If you’ve read some of my other posts, you might be familiar with my claim that the “calorie in calorie out” (CICO) theory isn’t as strict a rule as many mainstream nutritionists claim. They often try to affirm CICO by citing the law of thermodynamics. This law works great on machines like cars, but not on the dynamic metabolism of humans. Click here to see my post on how my claim can easily be proven with a simple example. And read on below to see studies further proving my claim, which expand and expand on the metabolic set point theory and other factors that make CICO more of a general starting guideline (at best), rather than any kind of a rule.

The Sims Vermont Prison Study, conducted in the 1960s by Dr. Albert J. Stunkard and his colleagues, including Dr. George A. Sims, was the first to investigate the challenges of weight gain to delve into the dynamic human metabolism. The study involved a group of volunteer prisoners who were tasked with increasing their body weight by 25%.

For 200 days, these men consumed heroically large amounts of food, with caloric intakes roughly twice their usual amount. Despite their valiant efforts, all but two of the participants found it nearly impossible to gain the targeted weight. Most reached a certain weight and despite increasing their intake to 10,000 calories a day, got stuck at that weight. Their metabolism just adjusted up to burn off the excess calories (I bet this turned them into pretty sweaty guys). This outcome demonstrated that simply consuming more calories does not guarantee weight gain, as the human body has complex regulatory mechanisms governing energy balance and storage.

Once the participants achieved their increased weight, maintaining that weight proved challenging. To sustain their new weight, they required caloric intakes that were much higher than the simple arithmetic of energy balance would suggest. After the study ended, all the participants, except for the two with previously undiagnosed family histories of obesity and diabetes, returned to their original weights without any restriction on food. This result indicated that the human body has a strong tendency to maintain a specific weight set point, making it difficult to gain or sustain weight beyond that point through increased caloric intake alone.

Click here to see the original PDF of that study. I had to upload it to this site and link it within because, apparently (as of 8/8/2025 anyway), it had been scrubbed from the internet. I had to use a special unfiltered and unrestricted search engine (swisscows.com) to find it on another site, which had to embed it like I did here. Why do you suppose this is? Well, it’s likely because this study proves a fact of biology that destroys the mainstream CICO narrative, and most things contradicting the prevailing narrative get scrubbed so normies can’t be exposed to those truths.

Click here to see another less sensational study (but public) that tackles the same “set point” issues, but with a more watered-down (less controversial) delivery. It discusses topics such as neurohormonal, adaptive thermogenesis, genetics, epigenetics, obesogens, bariatric surgery’s effect on gut microbiome, and more.

Click here to see the set point theory discussing contributing factors such as genetics, epigenetics, environmental factors, energy balance mechanisms, macro nutrient metabolism, thermic effect of food, hormonal feedback signals, metabolic adaptations, fat mass versus lean mass, and more.

And explore further below to see several other studies confirming my claim that CICO is a flawed theory that should be thrown out completely, in favor of a more individualized approach that takes for following factors into consideration when counseling and advising people on weight loss (like I do with my X Gym members):

Keys A. The Biology of Human Starvation (1950)

• Citation: Keys A. The Biology of Human Starvation. Minneapolis, MN: University of Minnesota; 1950.
• Description: The seminal Minnesota Starvation Experiment demonstrated body weight regulation through the “catch-up fat phenomenon.” Subjects lost 66% of initial fat mass during semi-starvation but regained 145% of pre-starvation fat levels upon re-feeding, suggesting a biological drive to restore a set point. This study provides foundational evidence for asymmetric weight regulation, particularly in response to weight loss.
• Link: No direct online link due to the book’s age, but it’s available through academic libraries or purchase from publishers like University of Minnesota Press. Check WorldCat for library availability: WorldCat – The Biology of Human Starvation. Alternatively, excerpts or summaries may be found via Google Scholar or PubMed by searching the title.

Harris RB. Role of set-point theory in regulation of body weight (1990)

• Citation/Link: Harris RB. FASEB Journal. 1990;4(15):3310–3318. doi: 10.1096/fasebj.4.15.2253845.
• Description: This review outlines the set point theory, proposing that body weight is regulated by a feedback control system centered in the hypothalamus. It discusses how peripheral signals influence weight stability, providing a framework for understanding set point mechanisms in humans, though it notes the theory’s limitations in explaining obesity.

Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight (1995)

• Citation: Leibel RL, et al. N Engl J Med. 1995;332:621–8. doi: 10.1056/NEJM199503093321001.
• Description: This study explores metabolic adaptations to weight changes, showing that energy expenditure decreases with weight loss and increases with weight gain beyond what is expected from body mass changes. It supports the set point theory by demonstrating compensatory mechanisms that defend a specific weight range.

Hall KD. Computational model of in vivo energy metabolism during semistarvation and refeeding (2006)

• Citation: Hall KD. Am J Physiol Endocrinol Metab. 2006;291:E23–37. doi: 10.1152/ajpendo.00523.2005.
• Description: Using data from the Minnesota study, this computational model simulates weight changes during starvation and re-feeding, suggesting that fat mass restoration takes over a year to stabilize. It supports the idea of a loose set point or settling points, highlighting the complexity of long-term weight regulation.

