Glucagon, Dietary Protein, and Low-Carbohydrate Diets

Glucagon is a hormone that plays an important role in blood glucose control.  Like insulin, it's secreted by the pancreas, though it's secreted by a different cell population than insulin (alpha vs. beta cells).  In some ways, glucagon opposes insulin.  However, the role of glucagon in metabolism is frequently misunderstood in diet-health circles.

The liver normally stores glucose in the form of glycogen and releases it into the bloodstream as needed.  It can also manufacture glucose from glycerol, lactate, and certain amino acids.  Glucagon's main job is to keep blood glucose from dipping too low by making sure the liver releases enough glucose.  There are a few situations where this is particularly important:

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Does the Mediterranean Diet Reduce Cardiovascular Risk?

By now, most of you have probably heard about the recent study on the "Mediterranean diet" (1), a diet that was designed by diet-heart researchers and is based loosely on the traditional diet of Crete and certain other Mediterranean regions.  The popular press has been enthusiastically reporting this trial as long-awaited proof that the Mediterranean diet reduces the risk of cardiovascular events-- by a full 30 percent over a 4.8-year period.  I wish I could share their enthusiasm for the study.

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Why Do We Eat? A Neurobiological Perspective. Part IV

In this post, I'll follow up on the last post with a discussion two more important factors that can affect energy homeostasis and therefore our food intake and propensity to gain fat: age and menopause.

Age

Although it often isn't the case in non-industrial cultures, in affluent nations most people gain fat with age.  This fat gain continues until old age, when many people once again lose fat.  This is probably related to a number of factors, three of which I'll discuss.  The first is that we tend to become less physically active with age.  The second, related factor is that we lose lean mass with age, and so energy expenditure declines.

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Why Do We Eat? A Neurobiological Perspective. Part III

In the first post, I explained that all voluntary actions are driven by a central action selection system in the mesolimbic area (the reward system).  This is the part of you that makes the decision to act, or not to act.  This system determines your overall motivation to obtain food, based on a variety of internal and external factors, for example hunger, the effort required to obtain food, and the sensory qualities of food/drink.  These factors are recognized and processed by a number of specialized 'modules' in the brain, and forwarded to the reward system where the decision to eat, or not to eat, is made.  Researchers divide food intake into two categories: 1) eating from a true energy need by the body (homeostatic eating), e.g. hunger, and 2) eating for other reasons (non-homeostatic eating), e.g. eating for social reasons or because the food tastes really good.

In the second post of the series, we explored how the brain regulates food intake on a meal-to meal basis based on feedback from the digestive system, and how food properties can influence this process.  The integrated gut-brain system that accomplishes this can be called the satiety system.

In this post, we'll explore the energy homeostasis system, which regulates energy balance (energy in vs. energy out) and body fatness on a long term basis.

The Energy Homeostasis System

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Why Do We Eat? A Neurobiological Perspective. Part II

In the last post, I explained that eating behavior is determined by a variety of factors, including hunger and a number of others that I'll gradually explore as we make our way through the series.  These factors are recognized by specialized brain 'modules' and forwarded to a central action selection system in the mesolimbic area (the reward system), which determines if they are collectively sufficient cause for action.  If so, they're forwarded to brain systems that directly drive the physical movements involved in seeking and consuming food (motor systems).

The term 'homeostasis' is important in biology.  Homeostasis is a process that attempts to keep a particular factor within a certain stable range.  The thermostat in your house is an example of a homeostatic system.  It reacts to upward or downward changes in a manner that keeps temperature in a comfortable range.  The human body also contains a thermostat that keeps internal temperature close to 98.6 F.  Many things are homeostatically regulated by the body, and one of them is energy status (how much energy the body has available for use).  Homeostasis of large-scale processes in the body is typically regulated by the brain.

