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Anas Maqba

Anas Maqba

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What is Calorie?

Etymology     
The calorie comes from the Latin “Calor”, which means “heat” was first used as a unit of heat measurement in the field of chemistry in 1824 by chemists and physician ‘Nicolas Clement ‘. It was defined as the amount of heat required to raise the temperature of one gram of water by one degree Celsius.

The concept of the calorie was originally developed in the field of thermodynamics to describe the amount of heat energy, particularly in the fields of physics, chemistry.

In simple words, calorie is a unit used to measure energy in food or the human body. The way other units are used to measure, like for mass its kg, for liquid its litter and for area or length it is centimeters.

Who bought calories in Nutrition field and why?

The concept of calorie is based on the Law of Thermodynamics, which is the law of energy conversion. This law states the flow and transformation of energy.
“Energy cannot be created or destroyed, it can only be changed from one form to another”- Einstein.
Food gives us energy, which our body uses for different things.
Nutrition is a chemical energy that gets utilized during training, which is mechanical energy and gets converted into muscular energy. During the energy convention process, heat is formed, which is measured as calorie, which is a unit. 

In the 1860s, an American chemist ‘Wilbur Olin Atwater’ known for his studies of human nutrition and metabolism, and is considered the father of modern nutrition research and education. The Atwater method was used to measure both the energy contained in food by burning food samples such as carbohydrates, proteins, and fats by a bomb calorimeter machine.

The respirator calorimeter was used to measure the heat produced by a person in a controlled environment to determine their energy expenditure or calorie burn.
Which led to the concept of energy balance, that is, balancing the energy intake from food (calories in) with the energy expenditure of the body (calories out).
By the 1930s, the calorie had indeed become deeply ingrained in both the public consciousness and government policies related to nutrition and food labelling.

Some people from the community of Ketogenic, Carnivore and Intermittent fasting challenged the concept of calories for several reasons.
1) Questioning the method of the Atwater experiment methodology.
2) Reduced calorie intake does not lead to weight loss.

3) Obesity is related to hormonal issues, not excessive calorie intake.
4) Only Ketogenic nutrition is the right way to eat.
5) Intermittent fasting is particularly effective for long-term fat loss.
Let’s see each claim in detail!

What about Sugar industry funded research, which led to the growing obesity epidemic?

In the JAMA Internal Medicine in 2016, researchers at the University of California, San Francisco found evidence that the sugar industry from the 1960s funded research to shift the blame for heart disease and other health issues from sugar to dietary fat. PMID: 27695828
However, it’s important to note that this study focused specifically on the sugar industry’s influence on scientific research and not all studies blaming fat for obesity current scientific understanding or the entirety of nutrition research.

Though the sugar industry-funded research might have played a big role in the obesity epidemic by changes in dietary patterns and the overall food environment, but it is not a single factor, what about sedentary lifestyles?

The obesity epidemic related to sedentary lifestyle is also challenged by the ketogenic community! Their perceptive is obesity is related to sugar, which leads to overeating due to less satiety (hunger), blood glucose crash and addictive and not with calories intake.
A high fat and protein intake will help with blood glucose balance, maintaining muscle mass and appetite suppression, which happens due to balance between two hormones, Leptin and Ghrelin; Hence, if someone is living in sedentary lifestyle will not get into obesity due to overeating. But this is just a Hypothesis and yet not shown by any good study.

Burn Calories vs. Use Calories: What's the Difference?

Most people who want to lose weight are worried about how many calories they will burn. How many calories do you burn when you do weight training or cardio? What are the best ways to burn more calories? Like calories are some useless stuff that our body has stored in the form of fat. If you know how important it is to have fat in your body, you can use it to build strength, power, and endurance instead of wasting it. We never burn car fuel by simply riding it, we use it to get to our destination.

Why is the Calorie not recognized as an international system unit?

In the international system (SI) of scientific units, only the joule has been defined SI unit of energy and not the calorie in because calories are specific to the field of nutrition. Whereas, the joule has a broader range of applications beyond just nutrition.(1 joule (J) is approx to 0.239 calories or 1 cal = 4.2 J) PMID: 18086303

Why is it significant to eat according to hunger pangs without measuring foods?

