Shifting our ideas about… Weight Loss (perspective article)

Reducing calorie intake may not help you lose body weight – true or false? TRUE!

Weight-Centred Health Paradigm (WCHP)

It’s a good idea to be constantly checking what we think we know to be true. Asking questions about nutrition science, for example, and what it means for our health. Such as the weight-centered health paradigm (WCHP) underlying the weight-normative approach. This paradigm places emphasis on weight and weight loss when defining health and well-being, and it conveys weight management in terms of a calorie-centric model. By calorie we mean the energy value of foods calculated in caloric values.

In popular health, the calorie-centric model is synonymous with ‘calorie counting’, a euphemism for weight-watching, where calories are often erroneously described as good or bad (depending on nutritional value) and body ideal appearance is often conflated with good health. National dietary guidelines ‘eat less move more’ standard advice applies, alongside a notion of willpower. It’s a one size fits all approach, where a calorie is a calorie regardless of individual differences in the population.

Ultimately, maintaining a healthy weight requires regulation of energy balance between nutritional energy intake and energy expenditure. A fundamental principle of metabolism and nutrition is that body weight change is an imbalance between energy intake (content of food eaten) and energy expenditure (using energy to live and work).

Figure 1 depicts this as a schematic representation, where E_in is nutritional energy intake and E_out is nutritional energy expenditure. The equation implies that weight gain can occur when the body’s energy balance is positive and weight is lost when the body’s energy balance is negative. But is it really that simple?

 

Snapshot of Energy Homeostasis

Energy balance is a potentially powerful tool for investigating the regulation of body weight. The energy balance equation is the nuance of body energy homeostasis or ‘the regulation of daily total nutritional energy intake and expenditure in the maintenance and defence of energy balance’. The context of this defence is maintaining whole-body homeostasis or actively maintaining fairly stable conditions in the body, such as regulating  breathing and cellular activity. It is the case that all cells in the body have metabolic needs, including those that keep our neurons or brain cells firing.

So, how do our cells obtain energy from food to sustain these metabolic needs? Food energy is an example of “metabolic fuels” obtained from fats (or lipids), carbohydrates (or sugars) and proteins. These food molecules have differing energy density related to their proportions of carbon, hydrogen and oxygen atoms with a metabolic equivalent of calories (fats approximately 9kcal/g and proteins & carbohydrates 4kcal/g). Within cells, energy is provided by oxidation of these “metabolic fuels” and this happens in the mitochondria.

So, food is our fuel, and we burn or oxidise the fuel for energy, and we need oxygen to burn the fuel. The oxidation process results in free energy production that can be stored in molecules such as  ADP and ATP. ATP hydrolysis (or breakdown) provides the energy needed for various essential processes in our cells. These include DNA and RNA synthesis, intracellular and extracellular signaling, synaptic signaling, muscle contraction and active transport (used by cells to accumulate needed molecules, such as glucose and amino acids). Decreased ATP levels (falling below a certain threshold for particular cells), can induce apoptosis or cell death. Good nutrition then, is a central plank of good health.

The brain has the role of regulating energy metabolism as part of many different homeostatic activities. A key region in the brain taking charge is the hypothalamus, linking the endocrine system (hormones) with the nervous system, integrating multiple metabolic inputs. Hypothalamic regions primarily senses the body’s energy state, and projects signals to NTS neurons in the brainstem, that form critical circuits involved in dealing with incoming information from cells (including vagal afferents), involved in taste, gastrointestinal and cardio-respiratory processes.

These homeostatic inputs to and from the hypothalamus, are integrated with hedonic feeding signals from mesolimbic pathways (including dopaminergic neurons associating food-related reward stimuli), and signals from the amygdala, pre-frontal cortex and hippocampus. Directing attention, decision-making, and adiposity-related signals such as insulin and leptin, gut-derived hormones such as ghrelin, and activation of the gut-brain axis or biochemical message exchange between the host (us!) and our gut microbiota. 

These systems and processes drive glucose management, appetite, satiety, fat storage, and food seeking behaviours, among other things. If energy surplus (excess food intake), or starvation (dieting or fasting) is energetically too demanding, the brain will orchestrate changes across these brain networks, adapting cellular systems and hormones to manage any extremes in energy balance in defence of maintaining energy homeostasis. So, consider that what we eat or don’t eat changes our brain cell structure and function and other cell structures in the body, adjusting to ensure conditions that are optimal for survival.

