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The conventional prescription that people with obesity should “eat less and exercise more” remains widely used as a standard approach to weight management, despite repeated reports of its low long-term success rate [1].

At the same time, recent findings from genetics, epidemiology, physiology, and related fields have increasingly shown that body weight and body fat are biologically regulated within a certain range. These findings are helping to establish a biological framework that may explain why long-term success with weight-loss dieting is so difficult to achieve.

Following weight loss, adaptive responses are triggered through coordinated changes in metabolism, neuroendocrine function, autonomic nervous system activity, and even behavior. These responses have been shown to resist the maintenance of weight loss [4].

In this article, I will briefly introduce the biological mechanisms that may promote post-weight-loss weight rebound—or, in some cases, further weight gain. I will also explain how these mechanisms relate to, and differ from, my proposed “intestinal starvation” theory.

【Related Article】
The Spread of Dieting May Be Fueling the Rise in Obesity

Energy restriction is associated with a reduction in resting energy expenditure (REE) [5]. Many studies have reported that behavioral weight loss leads to a greater decrease in both resting and total energy expenditure than would be predicted based on changes in body composition and the thermic effect of food [4,6]. 

However, regarding the timing of its onset, the evidence is inconsistent [9]. Some studies have detected adaptive thermogenesis (AT) within a week of energy restriction, which has been associated with rapid declines in insulin secretion, depletion of glycogen stores, and loss of intracellular and extracellular fluid [10].

In contrast, a growing body of evidence suggests that underfeeding-associated AT takes weeks to develop, in association with reduced leptin secretion following the loss of body fat, among other physiological adaptations [9,11,12].

   
Although the persistence of AT also remains a subject of debate [7], some studies indicate that this metabolic adaptation may continue for years even after energy balance has been reestablished at a lower weight [13]. 
       

A number of hormones secreted from the gastrointestinal tract and adipose tissue are known to play key roles in regulating appetite, food intake, energy expenditure, and body weight [14,15].

     
Leptin is a hormone secreted by fat cells that helps regulate body weight by suppressing appetite and influencing energy expenditure. High leptin levels signal to the brain that energy stores are sufficient, whereas low leptin levels indicate that energy stores are low [16].

It has been shown that leptin levels drop within 24 hours of energy restriction [17]. Interestingly, many studies have reported a greater reduction in leptin levels than would be expected based on the loss of body fat [18,19].

It has been suggested that the primary role of leptin may be the prevention of starvation, rather than weight regulation per se [15,20]. When leptin levels fall below a certain threshold—the point at which specific physiological responses are triggered (Note1)—starvation defense mechanisms are activated, even if substantial fat stores remain [17]. This leads to a reduction in metabolic rate and physical activity, as well as an increase in hunger [21,22].

       
Furthermore, in individuals who have lost weight, an increase in the appetite-stimulating hormone ghrelin, along with decreases in the post-meal satiety signals peptide YY (PYY) and cholecystokinin (CCK), has been observed [23]. As a result, diet-induced weight loss may simultaneously reduce satiety and increase hunger, potentially promoting overeating [15].

Note 1: It has been suggested that this threshold rises as fat mass increases [17].

Food reward refers to the brain's reward response to food, which generates pleasure and satisfaction from eating, as well as the motivation to eat again. This process involves activation of the brain's reward circuitry, where neurotransmitters such as dopamine are released, leading to feelings of pleasure and increased appetite.

Modern neuroimaging studies using fMRI have shown that both nutritional status (e.g. hunger vs. satiety) and different food stimuli (e.g. high- vs. low-calorie foods, appetizing vs. bland foods) can alter activity in the brain's reward circuitry [27–29].

Recent studies in healthy individuals indicate that short- or long-term caloric restriction, as well as fasting, may increase the reward value of food—especially high-calorie, palatable foods [27,30].

These findings may help explain why calorie-restricted diets often fail in the long term [28,30].

Food addiction: similarities and differences from drug addiction

While drugs and food share certain characteristics, they also differ in important ways.

Drugs of abuse, such as cocaine, act directly on the brain's dopamine circuitry, whereas food influences these circuits more indirectly. Signals from taste and smell, nutrient sensors in the digestive tract [31], and hormones released during digestion and nutrient absorption all communicate with the brain, thereby influencing the dopamine system [25].

Food intake is primarily regulated by three interacting neural systems: the homeostatic, reward-related, and inhibitory systems [15].

The inhibitory system—mainly involving the brain region responsible for self-control and decision-making—helps regulate eating behavior and inhibit excessive food intake [34].

Cognitive control of food reward

In humans, the urge to seek and consume palatable foods can be moderated by executive functions—the cognitive processes involved in self-control and decision-making.

One of the central dilemmas in daily life is balancing one's internal goals (e.g. cutting back on sweets to maintain health and weight control) against the immediate reward of eating tempting foods. This conflict is particularly challenging when highly desirable foods, such as donuts or pizza, are readily available [25].

Prospective studies in young individuals, as well as rodent experiments, suggest that severe caloric restriction, characterized by 24-hour fasting or fat-free diets, may increase the risk of developing binge eating and bulimia in the future [37,38].

Weight-loss dieting may reduce the size, but not the number, of fat cells [39]. It remains unclear whether hyperplasia (an increase in adipocyte number) contributes to weight rebound in weight-suppressed individuals [15]. However, in a study of obese rats, adipocyte hyperplasia was observed following refeeding after fasting [40].

In humans, a similar possibility has been suggested.

The mechanisms described in Sections (1)–(5) are generally thought to represent a series of anti-starvation (or anti-weight-loss) responses (Note 2) that occur in association with energy restriction and weight loss [15].

In contrast, my intestinal starvation hypothesis proposes that when all ingested food is completely digested and no undigested matter remains in the intestinal tract, the body may interpret this condition as a starvation signal.

Intestinal starvation may occur not only during strict dietary restriction for weight loss (e.g. skipping meals or eating extremely small amounts of food), but also during more moderate dieting or even everyday eating habits that are not intended for weight loss, such as skipping breakfast, eating a light lunch, having dinner late at night, or eating only two meals a day.

Furthermore, in my intestinal starvation hypothesis, adaptive responses to intestinal starvation may lead to weight gain suggestive of an upward shift in the body-weight set point. This weight gain may involve not only body fat but also lean body mass, including skeletal muscle. Therefore, this mechanism may differ from conventional models of obesity, in which weight gain is explained primarily by an increase in body fat.

