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What Is Metabolic Flexibility, and Why Is It Important? J. Stanton's AHS 2013 Presentation, Including Slides
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February 5, 2014
4:33 am
Forum Posts: 2045
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February 22, 2010
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As you might have heard, nearly all of the AHS 2013 videos are unwatchable due to technical and production failures. Therefore, I'm publishing my own presentation here in written form, exactly as it was given at the 2013 Ancestral Health Symposium in Atlanta—including slides.

This work is likely to be controversial, as it directly contradicts a great deal of received wisdom—both within mainstream obesity research and within the ancestral health community. The evidence places the energy requirements of the individual cell, and defects of energy production at the cellular level, at the beginning of the causal chain of both obesity and the…

February 5, 2014
6:17 am

J. Thank you, thank you! This is a very fascinating and interesting presentation! It helps explain why some people are able to manage their weight and why others who try to lose have a difficult time. I recently have gone primal, no grains, no sugar and lots of quality meat and I feel great. Again thank you for your post. V

February 5, 2014
6:49 am
Danny J Albers

Very nice and informative write up and seems to confirm a lot of my totally anecodotally baesd advice found here:

(Not sure if links work here but its my keto adaptation vs low carb limbo page on my blog, by far my most read article).

One point on the "Dont exercise until you are fat adapted", I have never heard this and I also seem to think that we can all burn body fat just at impaired rates so think it may be good idea to state that outright incase someone reads this article and thinks they can't burn any at all. Just like impaired glucose metabolism slows the rate of glucose uptake but does not stop it completely...

Anyway on the dont exercise point, I have never heard that, I have always heard not to exercise until you are keto-adapted and the low carb flu has passed. Those not familiar with the more intricate details of a low carb way of eating often misquote this as "fat adapated" which is why I include terminology in my write up... There is a pretty massive differencee between keto and fat adapated states. And exercising during the "low carb flu" is a recipe for a huge uncontrollable urge to binge.

I think your main point though to start with exercise is very valid. I think you are quite right you are better off excercising a few weeks rather than charging head long into any diet (including low carb).

Exercise is a wonderful proven intervention and I have always stated in my own 100+ lb weight loss that I could not have done it without exercise, and I certainly cannot MAINTAIN it without exercise, even eating zero carb I had to include a fair amount of running (even did a half marathon 5 months zero carb).

Maintaining a massive weight loss, to me, is going to require more than one intervention. Exercise + paleo or + calorie restriction or + low carb or even all three! Further gains can seem near impossible without absolutely extreme efforts... there is a massive price to pay for being 400lbs for ten years it seems...

Eventually the course that brought you that surge of weight loss will indeed stall and you may even regain (I lost 150 total, regained 40 and exercised and ate fairly well the entire time!).

Now I focus on building strength and muscle and increasing my lean mass as focusing on further fat loss becomes such an extreme effort as to my mind its not worth missing out the rest of life to accomplish. I am very healthy and fit despite being "overweight" by medical standards. I am free of my old 3 blood pressure meds a day, have excellent labs and glucose control, can run distances, lift massives amounts of real weight, and hold my own in a boxing match, I have learned to accept this is simply more important then getting down to some six pack which, to accomplish, would simply require me to live a life so extreme I could not provide energy to my family and work.

A great article that got me thinking and appreciate that you took the time to share it, a shame the lecture itself did not film.

February 5, 2014
7:07 am
La Frite

Hi J,
Excellent, I will pass this article to friends and family as it summarizes what I am trying to tell them in a much more clumsy and complicated way. Will save some time 🙂


February 5, 2014
7:28 am

Good paper.

I prefer reading it like this, to watching a vid. I can read far faster than I can watch.

In passing: When you rework the slides for your next show, you need to use larger fonts. When I was teaching and using an 800x600 projector, I found that I couldn't use smaller than 16 pt font and have it ledgeable at the back of the classroom.

Specifics: On your graphs it is very difficult to tell the filled dots from the open dots. Print below the graph is next to impossible to read. Some of the axis text is difficult to read. And that is after hitting command plus to magnify. Twice.


The bibliography should be part of the page. You can have a hide/show button so that it isn't present unless someone wants to see it, but it means that someone who wants to save the web page has the bibliography as well.

