Lesson 1: Overview of metabolism

Table of Contents

Introduction

Welcome to Lesson 1! Before discussing the specifics of healthy nutrition and weight management, it is very helpful to understand the basics of metabolism. This is where calories come into play, and this is crucial for understanding what influences body weight (“BW”). Of note, there is a lot of individual variability in the various topics discussed below, so while learning about these topics can be very informative it may be difficult to see how you can apply the information to your particular situation. I provide more information regarding this in Lessons 2 and 3; by the end of Lesson 3 you’ll have a framework for applying all of this information that accounts for individual variability.

Note: Technically, 1 Calorie = 1000 calories = 1 kilocalorie, but I will use “calorie” and “kilocalorie” (which I will shorthand with “kcal”) interchangeably, as almost all people do when talking about food. You will likely never need to convert these for any practical reason.

Any given day you burn some total number of calories. If you consume the same number of calories as you burn, your weight should be relatively stable. Fluctuations can occur due to:Balance showing when calories in = calories out weight is maintained

  • retaining more or less water (due to variations in carbohydrate and sodium intake, stress levels, going through a menstrual cycle, etc)
  • undigested food in your gut
  • stool retention
  • obvious factors such as wearing different clothing when you step on the scale

Total daily energy expenditure (“TDEE”)

The total amount of calories you burn in any given day is referred to as your “total daily energy expenditure” (“TDEE”). This is comprised of multiple components(Melanson, 2017):

  • There are the calories you burn at complete rest doing nothing, which is called either the “basal metabolic rate” (“BMR”) or “resting metabolic rate” (“RMR”). BMR is generally measured first thing in the morning while in the awake state but lying still in a dark, temperature-controlled environment after having fasted overnight. RMR can be measured under other conditions and thus will generally be higher, but these terms are often used interchangeably. Some people will also refer to a “sleeping metabolic rate”.
  • There are the calories you burn in the process of digesting and absorbing food you eat, frequently called the “thermic effect of feeding” (“TEF”) or “dietary induced thermogenesis” (“DIT”).
  • There are the calories you burn while you purposefully exercise, called different things but I will go with “exercise activity thermogenesis” (“EAT”).
  • Additionally, there are the calories you burn with unplanned activity, which includes rolling over in bed, fidgeting in a chair, pacing, alterations in your posture, etc. This is called “non-exercise activity thermogenesis” (“NEAT”).

Putting all of this together:

TDEE = RMR + TEF + EAT + NEAT

Note: Not included here, as technically this is not energy you utilize, are calories lost in urine and feces. It’s estimated that ~1% of the calories you consume are lose in urine and ~2-9% of the calories you consume are lost in stool.(Lund, 2020) There can be significant variability between individuals; it is possible that people who lose fewer calories in stool have a more difficult time losing weight.

In general if you consume fewer calories than your TDEE you lose BW while if you consume more calories than your TDEE you gain BW. scales showing calories in greater than out leads to weight gainscales showing calories in less than out leads to weight loss

Remember, energy cannot be created or destroyed. As calories are a unit of energy, at the end of the day all calories must be accounted for.

Many different components that contribute to BW (bones, skin, other organs, fat, water, muscle, etc). These can be divided into “body fat” (“BF”) and “lean body mass” (“LBM” – everything other than subcutaneous and visceral BF).

Tip: While eating fewer calories than your TDEE is the key for losing BW, another consideration is what proportion of the weight you lose is LBM vs BF. A caloric deficit alone will yield weight loss and many health benefits (if your starting BF level is in an unhealthy range), but incorporating appropriate exercise is important to help maintain your LBM.(Broskey, 2019) Maintaining LBM (particularly skeletal muscle) is beneficial for overall health and is likely helpful to prevent weight regain long term.(Dulloo, 2018; Stubbs, 2021) Briefly, avoiding too rapid weight loss (discussed in Lesson 3), keeping protein intake sufficiently high (discussed in Lesson 4) and engaging in resistance training (see the general exercise course on this site) are the key steps to ensure LBM retention while BF is lost.

Now I will go through the components of TDEE in more detail.

Resting Metabolic Rate (“RMR”)

RMR is the largest contributor to TDEE & is primarily due to LBM.(Heymsfield, 2018) Total BF also contributes. Age and gender can contribute (higher in males, decreasing with age) but this seems mediated by alterations in LBM. Skeletal muscle burns more calories than BF (roughly 6 kcal/lb of skeletal muscle vs. 2 kcal/lb of BF per day), so if there are two people at the same BW but one has more LBM and the other has more BF, the former will likely burn more calories. Due to variations in organ size and possibly other unaccounted factors (ie, genetics), two people of the same size, age, and body composition can still have different RMRs. Approximate values for different organs are shown in the table below:

table showing contribution of different organs to resting metabolic rate
Residual includes intestines, pancreas, thyroid, etc. This example sums to 1685 kcal for a 71 kg person. Of note, as these are approximate values that change with age, gender, and BW, these numbers are not directly applicable to any one specific person. These values were primarily taken from (Heymsfield, 2018) & (Müller, 2013).

If you compare two people with different RMRs and they eat the same number of calories with no other differences between them, the person with the lower RMR will move to a higher BW than the person with the higher RMR. In practice there are other considerations (see discussion regarding NEAT below).