【Related article】
How Intestinal Starvation Can Lead to Weight Gain

Note ２: Because these responses are activated despite adequate energy stores, some researchers prefer the term “anti-weight-loss” rather than anti-starvation mechanisms [15].

At present, the causal relationship between the biological responses described in Sections (1)–(5) and post-weight-loss weight rebound has not yet been fully established [15]. Nevertheless, many people who have experienced weight rebound after dieting may find that these mechanisms are consistent with their own experiences.

Some researchers have pointed out that the biological forces that resist weight loss and promote the recovery of lost weight are extremely powerful and difficult to overcome for most individuals attempting to lose weight through behavioral interventions. They have also suggested that achieving long-term weight loss will require the development of interventions that weaken these biological responses themselves [15].

　　　
I generally agree with this perspective, although my approach differs somewhat. 

In my opinion, achieving long-term weight loss depends not only on developing interventions that weaken these biological responses, but also on adopting dietary and lifestyle habits that minimize activation of the body's anti-starvation (or anti-weight-loss) mechanisms in the first place. 

Maintaining this type of dietary pattern may help prolong satiety and reduce feelings of hunger. Over the long term, I propose that it may also facilitate the transmission, via the gut-brain axis, of information to the brain indicating that food remains sufficiently available.

Note 2. I do not believe that foods high in fat should necessarily be avoided. Depending on the overall composition of the diet and how such foods are consumed, they can be incorporated appropriately.

　　　
【Related Article】
Weight Loss Without Rebounding Requires Two Steps

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Introduction
In recent years, the number of people dieting for weight loss has been increasing worldwide. However, some have raised concerns that dieting itself may be accelerating the rise in obesity. 

For example, some female actors and television announcers appear to have gained weight compared to the past. However, it is unlikely that they are habitually overeating; rather, they may be restricting their food intake in an effort to manage their weight.

In this article, I would like to explore whether the spread of dieting may be related to the rise in obesity, based on findings from observational and intervention studies. 

(1) In 1992, a panel of experts convened by the U.S. National Institutes of Health concluded that, with continued participation in weight-loss programs conducted in controlled settings, participants typically lose about 10% of their body weight.

However, within one year after weight loss, one-third to two-thirds of the lost weight is regained, and within five years, almost all of it is regained [1].

Studies on long-term outcomes have also shown that at least one-third of dieters regain more weight than they lost [2]. This has raised concerns that dieting may, paradoxically, produce outcomes that are directly opposite to its original purpose [2,3].

    
(2) The 1983 book “Dieting Makes You Fat” proposed the idea that dieting to lose weight is counterproductive for weight control because people may regain more fat than they lose with each cycle of weight loss and regain [4]. Since then, whether dieting contributes to long-term weight gain remains a controversial and actively debated topic among scientists [5,6,7].

(4) Thus, the proportion of people attempting to lose weight has increased alongside the rising prevalence of overweight and obesity. However, this observation alone does not establish a causal relationship between the two.

Some researchers have suggested that the association between dieting and weight gain is, at least in part, causal [16,17]. Others, however, have argued that dieting is merely a proxy marker for individuals who are already prone to weight gain, and that without dieting, they would likely have gained even more weight [18].　

     
(5) Several prospective studies have suggested that dieting is a strong predictor of future weight gain among adolescents [17,19,20], middle-aged women [21], and even individuals who were initially of normal weight [5,21,22]. 

Note 1: Unhealthy weight-control behaviors include weight-loss practices that are generally not recommended, such as fasting, skipping meals, eating very little, and using food substitutes or diet pills.

In particular, “skipping meals” and “eating very little” were the most commonly reported unhealthy weight-control behaviors and were significantly associated with greater increases in BMI in both sexes. 

The use of food substitutes (e.g. powdered products or special beverages) among males and the use of diet pills among females were associated with greater subsequent increases in BMI.

Interestingly, among girls who were overweight (25 ≤ BMI < 30) at baseline, those who continued to engage in unhealthy weight-control behaviors experienced the greatest increase in BMI over the 10-year follow-up (more than 5 BMI units), whereas those who never engaged in such behaviors showed only a minimal increase in BMI [17].

In conclusion, these findings suggest that dieting and unhealthy weight-control behaviors during adolescence may contribute to long-term weight gain [17].

Previous observational studies on dieting and subsequent weight change have yielded inconsistent findings [22].

Many longitudinal observational studies have reported subsequent weight gain among self-reported dieters [17,20,21,22]. On the other hand, some studies have also reported that dieting predicts both weight loss and weight gain [24,25]. Several factors may help explain these differences in the findings.
      

Many studies have examined whether participants were dieting at baseline, or had a history of dieting. However, relatively few have investigated the specific methods used for weight loss [21,22,26].

   
In addition, the terms “dieting” and “weight-loss attempts” are somewhat ambiguous and may be interpreted differently by different individuals [17].
People who adopt healthy eating and exercise habits—for example, eating more natural foods such as vegetables, reducing ultra-processed foods, eating breakfast, and exercising regularly—may be able to achieve and maintain weight loss. 

In contrast, those who engage in unhealthy weight-control behaviors, such as skipping meals, eating very little, or using food substitutes (e.g. diet shakes or nutritional drinks), may experience only temporary weight loss, fail to maintain it over the long term, and eventually regain the weight. 

The duration of follow-up and the timing of dieting may also influence whether long-term weight change can be evaluated accurately.

Several studies have assessed changes in body weight or BMI several years later (e.g. 2, 5, or 10 years) based on participants' dieting status at baseline [20,21,22,26].

However, people who repeatedly go on and off diets are more likely to experience substantial fluctuations in body weight. 

From the perspective of body-weight homeostasis, as described by the body-weight set-point theory, individuals who were dieting at baseline may have been temporarily below their natural body weight (set point). Simply discontinuing the diet could therefore lead to subsequent weight gain.

Conversely, individuals who began dieting shortly before the end of the follow-up period may have experienced substantial weight loss because of the temporary effects of dieting. 

Furthermore, when the follow-up period is as long as five or ten years, weight-control behaviors that were started or discontinued during that interval may not have been captured. 

   
*Although not discussed here, observational studies also require caution regarding the limitations of self-reported data and the influence of confounding factors that may contribute to weight gain.

Moreover, in studies of adolescents, the natural increases in muscle mass and body weight that occur during growth should also be taken into account.

In conclusion, observational studies alone cannot establish a causal relationship between dieting and an increased risk of weight gain. However, for the following reasons, I believe that dieting is likely to contribute to weight gain.

