March 11, 2022 by Dr Kar

(Updated from an earlier version on the MDS Program website)

Often we hear that Intermittent Fasting/Time-Restricted Eating (TRE/IF) is just a different version of a low-calorie diet. Is that true? While it is true that when you follow a TRE/IF way of eating, you do end up eating less food than you would otherwise do, the critical difference is on TRE/IF you don’t have to deliberately, consciously monitor the amount of food you eat; it happens by default! You feel less hungry! (For convenience, I will consider a fasting period of 24 hours or longer as Intermittent Fasting, while a fasting window of fewer than 24 hours is Time-Restricted Eating)

On a low-calorie diet, you get what I call the “Revenge of the Deprived Calorie.” Hunger is worse, which is one of the reasons why this diet is not sustainable long-term. ⁽¹⁾ Ref Additionally, on a low-calorie diet, your metabolic rate reduces. Reducing your metabolic rate is not good for weight loss. ⁽²⁾ Ref

Are there any other factors that differentiate a low-calorie diet from TRE/IF?

COMPARISON OF LOW-CALORIE DIETS WITH INTERMITTENT FASTING

FEATURES	LOW-CALORIE DIET	INTERMITTENT FASTING
Weight Loss	Yes, but not sustained over long-term	Yes. Long-term studies have not been done, but case reports show long-term benefits are maintained.
Fat-Free Mass (FFM)	Reduced	Less reduction compared to a low-calorie diet.
Hunger	Often not reduced. This is why compliance is difficult	Hunger reduced.
Muscle Loss	May be expected	Usually, no muscle loss
Ease of following the plan	Difficult for some	Most people find this easy to adapt to their lives.
Brain Function	Usually unchanged	Most people report better brain function. Less “brain fog.”
Metabolic Rate	Usually reduced	Metabolic rate increased
Fasting Insulin	Reduced	Higher reduction than in calorie-restricted diet
Growth Hormone (GH) (Preserves muscle mass)	No change in GH	Increased secretion of GH

Weight Loss

In studies comparing calorie-restricted diet with intermittent fasting, both are equally effective for weight loss. In clinical studies, these are called Daily Calorie Restriction (DCR) versus Intermittent Calorie Restriction (ICR). However, the type of weight loss was different in the two methods. ⁽³⁾ Ref

Change In Body Composition

Although total weight loss is the focus of most weight loss programs, the change in body composition significantly impacts long-term results. What do I mean by that?

Your body weight includes fat, muscles, bone, organs and body fluids. You are interested in fat loss, and you don’t want to lose bone and not your muscles! Fat-free mass (FFM) is the part of your weight that includes everything OTHER than your body fat.

Fat-free mass (FFM) is extremely important for long-term weight loss. FFM decides your metabolic rate. The higher the amount of FFM, the higher is your metabolic rate. Therefore, you don’t want to lose FFM.

In most studies, weight loss by Daily Caloric Restriction resulted in a 75–80% decrease in fat mass and a 20–25% decrease in FFM. However, Intermittent Caloric Restriction showed a 90% weight loss of fat and 10% weight loss of FFM.  ⁽⁴⁾ Ref

In a study on postmenopausal women ⁽⁵⁾ Ref, the authors looked at comparing the long-term (1 year) effects of moderate versus severe energy restriction on body composition. Those in the moderate energy restriction group reduced their energy intake by 25-35%. The severe energy restriction group reduced their energy intake by 65-75% for four months, followed by eight months of moderate energy restriction.

What did they find?

The amount of weight lost by those on the severe energy-restricted diet was about two times more than those on moderate calorie restriction. The loss in muscles was also proportional to the weight loss. This means that people who lost more weight also lost more muscle mass (FFM).

Bone Loss:

A somewhat disconcerting effect was seen on Bone Mineral Density (BMD). Those women on the moderate energy-restricted diet lost about as much bone density as similar-aged postmenopausal women. Still, those on the severe energy-restricted diet didn’t fare as well.

In the severe energy-restricted group, the bone loss continued over a whole year! These women were asked to eat proteins at 1 gram/kilogram of body weight, and the meal replacement product they used contained adequate vitamin D and calcium. (Bone density is affected by protein intake, vitamin D3 and calcium). The women were not on hormone therapy.

Hunger

One of the most prominent weight loss problems by using a low calorie or calorie-restricted diet is hunger, and weight regain. The increase in hunger (The Revenge of The Deprived Calorie) is compounded by a reduction in metabolic rate.