Once again thanks.

February 5, 2014
7:56 am
Dan Brown

Thanks, J. Good read. On a critical note, though, you mention "going catabolic" three times, but don't explain what this means. Catabolism, to me, means "breaking down," as in a triglyceride breaking down to 3 fatty acid molecules and a glycerol molecule, which I take to be a good thing, to "burn" (oxidize) fat for energy. However, that doesn't seem to conform with your context. Where have I gone wrong?

February 5, 2014
9:30 am
Brian Beaven

J. I really like this presentation. It explains a lot about what is going on at a cellular level. Would you mind if I put a small quote from this article on facebook and shared a link to the article?

This is what I'd like to quote:

"So, we have successfully restated the problem as “To lose fat, first you must lose fat.”

And now it’s time to talk about exercise. We know that exercise temporarily helps dispose of blood glucose even in the insulin resistant, and that insulin sensitivity temporarily increases after exercise. However, what’s far more important is that exercise, unlike weight loss, is proven to restore fat oxidation—both basal RER and in response to a high-fat challenge meal. "

February 5, 2014
9:55 am

@Dan Brown

My guess is that he meant it as something along the lines of breaking down your muscle mass to use as a source of energy, thus the protein recommendation.

@ J.

Great content. I like the abundance of references and the topic itself is very interesting. It's a shame about the lost video, but I too actually prefer it in writing.

February 5, 2014
9:58 am
neal matheson

Brilliant J, very informative and nicely pitched.
"And why did that process accelerate so dramatically after 1979" Do you have data from other countries that also suffer from a large diabetic/obese population, and more importantly does that data corrolate with current dietary guidelines?

February 5, 2014
2:34 pm

I like the content, especially the part about normoglycemic obese individuals (2 of my siblings) and skinny type 2's ( I am a normal weight person who can easily put up pre-diabetic numbers. I also love the pacing, symmetry, and clarity of your language. I did not understand the graphs...

February 5, 2014
2:38 pm

ps what is a moderate aerobic session- would that be fast walking, slow running? being slightly out of breadth but able to hold a conversation running or biking, or being not out of breadth at all, but pushing it a little? again, I like the elegance of language and thought in this presentation.

February 5, 2014
3:05 pm

Would meal timing help fat oxidation, like eating 3x a day instead of 6x a day?

February 5, 2014
6:37 pm

This was very interesting. Thank you for taking the time to make your presentation available despite the technical glitches at AHS 2013.

I have one question though:
You write that metabolic inflexibility is caused by a defect in the cells, independent of neuronal or hormonal inputs. Yet, you state that exercise can restore met flex in ten days. How is that possible? If the defect is in the cells, ten days seems largely insufficient to change anything about it (I mean, cell or mito turnover must be much longer than that, and neuronal and hormonal changes are irrelevant).

February 5, 2014
7:58 pm

Another great article. This has give me a wholenew perspective on the issue. Of course, I've read a lot about mitochondria and understand how exercise can increase their number and make them more efficient, but, even so, I've never really grasped the fact that it's really a bottom up rather than a top down issue. This opens up all kinds of possibilities. It'll be interesting to see where the research leads.

February 5, 2014
8:47 pm

J, a quick mostly unrelated question. I have read very little on variety in diet in the ancestral health community. do you think from a health perspective this offers any benefit given the wider variety of nutrients you would be exposed to? I know for myself that it helps a lot with making sticking with paleo a non issue when you are always eating something new you never really get tempted to eat Neolithic foods but is there anything else to gain from it? I know palaeolithic man ate in excess of 300 types of food per week so maybe we can benefit from it also? Can't find the study that I got those statistics from unfortunately.

Many thanks!

February 5, 2014
9:51 pm
Forum Posts: 2045
Member Since:
February 22, 2010
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Yes, mitochondrial (dys)function provides a plausible mechanism for the strong genetic and epigenetic influence on obesity, T2D, and health in general.  As I've said elsewhere:

This [the fact that the majority of obesity is genetically controlled: see, for instance, Maes 1997] does not mean that people bear no responsibility for their decisions! What it does mean is that the same decisions will lead to wildly varying results.

