Tag Archives: energy expenditure

The carb/insulin model of obesity was tested again, and it fared better this time.

Posted on November 15, 2018 | Leave a comment

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial (Ebbeling et al., 2018)

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This is another NuSi study designed to evaluate certain aspects of the carb/insulin model of obesity. Understanding the design of this study is critical to being able to properly evaluate the results.

Very important:

 

1. All food was provided, all the diets were healthy, and most people complied.

2. This was a very expensive study. They used great methods.

Study design: during the “Run-in diet,” everyone followed the same diet (C/F/P: 45%/30%/25%) at 40% caloric restriction in order to lose about 10% of their initial body weight.

Importantly, insulin sensitivity was assessed and this may have influenced what happened next, in the weight maintenance phase. I used to put a lot of weight on this theory — eg, the top 25% most insulin sensitive people will do better on low fat whereas the bottom 25% insulin sensitive people (the most insulin resistant, ie) will do better on low carb — this theory has fared better or worse depending on which study you look at. In this study, it did pretty well.

 

 

In the end, we had 38 people in the entering into the high carb arm of the weight maintenance phase and 43 on low carb.

Remember, they all lost weight on the same diet. Now they’re being fed enough to maintain body weight (low carb, moderate carb, or high carb) and we’re measuring things.

Really exciting stuff!

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The current state of affairs in nutri-Twitter

Posted on November 6, 2018 | Leave a comment

Rant.

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1) It’s almost as if you’re either:

a red meat-eating 110% keto-advocate

or

you think red meat and a ketogenic diet is harmful.

 

If you don’t say the diet is magical, the zealots will try to trick you into, or outright accuse you of saying it’s harmful.

Further,

 

2. And the protein/kidney debate re-surfaced again recently. To be clear: no studies have shown direct harmful effects of protein on kidney function. The studies cited by KDOQI are observational and on end-stage renal disease. Not mild kidney disease or slightly impaired renal function. If I had ESRD, I’d rather play it safe and not enroll in one of Jose Antonio’s high protein diet studies (~4.4 g/kg lol).

I’m pro-LC and HP but not anti-LF. Humans have thrived on a wide variety of diets over time regardless of macronutrient composition. Food quality seems more important in this context.

3. If ketones are muscle-sparing, then…

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Posted in Advanced nutrition, diet, Dietary fat, empty calories, Ketosis, muscle, Protein, strength

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Start paying attention to REV-ERB alpha

Posted on January 17, 2018 | 2 comments

Hey team, remember when I was making wild predictions about REV-ERB alpha?

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“Food for thought: an endogenous ligand of Rev-erb is heme (the iron-binding element in red blood cells). Heme is degraded into bilirubin.  Elevated levels of bilirubin cause jaundice. A treatment of neonatal jaundice is exposure to blue light. Blue light is a major regulator of circadian rhythms and Rev-erb is an executive-level player in this game. The primary mechanisms of blue light appear unrelated in these two models (melanopsin activation vs. bilirubin photoisomerization), but seem intertwined, because heme activates Rev-erb.  Cool.” (From HERE)

and statements:

“Pharmaceutical-grade circadian augmentation = unwittingly better-timed meals? Improved body composition? …they were eating more and moving less. … One possible mechanistic explanation comes from mice lacking Rev-erb in skeletal muscle (Woldt et al., 2013). Mitochondrial biogenesis was impaired and exercise tolerance was reduced in these mice. Spontaneous physical activity was lower; thus, it stands to reason that Rev-erb agonism may improve skeletal muscle mitochondrial function. This isn’t entirely consistent with the drug study, but pretty close.” (From HERE)

 

REV-ERB is really really good for skeletal muscle.

Beta-hydroxybutyrate inhibits activation of the NLRP3 inflammasome.

 

 

Well, so does REV-ERB alpha! In a new study, knocking down REV-ERB alpha jacked up NLRP3 and pharmacologically enhancing it attenuated NLRP3 (Pourcet et al., 2017). The consequence of this in REV-ERB KO mice injected with LPS was hyper-inflation. No bueno. Mice given the commercially-available REV-ERB alpha agonist “Stenabolic” were protected.

I’m geeking out about REV-ERB alpha & SR9009. And fwiw, I don’t think anything will actually fully replace the benefits from actual physical activity and/or exercise, although it’s very hard for some people; eg, COPD, CHD, etc. In those populations, if they can’t exercise enough to really improve their condition, something like this might help. But I’m sure perfectly healthy people are going to try it. If you do, let us know in the comments!