One interpretation is that dieting is simply a proxy marker reflecting the global trend toward increasing body weight, rather than a cause of weight gain itself. From this perspective, it is argued that without dieting, people would gain even more weight [18].

However, the 10-year study of adolescents discussed in Section 1(5) made it possible to compare the weight trajectories of participants who were dieting at baseline but had stopped dieting five years later with those who continued dieting. 

The researchers found that those who stopped dieting gained substantially less weight than those who continued dieting. Based on these findings, they did not support the claim that people would gain even more weight if they did not diet [17].

Another explanation for the association regarding dieting and obesity is that dieting itself does not cause subsequent weight gain. Rather, people who are genetically prone to obesity may simply be more likely to go on a diet [6].

However, the 10-year study of adolescents yielded findings that were not consistent with this claim.
Among girls who were already overweight at baseline, those who continued to engage in unhealthy weight-control behaviors showed significantly greater increases in BMI than those who had never engaged in such behaviors. The researchers suggested that dieting itself may contribute to subsequent weight gain [17]. 

           
Furthermore, a longitudinal twin study conducted in Finland examined changes in body weight among twins with different numbers of intentional weight-loss episodes of at least five kg.

Although the study could not rule out the influence of genetic and shared family factors on weight gain, it also suggested that dieting itself may contribute to subsequent weight gain [16].

Recent research has greatly improved our understanding of energy homeostasis and the mechanisms that regulate body weight. 

Severe dietary restriction accompanied by substantial weight loss can trigger biological starvation responses involving changes in metabolism, hormones, and the nervous system, potentially leading to increased appetite and overeating. As a result, body weight tends to return toward its previous level and may even exceed the pre-weight-loss level in some individuals [27,28].

     
In addition, fasting for weight control (going without food for 24 hours) has been suggested to be associated with a greater risk of developing binge-eating disorder in the future than less severe dieting behaviors [29]. 

Furthermore, an overshoot in body weight during the recovery period has been documented in normal-weight participants in both the classic Minnesota Starvation Experiment and the U.S. Army Ranger multistressor study [30,31].

My intestinal starvation theory suggests that when all ingested food has been completely digested within the intestinal tract, the body may perceive this as a state in which no food is present. This may be described as a modern form of hunger that can occur even in affluent societies—a condition that may have become more likely with advances in food processing and the spread of ultra-processed foods.

Calorie-restricted dieting, especially unhealthy weight-control behaviors such as skipping meals, eating very little, or using food substitutes instead of regular meals, may further promote this intestinal starvation. 

Not all dieting leads to weight gain. Some people successfully lose weight and maintain their weight loss by adopting healthy dietary patterns and regular physical activity.

In fact, adherence to the Mediterranean diet has been reported to be inversely associated with the risk of overweight, obesity, and long-term weight gain [32].

Recent research has shown that severe dietary restriction accompanied by substantial weight loss can trigger biological starvation responses involving changes in metabolism, hormones, and the nervous system [27,28,34]. These changes may help explain why body weight often returns after weight loss and, in some cases, even exceeds the pre-weight-loss level.

         
In addition to these biological responses, I believe that unhealthy weight-control behaviors, particularly dietary restriction, are also likely to promote intestinal starvation, thereby contributing to an upward shift in the body-weight set point. 

<References>

[1] Methods for voluntary weight loss and control. NIH Technology Assessment Conference Panel. Ann Intern Med. 1992 Jun 1;116(11):942-9. 

[2] Mann T et al. Medicare's search for effective obesity treatments: diets are not the answer. Am Psychol. 2007 Apr;62(3):220-33. 

[3] Bacon L, Aphramor L. Weight science: evaluating the evidence for a paradigm shift. Nutr J. 2011 Jan 24;10:9. 

[4]Cannon G, Einzig H. Dieting makes you fat. London: Century Publishing; 1983.

[5] Jacquet P et al. How dieting might make some fatter: modeling weight cycling toward obesity from a perspective of body composition autoregulation. Int J Obes (Lond). 2020 Jun;44(6):1243-1253. 

[6] Hill AJ. Does dieting make you fat. Br J Nutr. 2004 Aug;92 Suppl 1:S15-8. 

[7] Lowe MR. Dieting: proxy or cause of future weight gain? Obes Rev. 2015 Feb;16 Suppl 1:19-24. 

[8] Cleland R et al. Commercial weight loss products and programs: what consumers stand to gain and lose. Crit Rev Food Sci Nutr. 2001 Jan;41(1):45-70. 

[9] National Center for Health Statistics, National Health and Nutrition Examination Survey, 1999–2018.

[10] Montani JP et al. Dieting and weight cycling as risk factors for cardiometabolic diseases: who is really at risk? Obes Rev. 2015 Feb;16 Suppl 1:7-18. 

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【 Full text 】

The ongoing debates surrounding various dietary approaches—such as low-carbohydrate, ketogenic, paleo, low-fat, and vegan diets—have created considerable public confusion and contributed to growing mistrust in nutritional science.

However, it is less widely recognized that diverse diets recommendations often share a common piece of advice: to avoid ultra-processed foods[1]. 

In fact, in many countries, rising obesity rates have been reported to closely parallel increases in the consumption of ultra-processed foods[1]. In this article, I would like to examine some of the factors that may underlie this association. Finally, I will also discuss how these issues may relate to my intestinal starvation theory. 

NOVA (not an acronym) is the food classification system that categorizes foods based not on their nutrient content, but on the nature, extent, and purpose of food processing. It was developed in 2009 by a research group at the University of São Paulo in Brazil [2].

The NOVA classification system divides foods into the following four groups according to the nature, extent, and purpose of processing.

Food processing, in essence, refers to the operations by which raw food materials are made suitable for consumption, cooking, or storage, and virtually all foods undergo some form of processing before being eaten. In other words, processing itself is not inherently harmful.

However, ultra-processed foods may contain little or none of the natural foods classified in Group 1.
Furthermore, because they are formulations produced by combining food-derived substances and additives through multiple industrial processes, they possess characteristics that differ from those of partially modified foods [3]. 

Because UPFs are highly palatable, inexpensive, convenient, and have a long shelf life, they have gained widespread popularity among consumers.　

Research based on the NOVA classification system has shown that the decline in minimally processed foods and home cooking, together with the increasing replacement of traditional diets by UPFs, is associated with unhealthy nutritional profiles and a higher prevalence of several diet-related diseases [3].

