Calories in, calories out: the fuller story of appetite and metabolism

The saying "calories in, calories out" is accurate, but it does not tell the entire story.

From the instant food reaches your tongue until it is expelled from your body, your digestive system and gut microbiome work together to draw out nutrients.

Enzymes in the mouth, stomach and small intestine break food down so it can be absorbed, whereas microbes in the large intestine digest what remains.

"Calories in, calories out" describes the idea that changes in body weight depend on the difference between the calories consumed and the calories expended.

That balance involves not just the calories you eat in response to appetite and take in through digestion, but also the efficiency with which your metabolism burns those absorbed calories.

Recent studies suggest that biologically active residual food compounds, called bioactives, are an important influence on the ways people's appetite, digestion and metabolism differ.

These bioactives are central to regulating the body's metabolic control centres: the hypothalamus, which controls appetite in the brain; the microbiome, the gut's digestive bioreactor; and mitochondria, the metabolic powerhouses within cells.

As a gastroenterologist who has investigated the gut microbiome's role in metabolic disease for the past 20 years, I will explain how dietary bioactives may clarify why some people eat more yet gain less weight, and outline dietary tools that can support metabolism.

Considering appetite and digestion

Studies have found that eating whole foods still "packaged" in their natural fibre and polyphenols - the plant cell coverings and colourful compounds responsible for many health benefits - results in more calories being lost in stool than eating processed foods that factories have "predigested" into simple carbohydrates, refined fats and additives.

This is one example of how calorie-free influences affect the "calories in, calories out" equation, which may be useful in a society where calorie consumption frequently exceeds requirements. Choosing more whole foods and fewer processed foods can simply allow you to eat more, because a greater proportion of those unprocessed calories passes out of the body unused.

Fibre and polyphenols also influence appetite and calorie consumption via the brain. The microbiome converts these residual bioactives into metabolites - molecular products of digestion - which naturally suppress appetite.

Those metabolites regulate the same gut hormones that originally inspired the widely used weight-loss medicines Wegovy, Ozempic and Mounjaro, influencing appetite through the hypothalamus, the brain's satiety centre.

Processed foods do not contain these bioactives and are additionally designed with salt, sugar, fat and additives to make them hyperpalatable, encouraging cravings and greater consumption.

Mitochondria and calorie burning

A complete calculation of calories must also consider how efficiently the body burns them to support movement, thinking, immunity and other processes - work that mitochondria largely coordinate.

People in good health generally have high-capacity mitochondria that readily process calories to power cellular activity. In people with metabolic diseases, mitochondria function less effectively, helping to drive larger appetites, reduced muscle mass and greater fat storage.

They also possess less brown fat, a mitochondria-rich form of fat. Instead of storing calories, brown fat burns them to generate heat.

Having less brown fat could partly account for why some people with obesity have lower body temperatures than people who are not obese, as well as the fall in average body temperature in the U.S. since the industrial revolution.

Well-functioning mitochondria that burn more calories could also help explain how certain people eat more without gaining weight. This prompts another question: Why do some people have healthier mitochondria than others?

Ultimately, mitochondrial health is shaped by numerous factors commonly linked to general well-being, including regular physical activity, sufficient sleep, stress management and a healthy diet.

What switches off metabolic activity?

New nutritional research is uncovering how dietary components that were previously overlooked contribute to mitochondrial health.

In addition to the essential macronutrients - fat, protein and carbohydrates - and micronutrients including vitamins and minerals, other residual food components, such as fibres, polyphenols, bioactive fats and fermentation products, are also vital to metabolism.

In contrast with a Western diet, which commonly provides too few of these bioactives, traditional eating patterns including the Mediterranean and Okinawan diets contain abundant foods - nuts, seeds, fruit, vegetables, whole grains and fermented foods - that are rich in these compounds.

A large number of bioactives travel undigested through the small intestine to the large intestine, where the microbiome transforms them into activated metabolites. The body then absorbs these metabolites, which affect both the number of mitochondria in cells and their performance.

At the most basic level of cell biology, metabolites activate and deactivate molecular switches in genes through epigenetics, a process that can influence both you and your offspring.

When metabolic "lights" are switched on, they activate mitochondria, supporting a faster metabolism and effectively raising the number of calories you use.

Addressing the microbiome gap

A healthy microbiome generates a broad spectrum of helpful metabolites that promote calorie-burning brown fat, muscle endurance and metabolic health. However, not everybody has a microbiome able to convert bioactives into their active metabolites.

Eating processed foods over the long term, when they are low in bioactives and high in salt and additives, can weaken the microbiome's capacity to make the metabolites required for optimal mitochondrial health. Excessive antibiotic use, high stress and insufficient exercise can likewise harm microbiome and mitochondrial health.

This produces a double nutrition gap: too little healthy food and too few microbes able to convert its bioactives.

Consequently, extensively studied dietary strategies such as the Mediterranean diet may work less well for some people with an impaired microbiome, potentially causing gastrointestinal symptoms including diarrhoea and adversely affecting metabolic health.

For these circumstances, nutrition research is examining the possible health benefits of various low-carbohydrate diets that could bypass the requirement for a healthy microbiome.

Although the increased protein in these diets may lower the microbiome's output of beneficial metabolites, reduced carbohydrate intake stimulates the body's production of ketones. Beta-hydroxybutyrate, one such ketone, may act in a similar way to butyrate, a microbiome metabolite, in regulating mitochondria.

Developing approaches that target the microbiome may also help improve metabolic health: butyrate and other postbiotics can supply preformed microbiome metabolites; personalised nutrition can adapt diets to the microbiome; intermittent fasting may assist microbiome repair; and live bacterial therapies may eventually restore microbiome health.

Tools for turning fat into fuel

For most people, it remains biologically possible to restore the microbiome through traditional diets such as the Mediterranean diet, although practical obstacles including time, cost and taste preferences can make this difficult.

Ultimately, metabolic health still rests on the seemingly straightforward pillars of a healthy lifestyle: exercise, sleep, stress management and a nutritious diet.

Even so, several straightforward tips and tools can make nutritious dietary choices easier. Memory aids such as the 4 F's of food - fibres, polyphenols, unsaturated fats and ferments - can direct attention towards foods whose "leftovers" most effectively support the microbiome and mitochondria.

Calculators and apps powered by bioactives can also help people choose foods that regulate appetite, digestion and metabolism, helping to rebalance calorie "ins and outs."

Christopher Damman, Associate Professor of Gastroenterology, School of Medicine, University of Washington

This article is republished from The Conversation under a Creative Commons licence. Read the original article.