Do Calories Matter?

Is the obesity epidemic really just a matter of eating too much?
While calories in versus calories out sound like a very logical system to us, it is somewhat outdated. If we look at the research, there are at least 4 factors that matter more than calories:

Being knowledgeable about how these four factors regulate our bodies will give us a better understanding why focusing on calories is not the smartest way to achieve the ideal weight.

Macronutrient Composition

For decades, the government recommends diets low in fat, which again sounds logical…you eat fat, you gain fat. However, if we look at some studies, we see that it is quite the opposite.
Researchers put patients on a 1000-calorie per day diet and divided the patients into 4 groups [1]:

Daily weight change on a 90%-Carn diet, a 90%-Protein diet, a 90% Fat diet, and a Mixed diet [1]

Daily weight change on a 90%-Carn diet, a 90%-Protein diet, a 90% Fat diet, and a Mixed diet [1]

  1. Diet with a mixed macronutrient composition

  2. Diet with 90% of calories from fat

  3. Diet with 90% of calories from protein

  4. Diet with 90% of calories from carbohydrates

Assuming that "a calorie is a calorie no matter where it comes from" we would expect the patients to lose weight equally.

On a mixed diet, the volunteers lost on average 200 grams of body weight per day. The patients on a 90% fat diet showed 400grams of weight loss per day, and a diet of 90% protein diet showed a similar loss with 300grams per day. But surprisingly, the patients who consumed 90% of their calories from carbohydrate actually gained on average 100 grams per day!

One would wonder how this is possible with such a high caloric deficit, but don’t worry we will get to this!

Body weight change of men and women on a very-low carbohydrate ketogenic diet (VLCK) compared to a low-fat diet (LF) [2]

Body weight change of men and women on a very-low carbohydrate ketogenic diet (VLCK) compared to a low-fat diet (LF) [2]

Sure only eating 1000 calories per day and getting 90% of your calories from just one macronutrient source sounds a little extreme. In another more recent study, overweight participants were divided into two groups. Both groups caloric intake was restricted by 500 calories per day and one group was prescribed a very-low-carbohydrate diet and the other group a low-fat diet. Both diets contained an equal amount of proteins.
While both groups lost weight, the participants on a very low carbohydrate diet lost on average twice the amount of body mass mainly in the form of fat! [2]

In fact, the science is quite clear here. There are many studies that show the efficiency of a low-carb diet compared to a low-fat diet [3-5].


Average, minimal and maximal weight gain of students after 120 days [6]

Average, minimal and maximal weight gain of students after 120 days [6]

Another factor that we need to take into consideration when we talk about weight loss is our genes. In a study from the 90s nicely demonstrates the importance of genetics:
Twins were enrolled in a study that isolated them from the rest of the world and the participants of the study were only allowed to eat, sleep, watch tv, and read. The students were restricted from all physical activity and were over-fed 1000 calories extra per day.
After the 120 days, the students gained on average 8.1kg of body weight, which is not very surprising. What was surprising, however, was the range of weight gain. While some students only gained 4.3kg, others gained up to three times more weight (13.3kg)! There was some variation in weight gain among the twins, however, the similarity of weight gain was significant! [6]

Nevertheless, consider the following: The human DNA is 99.9% similar between individuals! Additionally, the obesity epidemic exploded in just one generation. Nothing we could simply explain with genetics [7].

Obesity rates in different countries from 1972 to 2012

Obesity rates in different countries from 1972 to 2012


The Microbiome

Mice that received microbes from obese people gained more fat [8]

Mice that received microbes from obese people gained more fat [8]

This brings me to the next point. Research over the last years has shown that our gut microbiome plays an essential role in weight control. While our DNA is highly similar, our microbiomes can vary extremely from person to person.
In a study, researchers sucked the microbes from obese or lean human twins and injected them into mice whose own microbiome was deleted. The mice that received the “obese” microbes gained more body weight, especially fat, than the mice with the lean microbiome. [8]

And further research has shown how the ingestion of probiotics doubled the weight loss in slightly overweight women. [9]

The question might arrise, why the microbiome has such a big saying in our weight. There are many ways on how our gut bacteria regulate our weight:

  1. The microbes digest the fiber, we don’t digest and provide us with Short-Chain Fatty Acids, which have been shown in research studies to protect from obesity. [10]

  2. Our gut bacteria also regulate our hunger and satiety hormones. Researchers found that mice without a microbiome have generally lower levels of leptin, the satiety hormone. [11]

  3. Besides from controlling our hormones, research has also shown us that many bacteria produce peptides, which are similar to our appetite-regulating hormones, including leptin and ghrelin. [12]  


All previous three factors are seemingly coming back to the last one: Hormones. Depending on the food we eat our body produces different hormones. One of the most anabolic, if not even the most anabolic hormone is insulin. When we eat carbohydrates, they are broken down into glucose. High blood glucose levels initiate the release of insulin from the pancreas. Insulin then stimulates the uptake of glucose into the muscle, liver and fat cells. In these cells, the absorbed nutrients are converted either into glycogen via glycogenesis or into fats via lipogenesis, or, in the case of the liver, into both.

