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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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More Thoughts on Cold Training: Biology Chimes In

Now that the concept of cold training for cold adaptation and fat loss has received scientific support, I've been thinking more about how to apply it.  A number of people have been practicing cold training for a long time, using various methods, most of which haven't been scientifically validated.  That doesn't mean the methods don't work (some of them probably do), but I don't know how far we can generalize individual results prior to seeing controlled studies.

The studies that were published two weeks ago used prolonged, mild cold exposure (60-63 F air) to achieve cold adaptation and fat loss (12).  We still don't know whether or not we would see the same outcome from short, intense cold exposure such as a cold shower or brief cold water plunge.  Also, the fat loss that occurred was modest (5%), and the subjects started off lean rather than overweight.  Normally, overweight people lose more fat than lean people given the same fat loss intervention, but this possibility remains untested.  So the current research leaves a lot of stones unturned, some of which are directly relevant to popular cold training concepts.

In my last post on brown fat, I mentioned that we already know a lot about how brown fat activity is regulated, and I touched briefly on a few key points.  As is often the case, understanding the underlying biology provides clues that may help us train more effectively.  Let's see what the biology has to say.

Biology of Temperature Regulation

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A Roadmap to Obesity

In this post, I'll explain my current understanding of the factors that promote obesity in humans.  

Heritability

To a large degree, obesity is a heritable condition.  Various studies indicate that roughly two-thirds of the differences in body fatness between individuals is explained by heredity*, although estimates vary greatly (1).  However, we also know that obesity is not genetically determined, because in the US, the obesity rate has more than doubled in the last 30 years, consistent with what has happened to many other cultures (2).  How do we reconcile these two facts?  By understanding that genetic variability determines the degree of susceptibility to obesity-promoting factors.  In other words, in a natural environment with a natural diet, nearly everyone would be relatively lean, but when obesity-promoting factors are introduced, genetic makeup determines how resistant each person will be to fat gain.  As with the diseases of civilization, obesity is caused by a mismatch between our genetic heritage and our current environment.  This idea received experimental support from an interesting recent study (3).

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AHS11 Talk Posted

After a one-year delay, my talk from the 2015 Ancestral Health Symposium is online with slides synched.  The talk is titled "Obesity: Old Solutions for a New Problem", and it's an overview of some of the research linking food reward to food intake and body fatness.  This is the talk that introduced a fundamentally new idea to the ancestral community: not only does the chemical composition of food matter, but also its sensory qualities-- in fact, the sensory qualities of food are among the primary determinants of food intake.  I didn't come up with the idea of course, I simply translated the research for a more general audience and put my own evolutionary spin on it.

The talk would be a bit different if I were to give it today, as my understanding of the subject has expanded, and my speaking skills have improved.  However, the central message remains as true today as it was a year ago.  You can find the talk here.

The slide synching was done by an extremely generous man named Ben Fury.  As you can see in the video, he did an excellent job.  Without Ben, this video would have remained in internet limbo forever.

Below, I've published a message from Ben explaining the interesting work that he does.  Please contact him if you think it's interesting.

A Message from Ben Fury

I was writing a book on health, fitness and diet in 2009 when my house burned down in the Station Fire, along with 165,000 acres of my beloved Angeles National Forest. Since then, I've had a series of people needing help come through my life, that have upgraded and morphed my talents...

Seniors with chronic pain, falls, brittle bones, and stiff shrunken muscles.
Diabetics with out of control blood sugars, going blind, and having limbs lopped off.
Neurologically challenged people with spastic limbs and foggy brains.
Fat, listless, unhappy people with no idea how they got that way, seeing no way out of the darkness.
Each of them needing help in different ways, but all with an underlying theme of what works to help heal our conditions:
  •     Remove flour, sugar, beans, and heavily processed oils from our diet. Eat real food.
  •     Get strong.
  •     Get flexible.
  •     Stop ceding health responsibility to outside forces, and take charge of our own wellness.
  •     Only use truly evidence based medicine. Don't just pop the latest pill or get the latest surgery all the other people are doing. Be wary of the disease mongers in both the conventional and alternative camps.
  •     Find our "happy thoughts." Use the simple restoratives of sleep, play, and reflection, to let go of pain, find inner peace, and let in joy and purposeful outer direction.
The methods to accomplish these goals are varied, and I have both non-profit and for-profit ventures to share them.
Their websites are currently in development.
The for-profit is BenFury.com
The non-profit is PainRelieversUSA.org , whose mission statement is:

To move beyond pain management...
and learn to live pain free.