We can divide the factors that determine feeding behavior into two categories, homeostatic and non-homeostatic.  Homeostatic eating is when food intake is driven by a true energy need, as perceived by the brain.  For the most part, this is eating in response to hunger.  Non-homeostatic eating is when food intake is driven by factors other than energy need, such as palatability, habitual meal time, and food cues (e.g. you just walked by a vending machine full of Flamin' Hot Cheetos).

We can divide energy homeostasis into two sub-categories: 1) the system that regulates short-term, meal-to-meal calorie intake, and 2) the system that regulates fat mass, the long-term energy reserve of the human body.  In this post, I'll give an overview of the process that regulates energy homeostasis on a short-term, meal-to-meal basis.

The Satiety System (Short-Term Energy Homeostasis)


The stomach of an adult human has a capacity of 2-4 liters.  In practice, people rarely eat that volume of food.  In fact, most of us feel completely stuffed long before we've reached full stomach capacity.  Why?

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Why Do We Eat? A Neurobiological Perspective. Part I

As with all voluntary movements, eating food is an expression of activity in the brain.  The brain integrates various inputs from around the body, and outside the body, and decides whether or not to execute the goal-directed behaviors of food seeking and consumption.  Research has uncovered a lot about how this process works, and in this series I'll give a simplified overview of what scientists have learned about how, and why, the brain decides to eat.

The Gatekeeper of Voluntary Behaviors

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Announcing the Ideal Weight Program

I often receive requests from people asking for my overall perspective on fat loss and health.  I share my opinions here, but they're scattered throughout hundreds of posts, there's a lot I haven't had a chance to write about, and I rarely give practical recommendations.  However, I knew I'd eventually put everything together into a cohesive fat loss program-- it was only a matter of finding the right opportunity.

That opportunity presented itself in 2011 when I met Dan Pardi, a researcher whose work focuses on sleep and food intake, and the CEO of a company called Dan's Plan.  I was immediately impressed by Dan because he stood out as someone with a high level of expertise in sleep and physical activity, as well as someone who has successfully lost a substantial amount of fat and kept it off for several years.

Dan and his team had developed a set of unique and engaging tools for tracking weight, sleep, and physical activity to help people maintain daily mindfulness over the simple fundamentals of health.  These tools are 100 percent free and incredibly easy to use, particularly if you sync them with an electronic scale and step counter.  When synced with these devices, the Dan's Plan website automatically uploads and displays your weight, sleep, and physical activity score, as well as integrating them all into a single user-friendly Health Zone Score that lets you know your overall performance at a glance.  Even if you have no interest in fat loss, I highly recommend using the free tracking tools on the Dan's Plan site-- I do.

In early 2012, Dan approached me about creating a fat loss program for Dan's Plan that incorporates their unique tracking tools.  This struck me as an excellent opportunity to create a diet and lifestyle program that combines sound science with exciting new technology.  Dan and I both brought science to the table, and Dan also brought the perspective gained from working with others to help them lose fat, as well as his own successful fat loss experience.  Dan and I have been working hard on this project, and we're finally ready to launch.

I'm happy to announce the Ideal Weight Program, an effective new system for fat loss and maintenance.

What is the Ideal Weight Program?

The Ideal Weight Program is a unique system for fat loss and maintenance that draws from the latest science on diet, physical activity, sleep, and behavior modification, and pairs it with engaging tools that help you define your goals and meet them.  It keeps you consistently focused on the everyday factors that really matter for fat loss, and gives you the skills you need to make sustainable diet and lifestyle changes.  Based on your own goals and priorities, you can choose one of two diet strategies for the initial fat loss phase:

• The Fat Loss and Sustainable Health (FLASH) diet, an intensive high-protein diet for rapid fat loss.
• The Simple Food Diet, a more flexible diet based on whole, natural foods specifically selected for fat loss.  One important goal of this diet is to teach healthy cooking skills, using recipes and tips provided.