Alterations with weight loss

When you diet to lose weight, your RMR will tend to decrease (this is not always the case, see the figure below). This occurs in part due to the loss of LBM and BF. When losing a significant amount of BW some of your organs (which are very metabolically active) may decrease in size, further leading to a decrease in your RMR.(Bosy-Westphal, 2009) This is less likely to occur if you start dieting from a non-obesity state, though it may still occur to a degree in the liver.(Shen, 2021) On the other hand, exercise has at most a minimal impact on your RMR, and possibly has no impact.(MacKenzie-Shalders, 2020)

Additionally, there is an adaptive component frequently termed “adaptive thermogenesis” that leads to a further decrease in your RMR and other aspects of energy expenditure while you actively lose weight (you can think of this as your body trying to fight to maintain your current BW); this is variable between people.(Müller, 2023) Thus, some will have their RMR drop more than others in response to dieting, and this may significantly slow down the dieting process.(Martins, 2022) It is not clear exactly how this should be measured, and different measurement strategies yield different results, leading some to question if this is even a real phenomenon.(Nunes, 2022b; Westerterp, 2022) Of note, several studies have shown that adaptive thermogenesis typically disappears once you are maintaining your new lower BW; when you are not actively dieting it will trend back to what you would expect from your overall new LBM and BF.(Ostendorf, 2018; Martins, 2020; Müller, 2021; Nunes, 2022a)

I want to include one study that demonstrates how variable changes in RMR can be with dieting and weight loss. In a study using data from the CALERIE trial, which only included people without obesity, long-term calorie restriction led to an average loss of 8.0 kg BW over the course of 12 months with variable changes in each participant’s RMR. This is shown in the figure below. Notice the variable change in both RMR and adaptive thermogenesis (termed “metabolic adaptations” in the figure) between different participants

Reproduced from: Martin A, Fox D, Murphy CA, Hofmann H, Koehler K. Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss. Int J Obes (Lond). 2022 Feb 18. doi: 10.1038/s41366-022-01090-7. Epub ahead of print. PMID: 35181758.

Note: The data from the CALERIE trial shown above may seem to contradict the other cited data that indicates adaptive thermogenesis dissipates when weight loss stabilizes, but there are a few points to consider:

  • It’s not clear that the participants were in energy balance at the time of the measurements. They may have still been actively losing weight, particularly if they knew measurements were upcoming.
  • This study used DXA (dual-energy x-ray absorptiometry) scans to determine the quantity of different metabolic tissues, and while fairly accurate this may not be accurate enough to precisely determine small changes over time for this type of calculation.
  • As this trial excluded individuals with obesity, it’s possible different changes occurred in this study cohort not seen in other studies including participants with obesity.
    • However, while not examining adaptive thermogenesis, a separate review evaluating changes in various aspects of energy expenditure with weight loss found there do not seem to meaningful differences between individuals with and without obesity for similar levels of weight loss.(Magkos, 2022)

Example: You may have read that a 3,500 kcal deficit equates to losing 1 pound of BF. So if you normally eat 2,000 kcal/day with a TDEE of 2,000 kcal/day and decrease your calories by 500 kcal/day (500/day = 3,500/week) to 1,500 kcal/day, you may expect to lose 1 pound of BF in 1 week. However, if your RMR drops by say 150 kcal/day, your new TDEE is 1,850 kcal/day. With your current 1,500 kcal/day diet your caloric deficit is actually 1,500 – 1,850 = 350 kcal/day. Thus, instead of taking 7 days to lose 1 pound of BF you may expect it to take 10 days (3,500 kcal/lb / 350 kcal/day = 10 days/lb). However, other changes also occur which further alter this (see examples below).

Note: A 2021 analysis quantified the change in TDEE (using >6,000 subjects) & basal expenditure (using >2,000 subjects, basal expenditure is similar to BMR and RMR) across the lifespan. The authors found(Pontzer, 2021):

  • In the first month of life the size-adjusted TDEE & basal expenditure are similar to that of young adults.
  • Throughout the remainder of the first year these energy expenditures increase such that they are ~50% higher than that of young adults (when adjusting for body size) by age 9-15 months.
  • They then steadily decline at ~2.8% per year until age ~20 years and thereafter remain stable until age ~60 years.
  • Subsequently, they decline by ~0.7% per year for the remainder of the lifespan.
  • Of note, these results incorporate age-related changes in physical activity as well as age-related changes in tissue-specific metabolism.
  • Lastly, there was significant individual variability within the data sets.

The authors note there are no gender differences and also that during pregnancy there are no differences; thus even neonates not-yet-born have a metabolism similar to that of adults (when adjusting for body size).

The two key takeaways here in my opinion are:

  • In young and middle-age adulthood metabolism does not decrease beyond what is expected due to changes in body size and composition. Weight gain commonly observed during this time period is more likely due to increases in caloric intake, decreases in physical activity, or changes in body composition as opposed to an innate slowing of one’s metabolism.
  • There is significant variability at the individual level with respect to TDEE and basal expenditure. I will comment on this more in the example at the end of this lesson as well as in the next lesson.

Thermic Effect of Feeding (“TEF”)

You will commonly read that 1 gram of fat has 9 kcals, 1 gram of carbohydrate has 4 kcals, 1 gram of protein has 4 kcals, and you will less commonly read that 1 gram of alcohol has 7 kcals while 1 gram of fiber has ~0-2 kcals. Fiber and alcohol are discussed in lessons 7 & 8. The numbers for fats, carbohydrates, and proteins are general ballpark figures and some sources of these nutrients will have greater or fewer calories. If curious about these differences, there is an excellent overview here. However, this variability is generally quite small and it is typically fine to just use the 9/4/4 numbers, though there are some exceptions (see the tip below).

Tip: If you are looking at a nutrition label and the overall calories on the label do not match up with the stated grams of carbohydrates, protein, and fat when using the 9/4/4 numbers, this is likely due to fiber, sugar alcohols, or the 9/4/4 numbers not being accurate for that specific food. As one extreme example, let’s look at 92% cacao:

                      

*The numbers for the adjusted kcals are taken from the Atwater factors specific for cocoa.