Feel free to write to me  at:
 ben [at] benfury dot com

Seed Oils and Body Fatness-- A Problematic Revisit

Anthony Colpo recently posted a discussion of one of my older posts on seed oils and body fat gain (1), which reminded me that I need to revisit the idea.  As my knowledge of obesity and metabolism has expanded, I feel the evidence behind the hypothesis that seed oils (corn, soybean, etc.) promote obesity due to their linoleic acid (omega-6 fat) content has largely collapsed.

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Reflections on the 2015 Ancestral Health Symposium

I just returned from the 2015 Ancestral Health Symposium in Atlanta.  Despite a few challenges with the audio/visual setup, I think it went well.

I arrived on Thursday evening, and so I missed a few talks that would have been interesting to attend, by Mel Konner, Nassim Taleb, Gad Saad, and Hamilton Stapell.  Dr. Konner is one of the progenitors of the modern Paleo movement.  Dr. Saad does interesting work on consummatory behavior, reward, and its possible evolutionary basis.  Dr. Stapell is a historian with an interest in the modern Paleo movement.  He got some heat for suggesting that the movement is unlikely to go truly mainstream, which I agree with.  I had the opportunity to spend quite a bit of time with him and found him to be an interesting person.

On Friday, Chris Kresser gave a nice talk about the potential hidden costs of eradicating our intestinal parasites and inadvertently altering our gut flora.  Unfortunately it was concurrent with Chris Masterjohn so I'll have to watch his talk on fat-soluble vitamins when it's posted.  I spent most of the rest of the day practicing my talk.

On Saturday morning, I gave my talk "Insulin and Obesity: Reconciling Conflicting Evidence".  I think it went well, and the feedback overall was very positive, both on the content and the delivery.  The conference is fairly low-carb-centric and I know some people disagree with my perspective on insulin, and that's OK.   The-question-and-answer session after the talk was also productive, with some comments/questions from Andreas Eenfeldt and others.  With the completion of this talk, I've addressed the topic to my satisfaction and I don't expect to spend much more time on it unless important new data emerge.  The talk will be freely available online at some point, and I expect it to become a valuable resource for people who want to learn more about the relationship between insulin and obesity.  It should be accessible to anyone with a little bit of background in the subject, but it will also be informative to most researchers.

After my talk, I attended several other good presentations.  Dan Pardi gave a nice talk on the importance of sleep and the circadian rhythm, how it works, how the modern world disrupts it, and how to fix it.  The relationship between sleep and health is a very hot area of research right now, it fits seamlessly with the evolutionary perspective, and Pardi showed off his high level of expertise in the subject.  He included the results of an interesting sleep study he conducted as part of his doctoral work at Stanford, showing that sleep restriction makes us more likely to choose foods we perceive as unhealthy.

Sleep and the circadian rhythm was a recurrent theme at AHS13.  A lot of interesting research is emerging on sleep, body weight, and health, and the ancestral community has been quick to embrace this research and integrate it into the ancestral health template.  I think it's a big piece of the puzzle.

