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The Science Behind The "Low Carb Flu", and How To Regain Your Metabolic Flexibility
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November 19, 2013
2:25 pm
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The Pooch:

Yes, the more intense you exercise, the more glucose you will burn...and as you approach VO2Max, fat-burning actually shuts off.  Reason: though fat is more efficient and energy-dense, and is the preferred fuel of the body, glucose contains a lot of oxygen in the molecule itself (C6-H12-O6), so fat requires more oxygen intake to burn.

However, this is a bit of a red herring, because we don't spend very much time close to VO2Max.  Most fat burning occurs at rest -- and an intense sprint session elevates resting metabolism for hours due to the demands of recovery, so you'll burn plenty of fat that way too.

There are a few things to keep in mind when doing intense exercise:

1. You'll need more carbs in your diet than a sedentary couch potato trying to lose weight.  It's very difficult to do a Whole 30 and Crossfit at the same time: you'll basically need to force-feed yourself bananas and sweet potatoes.

2. You don't need to kill yourself for half an hour or more to get the benefits of elevated metabolic rate: even 30 seconds of sprinting will push up HGH levels and RMR for a while, and 6-8 minutes of HIIT will make you want to puke if you're doing it right.  After a while you're just trashing your ANS.

3. If you do decide to go all-out and do a WOD, it takes at least three days for your ANS to recover.  Jamie Scott's 2013 AHS presentation talks about this in detail.  Low to medium-intensity cardio is fine, but trying to go all-out every day, or even every other day, is usually a recipe for burnout and failure.

JS

November 20, 2013
7:48 am
Steve
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Different people are different.

A Type 2 Diabetic friend of mine actually handles a modest amount of carbohydrates better than I do!

Just a few steamed mushrooms or a bit of spinach is enough to knock me out of ketosis! That's only about 6 grams of carbohydrate.

Considering that Type 2 Diabetes runs in my family, I need to be careful.

So, I'm aiming for hard-core ketosis to the point where I'm obsessing over the carbs in liver and eggs...

But fear not for exercise - although my body seems to view carbohydrates as poison, my athletic performance is quite good (relatively speaking) on lots of fat with no carbohydates - even during extended fasting.

I'll never be competing at the elite level of athletics, but I am quite happy with my athletic performance fueled almost entirely by fat. As a bonus, my endurance is much better this way.

The notion that people NEED carbs to train is simply incorrect. Carb-tolerant people, go ahead and load up, but understand this does not work for everyone.

November 22, 2013
1:42 pm
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Steve:

Future installments of this series will talk about metabolic individuality -- a concept well-understood in older research, but which fell by the wayside in the rush to solve the obesity crisis via government fiat.

JS

December 1, 2013
9:40 am
Steve
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Looking forward to it!

Your block rocks, by the way. I've got "The Gnoll Credo" on order from Amazon and have been spending the past couple months poring through your blog as well as those of Peter Attia, Dr Eades, and Hyperlipid.

December 1, 2013
9:41 am
Steve
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blog, not block, lol... meh, I guess it works either way 🙂

December 2, 2013
1:52 am
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Steve:

Thank you!  I greatly appreciate the support.  Feel free to discuss the book in the Talk forums once you've read it.

JS

December 4, 2013
8:21 am
Steve
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I wonder if a major factor regarding individuation is the capacity and tendency of a specific person's liver to produce glucose from protein.

The unwritten assumption seems to be that this is similar among all people, but I've yet to see any evidence at all to support that position. Yet, it seems to be regarded as axiomatic.

Actually, it is now known that many type 2 diabetics tend to produce larger quantities of glucose from protein than normal people, but this is usually written off as some sort of defect, perhaps due to insulin resistance.

But what if it isn't simply a symptom of disease? What if this is just how that person's body is actually INTENDED to work? What if there's not actually anything wrong with that person's liver, or at least perhaps the state of insulin resistance is exaggerated?

This is important to consider because a major adaptation of carnivorous animals is the ability and tendency to process large quantities of protein into glucose, while at the same time being extremely intolerant of dietary carbohydrates.

A specific human being who has the biology more on the carnivorous side would tend to be viewed as "defective" and be instructed to continue consuming carbohydrates while then taking insulin and metformin to control blood sugar.