Most foods are not this extreme, but here it is clear that there is a difference of almost 40 kcals per serving when using the adjusted vs unadjusted numbers. Importantly, the nutrition label lists the correct total calories. In general, when looking at nutrition labels the total calories should be trusted more than the sum of the components.

What these numbers do not consider is how much energy you have to use to actually digest nutrients you consume. It turns out we use little energy to digest fats (likely 2-3% of the kcals in fats are needed to digest them), more for carbohydrates (5-10%), and considerably more for protein (20-30%). For an overall diet, a lot of people average all three components to roughly 10%, meaning that the equivalent of 10% of the calories you consume are used in the process of absorbing & digesting food.(Westerterp, 2004) In addition to macronutrient content there are other contributing factors leading to variability, such as(Calcagno, 2019):

  • insulin resistance tends to decrease one’s TEF, likely due to the body not processing nutrients to the same degree in an insulin resistant state (as less glucose will enter cells) – this is likely the largest determining factor in interindividual variability of the TEF
  • as one ages a handful of studies indicate the TEF decreases
  • a few studies indicate that both physical activity as well as an increase in meal size seem to increase the TEF
  • of note, most of the studies evaluating this are small and there are few in number

While some research previously indicated that your TEF may be highest in the morning, more rigorous methodology indicates this is not the case and that it is consistent throughout the day; prior calculations showing an elevated TEF in the morning did not account for the fact that your RMR is generally lower in the morning than the evening and that your TEF can remain elevated for ≥6 hours after a large meal.(Ruddick-Collins, 2022)

For dieting purposes, if you eat less food your TEF will go down, so instead of having a TEF of 200 kcal while eating 2,000 kcal/day, it will drop to 150 kcal while eating 1,500 kcal/day.

Example: As a continuation of the prior example, by going from 2,000 kcal/day to 1,500 kcal/day your TDEE drops not only to 1,850 kcal/day due to a reduction in your RMR but an additional 50 kcal/day due to a reduction in your TEF. Thus, your TDEE is now 1,800 kcal/day. Not a huge difference but worth knowing about, and because the total deficit is now 1,500-1,800 = 300 kcal/day, you may expect it to take 11-12 days to lose 1 pound of fat (3,500 kcal/lb / 300 kcal/day = 11.7 days). However, other changes also occur (see examples below).

Exercise Activity Thermogenesis (“EAT”)

There are really two components here:

  • the amount of calories you burn during exercise
  • the amount of calories you burn after exercise (termed “excess post-exercise oxygen consumption” (“EPOC”))

Figure illustrating physiologic rationale for EPOC

A figure describing excess post exercise oxygen consumptionFrom: Clark, M., Lucett, S. McGill, E., Montel, I., Sutton, B. National Academy of Sports Medicine. (2018). NASM essentials of personal fitness training. 6th edition. Jones & Bartlett Learning.

A: Prior to exercise. B: When running on a treadmill an oxygen deficit develops as anaerobic pathways are utilized first. C: With continued exercise aerobic pathways turn on and oxygen utilization eventually meets demand. D: After exercise stops excess oxygen is still consumed to make up the deficit;  this declines rapidly as the initial deficit is mostly replaced. E: For an extended period of time there is still a slight increase in oxygen consumption until the body returns to a physiologic resting state.

The total calories burned during exercise is hard to predict. This varies considerably depending on exercise modality, duration, intensity, individual level of fitness(Levine, 2003), and efficiency of movement. In general, resistance training without a cardiovascular component will burn considerably fewer calories than aerobic training. See the tip below regarding cardio machines.

In regards to EPOC, this is generally not a big contributor unless you do a lot of intense exercise (getting your heart rate up pretty high) for extended periods of time; you need to be in rather good shape to get a decent-sized contribution from EPOC.(Moniz, 2020; Panissa, 2020)

Tip: When using cardio machines you should not trust the calorie counts they provide without careful thought. The machines generally overestimate caloric expenditure and can do so by a factor of 2-3x.(Glave, 2018) They also do not necessarily subtract your RMR; the calories they state may include the calories you would have burned at rest plus the additional calories you burned with exercise rather than just the calories you burned with exercise. Regardless, you can still compare the calorie counts from one session to another to reasonably track progress.

Example: Continuing the prior examples, you started at 2,000 kcal/day intake with a TDEE of 2,000 kcal/day, decreased your intake to 1,500 kcal/day and had a drop in your RMR and TEF resulting in a new TDEE of 1,800 kcal/day. If you don’t exercise at all you may expect to lose 1 pound of fat in 11-12 days. If you do exercise, any calories you burn with the exercise may get added to your TDEE. So if you do any form of additional exercise that burns 300 kcal/day while starting your diet, your TDEE may go up to 2,100 kcal/day, and thus your daily deficit now may be 2,100 – 1,500 = 600 kcal/day. You now may expect to lose 1 pound of fat in 6 days (3,500 kcal/lb / 600 kcal/day = ~6 days). However, this ignores the last factor in the equation, which is NEAT (see the next example below).

Non-Exercise Activity Thermogenesis (“NEAT”)

NEAT helps explain why some people have so much more trouble losing or gaining weight than others.(Levine, 2003) This varies considerably between people at least in part due to genetics. When eating an excess of food, some people naturally tend to move around a lot more, and these people will put on less weight. Others will move around less and put on more weight. When losing weight this can manifest by making people feel more sluggish. If you have ever tried to lower your caloric intake to lose weight and find yourself feeling more “lazy”, that is most likely NEAT working against you. There is also evidence that as more weight is lost NEAT decreases further.(Rosenbaum, 2016) Counteracting NEAT can be a key factor in ensuring successful dieting (see tip below).