Jeff Rothschild gave a nice summary of the research on time-restricted feeding, body weight and health in animal models and humans.  Research in this area is expanding and the results are pretty interesting, suggesting that when you restrict a rodent's feeding window to the time of day when it would naturally consume food (rather than giving constant access during both day and night), it becomes more resistant to obesity even when exposed to a fattening diet.  Rothschild tied this concept together with circadian regulation in a compelling way.  Since food is one of the stimuli that sets the circadian clock, Rothschild proposes to eat when the sun is up, and not when it's down, synchronizing eating behavior with the natural seasonal light rhythm.  I think it's a great idea, although it wouldn't be practical for me to implement it currently.  Maybe someday if I have a more flexible schedule.  Rothschild is about to publish a review paper on this topic as part of his master's degree training, so keep your eyes peeled.

Kevin Boyd gave a very compelling talk about malocclusion (underdeveloped jaws and crowded teeth) and breathing problems, particularly those occurring during sleep.  Malocclusion is a modern epidemic with major health implications, as Dr. Boyd showed by his analysis of ancient vs. modern skulls.  The differences in palate development between our recent ancestors (less than 200 years ago) and modern humans are consistent and striking, as Weston Price also noted a century ago.  Dr. Boyd believes that changing infant feeding practices (primarily the replacement of breast feeding with bottle feeding) is the main responsible factor, due to the different mechanical stimulation it provides, and he's proposing to test that hypothesis using the tools of modern research.  He's presented his research at prestigious organizations and in high-impact scientific journals, so I think this idea may really be gaining traction.  Very exciting.

I was honored when Dr. Boyd told me that my 9-part series on malocclusion is what got him interested in this problem (1, 2, 3, 4, 5, 6, 7, 8, 9).  His research has of course taken it further than I did, and as a dentist his understanding of malocclusion is deeper than mine.  He's a middle-aged man who is going back to school to do this research, and his enthusiasm is palpable.  Robert Corruccini, a quality anthropology researcher and notable proponent of the idea that malocclusion is a "disease of civilization" and not purely inherited, is one of his advisers.

There were a number of excellent talks, and others that didn't meet my standards for information quality.  Overall, an interesting conference with seemingly less drama than in previous years.

Food Palatability and Body Fatness: Clues from Alliesthesia

Part I: Is there a Ponderostat?

Some of the most important experiments for understanding the role of food palatability/reward in body fatness were performed by Dr. Michel Cabanac and collaborators in the 1970s (hat tip to Dr. Seth Roberts for the references).  In my recent food reward series (1), I referenced but did not discuss Dr. Cabanac's work because I felt it would have taken too long to describe.  However, I included two of his studies in my Ancestral Health Symposium talk, and I think they're worth discussing in more detail here.

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Ancestral Health Symposium 2015

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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I Got Boinged, and Other News

The reaction to my post "The Carbohydrate Hypothesis of Obesity: a Critical Examination" has been overwhelmingly positive, particularly among the scientists I've heard from. 

On Saturday, the inimitable maker and writer Mark Frauenfelder posted a link to my post on the variety blog BoingBoing.  BoingBoing has been on my sidebar for three years, and it's the place I go when I need a break.  It's a fun assortment of science, news, technology and entertainment.  BoingBoing was originally a zine started by Frauenfelder and his wife in 1988, and it has been on the web since 1995.  Today, it has multiple contributing authors and it draws several hundred thousand hits per day.  I'm thrilled that Frauenfelder posted my article there.  Apparently he likes my blog.  Thanks!

I added a new section (IIB) to my original post.  It discusses what human genetics can teach us about the mechanisms of common obesity.  It is consistent with the rest of the evidence suggesting that body fatness is primarily regulated by the brain, not by fat tissue, and that leptin signaling plays a dominant role in this process. 

AHS Talk This Saturday

For those who are attending the Ancestral Health Symposium this year, my talk will be at 9:00 AM on Saturday.  The title is "Insulin and Obesity: Reconciling Conflicting Evidence", and it will focus on the following two questions:
  1. Does elevated insulin cause obesity; does obesity cause elevated insulin; or both?
  2. Is there a unifying hypothesis that's able to explain all of the seemingly conflicting evidence cited by each side of the debate?
I'll approach the matter in true scientific fashion: stating hypotheses, making rational predictions based on those hypotheses, and seeing how well the evidence matches the predictions.  I'll explore the evidence in a way that has never been done before (to my knowledge), even on this blog.