All some people have to do to lose a bit of weight is to stop drinking four beers or sodas per day, or to stop eating gluten grains. Some people must strictly follow a Primal or Paleo diet -- including restricting all "food villains" -- and exercise daily. Some people must additionally supplement with vitamin D3, magnesium chelates, sufficient iodine, and/or other nutrients. Some people have to do all the above, plus dramatically restrict certain classes of nutrients and their overall food intake, in order to maintain a weight-reduced state. And despite their best efforts, many of these people will never have a "six-pack" without surgical intervention.

I'm glad you're seeing success with this new way of eating!



"I have always heard not to exercise until you are keto-adapted and the low carb flu has passed."  That's what I'm contending may be the wrong approach, and you seem to agree: exercise (particularly fasted exercise) helps restore your ability to oxidize fat, and that will help you adapt to LC, VLC, or keto more quickly.  (And yes, we also agree that "fat-adapted" and keto-adapted are not the same thing.  "Fat-adapted" just means metabolically flexible.)

The upside of being prone to fat gain is that you are probably also prone to muscle gain.  I recently told a friend of mine, who has seen success with paleo but is still big, "You are a big, strong, burly dude.  Embrace that.  Instead of trying to starve yourself down to being skinny, just lift heavy and bulk up until you don't look or feel fat anymore." 

You're a bear, not a panther.  Embrace that and get big.  No one gives strong 250-pound dudes flack about carrying an extra 30# of fat.


La Frite:

It's always great when I can boil the science down to a few practical takeaways.  Thank you!



The presentation is an artifact of being originally given as a speech with slides: obviously if it were intended as a journal article, I'd have formatted it differently!  (For example, I deliberately left the citations and attributions in Flyspeck 8 because they weren't meant to be read by the audience at the talk: the slides go by far too quickly.)

Meanwhile, you can click the graphics to open the originals, which are full-screen resolution and will be much easier to read.


Dan Brown:

"You mention "going catabolic" three times, but don't explain what this means."

In the world of exercise physiology, from which much of the RER/RQ literature comes, "going catabolic" refers specifically to catabolizing protein, in the form of lean mass, in order to produce energy (mostly glucose via gluconeogenesis).


More soon!


February 6, 2014
2:29 am
eddie watts

hey J this piece is great, I have just shared it on my Facebook.
what I especially like is how it fits in with all the performance trainers and nutritionists out there too.
the whole cycling of nutrients to get through plateaus (carb/fat/protein cycling while always keeping a baseline of protein etc)
this is fantastic.
I was looking forward to seeing your talk though so am sad about that.
you come across as similar to Dr Ben Goldacre
which is so nice for me, as someone who talks fast and processes information fast, many people in interviews talk too slow and I can't maintain interest.
well the article was still brilliant, if you decide to do this as a video off your own back please let me/us gnolls know!

February 6, 2014
4:36 am
Forum Posts: 2045
Member Since:
February 22, 2010
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Brian Beaven:

Please feel free to quote my article, and to share it as widely as possible! 



The web stats say that many of my readers agree with you.  And yes, you're correct about my use of "catabolic".


neal matheson:

I have my hands full making sense of the US data...and the data from other countries is usually more dubious and of poorer quality.

That being said, the conclusions I've drawn are consonant, at least, with the basics -- in which a Westernized diet reliably produces obesity, diabetes, and other pathologies, almost irrespective of your dietary starting point.  I'll be presenting some of them soon.



As an author, I'm proud of my writing, and do my best to make it aesthetically pleasing as well as informative.  Thank you for noticing!

The intensity of the aerobic exercise sessions in the interventions ranged (if I recall correctly) from 60% to 80% of VO2Max.  This can mean anything from a normal walk, for someone very obese, to a moderately fast run for someone in excellent shape.  And the problem with the "talk test" is that trained people can converse at a much higher % of VO2Max than untrained people.  For instance, a trained person might be able to converse at 80% VO2Max, while an untrained person might have trouble at 60%.