These diets are designed to naturally promote a lower calorie intake and fat loss, without requiring calorie counting.  The Ideal Weight Program also includes important physical activity and sleep components, and explains why these are so critical for fat loss and health.  Dan and I discussed some of the principles underlying the Ideal Weight Program on Chris Kresser's podcast recently.

Here's what you get when you sign up:

• Detailed documents that walk you through the program
• Weight, sleep, and physical activity tracking tools tailored for fat loss
• Simple recipes and cooking tips that work with almost anything in your fridge
• Videos that explain the key concepts behind fat loss and maintenance
• An e-book explaining the scientific rationale behind the program

Signing up for the Ideal Weight Program gives you lifetime access to everything.  We've discounted the initial price, because we want to hear your feedback so that we can continue to improve the program over time.  If you follow the link below, first you'll be prompted to sign up for a basic Dan's Plan account, and once you have your account set up, you'll be able to purchase the Ideal Weight Program:

Ideal Weight Program



Financial disclosure: I will receive a portion of the revenue from the sale of the Ideal Weight Program.  I do not receive revenue from the sale of other products associated with Dan's Plan or the Ideal Weight Program (such as the Fitbit, cooking tools, and other programs).

Overfeeding and Elevated Insulin

It's commonly accepted in the obesity research community that fat gain causes insulin resistance and an increase in circulating insulin, and that this is a major reason why obese people usually have insulin resistance and high circulating insulin. Part of the rationale is that substantial fat loss by almost any means improves insulin sensitivity and causes circulating insulin to decline, and substantial fat gain from deliberate overfeeding causes insulin sensitivity to decline and circulating insulin to increase.  I recently cited three references to support this contention on another blog, and was challenged, so I decided to revisit these references to make sure I had understood them correctly (1, 2, 3).  Since I took the time to do this, I figured I may as well write it up for my readers, since these studies are quite informative.

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More Thoughts on Macronutrient Trends

I had a brief positive exchange with Gary Taubes about the NuSI post.  He reminded me that there's an artifact (measurement error) in the USDA data on fat consumption in the year 2000 when they changed assessment methods.  Here are the USDA data on macronutrient consumption since 1970, corrected for loss (28.8%) but not corrected for the artifact:

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Nutrition Science Initiative (NuSI)

Some of you may have heard of an ambitious new nutrition research foundation called the Nutrition Science Initiative (NuSI).  In this post, I'll explain what it is, why it matters, and how I feel about it-- from the perspective of an obesity researcher. 

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Calories and Carbohydrate: a Natural Experiment

In the lab, we work hard to design experiments that help us understand the natural world.  But sometimes, nature sets up experiments for us, and all we have to do is collect the data.  These are called "natural experiments", and they have led to profound insights in every field of science.  For example, Alzheimer's disease is usually not considered a genetic disorder.  However, researchers have identified rare cases where AD is inherited in a simple genetic manner.  By identifying the genes involved, and what they do, we were able to increase our understanding of the molecular mechanisms of the disease.

The natural experiment I'll be discussing today began in 1989 with the onset of a major economic crisis in Cuba. This coincided with the loss of the Soviet Union as a trading partner, resulting in a massive economic collapse over the next six years, which gradually recovered by 2000. 

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Does Calorie Restriction Extend Lifespan in Mammals?

Until about two years ago, the story went something like this: calorie restriction extends lifespan in yeast, worms, flies, and rodents.  Lifespan extension by calorie restriction appears to be biologically universal, therefore it's probably only a matter of time until it's demonstrated in humans as well.  More than 20 years ago, independent teams of researchers set out to demonstrate the phenomenon in macaque monkeys, a primate model closer to humans than any lifespan model previously tested.