Why am I giving this talk?  Two reasons.  First, it's an important question that has implications for the prevention and treatment of obesity, and it has received a lot of interest in the ancestral health community and to some extent among obesity researchers.  Second, I study the mechanisms of obesity professionally, I'm wrapping up a postdoc in a lab that has focused on the role of insulin in body fatness (lab of Dr. Michael W. Schwartz), and I've thought about this question a lot over the years-- so I'm in a good position to speak about it.

The talk will be accessible and informative to almost all knowledge levels, including researchers, physicians, and anyone who knows a little bit about insulin.  I'll cover most of the basics as we go.  I guarantee you'll learn something, whatever your knowledge level.

The Carbohydrate Hypothesis of Obesity: a Critical Examination

Introduction

I'd like to begin by emphasizing that carbohydrate restriction has helped many people lose body fat and improve their metabolic health.  Although it doesn't work for everyone, there is no doubt that carbohydrate restriction causes fat loss in many, perhaps even most obese people.  For a subset of people, the results can be very impressive.  I consider that to be a fact at this point, but that's not what I'll be discussing here. 

What I want to discuss is a hypothesis.  It's the idea, championed by Gary Taubes, that carbohydrate (particularly refined carbohydrate) is the primary cause of common obesity due to its ability to elevate insulin, thereby causing increased fat storage in fat cells.  To demonstrate that I'm representing this hypothesis accurately, here is a quote from his book Good Calories, Bad Calories:

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Food Reward Friday

This week's lucky "winner"... cola!

Thirsty yet?  Visual cues such as these are used to drive food/beverage seeking and consumption behavior, which are used to drive profits.  How does this work?  Once you've consumed a rewarding beverage enough times, particularly as a malleable child, your brain comes to associate everything about that beverage with the primary reward you obtained from it (calories, sugar, and caffeine).  This is simply Pavlovian/classical conditioning*.  Everything associated with that beverage becomes a cue that triggers motivation to obtain it (craving), including the sight of it, the smell of it, the sound of a can popping, and even the physical and social environment it was consumed in-- just like Pavlov's dogs learned to drool at the sound of a bell that was repeatedly paired with food.

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Ancestral Health Symposium

Last weekend I attended the Ancestral Health Symposium at the University of California, Los Angeles, organized by Aaron Blaisdell, Brent Pottenger and Seth Roberts with help from many others.  It was a really great experience and I'm grateful to have been invited.  I was finally able to meet many of the people who I respect and admire, but knew only through the internet.  I'm not going to make a list because it would be too long, but if you take a look at the symposium schedule, I think you'll understand where I'm coming from.  I was also able to connect with a number of Whole Health Source readers, which was great.  I recognized some of them from the comments section.  Now I know it wasn't just my mom with 57 Google accounts.

The symposium was the first of its kind, and represented many facets of the ancestral health community, including "Paleolithic" diet and exercise patterns, low-carbohydrate diets, Weston Price-style diets, traditional health-nutrition researchers as well as other camps.  For the most part they coexisted peacefully and perhaps even learned a thing or two from one another. 

I was very impressed by the appearance of the attendees.  Young men and women were fit with glowing skin, and older attendees were energetic and aging gracefully.  It would be hard to come up with a better advertisement for ancestrally-oriented diets and lifestyles.  I saw a lot of people taking the stairs rather than the elevator.  I like to say I'll take the elevator/escalator when I'm dead.  I think integrating exercise into everyday life is healthy and efficient.  Escalators and elevators of course make sense for people with physical disabilities or heavy suitcases.

