Ketoadaptation

Athletes who drop carbs cold turkey suddenly suck.  It is known.  

But with a smidge of stick-to-it-iveness, performance completely recovers, in virtually every.  measurable.  aspect.  

This was shown years and years ago, in a seminal study by Drs Phinney, Bistrian, Evans, Gervino, and Blackburn.

The human metabolic response to chronic ketosis without caloric restriction: preservation of submaximal exercise capability with reduced carbohydrate oxidation (1983)

Normally, fatty acids fuel low intensity exercise and carbs fuel high.  This is because high intensity exercise requires a high rate of ATP production, and glycogen to lactate generates ATP faster than a speeding bullet.  This is what makes power.  Getting ATP from fatty acids is like draining maple syrup from trees [at first].

mito pic

However, go low carb for long enough and the syrup begins to flow like water.  I lack the time to show what “long enough” entails, but  4 out of 5 studies on low carb diets and performance that only last a few days will show this.  Ketoadaptation takes time; ~3 weeks.


What Phinney and colleagues did was simple: take a few cyclists and measure their physical performance before and after 4 weeks of an isocaloric super-low carb diet (~20 grams of carbs per day).  That’s all.  But in my opinion, this study and the preceding one in 1980 are two of the most important diet & exercise performance studies conducted to date.Phinney 1983While medals and trophies generally reflect fitness levels, aerobic power, and overall physical prowess, they aren’t very scientific.  For this, one thing we have is VO2 max.  It is basically how well you can get more oxygen when you need it.  And RQ reflects the source of the fuel being burned (1 = carbs; 0.7 = fat).  After ketoadaptation, the athletes in Phinney’s study were able to perform just as well while burning fat as they were while burning carbs (ie, same VO2 max but lower RQ).

With me so far?

What happens during ketoadaptation that makes it possible to jump-lift-run-climb just as good as high carb?
1. magic
2. requires more information:

Going back to that analogy, syrup in the tree is like stored fat, the spout is mitochondria, and ATP is the rate of syrup flowing into your bucket.

spout

On the other hand, gas in the tank is glycogen, the hose is mitochondria, and ATP is the how fast your tank fills.  The faster ATP collects in either scenario, the better athletic performance.

It doesn’t make perfect sense, but that analogy will start to grow on you.

So how would you get your bucket filled with syrup faster?  Try “more spouts.”  And reduce the viscosity of your maple syrup by diluting with some ketones.  More than 3 weeks on a ketogenic diet and you have more better mitochondria and can generate ATP just as fast as high carb.


This is biochemistry on a 600-level and you’d need to ask Drs Veech or Watford for the details, but for now, just believe that more better mitochondria means faster ATP production, which is why after ketoadaptation it’s possible to perform as well as high carb.  It’s also why before ketoadaptation on a low carb diet, athletes suck.  You need either mito & ketones or glucose.  Before ketoadaption, you have neither.  Enter: the mice.

Ketogenic diet slows down mitochondrial myopathy progression in mice (Ahola-Erkkila et al., 2010)

Admittedly, this isn’t the best study to demonstrate the point because a ketogenic diet made from trans fats will have some detrimental effects down the line, but the high fat ketogenic nature of such a diet is sufficient to induce ample mitochondrial biogenesis.

Pictures at an exhibition of murine muscles from mice fed chow (CD) or a low carb ketogenic diet (KD).  See all those new mitochondria (arrows)?Mito 1

And again, see all those BIG mitochondria (asterisks’)?Mito 2

This isn’t an isolated finding.  Take a group of mice and jack up their plasma free fatty acid levels to those seen in Phinney’s ketogenic dieters for a short while and you get a similar effect.  Increased mitochondrial everything (Garcia-Roves et al., 2007):mito 3

The magic of a low carb ketogenic diet takes time to develop.  During ketoadaptation, the ability to get ATP from fat & ketones soon rivals that of glucose.  Mitochondria don’t happen overnight…  they take about 3 weeks.

calories proper  <– kindle edition!

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  • Jonathan

    Hey Bill, thanks for all the great articles. (I found your blog through BuiltLean.)