Of interest, a 2018 systematic review evaluating 36 articles of dietary, exercise, or dietary + exercise interventions found that many of them did not result in a decrease in NEAT or NEPA (NEPA is non-exercise physical activity – distinct from NEAT which is the actual energy expenditure associated with the physical activity).(Silva, 2018) Only 63%, 27%, and 23% of the articles found a decrease in NEAT/NEPA with dietary, exercise, or dietary + exercise interventions, respectively. Of particular interest, none of the interventions that incorporated resistance training found a downregulation of NEAT/NEPA.

However, the interventions in this latter review that led to greater amounts of weight loss (~10kg vs 5kg) had significantly greater amounts of downregulation of NEAT/NEPA. The authors also acknowledged many trials were underpowered and potentially had other methodologic issues. Thus, it is likely that downregulation of NEAT/NEPA is more significant as individuals lose more weight, and we need larger and better-designed trials to more formally evaluate the characteristics of the downregulation.

Tip: You can make lifestyle choices to attempt to counteract a decrease in NEAT when dieting.(Villablanca,2015) Examples include:

  • take the stairs instead of the elevator and park further away from buildings
  • wear a step counter of some sort (or use a smart phone) and set a minimum step count to aim for daily
  • stand up and walk during commercials, march in place or pace while watching things on screens
  • dance to music while relaxing
  • set up a standing desk for work or obtain a pedal exerciser to use when sitting
  • set a 5 or 10 minute timer on repeat and get up & move around when it goes off

Example: Continuing the prior examples, you are eating 1,500 kcal/day with a TDEE of 1,800 kcal/day (with no exercise) or 2,100 kcal/day (with exercise). Let’s say your NEAT decreases by 100 kcal/day without exercise and 150 kcal/day with exercise. This makes your new TDEE 1,700 kcal/day (with no exercise) or 1,950 kcal/day (with exercise). This makes your final caloric deficit either 200 kcal/day (with no exercise) or 450 kcal/day (with exercise). Thus you may expect it to take 18 days to lose 1 pound of fat without exercise (3,500 kcal/lb / 200 kcal/day = 17.5 days) or 8 days to lose 1 pound of fat with exercise (3,500 kcal/lb / 450 kcal/day = 7.8 days).

Below is a visual depiction of the above example using the same numbers. Scenario 1 is at baseline when you are eating 2,000 kcal/d, which matches your TDEE, and thus your weight is stable. Scenario 2 is when you eat 1,500 kcal/d without additional exercise, decreasing your TDEE to 1,700 kcal/d for a deficit of 200 kcal/d. Scenario 3 is when you eat 1,500 kcal/d & add in 300 kcal/d of exercise, yielding a 450 kcal deficit.

figure showing the magnitude that various aspects of metabolism change when dieting

Constrained model of TDEE

First published in 2016(Pontzer, 2016), there have been several data sets indicating that as physical activity increases the overall TDEE does not increase in an additive fashion, but rather in a constrained fashion. This is shown in the following image.

Thus, there are two models here:

  • The additive model on the left indicates that all of the energy expenditure from physical activity that you perform is added to all of the other components of your energy expenditure with those other components not compensating in any way; thus this extra energy expenditure “adds” to your TDEE.
  • The constrained model indicates that as you increase your physical activity the other components of your energy expenditure decrease in some way (ie, your RMR decreases, your NEAT decreases, perhaps your body becomes more efficient when engaging in physical activity so you burn fewer calories with it, etc). Thus, these extra calories do not directly add to your initial TDEE. This is referred to as the “constrained” model because the overall TDEE seems to reach a maximal point (or at least slow down in its rate of increase) where an even greater amount of physical activity disproportionately low further increases in the TDEE.

As this constrained model was initially published relatively recently, it has generated a lot of debate and further research. Importantly, this model was initially published when evaluating energy expenditure of different populations of people at baseline, not when adding in additional physical activity for an intervention.

Additional research

Further providing evidence for the constrained model, a 2021 analysis found at baseline there is an energy compensation of 28% (this implies for more active people their RMR and/or NEAT may decrease by 28% of the additional calories they would burn by being more active); this compensation increases to 49% for individuals at the 90th percentile of the BMI distribution (in the obesity range).(Careau, 2021) There are other lines of evidence that support this and additionally show that with continued increases in physical activity (via natural lifestyle and also planned exercise) one’s TDEE may not increase substantially due to these various compensatory mechanisms as well as increases in skeletal muscle efficiency.(Pontzer, 2016; Westerterp, 2018; Hand, 2020; Broskey, 2021; Fernández-Verdejo, 2021) In contrast, one study in adults with a mean age of 63 years found that this compensation did not seem to occur to the same degree in people currently in energy balance or gaining weight compared to those who were losing weight.(Willis, 2022)

If you are interested in reading more about the physiology underlying this constrained model of total energy expenditure, I suggest reading this perspective(Halsey, 2021), which highlights areas of controversy in the field and summarizes the evidence for putative mechanisms. Another critical commentary is available here; this article examines various publications and points out areas where the evidence seems to support or potentially refute various aspects of the constrained model. Another review article emphasizes that even if the constrained model has merit, this doesn’t preclude the utility of increasing physical activity to assist with weight loss and the prevention of weight gain as most people are well below the threshold where significant compensation seems to occur.(Bourdier, 2022) Yet another commentary notes physical activity seems to have benefits for appetite regulation that would be worthwhile for weight loss even if the constrained model is accurate, but the data for the constrained model largely revolves around group means instead of individual variation and thus it quite possibly isn’t accurate for all people.(Blundell, 2023)

More recently than the above, a review article has discussed in detail many flaws with the constrained model of TDEE, going through various aspects of the methodology of the various studies used to build this model, and is particularly against the notion that a point is achieved where further increases in physical activity have no impact on one’s TDEE.(Gonzalez, 2023) The authors here belive that further physical activity will increase one’s TDEE, but not as much as the additive model will predict.