Studies in adults reporting the proportion of total energy intake derived from ultra-processed foods (UPFs) have shown that the proportion exceeds 50% in the USA and the UK, and reaches approximately 45–52% in Canada.

In contrast, the proportion is relatively lower in countries such as France, Spain, Brazil, and Malaysia, although it still accounts for roughly 20–36% of total energy intake [6].

　　
♦A cross-sectional study (2005–2014) of American adults found that, on average, participants obtained 56.1% of their total energy intake from UPFs. In the highest quintile group (Note 1), UPFs accounted for 84.5% of total energy intake, whereas in the lowest quintile group, the proportion was 25.4% [7].

Note 1: Quintiles divide ranked data into five equal groups.

Increasing consumption of UPFs has been reported to be associated with rising obesity rates in many countries.

♦A cross-sectional study based on data from Brazil’s 2008–2009 Household Budget Survey found that household consumption of UPFs was positively associated with both average BMI and obesity prevalence. Individuals in the highest UPF consumption group were 37% more likely to be obese than those in the lowest consumption group [9].　 

　　　
♦A cross-sectional study using data from the UK National Diet and Nutrition Survey (2008–2016) found that the proportion of total energy intake derived from UPFs ranged from approximately 35% (1st quartile; Note 2) to 74% (4th quartile).

Higher UPF consumption was associated with greater BMI, waist circumference, and obesity prevalence. In addition, for every 10% increase in the proportion of total energy intake from UPFs, obesity risk increased by 18%.

Higher UPF consumption was also more common among men, smokers, younger individuals, and lower socioeconomic groups [10].

Note 2: Quartiles divide ranked data into four equal groups.

♦A prospective cohort study conducted among graduates of the University of Navarra in Spain followed 8,451 participants who were not overweight or obese at baseline for about nine years.

Participants in the highest UPF consumption group had a 26% higher risk of developing overweight or obesity than those in the lowest consumption group. In contrast to their UPF intake, this group had the lowest average vegetable consumption. Overall, higher UPF consumption was associated with lower adherence to the Mediterranean diet [11].

　　　
Similar associations have also been reported in studies conducted in 15 Latin American countries, as well as in studies from other countries, including the USA and Canada [4,7,8].

♦A U.S. research group used data from the National Health and Nutrition Examination Survey (2015–2018) to investigate the relationship between UPF consumption and overall diet quality.

The study included 5,919 children and 10,064 adults, and diet quality was assessed using the American Heart Association (AHA) Diet Score and the Healthy Eating Index (HEI)-2015 [12].

   
The results showed that overall diet quality declined substantially as UPF consumption increased. Among children, the estimated proportion with a poor diet was 31.3% in the lowest UPF consumption group, but rose to 71.6% in the highest consumption group. A similar pattern was observed among adults.

♦An Italian research group investigated the relationship between meal timing and the degree of food processing.

An analysis of data from 8,688 participants in the Italian Nutrition & Health Survey (2010–2013) found that individuals who ate breakfast, lunch, and dinner at later times tended to consume fewer unprocessed or minimally processed foods and more processed foods and UPFs [13]. 

Furthermore, later meal timing was inversely associated with adherence to the Mediterranean diet [13]. The Mediterranean diet is a dietary pattern centered on fruits, vegetables, legumes, nuts, olive oil, and fish, and has been associated with a lower risk of weight gain [14].

♦A U.S. research group conducted a crossover study to compare the effects of processed foods (PF) and whole foods (WF) on energy expenditure. Eighteen participants consumed two isocaloric sandwiches that differed only in their degree of processing.

The WF meal consisted of multigrain bread (containing whole grains and sunflower seeds) and cheddar cheese, whereas the PF meal consisted of white bread and a processed cheese product.

As a result, diet-induced thermogenesis (DIT) (Note 3) following the PF meal was 46.8% lower than that observed after the WF meal. The researchers concluded that this difference in DIT resulted in a 9.7% increase in net energy gain for the PF meal [15]. 

Note 3: Diet-induced thermogenesis (DIT) refers to the increase in energy expenditure that occurs for several hours following food intake.

Furthermore, a reduction in dietary fiber decreases the bulk of food, which may delay the onset of satiety and ultimately contribute to an increase in total energy intake [15,18].

In 2019, a research group at the U.S. National Institutes of Health (NIH) conducted a randomized controlled trial to examine the effects of UPFs on ad libitum energy intake in 20 weight-stable adults [19].

Participants were admitted to the NIH Clinical Center and consumed an ultra-processed diet and an unprocessed diet for two weeks each. The two diets were designed to be closely matched in presented calories, energy density, macronutrients, and other key nutritional characteristics. They were instructed to eat as much or as little as they desired.

　　　
As a result, during the ultra-processed diet period, participants consumed about 459 kcal more per day than during the unprocessed diet period and gained 0.9± 0.3 kg from baseline. In contrast, during the unprocessed diet period, participants lost 0.9± 0.3 kg [19]. 

Notably, the eating rate was significantly higher during the ultra-processed diet than during the unprocessed diet.

In addition, during the unprocessed diet period, levels of the appetite-suppressing hormone PYY increased, whereas levels of the hunger hormone ghrelin decreased.

The researchers suggested that the oral sensory properties of UPFs—such as their ease of chewing and swallowing—may have increased the eating rate and delayed satiety signals, ultimately leading to greater energy intake [19,20]. 

Until now, the global rise in obesity has often been explained in terms of a relative increase in caloric intake. Indeed, UPFs possess several characteristics that appear to support this view:

・High energy density
・High palatability and ease of consumption
・Potential to increase net energy gain through reduced DIT
・Delayed satiety, which may lead to greater ad libitum energy intake

　　　
At the same time, however, studies using the NOVA classification system has begun to highlight factors beyond calories alone.

Studies conducted in many countries have shown that the greater the proportion of total energy intake derived from UPFs, the higher the risk of obesity. However, this association may not be fully explained by an increase in caloric intake alone.

In today's food environment, where efficiency and convenience are highly valued, opportunities to consume ready-to-eat foods such as refined carbohydrates and UPFs have increased. These foods are typically soft, require little chewing, and can be consumed quickly. At the same time, the consumption of unprocessed or minimally processed foods has declined.

As a result, the intake of dietary fiber and other less digestible substances may have decreased, creating conditions in which undigested matter is less likely to remain in the intestinal tract.

　　
The intestinal starvation theory proposes that when ingested food has been completely digested within the intestinal tract, the body may perceive this as a state in which no food is present. I believe that advances in food-processing technology and the increasing availability of ultra-processed foods since the 1970s may have contributed to the occurrence of such conditions.