Coming Soon

CONTROVERSY 
Calories in vs. Calories out or Calories Consumed vs. Calories Burned, or A calorie is not a calorie vs. A calorie is a calorie

Calories Don't Matter 

The method of the Atwater experiment methodology

The bomb calorie meter, which is a closed system that has some limitations.
1) Nutrient bioavailability: Bomb calorie meter measures calories (energy) stored in food based on combustion. However, it does not measure differences in nutrient bioavailability or the body’s ability to extract and utilize those nutrients efficiently.Eg Fiber or other complex carbohydrates don’t get absorbed and utilized efficiently. Not all sources of protein have the same bioavailability. Other essential nutrients like vitamins & minerals which have a specific role in our body. 
2) Species and places:The density of nutrients is influenced by the location and species of food production, which may further impact the calories stored in the food.
3) Metabolic differences:Factors such as age (For older people, changes in the gastrointestinal tract, such as decreased stomach acid production and reduced efficiency of nutrient absorption, reduce muscle mass, etc.). Genetics, Thermic effect of food, body composition, and hormone levels can influence calorie metabolism.
4) Food processing and thermic effect:Cooking food changes the molecular structure, which in turn changes the calories content and its utilization. For example, cooked eggs have a higher absorption than raw eggs.

Hence, according to the bomb calorimeter, Protein, and carbohydrates are the same because they have the same calories. That is
1 gram of Protein = 4 calories.
1 gram of carb = 4 calories 
1 gram of fat  = 9 calories
in a closed system, which comes under the first law of thermodynamics. But our body is an open system; hence it comes under the concept of entropy, which is a second law of thermodynamics. The measure of entropy is a measure of the disorder or randomness of microscopic parts such as atoms, molecules, and particles within a given macroscopic state of the system.
Which states that the total entropy of an isolated system always increases or remains constant, whereas an open system exchanges energy with its surroundings because energy moves towards a state of greater disorder or randomness. For example, heat spontaneously flows from a hot object to a cooler object, and a gas expands to fill its available volume. 

Hence, though Protein and carbohydrates have the same stored energy (calories) this energy behaves differently in the body. That is why protein is more important than carbohydrates according to the body, but not through the Bomb Calorie meter.
Therefore, a calorie is a calorie according to a bomb calorimeter, which is a closed system; however, for the body, which is an open system, a calorie is not a calorie.
The bomb calorimeter can provide valuable insights and measurements, but they cannot directly apply to the complexities like the human body.

The respiratory calorimeter has some Limitations.
1) Assumptions and variability:Energy expenditure calculation is based on different assumptions and equations based on oxygen consumption and carbon dioxide production. Body Energy expenditure calculation can vary because of metabolic rate, energy use, and respiratory exchange ratio.
2) Adaptation duration: During long stays in calorimeters, metabolic rate and energy expenditure may be adapted, whereas in real life, body metabolic adaptation varies based on long-term environmental changes.
3) Specificity:The calculation of energy expenditure is based on rest or controlled activities, whereas in free-living conditions, the body energy expenditure varies as a result of various types of physical activity, dietary patterns, and other factors such as stress.
Therefore, respiratory calorimeters have contributed to our understanding of energy metabolism, they are not the entire story. 

CALORIES RESTRICTION AND WEIGHT LOSS: Even as a hypothetical, if we consider calories, it would contradict the bodies mechanisms related to Calories restriction and calories surplus.

The quality of food is more important than the quantity of food.

Food that has more protein can help you lose weight faster than food that has fewer calories but more carbs. PMID: 14525681
The amount of energy extracted from fibre is less than that of other carbohydrates due to incomplete absorption of fibre, and therefore the number of calories extracted from fibre is less than that of other carbohydrates. PMID: 15113737
The 2019 Study showed that participants lost weight on an unprocessed diet and gained weight on ultra-processed, even though the calories were the same.PMID: 31105044
Which means intake of high-protein/fat and low carbohydrate food without tracking calories will not lead to weight fat (fat gain).

1000 calories from sugar on a Calories restriction Diet should not be able to store fat. A calorie of carbohydrate and a calorie of protein both have the same amount of stored energy, but those calories in bodies behave quite differently.

Eg: Person A eats 1500 calories only from carbs and Person B consumes 1500 calories from protein, fats, and carbs. Now who will retain muscle mass and hormonal balance? Person B and because it will retain Muscle Mass and regulate hormones properly. Just because of Protein and fat intake, its total metabolism will be different from person A. Now they both may lose fat because of the same calories that are due to metabolic adaptation. But the point is whose metabolism will get sluggish and who will gain more fat after coming out of calorie restriction.

CALORIE RESTRICTION AND SLUGGISH METABOLISM:Several studies have shown that calorie restriction can sluggish the metabolism by decreasing RMR and NEAT and burning fewer calories as a survival mode. Its impact remains longer even after stopping calorie restriction, and hence people gain weight easily once they get off their calories restriction diet.PMID: 20935667 PMID: 23404923 PMID: 27136388  PMID: 18198305  PMID: 21292847

The theory of reducing caloric intake leads to weight loss is false, since decreased caloric intake necessarily leads to decreased caloric expenditure. The body reduces its caloric expenditure to meet the lower caloric intake, this adaptation occurs immediately and remains long term. So if anyone eats 500 calories less, than body will burn 500 fewer calories, resulting in no weight loss and this is not thermodynamics it’s the BMR which remains stable.

