Everyone wants to lose excess body fat. However, the Holy Grail of weight loss is losing excess body fat while maintaining, if not increasing, lean body mass. So why is maintaining lean body mass so critical?
The first question is, what exactly is lean body mass? It is defined as your total weight minus your total body fat. The gold standard for such measurements has always been underwater measurements since fat weighs less than water or tissue. What is left behind after that calculation is your muscles, organs, and bones, as well as the water they need to function. These are parts of your body you don’t want to lose.
Unfortunately, for individuals using GLP-1 weight loss drugs, the loss of lean body mass can be a significant part of their total weight loss. The published data indicate that nearly 40% of the weight loss from using Ozempic comes from lean body mass (1). So, what happens when you stop taking Ozempic or other GLP-1 drugs? The weight initially lost begins to return rapidly (2). Unfortunately, this new weight is most likely to consist of increased fat, not new lean body mass.
A recent study has indicated that in animals, after losing weight by calorie restriction, they had accelerated development of heart disease when they increased their calorie intake (3). What this suggests is that the people who have lost weight using GLP-1 drugs and then stopped taking the drugs, their regained weight is likely to consist primarily of body fat, which will accelerate their risk of heart disease. That’s not good medicine.
So, how many calories do you need to lose fat, but also gain lean body mass? The answer is far fewer than you think. Remember, excess stored body fat serves as a high-octane fuel source to generate the energy you need to survive. The secret is being able to access it for energy. For that to happen, you need to activate AMPK, as it increases the breakdown of stored fat into chemical energy (4).
However, the efficiency of burning stored fat is highly dependent on the protein-to-carbohydrate ratio in your calorie-restricted diet. You need some protein at every meal to stimulate the release of GLP-1 from the gut to travel to the brain to signal you to stop eating. But how much protein? Approximately 30 grams per meal, but not more than 40 grams, as this level may begin to inhibit AMPK.
However, you also need to balance that protein with low-glycemic carbohydrates. What are those? They are primarily non-starchy vegetables. These carbohydrates enter the bloodstream at a slower rate.
What about fruits? While fruits contain polyphenols that help reduce oxidative stress, they also include a significant level of simple sugars, which are inhibitors of AMPK. Polyphenols are essential, but their benefits can be significantly reduced by the simple sugars they are associated with. Thus, isolated polyphenols are a better choice to keep your total carbohydrate intake at about 40-45 grams of carbohydrate per meal and still maintain adequate levels of polyphenols to reduce oxidative stress.
Finally, you add a dash of fat to each meal, but no more than 15 grams of fat per meal. Add all of these macronutrients together, and that’s going to be about 1,200 to 1,500 calories per day. This is approximately the level of total calorie intake of individuals who take GLP-1 drugs, but with a very different macronutrient ratio (5).
According to the USDA, the average American consumes approximately 3,800 calories per day; therefore, reducing this level of calorie intake represents a significant degree of calorie restriction (6). Furthermore, any type of calorie restriction will need to be continued for an extended period to lose enough excess body fat to make a considerable difference in losing enough excess body fat to become metabolically fit. Unfortunately, most individuals starting with GLP-1 to lose weight quit after one year due to side effects (7).
When can you start increasing your calorie intake? The answer is as soon as your percent body fat reaches a level of 14-17 percent for males or between 21-24 percent body fat for females (8). This is the level of body fat that indicates you are metabolically fit, and your stored body fat meets your metabolic requirements. Also, remember that while BMI measurements are convenient, they are not nearly as predictive of future heart disease mortality as percent body fat (8). Furthermore, when you define obesity using percent body fat instead of BMI, Americans are more obese than we are led to believe (9).
Measuring your percent body fat is easy. All you have to do is use my fat calculator which is based on underwater measurements. If your percent body fat is greater than the percentages for a metabolically fit individual, then you have plenty of excess fat to lose before you think about consuming more calories, as long as you are consuming adequate protein at each meal.
Furthermore, it is not simply reducing calorie intake that counts, because the protein-to-glycemic load ratio in those reduced calories is essential for your success. There are 100 million Americans who are pre-diabetics and 30 million Americans who have type 2 diabetes. Both conditions are characterized by extensive insulin resistance.
