Is "Calories In, Calories Out" True? The Role of Bioactives

Is the saying "calories in, calories out" accurate? In brief, yes - although the reality is more complex.

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

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

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

That balance involves more than the calories you eat in response to appetite and absorb during digestion. It also depends on how efficiently those absorbed calories are burned through metabolism.

Recent studies suggest that biologically active food remnants, known as bioactives, are an important influence on the ways people's appetites, digestion and metabolism differ.

These bioactives help regulate the body's metabolic control centres: the hypothalamus, which governs appetite in the brain; the microbiome, the gut's digestive bioreactor; and the mitochondria, the metabolic powerhouses within cells.

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

Rethinking appetite and digestion

Research has found that eating whole foods still "packaged" in their natural fibre and polyphenols - the cellular coverings and colourful plant compounds responsible for many health benefits - results in more calories being lost in stools than eating processed food. Factories have effectively "predigested" these processed foods into simple carbohydrates, refined fats and additives.

This is one route through which calorie-free factors affect the "calories in, calories out" equation, potentially helping in a society where calorie consumption commonly 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 leaves the body unused.

Fibre and polyphenols can also regulate appetite and calorie intake via the brain. The microbiome converts these remaining bioactives into metabolites - molecular by-products of digestion - that naturally suppress appetite.

These metabolites influence the same gut hormones that originally inspired the popular weight-loss medicines Wegovy, Ozempic and Mounjaro. They control 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 calculation of calories must also consider how efficiently the body burns them to support movement, thinking, immunity and other processes. This work is largely directed by mitochondria.

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

They also tend to have less brown fat, a type of fat rich in mitochondria. Instead of storing calories, brown fat burns them to create heat.

Reduced brown fat could partly explain why some people with obesity have lower body temperatures than people who are not obese, and why average body temperature in the US has fallen since the industrial revolution.

Mitochria that are healthy and burn more calories may also help explain why certain people can eat more without putting on weight. That prompts another question: why do some people have healthier mitochondria than others?

Ultimately, mitochondrial health is shaped by numerous factors commonly linked with overall wellbeing, including regular physical activity, sufficient sleep, stress management and a healthy diet.

Dietary bioactives and metabolic health

The newest nutrition studies are uncovering how dietary factors 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 crucial to metabolism. These include fibre, polyphenols, bioactive fats and fermentation products.

Unlike a Western diet, which frequently contains few of these bioactives, traditional eating patterns such as the Mediterranean and Okinawan diets contain plentiful nuts, seeds, fruit, vegetables, whole grains and fermented foods that are rich in them.

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

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

When these metabolic "lights" are switched on, they energise the mitochondria that underpin a faster metabolism, effectively raising the number of calories you burn.

Please mind the microbiome gap

A healthy microbiome creates a complete range of beneficial metabolites that promote calorie-burning brown fat, muscle endurance and metabolic health. However, not everybody has a microbiome able to convert bioactives into active metabolites.

A long-term diet of processed foods that is low in bioactives and high in salt and additives can weaken the microbiome's capacity to produce the metabolites required for optimal mitochondrial health. Excessive antibiotic use, high stress and insufficient exercise can likewise harm microbiome and mitochondrial health.

The result is a double nutrition gap: both a shortage of healthy food and a deficiency of the microbes needed to convert its bioactives.

Consequently, well-researched dietary approaches such as the Mediterranean diet may be less effective for some people with an impaired microbiome. This could potentially cause gastrointestinal symptoms, including diarrhoea, and adversely affect metabolic health.

In such circumstances, nutrition research is examining the possible health benefits of a range of low-carbohydrate diets that may avoid the need for a healthy microbiome.

Although the higher protein content of these diets can reduce the microbiome's creation of beneficial metabolites, lower carbohydrate intake prompts the body to make ketones. One ketone, beta-hydroxybutyrate, may act similarly to butyrate, a microbiome metabolite, in regulating mitochondria.

New microbiome-targeted methods may also help improve metabolic health. These include butyrate and other postbiotics that supply preformed microbiome metabolites; personalised nutrition that adapts diet to the microbiome; intermittent fasting to assist microbiome repair; and the future potential for live bacterial therapies to restore microbiome health.

Tools to transform fat into fuel

For most people, restoring the microbiome through traditional diets such as the Mediterranean diet remains biologically possible. Yet it is not invariably practical because of obstacles including time, cost and taste preferences.

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

Even so, several simple tools and tips can make nutritious food choices easier. Memory aids such as the 4 F's of food - fibres, polyphenols, unsaturated fats and ferments - can help focus attention on the foods that best nourish the microbiome and mitochondria with "leftovers."

Calculators and apps powered by bioactives may 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.