Conclusions regarding the constrained model of TDEE

So what are the key takeaways from this constrained model? From my understanding and looking at the data presented in the citations above, my conclusions are:

  • For people who are sedentary the additive model does more likely apply for people who initially begin to increase their physical activity (ie, by using the strategies in the tip box above that discussed how to counteract a decrease in NEAT).
  • For people who live an active lifestyle, making their lifestyle “more” active will increase overall energy expenditure to some degree though it will be less than the additive model predicts, and this will quite possibly help with appetite regulation and provide additional health benefits.
  • It may take a few months for the body to compensate for a general increase in physical activity, thus you may be able to burn more calories with additional activity initially until your body fully adjusts.

Note: You may recall seeing a news story around 2016 about a study of The Biggest Loser participants who lost a lot of weight and still had significant downregulation of their metabolism 6 years later.(Fothergill, 2016) At the time this was thought to occur due to the very extreme methods used to rapidly lose weight on that show, but some of the media ran with it to indicate that losing weight will “kill” your metabolism and make weight gain inevitable. However, as recently described by the author in charge of that study, given the above evidence that overall energy expenditure is constrained and the fact that many of these participants still had significantly increased levels of physical activity 6 years after the show, it’s possible this constrained model of TDEE alone accounts for a lot of the measured metabolic adaptation rather than the initial weight loss itself.(Hall, 2022)

Tip: It is generally easier to maintain a larger caloric deficit by including exercise and increased physical activity. This also generally makes it easier to maintain weight loss. Increasing your “energy flux”, which has different definitions but essentially means the total amount of energy you consume and expend while maintaining your body weight, seems to be an effective strategy to help keep weight off after weight loss.(Melby, 2019)

The basic idea is that we live in an “obesogenic environment” where there is lots of easy access to tempting calories, and it is difficult to continuously utilize willpower to fight these temptations. By increasing activity levels we are allowed to indulge a bit more with caloric intake, and this may help stave off cravings and feelings of hunger. This also may have additional health benefits given the increased exercise, but one consideration if using this strategy is whether or not you will be able to maintain higher activity levels long-term; if not then this may set you up for weight regain once your activity levels decrease.(Bosy-Westphal, 2021)

Thus, adding in exercise is helpful for the various health benefits, and will likely provide some benefit to one’s TDEE (though perhaps not as much as initially thought as discussed in the section above on the constrained TDEE model). So how much physical activity should you perform? Due to individual variability in the metabolic adaptations described above it is difficult to provide a specific recommendation for the purpose of increasing caloriec expenditure. However, the general exercise course on this site goes into much greater detail regarding how much exercise and activity to perform for overall health benefits. Specifically for weight loss, I will discuss a strategy to account for individual variability in the next two lessons.

Example: One final example in this lesson. I am reproducing images from a 2021 publication where the authors performed a very careful assessment of energy expenditure in individuals during a 24 hour fast and during 5 different overfeeding diets (at ~200% of their TDEE).(Hollstein, 2021).  Compensatory exercise was not allowed in this trial. The point of showing these images is to highlight the significant variability in energy expenditure between individuals in these different conditions.

In the below image each circle represents a participant. FST = fasting, the other columns correspond to diets. LPF = (3% protein, 51% carbohydrate, 46% fat), HPF = (30% protein, 26% carbohydrate, 44% fat), FNP = (20% protein, 20% carbohydrate, 60% fat), CNP = (20% protein, 75% carbohydrate, 5% fat), and BOF = (20% protein, 50% carbohydrate, 30% fat). The Y axis shows the change in TDEE measured over 24 hours. The median change in TDEE while fasting was -177 kcal. People with a decrease of a greater magnitude than this were considered to have a “thrifty” phenotype while people with a decrease of lesser magnitude (or a positive change) were considered to have a “spendthrift” phenotype.

Note the large variability in change in energy expenditure and the mostly consistent placement of the most spendthrift and thrifty participants in each trial. This indicates individual variability is consistent across dramatically different dietary conditions.

Reproduced from: Hollstein T, Basolo A, Ando T, Krakoff J, Piaggi P. Reduced adaptive thermogenesis during acute protein-imbalanced overfeeding is a metabolic hallmark of the human thrifty phenotype. Am J Clin Nutr. 2021 Oct 4;114(4):1396-1407. doi: 10.1093/ajcn/nqab209. PMID: 34225360; PMCID: PMC8488870.

As shown by the mostly consistent placement of the red and blue dots, individuals with a spendthrift phenotype, which was defined by a smaller decrease in TDEE when fasting, generally have a greater increase in TDEE with overfeeding. Therefore, people with a spendthrift phenotype have an easier time losing weight when decreasing caloric intake (as they have a smaller decrease in their TDEE) and a harder time gaining weight when in a caloric surplus (as they have a greater increase in their TDEE). This is likely a key factor in why some people can more easily maintain a healthy body weight than others.

Note: As seen throughout this lesson, there are many aspects of physiologic adaptations to weight loss, but they impact people to different degrees.(Martínez-Gómez, 2021; Miles-Chan, 2023) Given so much individual variability in the various aspects of metabolism and energy expenditure, it is tempting to think that some day we will be able to measure these individual qualities to yield personalized interventions. Unfortunately we are still far away from being able to do this on a regular basis.(Löffler, 2021)

Thus, throughout this course and the general exercise course I provide general advice that applies to most people, but keep in mind there will frequently be exceptions and it is difficult to predict for whom these exceptions will occur. As discussed in the next couple of lessons, monitoring progress and then making adjustments when indicated is a key component to an effective dietary strategy.