Basal Metabolic Rate and Resting Metabolic Rate

Two key parameters in determining energy balance are Basal metabolic rate (BMR) and resting metabolic rate (RMR). The two are often used synonymously, referring to the rate of oxygen uptake, with a metabolic equivalent of calories burned or energy expended for basic functions. RMR is while at rest (without any physical activity) and BMR is while at rest and fasted (calculated 12-18 hours following the last meal). 

BMR makes up 60 -70% of the energy expended or oxygen consumption. Diet-induced thermogenesis or energy expended after a meal is 10 -15%, and adaptive thermogenesis or body temperature regulation and physical activity is 10 -15%. Postural maintenance and even fidgeting accounts for 6-10% of the energy expended. BMR has been reported as proportional to body mass. This means basal oxygen consumption tends to be higher in men than in women, and relative to body mass index or BMI.

BMR increases as body weight increases and decreases as body weight decreases. However, energy expended (the equivalent of calories burned per kilogram of body weight), decreases as body weight decreases (with dietary reductions resulting in metabolic inefficiencies), or increases (despite having higher total daily energy expenditure levels, as energy expenditure is actually lower in relation to body weight). Creating the ideal situation in either case for weight gain and regain.

So, when we hear people saying they keep ‘sabotaging their diet’, what’s really going on is their metabolic defences orchestrated by the brain are persisting in maintaining energy balance in times of starvation or surplus. In the same vein, we may also hear reports of weight ‘yo-yoing’ or repeated bouts of weight cycling between weight loss and regain (1994), and rapid weight loss, followed by a weight plateau and progressive regain (2018).

Ultimately, a low BMR which represents decreased overall body metabolism, is an independent predictor of future weight gain, and a high BMR represents increased overall body metabolism (i.e., you need to burn more calories to sustain yourself through the day) is a risk factor for morbidity or disease. Characterised by pro-inflammatory and immunological over-activation, or an inflamed body that affects immune system activity and many other systems in the body, attributable to energy homeostatic dysregulation. Herein lies the WCHP conundrum. 

INTERLUDE: Macronutrients in Health and Disease

Dietary carbohydrates (simple sugars or complex starches) are metabolised into glucose in the body. Glucose is one of the main energy sources for cellular metabolism, so we must have glucose, so the cells on uptake of glucose can produce ATP that is critical for metabolic and cellular processes (transfer of energy to cells). 

When we eat, our blood glucose levels rise and our pancreas is triggered to release a hormone called insulin. Insulin has many jobs, one of which is blood sugar control, stimulating glucose, (amino acids, and fatty acids) uptake into the liver, muscle and fat cells, promoting their storage in the form of glycogen, protein and fat respectively. 

Thereby, lowering blood glucose levels back to normal 1-2 hours following food intake. When we look at blood sugar levels after a meal, we see that some foods cause large ‘spikes’, that takes longer for the body to return to normal levels. If blood sugar spikes are not controlled, over time your body may not be able to lower blood sugar effectively. Which can lead to hyperinsulinemia (or too much insulin in the body) and insulin resistance. 

Insulin resistance can be a feature of metabolic diseases, such as metabolic syndrome and type II diabetes, with symptoms of systemic inflammation, high blood pressure, poor energy and hunger control, elevated fatty acids in the bloodstream (cholesterol), and increased abdominal obesity. In-fact much research documents a positive relationship between obesity and elevated insulin levels in the bloodstream. 

This makes it difficult to lose weight, as insulin primes fat cells to store fat. It is not well known that fat cells, stimulate glucose uptake, which the fat cell will use to turn glucose into fat. In-fact, insulin plays a role in inhibiting the breakdown of that fat, so the fat cell starts to grow. Insulin resistance then, makes it difficult to lose weight. So, it is not only about managing blood sugar; it is also important to stabilise blood lipid or fat levels and so fat responses.

Age, health and lifestyle have a big influence on blood sugar control. Dehydration and low salt intake, for example, can negatively affect blood sugar control, as can pro-inflammatory diets that negatively impact your blood sugar responses, and this differs by individual.

