Obesity is not about calories
The dogma that obesity is simply an imbalance between calories in and calories burnt is wrong. Obesity is a disease of metabolism and behaviour and should be treated as such.
This study in this week’s Science on daily energy expenditure is getting an extraordinary amount of media coverage. The central claim is that it slays a central dogma that adult obesity is due to a gradual reduction in metabolic rate that occurs with age. This study shows that metabolic rate is essentially constant in adults until about 60 years of age and only then does it slow down.
One not so well informed commentator has already stated that this study confirms that obesity remains a problem of too many calories in and too few calories burnt. I thought this worldview of obesity had been slain a decade or more ago. Obesity is a metabolic or endocrine disorder and the calories are a secondary problem; sort out your metabolism and the calories sort themselves out. This is called homeostasis and the human body is amazingly adept and looking after itself.
It is now well known that not all calories are made equal in the context of human biology. Adipose or fat tissue is an organ that is controlled by a complex array of hormones and neuronal signals. Insulin is the master regulator that stores excess calories in adipose tissue. If you want to prevent adipose tissue from forming you need to try and keep your insulin levels low, very low. How do you do this? In short, you need to limit the quantity of carbohydrates or sugars, you eat. Glucose and fructose are the smallest building blocks of the sugars we consume in our diets. The higher your blood glucose and fructose levels go the more insulin your body produces and hence more of the calories you consume will be converted into fat. In comparison, proteins and fats don’t increase insulin levels and hence don’t stimulate the metabolic programme that drives adiposity (fat storage).
This is why high-fat (e.g. Banting) and high-protein (e.g. Atkins, Dukan, etc.) diets are so effective in causing weight loss. Both these diets keep your insulin levels low and deplete your body of glycogen. Glycogen is the way your liver and muscles store carbohydrates. When your blood levels of glucose drop it triggers a process that results in your liver releasing glucose from its glycogen stores. The stores of glycogen are quite limited and when they run out your body turns on two other metabolic programs. One program is called gluconeogenesis; this is when your body starts breaking down protein and converting it to glucose. The second process is called ketosis; ketosis is the metabolic programme that mobilises fats, typically from adipose tissue, or from dietary fat and converts the mobilised fat to ketones. Ketones are then used by the brain, and the body, as an alternative energy source to glucose.
Please note that if you are on a high-fat, high-protein, low-carbohydrate (<50g of net carbohydrates per day) diet the calories you consume will not raise insulin levels and hence you won’t necessarily put on weight. The exception to this is if you eat very very large quantities of protein and create the stimulus to build muscle, e.g. bodybuilding. In general, however, with a low carbohydrate diet, you will lose weight because ketosis rapidly mobilises fats from your adipose tissue. The problem with ketogenic diets is that you really need to keep the quantity of carbohydrates you consume very low. If you don't, the carbohydrates you eat will raise your insulin levels and you then flip-and-flop between a state of ketosis and non-ketosis. In the non-ketotic state, your body will store the excess calories provided by the high-fat diet as adipose tissue and your weight will stay steady.
Please note the amount of carbohydrates you are allowed to eat on a low-carb diet will vary from individual to individual, which is why nutritionists often advise using urine dipsticks or exhalation devices to monitor ketosis and to adjust your carbohydrate intake accordingly.
Another important aspect of high-fat and high-protein diets is that they don’t generally restrict the number of calories you consume. Why? Firstly, eating enough calories in the form of protein prevents gluconeogenesis and hence it protects your lean muscle mass. If you lose muscle mass you are catabolic, i.e. breaking down tissue, which implies you are too calorie-restricted and not consuming enough protein in your diet. Calorie restriction triggers gluconeogenesis to maintain glucose levels until ketosis develops. Please note ketosis takes time to kick in, anything from 2 to 7 days, during which time gluconeogenesis has to provide energy for the brain. Therefore, flip-floppers tend to lose more muscle mass than dieters who maintain ketosis over prolonged periods of time.
Another aspect of ketogenic diets is that before your brain switches into its ketone utilisation mode it has to rely on a dwindling supply of glucose that is being provided by gluconeogenesis. During the crossover period from gluconeogenesis to ketosis, you don’t feel very well; i.e. you feel tired and lethargic, you find exercise hard and you may develop a headache. However, once you become ketotic these symptoms resolve and you start to feel normal; in fact, some people report feeling supernormal when ketotic. Euphoria and a mild sense of being intoxicated is a well-described effect of ketosis. I suspect the latter is why there are so many ketosis addicts out there; they crave the sense of well-being that comes with being ketotic.