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Regulation of Circadian Behavior and Metabolism by Synthetic Rev-erb Agonists (Solt et al., 2013)

Rev-erb alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy (Woldt et al., 2013)

SERcadian Rhythms

“Seriphos“

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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, depression, Dopamine, Exercise, melatonin, muscle, sex, sleep, strength, Sun, vasopressin

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Yet another study showing low carb doesn’t impair performance +

Posted on November 6, 2017 | 1 comment

and by some metrics, at least in this study, might even improve it.

Ketoadaptation enhances exercise performance and body composition responses to training in endurance athletes (McSwiney et al., 2017)

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Advantage of this study over previous ones: 12 weeks. I believe the choice to opt for self-selection over randomization was to improve adherence (which was pretty good for this 12 week-long study). Downside is, well, it’s not randomized. Crossover RCT is best but it’s always a trade-off: sample size, duration, tools, etc., everything has a price. Literally.

Tl;dr: Ketoadaptation doesn’t diminish performance at high intensity even after “draining the tank.”

The study: we aren’t told much about the diets, just high carb vs. ketogenic. And keto group was advised to drink broths for salts, mins, electrolytes, etc.* Speaking of which 🙂 Kettle & Fire is offering 20% off their delish broths/stock HERE.

*I don’t think this qualifies as cheating in this #context.

Before and after the 12-week dietary intervention, a battery of tests were performed: a six second all-out bicycle sprint (SS), immediately followed by a 100 km time trial (TT), immediately followed by a 3-minute sprint (CPT).

These were well-trained, healthy individuals who continued their training throughout the study. This & duration are two important nuances of this study (more on this below).

The biggest finding …*drumroll* … significantly greater fat loss in the keto group and this wasn’t even a weight loss study. They also jacked up protein intake so they didn’t lose muscle mass. Protein declined in the high carb group, but they were able to maintain muscle because carbs increased.

 

WHERE HAVE WE SEEN THIS BEFORE

HINT: HERE

 

 

Whether they knew it or not, this study was designed to test peak power output before (SS) and after (CPT) exhaustively draining the tank (TT). The theory is that ketoadaptation: 1) spares glycogen so there’s some juice left in the tank for the second peak power test, although racing 100 km is pretty tough so there couldn’t have been much juice left in either group; and 2) ketoadaptation relies more on fatty acids at every level of output, as evidenced by the RER figure (below). Fuel usage comes close at high levels of output (both groups rely more heavily on glucose), but ketoadapted is always a little lower (eg, see the right-most point in the figure below). And fat stores are basically limitless whereas glycogen is not. This may or may not have been a factor here.

 

PEAK PERFORMANCE

I don’t know why the authors reported peak power relative to body weight. I could understand lean mass, maybe, but keto lost a lot of weight via body fat. If peak power remained the same (as has previously been shown), it would [falsely] appear to increase in this study.

For a more nuanced interpretation of this study (which is good, I promise!), head over to Patreon! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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20% off some delish stocks and broths from Kettle and Fire HERE. 

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.

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Posted in Advanced nutrition, diet, Dietary fat, insulin, Ketosis, muscle, Protein, strength

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The importance of entraining skeletal muscle’s circadian clock (and how)

Posted on September 19, 2017 | 9 comments

“Literally, every single model of skeletal muscle circadian arrhythmia mimics aging sedentary people who skip breakfast, stay up late, and get sick.”

But first, the human studies that confirm these newer findings aren’t restricted to preclinical models: 1) a randomized CROSSOVER study; two weeks of modest caloric restriction. Same diet; either 5.5 or 8.5 hours of sleep.

In other words, circadian rhythms broke or woke (Nedeltcheva et al., 2010):

 

 

Same diet & energy expenditure + circadian arrhythmia = lose less fat and more muscle. This is basically the opposite of optimal. Large error bars because it was a CROSSOVER study, although it still managed to reach statistical significance.

And this happened despite lower 24-hour insulin AUC (Nedeltcheva et al., 2012). GRAVITAS.

 

 

And in an ad lib setting, “Laboratory studies in healthy young volunteers have shown that experimental sleep restriction is associated with a dysregulation of the neuroendocrine control of appetite consistent with increased hunger and with alterations in parameters of glucose tolerance suggestive of an increased risk of diabetes” (Van Cauter et al., 2007).

 

 

Part 2. THE BETTER PART: The muscle clock, how it works, and how to fix it.

