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 metabolic syndrome.
However, as my bibliography shows, both metabolic flexibility and its origin in mitochondrial energy production are well-established, easily measurable phenomena—particularly within the field of exercise physiology—and the body of research continues to accumulate, finding defects of cellular energy production within the pathology of numerous diseases, from Alzheimer’s to Type II diabetes. It’s an exciting field—and it gives us both a theoretical framework in which to understand real-world phenomena, and many useful takeways for everyday life.
Yes, these pathologies are multifactorial. And, as I said in my 2012 AHS presentation on hunger, I don’t claim to have made a revolutionary new discovery. I’m bringing an existing field of research to light, and integrating it into our understanding.
So: here it is. Put on your thinking cap and enjoy.
Introduction
Hello. I’m J. Stanton, gnolls.org.
You may wish to open the bibliography in another browser tab or window so that you can follow the references.
Life requires energy.
The human body contains somewhere between 10 and 100 trillion individual cells. Each one of these trillions of cells must continually convert fuel into energy in order to keep itself alive—and, thereby, keep us alive. In fact, a substantial fraction of our body mass is dedicated to providing a constant supply of fuel to every one of our trillions of cells, and removing the waste products of their energy production. Our respiratory system; our digestive system; our circulatory and lymphatic systems; substantial parts of our endocrine and nervous systems; and, lest we forget, each of these systems is itself made up of cells with their own energy requirements.
In short, the reason that large animals, including humans, are so heinously complicated is because every one of our 50-plus trillion cells requires a massive, complex, interdependent infrastructure to ensure it receives both an uninterrupted supply of fuel and of the cofactors required to burn it—independent of wild variances in energy demand via activity level and external temperature, and wild variances in energy supply via meal timing and composition.
Therefore, when we’re asking high-level questions such as “What causes obesity and the metabolic syndrome? And why did that process accelerate so dramatically after 1979?” it behooves us to examine our internal infrastructure—our energy supply chain—for bottlenecks and disruptions.
(Please note: While I’m happy to throw around terms like homeostasis and oxidative phosphorylation, I will use layman’s terms when possible in order to make this talk more accessible.)
What Is Metabolic Flexibility?
Unlike an automobile engine, which usually requires one very specific type and composition of fuel, most of the cells in our body can burn several very different fuels. However, we produce the overwhelming majority of our energy from two of them: glucose, the sugar from which starch is also formed, and fat. Metabolic flexibility is the ability to switch back and forth between the two major energy substrates—glucose and fat—based on availability and need.
How Is Metabolic Flexibility Measured?
Without a steady supply of oxygen, our cells can only produce a small amount of energy; they can only produce it from glucose; and the waste products quickly build up within the cell and prevent further energy production. This is called anaerobic respiration: it’s why we can’t sprint or hold our breath for very long, and why lack of oxygen, via blood loss, heart failure, or stroke, kills us so quickly.
In contrast, our cells require oxygen to efficiently extract all the energy from glucose. Furthermore, they require oxygen to burn fat at all! So except for a few specialized tissues, like red blood cells, and a few temporary conditions, like heavy sprinting and holding our breath, almost all of our energy comes from burning fuel with oxygen—called aerobic respiration.
Now. It turns out that a molecule of glucose contains six oxygen atoms—whereas a fat molecule contains only one, and releases a far greater amount of energy to the cell when we burn it. So while fat contains more energy by weight, it takes more oxygen to extract that energy from fat than it does from carbohydrate.
Next: Oxygen enters our body as oxygen gas (O2), but once it’s been used to burn fuel, it leaves as CO2—carbon dioxide. So we can hook a person up to a respirator, and compare how much oxygen and carbon dioxide they inhale with how much they exhale. This process is called “indirect calorimetry”, and it produces two things. First, we get an approximation of how much energy a person is consuming. Second, it produces what is called the Respiratory Exchange Ratio, also called the Respiratory Quotient— an approximation of how much glucose vs. how much fat your body is burning for energy. The RER, or RQ, varies between 0.7, representing 100% fat oxidation, and 1.0, representing 100% glucose oxidation…so lower values mean we’re burning more fat, and higher values mean we’re burning more glucose.
It’s important to note that the RER, or RQ, is a somewhat blunt instrument: it doesn’t account for protein oxidation, gluconeogenesis, or anaerobic respiration, and rapid changes can throw it off. However, it’s a good approximation that is relatively easy and non-invasive to measure.
Why Is Metabolic Flexibility Important?
Both the availability of energy, and our usage of it, change dramatically over time. We can be sleeping or sprinting; cold or hot; eating or fasting; consuming meat, fish, vegetables, potatoes, popcorn, or a Big Gulp. Our ability to adapt to these conditions depends greatly on the ability of our individual cells to be metabolically flexible—particularly our muscle cells, which use the majority of energy from our bodies. For instance:
- When we ingest carbohydrate, metabolic flexibility helps us control blood glucose, by burning glucose instead of fat. Our RER should be high.
- When we ingest fat without carbohydrate, met flex helps us burn the fat instead of storing it. Our RER should be low.
- When we fast (and everyone “fasts” while they sleep), met flex helps us burn the fat stored on our butt, instead of becoming hungry for sugar or going catabolic. Our RER should be low.
- When we exercise, met flex lets us burn more stored fat and produce more energy at all levels of effort. We can run faster, jump higher, move more weight, and go longer on less food before we “hit the wall.”
What Happens When Metabolic Flexibility Is Impaired?
When met flex is impaired, our cells can’t easily switch fuel sources: the RER, or RQ, is stuck in the middle. This leaves us unable to respond well to changing conditions. For instance:
- When we ingest carbohydrate, we cannot dispose of blood glucose as quickly as we should. This causes poor glycemic control—wide blood sugar swings.
- Our ability to burn fat in response to high-fat meals is reduced.
- Consequently, we have a decreased ability to increase energy output after meals (called “post-prandial thermogenesis”.)
- When we fast, our ability to burn our own fat is diminished.
- Since our ability to burn fat is diminished, we have a continual demand for glucose, even at rest. Therefore, fasting makes us hungry more quickly—and becomes catabolic more quickly.
- Therefore, a metabolically inflexible person attempting to fast or restrict food intake is very likely to also reduce their metabolic rate.
- When we exercise, our ability to burn our own fat is diminished, and our demand for glucose increases.
What Are The Real-World Consequences Of Impaired Metabolic Flexibility?
Now that we know what’s happening internally, let’s examine what that means. In particular, I ask those with experience losing weight, and in attempting to maintain a weight-reduced state, to listen closely and critically.
- If we have poor glycemic control, that means we have higher and more rapid blood sugar spikes and crashes. We all know this is unhealthy—but it also makes us more dependent on stimulants and bready, sugary snacks to maintain our mood, our attention span, and our ability to stay awake after meals.
- A continual demand for glucose at rest means we will become hungry much sooner after eating. Specifically, we become hungry for sugar and carbohydrate in order to “keep our energy up”
- Then, if we manage to ignore these hunger signals through willpower, our body is likely to reduce our energy expenditure in response, making us feel tired and listless, and making weight loss even more laborious. (At extremes, this can manifest itself as poor cold tolerance, and other signs and symptoms of hypothyroidism.)
- Consequently, intermittent fasting and heavy caloric restriction are likely to be both difficult and unsuccessful for the metabolically inflexible. And I suspect this to be a primary mechanism behind the so-called “low carb flu”.