Conclusion

Hopefully it is clear why trying to lose weight solely by eating fewer calories can be problematic. RMR, TEF, and NEAT all decrease, slowing weight loss significantly, as your body fights your efforts to lose the weight. Without exercise it is hard to counteract these changes and the only way to continue losing weight at a faster rate is to further reduce calories, making it harder to get in all of the nutrients your body needs to live healthily. You can counteract this with increased exercise; this will increase your caloric deficit and if employing resistance training will help you maintain your LBM as you lose BF, a potential key factor in staving off weight regain in the long run.

Thus, while nutrition is key for weight loss, exercise is still very helpful even beyond the health benefits it confers. Additionally, while there can be significant individual variability in the above aspects of metabolism, the same basic concepts apply to everyone.

Now with this basic understanding of metabolism, in the next lesson we will begin to discuss more practically how to determine what your caloric intake should be, and if you even need to track calories in the first place.

Click here to proceed to Lesson 2

References

  1. Blundell JE, Beaulieu K. The complex pattern of the effects of prolonged frequent exercise on appetite control, and implications for obesity. Appetite. 2023 Feb 6;183:106482. doi: 10.1016/j.appet.2023.106482. Epub ahead of print. PMID: 36754171.
  2. Bosy-Westphal A, Kossel E, Goele K, Later W, Hitze B, Settler U, Heller M, Glüer CC, Heymsfield SB, Müller MJ. Contribution of individual organ mass loss to weight loss-associated decline in resting energy expenditure. Am J Clin Nutr. 2009 Oct;90(4):993-1001. doi: 10.3945/ajcn.2008.27402. Epub 2009 Aug 26. PMID: 19710198.
  3. Bosy-Westphal A, Hägele FA, Müller MJ. Impact of Energy Turnover on the Regulation of Energy and Macronutrient Balance. Obesity (Silver Spring). 2021 Jul;29(7):1114-1119. doi: 10.1002/oby.23133. Epub 2021 May 17. PMID: 34002543.
  4. Bourdier P, Simon C, Bessesen DH, Blanc S, Bergouignan A. The role of physical activity in the regulation of body weight: The overlooked contribution of light physical activity and sedentary behaviors. Obes Rev. 2022 Nov 16:e13528. doi: 10.1111/obr.13528. Epub ahead of print. PMID: 36394185.
  5. Broskey NT, Marlatt KL, Most J, Erickson ML, Irving BA, Redman LM. The Panacea of Human Aging: Calorie Restriction Versus Exercise. Exerc Sport Sci Rev. 2019 Jul;47(3):169-175. doi: 10.1249/JES.0000000000000193. PMID: 30998529; PMCID: PMC6579613.
  6. Broskey NT, Martin CK, Burton JH, Church TS, Ravussin E, Redman LM. Effect of Aerobic Exercise-induced Weight Loss on the Components of Daily Energy Expenditure. Med Sci Sports Exerc. 2021 Oct 1;53(10):2164-2172. doi: 10.1249/MSS.0000000000002689. PMID: 34519717; PMCID: PMC8441008.
  7. Calcagno M, Kahleova H, Alwarith J, Burgess NN, Flores RA, Busta ML, Barnard ND. The Thermic Effect of Food: A Review. J Am Coll Nutr. 2019 Aug;38(6):547-551. doi: 10.1080/07315724.2018.1552544. Epub 2019 Apr 25. PMID: 31021710.
  8. Careau V, Halsey LG, Pontzer H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Buchowski MS, Butte NF, Camps SGJA, Close GL, Cooper JA, Das SK, Cooper R, Dugas LR, Eaton SD, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin CK, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reilly JJ, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl CU, Luke AH, Rood J, Sagayama H, Schoeller DA, Wong WW, Yamada Y, Speakman JR; IAEA DLW database group. Energy compensation and adiposity in humans. Curr Biol. 2021 Oct 25;31(20):4659-4666.e2. doi: 10.1016/j.cub.2021.08.016. Epub 2021 Aug 27. PMID: 34453886; PMCID: PMC8551017.
  9. Dulloo AG, Miles-Chan JL, Schutz Y. Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition. Eur J Clin Nutr. 2018;72(5):657‐664. doi:10.1038/s41430-018-0138-6
  10. Fernández-Verdejo R, Alcantara JMA, Galgani JE, Acosta FM, Migueles JH, Amaro-Gahete FJ, Labayen I, Ortega FB, Ruiz JR. Deciphering the constrained total energy expenditure model in humans by associating accelerometer-measured physical activity from wrist and hip. Sci Rep. 2021 Jun 10;11(1):12302. doi: 10.1038/s41598-021-91750-x. PMID: 34112912; PMCID: PMC8192775.
  11. Fothergill E, Guo J, Howard L, Kerns JC, Knuth ND, Brychta R, Chen KY, Skarulis MC, Walter M, Walter PJ, Hall KD. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016 Aug;24(8):1612-9. doi: 10.1002/oby.21538. Epub 2016 May 2. PMID: 27136388; PMCID: PMC4989512.
  12. Glave A, Didier J, Oden G, Wagner M. Caloric Expenditure Estimation Differences between an Elliptical Machine and Indirect Calorimetry. Exercise Medicine. 2018;2(8):1-5. doi.org/10.26644/em.2018.008