Eventually, calorie restriction is hard to maintain and biology needs a correct nutrition approach.

Hormones

Once we came to know that calories are more important than macros, now it’s time to figure out the importance of Macros in how carbohydrates, protein, and fats respond to different hormones.
If we say calories are like bodies budget like companies have a budget, so let’s understand first company budget is fixed, salaries of employees and other debits, but the body budget is not fixed just because Energy expenditure is variable. It keeps on changing every single day and to take care of that we have two hormones, Leptin and Ghrelin.

It’s not how many calories you eat that makes the body fat, but how many calories the body requires sustaining the Body will make the body fat or lean. This is decided by metabolism.
That also doesn’t mean one has a slow or fast metabolism, but there is a difference in individual metabolism due to many factors, we give it the name Sluggish metabolism.

For Eg Person A and B, both have the same height, age & gender, but Person A is lean & Person B is obese on this basis Person A requires more calories compared to person B just to sustain life. Does that mean Person A is overeating? Of course not. Both people have to consume calories to sustain life.

A body with the same height, size, body composition produces different results on the same calories.Eg: A man carries more muscle & less fat than a woman with the same height & age because of testosterone. A 20-year boy will carry less fat than a 40-year-old because of muscle loss.

There is an inverse relationship between Muscle & Fat. When you restrict calories and nutrients, the focus of cells shifts from growth to survival, on a Cellular basis, mTOR drops, and AMPK rises, which favors muscle breakdown.

The intermittent fasting, ketogenic and carnivore communities always refer to the hormone ‘Insulin’ and its high level due to sugar or excess carbohydrates is a root cause of obesity, type 2 diabetes, PCOS, cancer, and almost all the diseases and disorders in the human body.
They also claim that intermittent fasting has benefits like an increase in Growth Hormone, Autophagy, and Fiber is overestimated. Furthermore, fasting is one of the oldest remedies in human history and practice of every culture and religion on earth.

Hence, Obesity (insulin insensitivity, leptin insensitivity) is a hormonal problem, not a calorie (overeating) problem!
From here, the discussion takes a new direction, called HORMONE.

When we eat food, our body response to it with hormones according to food composition.
For
carbohydrate intake, the hormone insulin is released, a hormone whose functions are uptakes of glucose into cells, conversion of excess glucose into glycogen, Inhibition of Gluconeogenesis and conversion of glucose into fatty acids (Lipogenesis). Protein-rich foods trigger the release of hormones like glucagon, which regulate blood glucose through glycogenolysis, gluconeogenesis, and inhibition of glycolysis. Insulin-like growth factor 1 (IGF-1) promotes tissue growth and repair.
Fat intake triggers the release of gut hormones, such as cholecystokinin (CKK) which stimulates the release of bile, Regulating Satiety and Slows Gastric Emptying and peptide YY (PYY) which also regulates satiety and Slows Gastric Emptying.

Now Insulin is the hormone which makes fat hence, the body will gain fat or reduce fat is based on hormones and not calorie restriction.100 calories will make fat or burn fat is depending on hormones and not calories. The total number of daily calorie intake is not important but what the body does with those calories is important and so there is a need to change the hormonal system in our body. It was taught that reduce fat intake because fat contains double the number of calories.

In 2007 Study showed that a single meal per day found significantly more fat loss and no muscle loss, compared to eating three meals per day, despite the same caloric intake.PMID: 17413096

In 2011 Study showed that the combination of intermittent fasting with caloric restriction is effective for weight loss.PMID: 23171320

Calories Surplus

Turning protein into energy requires more energy by our body compared to carbs or fats. The conversion of alanine to glucose during gluconeogenesis (production of glucose from amino acids and other substrates) requires 6 ATP molecules, and the conversion of pyruvate to glucose also consumes 6 ATP molecules. Moreover, 4 molecules of ATP are required to dispose of the nitrogen as urea. Furthermore, making and breaking down proteins is expensive because they require a lot of energy to do.PMID: 15282028 PMID: 21723500 
Thus, one does not have to worry about calories. Intake of a high-protein/low-carbohydrate/increased fibre diet leads to a far smaller net energy (weight) gain than intake of a typical higher carbohydrates diet.

Insulin is not an anabolic hormone.

The Ketogenic community claims

Dietary carbohydrates are not essential for survival; hence it raises questions about the amount and type of this macronutrient needed for optimal health, longevity, and sustainability, and as a result of the consumption of carbohydrates, blood glucose and insulin levels are not maintained at a normal level, resulting in an imbalance between the leptin-ghrelin hormone, which regulates appetite. Therefore, counting calories is not important, but prioritizing macros is important to regulate appetite and blood glucose level because this constant fluctuation has led to hunger and obesity. Furthermore, our ancestors ate lots of fat and protein and very little carbs, like fruits as a desert, and they were the fittest people to walk on earth.