- Finally, a continual demand for glucose during exercise means we will be dependent on a steady supply of energy drinks, bars, gels, and other sugary treats in order to perform physical activities that usually don’t even burn the energy we’ve ingested.
Do these consequences sound familiar to anyone?
Why Is Metabolic Flexibility Impaired?
To answer this question, we must first ask “Is metabolic flexibility a byproduct of neural and endocrine signaling, or is it an intrinsic property of individual cells?”
It turns out that if we measure the metabolic flexibility of individuals, then remove a sample of their muscle tissue and measure its response to fat and glucose in vitro (i.e. outside its neural and endocrine environment), we find the following:
“The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment, which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle.” (Ukropcova 2005. Also see Corpeleijn 2010, Berggren 2008)
So: while elucidating the precise mechanisms involved is still what’s known as an “active research area,” we can be reasonably sure that we are not just looking at an artifact of a broken hypothalamus or a dysfunctional HPTA axis.
What is this defect? Actually, there are two.
Metabolic inflexibility towards glucose—a low “insulin-stimulated RER”, the inability to increase glucose oxidation—appears to be limited by the glucose disposal rate: cells can’t burn more glucose because they’re insulin resistant. They can’t absorb it quickly enough.
In contrast, metabolic inflexibility towards fat—the inability to increase fat oxidation in response to fasting or fat intake—appears to be caused by mitochondrial dysfunction. (Mitochondria are the tiny organelles within each of our cells that actually perform aerobic respiration, turning fuel and oxygen into energy via the citric acid cycle—also known as the Krebs cycle or the TCA cycle.)
And while I’ll save the citation bombardment for my bibliography, which is available online,
I’ll note that this is both a subject of extensive recent research and a robust experimental result. Sample quote:
“Upon a more thorough analysis of the different components of metabolic flexibility, we found that in vivo mitochondrial function was the single predictor of basal RER.” (van den Weijer 2013)
To summarize the current consensus:
- Impaired glucose oxidation, an inappropriately low RER, is due to insulin resistance.
- Impaired fat oxidation, an inappropriately high RER, is due to mitochondrial dysfunction.
- Both are metabolic defects at the level of the individual cell.
How Does Metabolic Flexibility Become Impaired?
This is a fascinating subject and a continuing area of active research, and I would require another presentation to do it justice—so permit me to summarize the current state of the scientific literature.
First, an important note: obesity and metabolic inflexibility are not equivalent! Significant populations exist of both obese normoglycemics and skinny Type 2 diabetics. That being said, let’s explore some possible causal relationships.
- Higher basal RER is associated with subsequent weight gain, independent of total energy expenditure. (Zurlo 1990)
- Fasting, post-prandial, and exercise-stimulated fat oxidation are impaired in the prediabetic. (Corpeleijn 2010)
- When overfed, healthy first-degree relatives of Type 2 diabetics gain substantially more weight than those without such a family history. (Jenkins 2013)
- Quote: “…An impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals.” (Heilbronn 2007)
- Quote: “Metabolic inflexibility, lower adaptation to a HFD, and reduced muscle mitochondrial mass cluster together in subjects with a family history of diabetes, supporting the role of an intrinsic metabolic defect of skeletal muscle in the pathogenesis of insulin resistance.” (Ukropcova 2007)
In other words, fat oxidation seems to fail first—and though we don’t yet know how, insulin resistance appears to be among the consequences of it. And in support of the mitochondrial theory:
- Quote: “…Mitochondrial content is lower across the continuum of insulin sensitivity and is not limited to T2DM.” (Chomentowski 2011)
- Mitochondria from obese Type 2 diabetics oxidize fat at a lower rate, even after adjusting for mitochondrial mass.
- Mitochondrial dysfunction is observed in relatives of Type 2 diabetics that are not yet themselves insulin-resistant.
In summary:
- Impaired met flex begins with an inability to increase fat oxidation in response to fasting, diet, or exercise.
- This propensity is strongly heritable, probably due to mitochondrial dysfunction.
- Insulin resistance follows, which causes an inability to increase glucose oxidation in response to diet. We are now metabolically inflexible.
- Impaired metabolic flexibility is not a byproduct of a broken brain, a damaged liver, or a faulty thyroid. It is a pair of metabolic defects at the level of the individual cell, multiplied by the trillions of cells that make up our muscle tissue until the effects become directly and objectively measurable via the respiratory exchange ratio.
How Can We Regain Our Metabolic Flexibility?
First, we must remember that we have multiple problems: metabolic inflexibility towards glucose, which manifests itself as poor glycemic control—and metabolic inflexibility towards fat, which manifests itself as poor response to fasting, calorie restriction, and low-carb diets.
The proven way to improve your insulin sensitivity—and, thereby, your met flex towards glucose—is to decrease your fat mass. However, weight loss alone does not improve fat oxidation! Basal RER remains just as elevated in the post-obese as it does in type 2 diabetics and the pre-obese.
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.
“…A defect in the ability to oxidize lipid in skeletal muscle is evident with obesity, which is corrected with exercise training but persists after weight loss.” (Berggren 2008)
So. How much exercise do we need? We don’t know the minimum amount…but 3-5 45-minute sessions of moderately intense aerobic exercise per week, or 3 30-minute moderate aerobic sessions and one session of weight training, have been tested and proven sufficient to restore basal rates of fat oxidation to the level of healthy control subjects. And if you’re willing to do that 30-45 minutes every day, you can do so in about ten days.
Let me be clear. Exercise is not important because it burns calories! Exercise without calorie restriction is a remarkably ineffective weight loss intervention, because it usually makes us hungry enough to replace the calories we burn. Exercise is important because it restores your ability to oxidize fat—both when fasting and after meals. And we can tie this in with mitochondrial dysfunction by noting that exercise is proven to increase mitochondrial volume.
Caveat: your results may vary. Here’s the response of several healthy, lean individuals to a decrease in carbohydrate content of their diet: all over the place. So just because a study says the average obese person restored their metabolic flexibility after ten days of consistent exercise doesn’t mean you will.
Other interventions: We can decrease the carbohydrate content of our diet. For someone in energy balance, over time, basal RER will tend to converge towards the ratio of carbohydrate to fat in the diet. However, contrary to dogma which says “Don’t exercise until you’re fat-adapted,” it might be better to start exercising before playing with macronutrients—so that you have the metabolic flexibility to use them.
Finally, since the metabolically inflexible will tend to go catabolic more quickly, it’s probably a good idea to ensure you’re eating plenty of good-quality protein with each meal. And, while continual snacking is counterproductive, it’s probably not a good idea to try intermittent fasting right away. In fact, tolerance for fasting is a reasonably good diagnostic for impaired fat oxidation: if you feel light-headed after a few hours without food, you may be experiencing metabolic inflexibility regardless of your weight, bodyfat percentage, or BMI.
Conclusions and Summary
- Metabolic flexibility is the ability of our bodies to switch back and forth between their two major energy substrates: glucose and fatty acids.
- Met flex allows us to control blood sugar after eating, burn fat while fasting, and otherwise respond appropriately to changes in energy supply and demand.
- Met flex is typically measured via changes in the Respiratory Exchange Ratio (RER), aka the Respiratory Quotient (RQ), which approximates the ratio of fat to carbohydrate our bodies are burning during the time period measured.
- Metabolic inflexibility begins as a cellular-level impairment of the ability to increase or diminish fat oxidation.
