Tag Archives: exercise

Fasting, circadian biology, and epigenetics

From the best I can gather, one of the more immediate players in circadian biology is the coenzyme nicotinamide adenine dinucleotide (NAD), which participates in a variety of redox reactions.  Fasting increases the intracellular NAD/NADH ratio, setting off a cascade of events involving epigenetics and the regulation of metabolism.

NAD activates sirtuins, a family of deacetylase enzymes.  This is epigenetics.

SIRT1

 

SIRT1 regulates the activity of BMAL1 and CLOCK, two circadian transcription factors, which target NAMPT, an enzyme that synthesizes NAD.  And in a curious feed-forward mechanism, CLOCK and BMAL1 enhance SIRT1 expression… genetic deletion of any of these players induces insulin resistance (Zhou et al., 2014), and this can be recapitulated with constant darkness: reduced BMAL1 and SIRT1, hepatic insulin resistance; the latter can be reversed with resveratrol (which may or may not be acting through SIRT1; this is controversial).  While alcohol does no great favors for circadian biology, if you’re going to imbibe, perhaps a resveratrol-rich Argentinian malbec served, and this might be the important part, at night, when all of this stuff is going on… coincidentally [fortunately], that’s precisely when most choose to imbibe.

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More on physical performance and ketoadaptation

The various studies on how low carbohydrate diets impact physical performance are very nuanced.  Here’s what I mean by that.

Exhibit A. Phinney 1980

Phinney 1980

In this [pioneering] study, obese patients were subjected to a variety of performance assessments in a baseline period, then after 1 and 6 weeks of weight loss via protein-sparing modified fast (1.2 g/kg ideal body weight from lean meat, fish, or fowl; probably around 80 grams of protein/d, 500-750 kcal/d). They lost a lot of weight, 23 pounds on average, two-thirds of which was body fat. There was no exercise intervention, just the performance assessments.

During the ‘exercise to exhaustion’ treadmill exercise, RQ steadily declined from baseline to week 1 to week 6, indicating progressively more reliance on fat oxidation.  This was confirmed via muscle glycogen levels pre- and post-exercise: during the baseline testing, they declined by 15%; after 6 weeks of ketoadaptation, however, they only declined by 2%, while ‘time to exhaustion’ increased by 55%.  After only 1 week of the diet, time to exhaustion plummeted, as expected, by 20%.

This was, as mentioned above, a pioneering study in the field of ketoadaptation. It also challenges one of the prevailing theories of ‘fatigue’ …while carb-adapted, the subjects fatigued after 168 minutes, with muscle glycogen levels of 1.29 (reduced by 15%); while ketoadapted, they fatigued after 249 minutes with muscle glycogen levels of 1.02 (reduced by 2%).  In other words, they had less glycogen to begin with, used less glycogen during exercise, and performed significantly better (running on fat & ketones).

Exhibit B. Vogt 2003

Highly trained endurance athletes followed a high fat (53% fat, 32% carbs) or high carb (17% fat, 68% carbs) diet for 5 weeks in a randomized crossover study. In contrast to Phinney’s study, these participants were: 1) highly trained; and 2) exercised throughout the study.

Maximal power output and VO2max during a similar ‘time to exhaustion’ test was similar after both diet periods.  Same for total work output during a 20 minute ‘all-out’ cycling time trial and half-marathon running time.  Muscle glycogen was modestly, albeit statistically non-significantly lower after ketoadaption; however, ketoadapted athletes relied on a higher proportion of fat oxidation to fuel performance as indicated by lower RQ at every level of exercise intensity:

Vogt RQ

Again, this is the essence of ketoadaptation. Physical performance as good as or better using fat and fat-derived fuels.

One reason Phinney’s glycogen-depeleted ketoadapted subjects may have done so well is their reliance on ketones (probable) and intramyocellular lipids (IMCL) (possible).  In Vogt’s study, IMCL increased from 0.69 to 1.54% after ketoadaptation…

Also, food intake and body fat declined, and training volume increased in the low fat group; whereas food intake increased, and body fat and training volume declined in the high fat group.  Reminiscent of anything?

High fat, low carb -> eat more, exercise less, STILL LOSE BODY FAT.

Vogt data

Sorcery?  No.  Diet impacts more than just mood and body composition – resting energy expenditure increased in the ketogenic dieters.  This isn’t an isolated finding.