Dietary fat and oil or triglycerides are converted to fatty acids and glycerol and stored in adipocytes (lipids or fat cells). Lipolysis is the process of mobilising this stored energy to fuel the body, and for insulation, temperature control, and other critical functions for life. Blood glucose homeostasis is closely linked with our fat cells. It is the glycerol component of the triglyceride, that gets readily converted into sugar or glucose for use as energy by the body. Insulin is secreted from the pancreas, signalling our fat cells to take up glucose for use as fuel for proper functioning, without which our cells would start malfunctioning. 

So, dietary ‘unsaturated‘ fats such as olive oil, avocado, nuts and seeds, is really important for normal regulation of insulin and for the biological action of insulin on our fat cells. This is contrary to popular health low fat regimen. We know that prolonged exposure to excess dietary ‘saturated’ fat can manifest in high BMI and can elevate fatty acids and so insulin in the bloodstream. This is strongly associated with longer-term metabolic inflammation, risking metabolic conditions including obesity and insulin resistance.

Proteins in food are used to make amino acids that in turn make proteins used in the body, serving as the backbone for compounds like our hormones and neurotransmitters in the brain. Just 20 amino acids make many thousands of proteins in the human body, required for neural and cell function, repair and regeneration. 

Some proteins are made in the body and some are essential amino acids, or must be supplied by dietary means. For example, dopamine is a derivative of the amino acid phenylalanine (which is essential) and tyrosine. High phenylalanine foods include meat and poultry, fish, tofu, beans, milk, nuts, seeds, pasta, whole grains, and vegetables like sweet potatoes. High tyrosine foods are sesame seeds, cheese, soy beans, turkey, beef, pork, fish, eggs, nuts and legumes.

Serotonin is synthesised from the essential amino acid tryptophan. Tryptophan can be found in nuts, seeds, diary, red meat, poultry, pork, fish, oats, beans, lentils, eggs, dark chocolate, peanut butter, pumpkin seeds, sesame seeds, sunflower seeds, soybeans, tofu, soy milk, spirulina and wheat flour. See here for guidelines of how much is required by kg of body weight.

Any excess protein is turned into glucose via glucogenesis in the liver (by a hormone called glucagon). Any excess glucagon with the help of insulin, is converted in to fatty acids and stored as fat and glucogen in the liver. These reserves are used to prevent low blood sugar when we are sleeping or in a fasted state. However excessive reserves can also underlie insulin resistance, and fatty liver disease.

Evaluating Some of the Evidence for a Shift in Paradigm

On paper, the WCHP suggests that we will lose weight if we make relatively consistent negative energy changes (caloric deficit) over time, alongside some kind of aerobic physical activity. To quantify this, the caloric equivalent to lose one pound of body fat is 3750 calories. This applies the first law of thermodynamics to human metabolism, which assumes: 

1) We are a perfect thermodynamic machine (i.e., able to capture and qualify and account for every unit of energy); and 

2) That the metabolic value of calories from different fuels (fat, carbohydrates and protein) behave the same metabolically in different people. 

However humans are an open system? Plus, we know that ‘no two people’s responses to individual foods are the same, even between identical twins‘.

A professor of bioenergetics in the US, Ben Bikman, surmises an alternative ‘endocrine centric paradigm‘ to WCHP, which reduces the obsessive focus on caloric energy, and refocuses on the relevance of hormones, whose job is telling the cells what to do with energy. His Latest research in this arena talks about an experiment in his lab: 

“In a petri dish I can have ample calories from glucose and fatty acids or fat, and the fat cells won’t grow at all…, until we spike insulin into the culture. At the moment we add insulin …  we can start to detect fat droplets … and over time these become big bubbly fat cells. This cannot happen unless insulin is elevated. It’s impossible. So a fat cell needs to be told by the hormone insulin, what to do with energy”.

We know that high sugar foods spike insulin; this could even be foods like bananas, mango, pineapple and white rice (so not always obvious). However, we also know there is high variability in blood glucose responses, as well as blood fat responses and inflammatory responses, in individual’s biological responses to specific foods. Critical in this energy equation is also stabilising gut health (or gut microbiota). So its not about calorie counting, but food quality, as well as when we eat, and even food combinations.

What of genetic factors at play in weight management? We know that people carrying two copies of the FTO gene (associated with high obesity risk variant) are on average heavier than those carrying two copies of the protective version (associated with low obesity risk variant). This absolute risk runs alongside a predisposition (or genetic susceptibility) to obesity, whereby ongoing studies show human obesity can be inherited as a ‘polygenic trait’, which means many genetic mutations cumulatively might increase risk of obesity, that are ‘switched on’ by a complex interplay with environmental factors, including lifestyle and obesogenic environments.