<References>
[1]Katz DL, Meller S. Can we say what diet is best for health?  Annu Rev Public Health. 2014;35:83-103. 

[2]Monteiro CA et al. NOVA. The star shines bright. Food classification. Public Health. World Nutr. J. 2016, 7, 28–38.

[3]Monteiro CA et al. The UN Decade of Nutrition, the NOVA food classification and the trouble with ultra-processing. Public Health Nutr. 2018 Jan;21(1):5-17. 

[4]Nardocci M et al. Consumption of ultra-processed foods and obesity in Canada. Can J Public Health. 2019 Feb;110(1):4-14. 

[5]Fiolet T et al. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. BMJ. 2018 Feb 14;360:k322. 

[6]Elizabeth L et al. Ultra-Processed Foods and Health Outcomes: A Narrative Review. Nutrients. 2020 Jun 30;12(7):1955. 

[7]Juul F et al. Ultra-processed food consumption and excess weight among US adults. Br J Nutr. 2018 Jul;120(1):90-100. 

[8]Ultra-processed food and drink products in Latin America: trends, impact on obesity, policy implications. Pan American Health Organization, Washington (DC) (2013)

[9]Canella DS et al. Ultra-processed food products and obesity in Brazilian households (2008-2009). PLoS One. 2014 Mar 25;9(3):e92752. 

[10]Rauber F et al. Ultra-processed food consumption and indicators of obesity in the United Kingdom population (2008-2016). PLoS One. 2020 May 1;15(5):e0232676. 

[11]Mendonça RD et al. Ultraprocessed food consumption and risk of overweight and obesity: the University of Navarra Follow-Up (SUN) cohort study. Am J Clin Nutr. 2016 Nov;104(5):1433-1440. 

[12]Liu J et al. Consumption of Ultraprocessed Foods and Diet Quality Among U.S. Children and Adults. Am J Prev Med. 2022 Feb;62(2):252-264. 

[13]Bonaccio M et al. Association between Late-Eating Pattern and Higher Consumption of Ultra-Processed Food among Italian Adults: Findings from the INHES Study. Nutrients. 2023 Mar 20;15(6):1497. 

[14]Beunza JJ et al. Adherence to the Mediterranean diet, long-term weight change, and incident overweight or obesity: the Seguimiento Universidad de Navarra (SUN) cohort.  Am J Clin Nutr. 2010 Dec;92(6):1484-93. 

[15]Barr SB, Wright JC. Postprandial energy expenditure in whole-food and processed-food meals: implications for daily energy expenditure. Food Nutr Res. 2010 Jul 2;54. 

[16]Fereidoon Shahidi. Nutraceuticals and functional foods: Whole versus processed foods. Trends in Food Science & Technology, Volume 20, Issue 9, 2009, Pages 376-387.　

[17]Secor SM. Specific dynamic action: a review of the postprandial metabolic response. J Comp Physiol B. 2009 Jan;179(1):1-56. 

[18]Roberts SB. High-glycemic index foods, hunger, and obesity: is there a connection? Nutr Rev. 2000 Jun;58(6):163-9. 

[19]Hall KD et al. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metab. 2019 Jul 2;30(1):67-77.e3. 

[20] de Graaf C, Kok FJ. Slow food, fast food and the control of food intake. Nat Rev Endocrinol. 2010 May;6(5):290-3. 
　　　　

【 Full text 】

I view the human body as possessing a homeostatic system that attempts to maintain body weight within a certain range, and from this perspective, I believe that the concept of a body-weight set point carries important implications.

In this article, I will discuss the background and challenges of set-point theory, which has received renewed attention in recent years. I believe that understanding the environmental and behavioral factors that may contribute to upward shifts in the body-weight set point is important for addressing the growing problem of obesity.

Obesity and weight loss attempts

♦An obese individual who insists that a lean friend has consistently eaten more than the fat person does, may well be telling the truth.（*snip*）

The group of obese patients who are greatly in need of our understanding are those who keep to a calorie intake of perhaps 1,000 kcal per day, yet lose less than one kg per week. There is no doubt whatsoever that such people exist, and can be studied in a metabolic ward under conditions where 'cheating' is virtually impossible without being detected.

Usually these are middle-aged women who have been perhaps 40 kg overweight, and who have already lost about 20 kg. They are often depressed, hypothermic, and have a low metabolic rate. The nature of this metabolic adaptation to a low-calorie diet is not known (as of 1973), but it is a phenomenon  that has been recognized since before the 1920s (J S Garrow, 1973)[1].　

     
♦For obese individuals, a certain amount of weight loss is possible through a range of treatments, but long-term maintenance of weight loss is much more challenging, and in most cases, the weight is regained [2]. In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years, more than 80% of lost weight was regained [3,4].

In addition, studies of those who are successful at sustained weight loss indicate that the maintenance of reduced body fat will probably require close attention to energy intake and expenditure, perhaps for life [5].

Contrary to popular belief, people with obesity generally have a higher absolute REE compared to leaner subjects. This is because obesity increases both body fat and metabolically active fat-free mass [7,8].

PAEE can be subdivided into "voluntary exercise" and “activities of daily living.” Despite typically engaging in less physical activity, obese individuals often have a daily energy cost for physical activity similar to that of non-obese individuals since PAEE is proportional to body weight [7,9]. Additionally, due to greater food intake, their DIT also tends to be higher [7].

Dynamic changes in energy expenditure

♦Obesity prevention is often erroneously described as a simple bookkeeping matter of balancing caloric intake and expenditure [10].

In this model, energy intake and expenditure are considered independent parameters determined solely by behavior. It is assumed that an obese person can steadily lose weight by eating less and/or moving more at a rate of one pound for every 3,500 kcal (or one kg for every 7,200 kcal) of accumulated dietary caloric deficit [7,11]. This view has been referred to as a “static model” of weight loss, but it has been shown to be physiologically impossible [7,12]. 

Body weight set point theory

♦In recent years, the influence of homeostatic control has become increasingly recognized, and growing evidence suggests that the body employs physiological mechanisms to regulate energy balance and maintain body weight around a genetically and environmentally determined set point [12].

In 1953, Kennedy proposed that body fat storage is regulated [15]. In 1982, nutritional researchers William Bennett and Joel Gurin expanded on Kennedy's concept when they developed the set-point theory [16]. The model has been widely adopted, and strengthened particularly after the discovery of leptin in the 1990s [7,12].