- Impaired fat oxidation contributes to insulin resistance, and a consequent inability to increase or diminish glucose oxidation.
- Current evidence suggests that impaired fat oxidation is mitochondrial in origin, genetically and epigenetically heritable, and is among the causes, rather than the consequences, of obesity and insulin resistance.
- Moderate exercise can restore your ability to oxidize fat. Fat loss can restore your ability to absorb and oxidize glucose.
Takeaways
- You can’t exercise your way out of a bad diet.
- You can’t diet your way out of not exercising.
- Exercise is not important because it burns calories: it’s important because it restores metabolic flexibility.
So:
- Eat plenty of complete protein.
- Play frequently.
- Push your limits occasionally.
And whether we brand it as “Paleo,” “Primal,” “Ancestral Health,” or, as I do, “Eat Like A Predator”—it’s good to know that our recommendations are on a sound footing—evolutionarily, empirically, and biochemically.
I’m J. Stanton, gnolls.org. Thank you.
(My bibliography is available at this link.)
I am confident that this avenue of research will continue to provide both explanations for real-world phenomena, and useful takeaways for everyday living. Much more fascinating data has come to light in the months since this presentation—and though we are in the early stages of integration, I currently believe pathologies as disparate as depression, Parkinson’s, and the metabolic syndrome will be linked via defects of energy production at the level of individual cells. Further, I believe that the resulting neural and hormonal imbalances will frequently be shown as effects, not causes: attempts by the brain (and other regulatory organs) to maintain a broken homeostasis.
Yes, these pathologies are multifactorial…and we’re still trying to figure out exactly how mitochondrial energy production becomes impaired. However, I wish to be clear about which direction the evidence is currently leading me.
Live in freedom, live in beauty.
JS
I’m proud of this one: spread it using the widgets below. Also, this is your last chance to get a “Die Biting The Throat” T-shirt—so jump on over to the pre-order page and pick one up before they go away.
[…] / Posted on: January 01, 1970GNOLLS.ORG – As you might have heard, nearly all of the AHS 2013 videos are unwatchable due to technical […]
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
Very nice and informative write up and seems to confirm a lot of my totally anecodotally baesd advice found here:
http://primalnorth.blogspot.ca/p/keto-adaptation-vs-low-carb-limbo.html
(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.
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 🙂
LF
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 800×600 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.
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?
[…] and it would probably make all this discussion about sugar or not sugar somewhat superficial. What Is Metabolic Flexibility, and Why Is It Important? J. Stanton’s AHS 2013 Presentation, In… Reply With […]
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. “
@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.
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?
Neal
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…
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.
Would meal timing help fat oxidation, like eating 3x a day instead of 6x a day?
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).
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.
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!
Valerie:
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:
I'm glad you're seeing success with this new way of eating!
Danny:
“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!
Sherwood:
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!
JS
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!
Brian Beaven:
Please feel free to quote my article, and to share it as widely as possible!
Fmgd:
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.
v:
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.
tam:
“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.
ValerieD:
“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!
JS
ChrisM:
“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.
Jack:
“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!
eddie:
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.
JS
[…] This could be an important step in his career, so we're excited for him. For thought – checked out J. Stanton's What is Metabolic Flexibility and found it one of the best articles I've ever encountered – so much of what he wrote really […]
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!
[…] rice and beans or lentils cooked with ham in broth. I did stumble across this excellent post about metabolic flexibility, which I need to actually read in its […]
Great presentation, it ranks right up there with my other all time favorite series “why are we hungry”
I think one of the biggest changes that happened in the 80’s is snacking and meal frequency. When I grew up in the 70’s my mom would never give me an after school snack as it would “ruin my dinner”. We were too busy playing during the short morning recess at school so we didn’t snack then either, it was breakfast, lunch and dinner most days. Now it seems kids are constantly snacking. Every time my son’s have an afternoon play date there are always snacks.
Do you think that eating low fat, high carb meals every 3 hours can reduce our ability to use fat as a fuel since we are using mostly glucose all day? If we are not using the metabolic machinery that burns fat all day I would think our bodies would reduce the resources going into that pathway. I think this is the another difference between the SAD high carb diet and the kitavans and Okinawan high carb diets that no one talks about. I’m sure the okinawan’s didn’t come in from the fields to snack every couple of hours and they worked hard. This forced them to keep their metabolic flexibility and use stored body fat between meals.
I believe that snacking has played a huge roll in the obesity epidemic. Not because it added calories so much as it changed our metabolism, affected our metabolic flexability and made us hungry all the time. Once you start snacking it creates a cycle that makes you hungry so you snack more. But once you start eating like a predator your urge to snack stops and your hunger normalizes.
How does bad fat oxidation lead to bad glucose handling?
JS,
This is off topic- sorry. I originally followed Art De Vany Paleo or ‘Evolutionary Fitness’. He subscribes to no dairy of any kind except a little cream in your coffee and a little cheese as flavor in your salad. But as a 48 year old perimenopausal woman, I am worried about this. I hear that after menopause women rapidly lose calcium and we have to build up our stores before menopause. My blood work on no/little dairy shows my serum calcium at 8.5 mg/dL (2013) , 8.7 (2011), 8.5 (2010). I went Paleo in August of 2009 and in May of 2009 before Paleo I was 9.1. The reference range is mg/dL 8.5 – 10.6. I remember Art De Vany simply saying that I should remember to eat my leafy greens. The Chinese don’t traditionally eat dairy, but they have bone broth soup regularly. I am not lactose intolerant, but I lose more weight dairy-free. Since I have gained weight this winter I am considering cutting out dairy, but I’m not sure it is the wise thing to do. Any thoughts?
“I think one of the biggest changes that happened in the 80′s is snacking and meal frequency. When I grew up in the 70′s my mom would never give me an after school snack as it would “ruin my dinner”. We were too busy playing during the short morning recess at school so we didn’t snack then either, it was breakfast, lunch and dinner most days. Now it seems kids are constantly snacking. Every time my son’s have an afternoon play date there are always snacks.”
This is a consant rub with me and my children. If I am “lucky” the kids are given fruit but more often I end up being the ogre taking bisuits and crisps (cookies and chips) away.
Three squares is very much a modern invention.Medieval people generally ate two meals a day.
Danny:
Yes, lifting heavy will tend to partition extra “calories” towards muscle growth (which is energetically expensive) instead of fat gain. Especially if you're eating keto, it's very, very difficult for a healthy person to gain fat mass in that scenario.
Glen Nagy:
“Do you think that eating low fat, high carb meals every 3 hours can reduce our ability to use fat as a fuel since we are using mostly glucose all day?”
Yes, for several reasons.
And yes, I therefore agree that the increase in carb-heavy snacking has contributed to obesity and MetS. As I've shown in various installments of “No Such Thing As A Calorie” (e.g. part VIII), when you eat can affect both fat mass and health just as much as what you eat.
Of course, this is yet another case where the mainstream advice is not only wrong, it's actively injurious — so I don't expect it to change for a long time.
tam:
As I mention in the speech, we're still not sure how that happens. Petro at Hyperlipid has been doing some deep, grotty mitochondrial biochemistry that may elucidate the mechanism.
More soon!
JS
v:
If you're consuming bone broths, you've got plenty of calcium coming in, so that won't be your problem. Besides, the problem with calcium isn't usually under-ingestion, it's under-absorption and under-utilization.
