This is Why "Calories In, Calories Out" is Not the Whole Truth

Following outdated advice is keeping you frustrated with your results

Author

My Longevity Experiment
April 25, 2025

Calories In Calories Out Explained: The Full Story

The adage "calories in, calories out" is true, but a complete understanding reveals deeper nuances.

From the moment food enters the mouth to the time it exits the body, the digestive system and gut microbiome work to extract its nutrients. Enzymes in the mouth, stomach and small intestine break down food for absorption, while microbes in the large intestine digest what remains.

Subscribed

"Calories in, calories out" refers to the concept that weight change is determined by the balance between the calories consumed and the calories expended. This balance includes the calories eaten due to appetite, the calories absorbed via digestion, and how well those calories are burned through metabolism.

Recent research indicates that a significant factor influencing people's variable appetites, digestion and metabolism are biologically active leftover components of food, known as bioactives. These bioactives regulate the body's metabolic control centers: the brain's appetite center, the hypothalamus, the gut's digestive bioreactor, the microbiome, and the cells' metabolic powerhouses, the mitochondria.

A gastroenterologist who has spent the past 20 years studying the gut microbiome's role in metabolic disease explains how dietary bioactives help explain why some individuals can eat more but gain less, offering dietary tools to improve metabolism.

Appetite and Digestion

Research has demonstrated that consuming whole foods still packaged in their original fibers and polyphenols leads to more calories lost through stool compared to processed foods that have been predigested by factories into simple carbs, refined fats and additives. This is one way calorie-free factors influence the "calories in, calories out" equation, offering benefits in a society where calorie intake often exceeds needs. Eating more whole foods and fewer processed foods allows more unprocessed calories to pass unused through the digestive system.

Fiber and polyphenols also regulate appetite and calorie intake through the brain. The microbiome transforms these leftover bioactives into metabolites that naturally decrease appetite. These metabolites regulate the same gut hormones that inspired popular weight loss drugs Wegovy, Ozempic and Mounjaro, controlling appetite through the brain's satiety center, the hypothalamus.

Processed foods lack these bioactives and are formulated with salt, sugar, fat and additives to be hyperpalatable, leading to increased cravings and overeating.

Mitochondrial Function and Calorie Burning

A full accounting of calories depends on how effectively the body burns them to power movement, thoughts, immunity and other functions, largely orchestrated by mitochondria. Healthy individuals typically possess high-capacity mitochondria that efficiently process calories to fuel cellular activities. Conversely, people with metabolic diseases have poorly functioning mitochondria, leading to bigger appetites, reduced muscle mass and increased fat storage.

They also have less brown fat, a mitochondria-rich type of fat that burns calories to produce heat. Less brown fat may explain why some people with obesity have lower body temperatures compared to those who are not obese, and why average body temperature has declined in the U.S. since the industrial revolution.

Healthy mitochondria that burn more calories may help explain why some individuals can eat more without gaining weight. Mitochondrial health is influenced by multiple factors including regular exercise, adequate sleep, stress management and a healthy diet.

The Role of Bioactives in Mitochondrial Health

Recent nutrition research highlights the roles that previously underappreciated dietary factors play in mitochondrial function. Beyond essential macronutrients and micronutrients, other components such as fibers, polyphenols, bioactive fats and fermentation products are critical for metabolism.

Unlike the Western diet, traditional diets like the Mediterranean and Okinawan diets are rich in foods abundant in these bioactives, including nuts, seeds, fruits, vegetables, whole grains and fermented foods.

Many bioactives pass undigested to the large intestine where the microbiome converts them into activated metabolites. These metabolites influence the number and function of mitochondria in cells. At the cellular level, these metabolites turn on and off molecular switches through epigenetics, affecting both the individual and potential offspring.

When the metabolic "lights" are switched on, they energize mitochondria responsible for a faster metabolism, increasing the calories the body uses.

The Microbiome Gap

A healthy microbiome produces beneficial metabolites that support brown fat activity, muscle endurance and overall metabolic health. However, not everyone has a microbiome capable of converting bioactives into active metabolites.

Long-term consumption of processed foods, antibiotic overuse, high stress and lack of exercise can impair the microbiome's ability to produce these vital metabolites. This creates a double nutrition gap: a lack of healthy diet and a deficiency in the microbes needed to process it.

Consequently, well-studied diets like the Mediterranean diet might be less effective for individuals with an impaired microbiome, sometimes leading to gastrointestinal symptoms and negatively impacting metabolic health.

Nutrition research is also investigating low-carb diets that might bypass the need for a healthy microbiome. Although higher protein intake may reduce beneficial metabolite production, lower carbohydrate intake stimulates the body's production of ketones. One ketone, beta-hydroxybutyrate, may function similarly to the microbiome metabolite butyrate in regulating mitochondria.

Emerging microbiome-targeted strategies include butyrate supplements, personalized nutrition, intermittent fasting, and future live bacterial therapies to restore microbiome health.

Practical Tools to Improve Metabolism

For most individuals, restoring the microbiome through traditional diets remains biologically achievable but may be challenging due to cost, time constraints and taste preferences. Maintaining metabolic health ultimately returns to the simple pillars of exercise, sleep, stress management and nutritious diet.

Simple mnemonics like the 4 F's of food – fibers, polyphenols, unsaturated fats and ferments – can help individuals focus on foods that best support the microbiome and mitochondria. Bioactive-powered calculators and apps can also assist in choosing foods to better regulate appetite, digestion and metabolism, helping to balance calorie intake and expenditure.

Your Call to Action for Calories In Calories Out Explained

Understanding the truth behind "calories in, calories out" empowers individuals to make smarter choices that influence appetite, metabolism and weight management. Prioritize whole foods rich in fibers, polyphenols, unsaturated fats and ferments to nourish your microbiome and optimize mitochondrial health. Incorporate regular exercise, ensure adequate sleep, and manage stress effectively. By aligning your habits with these principles, you can rebalance your body's natural calorie-burning mechanisms and achieve lasting metabolic wellness.

Study Links: