Calorie restriction is the only proven way to extend lifespan. More importantly, it is also the best way to extend your healthspan, which is defined as the percentage of your life lived without being compromised by chronic disease.
However, most people forget that calorie restriction is defined as restricting calories without malnutrition. That means supplying adequate amounts of micronutrients (vitamins and minerals) and macronutrients (protein, carbohydrate, and fats). All of a sudden, calorie restriction seems like a lot of work. Therefore, “biohackers” come up with shortcuts like intermittent fasting programs that don’t require a lot of thinking. So, do intermittent fasting programs do better than classical calorie restriction? The research data suggests that there is no contest.
That particular research data was published last year (1). This study used a wide number of genetically diverse mice to study five different dietary interventions consisting of a control diet, a calorie-restricted diet with 20% fewer calories than the control diet, a calorie-restricted diet with 40% fewer calories than the control diet, the control diet, but fasting one day per week, and the control diet, but now fasting two days a week. The actual calorie restriction in the two fasting groups was actually less than projected since they could eat more food during their non-fasting days. The result was that the mice who fasted two days a week actually consumed only 12% fewer calories than the control diet. The mice started their diets six months after birth and were maintained on them until their deaths. Here are the results for the increase in their average lifespan:
| Diet | Increase in lifespan compared to control |
| Control diet | — |
| One day per week fasting | 12% |
| Two days per week fasting | 11% |
| 20% calorie restriction | 18% |
| 40% calorie restriction | 36% |
A fairly striking increase in lifespan was observed. However, the mice following the 40% calorie restriction had significantly lower lean body mass than the other groups. This is similar to humans taking GLP-1 drugs, in which the loss of lean body mass accounts for nearly 40% of the total weight loss (2). Remember, one of the criteria for calorie restriction is to be adequately supplied with macronutrients, which includes protein to maintain lean body mass. Individuals taking GLP-1 are definitely not achieving that criterion (3, 4, 5).
To reap the life extension benefits of calorie restriction, it must be practiced for a lifetime. Thus, what is the minimum daily protein intake that you need to maintain your lean body mass? It is likely to be at least 90 grams of protein per day, and ideally 30 grams of protein per meal to reduce hunger throughout the day. Furthermore, you probably need only 1,200 to 1,500 calories per day to achieve satiety as long as you balance that protein with low-glycemic load carbohydrates (primarily non-starchy vegetables) and adequate fat in a calorie-restricted diet containing a macronutrient balance of 40% carbohydrates, 30% protein, and 30% fat. It is also known as the Zone diet (6). The Zone diet is also patented to reduce insulin resistance. It is insulin resistance that causes excess fat gain and the acceleration of chronic diseases strongly associated with insulin resistance, such as type 2 diabetes and heart disease.
But does it work in humans? The answer is yes, especially in pre-diabetes and type 2 diabetes. In one 12-week open study in type 2 diabetes, every marker of diabetes was dramatically reduced in 12 weeks (7). More careful studies, in which all meals were prepared, have shown that following the Zone diet for 24 weeks resulted in the remission of both pre-diabetes and type 2 diabetes (8,9). More importantly, the individuals following the Zone diet gained lean body mass, even though the degree of calorie restriction was greater than that of those using GLP-1 drugs. The control groups in these studies received the same level of calorie restriction, but without the Zone macronutrient balance, did not have such remission, and actually lost lean body mass, just like those using GLP-1 drugs.
I use the word remission in these studies as opposed to cure, since once you go off the Zone diet, the clinical symptoms of pre-diabetes and type 2 diabetes will return. Thus, if you want to live longer like in the mice study I mentioned at the start of this blog, you have to be on the Zone diet for a lifetime. And if you want even better results, consider adding omega-3 fatty acids to reduce chronic low-level inflammation and polyphenol supplements to reduce oxidative stress. Now you have the Metabolic Engineering® dietary program. How long do you have to follow Metabolic Engineering®? It depends on how long you want to live.
References
1. Di Francesco A, Deighan AG, Litichevskiy L, et al. Dietary restriction impacts health and lifespan of genetically diverse mice. Nature. 2024 Oct;634(8034):684-692. doi: 10.1038/s41586-024-08026-3.
2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183.
3. Anyiam O, Phillips B, Quinn K, et al. 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.
4. Almandoz JP, Wadden TA, Tewksbury C, Apovian CM, et al. Nutritional considerations with anti-obesity medications. Obesity. 2024 Sep;32(9):1613-1631. doi: 10.1002/oby.24067.
5. Johnson B, Milstead M, Thomas O, et al. Investigating nutrient intake during use of glucagon-like peptide-1 receptor agonist: a cross-sectional study. Front Nutr. 2025 Apr 25;12:1566498. doi: 10.3389/fnut.2025.1566498.
6. Sears, B. The Zone. Regan Books. New York, NY (1995)
7. Hamdy O, Carver C. The Why WAIT program: Improving clinical outcomes through weight management in type 2 diabetes. Curr Diab Rep. 2008 8:413-20. doi: 10.1007/s11892-008-0071-5.
8. Stentz FB, Brewer A, Wan J, et al. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: Randomized control trial. BMJ Open Diabetes Res Care. 2016 4:e000258. doi: 10.1136/bmjdrc-2016-000258.
9. Stentz FB, Lawson D, Tucker S, et al. 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 4:100047. doi: 10.1016/j.obpill.2022.100047.