Calcium requires adequate vitamin A (not beta-carotene) and vitamin D3 in order to be absorbed, and adequate vitamin K2 to be deposited in bones and teeth (where you want it) instead of arteries (where you don't). This is why calcium supplementation famously does nothing for osteoporosis, and often increases heart disease.
K2 is a tricky one to get, because it's mostly available in grass-fed dairy and grass-fed organ meats. It's actually one of the few supplements I take: this is my preferred form, and the most cost-effective. (Yes, it's expensive, but the bottle will last over two years at 1 drop/day: the suggested dose of 15 drops is ridiculous. Also make sure they send you the K2-MK4 only: there's a combination K2/D Thorne sells that some people have been sent…which is worth about 1/3 as much but whose packaging is very similar. Verify that you got the K2-MK4 when you get it.)
neal:
These days it's more like one square meal (dinner) and eight snacks, some of which are passed off as meals (e.g. breakfast).
I'm finally caught up! Thank you, everyone, for your support…especially those who bought a copy of TGC or a DBTT T-shirt. And it's finally dumping rain and snow here in Tahoe after an extended drought, so I'm going to take a well-deserved day off and go ski it.
JS
what about natto for vitamin k2? i have just started to eat it and found that it cured my constipation that had recently started up from going lower carb higher protein. i tried to search how jaminet feels about it and tofu, but i didn’t find anything with a quick search of his site. i would be surprised if the PHD were against fermented soy since japanese women are the longest lived with Hong Kong women coming in second. i lived in taiwan 7 years and the consumption of tofu was quite high.
what is another good source of A outside of eating liver, which i can’t stand. lastly, do you know of any situation where the body would actively block the absorption of vitamin d? thanks!
from jenny ruhl:
“An interesting side note to the issue of high serum phosphate is the finding that rising serum phosphates will lower Vitamin D production as Vitamin D is one of the regulators of blood phosphate levels. (Discussed HERE). If you have abnormally low Vitamin D levels when not supplementing Vitamin D, this could be pointing to the fact that your serum phosphate level is unhealthily high.”
I am a teacher, so I have the summers off, during which time I try to be outside a lot. I am always tan. So in July when I had check-up bloodwork done, I was surprised that my Vitamin D was 25.4 Low out of a reference range of ng/mL 30.0 – 100.0 Since Vitamin D is also a major player in bone health, that is why I am mentioning this finding here. I take no supplements at all because I want to get all my nutrients from food. Once I have a clear symptom of a vitamin deficiency, I can take a supplement and more clearly see if it does what it is supposed to do. The problem with this strategy is by the time a symptom shows up (a broken wrist from significant bone loss, etc), it might be too late to do something about it. But thankfully my health is fairly good. I had one three day cold during which I took no medicine and I recovered quickly while many of my students and fellow teachers have gotten uncomfortably sick (fevers, throwing up, losing days of school). I don’t take any medications. I have diabetes in both parents and can run high blood sugars if I eat like most people, but I control what I eat so I’m OK that way. Anyway, I’m focusing on bone health right now since I am approaching the magic age on menopause, so any insights you have into the above would be much appreciated.
sorry for the double posts. here is the link to the jenny ruhl post mentioned above:
http://diabetesupdate.blogspot.com/search?q=vitamin+d
Enjoy your skiing!
v:
Natto is a source of K2-MK7. We think that MK-7 ought to have the same beneficial effects as MK-4, which we get from animal products, but the studies are all on MK-4, so that's what I take. And if you can stomach natto, you're a stronger person than I!
Foods containing actual vitamin A (not beta-carotene, a precursor which is inefficiently converted, and in some cases, not converted at all) include grass-fed butter, egg yolks, liver, organ meats (especially eyes) and shellfish. Fortunately, most of those are the same foods that contain K2-MK4. Keep in mind that the US government permits beta-carotene to be labeled as “Vitamin A” on nutrition labels…
Ruhl's posts confirms the biochemistry: too much vitamin D and calcium, with too little vitamin A and K2, can cause all sorts of problems since the calcium is absorbed but not deposited where it needs to go (bones and teeth).
The problem with getting D3 from sun is that during the winter in high latitudes, the sun barely gets high enough in the sky to be of sufficient intensity to produce D3 in our skin! Then there's the cloudy day problem. I, too, try to get as much sun as possible, but I take D3 when I can't. (Note that too much D3 is immunosuppressive…for me, 2000 IU is fine, but 4000 can be a bit over the line.)
JS
nice article. thanks for making complex things simple.
also kitavans live in a tropical island? yes? so they may get more sunshine. + they probably don’t snack all day long.
cheers,
(i have ordered a shirt.)
Before I can think of an intelligent question I simply wanted to say:
this piece is clear, concise, doesn’t go out on wild tangents, makes verifiable claims, is well supported by a lot of evidence of different types, & openly attempts to reconcile conflicting evidence rather than ignore contradictory findings.
This is a stand-out example of superlative scientific argument-building and communication. Bravo!
PS: You’ve temporarily restored my faith in humanity [1hr ago I read “Dr.” David Katz’s ad-hominem attack on Gary Taubes’ recent NYT article]
Thx for the reply, js. but you missed the vitamin d point. I should be getting plenty of D from sunshine in NJ in the summer, so why am I testing low in July when I’m out all the time and have a tan? that brought in the point about phosphates that jenny ruhl was making.
on another topic, i don’t get why you think the perfect health diet is so great. the safe starches jaminet recommends spikes my blood sugar for quite a while. he should advertise it for anyone BUT people with blood sugar problems/relatives with diabetes. and what’s with him trying to scare people off from eating meat and green veggies saying this causes glucose deficiency and he got scurvy and diverticulits gall stones etc from eating this way. what a joke. did his wife have all of these side effects he mentions? i think this guy is cuckoo cuckoo. and as for diverticulitis- how does he know he didn’t have it before the low carb diet? what he should have done is said all that crap in his book and then told people with diabetic relatives to eat to their meter and stay at a minimum under 140 one hour after a meal and 120 two hours after a meal. with the stuff he recommends, i don’t think i could do that. i had 20 carb grams of corn tortilla chips (about 16 pieces) and my blood sugar went to 135 in an hour. before paleo my A1c was a pre diabetic 5.9. after a year it was 5.6 (2010). last year with more biking after eating, it was 5.3- without his ‘safe starches’.
@v
Just so you know, the more tanned, the less vit D your skin produces with the same amount of UVs. I know it because I am a southerner (North-African) and tan super easily. Since I live in higher latitudes, I need to be outdoors A LOT during summer. My wife (northern-european) would fry in 30mn, while I can stand hours as long as I have developed the tan.
But yeah, I don’t pretend to know why your number was low, I was just mentioning a thing that definitely bit me in the past.
pam:
Thank you! I do my best.
And yes, the little I’ve seen about Kitavan dietary patterns indicates that they eat one big meal a day, with the rest of their calories coming as “by-the-ways” during work. They also smoke like chimneys.
rs711:
Thank you! Sometimes I feel overwhelmed by the Big Picture that I’m just beginning to see and understand, and wonder if I’ll ever be able to communicate it to others. I’m glad I’ve been able to bring this part of it into focus for you.
Yes, the nutrition field is full of hypotheses that don’t account for observed reality, and are therefore prima facie bankrupt. Furthermore, it’s become clear to me that most pathologies for which people are chasing brain-based or endocrine-based explanations are actually caused by failures of energy production at the cellular level. Brain and/or endocrine dysfunction is a downstream consequence: they’re just trying (but failing) to maintain a broken homeostasis. I expect the greater medical and research community to understand this in about 10 to 20 years, if we’re lucky.
v:
I don’t know enough about Vitamin D metabolism to know why that might be the case.