In a study reported in the International Journal Of Obesity, the authors looked at hunger and feelings of fullness in a group of men and women who had successfully lost weight on a very low-calorie diet. At the end of 1 year, they maintained a 15% weight loss, but hunger had increased, though post-meal fullness had increased as well. Women felt hungrier than men! As you can see in the image Fig 1, at 13 weeks, hunger was higher than at the end of 1 year. Interestingly, hunger levels were higher after weight loss than at baseline. ⁽⁶⁾ Ref

Alternate-day fasting and hunger: In a study of alternate-day fasting for weight loss, there was no increase in hunger at the end of 8 weeks of the study period. ⁽⁷⁾ Ref

Many factors control hunger. However, eating more protein and fewer carbohydrates keeps you satiated longer.

Number of Calories Consumed

Reducing daily calorie intake below the baseline is one of the most typical methods used for weight loss. The calorie restriction varies, and most calorie-restricted diets aim to reduce daily calories by at least 15-40% of the baseline energy requirement.

In studies on alternate-day “fasting,” where participants were allowed to eat 25 % of their calculated calorie requirement on ‘fast” days and 100 % on non-fast days, they found that people ate 20–30% of their energy needs on “fast “days, while on the eating days, they ate 100–110% of energy needs. Therefore, were they eating more or did it even out over several days?

When they calculated energy restriction over 48 hours (fast+eat days), they found that most people achieved 35-38% energy restriction. This was despite eating more on “eat” days and not consciously counting calories. However, those on daily calorie restriction managed only 18-23% energy restriction daily.

Metabolic Rate

Many of you ask me, “How can I increase my metabolism?” What does this mean?

Basal Metabolic Rate (BMR) is the number of calories your body needs to maintain essential body functions like breathing, circulation, digestion, temperature regulation. BMR is used interchangeably with the term Resting Energy Expenditure (REE). REE includes BMR plus the energy used in sitting, moving around etc. REE has a massive impact on long-term weight loss.

In the MATADOR study, men with obesity were divided into two arms, one arm on continuous energy restriction and the other on intermittent energy restriction. Weight loss reduces REE. However, in this study, they found that people on intermittent energy restriction had a minor reduction of REE compared to those on continuous calorie restriction ⁽⁸⁾ Ref

I have mentioned the “Biggest Loser “Study before. They followed a low-calorie diet. After six years, they were found to have a lower metabolic rate. ⁽⁹⁾ Ref

Insulin Levels

Fasting insulin levels are an important factor in weight loss. As this paper reports, they observed that higher fasting insulin levels were related to a higher weight over ten years. ⁽¹⁰⁾ Ref. Therefore, the eating plan that works best at lowering insulin levels should work better for fat loss.

Food and Insulin:

When you eat food, your insulin levels rise. Eating carbohydrates spike your insulin and blood glucose levels the most, followed by proteins and fat. As you can see in the image below (Fig.2), the graph in red shows the levels of insulin throughout the day in a person who is eating three meals and two snacks a day. The higher red peaks are the major meals, and the smaller ones are snacks.

The blue graph represents insulin levels while fasting. As you can see, the “area under the curve” (AUC) with normal eating is much bigger than the area under the fasting curve.

Your insulin levels do not increase when you don’t eat, i.e., when you fast, your insulin levels fall.

Growth Hormone (GH)

From the perspective of retaining muscle mass, Growth Hormone levels are critical. Adults with GH deficiency have more belly fat, worse lipid profiles and increased heart disease risks. ⁽¹¹⁾ Ref

In a 5- day fasting study, levels of GH were higher than in people who were not fasting. In fact, on day 1 of the fast, GH levels were about three times higher than baseline! ⁽¹²⁾ Ref

Bottomline

• Continuous calorie restriction and intermittent calorie restriction (TRE/IF) both lead to weight loss.
• TRE/IF is easier to implement and stick to.
• Hunger is less on TRE/IF and therefore it is easier to use long-term.
• Severe energy restriction (aka low-calorie diet) leads to higher weight loss, but at the cost of higher bone loss.
• Insulin levels reduce more on TRE/IF than on a low-calorie diet.
• Growth Hormone levels increase with fasting. This helps in maintaining a leaner body.
• Fat-free Mass is preserved on TRE/IF versus on continuous calorie restriction (low-calorie diet).

March 2, 2020 by Dr Kar

Bodyweight set-point, Leptin, Insulin Resistance, Energy Balance.