When an individual loses weight, the body significantly reduces energy expenditure to a degree that is often greater than predicted based on changes in body composition or the thermic effect of food. This process also causes an increase in appetite through hormonal regulation and alters food preferences through behavioral changes, to drive body weight back toward its set-point range[7,16]. 

♦Maintenance of a 10% or greater reduction in body weight in lean or obese individuals is accompanied by about 20 to 25% decline in 24-hour energy expenditure.  This decrease in weight maintenance calories is 10–15% greater than predicted based solely on changes in fat and lean mass [17,18].

Since obese individuals also display these compensatory metabolic adjustments in response to dietary restriction, obesity may be considered a natural physiological state for some people. Experimental studies on obesity in animals similarly suggest a view of obesity as a condition of body energy regulation at an elevated set point [19]. 

♦A meta-analysis of cross-sectional studies investigating adaptive thermogenesis (AT) by comparing formerly obese subjects who had lost weight with BMI-matched subjects who were never obese, found a 3–5% lower resting energy expenditure (REE) in formerly obese subjects compared to never obese controls [20].

This effect means, for example, that if an obese woman reduced her weight from 100 kg to 70 kg, she would have to consume fewer calories to remain at 70 kg than a woman who had consistently weighed 70 kg [6]. Similar results have been confirmed in animal experiments involving obese and normal-weight rats.

This suggests that the frequent claim made by obese people that they eat the same or less than their lean friends but lose no weight, must be given more credence than it is ordinarily accorded [19].

♦In addition, hyperphagia (overeating) has been demonstrated following experimental semi-starvation and short-term underfeeding, which is probably the result of homeostatic signals resulting from the loss of both body fat and lean tissue [7,21].

　
♦This theory also suggests that a person's body-weight set point is established early in life and remains relatively stable unless altered by specific conditions. However, the set point may change throughout one’s life due to factors such as marriage, childbirth, menopause, aging, and disease [16]. 

On the other hand, the set-point theory remains hypothetical because the molecular mechanisms involved in set-point regulation have not yet been fully elucidated, and some researchers may consider the theory overly simplistic [16].

On the other hand, some researchers have pointed out important limitations of the body-weight set-point model. 

If a homeostatic system truly exists to maintain body weight within a certain range, a fundamental question arises: why do so many individuals in Western countries continue to gain weight gradually throughout majority of their adult lives? In particular, this model does not adequately explain the increasing prevalence of obesity observed in many societies worldwide since around the 1970s [22].

　　
In response, some researchers have suggested that while metabolic resistance to sustaining a reduced body weight is strong, metabolic resistance to sustained increased adiposity may not be physiologically long-lasting. Indeed, the steady increase in obesity prevalence supports the idea that the human body may be physiologically more permissive of weight gain than of weight loss [17,23]. 

These explanations that continuous consumption of high-calorie diet leads to an increase in the body-weight set point may sound plausible at first. However, in my opinion, if body weight changes in only one direction in response to a single external factor, it can no longer be considered a true “set point.”

Moreover, when this hypothesis is applied to humans, it fails to account for the fact that some individuals remain lean despite frequently consuming similarly high-calorie foods. In practice, several contradictions can be identified, including the following: 

I propose that upward shifts in the body-weight set point are associated with adaptive responses to intestinal starvation.
The next section provides a more detailed explanation of this mechanism. 

At present, many international organizations classify obesity as a chronic disease.

Some researchers interested in the body-weight set-point theory have argued that determining whether obesity, as a chronic condition, is treatable requires a clear understanding of how genetic and environmental factors interact to regulate the set point. At the same time, it is also true that many important environmental and social influences remain insufficiently explained [22].

In this article, I will introduce the concept of “intestinal starvation” as a complementary perspective to address these challenges. The key points are outlined below in four parts.

It is generally assumed that weight gain requires a positive energy balance, and the recent rise in obesity is often explained by increased consumption of high-calorie foods and reduced levels of physical activity. Paradoxically, however, the fact that obesity rates have increased in parallel with the growing prevalence of dieting aimed at weight loss [30] suggests that our current understanding of energy balance may warrant reconsideration [12].

What I want to emphasize is that while short-term weight gain due to overeating can be explained by excess energy intake, long-term and potentially irreversible weight gain may instead be triggered by energy deprivation or by the body’s perception that food is scarce. This pattern is also consistent with the phenomenon in which body weight increases beyond its previous level following experimental starvation or weight-loss dieting. 

【Related Articles】The Spread of Dieting May Be Fueling the Rise in Obesity

It is certainly true that high-calorie foods have become increasingly common since the 1970s. However, an even more important factor affecting the human body may be the rise of food processing—particularly ultra-processing. As food processing advanced, hard-to-digest components were gradually removed, while softer and more easily digestible components became increasingly dominant. 

Intestinal starvation is a physiological state that is more likely to occur when four factors overlap simultaneously. This concept provides a framework for understanding obesity as a chronic condition arising from interactions between genetic and environmental factors.

【Related Article】Three (+1) Factors That Accelerate “Intestinal Starvation”

In cases of weight gain that may reflect an upward shift in the body-weight set point through intestinal starvation, the overall efficiency of nutrient absorption may increase. In other words, from the perspective of energy homeostasis, the balance point at which energy intake and expenditure are matched may itself shift to a higher level. This perspective may help explain why even obese individuals with substantial body fat often exhibit compensatory metabolic responses to caloric restriction.

【Related Article】How Intestinal Starvation Can Lead to Weight Gain
      

As mentioned in the section 2, an animal study in rats reported that 90 days of exposure to a “high-energy diet” resulted in irreversible weight gain suggestive of an upward shift in the body-weight set point (Rolls et al., 1980). However, the “fattening diet” used in this experiment consisted mainly of commercially available, highly palatable foods such as potato chips, cheese crackers, and cookies [25]. At the same time, these foods were also highly refined carbohydrates and (ultra-)processed foods.

In contrast, the solid chow provided to the control group consisted of cracked grains, soybean meal, fish meal, and similar ingredients, and may have contained larger amounts of less digestible matter, such as dietary fiber and the tough cell walls of plants. In this respect, the composition of the control diet may have resembled that of human diets commonly seen more than 50 years ago. 

         
Therefore, I believe that caution is needed before concluding that the long-term consumption of a high-energy diet directly caused weight gain suggestive of an upward shift in the body-weight set point.
            

<References>

[1]Garrow JS. Diet and obesity. Proc R Soc Med. 1973 Jul;66(7):642-4. PMID: 4741395; PMCID: PMC1645095.