Studies have shown that patients from each of these groups who followed the Zone diet for six months, containing 1,200-1,500 calories per day, lost fat and gained lean body mass (10 and 11). More importantly, they reversed their pre-diabetes and type 2 diabetes in six months. This is something no drug can do. On the other hand, the control group in these studies consumed the same number of calories with a lower protein-to-glycemic load ratio. They lost lean body mass and had a dramatically lower impact on reversing their existing disease condition.
Studies with GLP-1 drugs demonstrate there is little change in percent body fat. Subjects who were obese (43 percent body fat) before taking the drug were still obese (39 percent body fat) while taking the drug for more than one year (1). Furthermore, although their weight loss had stopped after one year, they were still obese based on their percentage of body fat.
Additional studies indicate that once they stopped taking the drug, there was an immediate regain in their weight, most likely due to increased fat accumulation (2). And if we believe the recent animal data on rapid fat regain, this will accelerate their risk for heart disease complications compared to never having lost the weight in the first place (3). Therefore, it is not unreasonable to assume that if the lost weight returns as primarily new body fat, their cardiovascular risk will likely be increased compared to the control group over the long term. So why take the weight loss drug in the first place?
Losing excess body fat is essential for treating any existing chronic disease, as it reduces inflammation. However, you must lose enough excess body fat to make a noticeable difference in reducing inflammation and then prevent it from returning. Adequate intake of omega-3 fatty acids ensures that outcome. Just make sure to increase your lean body mass at the same time if you want to live longer and better. Metabolic Engineering® consisting of the Zone diet, adequate intake of omega-3 fatty acids, and isolated polyphenols gives you that possibility.
References
1. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I,McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. STEP 1 Study Group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021; 384: 989-1002. doi: 10.1056/NEJMoa2032183.
2. Wilding JPH, Batterham RL, Davies M, Van Gaal LF., Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA Wharton S, Yokote K, Kushner RF. STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab 2022;24: 1553-1564. doi: 10.1111/dom.14725.
3. Scolaro B, Krautter F, Brown EJ, Guha Ray A, Kalev-Altman R, Petitjean M, Delbare S, Donahoe C, Pena S, Garabedian ML, Nikain CA, Laskou M, Tufanli O, Hannemann C, Aouadi M, Weinstock A, Fisher EA. Caloric restriction promotes resolution of atherosclerosis in obese mice, while weight regain accelerates its progression. J Clin Invest. 2025 Jul 8:e172198. doi: 10.1172/JCI172198.
4. Goransson O, Kopietz F, Rider MH. Metabolic control by AMPK in white adipose tissue. Trends in Endocrinology & Metabolism 34: 704-711 (2023)
5. Anyiam O, Phillips B, Quinn K, Wilkinson D, Smith K, Atherton P, Idris K. Metabolic effects of very-low calorie diet, semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus. Clinical Nutrition 2024; 43:1907-1913. doi: 10.1016/j.clnu.2024.06.034.
6. https://www.ers.usda.gov/data-products/chart-gallery/chart-detail?chartId=58376
7. Do D, Lee T, Peasah SK, Good CB, Inneh A, Patel U. GLP-1 receptor agonist discontinuation among patients with obesity and/or type 2 Diabetes. JAMA Netw Open. 2024;7(5):e2413172. doi:10.1001/jamanetworkopen.2024.13172
8. Zeng Q, Dong SY, Sun XN, Xie J, Cui Y. Percent body fat is a better predictor of cardiovascular risk factors than body mass index. Braz J Med Biol Res. 2012 Jul;45(7):591-600. doi: 10.1590/s0100-879×2012007500059.
10. Stentz FB, Mikhael A, Kineish O, Christman J, Sands C. High protein diet leads to prediabetes remission and positive changes in incretins and cardiovascular risk factors. Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1227-1237. doi: 10.1016/j.numecd.2020.11.027.
11. Stentz FB, Lawson D, Tucker S, Christman J, Sands C. Decreased cardiovascular risk factors and inflammation with remission of type 2 diabetes in adults with obesity using a high protein diet: Randomized control trial. Obes Pillars. 2022 Dec 1;4:100047. doi: 10.1016/j.obpill.2022.100047.