  13. Gonzalez JT, Batterham AM, Atkinson G, Thompson D. Perspective: Is the Response of Human Energy Expenditure to Increased Physical Activity Additive or Constrained? Adv Nutr. 2023 May;14(3):406-419. doi: 10.1016/j.advnut.2023.02.003. Epub 2023 Feb 23. PMID: 36828336; PMCID: PMC10201660.
  14. Hall KD. Energy compensation and metabolic adaptation: “The Biggest Loser” study reinterpreted. Obesity (Silver Spring). 2022 Jan;30(1):11-13. doi: 10.1002/oby.23308. Epub 2021 Nov 23. PMID: 34816627.
  15. Halsey LG. The Mystery of Energy Compensation. Physiol Biochem Zool. 2021 Nov-Dec;94(6):380-393. doi: 10.1086/716467. PMID: 34529542.
  16. Hand GA, Shook RP, O’Connor DP, Kindred MM, Schumacher S, Drenowatz C, Paluch AE, Burgess S, Blundell JE, Blair SN. The Effect of Exercise Training on Total Daily Energy Expenditure and Body Composition in Weight-Stable Adults: A Randomized, Controlled Trial. J Phys Act Health. 2020 Apr 1;17(4):456-463. doi: 10.1123/jpah.2019-0415. PMID: 32176862.
  17. Heymsfield SB, Peterson CM, Bourgeois B, et al. Human energy expenditure: advances in organ-tissue prediction models. Obes Rev. 2018;19(9):1177‐1188. doi:10.1111/obr.12718
  18. Hollstein T, Basolo A, Ando T, Krakoff J, Piaggi P. Reduced adaptive thermogenesis during acute protein-imbalanced overfeeding is a metabolic hallmark of the human thrifty phenotype. Am J Clin Nutr. 2021 Oct 4;114(4):1396-1407. doi: 10.1093/ajcn/nqab209. PMID: 34225360; PMCID: PMC8488870.
  19. Levine JA. Non-exercise activity thermogenesis. Proc Nutr Soc. 2003;62(3):667‐679. doi:10.1079/PNS2003281
  20. Löffler MC, Betz MJ, Blondin DP, Augustin R, Sharma AK, Tseng YH, Scheele C, Zimdahl H, Mark M, Hennige AM, Wolfrum C, Langhans W, Hamilton BS, Neubauer H. Challenges in tackling energy expenditure as obesity therapy: From preclinical models to clinical application. Mol Metab. 2021 Sep;51:101237. doi: 10.1016/j.molmet.2021.101237. Epub 2021 Apr 18. PMID: 33878401; PMCID: PMC8122111.
  21. Lund J, Gerhart-Hines Z, Clemmensen C. Role of Energy Excretion in Human Body Weight Regulation. Trends Endocrinol Metab. 2020 Oct;31(10):705-708. doi: 10.1016/j.tem.2020.06.002. Epub 2020 Jul 13. PMID: 32674987.
  22. MacKenzie-Shalders K, Kelly JT, So D, Coffey VG, Byrne NM. The effect of exercise interventions on resting metabolic rate: A systematic review and meta-analysis. J Sports Sci. 2020 Jul;38(14):1635-1649. doi: 10.1080/02640414.2020.1754716. Epub 2020 May 12. PMID: 32397898.
  23. Magkos F. Is calorie restriction beneficial for normal-weight individuals? A narrative review of the effects of weight loss in the presence and absence of obesity. Nutr Rev. 2022 Feb 22:nuac006. doi: 10.1093/nutrit/nuac006. Epub ahead of print. PMID: 35190812.
  24. Martin A, Fox D, Murphy CA, Hofmann H, Koehler K. Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss. Int J Obes (Lond). 2022 Feb 18. doi: 10.1038/s41366-022-01090-7. Epub ahead of print. PMID: 35181758.
  25. Martins C, Roekenes J, Salamati S, Gower BA, Hunter GR. Metabolic adaptation is an illusion, only present when participants are in negative energy balance. Am J Clin Nutr. 2020 Nov 11;112(5):1212-1218. doi: 10.1093/ajcn/nqaa220. PMID: 32844188; PMCID: PMC7657334.
  26. Martins C, Gower BA, Hunter GR. Metabolic adaptation delays time to reach weight loss goals. Obesity (Silver Spring). 2022 Feb;30(2):400-406. doi: 10.1002/oby.23333. PMID: 35088553; PMCID: PMC8852805.
  27. Melanson EL. The effect of exercise on non-exercise physical activity and sedentary behavior in adults. Obes Rev. 2017;18 Suppl 1(Suppl 1):40‐49. doi:10.1111/obr.12507
  28. Melby CL, Paris HL, Sayer RD, Bell C, Hill JO. Increasing Energy Flux to Maintain Diet-Induced Weight Loss. Nutrients. 2019 Oct 21;11(10):2533. doi: 10.3390/nu11102533. PMID: 31640123; PMCID: PMC6835968.
  29. Miles-Chan JL, Harper ME. Deconstructing interindividual variability in energy metabolism: implications for metabolic health. Am J Physiol Endocrinol Metab. 2023 Aug 1;325(2):E107-E112. doi: 10.1152/ajpendo.00060.2023. Epub 2023 Jun 14. PMID: 37315156.
  30. Moniz SC, Islam H, Hazell TJ. Mechanistic and methodological perspectives on the impact of intense interval training on post-exercise metabolism. Scand J Med Sci Sports. 2020;30(4):638‐651. doi:10.1111/sms.13610
  31. Müller MJ, Wang Z, Heymsfield SB, Schautz B, Bosy-Westphal A. Advances in the understanding of specific metabolic rates of major organs and tissues in humans. Curr Opin Clin Nutr Metab Care. 2013;16(5):501-508. doi:10.1097/MCO.0b013e328363bdf9
  32. Müller MJ, Heymsfield SB, Bosy-Westphal A. Are metabolic adaptations to weight changes an artefact? Am J Clin Nutr. 2021 Oct 4;114(4):1386-1395. doi: 10.1093/ajcn/nqab184. PMID: 34134143.
