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Showing posts with label overweight. Show all posts
Showing posts with label overweight. Show all posts

Does the Vitamin and Mineral Content of Food Influence Our Food Intake and Body Fatness?

The Claim: We Overeat Because Our Diet is Low in Vitamins and Minerals

We know that animals, including humans, seek certain properties of food.  Humans are naturally attracted to food that's high in fat, sugar, starch, and protein, and tend to be less enthusiastic about low-calorie foods that don't have these properties, like vegetables (1).  Think cookies vs. plain carrots.

In certain cases, the human body is able to detect a nutritional need and take steps to correct it.  For example, people who are placed on a calorie-restricted diet become hungry and are motivated to make up for the calorie shortfall (2, 3).  People who are placed on a low-protein diet crave protein and eat more of it after the restriction is lifted (4).  Humans and many other animals also crave and seek salt, which supplies the essential minerals sodium and chlorine, although today most of us eat much more of it than we need to.  At certain times, we may crave something sweet or acidic, and pregnant women are well known to have specific food cravings and aversions, although explanations for this remain speculative.  Research suggests that certain animals have the ability to correct mineral deficiencies by selecting foods rich in the missing mineral (5).

These observations have led to a long-standing idea that the human body is able to detect vitamin and mineral (micronutrient) status and take steps to correct a deficit.  This has led to the secondary idea that nutrient-poor food leads to overeating, as the body attempts to make up for low nutrient density by eating more food.  In other words, we overeat because our food doesn't supply the micronutrients our bodies need, and eating a micronutrient-rich diet corrects this and allows us to eat less and lose body fat.  These ideas are very intuitive, but intuition doesn't always get you very far in biology.  Let's see how they hold up to scrutiny.

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The Potato Diet

In 2010, I wrote a series of blog posts on the health properties of potatoes (1, 2, 3).  The evidence showed that potatoes are non-toxic, filling per calorie, remarkably nutritious, and can be eaten as almost the sole source of nutrition for extended periods of time (though I'm not recommending this).  Traditional South American cultures such as the Quechua and Aymara have eaten potatoes as the major source of calories for generations without any apparent ill effects (3).  This is particularly interesting since potatoes are one of the highest glycemic and most insulin-stimulating foods known.

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A Sign of the Times

Every now and then, I venture out to go shopping at mainstream chain clothing stores.  Although I find it onerous, there are certain things I can't get at thrift stores.  For example, I can never find nice jeans.

The last time I set foot in these stores was about two years ago.  It was tough to find pants my size at that time-- many stores simply didn't sell pants with a 30 inch waist.  This year, it was even harder, since some of the stores that formerly carried 30W pants no longer did.  I managed to find my usual 30W 30L size in two stores, but I had a bizarre experience in both cases.   I put them on, and they were falling off my waist.  Since my waist size hasn't changed in two years, and my old 30W 30L pants of the same brand still fit the same as they did when I bought them two years ago, I have to conclude that both stores have changed their definition of "30 inches".  My new size is 28W 30L, which is tough to find these days.
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Is it Time to Re-write the Textbooks on Insulin and Obesity? Part II

A new paper published on December 6th in the journal Science once again tackles the question of whether elevated insulin drives the development of obesity (1).  Mice were generated that lack Jun kinases 1 and 2 specifically in immune cells, impairing their ability to produce inflammation while having very few off-target effects.  These mice do not become insulin resistant when placed on a fattening diet, and their insulin levels do not increase one iota.  Are they protected from obesity?  People who read the last post should know the answer already.
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Does "Metabolically Healthy Obesity" Exist?

Obesity is strongly associated with metabolic alterations and negative health outcomes including diabetes, cardiovascular disease, and some types of cancer (1, 2, 3, 4).  Excess body fat is one of the primary causes of preventable health problems and mortality in the United States and many other affluent nations, ranking in importance with cigarette smoking and physical inactivity.  Obesity is thought to contribute to disease via the metabolic disturbances it causes, including excess glucose and lipids in the circulation, dysregulated hormone activity including insulin and leptin, and inflammatory effects.  This immediately raises two questions:
  1. Does metabolically healthy obesity exist?
  2. If so, are metabolically healthy obese people at an elevated risk of disease and death?

Does metabolically healthy obesity exist?

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60 Minutes Report on the Flavorist Industry

A reader sent me a link to a recent CBS documentary titled "Tweaking Tastes and Creating Cravings", reported by Morley Safer.

Safer describes the "flavorist" industry, entirely dedicated to crafting irresistible odors for the purpose of selling processed and restaurant food.  They focused on the company Givaudin.  Dr. David Kessler, author of The End of Overeating, makes an appearance near the end.