Another study researching such multiple gene-nutrient interactions with environmental factors, identified gene mutations looking across a diverse population, associated with susceptibility to common human obesity. This may account for the so-called obesity epidemic. In addition, new genome studies have discovered genetic traits behind disordered eating, and also variability in gut microbial composition as potentially having heritable influence on weight management, so, it is far more complex than WCHP might convey.

Evaluating further Evidence for a Shift in Paradigm

The percentage increase of age-specific population obese predicted in the U.K. at 2050 as compared with 2007 can be said to inform further the evidence of WCHP failure (see Figure 2). These results were modelled from a microsimulation using Department of Health obesity data and measures, on behalf of the U.K. Government initiated Foresight Programme. The results show correlative growth in obesity across the adult age groups, and combined three times percentage growth in the 1 to 20 age groups (2007, 17).

 

That same Foresight Report suggested that “we are on average consuming too many calories on a regular basis. Latterly, data gathered by Public Health England (PHE) in 2017 overlaid the Foresight observations, with findings that obesity prevalence in the U.K. adult population between 1993 and 2019 has indeed grown. Increasing from 27% to 64%’ over that period (2017). While roughly 1.4 million children aged between 2 and 15 were classified as obese in 2018, with obesity rates for older children (10- to 11-year-old’s) increasing from 18.7% to 20.2% between 2009/10 and 2018/19.

A Promising Life Course Approach

The Foresight Programme underpinned by the PHE findings and other public health research prompted a nationwide WCHP based programme of prescribed ‘calorie reduction’ strategies in the general population by 2020. It seems a promising approach, but why do we do this when we know this paradigm may be ineffective? WCHP has been a dominant strategy since the 1980’s, so it appears commonsense to think eating fewer calories will support weight loss, and for all intents and purposes, the model is not without its merits.

By way of the national programme incorporating long-term strategies for improving the food environment. Such as reducing access to calorie-dense foods and beverages by thinning the concentration of fast-food outlets, and aligning the food industry to cut excess calories from major brands, especially those directed at children. Underpinned by levies across the food chain encouraging review and reformulation of products, to lower levels of salt, sugar, and saturated fat calories. Alongside, health awareness campaigns such as Change4Life aimed at addressing the whole family, as well as identified health inequalities, including obesity stigma.

Importantly, the PHE programme recognises obesity as a chronic disease, in the health system, that predisposes to other diseases, while decreasing overall life expectancy. The WCHP programme under these auspices has shown some level of success when implemented as part of a long-term medical care regime. Protocols that have proven to work include clinical oversight (regular contact with health professionals), oversight from food and nutrition policy including basic nutrition, and physical education, alongside specialist support such as psychotherapeutic or pharmacological interventions, as may be required. Nevertheless, WCHP conundrum is the shadow of an obesity epidemic. So what else is going on here?

Calorie Reduction some Science

A review carried out by the National Institute for Health and Care Excellence (NICE, 2013) may begin to shed some light. Following cohorts on national clinical recommended weight loss interventions, they found strong evidence that within 1-year of completing the interventions, the population mean weight slowly increased. The average rate of weight regain is estimated as 0.56kg/y. That’s 5.6 kilograms or 12.35 pounds gained over 10-years based on an ideal daily intake of calories. However, obesity rates tell us the ideal is regularly exceeded.

Researchers have known for decades why WCHP does not work over the long term, a very early piece of research is a case in point and harks back to our earlier energy homeostasis discussion. The study was interested in ‘changes in energy expenditure resulting from altered body weight’ and they found that calorie surplus reflected increases in energy expenditure. Conversely, calorie deficits reflected decreases in energy expenditure. Reminder that energy expenditure refers to RMR/  BMR parameters in determining energy balance (accounting for approximately 60% of total energy expended at rest). Figure 3 shows comparisons of energy expenditure at the end of a period of weight gain and weight loss:

 

The study found that a 10% increase from usual weight was accompanied by a 12% increase in energy expenditure, suggesting an increased cardiorespiratory load related to an increased number of fat cells (probably reflecting hyperphagia or an abnormally increased appetite from raised levels of the hormone leptin). And a 10-20% decrease from the usual weight was accompanied by a 10-15% decrease in energy expenditure, suggesting metabolic resistance to the maintenance of the reduced body weight (possibly underlying are reduced levels of triiodothyronine from thyroxine and raised levels of the hormone insulin). This study has since been replicated many times over.