MECHANISM 

Biochemistry:Carbohydrate is the only macronutrient with no established minimum requirement.
The body has a glucose tolerance level and no fat tolerance level; therefore, there is no such thing as fat tolerance in scientific literature.
Lack of protein causes kwashiorkor and lack of energy causes marasmus. However, there is no specific carbohydrate deficiency syndrome.

Ancestors (Paleolithic era -Neolithic era) : Our ancestors were primarily hunter-gatherers in that is a Paleolithic era, also known as the Stone Age, had no access to agriculture (Grains—the seeds of cereal grasses, carbohydrates). Moreover, they don’t only consume animal foods but also plant foods with greater carbohydrate availability than leaves, including ripe fruit, honey, and eventually cooked starchy foods.PMID: 24746602 PMID: 26591850
This diet had a higher nutrient and energy density, which allowed for the development of a smaller gastrointestinal tract, this smaller gastrointestinal tract has been helped the brain use less energy for digestion and nutrient absorption.PMID: 17439362

Due to the development of agriculture, the transition from the Paleolithic era to the Neolithic era led to the cultivation of crops such as wheat, rice, corn, and other grains, which became staple foods in various regions, approximately 10,000 to 12,000 years ago years. Technology and Transportation of plants and animals further influenced human diets.

Gluconeogenesis :The liver can produce glucose (a simple form of carbohydrate) through a process called gluconeogenesis which synthesize glucose from non-carbohydrate sources, such as amino acids, glycerol and lactic acid to make sure ensures that the body can maintain adequate blood glucose levels even in the absence of dietary carbohydrate. Hence, dietary carbohydrates are not essential for survival. Science (Biochemical reaction) hasn’t found any important role for dietary carbohydrates in our bodies yet.

 Leptin – Ghrelin: Reducing carbohydrate intake leads to lower insulin levels and more stable blood sugar levels, which influence the balance between leptin and ghrelin hormones, improving sensitivity and resulting in better appetite regulation, reduced hunger and weight management.  

Fibers:Fibers are garbage, provide no energy, and It’s just hyped.

Nutrient density:Animal organs are nutrient dense and have high bioavailability form.

Anti nutrients:Almost all Carbohydrates source contain anti nutrients.

Calories Matter 

Bomb calorimeters remain a valuable tool for finding the energy content of food in a regulated manner. It helps estimate energy intake and understand energy balance. 

That doesn’t mean “A calorie is not a calorie”. A diet rich in protein and fats can have a significant impact on the caloric balance by influencing metabolic rate, the thermogenic effect of food, and satiety. This prevents overeating (calories) and therefore the body gets needed calories without leading to weight gain or fat gain. 

A calorie is a calorie, all calories are equal, but not all sources of calories have the same impact on energy expenditure. That means counting the calories but priorities food on bases of Satiety, TEF, and their role in the body.

Obese people appear to have decreased activity adenylate cyclase enzymes in fat cells, which is partially reversed by caloric restriction.PMID: 2166354

Will you lose weight differently if you change the ratio of Fat and Carbs by keeping the Protein same, but still eat the same number of calories? 
In 1992 study with a metabolic ward settings with same calories diet but different macros’ ratio (protein-15%, carbohydrate15-85%, and fat-0-70%) showed that caloric restriction seen weight loss and not macronutrient ratios. PMID: 1734671

Will you lose weight differently if you have changed the ratio of carbohydrates, but still eat the same number of calories?
In 1996,2 Studies showed the same weight loss results with a low or high carbohydrate content (15%,25% and 45%) diet.PMID: 8968851

Will you lose weight differently if you only eat carbs and protein and not fat, but still eat the same number of calories?
A 2004, study with no fat and a different protein and carbohydrate ratio (15% P, 55% C, and 30% P, 40% C) diet with the same number of calories showed the same weight loss results.PMID: 15007396

Will you lose weight differently if you only eat fat and protein and not carbs, but still eat the same number of calories?
In a 2005 study showed the same weight & fat loss when compared a low-fat/high-protein diet with a high-fat/standard-protein diet.PMID: 15817850

Will you lose weight differently if you change the ratio of carbs and proteins by keeping fat the same, but still eat the same number of calories?
A 2005 study showed the same weight loss when compared a high-protein diet (40% C, 30% P, 30% F)  with the high-carbohydrate diet (55% C, 15% P, 30% F) in type 2 diabetes patients.PMID: 15800559

Several studies have shown that the same calories with different macros ratios have shown the same results. Calories restriction led to weight loss, but not Macronutrient ratios.PMID: 30734418 
PMID: 12816768 PMID: 17023708
PMID: 10372237
PMID: 18025815

A 2008 study showed improvements in reproductive function, cardio metabolic abnormalities, and hormonal parameters in women with PCOS with only calorie restriction, but the addition of regular aerobic or combined aerobic-resistance training did not provide any additional improvement. The only exception was changes in body composition.PMID: 18583464.