[2]Wu T, Gao X, Chen M, van Dam RM. Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Obes Rev. 2009;10(3):313–323. 

[3] Hall KD, Kahan S. Maintenance of Lost Weight and Long-Term Management of Obesity. Med Clin North Am. 2018 Jan;102(1):183-197. 

[4]Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001 Nov;74(5):579-84. 

[5]Wing RR, Hill JO. Successful weight loss maintenance. Annu Rev Nutr. 2001;21:323-41. 

[6]Jou C. The biology and genetics of obesity--a century of inquiries. N Engl J Med. 2014 May 15;370(20):1874-7. 

[7]Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. 2017 May;152(7):1718-1727.e3. 

[8]Nelson KM, Weinsier RL, Long CL, et al. Prediction of resting energy expenditure from fat-free mass and fat mass. Am J Clin Nutr. 1992;56:848–856.

[9]Westerterp KR. Physical activity, food intake, and body weight regulation: insights from doubly labeled water studies. Nutr Rev. 2010;68:148–154.

[10] Levine DI. The curious history of the calorie in U.S. policy: a tradition of unfulfilled promises. Am J Prev Med. 2017;52:125–129.

[11] Hall KD, Chow CC. Why is the 3500 kcal per pound weight loss rule wrong? Int J Obes (Lond). 2013 Dec;37(12):1614. 

[12] Egan AM, Collins AL. Dynamic changes in energy expenditure in response to underfeeding: a review. Proc Nutr Soc. 2022 May;81(2):199-212. doi: 10.1017/S0029665121003669. Epub 2021 Oct 4. PMID: 35103583.

[13]Thomas DM, Martin CK, Lettieri S et al. (2013) Can a weight loss of one pound a week be achieved with a 3500-kcal deficit? Commentary on a commonly accepted rule. In Int J Obes 37, 1611–1613.)

[14]Hall KD, Heymsfield SB, Kemnitz JW et al. Energy balance and its components: implications for body weight regulation. Am J Clin Nutr. 2012 Apr;95(4):989-94. 

[15]KENNEDY GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci. 1953 Jan 15;140(901):578-96. 

[16] Ganipisetti VM, Bollimunta P. Obesity and Set-Point Theory. 2023 Apr 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 37276312.

[17] Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010 Oct;34 Suppl 1(0 1):S47-55. 

[18] Leibel R, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Eng J Med. 1995;332:621–28.

[19] Richard E. Keesey, Matt D. Hirvonen, Body Weight Set-Points: Determination and Adjustment, The Journal of Nutrition, Volume 127, Issue 9, 1997, Pages 1875S-1883S, ISSN 0022-3166.

[20]Astrup A, Gøtzsche PC, van de Werken K, et al. Meta-analysis of resting metabolic rate in formerly obese subjects. Am J Clin Nutr. 1999 Jun;69(6):1117-22.

[21] Dulloo AG, Jacquet J, Girardier L. Poststarvation hyperphagia and body fat overshooting in humans: a role for feedback signals from lean and fat tissues. Am J Clin Nutr. 1997;65:717–723.

[22]Speakman JR, Levitsky DA, Allison DB, et al. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech. 2011 Nov;4(6):733-45. 

[23] Schwartz MW, Woods SC, Seeley RJ, et al. Is the energy homeostasis system inherently biased toward weight gain? Diabetes. 2003 Feb;52(2):232-8. 

[24] Corbett SW, Stern JS, Keesey RE. Energy expenditure in rats with diet-induced obesity. Am J Clin Nutr. 1986 Aug;44(2):173-80.

[25] Rolls B.J., Rowe E.A., Turner R.C. Persistent obesity in rats following a period of consumption of a mixed high energy diet. J Physiol. 1980 Jan;298:415-27. 

[26](Deleted)

[27] Dykes J et al. Socioeconomic gradient in body size and obesity among women: the role of dietary restraint, disinhibition and hunger in the Whitehall II study. International Journal of Obesity 2004 Feb,:262-68.

[28] Poskitt EM. Countries in transition: underweight to obesity non-stop? Ann Trop Paediatr. 2009 Mar;29(1):1-11.

[29] Gary Taubes. 2011. Why we get fat. New York: Anchor Books. Pages 15-32.

[30] Montani JP, Schutz Y, Dulloo AG. Dieting and weight cycling as risk factors for cardiometabolic diseases: who is really at risk? Obes Rev. 2015 Feb;16 Suppl 1:7-18.
      

【Full text】

Until the 1960s, obesity was widely attributed primarily to “overeating” and a “lack of willpower,” and relatively little research focused on the biology of obesity itself. However, this view was significantly influenced by overfeeding experiments conducted by Professor Ethan Sims and his colleagues in the late 1960s [1].

Subsequent reports indicated that the overfeeding experiment lasted about 200 days and that the 20 participants gained an average of about 9–11 kg. However, when their energy intake returned to normal levels after the experiment, most participants returned to near their original weight over the following weeks and months. Only two were reported to have maintained the weight they had gained [2,3].

These overfeeding experiments showed that weight gained through short-term overfeeding is not necessarily easy to maintain over the long term. Furthermore, they suggest that biological factors not fully explained by energy intake alone may be involved in the development and maintenance of obesity [1].

■In 1990, researchers at Laval University conducted an overfeeding study involving 12 pairs of sedentary male identical twins. Each participant's daily energy requirements were measured before the experiment, after which they consumed an additional 1,000 kcal per day over a 100-day period (six days per week, for a total of 84 days). The participants lived in a university dormitory and were under staff supervision 24 hours a day [4].

On average, body weight increased by 8.1 kg, of which 5.4 kg (approximately 67%) was body fat. However, there was substantial individual variation in weight gain, ranging from 4.3 to 13.3 kg [4].

■Leaf and Antonio reviewed overfeeding studies conducted up to 2017 that reported changes in body weight and body composition. They identified 25 studies that reported changes in fat mass (FM) and fat-free mass (FFM) in addition to weight gain, with study durations ranging from 9 to 100 days. With the exception of four studies, all involved populations with low levels of habitual physical activity [6]. Because the studies had different objectives, changes in body weight several months after the overfeeding period were not necessarily reported. 

The review summarized the 25 studies according to dietary composition.

Among them, 10 studies used diets relatively high in carbohydrates and fat and relatively low in protein (11–15% of total energy intake). In these studies, most of the weight gained was FM, accounting for approximately 60–70% of the total weight gain. The authors also noted that, in the absence of exercise, much of the increase in FFM may reflect increases in body water rather than skeletal muscle [6,7].