Exhibit C. Fleming 2003 

This was another study in non-trained athletes, consuming high fat (61% fat) or control (25% fat) diets for 6 weeks.  The tests were the 30-second Wingate, to examine supramaximal performance, and a 45-minute timed ride, to examine submaximal performance.

This study differed from the previous two in several significant ways.  For starters, peak power output declined in both groups, slightly more so in the high fat group (-10% vs. -8%).  Furthermore, RQ didn’t wasn’t significantly lower during this test in the high fat group, which possibly suggests they weren’t properly ketoadapted.  In Phinney’s study, the large energy deficit ensured ketoadaptation; this study lacked that aspect, somewhat more similar to Vogt’s, although unlike Vogt’s, these participants weren’t athletes which presumably makes ketoadaptation more difficult.

There are many factors at play… I wasn’t kidding when I said these studies are very nuanced!

Exhibit D. the infamous, Paoli 2012 

These were ‘elite artistic gymnasts,’ who could likely beat you in a race running backwards.  The ketogenic phase consisted of 55% fat and much more protein than the control phase (39% fat; protein: 41% vs. 15%). The significantly higher protein content was modestly offset by slightly more calories in the control phase, which reduces the amount of protein required to maintain nitrogen balance.

In this study, performance was, for the most part, ‘maintained,’ with relative increases in a few of the tests; eg, the “legs closed barrier.”  Changes in body composition were more robust: significantly reduced body fat and increased lean body mass after 30 days of ketogenic dieting (with their normal exercise routine).

Paoli data

The major confounder in this study was the use of an herbal cocktail only in the ketogenic diet group; despite this, the results are largely in line with the other studies.  For more on this study, see here.

Exhibit E. the most dramatic one to date: Sawyer 2013 

Please see here for the details, but in brief, strength-trained athletes showed improvements in high intensity exercise performance after only 7 days of carbohydrate restriction.  The nuances of this particular study are discussed more here.

barbell

Collectively, these studies show that physical performance in both endurance and high intensity realms does not always suffer, can be maintained, and in some cases is improved by ketogenic dieting.  Important factors are duration (to ensure adequate ketoadaptation), energy balance, and regular physical activity (athletes and regular exercisers can adapt to burning fat much quicker than sedentary folks).

 

calories proper

Nutrient Partitioning: …a *very* high protein diet.

Or: what happens when you eat a ton of protein?

RDA: 0.8 g/kg

Active individuals: 1.2-2.0 g/kg (via ISSN)
Comment (1): I think sedentary, physically inactive, and non-exercisers should be in this range to offset disuse atrophy.  And they should exercise.
Comment (2): Do athletes really need more protein than non-athletes?  They have exercise, a powerful anabolic stimulus.  More protein may improve performance or body composition, but they might not *need* it, in terms of nitrogen retention… there’s probably a study on this.

NEED =/= OPTIMIZATION

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Insulin, sympathetic nervous system, and nutrient timing.

Insulin secretion is attenuated by sympathetic nervous system activity; eg, via exercise.  Theoretically, exercising after a meal should blunt insulin secretion and I don’t think this will lessen the benefits of exercise, but rather enhance nutrient partitioning.   And this isn’t about the [mythical?] post-workout “anabolic window.”

Sympathetic innervation of pancreas: norepinephrine –> adrenergic receptor activation = decreased insulin secretion & increased lipolysis (Stich et al., 1999):

Stich insulin

Stich CAS

note how quickly catecholamines are cleared upon exercise cessation

Stich NEFA

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Implications of the circadian nature of ketones.

Ketosis.  Happens during starvation and also by restricting carbohydrates (and protein, to a lesser degree)… might be important for epilepsy and bipolar disorder, too.

ketogenesis

Ketostix measure urinary acetoacetate (AcAc) and reflect the degree of ketosis in the blood probably about 2-4 hours ago.  Blood ketone meters measure beta-hydroxybutyrate (bHB) right now.  bHB fluctuates to a greater degree, eg, it plummets after a meal whereas AcAc takes longer to decline.  AcAc/bHB is usually around 1, but increases after a meal (Mori et al., 1990):Ketone body ratio

Conversely, when glucose levels decline and fatty acid oxidation increases, liver redox potential drops which reduces AcAc/bHB.

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Sarcopenia has little to do with aging

It has to do with the duration of time spent being sedentary.

They say a picture is worth a thousand words, but luckily enough today you get both.