From just a brief google search, I found this:
http://jn.nutrition.org/content/129/10/1896.full
"Nonavian carnivores such as house cats (Kettelhut and Migliorini 1980), rainbow trout (Palmer and Ryman 1972), white sturgeon (Hung 1991) and American alligators (Coulson and Hernandez 1983) are also glucose intolerant as indicated by prolonged glucose tolerance curves relative to omnivorous species such as chickens, rats and humans. In alligators, glucose intolerance is especially pronounced, and several days are required for normal blood glucose levels to be obtained after an intravenous glucose challenge. Rainbow trout are glucose intolerant due in part to the lack of hepatic glucokinase (GK;3 hexokinase type IV, EC 2.7.1.1), which is responsible for phosphorylating glucose and facilitating its uptake into hepatocytes (Palmer and Ryman 1972). Cats also lack hepatic glucokinase and are poor at down-regulating amino acid catabolism and gluconeogenesis when fed low protein diets, indicating obligatory gluconeogenesis. For example, feeding cats a 17.5% protein diet resulted in little change in the activity of hepatic enzymes phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.31), alanine aminotransferase (ALT; EC 2.6.1.2), aspartate aminotransferase (AST: EC 2.6.1.1), and fructose-bisphosphatase (FBP: EC 3.1.3.11) compared with cats fed a 70% protein diet (Rogers et al. 1977). Conversely, in the omnivorous rat (Eisenstein and Strack 1971, Kettelhut and Migliorini 1980, Peret et al. 1981) and Japanese quail (Featherston and Freedland 1973), PEPCK and amino acid transaminases are very adaptable to changes in dietary protein or glucose content."

This sounds similar to a person with Type 2 Diabetes!

But it's a discussion of actual carnivorous animals.

But what if the person isn't actually defective? What if the core assumption that all people are adapted to eating the same sort of omnivorous diet is incorrect?

Actually, this sounds EXACTLY like my own personal experiences with extended water fasting:
"Cats... are poor at down-regulating amino acid catabolism and gluconeogenesis when fed low protein diets, indicating obligatory gluconeogenesis."

I can water fast for several days, exercising every day, and if I ever don't exercise, my blood sugar rises even though I've consumed absolutely no dietary energy in several days, and long since burned through all of the glycogen I started with.

The only explanation I can think of is that my liver is continuing to produce significant quantities of glucose from muscle protein, at a rate which is perhaps "abnormally" high.

The solution for me thus far appears to be to eat a high fat, moderate protein diet, and watch out for any dietary carbohydrates. Nevertheless, I have absolutely no sign of any sort of "glucose deficiency" and actually my blood sugar is still a bit higher than "normal" people even though I am consuming almost no carbohydrates and exercising daily.

If I ever eat more than 150 grams of proten in a day, particularly if I don't exercise, sure enough my blood sugar skyrockets.

Perhaps my rate of gluconeogenesis will decline over time. But perhaps it won't.

Nevertheless, I find it interesting that while this topic is well-explored in other species, it hasn't been in humans. Any deviations from what is assumed to be proper are simply written off as being defects, rather than individuation worthy of further research.

December 5, 2013
2:48 am
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Steve:

You're correct about the biology of carnivores.  Apparently gluconeogenesis isn't something that can be turned on and off quickly...it seems to be slowly upregulated and downregulated over time in both carnivores and omnivores.

Based on my research so far, I think upregulated gluconeogenesis is more likely to be a consequence of impaired metabolic flexibility, rather than a cause.  However, yours is an intriguing hypothesis, and I'm open to evidence that it's the other way around.

JS

December 11, 2013
10:00 pm
Steve
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After reading "Perfect Health Diet" by Drs. Jaminet, today I experimented by eating ~100 grams of carbohydrates from white rice.

My exercise performance cratered: both maximum and sustained power output on an elliptical machine declined by ~30%! No matter how hard I pushed myself, I simply could not exceed about 70% of my normal workout intensity on a HFVLC diet. To top it off, pushing myself was much more of a mental challenge and my form suffered as I tried to push harder, but couldn't.

This is quite different from what you talked about regarding metabolic inflexibility.

My blood sugar has been elevated all day by about 20mg/dL and there are no more ketones in my urine, despite consuming my usual ~8tbsp of coconut oil.

While I'm not certain of all the hormonal and biochemical changes which happened in my body today, my body is clearly telling me: "Don't do that!"

December 12, 2013
1:08 pm
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Steve:

If you're keto-adapted, that means you've likely been VLC for quite a while -- and your tissues become insulin-resistant in order to save glucose for the tissues which absolutely require it (mostly your red blood cells and brain).  Petro at Hyperlipid named this state "physiological insulin resistance" to differentiate it from the pathological insulin resistance of T2D and the metabolic syndrome.

Result: a single glucose bolus is likely to result in bad times, since you're insulin-resistant...and the results you saw aren't surprising.  To really test your met flex, you'd need to eat a ~15% carb diet for several days in a row in order to overcome the physiological insulin resistance.

Whether you want to do that, of course, is your choice, because then you'll have to keto-adapt again going the other way (though it'll be much faster than the first time).

I see this going the other direction, too: people try VLC for three days and go "OMG terrible brain fog and no energy, VLC sucks".  It takes time to adapt either way, and the adaptation period is usually not very pleasant.