In 2015, a study showed dietary fat restriction results in more body fat loss than carbohydrate restriction in people with obesity.PMID: 26278052

A 2020 study found that many popular diets for weight loss don’t have scientific evidence to support them.
Currently, there is no optimal weight loss diet that is effective for all individuals.
Food quality is important in a weight loss diet that aims to improve health.
A diet that creates negative energy balance is important to lose weight.
It’s very important to stay on track to succeed.PMID: 31525701

Is an excess of protein intake exceeding the total calories’ requirement a factor in halting weight loss or leading to weight gain?

CALORIE RESTRICTION AND SLUGGISH METABOLISM:
Basal Metabolic rate (BMR) and Non exercise activity thermogenesis (NEAT) are the important components of Total daily energy expenditure (TDEE) they are not the whole metabolism equation. In some cases, like, people with hypothyroidism may experience reductions in BMR of up to 25%.PMID: 27465032 but BMR is just, one component of TDEE. There
 are other components like Thermic effect of food (TEF) and exercise activity thermogenesis (EAT).
TDEE = BMR + TEF + NEAT + EAT hence, with current understanding, whenever a word metabolism adaptation comes that means TDEE and not just it’s some components.
In fact, studies have shown that fasting decreases thyroid hormone and energy expenditure in the short term.PMID: 31298652 PMID: 26185280

Correct, During caloric restriction and weight loss, a phenomenon known as’ metabolic adaptation’ occurs, where your body reduces energy expenditure to preserve energy stores. PMID: 21677272
But there is a misinterpretation, metabolic adaptation doesn’t occur immediately when someone reduces calorie intake, moreover it adapts when the body loses a certain amount of body weight, which is a slow process.It becomes stronger when someone has lost a huge amount of body weight.
PMID: 27136388
PMID: 28925405
PMID: 31204775
otherwise, studies have shown far less metabolic adaptation in response( 5-15% reduction in BMR) to dieting.PMID: 32386226
PMID: 33762040 
PMID: 26399868 Moreover, Studies have shown that Metabolic adaptation occurs even with Intermittent fasting PMID: 32986097 
PMID: 32316561
PMID: 32844188 PMID: 30429127

Basal metabolic rate remains absolutely stable, is an entirely wrong statement. The body tries to compensate for changes in energy intake (CI) by adjusting energy expenditure.PMID: 22434603
PMID: 28193517
PMID: 22065844

There is no evidence that low-carb diets, low-glycemic diets, or intermittent fasting/time restricted feeding diets are superior for reducing metabolic adaptation.
People aren’t tracking calories, which does not mean they aren’t restricting calories, which they do in IF without knowing it.
IF/TRF works, however, it works by creating a calorie deficit through reductions in food intake, not by controlling insulin or increasing metabolic rate.
Criticizing some macronutrient, food, or putting any hormone in to a bad or good category makes diet rigid and through which people get results, but once they get out of diet, they binge-eat this food, which they avoided getting results, and thus end up with more body fat than people with a flexible food mindset.
The methods of intermittent fasting/ketogenic diets, which aid in weight loss and type 2 diabetes treatment, can be effective, but the reasons for their effectiveness are misleading, unsupported by evidence, and the long-term practicality is a question mark.

Our thoughts 
All these debates are about the benefits for people of being fit, healthy and not to get in obesity.
It is not necessary to maintain a calorie deficit for a long time. One can enter a calorie surplus and then return to calorie restriction, which allows one to build up more muscle and maintain body fat eventually.Are there any scientific data that supports a long-term body weight maintenance approach apart from calorie restriction?
These methods are suitable for people who wish to enhance their appearance, such as bodybuilders who are competing or not competing and whose goal is to improve their appearance by gaining muscle mass and maintaining a low body fat percentage, which is, undoubtedly, a challenging path. Moreover, many people may have a dream, but can’t get to that level due to many factors.
From observational data, intermittent fasting and ketogenic approaches may be helpful for people who aim to be fit and healthy without having to track calories. Will this be successful eventually, or will it help to keep improving aesthetics, gaining muscle, and maintaining body fat? Future scientific data is needed. 

 

Hormones

MECHANISM

Insulin has gotten a bad reputation because of carbohydrates.

High Carbohydrate Diet → High Insulin → Increased Lipogenesis/Decreased Lipolysis → Increased Body Fat → Obesity.

Low Carbohydrate Diet → Low Insulin → Decreased Lipogenesis/Increased Lipolysis → Decreased Body Fat.