Functions of insulin

Functions of insulin

Here is a short summary of what insulin does inside your body:

  1. insulin stimulates the uptake of glucose

  2. insulin increases fat synthesis

  3. insulin decreases lipolysis (breakdown of lipids)

  4. insulin induces glycogen synthesis

  5. insulin decreases proteolysis

  6. insulin decreases autophagy

  7. insulin increases uptake of potassium and decreases sodium secretion

However, insulin is not the only hormone do blame. Even though it explains why we are getting fatter, we need to look at two different hormones to explain why we are still hungry while we getting fat?!

Two main hormones regulate whether we feel hungry or full -> ghrelin and leptin. Leptin is the hormone that makes us feel full. It is secreted by our fat cells and tells our brain to stop eating. For most people, insulin resistance is something they have heard of. However, Leptin resistance is a very similar phenomenon.
There are three main factos for leptin resistance:

Cani summary.JPG
  1. Inflammation

  2. Free Fatty Acids in the blood

  3. Chronic high leptin concentrations

As an example, researchers found that mice on an unhealthy diet showed a leaky gut and by this had increased inflammation levels and developed insulin resistance. However, simply adding some fiber to the diet reversed the ill-effects of an unhealthy diet! The mice stayed leaner, developed less inflammation and became more insulin sensitive. [13]

Ghrelin levels decrease while 84 fast in obese and lean people_Espelund2.JPG

The counter hormone to leptin is ghrelin, our hunger hormone. It is produced by cells in the gastrointestinal tract and binds to the same cells of the brain as leptin. If we are hungry, ghrelin goes up and leptin goes down. However, one thing I need to mention here is that while your ghrelin levels rise when you eat less, your ghrelin levels go down if you don’t eat at all.

Volunteers fasted for 4 days and their ghrelin levels were measured every few hours. Periodically, their ghrelin levels went up but even though they didn’t eat, ghrelin levels went down again and the hunger disappeared. Their overall ghrelin pikes became smaller in the course of the fast. [14]

Hormonal adaption

The last thing I want to mention here is that there is also something called “Hormonal adaptation”. When we are in a caloric deficit for too long our bodies start to adapt and down-regulates our metabolism. Here is a great example for this: Researchers followed up with participants of the show “The Biggest Loser” over 6 years and found that all but one participant of the study regained weight! While being on a diet for many months, the body adapted to the low caloric intake and slowed down its metabolism. [15]

Take home message

We have seen that before cutting down calories you might want to consider changing your macronutrient composition and improving your gut health and by this letting your body naturally regulate how much food it needs.

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  2. Volek et al., Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women, Nutrition and Metabolism, 2004

  3. Brehm et al., A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women, The Journal of Clinical Endocrinology & Metabolism, 2003

  4. Samaha et al., A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity, N Engl J Med, 2003

  5. Shai et al., Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet, N Engl J Med, 2008

  6. Bouchard et al., The response to long-term overfeeding in identical twins, The New England Journal of Medicine, 1990

  7. Choquet and Meyre, Genetics of Obesity: What have we Learned?, Curr Genomic, 2011

  8. Ridaura et al., Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice, Science, 2013


  10. Lu et al., Short Chain Fatty Acids Prevent High-fat-diet-induced Obesity in Mice by Regulating G Protein- coupled Receptors and Gut Microbiota, Scientific Reports, 2016

  11. Xiong et al., Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41, PNAS, 2004

  12. Alcock et al., Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms, bioessays-journal, 2014

  13. Cani et al., Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia, Diabetologia, 2007

  14. Espelund et al., Fasting Unmasks a Strong Inverse Association between Ghrelin and Cortisol in Serum: Studies in Obese and Normal-Weight Subjects, JCEM, 2005

  15. Fothergill et al., Persistent metabolic adaptation 6 years after The Biggest Loser competition, Obesity, 2016