Here are a few notable quotes:

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Is it Time to Re-write the Textbooks on Insulin and Obesity?

A recent study in Cell Metabolism by Dr. Arya Mehran and colleagues found a result that, according to a press release, "could overturn widely accepted notions about healthy eating habits" (1), and has set the Internet abuzz.

In this study, researchers generated mice that lack one copy of the pancreatic insulin gene, and compared them to mice carrying both copies (2).  Then, they exposed both groups to a fattening diet, and found that mice lacking one copy of the insulin gene secreted less insulin than the comparison group (i.e., they did not develop the same degree of hyperinsulinemia).  These mice were also completely resistant to fat gain, while the comparison group became obese.  The authors came to some rather large conclusions based on these results, suggesting that the "accepted model" that hyperinsulinemia is the result of obesity is "incompatible with our results that put the insulin hypersecretion genetically upstream of obesity".  Ergo, diet causes hyperinsulinemia, which causes fat gain.  It's a familiar argument to those who frequent Internet diet-health circles, except in this case the hyperinsulinemia is caused by a high-fat diet.

The problem is that the "accepted model" they want to replace overnight didn't come out of thin air-- it emerged from a large body of research, which was almost completely ignored by the authors.  When carefully considered, this evidence suggests an alternative explanation for the results of Dr. Mehran and colleagues.

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New Review Papers on Food Reward

As research on the role of reward/palatability in obesity continues to accelerate, interesting new papers are appearing weekly.  Here is a roundup of review papers I've encountered in the last three months.  These range from somewhat technical to very technical, but I think they should be mostly accessible to people with a background in the biological sciences. 

Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction
Written by Dr. Nora D. Volkow and colleagues.  This paper describes the similarities between the mechanisms of obesity and addiction, with a focus on human brain imaging studies.  Most researchers don't think obesity is an addiction per se, but the mechanisms (e.g., brain areas important for reward) do seem to overlap considerably.  This paper is well composed and got a lot of media attention.  Dr. Volkow is the director of the National Institute on Drug Abuse, a branch of the National Institutes of Health.  The NIH is the main source of biomedical research funding in the US, and also conducts its own research.

Here's a quote from the paper:

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Another Simple Food Weight Loss Experience

Whole Health Source reader Sarah Pugh recently went on a six-week simple food (low reward) diet to test its effectiveness as a weight loss strategy, and she was kind enough to describe her experience for me, and provide a link to her blog where she discussed it in more detail (1). 

Consistent with the scientific literature and a number of previous reader anecdotes (2), Sarah experienced a reduction in appetite on the simple food diet, losing 15 pounds in 6 weeks without hunger.  In contrast to her prior experiences with typical calorie restriction, her energy level and mood remained high over this period.  Here's a quote from her blog:
Well, it looks like the theory that in the absence of nice palatable food, the body will turn quite readily to fat stores and start munching them up, is holding up. At the moment, the majority of the energy I use is coming from my insides, and my body is using it without such quibbles as the increased hunger, low energy, crappy thermo-regulation or bitchiness normally associated with severe calorie restriction.
I can't promise that everyone will experience results like this, but this is basically what the food reward hypothesis suggests should be possible, and it seems to work this way for many people.  That's one of the reasons why this idea interests me so much.

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A Brief Response to Taubes's Food Reward Critique, and a Little Something Extra

It appears Gary Taubes has completed his series critiquing the food reward hypothesis of obesity (1).  I have to hand it to him, it takes some cojones to critique an entire field of research, particularly when you have no scientific background in it, and have evidently not read any of the scientific literature on it.  As of 2015, a Google Scholar search for the terms “food reward” and “obesity” turned up 2,790 papers.

The food reward hypothesis of obesity states that the reward and palatability value of food influence body fatness, and excess reward/palatability can promote body fat accumulation.  If we want to test the hypothesis, the most direct way is to find experiments in which 1) the nutritional qualities of the experimental diet groups are kept the same or at least very similar, 2) some aspect of diet reward/palatability differs, and 3) changes in body fat/weight are measured (for example, 2, 3, 4, 5, 6, 7, 8, 9).  In these experiments the hypothesis has both arms and one leg tied behind its back, because the most potent reward factors (energy density, sugar, fat) have nutritional value and therefore experiments that modify these cannot be tightly controlled for nutritional differences.  Yet even with this severe disadvantage, the hypothesis is consistently supported by the scientific evidence.  Taubes repeatedly stated in his series that controlled studies like these have not been conducted, apparently basing this belief on a 22-year-old review paper by Dr. Israel Ramirez and colleagues that does not contain the word 'reward' (10).