This Theory of obesity is based on the ‘carbohydrate-insulin model’ proposed by obesity researcher David Ludwig. In some places, it is also placed as “hormonal obesity theory.” PMID: 29971406. Most of the scientific community does not believe that the carbohydrate-insulin model is well-supported by evidence.
Scientific findings have greatly weakened the argument.PMID: 29971320 PMID: 28074888

In 2007, a review study showed that there is no clear pattern that people with higher insulin levels gain more weight than people with lower insulin levels. Out of 22 studies, 5 found that higher insulin levels were linked to more weight gain, 8 found that higher insulin levels were linked to less weight gain, and 9 found no connection. PMID: 17130851

Does a high-carbohydrate (higher-insulin) diet would lead to more weight gain?
In 1995 and 2000, two tightly controlled studies showed that high-carbohydrate and high-fat diets produce about the same amount of fat gain when calorie intake is the same.PMID: 7598063 PMID: 11029975

The insulin model doesn’t lack any scientific backing, the observation states that people with diabetes gain weight when they start taking insulin, but everything needs a context. Fat cells require a certain amount of insulin to store fat efficiently, otherwise if insulin signaling is severely impaired, fat storage is ineffective. On the other hand, people with uncontrolled diabetes excrete glucose in their urine (Glycosuria), which is why they tend to lose weight and fat. PMID: 17890232 PMID: 28509408 PMID: 19817944
It makes sense that restoring the insulin signal in people with type 2 diabetes will promote weight gain, but currently the evidence is weak. However, we support the arguments and research is ongoing.

Intermittent fasting and low-carb diets are practicable approaches to reducing body fat, but they are not magic.
In 2015, 2016, 2018 (3 Studies) several Systematic reviews and Meta analysis showed that Intermittent fasting is a rightful way to control calorie intake and promote weight loss, but it does not appear to be superior to standard calorie restriction and the degree of weight loss is approximately the same as standard calorie restriction.PMID: 26135345 PMID: 26603882 PMID: 29419624  PMID: 28975722 PMID: 30583725

The 2007 Study also showed that eating one meal per day had a higher total cholesterol, blood pressure, and hunger and desire to eat than eating three meals per day. Due to the lack of supervision during most meals, it is not certain that the calorie intake estimates provided in the paper are accurate.PMID: 17413096

The 2011 study also showed that the group followed a moderately restricted calorie diet with periods of extremely low caloric intake also lost weight without the fasting, but less than other groups, and that the days of extremely low caloric intake were equivalent to fasting.PMID: 23171320

A review study in 2017 revealed that intermittent fasting reduced triglycerides but didn’t affect cholesterol; intermittent fasting reduced insulin resistance and lowered insulin concentrations, but didn’t affect glucose levels; and intermittent fasting also reduced blood pressure, but with a 6% decrease in body weight. This showed that the benefit may come from weight loss itself rather than from the diet used to lose weight. PMID: 28137935

There is even less information available on cancer regarding intermittent fasting, most of which relies on animal studies and epidemiological data.
A 2014 systematic review and meta-analysis study showed both general caloric restriction and ketogenic diets are effective at reducing cancer in animals, while intermittent fasting was not.PMID: 25502434

Insulin stops fat from breaking down and makes fat go to adipose tissue. But how it affects body fat is more complicated.PMID: 2573554 
PMID: 27931032
When it comes to losing body fat or gaining body fat, there is a simple equation, Body Fat Balance = Fat stored – Fat oxidized. 
Fat gets released from fat cells (lipolysis) which is stored in the form of triglycerides and which then gets into the beta oxidation process to form acetyl-CoA and then enters the Krebs cycle for energy production/oxidative respiration to produce adenosine triphosphate (ATP).
Now, if we consider that Insulin hinders this process, then we need to compare diets that are equal in calories but differ in insulin response by varying the amount of carbohydrate vs. fat in the diet while keeping protein constant because protein increases energy expenditure because it’s not calories, it’s hormone which makes body fat. Moreover
, a pharmaceutical drug Semaglutide, which effects large reductions in fat mass (due to appetite suppression) and importantly increases insulin secretion but over the long term, improves insulin sensitivity due to weight loss.PMID: 33567185

INSULIN AND HUNGER:The evidence, of insulin, makes you feel hungry is extremely thin, and it is also against a mechanistic perspective. Insulin acutely suppresses appetite, PMID: 16933179. Insulin increases leptin secretion, and leptin is the major satiety hormone. PMID: 8858224 Moreover, studies have shown that Insulin decreases energy intake in rodents and humans when infused in physiologic concentrations.PMID: 6380652 PMID: 2189441 PMID: 6395152
PMID: 22344561
and also shown no differences in energy expenditure, which can make feel hungry.PMID: 28193517

Insulin inhibited weight loss either by reducing body energy expenditure (reducing calorie burning) or by increasing energy intake (eating more calories), Insulin can’t produce physical substances or matter from nothing.
It is true that during the fasting period, insulin gets low but during the feeding period, the large single meal would give a massive insulin response. Hence, during fasting, fat oxidation will increase but after feeding this will get balanced by an increase in the amount of fat storage.
On the other side, of the coin, protein is quite insulinogenic, in some cases, like whey protein, is more than carbohydrates.PMID: 16002802 PMID: 24611935 
PMID: 22470009 protein is just as powerful at stimulating insulin as the carbohydrate.