Re: Perfect Health Diet, obviously someone who has a major disorder of glucose metabolism (diabetes) should be cautious with their glucose intake! And no, I wouldn’t advise anyone to eat in such a way that it dramatically spikes their blood sugar, no matter whether they are technically diabetic or not. You’ll note that I said in my review “…there are clearly some people with metabolic issues around carbohydrate (even “safe starches”). And not all VLC issues are caused by insufficient starch or solved by more starch.”
However, given their exhaustive treatment of the nutrients required for humans to survive and thrive, I still believe that, as I said, “The Perfect Health Diet is the new baseline from which all future attempts to determine the optimal human diet must be argued and measured.” I don’t know of any other single source that comes close to providing such a baseline, let alone recommend both specific foods and patterns of consumption that best satisfy those needs. So, yes, everyone should feel free to deviate from that baseline as necessary.
JS
for people who DON’T know that they need to measure blood sugar and have inherited problems using glucose , like me before about 2011, the perfect health diet is DANGEROUS. my fasting blood glucose was always good. that is the last thing to deteriorate. he should preface his book by saying ANYONE with diabetic relatives needs to get a cheap relion meter from wal-mart and measure their post prandial blood sugar after eating a serving of his safe starch. i think my caveat would be extrememly helpful to people like me who have stealth prediabetes/diabetes. in other words, i would have liked the above in your review.
ps the crux of the issue is how prediabetes/diabetes is commonly diagnosed. many people have glucose processing issues and don’t know it. this piece is MISSING from high profile bloggers like you, de vany, sisson. thank god i learned about it from jenny ruhl.
In the email you sent out announcing the publication of this article online you mentioned that the readership of your least popular article far outstripped the number of people who watched the 2012 AHS video.
For my part, I far prefer reading this kind of technical information rather than watching a video. While reading I can pause, reread, and ponder a point that I might miss entirely in a video.
Tom Naughton, does excellent, informative, and entertaining videos that I enjoy watching, but they aren’t nearly as technical or in depth as your work. I would encourage you to publish the written version of your 2012 presentation and any other such work you may have.
Modern technology has given us the means to produce amazing audio/visual presentations, but sometimes nothing can beat the written word.
How much is DHA/omega-3 a factor in fat oxidation?
i posted this over at wooo’s site who wrote in her latest post that you are the only paleo blogger she has any respect for:
my only problem with j.stanton is that he endorses the prefect health diet without enough of a warning to people with potential glucose processing issues. i just wrote this to the creator of that diet on his website the perfecthealthdiet.com:
after a google search i see that your diet is not recommended for diabetics:
you say: “Our “regular” diet is not specifically directed at diabetic or metabolically damaged persons. We have a basic diet that is designed for healthy people (represented in the apple – food plate) and we recommend modified versions of the diet for various health conditions – including diabetes.”
but i did not see that caveat in the book i borrowed from my public library published in in 2012. i looked in the index for all references to diabetes. actually, you have a testimonial from a diabetic in your book on page 391:
“I am down from 341 lbs. to 272 lbs. doing mostly Paleo, but modified with some safe starches per your book. Just so you know tis is not just about weight loss for me, I was a type 2 diabetic with full metabolic syndrome and most importantly, I had popping capillaries in my retinas that were leading to blindness. All is better now, no pills, etc. -J. Hippman”
Also, I did not see the modified version of you diet for diabetics on your site that you say you recommend. could you please link to it for me?
lastly, a person does not need to have diagnosed pre diabetes or diabetes to stay away for safe starch. i have neither at the moment, but i have two parents with diabetes. i ate 100 grams of a traditional taiwanese porridge made from white rice and sweet potato. that is a small amount which i measured on a food scale. my fasting bloos sugar upon waking was 95. one hour after eating the porridge of ‘safe’ starch my readings were 145/151. not very safe. i should say i usually eat low carb, so you might make the case that i would not have such alarming readings if i carbed up, however i don’t know if i would really drop that much, especially if i ate your recommended daily intake of a pound of safe starches. my husband, on the other hand, ate the same amount of safe starch as I, and his blood glucose actually dropped from a fasting level of 91 to 79/70 one hour later. so how an individual reaches to safe starch is very individual. my recommendation to you is to strongly recommend that any people thinking of starting your diet who have diabetic relatives should test their blood sugar before and 1 hour after eating your safe starch. if they get readings of 140 and above, your regular diet is not for them. they can buy cheap relion meters from walmart without a prescription. i think it would be irresponsible if you did not do something similar to what i recommend.
i am carrying my part of this conversation over to paul himself. a doctor also commented and wanted specifics so he could better help his patients. i’ll be waiting hopefully for something i can actually use.
ChrisM:
You're not the only person to give that feedback, so I'm sure my 2012 presentation will get a similar treatment.
tam:
That's beyond the scope of a comment: Petro digs into it in this very technical article.
v:
I think part of the problem is that, unlike (apparently) the rest of the Internet, I don't feel comfortable giving medical advice to diabetics.
I've been assuming, perhaps wrongly, that anyone with a major medical diagnosis — whether that be diabetes, anaphylaxis-level allergies, lupus, or anything else — would need to filter any of my recommendations for general health through the needs of their specific condition, let alone any second-hand recommendations from sources I've found valuable for myself.
If you feel misled by that, I apologize.
Yes, anyone with a known disorder of glucose metabolism should trust their glucometer over anything anyone else says. I have long-term diabetic relatives who were first diagnosed decades ago and given advice even worse than what diabetics get now. The reason they're still healthy is because they decided to trust the glucometer over the books full of terrible advice like “beans are great for diabetics.”
Anyway, I'll be interested to hear what Paul says. If I recall correctly, he does say that the “stock” PHD is not a diabetic diet, and that they will need to modify it appropriately to their needs.
JS
Excellent article! I had to read it a couple of times to fully digest it.
[…] could very well be highlighting your metabolic inflexibility. A mitochondrial dysfunction. What Is Metabolic Flexibility, and Why Is It Important? J. Stanton’s AHS 2013 Presentation, In… Skip to the end if you want the "so what do I do about it" bit. Reply With […]
[…] so much. Gives a bit of info on this stuff, but from a metabolic flexibility standpoint http://www.gnolls.org/3637/what-is-m…luding-slides/ : The short and sweet of this is that if you ARE eating more of one or the other (fat or carbs) as […]
[…] I was kind of thinking the same thing. I read this article on metabolic flexibility by J Stanton What Is Metabolic Flexibility, and Why Is It Important? J. Stanton’s AHS 2013 Presentation, In… I was wondering if something like this might help him: How Can We Regain Our Metabolic […]
Dave:
Thank you! I prefer to give my readers a meal of solid, information-dense meat — not a fluffy, sugary, low-information snack that leaves you hungry for real knowledge. (e.g. listicles)
And yes, it takes longer to digest the meat.
JS
Posting test. Paul & v continue their conversation here: http://perfecthealthdiet.com/2014/02/encore-day-paleocon-perfect-health-retreats/comment-page-1/#comment-389931
Very interesting article and information, thank you again! A couple of questions, if you have a moment:
1-What types, frequencies, or intensities of exercises are most likely to restore and/or improve metabolic flexibility?