Recent findings have caused me to seriously question this narrative.  One of the first challenges was the finding that genetically wild mice (as opposed to inbred laboratory strains) do not live longer when their calorie intake is restricted, despite showing hormonal changes associated with longevity in other strains, although the restricted animals do develop less cancer (1).  One of the biggest blows came in 2009, when researchers published the results of a study that analyzed the effect of calorie restriction on lifespan in 41 different strains of mice, both male and female (2).  They found that calorie restriction extends lifespan in a subset of strains, but actually shortens lifespan in an even larger subset.  Below is a graph of the effect of calorie restriction on lifespan in the 41 strains.  Positive numbers indicate that calorie restriction extended life, while negative numbers indicate that it shortened life:

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Ancestral Health Symposium 2012

I recently returned from AHS12 and a little side trip to visit family.  The conference was hosted at Harvard University through the Harvard Food Law Society.  Many thanks to all the organizers who made it happen.  By and large, it went smoothly.

The science as expected ranged from outstanding to mediocre, but I was really encouraged by the presence and enthusiastic participation of a number of quality researchers and clinicians. The basic concept of ancestral health is something almost anyone can get behind: many of our modern health problems are due to a mismatch between the modern environment and what our bodies "expect".  The basic idea is really just common sense, but of course the devil is in the details when you start trying to figure out what exactly our bodies expect, and how best to give it to them.  I think our perspective as a community is moving in the right direction.

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New Review Paper by Yours Truly: High-Fat Dairy, Obesity, Metabolic Health and Cardiovascular Disease

My colleagues Drs. Mario Kratz, Ton Baars, and I just published a paper in the European Journal of Nutrition titled "The Relationship Between High-Fat Dairy Consumption and Obesity, Cardiovascular, and Metabolic Disease".  Mario is a nutrition researcher at the Fred Hutchinson Cancer Research Center here in Seattle, and friend of mine.  He's doing some very interesting research on nutrition and health (with an interest in ancestral diets), and I'm confident that we'll be getting some major insights from his research group in the near future.  Mario specializes in tightly controlled human feeding trials.  Ton is an agricultural scientist at the University of Kassel in Germany, who specializes in the effect of animal husbandry practices (e.g., grass vs. grain feeding) on the nutritional composition of dairy.  None of us have any connection to the dairy industry or any other conflicts of interest.

The paper is organized into three sections:

1. A comprehensive review of the observational studies that have examined the relationship between high-fat dairy and/or dairy fat consumption and obesity, metabolic health, diabetes, and cardiovascular disease.
2. A discussion of the possible mechanisms that could underlie the observational findings.
3. Differences between pasture-fed and conventional dairy, and the potential health implications of these differences.

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What Causes Type 2 Diabetes, and How Can it be Prevented?

In the comments of the last post, we've been discussing the relationship between body fatness and diabetes risk.  I think this is really worth understanding, because type 2 diabetes is one of the few lifestyle disorders where 1) the basic causes are fairly well understood, and 2) we have effective diet/lifestyle prevention strategies that have been clearly supported by multiple controlled trials.

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Interview with Aitor Calero of Directo al Paladar

Aitor Calero writes for the popular Spanish cooking and nutrition blog, Directo al Paladar ("straight to the palate").  We did a written interview a while back, and he agreed to let me post the English version on my blog.  The Spanish version is here and here.

Without further ado, here it is:

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Why Did Energy Expenditure Differ Between Diets in the Recent Study by Dr. Ludwig's Group?

As discussed in the previous post, a recent study by Dr. David Ludwig's group suggested that during weight maintenance following fat loss, eating a very low carbohydrate (VLC) diet led to a higher metabolic rate (energy expenditure) than eating a low-fat (LF) diet, with a low glycemic index (LGI) diet falling in between the two (1).  The VLC diet was 30 percent protein, while the other two were 20 percent.  It's important to note that these were three dietary patterns that differed in many ways, and contrary to claims that are being made in the popular media, the study was not designed to isolate the specific influence of protein, carbohydrate or fat on energy expenditure in this context. 

Not only did the VLC diet lead to a higher total energy expenditure than the LF and LGI diets, the most remarkable finding is that it led to a higher resting energy expenditure.  Basically, people on the VLC diet woke up in the morning burning more energy than people on the LGI diet, and people on the LGI diet woke up burning more than people on the LF diet.  The VLC dieters burned 326 more calories than the LF dieters, and 200 more than the LGI dieters.