Another way to test the hypothesis is to see if people with higher food reward sensitivity (due to genetics or other factors) tend to gain more fat over time (for example, 11, 12, 13, 14, 15, 16).  In addition, studies that have examined the effect of palatability/reward on food intake in a controlled manner are relevant (17, 18, 19, 20, 21, 22), as are studies that have identified some of the mechanisms by which these effects occur (reviewed in 23).  Even if not all of the studies are perfect, at some point, one has to acknowledge that there are a lot of mutually buttressing lines of evidence here.  It is notable that virtually none of these studies appeared in Taubes's posts, and he appeared unaware of them. 
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Recent and Upcoming Appearances

Smarter Science of Slim

Jonathan Bailor recently released an interview we did a few months ago on the neurobiology of body fat regulation, and the implications for fat loss.  It's a good overview of the regulation of food intake and body fatness by the brain.  You can listen to it here.

Super Human Radio

Carl Lanore interviewed me about my lab's work on hypothalamic inflammation and obesity.  I'm currently wrapping up a postdoctoral fellowship with Dr. Michael Schwartz at the University of Washington, and the interview touches on our recent review paper "Hypothalamic Inflammation: Marker or Mechanism of Obesity Pathogenesis?"  Dan Pardi and I are frequent guests on Carl's show and I'm always impressed by how well Carl prepares prior to the interview.  You can listen to the interview here.

The Reality Check podcast

Pat Roach of the Reality Check podcast interviewed me about the scientific validity of the "carbohydrate-insulin hypothesis" of obesity.  The Reality Check podcast "explores a wide range of controversies and curiosities using science and critical thinking", and a dash of humor.  This one should be very informative for people who aren't sure what to believe and want a deeper perspective on the science of insulin and body weight regulation.  You can listen to it here.

Obesity Society conference

Next Thursday 11/9, I'll be speaking at the 2015 Obesity Society conference in Atlanta.  My talk is titled "The Glial Response to Obesity is Reversible", and it will be about my work on the reversibility of obesity-associated hypothalamic neuropathology in mice.  My talk will be part of the session "Neuronal Control of Satiety" between 3:00 and 4:30, specific time pending.  See you there!

Does High Circulating Insulin Drive Body Fat Accumulation? Answers from Genetically Modified Mice

The house mouse Mus musculus is an incredible research tool in the biomedical sciences, due to its ease of care and its ability to be genetically manipulated.  Although mice aren't humans, they resemble us closely in many ways, including how insulin signaling works.  Genetic manipulation of mice allows researchers to identify biological mechanisms and cause-effect relationships in a very precise manner.  One way of doing this is to create "knockout" mice that lack a specific gene, in an attempt to determine that gene's importance in a particular process.  Another way is to create transgenic mice that express a gene of interest, often modified in some way.  A third method is to use an extraordinary (but now common) tool called "Cre-lox" recombination (1), which allows us to delete or add a single gene in a specific tissue or cell type. 

Studying the relationship between obesity and insulin resistance is challenging, because the two typically travel together, confounding efforts to determine which is the cause and which is the effect of the other (or neither).  Some have proposed the hypothesis that high levels of circulating insulin promote body fat accumulation*.  To truly address this question, we need to consider targeted experiments that increase circulating insulin over long periods of time without altering a number of other factors throughout the body.  This is where mice come in.  Scientists are able to perform precise genetic interventions in mice that increase circulating insulin over a long period of time.  These mice should gain fat mass if the hypothesis is correct. 

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Losing Fat With Simple Food-- Two Reader Anecdotes

Each week, I'm receiving more e-mails and comments from people who are successfully losing fat by eating simple (low reward) food, similar to what I described here.  In some cases, people are breaking through fat loss plateaus that they had reached on conventional low-carbohydrate, low-fat or paleo diets.  This concept can be applied to any type of diet, and I believe it is an important characteristic of ancestral food patterns.

At the Ancestral Health Symposium, I met two Whole Health Source readers, Aravind Balasubramanian and Kamal Patel, who were interested in trying a simple diet to lose fat and improve their health.  In addition, they wanted to break free of certain other high-reward activities in their lives that they felt were not constructive.  They recently embarked on an 8-week low-reward diet and lifestyle to test the effectiveness of the concepts.  Both of them had previously achieved a stable (in Aravind's case, reduced) weight on a paleo-ish diet prior to this experiment, but they still carried more fat than they wanted to.  They offered to write about their experience for WHS, and I thought other readers might find it informative.  Their story is below, followed by a few of my comments.

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Sleep and Genetic Obesity Risk

Evidence is steadily accumulating that insufficient sleep increases the risk of obesity and undermines fat loss efforts.  Short sleep duration is one of the most significant risk factors for obesity (1), and several potential mechanisms have been identified, including increased hunger, increased interest in calorie-dense highly palatable food, reduced drive to exercise, and alterations in hormones that influence appetite and body fatness.  Dan Pardi presented his research at AHS13 showing that sleep restriction reduces willpower to make healthy choices about food.