In 2008 study showed that a meal that contained 485 calories, 102 grams of (High) protein, 18 grams of (low) carbohydrate, and almost no fat exaggerated insulin response in the obese subjects compared to lean, probably due to insulin resistance.There was no relationship between the glucose response and insulin. In other words, even though obese individuals had higher insulin levels, it didn’t necessarily mean they had significantly higher levels of glucose in their blood. This suggests that their bodies were having trouble effectively using the insulin to regulate blood sugar levels, despite the increased production of insulin.PMID: 18249201

In 2010 study showed 21 grams of protein + 125 grams of carbohydrate (high-protein meal) response higher insulin (not statistically significant) compared to 75 grams of protein + 75 grams of carbohydrate with same calories (675K) PMID: 20060863
The point is that the high-carb meal had twice as many carbohydrates and a higher glucose response, but insulin secretion was slightly lower. Furthermore, insulin (45 uU/mL at 20 minutes) reaches its peak faster in the high-protein post-meal than in the low-carb meal (30 uU/mL). The higher insulin response was associated with a greater suppression of appetite. 

In 2010 study showed 4 different types of protein shake (11 gm carbs and 51 gm protein) produced a different insulin response between the proteins, with whey producing the highest insulin response, peaking within 30 minutes and coming back down quickly at 60 minutes. Whey protein, which caused the greatest insulin response, caused a drop in blood glucose. Again, insulin response was associated with appetite suppression PMID: 20456814

But why whey protein cause rapid rises in insulin? Amino acids can directly stimulate the pancreas to produce insulin, without having to be converted to glucose first.  For example, the amino acid leucine directly has   a dose-response relationship, the more leucine, the more insulin is produced.PMID: 20500788 PMID: 6800820

Moreover, one study found 240 calories of beef raised the same insulin secretion as 240 calories of brown rice and 240 calories of fish raised the same insulin response as 240 calories of white rice.

Foodinsulin AUC
Brown Rice6240 ± 616
White Rice 8143 ± 683
Beef 7910 ± 2193
Fish 9350 ± 2055

PMID: 9356547

Hence, rapid spikes in insulin is not a problem because even Protein does as well!

If insulin was truly the cause of obesity, then high-protein diets also be harmful for fat loss and insulin sensitivity, but actually data shows the opposite.PMID: 15051856
PMID: 19158228 PMID: 16046715 PMID: 12566476
PMID: 18810296

In 2017, a meta-analysis of over 20 controlled feeding studies showed no differences in fat loss between diets that were high in carbohydrate vs. those low in carbohydrate when calories and protein were equated. Actually, this study showed that people who ate less fat were more likely to lose fat. But this difference is probably not important in clinical practice.PMID: 28193517


In 2016, a meta-analysis showed that when a very low-carb (~30g/d) ketogenic diet compared with a very high carb (>300g/d) diet and calories/protein were equated, fat
loss slightly favored the low-fat group also total daily insulin levels that were ~47% lower than the low-carb group. PMID: 27385608 
But why such results? It is against the biochemistry of insulin! This is because when calories are the same, the body creates equilibrium to balance body fat. on a High Fat Low-Carb Diet, fat burning increases significantly PMID: 27385608
but also fat storage increases and on a low fat, high-carb diet, fat burning is less but PMID: 12908902 fat storage is also less. Hence, equals the net fat balance. Hence, to break this equilibrium, one needs to get into a calorie deficit despite following the LCHF or HFLC diet.

Studies have shown similar improvements’ insulin sensitivity like HbA1c when compared to intermittent fasting, time restricted feeding and alternate day fasting with normal calorie restriction.PMID: 31614992 
PMID: 29419624
PMID: 32060194
So, fat loss doesn’t happen because of low insulin; it happens by restricting calories.
The Body Can Synthesize and Store Fat Even When Insulin Is Low. There is an enzyme in your fat cells called hormone-sensitive lipase (HSL).HSL helps break down fat. Insulin suppresses the activity of HSL, and thus suppresses the breakdown of fat. Hence, the biggest misconceptions are that to store fat, insulin is needed. However, even fat also suppresses HSL even when insulin levels are low.PMID: 9950782 this means fat loss can be hindered even when carbohydrate intake is low, but calorie intake is high.

Hormones such as insulin and thyroid do play a role in weight loss or weight gain by modifying either energy intake or energy expenditure, but they are not the dominant factor.
If fasting is more important than caloric restrictions to control insulin, then why do these data not show differences in fat loss when calories are equated?