JS

December 26, 2013
8:18 pm
Steve
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Well, considering that blood sugar control issues got me started down this path in the first place, I think I'll stick with a ketogenic diet for a while longer before I try experimenting with reintroducing carbs on a regular basis. To this point, being in a ketogenic state has done me nothing but good. However, life is change...

Yeah, I know about the whole physiological insulin resistance thing from Hyperlipid.

I was just surprised that my athletic performance went to crap so quickly after just one meal.

December 27, 2013
9:03 pm
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Steve:

You have to train in the energy system you want to improve.  Just like squats exercise different muscles than pullups, aerobic performance while keto exercises a different energy system than HIIT sprinting. 

Most people, of course, have the opposite problem than you: they're so used to training on a sugar high that they "bonk" the instant their glycogen runs low.

JS

January 11, 2014
4:53 pm
Steve
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FWIW, my exercise routine consists of several strength training exercises to failure, followed by HIIT on an elliptical machine. I do this as frequently as my body feels up to the task, about 3x per week.

In addition to that, I use a Desk Cycle at low intensity for several hours per week while doing things like reading and commenting on blogs 🙂

I'm not sure to what extent any of these things really stresses the "keto" energy system... that would seem to be endurance exercise at significant "aerobic" exertion levels.

Come Spring, I will likely resume bicycling about 20 miles per day several days per week - that being perhaps more of a keto exercise than my current regimen.

January 11, 2014
5:01 pm
Steve
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...and it was HIIT which took the hit from carb-refeeding... I've tried it a few times now with the same result.

I can HIIT with higher power output while I'm in ketosis than after carb refeed.

I speculate that's probably due to insulin blocking fat metabolism while my skeletal muscles are simultaneously insulin resistant, leaving my muscles starved for energy.

Additionally, my HIIT performance on a ketogenic diet is also higher than it was before I adopted a low-carb lifestyle.

I believe this is probably due to my familial pre/type-2 diabetes. So, more than just a temporary thing which I could adapt out of in 3 days of carb-refeeding.

I believe this is a longer-term situation which will probably only ever change when/if the underlying type-2 diabetic disorder is fully controlled. My fasting blood sugar, while now "normal", is still higher than I would like.

January 13, 2014
2:47 pm
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Steve:

Low-rep strength training takes place in the phosphocreatine energy system, so it won't be strongly affected by glycogen depletion.  The glycolytic (sugar-burning) pathway starts being stressed as the reps go up, anywhere from 5 to 10.

HIIT is a combination of PCr (when you start out) and glycolytic (as you continue).  Usually HIIT/sprint/intense performance lasting longer than 8-10 seconds is what takes a hit when you're keto.  However, if you've got both a family and personal history of type II, it may be the case that your glucose metabolism has some intrinsic defects, probably mitochondrial.

As you supposed, low-intensity long-term aerobic activity is definitely the aerobic fat-burning zone, and is what improves on keto.  That's why it's finding favor with some ultra-endurance athletes.

JS

January 18, 2014
11:07 am
Rick
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I'm as confused as ever. Every time I add some carbs back into my diet like oatmeal, rice or a sweet potato, I get fat, and I am already at a 50 gms of carbs per day.

January 19, 2014
12:42 am
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Rick:

People are different, metabolically and hormonally. 

For instance, an obese 55-year-old post-menopausal woman with a history of dieting and weight regain, and a family history of type 2 diabetes, is very different, metabolically, and hormonally, than a 20-year-old male competitive college swimmer sporting 6% bodyfat.  As such, their responses to the exact same diet will be very different!

Yes, "eat more carbs" is the current fashionable solution to every problem...but some people have metabolic defects at the mitochondrial level that don't respond well to that no matter what they do, resulting in lack of met flex.

In order to raise your basal rate of fat oxidation, try a combination of moderate-intensity aerobic exercise at least 3x/week (bonus: do this fasted) and heavy weight/strength work at least 1x/week.  Since exercise causes mitochondrial proliferation, this often helps...unless your base population is too trashed to even get that going: see, for instance, Hernandez-Alvarez 2010 and Ritov 2010.  However, it's worth a try, especially if you've hit a long-term plateau.

JS

February 7, 2014
9:40 pm
tam
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Maybe this post should have a 'metabolic flexibility' tag.

February 9, 2014
1:07 am
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tam:

Added.  Also added links to my 2013 AHS presentation, which covers this subject in more detail.

JS

April 3, 2014
3:56 pm
bea
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I know it was a while ago you asked for input from other women regarding meal timing but thought I'd comment anyway. I only eat 2 meals and tried to push it till later in the day but could not. My BG is always low normal in the mornings so I think I run on cortisol during the day if I don't eat breakfast. I like to eat 60-70 % energy need for breakfast. With most of my carbs then since I've got the wiggle room in the BG#. Top myself off around 2:00pm and upper gut clear of food by bed. I don't think women can handle the full belly load at bedtime. I just can't comprehend 3 meals a day anymore. Too much food and too much time and work.

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