Sarcopenia: “poverty of flesh,” or the age-induced loss of skeletal muscle mass, strength, and function = reduced quality of life.  Sorry old-timers, but I hereby officially revise the definition from “aging-induced” to “sedentary-induced.”  Herein, I present evidence that sarcopenia is not a phenomenon of aging per se, but rather of disuse atrophy.  Dear Webster’s & Britannica, please revise accordingly.

Skeletal muscles: use ‘em or lose ‘em #TPMC

Thanks to Julianne Taylor & Skyler Tanner for directing me to these images.

divide and conquer

Exhibit A. Chronic exercise preserves lean muscle mass in masters athletes (Wroblewski et al., 2011)

This study evaluated “high-level recreational athletes.”  “Masters” just means they were over 40.  And “high-level” doesn’t mean “elite,” it just means they exercised 4-5 times per week.  These weren’t super-obsessed gym rats… it’s probably who I’ll be in 7 years [sigh].

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Look AHEAD – Nutrition Disinformation 2.0

The day you’ve all been waiting for has finally arrived.  Results from the Look AHEAD study have been published.  When I first wrote about this study (HERE), it had been prematurely halted because the intervention was providing no benefits.  Everybody was in a state of shock and awe because Low Fat didn’t save lives.  But that was before we even had the data.  

Reminder: the “intensive lifestyle intervention” consisted of a Low Fat Diet & exercise.  The results?  Yes, they lost more weight than control, but they also took more Orlistat (of which I’m not a fan, see HERE for why):

orlistat

Orlistat = pharmaceutically enhanced low fat diet. 

Their normal diets were not healthy, but neither was low fat –>

med use

Medication use increased drastically in both groups.  The pundits have gone wild because medication use was lower in the intensive Low Fat group at the end of the study, but this is Nutrition Disinformation 2.0.  Eerily reminiscent of the recent Mediterranean Diet study, the conclusions are the same: keep eating poorly and the need for medications will increase.  You can call it a lot of things, but not “healthy.”  The alternative –>  How to define a “healthy” diet.  Period.


Significant adverse events:SAE

The only thing to reach statistical significance was more fractures in the intensive Low Fat group, but you didn’t read any headlines that said “Low Fat breaks bones.”  Imagine if that happened on low carb [sigh]  The next closest thing to statistical significance was increased amputations in the intensive Low Fat group :/

gem:History of CVD

Translation: if you were healthy at baseline, then you could tolerate a low fat diet.  Otherwise, not so much.  This is exactly what happened in the Women’s Health Initiative.

Ha

needless to say, none of the “possible explanations” they considered were Low fat diet Fail.

calories proper

Westside Barbell, Hormesis, and Antifragility

Some people think Westside makes some of the strongest athletes in the world because unlike most other training regimes, they are constantly lifting very heavy weight.  Other protocols restrict heavy lifting to certain times of the year, in-season / off-season, etc.  At Westside, you’re going heavy on an exercise that changes very frequently (every 1 – 3 weeks).  And it’s this latter point that provides the basis for why other people think Westside works.  By constantly changing which exercise is lifted at maximal intensity, the body never fully adapts, or gets into a rut – this is part of Westside’s ‘Conjugate Method.’

The principle is embraced by Crossfit, as per their random workouts-of-the-day, and also follows a tangent of the Hormesis theory: small doses of individual exercises, eg, conventional deadlifts one week, good mornings the next, sumo deads the next week, and so on and so forth – will improve your squats; the body never knows what’s coming (even though you might have planned it weeks in advance, or at least planned to check The WOD Shop).  Also discussed albeit briefly, in Taleb’s Antifragile, wherein being prepared for “random” shocks seem to benefit the system as a whole, or make it stronger.  Sedentary makes you fragile, weak, and soft; exercise makes you robust; Westside is Antifragile.

Antifragile

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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.

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Biohacking holiday weight gain

What should you eat before the big feast?  (hint: eggs.)  And don’t try to compensate in advance by eating less, this will only make you hungrier.  Furthermore, foods in your regular diet are probably healthier than holiday fare, so you definitely don’t want to eat fewer healthy foods to make room for empty calories.

Tip 1. 

Variation in the effects of three different breakfast meals on subjective satiety and subsequent intake of energy at lunch and evening meal (Fallaize et al., 2012)

Participants were served only one of these for breakfast:

And given unlimited amounts of these for lunch and dinner:

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