(This article was posted on the mdsprogram.com website earlier)

Weight gain or more accurately, fat gain is a complex problem of hormones and the nervous (neuroendocrine) system. Most of you have lost weight in the past. However, did you regain all the weight? Some of you have probably reached a plateau in your fat loss. Why is that so?  We don’t have all the answers yet, but here is my effort at (hopefully) simplifying the science 

“Make everything as simple as possible but not simpler.” (Albert Einstein).

Why do I gain weight?

Complexity Of The Problem

As you can see in the graphic below, there are several factors that influence your body weight.

My goal in sharing the image above is to highlight the complexity of the problem. Something as complex as that definitely cannot be solved with solutions like “eat less and exercise more” or ” all you need is willpower” or “eat 3 meals and 3 snacks a day”.

Three Models to Explain Weight Gain

1. Calorie-In-Calorie-Out (CICO) Model
2. Carbohydrate-Insulin Model (CIM)
3. Energy Balance

1) Calorie-In-Calorie-Out (CICO) Model:

You gain weight because you eat more calories than your body can utilize. Therefore if you can figure out how to eat less and move more, you will lose weight. It is only a problem of having too little willpower! How well does that work?

If you have used this plan of Eat-Less-Move-More, you know that it doesn’t work in the long term! This model assumes that fat loss is a problem of personal shortcomings.

Years of research have shown that over the long term, your body weight is controlled by biochemistry, rather than mere will power.  On a low-calorie diet, the body fights back……The Revenge of The Deprived Calorie by making you hungry and reducing your body’s Resting Energy Expenditure (more on this later).

If calories were all that mattered, then it means eating 100 calories of chicken is the same as eating 100 calories of biscuits (cookies). You know that is not true! The two are very different in terms of the metabolic response in your body.

The CICO model has been abandoned by most obesity researchers. In fact, obesity researcher, Dr. Zoe Harcombe, calls this the “psycho diet”.Unfortunately, it still has a large following amongst people who are probably not as familiar with the science (Including doctors! I was one of them until I learnt more!). 

Now, wait a minute, you are probably thinking….”But I have lost weight by counting calories and eating less and moving more, so why is she saying it doesn’t work?”

Over a short period of time, a low-calorie diet may work, but we are talking about long-term fat loss.

The Biggest Loser Study:

The Biggest Loser is a reality TV show which included contestants who struggled with extreme obesity (BMI >40). Over a period of 30 weeks, the contestant who lost the maximum amount of weight was considered the winner. They had followed the eat-less-move-more method. They lost a lot of weight over a short span of time, but over the long term, it wasn’t that great.

A follow-up study ⁽¹⁾ Ref done after 6 years on 14 of the contestants showed that not only had they regained the weight, their metabolism had slowed down drastically.

2) Carbohydrate-Insulin Model (CIM) :

This model is based on the actions of the hormone insulin that is produced by your pancreas. According to the Carbohydrate-Insulin Model (CIM) of obesity, eating more processed, high carbohydrate and sugary food produces hormonal changes that promote fat deposition, increase hunger and reduce your metabolic rate. ⁽²⁾ Ref

You can see in the image below a comparison between the conventional model and the carbohydrate-insulin model of obesity.

You are probably familiar with the drug insulin, which is used as a prescription medication for the treatment of diabetes (Types 1 and 2). But here I am talking about the hormone insulin produced by your pancreas.

Insulin resistance is a condition where your cells become resistant to the actions of the hormone insulin. As Endocrinologist Dr. David Ludwig says, “Insulin is your fat fertilizer hormone.”

When you have insulin resistance you gain excess unhealthy fat in parts of your body like the abdomen (belly fat). Your body cannot manage your blood sugar levels well and over a period of time, you will likely develop type 2 diabetes.

Carbohydrates that you eat spike your insulin levels. Therefore, to lose weight you need to eat fewer carbohydrates than your body can tolerate. This carbohydrate tolerance level is different for each one of you. For some of you this carbohydrate tolerance level may be as low as 20-30 grams! As a reference, one apple is 20 grams of carbohydrate!

Personalized Blood Glucose Response (Video)

How will you know if you are Insulin Resistant?

Please check this infographic.

3) Energy Balance (or Energy Homeostasis)

At the centre of Figure 1 above is “Energy Balance”(I know you can’t read it clearly!). As you can see, all the different factors like food, activity, psychology etc. affect this important area.

Energy balance or homeostasis includes different biological processes that help your body maintain a specific weight. This is the body weight set-point.

What is the bodyweight set-point?

When you gain or lose weight, your body has the unique ability to go back to your previous weight. There are several mechanisms involving hormones, energy intake, energy expenditure and brain changes that will bring your weight back to where it was.