The first talk was by Dr. Boyd Eaton, considered by many to be the grandfather of the paleolithic diet concept.  I was very impressed by his composure, humility and compassionate attitude.  Half his talk was dedicated to environmental and social problems.  Dr. Staffan Lindeberg gave a talk titled "Food and Western Disease", which covered his paleolithic diet clinical trials as well as other evidence supporting ancestral diets.  I like Dr. Lindeberg's humble and skeptical style of reasoning.  I had the great pleasure of having dinner with Dr. Lindeberg and his wife, Dr. Eaton, Pedro Bastos, Dr. Lynda Frassetto, Dr. Guy-Andre Pelouze and his son Alexandre.  Pedro gave a very nice talk on the complexities of traditional and modern dairy.  The following night, I was able to connect with other writers I enjoy, including Chris Masterjohn, Melissa McEwen, John Durant, and Denise Minger

Dr. Pelouze is a french cardiovascular surgeon who strongly supports the food reward/palatability concept of obesity.  We had a conversation the evening before the conference, during which he basically made the same points I was going to make in my talk.  He is particularly familiar with the research of Dr. Michel Cabanac, who is central to the food reward idea.  He eats an interesting diet: mostly raw, omnivorous, and extremely simple.  If I understood correctly, he mostly eats raw meat, fish, fruit and vegetables with little or no preparation.  He sometimes cooks food if he wants to, but most of it is raw.  He believes simple, raw food allows the body's satiety systems to work more effectively.  He has been eating this way for more than twenty years, and his son was raised this way and is now about my age (if I recall correctly, Alexandre has a masters and is studying for an MD, and ultimately wants to become an MD/PhD).  Both of them look very good, are full of energy and have a remarkably positive mental state.  Alexandre told me that he never felt deprived growing up around other children who ate pastries, candy et cetera.  They woke up early and ran six miles before the conference began at 8 am. 

I gave my talk on Friday.  Giving a talk is not like writing a blog post-- it has to be much more cohesive and visually compelling.  I put a lot of work into it and it went really well.  Besides the heat I got from from Gary Taubes in the question and answer session, the response was very positive.  The talk, including the questions, will be freely available on the internet soon, as well as other talks from the symposium.  Some of it will be familiar to people who have read my body fat setpoint and food reward series, but it's a concise summary of the ideas and parts of it are new, so it will definitely be worthwhile to watch it.  

We have entered a new era of media communication.  Every time someone sneezed, it was live tweeted.  There are some good aspects to it-- it democratizes information by making it more accessible.  On the other hand, it's sometimes low quality information that contains inaccurate accounts and quotes that are subsequently recirculated. 

It was a great conference and I hope it was the first of many.

Lorcaserin: the Latest FDA-approved Obesity Drug

The FDA recently approved a new drug called lorcaserin (brand name Belviq) for the treatment of obesity.  Lorcaserin causes an average of 13 lbs (5.8 kg) of weight loss over a year, compared to 5 lbs (2.2 kg) for placebo (1), which is less than the other recently approved drug Qsymia (formerly Qnexa; topiramate/phentermine).

Learning about obesity drugs is always a good opportunity to gain insight into the mechanisms that underlie the development and reversal of obesity.  If you've been following this blog for a while, you already have a pretty good guess what organ this new drug acts on.  Make your guess and read on!

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Two Great Quotes About Obesity (technical)

By Dr. Hans-Rudolf Berthoud, from a recent paper, "The Neurobiology of Food Intake in an Obesogenic Environment" (1).  I came across it because it cites my review paper (2).  My perspective on obesity is similar to his.  From the abstract:
The modern lifestyle with its drastic changes in the way we eat and move puts pressure on the homoeostatic system responsible for the regulation of body weight, which has led to an increase in overweight and obesity. The power of food cues targeting susceptible emotions and cognitive brain functions, particularly of children and adolescents, is increasingly exploited by modern neuromarketing tools. Increased intake of energy-dense foods high in fat and sugar is not only adding more energy, but may also corrupt neural functions of brain systems involved in nutrient sensing as well as in hedonic, motivational and cognitive processing.
And a nice one from the conclusions:
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Food Reward Friday

This week's lucky winner... salted nuts!!


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