    Are you aware of any studies that have looked at keto-adapted resistance training? Specifically weight training, as opposed to the bodyweight exercises studied in the Paoli, et al. gymnastics paper.

    It seems that a keto diet + general exercise preserves strength and lean mass. Does a keto diet + resistance training allow for strength and lean mass gains or would that regimen simply be preservative as well?

    • Hi Jonathan, thanks and I’m glad you like the site.

      I’m not aware of any studies on ketoadapted / resistance
      exercise / strength gains / muscle hypertrophy.

      But IMO with an adequate protein intake and
      high-enough-intensity resistance training, there’s nothing to prevent strength/muscle gains on keto. Unfortunately most studies are about weight loss, so the best we get is ‘preservation of lean mass’ (eg, Brinkworth 2009, Jabbek 2010, etc.).

      -Bill

  • Great article. I commend you for referencing a very insightful study. I will point readers to the VO2max RQ (0.9) after ketoadaptation…Amazing! This means that at their peak aerobic capacity they are still burning some fat. Most (99%) athletes would have a RQ well above 1. Metabolic adaptation at it’s best!
    Would you comment on why athletes would want to switch to a ketoadapted diet?

    • Hey Pat, thanks for the comment and I knew you’d be interested in this topic! WRT that 0.9 RQ, yeah, I think if
      you get enough mitochondria (ie, ketoadapt), the fat will burn and produce enough ATP to achieve a respectable VO2max.

      On the other hand, I would love to see some RCTs of ketoadapted vs. isocaloric standard diets on athletic performance, strength, etc. I don’t think there would be much of a difference, but I would still love to see the study.

      -Bill

  • Miodrag Mili?

    So you can fall into the middle zone and stay there… glucose to high for ketoadaptation but too low for sufficient ATP production.

    Wouldn’t this be the worst ? Is it possible at all?

    • Are you talking about too much protein or resistance exercise? You could probably get protein pretty high and stay in ketosis (>25 kcal%?), but I’d monitor it closely. Is this what you were referring to?
      If not, then yes, the period after onset of a ketogenic diet but prior to ketoadaptation is probably the worst time for exercise.

  • Solid article as usual. Another point of interest is that increased LPL activity leads to increased IMTG content on a HF diet. Increased IMTG + increased mitochondria content = increased ATP production leading to sustained performance. However, as Pat pointed out, WHY would anyone want to ketoadapt? That is the $64,000 question.

    • Hi Dylan, thanks for the comment.
      Increased IMTG, even better! (I hadn’t thought of that). As to those sixty four thousand dollars, perhaps Pat is holding out on us – the Paoli study Jonathan mentioned doesn’t bring much to the table.
      Dr Phinney, if you’re reading this, care to weigh in?
      best,
      Bill

      • Haha, I’ll be seeing Pat tomorrow, and Dr. Volek on Friday actually. Perhaps we can flesh out some of the theoretical details then. The one thing I do enjoy about ketogenic diets and their ability to sustain performance (at least for endurance athletes), is that it speaks to an individuals personal preference if they’re so inclined. As far as ketoadaptation for performance being superior, that has yet to be seen.

  • There was a large variation in results from person to person, though.
    “2 of the 5 subjects experienced substantial drops in endurance capacity
    (48 and 51-minute declines in TTE, to be exact). One of the subjects had
    a freakishly high 84-minute increase in TTE, while the other increases
    were 3 and 30 minutes.”

  • Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis.
    (Bartlett et al., 2013) http://www.ncbi.nlm.nih.gov/pubmed/23364526

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  • Ketoadaptation works in the brain, too –>
    “A ketogenic diet also increases the number of mitochondria, so called “energy factories” in brain cells.”
    from: The fat-fueled brain: unnatural or advantageous?
    http://blogs.scientificamerican.com/mind-guest-blog/2013/10/01/the-fat-fueled-brain-unnatural-or-advantageous/

    citing this study:
    A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet.
    http://www.ncbi.nlm.nih.gov/pubmed/15469884

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  • Chris

    I personally didnt experience any decrease in lifting performance after passing from a low-carb (1 binging day) to a ketogenic diet…And now I’m 2 months in ketosis (without getting out of the state) and it feels great. I dont feel muscle fatigue after gym and I’m gradually increasing my performance (with HIIT training).