2-How might pre- or post-exercise feeding interact with the effects of exercise on metabolic flexibility? Are there eating strategies, e.g. re-fueling with carbs after a HIIT workout, that might be improving or diminishing the effects of the exercise on metabolic flexibility? Is there any value or harm in exercising in a fasted state?
Thanks!
The Pooch:
Those are excellent questions, which I've spent a lot of time on since I wrote and gave this presentation, and I'll probably write a full article on the subject someday.
Working on the principle that you train in the energy system you're trying to improve, it seems like a combination of two types of exercise would work:
1. Maximal fat oxidation usually occurs somewhere around and between 50-70% VO2Max, depending on how trained you are. You can go a bit higher and you just end up burning carbs along with the fat, but once you get too close to VO2Max fat burning actually decreases.
Therefore, anything that elevates your heart rate via doing work for an extended period of time should help increase your fat-burning efficiency. This includes all the variants of “cardio”, but it also includes farmer's walks, high-rep kettlebells, barbells, or dumbbells — and most importantly, playing around, whether via organized sports, solo sports, or (even better) unorganized play like climbing trees.
2. Resistance training (which means “weight training” for most of us) increases muscle mass, which improves our ability to dispose of both glucose and fat at all levels of mitochondrial efficiency.
As far as fasted vs. fed training, that gets into mitochondrial biodynamics.
1. Fed training will help increase your mitochondrial mass and population.
2. Fasted training will increase autophagy, which culls the most broken of your mitochondria. For maximum autophagy, train fasted and then don't eat for a few hours afterward, or as long as you can stand it.
There is a place for both: you can't train and recover fasted too much or you'll never gain any mass, but I believe it's good to do so occasionally in order to “take out the trash”, so to speak. It's an iterative cycle: by repeatedly culling the worst and causing the rest to reproduce, you should be able to build up a population of the best, most efficient mitochondria you have left, thereby maintaining the best health possible for you.
JS
still caught in the spam filter i guess :{
no i not! 🙂
[…] deal of metabolic flexibility. Is suspect they are the ones that crash and burn on a VLC protocol: What Is Metabolic Flexibility, and Why Is It Important? J. Stanton’s AHS 2013 Presentation, In… Reply With […]
test
J., this is absolutely *fantastic.* Thanks for putting it all together so cohesively and coherently. I *love* the notion of metabolic flexibility. As a (long time ago) former “cardio queen,” back in the day, exercise was–as it still is for the uninformed–simply about “burning calories.” After joining the lower-carb world and learning about fuel partitioning, and also about nutrient timing, a la Dr. John Berardi’s Precision Nutrition’s emphasis on proper post-workout nutrition & recovery meals, exercise became less about the calories and more about “giving glucose somewhere to go.” I think that idea still has some merit, but over the past couple of years, I’ve learned more about what you’ve presented here — and maybe the reason the “giving glucose somewhere to go” idea is at least somewhat accurate is *because* of metabolic/mitochondrial flexibility (including glycogen stores being flux, as they probably were to some extent throughout evolutionary history). I suspect there are plenty of people out there who’ve never really depleted their glycogen and have no idea what it’s like to *not* have a full tank that keeps gets getting topped off…again and again. (High-sugar breakfast at 7, fat-free muffin at 10, pasta lunch at 1, cookies or pretzels at 3, you know the drill.)
As someone who spent years and years doing “all the right things” (tons of exercise, low-fat diet), yet remained chubby and inflamed, I truly love learning the biochem behind all this, because it’s given me a new appreciation for exercise. The idea of exercise as a penance to be done for the “sin” of eating something nutritionally obscene is completely gone. (Thank goodness! What a terrible reason to want to get one’s body moving, right?!) I see physical movement from a completely different perspective now.
I still go to the gym for a hard workout a few times a week, but I also do a ton of long, slow walks outdoors (even in the cold, I’ll just bundle up) and some low-level lifting with weights at home. I can honestly say it’s all a pleasure now. Instead of a punishment like it was so long ago, working out is an opportunity to keep myself healthy and fit for the long-term. I think lots of walking and other low-level activity is completely appropriate in an ancestral health paradigm, and I love how throwing in the occasional sprint session or bout of heavy lifting gives the mitochondria a reason, or a stimulus, if you will, to *remain* flexible. It’s almost like “use it or lose it.” If the metabolism has no reason to adapt to fat, or ketones, or carbs, or *whichever* of those is available at a given time, then it won’t.
Being flexible and able to comfortably go many, many hours without eating, I have to suppress a chuckle (or maybe a pitiful head shake) when I overhear my coworkers talking about needing sugar at about 3pm…
And I’ve always wondered about hypoglycemics. To me, they are some of the most metabolically *in*flexible of all. If the blood glucose is going to dangerously low levels, that’s a sign that whatever mechanism is supposed to bring it back up and keep things on an even keel is failing–be it cortisol, glucagon, epinephrine, etc. Either that, or obviously they haven’t built up the ability to switch easily over to fat. Really fascinating stuff. (And of course, “dangerously low” means different things to different people. I can be in the mid to high 60s and feel fine, but someone who’s accustomed to constant carbohydrate feedings throughout the day could be bonking in the low 80s.)
You are so very onto something here. Metabolic flexibility is likely at the heart of so much more than obesity. Are you familiar with Carl Lanore and his Superhuman Radio show? He likes to say, “Muscle is metabolic currency, so go to the gym and make a deposit today.” Spot on, except it seems we can make those deposits in a lot of different ways. Heavy lifting once in a while is indispensable, but probably just movement in general, along with occasional fasting — keeping our bodies doing what they were designed to do — works flexibility wonders.
use it or lose it: a saying that keeps its meaning, but can now be applied to so much more than it was originally intended.
it applies to everything in the body i think, if you don’t exercise your mind through learning new things then the ability to actually learn becomes inhibited.
i think this is why older people struggle with learning new things when compared to younger people.
consider the learning curve of life in general: we learn so much from 0-20 years of age
then we mostly learn work and hobby related stuff moving forwards, as a consequence of getting older there is simply less available to learn *about* unless you make a conscious effort to find it.
is it really any wonder that a 60 year old finds it harder to learn new things?
chances are they have not learned new things for what? 20 years?!
(obviously not ALL older people, some will learn absolutely fine)
on the other side of things do any kind of general knowledge quiz and it seems to favour older people: even in groups where the age range is only 20-45 those falling into 35-40 and 40-45 just know so much more than those in the younger 20-25 group (in my personal experience)
i mostly fell across this idea because a paper in the UK ran a story along the lines of “old people struggle to learn new things because their brains are already so full of other information”
which just seems ridiculous to me!
Further to this, consider how we've set up our environment and society so that we can simply glide through – pavements are smooth, roads are flat, automatic cars, desensitising footwear and so on.
My point being, get off the man-made and into the country – walking in the wild is so stimulating, eyes constantly scanning the way ahead, more minimalist footwear feeding back constantly. No wonder we feel so good, not only have we had a deserving break from the urban, but we've given our brains a new constant stimulation through nervous feedback.
Our brains do so much more than learn.
Amy:
“maybe the reason the “giving glucose somewhere to go” idea is at least somewhat accurate is *because* of metabolic/mitochondrial flexibility”
“Giving glucose somewhere to go” is only one part of it. Exercise allows glucose to be transported into muscle tissues independent of pre-existing insulin resistance, post-exercise, which indeed helps dispose of glucose. But met flex towards fat is an independent issue, which is mitochondrially mediated and improves over time as we exercise consistently: the mitos that reproduce tend to be those that are in the best shape, e.g. spewing less ROS.