Hall KD. Predicting metabolic adaptation, body weight change, and energy intake in humans (2010)

• Citation: Hall KD. Am J Physiol Endocrinol Metab. 2010;298:E449–66. doi: 10.1152/ajpendo.00559.2009.
• Description: This study advances computational modeling of metabolic fluxes, predicting how energy intake and expenditure adjust to maintain body weight. It argues for settling points influenced by dietary intake, challenging a strict set point in humans under modern dietary conditions.

Prentice AM, et al. Effects of weight cycling on body composition (1992)

• Citation: Prentice AM, et al. Am J Clin Nutr. 1992;56:209S–216S. doi: 10.1093/ajcn/56.1.209S.
• Description: This study examines weight cycling in Gambian women under seasonal food shortages, finding minimal body weight remained stable (±1.5 kg) over 10 years despite fluctuations. It supports set point regulation under traditional diets, contrasting with disrupted control in Western environments.

Dulloo AG, Jacquet J, Girardier L. Poststarvation hyperphagia and body fat overshooting in humans: a role for feedback signals from lean and fat tissues (1997)

• Citation: Dulloo AG, et al. Am J Clin Nutr. 1997;65:717–23. doi: 10.1093/ajcn/65.3.717.
• Description: This study analyzes post-starvation hyperphagia, linking it to feedback signals from fat and lean tissues. It supports the set point theory by showing a drive to restore fat mass after depletion, with overshooting suggesting a strong regulatory mechanism.

Keesey RE, Hirvonen MD. Body Weight Set-Points: Determination and Adjustment (1997)

• Citation: Keesey RE, Hirvonen MD. The Journal of Nutrition. 1997;127(9):1875S–1883S. doi: 10.1093/jn/127.9.1875S.
• Description: This review explores set point regulation in animals and humans, suggesting obesity may reflect an elevated set point. It discusses how genetic and environmental factors adjust set points, providing evidence for active biological control.

Pasquet P, Apfelbaum M. Recovery of initial body weight and composition after long-term massive overfeeding in men (1994)

• Citation: Pasquet P, Apfelbaum M. Am J Clin Nutr. 1994;60:861–3. doi: 10.1093/ajcn/60.6.861.
• Description: This study of Cameroonian men showed that after massive overfeeding (19 ± 3.2 kg weight gain), a return to a traditional low-fat diet led to spontaneous weight recovery within 2.5 years, supporting set point regulation under non-Western dietary conditions.

Rosenbaum M, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight (2005)

• Citation: Rosenbaum M, et al. J Clin Invest. 2005;115:3579–86. doi: 10.1172/JCI25977.
• Description: This study demonstrates that leptin replacement mitigates metabolic and neuroendocrine adaptations (e.g., reduced energy expenditure) after weight loss, supporting leptin’s role in defending a set point, particularly against fat loss.

AND:

• https://pmc.ncbi.nlm.nih.gov/articles/PMC6039924/
• https://pubmed.ncbi.nlm.nih.gov/23359004/

These are just a few of the numerous studies. There are many more you can easily find, especially on elicit.com, if you want to take a deeper dive for those still not convinced that the CICO theory is hogwash.

Final note: Being the biohacker and experimental scientist that I am, I tried my own weight gain and weight loss experiment back in 1999, where I gorged myself on fast food and processed food to see how fast I could gain weight and to find what my upper set point might be. I found it. After 4 months, I had gone from 170 lbs to 204 lbs, and no matter how hard I tried, even after increasing my calories to 5000 per day, which is as much as I could bear, I could not punch through that 204 number. I was just hot and sweaty all the time as my metabolism adjusted upward to match what I was consuming.

I only pounded away at my top limit for about a month because I remember playing basketball with my son, and after going up for a rebound and coming back down, I felt a compression sprain in my ankle. It was then that I realized I had gained weight so fast that my joints weren’t adapted, and that’s how the injury happened, so I was set up, and I ended the experiment.

Had that not happened, I probably would’ve kept going, but based on all the studies, I wouldn’t have had much luck getting past 204 because that was my upper limit set point. Studies also show that the upper limit set point can be broken through with enough time and effort. Those people who insist on hammering against it will eventually succeed, and from what I’ve seen, once they break through that ceiling, the sky’s the limit, and the body gives up the whole set point concept, allowing them to gain weight with no new limit.

What I’ve also seen anecdotally is that when this happens, the previous set point ceiling becomes a floor, so when those people decide to lose weight, when they hit that set point limit they previously destroyed, they have a hard time getting back through it. With the same amount of time and determination, they put into breaking through it to go higher, the same as required to break through it to go lower and below it.

I have no studies to prove this, other than observation in other people as I help them back down through those floors, but it’s a pretty brutal struggle, so I would highly suggest against hammering away at your set point ceiling because once you break through it, you just made your life a lot harder if you ever wanna get back down again.

P.S. My updated Kindle book provides a deeper dive into this topic and many more, for those interested.