Most people ask ‘How can anyone lose weight on a ketogenic high-fat high-protein diet when I am consuming so many calories?’. The reason is the body has homeostatic (balance) mechanisms to control caloric intake. Fats and proteins are particularly effective at triggering the hormonal response that induces satiety, i.e. the feeling of fullness you get after a meal. In comparison, carbohydrates are very poor at inducing satiety, which is why people on a low-fat high-carbohydrate diet always feel hungry. People on a high-fat high-protein diet are not continuously hungry and don’t spend their day thinking of food.
Another positive effect of ketogenic diets is that ketones affect the brain in other positive ways and are anorexigenic (reduce appetite). Ketosis triggers complex hormonal changes in the body that reduce appetite. Contrary to what people expect, caloric intake on high-fat high-protein diets actually drop spontaneously and people don’t overeat. This rule however only holds true if you are ketotic. As soon as you eat carbohydrates and switch off ketosis, your appetite comes back with a vengeance and you overeat to compensate for the adipose tissue you have just lost. From an evolutionary perspective, people with lots of adipose tissue were protected in times of famine. This is why when carbohydrates became available to our ancestors, e.g. seasonal fruits, nuts and honey, they were endowed with the metabolic programme to store the excess calories as fat and to not switch off their appetites when eating carbohydrates; the so-called gorging response. The fact that most modern societies don’t live a seasonal life, i.e. we now have access to a high carbohydrate diet all year round, partially explains why obesity has reached such epidemic proportions.
It is quite clear from archaeological and historical studies that our ancestors lived on a high-fat high-protein and low carbohydrate diet most of the year. Our ancestors were seasonal eaters and hence only switched to a high-carbohydrate diet at specific times of the year when fruits, nuts and vegetables were in abundance. What is important to note from the above is that our bodies, or metabolism, has been optimised by evolution to use the time of plenty (late summer and autumn) to store as much of the calories consumed as carbohydrates as fat. In comparison, when carbohydrates were scarce our ancestor’s metabolism was optimised to survive on a high-fat high-protein diet provided by animals (man is firstly a carnivore and only secondly an omnivore). Contrary to what many nutritionists say, from an evolutionary perspective a high-fat high-protein diet is very healthy. In comparison, a low-fat high-carbohydrate diet is an outlier; a continuous high-carbohydrate diet is unnatural from an evolutionary perspective and is one of the reasons behind our obesity epidemic.
Evolution has not made all calories equal when it comes to adiposity. Calories consumed as carbohydrates, or in the presence of carbohydrates, are more likely to be stored as fat because of high insulin levels (hyperinsulinemia). Calories consumed as fat, in the relative absence of carbohydrates and insulin, will be converted to energy in the form of ketones. The high protein consumption that occurs in parallel with fat is used by our bodies to maintain our organs, in particular our muscle mass.
Obviously, energy expenditure is another factor and as we move from adolescence to adulthood our behaviours change and we tend to do less exercise. However, if our metabolism is allowed to work the way it was designed to by evolution this would naturally be accompanied by reduced energy intake. By perturbing our metabolism by creating a hyperinsulinemic state 24/7 with rapid blood glucose cycling the homeostatic mechanisms that control long term energy balance are hijacked by short-term behavioural responses to hunger and the reward, or dopamine hit, our brains receive from eating high-energy foods, particularly processed carbohydrates. This is the real reason why we get fat. Sadly, we are addicted to sugar.
So I don’t agree with these commentators that obesity is simply an imbalance between calories in and calories burnt. It is this kind of mindset that has resulted in failed public health efforts to curtail the obesity epidemic. Until we accept obesity as a metabolic and behavioural disorder and treat it as such obesity levels will continue to rise.
Please don’t believe everything you hear and see on television or read in newspapers.
Pontzer et al. Daily energy expenditure through the human life course. Science 13 Aug 2021: Vol. 373, Issue 6556, pp. 808-812.
A lifetime of change: Measurements of total and basal energy in a large cohort of subjects at ages spanning from before birth to old age document distinct changes that occur during a human lifetime. Pontzer et al. report that energy expenditure (adjusted for weight) in neonates was like that of adults but increased substantially in the first year of life (see the Perspective by Rhoads and Anderson). It then gradually declined until young individuals reached adult characteristics, which were maintained from age 20 to 60 years. Older individuals showed reduced energy expenditure. Tissue metabolism thus appears not to be constant but rather to undergo transitions at critical junctures.
Abstract: Total daily energy expenditure (“total expenditure”) reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass–adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.