It's always tempting to view each new study in isolation, without considering the numerous studies that came before it, but in this case it's essential to see this study through a skeptical lens that places it into the proper scientific context.  Previous studies have suggested that:

1. The carbohydrate:fat ratio of the diet has little or no detectable impact on energy expenditure in people who are not trying to lose weight (2, 3).
2. The carbohydrate:fat ratio of the diet has little or no detectable impact on energy expenditure in people who are being experimentally overfed, and if anything carbohydrate increases energy expenditure more than fat (4, 5).
3. The carbohydrate:fat ratio of the diet has little or no detectable impact on energy expenditure during weight loss (6, 7, 8), and does not influence the rate of fat loss when calories are precisely controlled. 

This new study does not erase or invalidate any of these previous findings.  It fills a knowledge gap about the effect of diet composition on energy expenditure specifically in people who have lost weight and are trying to maintain the reduced weight.

With that, let's see what could have accounted for the differences observed in Dr. Ludwig's study.
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New Study: Is a Calorie a Calorie?

A new study in JAMA led by Dr. Cara B. Ebbeling and colleagues purports to challenge the idea that all calories are equally fattening (1).  Let's have a look.  When thinking about the role of calorie intake in body fatness, there are basically three camps:

1.    Calories don’t matter at all, only diet composition matters.
2.    Calories are the only thing that matters, and diet composition is irrelevant.
3.    Calories matter, but diet composition may also play a role.

The first one is an odd position that is not very well populated.  The second one has a lot of adherents in the research world, and there’s enough evidence to make a good case for it.  It’s represented by the phrase ‘a calorie is a calorie’, i.e. all calories are equally fattening.  #1 and #2 are both extreme positions, and as such they get a lot of attention.  But the third group, although less vocal, may be closest to the truth. 
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New Study Demonstrates that Sugar has to be Palatable to be Fattening in Mice

Dr. Anthony Sclafani's research group just published a study definitively demonstrating that high palatability, or pleasantness of taste, is required for sugar to be fattening in mice (1).  Dr. John Glendinning was lead author. Dr. Sclafani's group has done a lot of excellent research over the years.  Among other things, he's the person who invented the most fattening rodent diet in the world-- the 'cafeteria diet'-- composed of human junk food. 

Mice and rats love sweet food and drinks, just like humans.  If you give them a choice between plain water and sugar water, they'll overconsume the sugar water and become obese.  I have argued, based on a large body of evidence, that the reward value and palatability* of these solutions are important to this process (2, 3, 4).  This is really just common sense honestly, because by definition if the solution weren't rewarding the mice wouldn't go out of their way to drink it instead of water, the same way people wouldn't go out of their way to get soda if it weren't rewarding.  But it's always best to confirm common sense with research.
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Sugar Intake and Body Fatness in Non-industrial Cultures

Around the world, non-industrial cultures following an ancestral diet and lifestyle tend to be lean. When they transition a modern diet and lifestyle, they typically put on body fat and develop the classic "diseases of civilization" such as diabetes and cardiovascular disease.  If we can understand the reasons why this health transition occurs, we will understand why these problems afflict us today.  Research has already identified a number of important factors, but today I'm going to discuss one in particular that has received a lot of attention lately: sugar.

There's an idea currently circulating that sugar is the main reason why healthy traditional cultures end up obese and sick.  It’s easy to find non-industrial cultures that are lean and don’t eat much sugar, and it’s easy to find industrial cultures that are obese and eat a lot of it.  But many factors are changing simultaneously there.  We could use the same examples to demonstrate that blue jeans and hair gel cause obesity.  If sugar is truly the important factor, then cultures with a high sugar intake, but an otherwise ancestral diet and lifestyle, should also be overweight and sick.  Let’s see if that's true. 

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