This bodyweight set-point applies to people who are overweight as well as to those of normal weight! You may have noticed that some of your friends have remained almost at the same weight for many years. They don’t seem to gain weight even when they eat about as much as you do! (However, they may not necessarily be healthy. Bodyweight is ONLY one measure of health).

Overfeeding studies ⁽³⁾ Ref done in people with obesity and lean people have shown that it is equally difficult for both to remain at a higher weight. Essentially your body defends a certain fat level, whether you are at a normal weight or have excess fat.

This is achieved by matching energy intake to energy expenditure over time. This is not as simple as it sounds. Energy balance is not merely eating food and spending food energy by exercising.

Rather than being a problem of simple passive accumulation of fat, obesity is a problem of disordered energy balance.

Leptin and Energy Balance: Should you test your leptin levels?

A few years ago one of my patients told me, “Doctor, you probably haven’t heard of this hormone called leptin.”

My know-it-all self wanted to tell her a lot of things 🙂 but fortunately, wiser counsel prevailed and I responded, “We still have a long way to go with leptin, therefore please don’t waste your money getting your blood leptin levels tested.” Why did I say that?

Leptin is a hormone produced from your fat tissue (White Adipose Tissue). The name comes from the Greek word “leptos”, meaning thin. Does it mean that leptin makes you thin? The answer is more complex than that! 

The discovery of Leptin in 1994 was a landmark in the history of endocrinology (the study of hormones). The initial enthusiasm about using leptin for the treatment of obesity did not pan out as expected. It was thought that Leptin signals the level of energy stores to the brain. Therefore, as energy stores increase in fat, leptin levels rise, thereby telling the control centres in the brain to limit obesity by reducing food intake and increasing energy expenditure.

However, the amount of circulating leptin required to affect the central nervous system differs amongst individuals. This is dependent on genes, development and diet. Some people may simply require more leptin than others.

However, studies have shown that the more body fat you have, the higher your levels of leptin.  Enter the term leptin resistance.

Leptin Resistance: Does it exist?

Just as insulin resistance causes fat gain, is there leptin resistance too? The term “leptin resistance” is often used to describe states of obesity in which high leptin levels and/or decreased responsiveness to leptin is observed. This led the National Institutes of Health to hold a workshop, “Toward a Clinical Definition of Leptin Resistance”. However, as this paper ⁽⁴⁾ Ref in the journal Cell Metabolism concludes

“……no universal, quantifiable, and clinically useful definition of the term “leptin resistance” is feasible”. It is clear that the availability of relevant human data is limited, however, and a substantial amount of new information must be acquired and disseminated to accomplish these goals.”

What is known about leptin’s actions is listed below:

• Leptin and insulin resistance are intimately related. Therefore, if you can manage your insulin resistance well, leptin will work better too. 
• Cortisol has an important relationship with leptin. ⁽⁵⁾ Ref
• Leptin levels are related to the amount of fat in your body. Therefore the more the body fat, the higher the levels of leptin.
• Fasting reduces leptin levels by 50% on the first day, even before fat loss kicks in ⁽⁶⁾ Ref
• Leptin levels are impacted by estrogens in women and male hormones (androgens) in men.
• Leptin and fuel switch: Leptin helps in maintaining blood glucose levels during fasting. When you stop eating or when you eat very little carbohydrates, your body switches from using carbohydrates from food as fuel to using your body fat stores as fuel. Therefore, when you fast your blood sugar doesn’t go down to dangerous levels. (Caveats for those of you on anti-diabetic medications). ⁽⁷⁾ Ref
• Leptin is linked to autoimmunity. ⁽⁸⁾ Ref
• Leptin affects reproductive functions, bone metabolism, and lipid and liver fat metabolism.
• Using leptin as a drug helps ONLY in very rare conditions. In those with genetic defects of the leptin gene, it works dramatically. And in those people who have lipodystrophy, a condition where there is too little fat on the outside and severe insulin resistance and excessive organ fat. But that doesn’t apply to most of you.

[Important article to understand obesity (Nerd alert) ⁽⁹⁾ Ref ]

Bottom Line:

• Obesity is a complex problem and therefore simplistic solutions like “eat-less and move-more “do not work over the long term.
• Most of you with weight loss challenges are insulin resistant. If you are insulin resistant, a low carbohydrate diet and time-restricted eating will probably work better for weight loss.
• If you are not insulin resistant (a very small percentage), then there are other areas that have to be looked into.