  33. Müller MJ, Heymsfield SB, Bosy-Westphal A. Changes in body composition and homeostatic control of resting energy expenditure during dietary weight loss. Obesity (Silver Spring). 2023 Mar 2. doi: 10.1002/oby.23703. Epub ahead of print. PMID: 36863769.
  34. Nunes CL, Casanova N, Francisco R, Bosy-Westphal A, Hopkins M, Sardinha LB, Silva AM. Does adaptive thermogenesis occur after weight loss in adults? A systematic review. Br J Nutr. 2022a Feb 14;127(3):451-469. doi: 10.1017/S0007114521001094. Epub 2021 Mar 25. PMID: 33762040.
  35. Nunes CL, Jesus F, Francisco R, Matias CN, Heo M, Heymsfield SB, Bosy-Westphal A, Sardinha LB, Martins P, Minderico CS, Silva AM. Adaptive thermogenesis after moderate weight loss: magnitude and methodological issues. Eur J Nutr. 2022b Apr;61(3):1405-1416. doi: 10.1007/s00394-021-02742-6. Epub 2021 Nov 27. PMID: 34839398.
  36. Ostendorf DM, Melanson EL, Caldwell AE, et al. No consistent evidence of a disproportionately low resting energy expenditure in long-term successful weight-loss maintainers. Am J Clin Nutr. 2018;108(4):658‐666. doi:10.1093/ajcn/nqy179
  37. Panissa VLG, Fukuda DH, Staibano V, Marques M, Franchini E. Magnitude and duration of excess of post-exercise oxygen consumption between high-intensity interval and moderate-intensity continuous exercise: A systematic review. Obes Rev. 2021 Jan;22(1):e13099. doi: 10.1111/obr.13099. Epub 2020 Jul 12. PMID: 32656951.
  38. Pontzer H, Durazo-Arvizu R, Dugas LR, Plange-Rhule J, Bovet P, Forrester TE, Lambert EV, Cooper RS, Schoeller DA, Luke A. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans. Curr Biol. 2016 Feb 8;26(3):410-7. doi: 10.1016/j.cub.2015.12.046. Epub 2016 Jan 28. PMID: 26832439; PMCID: PMC4803033.
  39. Pontzer H, Yamada Y, Sagayama H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SG, Close GL, Cooper JA, Cooper R, Das SK, Dugas LR, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin C, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl C, Luke AH, Rood J, Schoeller DA, Westerterp KR, Wong WW, Speakman JR; IAEA DLW Database Consortium. Daily energy expenditure through the human life course. Science. 2021 Aug 13;373(6556):808-812. doi: 10.1126/science.abe5017. PMID: 34385400; PMCID: PMC8370708.
  40. Rosenbaum M, Leibel RL. Models of energy homeostasis in response to maintenance of reduced body weight. Obesity (Silver Spring). 2016 Aug;24(8):1620-9. doi: 10.1002/oby.21559. PMID: 27460711; PMCID: PMC4965234.
  41. Ruddick-Collins LC, Flanagan A, Johnston JD, Morgan PJ, Johnstone AM. Circadian Rhythms in Resting Metabolic Rate Account for Apparent Daily Rhythms in the Thermic Effect of Food. J Clin Endocrinol Metab. 2022 Jan 18;107(2):e708-e715. doi: 10.1210/clinem/dgab654. PMID: 34473293; PMCID: PMC8764350.
  42. Shen W, Chen J, Zhou J, Martin CK, Ravussin E, Redman LM. Effect of 2-year caloric restriction on organ and tissue size in nonobese 21- to 50-year-old adults in a randomized clinical trial: the CALERIE study. Am J Clin Nutr. 2021 Oct 4;114(4):1295-1303. doi: 10.1093/ajcn/nqab205. PMID: 34159359; PMCID: PMC8645192.
  43. Silva AM, Júdice PB, Carraça EV, King N, Teixeira PJ, Sardinha LB. What is the effect of diet and/or exercise interventions on behavioural compensation in non-exercise physical activity and related energy expenditure of free-living adults? A systematic review. Br J Nutr. 2018 Jun;119(12):1327-1345. doi: 10.1017/S000711451800096X. PMID: 29845903.
  44. Stubbs RJ, Turicchi J. From famine to therapeutic weight loss: Hunger, psychological responses, and energy balance-related behaviors. Obes Rev. 2021 Mar;22 Suppl 2:e13191. doi: 10.1111/obr.13191. Epub 2021 Feb 1. PMID: 33527688.
  45. Villablanca PA, Alegria JR, Mookadam F, Holmes DR Jr, Wright RS, Levine JA. Nonexercise activity thermogenesis in obesity management. Mayo Clin Proc. 2015;90(4):509‐519. doi:10.1016/j.mayocp.2015.02.001
  46. Westerterp KR. Diet induced thermogenesis. Nutr Metab (Lond). 2004;1(1):5. Published 2004 Aug 18. doi:10.1186/1743-7075-1-5
  47. Westerterp KR. Exercise, energy expenditure and energy balance, as measured with doubly labelled water. Proc Nutr Soc. 2018 Feb;77(1):4-10. doi: 10.1017/S0029665117001148. Epub 2017 Jul 20. PMID: 28724452.
  48. Westerterp KR. Adaptive thermogenesis during energy deficits: a different explanation. Eur J Clin Nutr. 2022 Mar 11. doi: 10.1038/s41430-022-01107-4. Epub ahead of print. PMID: 35277671.
  49. Willis EA, Creasy SA, Saint-Maurice PF, Keadle SK, Pontzer H, Schoeller D, Troiano RP, Matthews CE. Physical Activity and Total Daily Energy Expenditure in Older US Adults: Constrained versus Additive Models. Med Sci Sports Exerc. 2022 Jan 1;54(1):98-105. doi: 10.1249/MSS.0000000000002759. PMID: 34334719; PMCID: PMC8678174.
Scroll to Top