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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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March 21, 2014
12:32 am
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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

April 2, 2014
12:02 pm
Jack LaBear
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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!

April 2, 2014
3:21 pm
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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

April 3, 2014
2:57 pm
tam
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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

April 5, 2014
5:18 pm
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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

July 17, 2014
6:01 pm
Jenny
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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.

July 17, 2014
8:27 pm
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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

November 9, 2014
12:10 pm
Hal
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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 :)

November 13, 2014
11:55 am
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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:

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 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

December 21, 2014
7:09 am
Patricia
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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!

December 25, 2014
1:36 am
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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

March 24, 2018
8:50 am
Daniel Antinora
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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?

March 24, 2018
10:07 am
Daniel Antinora
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July 7, 2019
9:41 pm
Petra
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Thanks for doing this work.

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