I am convinced this is what's behind the need to keep snacking every few hours: blood tests show that you're not actually hypoglycemic (the common refrain from the medical profession “Reactive hypo is a myth”), but if you have trouble using fat for energy, you're going to feel crummy and need a sugar hit to keep going, regardless of whether your blood glucose has dropped or not.
And I strongly agree that leaving behind the concept of “I must burn X calories” frees us to do what we enjoy instead of grinding away on a treadmill/Stairmaster/bicycle that goes nowhere. There are many mental benefits to being outside and physically moving around, in addition to the physical benefits of activity — benefits lost by moving in place on a machine.
“If the metabolism has no reason to adapt to fat, or ketones, or carbs, or *whichever* of those is available at a given time, then it won't.” –> Yes. Train in the energy system you want to improve. PCr, glycolytic, aerobic glucose, aerobic fat…
And I've met Carl, but I've never been on his show. Perhaps that should change.
Thank you for the note of appreciation! Once you really “get” met flex, the light goes on — and so many real-world phenomena that were once dark become illuminated.
eddie:
I agree completely. I have to make a conscious effort to continue learning, because there is no encouragement to do so as you get older, particularly in today's emotion-driven consumer society. Don't think! Don't make rational decisions! Let the beautiful flashing images on the TV screen determine your wants…and go consume them.
People who make rational decisions don't make the economy grow in the absence of actual productivity (long since outsourced to Asia). For that you need a population willing to take on debt.
JS
Where can I get one of those RER tests? Maybe one day they’ll sell it like breathalyzers.
J — you’re right about hypoglycemia — many people experience the symptoms while their BG is in the 80s — well above any danger zone. And this really hammers home how very INflexible they are, that they need constant infusions of glucose because they don’t have the metabolic machinery in place to switch to fat as needed. (Or if they do have the machinery, it’s not working properly. Mitochondria asleep at the wheel after years of abuse.) I am so fascinated by all this. Proud to be a nerd! 😉
I’ve also heard that some people feel hypoglycemic not necessarily because their BG is “low,” but because of how fast and how far it fell from where it *had been* previously. So they could be in the 80s or possibly even low 90s, but if it was much higher than that earlier and it fell rapidly, they get those hypo symptoms. Do you have any insight on that?
“You can’t exercise your way out of a bad diet.” & vice versa.
i have noticed that runners around me often think they can “run off” a candy bar (or whatever
(maybe bicyclists too)
i think PHD (moderately low carb 10-30% + low protein) should work for most tho.
cheers,
Paul:
The irony in having made our lives so effort-free that we must “exercise” to remain healthy has not been lost on me.
Seriously: drive to the health club so I can ride a bicycle that goes nowhere? As I said to Amy, there are many mental benefits to being outside and physically moving around, in addition to the physical benefits of activity. Standing on a treadmill and watching TV isn't the same thing at all.
tam:
The equipment is usually found in exercise physiology labs. It's generally used to measure athletic performance — and I'm not aware of any MD who uses it as a health diagnostic.
Amy:
I've heard the same thing, that a rapid fall in BG produces hypos even though the absolute level is still “OK”. I'm still inclined to pin this on metabolic inflexibility, because as I note in the presentation, fat oxidation fails first. You don't just randomly start having poor BG control (perhaps unless you're an incipient Type I diabetic)…the failure of fat oxidation is what appears to cause the poor BG control. Petro at Hyperlipid has been going through the mechanisms for how this might be happening at the mitochondrial level.
pam:
It's interesting how everyone always gets hungry enough about 30-45 minutes after exercise to replace the calories they just burned!
Yes, the PHD is a good starting point for most people. I tend to consume somewhat higher protein than it recommends, but I'm nowhere close to sedentary.
JS
[…] What Is Metabolic Flexibility, and Why Is It Important? J. Stanton’s AHS 2013 Presentation, In… […]
[…] Exercise is the key if you have lost the capacity to burn your own body fat for fuel. Look here: What Is Metabolic Flexibility, and Why Is It Important? J. Stanton’s AHS 2013 Presentation, In… Conclusions and Summary Metabolic flexibility is the ability of our bodies to switch back and […]
Thanks JS. Really interesting article.
One question – in those who can’t oxidise fat to produce energy, where does all the fat go? Is it just wasted i.e. excreted? Or is it stored?
I ask because I suspect I might have a problem with this, although I’m not sure. I seem to only function with carbohydrates but I don’t store fat – I’m very lean (skinny guy – 5’9 and 120lbs) – so I’m assuming it just leaves me.
i know a person who fuels before working out. then refuel after working out.
the shirt arrived. very cool.
(you should have “Die biting the throat” mug, pins, etc etc)
Hal:
Except in certain rare pathologies, fat floats around in the bloodstream for a while (not by itself in any significant quantity — it's packaged into lipoproteins, because oil and water don't mix), after which it gets either burned or reabsorbed by your fat cells.
Fat is not a passive storage vault! Adipocytes are continually releasing fat into circulation and taking it up from circulation.
Lack of met flex has little to do with your absolute amount of bodyfat. (It's a lot easier to accumulate more bodyfat if you're metabolically inflexible, but the fat didn't cause the dysfunction.) The best way I've found to address it is to get regular exercise, both aerobic and resistance, stop snacking, and eat like a predator.
Note that I used to be the guy you had to feed every three hours or I got cranky with everyone — and this was with daily exercise!
pam:
You can even get “peri-workout” shakes now — so you can eat DURING your workout, too. Pretty soon we'll just be walking around with IV glucose drips.
I'm glad you like the shirt! I don't want to overload my fans with nerga, but I'll look into other potentially useful stuff.
(Yes, I could open a Cafepress/Zazzle/etc. store…the problem is that they charge so much for what they make that it's not worth my time to sell them to anyone!)
JS
[…] I talk about in the book, this is likely largely due to stabilization of blood sugar (from improved metabolic flexibility) and the healing of the gut lining (which then prevents migraine-inducing components of foods from […]
The diabesity epidemic is spreading world wide, even in poor countries where people have trouble getting enough calories. Why might that be, what is a common factor? Perhaps the export of the products (corn wheat, soybeans) of industrial farming methods, with GMOs, pesticide residues etc. ?
The result of agriculture has been a planet of 7 billion people, most of whom have to eat crap food!
Jack:
I highly suspect it's due to the same dietary trends we've seen in the USA. As to the mechanisms involved, I'm working on that, and it'll be the subject of this year's AHS presentation!
JS
I wonder if it’s outdoor exercise before noon that does the trick: http://www.ctvnews.ca/health/more-sunlight-could-help-shed-the-pounds-study-1.1759034
tam:
Most of the citations in my bibliography showing improved met flex are via exercise done indoors — so while I've always encouraged outdoor exercise and being outdoors in general, it's not the mechanism by which exercise improves met flex.
That said, there are many benefits to sunlight exposure! However, interpret that article with caution, as it's a small associational study, with all the confounders you'd expect.
JS
[…] “What Is Metabolic Flexibility, and Why Is It Important?” By gnolls.org […]
[…] —J. Stanton […]
What does research show regarding post heaving lifting protein drinks? My teenaged boys can’t be dissuaded that those are necessary and improve muscle building. They are skinny guys so do need a lot of calories and play varsity soccer and wrestle.