These findings could explain ‘weight plateaus’, and potentially the high prevalence of weight regain, driven by energy homeostasis defending energy balance in returning the body to its so-called setpoint. In obesity where the setpoint is set too high (body fat percentage), then attempts at losing weight will result in adaptive homeostatic controls driving weight regain to return to the setpoint. Another study found that energy deficits predispose homeostatic changes in some people lean from weight loss, to accumulate more fat than was lost over time in weight regain and loss of muscle mass, hence the notion posited of ‘fat overshoot’.

Energy Homeostasis as a New Paradigm?

We have briefly discussed why the WCHP as the central plank of anti-obesity strategies may be failing. Taking on an energy homeostatic perspective as to why this may be. The evidence shows that when our cell’s experience disturbance in reacting to WCHP uncertainty (starvation or caloric surplus), neurobiological compensatory measures will defend energy balance. One way is reductions or increases in RMR / BMR, adaptations in how the body uses caloric energy, and hormonal or humoral signalling disturbance manifesting in potential for insulin, leptin, ghrelin and also fat cell resistance.

Figure 4 schematic helps us to model this discussion, taken from a paper that discuses ‘The Energy Homeostasis Principle’ as a conceptual paradigm:

 

The energy homeostasis principle stipulates that: ‘the brain’s role in energy regulation drives local network dynamics, generating behaviours’. And like any other physical system, it is subject to boundaries of operation. This includes our genetics (inheritable risk). Highlighting the extraordinary role of our cells, genetics, and hormones, on individual homeostatic differences, and their high sensitivity to changes in the environment. In other words, such homeostatic adaptations, that have been confirmed across different studies, are the brain’s best endeavours to reduce uncertainty, in what is an uncertain WCHP environment.

Ultimately driving our homeostatic controls in the brain to assure sufficient energy availability to meet all cell population energy demands in the body, including its own. So, in order to understand how we might better manage our bodyweight, it seems we need to better understand the dynamics that are orchestrating energy homeostatic behaviours at a cellular, genetic, and behavioural level? 

Looking to some of the latest research for the answers, longstanding twin studies is illuminating how individuals that are genetically identical can exhibit distinctly different weight traits and behaviours. Providing a possible reinterpretation of weight management under the guise of precision nutrition. Precision nutrition factors individual differences in the population, and provides clear evidence that our body’s responses to food vary by way of genes and also gut microbes, blood sugar and blood fat control differences, driving energy homeostasis that is unique to each of us.

The latest metabolic health research complements this ground breaking science of precision nutrition. Helping to answer some of the enduring questions; ‘why does my weight yo-yo’ or ‘why does my weight cycle between repeated bouts of weight loss and regain’ or ‘why do I have progressive regain’ (weighing more than when I started)? Answers may also come from ongoing research around weight setpoint or the notion of ‘a constant body-inherent weight’. 

The implication is that there is an active biological feedback system linking our fat cells (stored energy) to intake and expenditure via a set point. This set point is so-say avidly defended by our energy homeostatic system. Moreover, obesogenic environments, social, economic, and cultural influences may mean adaption to various ‘settling points’ in relation to heritable susceptibility risk to obesity, in the body’s endeavour to achieve energy balance.

Meantime, the latest ageing science research is informing us that what we eat and when we eat, and even certain combinations of foods and cooking methods, can be critical for understanding weight management, shifting to a new paradigm that considers strategic science of fat loss and health. Hot topics in this area of research include longevity diets, and new insights into circadian biology and intermittent fasting that are changing the face of how we think about weight and weight loss. 

Overall this discussion has hopefully shifted our ideas about weight loss, i.e., moving emphasis away from the entrenched WCHP model and related body ideal aesthetic, and toward the function of our humble cells and hormones. After-all, our brain dictates the direction of all our cellular (and homeostatic metabolic) processes. So, this seems a very good place to start for a paradigmatic shift in our thinking!

Author: Treesje Verlinden

This article expresses a new perspective on existing problems, prevalent notions and fundamental concepts relating to existing research and future directions on the topic, and includes personal opinion. It is designed to open up conversation, exploration and debate.