    • awesome; I wouldn’t expect a big difference in performance going from LC IF to keto; most of the hard work is already done! …it’s when athletes shift from high carb to LC, that’s when performance really suffers.

      • Chris

        I agree. however, you know that 90% of the athletes venerate carbs as they have been brainwashed by the supplement industries.

        I have a friend of mine who does commission sales for HerbaLife (a supplement company) and he has little knowledge about metabolism and nutrition but he has been trained to say that: people need 30g of protein per meal (as the body cannot use more than that at once), that athletes need carb loading when running marathons, and many other myths.

        I cannot blame these guys, but I’m really sorry this happens and I’m thinking of ways on how to make people more conscious about nutrition and not take everything for granted.

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  • togume

    Good post!

    How well would this work for high-intensity, intensely glycogen depleting activities for people who are already in top-shape? Can the more-mito & less-viscous syrup analogy hold to replete the fuel tank in cases such as squash, sprinting, soccer, etc?

    Thoughts Lyle McDonald’s (1999) conclusions that for high intensity/interval-training type sports performance will be hurt?

    • Thanks! I understand why people think it wouldn’t work for high intensity activity, but the data keep saying otherwise. I’ve summed up a few more studies here: http://caloriesproper.com/?p=4862

      • togume

        Great! Thanks for pointing me to that. The first comment is interesting, though, when we start talking about D1/Professional athletes who need high intensity activities.

        Most of the data/research is focused on either “broken” subjects, or some lower intensity definition of intense glycogen depleting activities (even the “elite artistic gymnasts”, who may not be hitting lactic threshold/HiiT as others).

        From a purely evolutionary perspective we’re not designed to be putting that kind of activity load on the body with multiple workouts/day, many days in a row.

        Let’s do an experiment ;). However, I’d hate to lose my turbo button again.

        • Yeah, some of the highest intensities I’ve seen was the gymnasts and the Wingate (http://caloriesproper.com/?p=4840).

          I agree, it doesn’t seem like we should be able to do it, and I’m not entirely sure if my syrup & bucket analogy is correct… but there are quite a lot of studies and none have found a “limit,” or level of intensity where ketoadaptation fails…

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  • Ronnie

    ?-hydroxybutyrate is an HDAC inhibitor. This is almost certainly what’s behind ketoadaptation. The following paper shows that Class I HDAC inhibitors promote mitochondrial biogenesis in skeletal muscle. BOHB is a Class I HDAC inhibitor.

    Histone Deacetylase inhibitors modulate mitochondrial biogenesis in skeletal muscle
    http://www.fasebj.org/cgi/content/meeting_abstract/24/1_MeetingAbstracts/lb119

    “These results underscore a central role of HDACs, and most probably of Class I HDACs, in modulating metabolic adaptation in cells and suggest HDACi as valuable tools to study molecular mechanisms implicated in energy metabolism and possibly in metabolic diseases”

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  • spartaman16

    What about after ketoadapting? Does reintroducing carbohydrates into your diet “kick you out” of ketoadaptation? And how much carbs does it take for that to happen? Does being ketoadapted mean that one would have to remain on a low-carb diet exclusively moving forward?

    • it’s easy to get “kicked out of ketosis,” but ketoadaptation entails a lot of enzymatic changes and mitochondrial proliferation which isn’t as easily reversed

  • Jord

    Sure, “fat adaptation” is fine for ultra endurance pissing around at 60% v02 max.
    Anaerobic sports are a different story.
    For max performance, you need carbs. PERIOD.
    Sure, the recent 6 week crossfit study showed similar performance benefits as the other group. Take it out to 12 weeks, 6 months, see what happens.

    Athletes like that eventually hit the wall, burning all that glycogen. The early paleo/zone crossfitters found out the hard way. Sure, felt awesome at first. Then messed their hormone panels eventually.

    I dont understand the magic of ketosis, or the fear of carbs if you’re in an anaerobic sport?
    Sure, you can eat boatloads of fat+pro to replenish glycogen in some convoluted, efficient way… or you could just eat some carbs post workout!
    You probably wont get ft either!