Calories Surplus

A higher quantity of food may be required to exceed one’s caloric expenditure on a high-protein fat/low carbohydrate diet, but it can still be done and lead to weight gain. Therefore, the quantity of food must be controlled.

In 2000 Study showed that overfeeding both carbohydrates and fat are equally fattening.PMID: 11029975

Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling PMID: 20484484

If yes, then how much weight will a sedentary and training person put on a high-protein fat/low carbohydrate diet without tracking calories? Will this lead to obesity? It requires further studies! 

The Ketogenic community claims

 1) Are Dietary carbohydrates are not essential?

2) Does carbs makes imbalance between the leptin-ghrelin hormones?

3) Does high fat and protein regulate appetite?
.Insulin acutely suppresses appetite, PMID: 16933179

4) Does our ancestors eat lots of fat and protein and very little carbs?

MECHANISM 

Our ancestors had no access to agriculture (and therefore carbohydrates) is not entirely accurate.Before the development of agriculture, the human diet consisted of a wide variety of plants, fruits, Honey, nuts, seeds, roots and tubers, all of which provided carbohydrates.The types and amounts of carbohydrates consumed by early humans would have varied based on geographical location, climate, and seasonal availability of food.


As the brain got bigger, it needed more energy to keep growing and thinking better. But the body couldn’t process and get enough energy from food, so we needed a bigger stomach to get enough energy from a low-energy diet.
Carbohydrates are a source of energy that humans can get easily and quickly.It provided an evolutionary advantage that allowed humans to divert major energy sources away from the digestive system towards the development and functioning of the brain.
This energy saving allowed the brain to grow and evolve while keeping a smaller, more energy-efficient gastrointestinal tract. 

Carbohydrates are the body’s main source of energy.The brain and heart prefers glucose as its primary fuel source, whereas red blood cells exclusively use glucose for their energy needs.It also spares protein from being used as an energy source.

Though carbs are not dietary, essential, Glycogen in the liver and muscle can play an essential role in providing energy and supporting various physiological functions. It is important to note that carbohydrates are the bodies preferred and most efficient source of energy, especially for the brain and muscles during intense physical activity.
Dietary fiber, is essential for maintaining regular bowel movements, and supports a healthy gut microbiome, which is crucial for digestive health.

5) Are carbs important for intense training?

GLUCAGON: A common theory is that even though protein triggers insulin production, this won’t suppress fat-burning because it also triggers glucagon production, which counteracts insulin’s effects, and hence glucagon surpasses it and increases lipolysis to cancel this out.
These theories that glucagon increases lipolysis are based on three things.1) Human fat cells have glucagon receptors, PMID: 8263154. 2)Glucagon increases lipolysis in animals, PMID: 32506830. 3) Glucagon has been shown to increase lipolysis in human fat cells in vitro (in a cell culture) PMID: 2755873.
But using modern techniques, the study has shown that glucagon does not increase lipolysis in humans as well as in vitro PMID: 11344211
PMID: 11238513
what happens in vitro isn’t necessarily what happens in vivo (in your body)!
But why whey protein stimulate Glucagon and Insulin both? Insulin secretion will cause a rapid drop in blood glucose if no carbohydrate is consumed with the protein, whereas Glucagon prevents this rapid drop in blood glucose by stimulating the liver to produce glucose.

may have developed a relapse of acute variegate porphyria.PMID: 6826807

The muscle fibers most retained by Calories Restriction are the slow-twitch fibres, which are less prone to muscular growth.

Law of conservation of energy:

To maximize muscle growth (also known as muscular anabolism or hypertrophy), hypercaloric conditions (a caloric surplus) must be maintained to prepare the physiological environment for growth.

While muscle development is possible under caloric maintenance and deficit situations, it cannot be maximized unless an excess of energy is eaten.

Hypocaloric conditions compromise nutrient & energy availability. This suppresses anabolic signalling and muscle protein synthesis (MPS), ultimately compromising the rate of muscle growth.

Maintaining a caloric surplus promotes muscle development by boosting not just anabolic signalling and MPS, but also by supporting the rising demands of progressive resistance training volume.

EAT TO TRAIN, DON’T TRAIN TO EAT

For Untrained Population, Approximately 20-40% above maintenance needs (~500 – 1000 kcal) due to greater potential benefit of a predominance of carbohydrate.

For optimizing high-intensity fuelling requirements of progressive resistance training, an energy surplus should focus on increasing carbohydrate. 

For trained Population, Approximately 10-20% above maintenance needs (~250-500 kcal) due to lesser potential benefit of carbohydrate predominance.

More experienced trainees nearing their potential have less capacity for surplus energy partitioning into lean tissue and may prefer to utilize protein-focused surpluses.

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