Keep in mind that you don't need to run to get aerobic exercise!  Lifting heavy weights in compound movements (e.g. squat, deadlift, row, pullup, many kettlebell exercises) with short rest periods will keep your heart rate high -- as will many sports. Box jumps; farmer walks; cartwheels and pushups and other bodyweight movements...there are many options that are more fun, and develop more skills, than just running.



"Would meal timing help fat oxidation, like eating 3x a day instead of 6x a day?"

In combination with exercise, yes.  If you eat and/or snack often, you never leave the post-prandial state.



"You write that metabolic inflexibility is caused by a defect in the cells, independent of neuronal or hormonal inputs. Yet, you state that exercise can restore met flex in ten days. How is that possible?"

The average textbook presents mitochondria as little static bean-shaped things.  This is completely wrong.  Mitochondria are constantly reorganizing themselves to meet the energy demands of the cell, both at the macro level (they join together into big blobby networks and split apart into smaller units) and at the micro level (the respiratory complexes organize into "supercomplexes").  And they are continually duplicating themselves to meet greater energy demand, and being reabsorbed via autophagy as they age and suffer damage.

Result: if you have any healthy mitochondria left, a combination of energy demand (via exercise), adequate nutrition, and adequate sleep will cause their population to increase.  The problem is if you don't, in which case exercise won't help and you're probably on some combination of VLC and metformin for life.


More soon!


February 6, 2014
5:01 am
Forum Posts: 2045
Member Since:
February 22, 2010
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"I've never really grasped the fact that it's really a bottom up rather than a top down issue. This opens up all kinds of possibilities."

"I used to think my brain was the most important organ in my body.  Then I realized who was telling me this." -Emo Phillips

As I'm fond of saying, most hypotheses of obesity fail trivially when measured against the facts and statistics.  Food didn't suddenly become "rewarding" in 1979, and Americans didn't suddenly become gluttonous and lazy in 1979.  Result: we must look elsewhere for explanations.

Amongst the reason I continue to investigate the mitochondrial pathway is that it fits with the observed reality of both statistics and experience.  I'll be exploring this further in future articles.



"I have read very little on variety in diet in the ancestral health community. do you think from a health perspective this offers any benefit given the wider variety of nutrients you would be exposed to?"

It's instructive to remember that the "wide variety" of ancestral diets is mostly in gathered plants, which make a very small caloric contribution, and whose availability is strongly seasonal in the ancestral world where humans can't fly fruit and vegetables in from Mexico and Chile.  The bulk of calories in the Paleolithic still came from hunted meat.

"Eat what's fresh in your area" is a good guide: usually that means fruit and veggies during spring and summer, nuts and tubers in fall and winter, fish and shellfish when you can get them, and red meat anytime.  If we needed nutrients from twenty different kinds of plants every week, we would never have survived winter!



It is indeed instructive to watch and learn from the athletic performance folks, because there is a lot of money and pride riding on the outcome, and results trump entertaining hypotheses.  Physique competitors and weight-class athletes might not know the biochemistry of antinutrients, but they sure know how to get ripped.  Strength athletes might not know the details of mitochondrial bioenergetics, but they know how many reps to do in order to get stronger vs. get bigger.  Any hypotheses we advance need to take this body of empirical knowledge into account...

...knowledge sadly lacking amongst many academics and self-proclaimed "experts".

At the same time, we must be careful not to assume these solutions are optimal, because they're probably not.

Anyway, yes, please share this article as widely as you can!  It's both important and useful knowledge, and I'm proud to bring it to the attention of the community.  And yes, I'm flattered by a comparison with Ben Goldacre.


February 6, 2014
12:18 pm
Danny J Albers

Thanks for the feedback JS and you are correct I am definately mostly bear, I think I have more neanderDNA then most LOL

One thing I find with lifting extremely heavy and volumously 6 days a week its near impossible to add body fat no matter what I eat so long as I am not adding a tonne of extra bogus calories like 6 bullet proof coffees daily or smothering everything in a pound of butter. And its not like those workouts are not accompanied by massive spikes in appetite. When your fat or emotions crave food willpower can hold it off, but when you do 20 sets of bench presses plus another 45 minutes of support work, or a total of 150 to 200 heavy squats, you erupt into a "don't you dare deny me a massive feed" hunger and pretty much none of that ends up as pastry around the middle!

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