If you want to build muscle, it’s important to make sure you have protein in your system soon after a heavy weight workout. Protein powder is one way to do this, and it’s quite convenient! However, there are both alternatives and caveats to this.
Caveats:
1. Most commercial “protein drinks” or “protein bars” have very little protein and a lot of sugar (or artificial sweetener)…and oftentimes it’s soy protein or some other Frankenfood. (*cough* Muscle Milk *cough) I don’t recommend anything but pure whey isolate for this reason (see below for my recommendation).
2. Because of all the filler, they’re also very expensive *per gram of protein*. Someone pays for all that advertising. Hint: it’s you.
3. If you’re not consuming enough energy (“calories”), it doesn’t matter how much protein you consume or you won’t get any bigger…especially if you’re trying to do endurance exercise, like soccer, at the same time.
4. If you really want to Get Big you’ve pretty much got to give up on cardio and just start eating and full-body working out. No “bodypart splits”…just the basic compound movements. Squats, deads, power cleans, presses, pulls (chins and rows), loaded carries. The assistance exercises come in when you need sport-specific training or aren’t satisfied with what you get after all that! I refer you all to the work of Dan John (danjohn.net)…”Mass Made Simple”, “Even Easier Strength”, etc.
Alternatives:
1. EAT FOOD. Cans of tuna are cheap, portable, and a lot better for you than “ProMax 36000 Muscle Fuel Deluxe Gainer (blueberry donut flavor)”. Leave a can opener in your kit and suck one down right after lifting.
2. So long as you eat a protein-heavy meal within perhaps 30 minutes after lifting, you’re still fine. Skip the post-workout fluff: just head home and eat. You can foam roll at home and do bosu ball stuff never.
3. I think of “protein powder” as a bridge between PWO and getting real food. As such, half a scoop (15g) is fine and it will last you forever at that rate. The only “protein powder” product I consume is unflavored whey isolate from NOW Foods, because it’s basically 100% whey and zero fillers. Get a 10# bag of that, take 15g (half a scoop) at a time as a bridge between PWO and dinner, and the bag will last you about forever. No, it doesn’t taste like a blueberry donut. Suck it up, princess!
JS
[…] —J. Stanton […]
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Hi JS
I keep re-reading this article every month or so: it’s one of the most enlightening articles I’ve encountered with regard to my personal medical matters and, as my knowledge of human nutritional science grows, I appreciate the significance of another sentence every time I read it.
This time it was the claim that “we can be reasonably sure that we are not just looking at an artefact of a broken hypothalamus or a dysfunctional HPTA axis” which caught my attention.
Is it not possible that, although the immediate cause of poor met flex is poor ability to switch between energy sources at the cellular level, that that inability is itself caused by endocrine dysfunction (such as abnormal levels of cortisol or thyroid hormone)? I suspect that this is the case, in addition to inherited genetic tendencies to poor fat metabolism.
Even though variability of metabolic function is preserved when cells are separated from their endocrine environment, metabolically healthy cells would surely lose some of their function when exposed long enough to an especially destructive one?
I’d be interested to hear your views on this.
I think your site’s great. I appreciate your efforts to provide advice in curing these various pathologies as well as elucidating their biological causes
Hal
I’m glad you find my work illuminating!
It is indeed possible for a primary HPTA axis disorder to cause mitochondrial damage and impaired metabolic flexibility as a consequence — but these cases (e.g. Cushing’s, Hashimoto’s, certain cancers) are rare compared to those caused at the mitochondrial level by species-inappropriate diet and lack of exercise. Exogenous T3 isn’t solving the obesity epidemic! That being said:
I agree: it is very likely that once your higher-level systems like HPTA are no longer able to compensate for broken mitochondria and start breaking, the resulting neural, hormonal, and biochemical environment (“milieu interieur”, if you’re trying to impress people) is indeed disruptive to mitochondrial health — resulting in further impaired met flex –> impaired glucose tolerance and fat oxidation. Like many situations, it’s a positive feedback loop that only ends once your body settles into a stable disease state, usually Type 2 diabetes.
Meanwhile, while it’s often beneficial to treat side effects, it’s important to keep the first cause in mind — because most treatments are either wholly ineffective, or they focus on “fixing” side effects like impaired glucose tolerance, and thus can never fix the underlying mitochondrial problem to pull you out of the disease state into health. (Remember, weight loss alone does not and cannot improve fat oxidation.)
(Note that depending on how long you’ve been Type 2 diabetic, and especially if you have inherited broken mitochondrial from a diabetic mother, you may be stuck for life with palliative measures like metformin and low-carb diets. This is consonant with the empirical evidence that the longer you’ve been T2D, the less likely you are to be able to recover from it.)
That’s actually a good series of questions: thank you for asking them!
JS
I’m curious as to whether estrogen levels (estradiol : estrone : estriol ratios) and estrogen : progesterone ratios were taken into consideration?
I have a budding theory of my own regarding the worldwide (people and animals) phenomena going on – getting fatter for no obvious reason, possibly having much to do with increased widespread exposure to xenoestrogens – which also suppresses thyroid function and dopamine levels (says the brain: “help! can’t get that reward! must eat more sugar! or fat! or fat and sugar!”).
I don’t think there’s much left in the world anymore that isn’t exposed to these poisons, which may account for all the metabolic troubles happening to people all around the world as well as in wildlife… one wonders if there is any safe food left in the world.
Without properly functioning thyroid activity, the mitochondria can’t do their job right… and with too much estrogen (including the the imbalance favoring the “bad” estrogens and little-to-no progesterone to balance) the thyroid can’t work right, nor can the liver, nor can the adrenals.
Sleep is disturbed, the body has cortisol and adrenaline flooding when it should be asleep and repairing (happy little mitochondria) and hypothalamic signaling goes all over the place, which further compounds the problem, because then the body is out of sync with Earth, and disrupted circadian rhythm means nothing in the body can function properly. The timing belt is broken. (I think artificial light is also part of the larger problem, which could also explain more of the worldwide fat conundrum.)
I’d love to know your thoughts on this!
Patricia:
The endocrine disruptor hypothesis is plausible. I suspect that it does indeed contribute to the problem — but without good historical statistics on both the use of such chemicals and the levels of them found in human blood/tissue, I don’t have a good way to evaluate or quantify the contribution. If you know of anyone who’s done that, or tried, do let me know!
JS
[…] all about timing. Eating the right carbs at the right time helps improve your body’s metabolic flexibility, or the ability to burn both glucose and fat as energy. When you fuel your body with carbohydrates, […]
I don’t understand how the study authors come to this conclusion:
“In conclusion, evidence indicating mitochondrial defects as a driving factor of metabolic inflexibility and insulin resistance are far from conclusive or even unavailable. It will be important to test whether whole body or skeletal muscle metabolic flexibility to lipid is affected by muscle mitochondrial characteristics such as density, morphology, and activity. In addition, the role of metabolic flexibility in muscle lipid accumulation and the development of insulin resistance requires further studies. Only this kind of data will allow us to establish a causal link among impaired capacity to metabolize fat, muscle lipotoxicity, and insulin resistance.”
in the Metabolic flexibility and insulin resistance study. It seems like they are making too much of the outlier cases. What do you think J?
Think you might appreciate this one:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710317/
Thanks for doing this work.
The site is back up! I hope this means you’ll be writing again. Your voice is deeply missed.
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