Calories in, calories out: the fuller story

The saying "calories in, calories out" is accurate in brief, although the complete picture is more complex.

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

Enzymes in the mouth, stomach and small intestine break food apart so it can be absorbed, while microbes in the large intestine process what remains.

"Calories in, calories out" describes the idea that changes in body weight depend on the relationship between the calories consumed and those used.

That calculation involves not just the calories eaten in response to appetite and absorbed during digestion, but also the efficiency with which the absorbed calories are used by metabolism.

Newer studies suggest that biologically active food remnants, called bioactives, substantially shape differences between people in appetite, digestion and metabolism.

These bioactives help govern 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.

I am a gastroenterologist who has investigated the gut microbiome's part in metabolic disease for the past 20 years. Here, I explain how dietary bioactives may clarify why certain people eat more yet gain less weight, and set out dietary tools that may support metabolism.

Ruminating on appetite and digestion

Studies have found that eating whole foods still "packaged" with their natural fibre and polyphenols – the cellular structures and colourful plant compounds responsible for many health benefits – results in more calories being lost in stool than eating processed foods. Factories have effectively "predigested" those processed foods into simple carbohydrates, refined fats and additives.

This offers one example of how calorie-free influences affect the "calories in, calories out" equation, which may be useful in a society where people commonly consume more calories than they need. Choosing more whole foods and fewer processed options can simply allow you to eat more, since a greater share of calories from unprocessed food leaves the body unused.

Fibre and polyphenols can also influence appetite and calorie consumption through the brain. The microbiome converts these residual bioactives into metabolites – molecular products of digestion – that naturally curb appetite.

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

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

Mitochondrial maestros in the middle

A complete calorie calculation must also consider how efficiently the body burns calories to support movement, thinking, immunity and other processes. Mitochondria largely direct this process.

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

They also have lower amounts of brown fat, a form of fat rich in mitochondria. Instead of storing calories, brown fat uses them to generate heat.

Reduced brown fat could partly account for why some people with obesity have lower body temperatures than people without obesity, as well as the fall in average body temperature in the US since the industrial revolution.

Mitochondria that are healthy and burn more calories may also account for why some individuals can eat more without putting on weight. This leads to an important question: why are some people's mitochondria healthier than others'?

Ultimately, mitochondrial health is shaped by numerous factors commonly linked with overall well-being, including routine exercise, sufficient sleep, managing stress and eating healthily.

Who turned off the metabo-lights

The newest nutrition studies are uncovering how dietary influences that were once overlooked contribute to mitochondrial health.

In addition to essential macronutrients – fat, protein and carbohydrates – and micronutrients including vitamins and minerals, other food remnants are important for metabolism. These include fibre, polyphenols, bioactive fats and fermentation products.

Western diets frequently provide too few of these bioactives, unlike traditional eating patterns such as the Mediterranean and Okinawan diets. These diets include abundant nuts, seeds, fruit, vegetables, whole grains and fermented foods that are rich in such components.

Numerous bioactives travel undigested through the small intestine and reach the large intestine, where the microbiome transforms them into activated metabolites. The metabolites are then absorbed and affect both the number of mitochondria in cells and the way they work.

At the most basic level of cellular biology, metabolites switch molecular controls in genes on and off through epigenetics, a process that can influence both you and your offspring.

Once the metabolic "lights" have been activated, they invigorate the mitochondria that drive a faster metabolism, in effect raising the number of calories used.

Please mind the microbiome gap

A healthy microbiome creates a broad range of beneficial metabolites that promote calorie-burning brown fat, muscle endurance and metabolic health. However, some people do not have a microbiome able to turn bioactives into active metabolites.

Eating processed food over the long term – food low in bioactives but high in salt and additives – may damage the microbiome's capacity to make the metabolites required for ideal mitochondrial health. Excessive antibiotic use, substantial stress and insufficient exercise may likewise harm microbiome and mitochondrial health.

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

Consequently, established nutritional strategies such as the Mediterranean diet may work less well for people whose microbiome is impaired. This could trigger gastrointestinal symptoms including diarrhoea and have a negative effect on metabolic health.

For these circumstances, nutrition researchers are examining the possible health advantages of different low-carb diets that could avoid the requirement for a healthy microbiome.

Although the extra protein in these diets may lower the microbiome's production of beneficial metabolites, their reduced carbohydrate content encourages the body to produce ketones. Beta-hydroxybutyrate, one such ketone, may act in a similar way to butyrate, a microbiome metabolite, when regulating mitochondria.

New microbiome-focused methods may also help improve metabolic health: butyrate and other postbiotics that supply ready-made microbiome metabolites; personalised nutrition that matches diet to the microbiome; intermittent fasting that may help repair the microbiome; and the future potential for live bacterial therapies to restore microbiome health.

Tools to transform fat into fuel

For the majority of people, rebuilding the microbiome through traditional dietary patterns such as the Mediterranean diet remains biologically possible. It is not invariably practical, however, because of barriers including time, cost and taste preferences.

Ultimately, metabolic health still rests on the apparently simple foundations of a healthy lifestyle: exercise, sleep, stress management and a nutritious diet.

Straightforward tips and tools may nevertheless 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 that best nourish the microbiome and mitochondria with "leftovers."

Calculators and apps powered by bioactives may also help with selecting foods that manage 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.