Do our bodies have an evolutionary defense mechanism that resists weight loss? A closer look at very low calorie diets.

Posted on: April 28th, 2025 by Our Team

In an age where GLP-1 drugs are pervasive (but unaffordable and inaccessible) – many people instead attempt very low calorie diets (VLCDs). These diets clock in around 1,000-1,200 kcal/day– an intake well below almost everyone’s RMR, or the level required to sustain bodily functions at rest. Initially these diets work, but after a few months people reach a plateau– and in my clinical practice, it’s not just sedentary patients who present with near-starvation eating habits. Competitive athletes– especially those who participate in sports emphasizing leanness or a certain body image– who follow VLCDs are at risk for RED-S, or Relative Energy Deficiency in Sports. For example, I recently worked with a top-flyer from the Cirque De Soleil who, like many gymnasts, had strict weight requirements. Endurance runners and cyclists also care a lot about their power to weight ratio, and how that affects performance. Similar to a VLCD, REDs is associated with lower bone density, depressed immune function, impaired recovery from workouts, increased risk of injury (especially stress fractures) – and even menstrual cycle dysfunction.

Initially, even though we are eating less– the amount of energy we’re expending remains relatively unchanged. While this deficit brings about some weight loss, changes in body fat are negligible. Instead, we have lost appreciable water, sodium and glycogen1. During the first 3 weeks on a diet we lose ~40% of our liver’s baseline mass and only about 15% from fat (adipose tissue)2. Since the liver is the primary storage site for carbohydrate (glycogen), active people who undereat to this degree will feel slower, fatigue earlier, and recover poorly from cardiovascular exercise.

As we continue a VLCD, the sustained increase in fat burning eventually leads to a pronounced decrease in body fat. Around week five we begin to lose muscle– perhaps the greatest risk of a VLCD, aside from the nutritional adequacy of the diet being likely suboptimal. The magnitude of our muscle loss will depend upon many factors, but our age and baseline body composition matter most. This is because quantitatively, RMR accounts for 65-70% of EE and depends upon how much muscle mass we have when we embark on the diet. The more muscle we lose, the greater the decline in resting metabolic rate. And because muscle accounts for a significant portion of our body’s glucose disposal, loss of muscle is associated with insulin resistance.

Other important factors for maintaining lean mass are protein intake, whether or not we’re engaged in resistance training, the length of time dieting, and other lifestyle factors (such as sleep quality and stress management). It’s been repeatedly demonstrated that combining heavy weight training with adequate protein doses– spread across multiple feedings per day – mitigates the drop in muscle protein synthesis, even during a caloric deficit. This optimal dose for maximizing muscle protein synthesis (for people 35-65 yrs) is 35-40g protein per meal 1, and for seniors older than 65, a relative dose of 0.4-0.5 g/ kg body weight / per meal is optimal 1.

Back to our VLCD: since we’ve now lost 10 lbs, we aren’t expending as much energy. And here’s where it gets truly wild: over time, our food intake and energy expenditure approximate each other until they reach an equilibrium. This is known as metabolic adaptation. In research, metabolic adaptation after 3 months of dieting was found to be as high as 8% during sleep and 13% under free-living conditions2. Such adaptations are due not only changes in metabolism, but compensations in our behaviors in an effort to conserve energy. We may sleep longer, sit more, move less and over time– adherence to the diet itself wanes.

Now we have lost a disproportionate amount of our “fat free mass”- this refers to the total weight of anything that is not fat or bone, but includes organs and connective tissue. The metabolic rate of organs is much greater than that of skeletal muscle– up to 20 times higher for some! In one study, people who lost 11% of their body weight also lost 26% of heart mass (cardiac muscle) and 19% of kidney mass3. Rapid weight loss in particular weakens heart muscle, impairs cardiac output, reduces oxygen and nutrient delivery to the body, disrupts electrolyte balance and can even cause arrhythmias.

VLCDs also bring about metabolic adaptation due to changes in hunger hormones (leptin and insulin) as well as thyroid hormones. This is why our appetite seems to be magnified following weight loss 4. However, it’s uncertain if metabolic adaptation increases the timeline for people to achieve weight loss goals, and the evidence for it causing weight regain is extremely weak 5. At the level of RMR, metabolic adaptation after weight loss was not associated with weight regain up to 2 years follow-up5.

The mechanisms discussed above are clinically relevant because they explain why individuals who are struggling to achieve weight loss (despite assuring compliance with their diet) may indeed be suffering from the very real phenomenon of metabolic adaptation. There is a saying: “the best diet is the one you can stay on” and there is so much truth in this! Diets that are too restrictive or feel like utter deprivation are not likely to be maintained long-term. A sustainable diet is one you can realistically incorporate into your everyday life without feeling overwhelmed, and will ensure you maintain not only the weight lost, but also the enduring metabolic benefits.

Sources:

1. Witard et al. Growing older with health and vitality: a nexus of physical activity, exercise and nutrition. Biogerontology (2016) 17:529–546
2. Most and Redman. Impact of calorie restriction on energy metabolism in humans. Exp Gerontol. 2020 Feb 11;133:110875.
3. Gallagher et al. Changes in skeletal muscle and organ size after a weight-loss intervention in overweight and obese type 2 diabetic patients. Am J Clin Nutr. 2016 Nov 23;105(1):78–84.
4. Martins et al. Metabolic adaptation is associated with a greater increase in appetite following weight loss: a longitudinal study
5. Martins et al. Metabolic adaptation delays time to reach weight loss goals. Obesity (Silver Spring). 2022 Feb;30(2):400–406
6. Heymsfield et al. Voluntary weight loss: systematic review of early phase body composition changes. Obes. Rev 12, e348–e361.
7. Rondanelli, M et al. Review Current opinion on dietary advice in order to preserve fat-free mass during a low-calorie diet. Nutrition 72 (2020)
8. Janssen et al. The impact and utility of very low-calorie diets: the role of exercise and protein in preserving skeletal muscle mass. Current Opinion in Clinical Nutrition and Metabolic Care 26(6):p 521-527, November 2023.
9. Van Gaal et al. Factors determining energy expenditure during very-low-calorie diets. The American Journal of Clinical Nutrition. Volume 56, Issue 1, July 1992