementation is what I term Pro-Resolution Nutrition. Pro-Resolution Nutrition is also the best way to optimize your healthspan (2).



  1. Barden A et al. “Effect of weight loss on neutrophil resolvins in the metabolic syndrome.” Prostaglandins, Leukotrienes, and Essential Fatty Acids 148 25-29- (2019)
  2. Sears B. The Resolution Zone. Zone Press. Palm City, FL (2019)
  3. El Kholy K et al. “Resolvin E1 promotes bone preservation under inflammatory conditions.”

Front Immunol 9: 1300 (2018)

  1. Sima C et al. “Function of pro-resolving lipid mediator resolvin E1 in type 2 diabetes.

Crit Rev Immunol 38: 343-365 (2018)

  1. Sulciner ML et al. “Resolvins suppress tumor growth and enhance cancer therapy.

J Exp Med 215: 115-140 (2018)

  1. Carracedo M et al. “The resolution of inflammation through omega-3 fatty acids in atherosclerosis, intimal hyperplasia, and vascular calcification.” Semin Immunopathol 41: 757-766 (2019)
  2. Siddiquee A et al. Effect of omega-3 fatty acid supplementation on resolvin (RvE1)-mediated suppression of inflammation in a mouse model of asthma. Immunopharmacol Immunotoxicol 41: 250-257 (2019)
  3. Freire MO et al. “Neutrophil resolvin E1 receptor expression and function in type 2 diabetes.” J Immunol 198: 718-728 (2017)
  4. Hasturk H et al. “Resolvin E1 (RvE1) attenuates atherosclerotic plaque formation in diet and inflammation-induced atherogenesis.” Arterioscler Thromb Vasc Biol 35: 1123-33 (2015)
  5. Sears B. The Zone. Regan Books.   New York, NY (1995)
  6. Johnston CS et al. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 83: 1055-61 (2006)
  7. Trepanowski JF et al. “Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults.” JAMA Intern Med 177: 930-938 (2017)
  8. Schubel R et al. “Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial.” Am J Clin Nutr 108: 933-945 (2018)
  9. Shukla AP et al.   “Food order has a significant impact on postprandial glucose and insulin levels.” Diabetes Care 38: e98–e99 (2015)
  10. Shukla AP et al. “Carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes.” BMJ Open Diabetes Res Care 5: e000440 (2017)
  11. Cai D. “Neuroinflammation and neurodegeneration in overnutrition-induced diseases.”Trends Endocrinol Metab 24: 40–47 (2013)
  1. Kelly KP et al. “Eating breakfast and avoiding late-evening snacking sustains lipid oxidation.” PLoS Biol 18: e3000622 (2020)

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