We also know that genetics has an outsized influence on obesity risk, accounting for about 70 percent of the variability in body fatness between people in affluent nations (2).  I have argued that "fat genes" don't directly lead to obesity, but they do determine who is susceptible to a fattening environment and who isn't (3).  I recently revisited a 2010 paper published in the journal Sleep by University of Washington researchers that supports this idea (4).

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The Case for the Food Reward Hypothesis of Obesity, Part II

In this post, I'll explore whether or not the scientific evidence is consistent with the predictions of the food reward hypothesis, as outlined in the last post.

Before diving in, I'd like to address the critique that the food reward concept is a tautology or relies on circular reasoning (or is not testable/falsifiable).  This critique has no logical basis.  The reward and palatability value of a food is not defined by its effect on energy intake or body fatness.  In the research setting, food reward is measured by the ability of food or food-related stimuli to reinforce or motivate behavior (e.g., 1).  In humans, palatability is measured by having a person taste a food and rate its pleasantness in a standardized, quantifiable manner, or sometimes by looking at brain activity by fMRI or related techniques (2).  In rodents, it is measured by observing stereotyped facial responses to palatable and unpalatable foods, which are similar to those seen in human infants.  It is not a tautology or circular reasoning to say that the reinforcing value or pleasantness of food influences food intake and body fatness. These are quantifiable concepts and as I will explain, their relationship with food intake and body fatness can be, and already has been, tested in a controlled manner. 

1.   Increasing the reward/palatability value of the diet should cause fat gain in animals and humans

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The Case for the Food Reward Hypothesis of Obesity, Part I

Introduction

When you want to investigate something using the scientific method, first you create a model that you hope describes a natural phenomenon-- this is called a hypothesis.  Then you go about testing that model against reality, under controlled conditions, to see if it has any predictive power.  There is rarely a single experiment, or single study, that can demonstrate that a hypothesis is correct.  Most important hypotheses require many mutually buttressing lines of evidence from multiple research groups before they're widely accepted.  Although it's not necessary, understanding the mechanism by which an effect occurs, and having that mechanism be consistent with the hypothesis, adds substantially to the case.

With that in mind, this post will go into greater detail on the evidence supporting food reward and palatability as major factors in the regulation of food intake and body fatness.  There is a large amount of supportive evidence at this point, which is rapidly expanding due to the efforts of many brilliant researchers, however for the sake of clarity and brevity, so far I've only given a "tip of the iceberg" view of it.  But there are two types of people who want more detail: (1) the skeptics, and (2) scientifically inclined people who want mechanism.  This post is for them.  It will get technical at times, as there is no other way to convey the material effectively.

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Humans on a Cafeteria Diet

In the 1970s, as the modern obesity epidemic was just getting started, investigators were searching for new animal models of diet-induced obesity.  They tried all sorts of things, from sugar to various types of fats, but none of them caused obesity as rapidly and reproducibly as desired*.  1976, Anthony Sclafani tried something new, and disarmingly simple, which he called the "supermarket diet": he gave his rats access to a variety of palatable human foods, in addition to standard rodent chow.  They immediately ignored the chow, instead gorging on the palatable food and rapidly becoming obese (1).  Later renamed the "cafeteria diet", it remains the most rapid and effective way of producing dietary obesity and metabolic syndrome in rodents using solid food (2).

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Speaking in Lisbon on October 5

My friend Pedro Bastos graciously invited me to speak at a conference he organized in Lisbon on October 5 titled "Food, Nutrition and the Prevention of Chronic Diseases".  I will give two talks:

  • "Ancestral Health: What is Our Human Potential?"  This talk will explore the health of non-industrial cultures in an effort to understand how much of our modern chronic disease burden is preventable, and it will briefly touch on one major aspect of non-industrial life that may protect against the "diseases of civilization".  This presentation will focus on age-adjusted data from high quality studies.  
  • "Why Do We Overeat: a Neurobiological Perspective."  This talk will attempt to explain why most of us consume more calories than we need to maintain weight-- a phenomenon that is a central cause of morbidity and mortality in the modern world.  It will touch on some of the brain mechanisms involved in ingestive behavior, and outline a framework to explain why these mechanisms are often maladaptive in today's environment.
Pedro will speak about dairy consumption, vitamin D, and chronic disease.  

The conference is targeted to health professionals and students of nutrition, however it's open to anyone who is interested in these topics.  It's sponsored by NutriScience, a Portuguese nutrition education and consulting company.  Sadly, I don't speak Portuguese, so my talks will be in English.  

Access the full program, and register for the conference, using the links below:

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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