In contrast, even with a similar energy surplus, higher-protein diets were associated with less gain in FM and more favorable changes in body composition [6,8].

Energy expenditure (EE) increases with overfeeding and weight gain. This is because resting energy expenditure, diet-induced thermogenesis, and energy expenditure from physical activity all increase[9].

An increase in EE beyond what would be predicted from changes in body weight and body composition is referred to as “metabolic adaptation” [9,10].

Historically, this concept is thought to have originated from early observations that body weight did not increase as much as expected despite increased food intake. Researchers hypothesized that there might be an adaptive mechanism of energy expenditure that acts to dissipate excess energy [1,10].

Subsequent studies have made it possible to strictly control energy intake and examine the various components of EE in greater detail [10]. However, studies have produced inconsistent findings regarding the extent to which metabolic adaptation occurs in response to overfeeding [11,12,13]. 

   
    
■In 1995, Leibel et al. examined energy expenditure (EE) in 18 individuals with obesity and 23 who had never been obese after their body weight was reduced by 10–20% below their usual weight or increased by 10% through overfeeding.

The study suggested that maintaining body weight below or above its usual level may induce changes in EE that oppose the change in weight, potentially acting to return body weight toward its previous  level [9].

■Johannsen et al. studied 35 young adults (mean BMI, 25.6 ± 2.3) who consumed a diet providing 40% more energy than their baseline energy requirements for eight weeks. Sleeping metabolic rate (SMR), sedentary 24-hour energy expenditure (24h-EE), and other measures were assessed before and after overfeeding.

On average, participants gained 7.5 kg (range, 2.3–10.7 kg), of which 4.2 kg—more than half—was fat. Overfeeding increased SMR, sedentary 24h-EE, and EE on average, although there was substantial individual variation in these responses [10].

During weight loss, metabolic adaptation—a reduction in EE beyond what would be expected—is observed relatively consistently. In contrast, findings are inconsistent as to whether a similar metabolic adaptation occurs during overfeeding to dissipate excess energy [10].

Some studies have reported metabolic adaptation in response to overfeeding [4,7,16], whereas others have found that much of the increase in EE can be explained by the normal increase in energy requirements associated with gains in body weight and changes in body composition [12,13,17,18]. In the study by Johannsen et al., no clear metabolic adaptation to overfeeding was observed overall, although there was substantial individual variation in the response [10].

These findings suggest that metabolic adaptation during weight loss and the EE response to overfeeding may not necessarily be symmetrical. 

As discussed above, there is substantial individual variation in how body weight and EE respond to overfeeding. However, most overfeeding experiments last only a few weeks to a few months and therefore do not fully replicate the processes underlying obesity that develops gradually over several years.

I believe this difference may be explained using the concept of a “body-weight set point.” 

For example, if a person whose weight is normally stable at 70 kg temporarily increases to 73 kg as a result of overeating, this can be viewed as a change caused by increased energy intake.

I believe that an upward shift in the body-weight set point may involve adaptive physiological responses that occur when the body perceives a state of starvation. However, this has not been directly demonstrated by overfeeding experiments; rather, it is a hypothesis proposed in this blog.

Final thoughts
What these overfeeding studies show is that although overfeeding can increase body weight, the weight gained is not necessarily maintained. Weight gain resulting from short-term overfeeding may therefore need to be distinguished from obesity as a chronic condition that develops over several years.

As Bray has pointed out, the history of these overfeeding and underfeeding studies suggests that preventing and treating obesity may require more than the traditional advice to simply “eat less and exercise more” [1].
                    

<References>
[1]Bray GA. The pain of weight gain: self-experimentation with overfeeding. Am J Clin Nutr. 2020 Jan 1;111(1):17-20. 

[2]Sims EA et al. Experimental obesity in man. Trans Assoc Am Physicians. 1968;81:153-70. PMID: 5721398. 

[3]Sims EA et al. Endocrine and metabolic effects of experimental obesity in man. Recent Prog Horm Res. 1973;29:457-96. doi: 10.1016/b978-0-12-571129-6.50016-6. PMID: 4750591.

[4]Bouchard C et al. The response to long-term overfeeding in identical twins. N Engl J Med. 1990 May 24;322(21):1477-82. 

[5] Bouchard C et al. Overfeeding in identical twins: 5-year postoverfeeding results. Metabolism. 1996 Aug;45(8):1042-50. 

[6]Leaf A, Antonio J. The Effects of Overfeeding on Body Composition: The Role of Macronutrient Composition - A Narrative Review. Int J Exerc Sci. 2017 Dec 1;10(8):1275-1296. 

[7]Norgan NG, Durnin JV. The effect of 6 weeks of overfeeding on the body weight, body composition, and energy metabolism of young men. Am J Clin Nutr. 1980 May;33(5):978-88. 

[8].Bray GA et al. Effect of protein overfeeding on energy expenditure measured in a metabolic chamber. Am J Clin Nutr. 2015 Mar;101(3):496-505. 

[9]Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. 

[10]Johannsen DL et al. Metabolic adaptation is not observed after 8 weeks of overfeeding but energy expenditure variability is associated with weight recovery. Am J Clin Nutr. 2019 Oct 1;110(4):805-813. 

[11]Westerterp, K. Metabolic adaptations to over—and underfeeding—still a matter of debate?. Eur J Clin Nutr 67, 443–445 (2013). 

[12]Ravussin E et al. Short-term, mixed-diet overfeeding in man: no evidence for "luxuskonsumption". Am J Physiol. 1985 Nov;249(5 Pt 1):E470-7. 

[13]Diaz EO et al. Metabolic response to experimental overfeeding in lean and overweight healthy volunteers. Am J Clin Nutr. 1992 Oct;56(4):641-55. 

[14]Reinhardt M et al. A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction. Diabetes. 2015 Aug;64(8):2859-67. 

[15]Schlögl M et al. Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change. Diabetes. 2015 Nov;64(11):3680-9. 

[16] Webb P, Annis JF. Adaptation to overeating in lean and overweight men and women. Hum Nutr Clin Nutr. 1983 Mar;37(2):117-31.

[17] Forbes GB et al. Deliberate overfeeding in women and men: energy cost and composition of the weight gain. Br J Nutr. 1986 Jul;56(1):1-9. 

[18]Roberts SB et al. Energy expenditure and subsequent nutrient intakes in overfed young men. Am J Physiol. 1990 Sep;259(3 Pt 2):R461-9.