 

 

 

Similar to other peripheral circadian clocks (eg, liver, adipose, lung, etc.), the muscle clock is entrained by LIGHT via the central pacemaker located in the SCN and feeding (via an as of yet unclear mechanism), but also scheduled exercise.

Interestingly, mice who had been subjected to a 6-hour phase advance adapted faster if they exercised early in the active phase (would be morning for humans).

 

 

Much of these data are summarized in a review in Frontiers in Neuroscience (Aoyama and Shibata, 2017).

The muscle clock is entrained by timed exercise but also feeding. This was demonstrated by showing the circadian rhythms in a subset of muscle-specific genes in fed mice were absent in fasted mice.

It is thought that the muscle clock’s function is to prepare us for the transition from the resting/fasting phase (night) to the active/fed phase (day)… and although I like that phrasing, this seems somewhat subjective (and really hard  to test/prove even on a hypothetical level).

 

 

Part 3. The BEST part: impact of various muscle clock disruptions.

Hint: THEY’RE ALL BAD.

 

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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, Dopamine, melatonin, muscle, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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Ketosis in an evolutionary context

Posted on August 15, 2017 | 104 comments

Humans are unique in their remarkable ability to enter ketosis.  They’re also situated near the top of the food chain.  Coincidence?

During starvation, humans rapidly enter ketosis; they do this better than king penguins, and bears don’t do it at all.

Starvation ketosis

 

Starvation ketosis

Humans maintain a high level of functionality during starvation.  We can still hunt & plan; some would even argue it’s a more finely tuned state, cognitively.  And that’s important, because if we became progressively weaker and slower, chances of acquiring food would rapidly decline.

Perhaps this is why fasting bears just sleep most of the time: no ketones = no bueno..?

Observation: chronic ketosis is relatively rare in nature. This doen’t mean animals evolved a protective  mechanism against ketosis.

 

 

Animals with a low brain/carcass weight ratio (ie, small brain) don’t need it. Babies and children have a higher brain/carcass weight ratio, so they develop ketosis more rapidly than adults. Is this a harmful process? No, more likely an evolutionary adaptation which supports the brain.

ketones age

The brain of newborn babies consumes a huge amount of total daily energy, and nearly half comes from ketones.  A week or so later, even after the carbohydrate content of breast milk increases, they still don’t get “kicked out of ketosis” (Bourneres et al., 1986).  If this were a harmful state, why would Nature have done this?  …and all those anecdotes, like babies learn at incredibly rapid rates… coincidence?  Maybe they’re myths.  Maybe not.




 

Ketosis in the animal kingdom

Imagine a hibernating bear: huge adipose tissue but small brain fuel requirement relative to body size and total energy expenditure.  No ketosis, because brain accounts for less than 5% of total metabolism.  In adult humans, this is around 19-23%, and babies are much higher (eg, Cahill and Veech, 2003 & Hayes et al., 2012).

 

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Posted in Advanced nutrition, circadian, clamp, coconut, diet, Dietary fat, Exercise, fat, insulin, Ketosis, Protein, Trans fat

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Exercise & protein, man. Exercise & protein.

Posted on July 1, 2017 | 4 comments

-Basically, any beginner can make decent gains upon starting a new exercise regimen… it’s actually hard not to. Noob gainz.

-What’s easier than doubling exercise volume? PROTEIN.

Patreon link https://www.patreon.com/posts/exercise-protein-12248945

Protein Supplementation to Augment the Effects of High Intensity Resistance Training in Untrained Middle-Aged Males: The Randomized Controlled PUSH Trial (Wittke et al., 2017)

Four groups: 1) high intensity training (HIT); HIT + high protein diet (HIT+P) (1.6 g/kg/d); HIT + high volume (HVHIT); and control. Baseline protein intake was ~1.2 g/kg, so it was about a ~33% increase.

Duration: 22 weeks, which is long enough to actually make some measurable noob gainz.

Results:

Exercise alone (HIT) wasn’t particularly effective but doubling the volume worked.  What’s easier than doubling the volume?  PROTEIN.  Protein is better than doubling the volume for n00b gainz in LBM.

More gainz in leg & arm muscle mass and strength.  Doubling the volume was slightly better for fat loss. CICO? Energy intake declined slightly in HIT but remained stable in HIT+P & HVHIT.

My take? Protein is way easier than double-volume high intensity training.

Protein & exercise, man. Protein & exercise.

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Posted in Advanced nutrition, diet, Exercise, muscle, Protein, strength

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Light and food in the morning

Posted on May 31, 2017 | 6 comments

Suggested pre-reading: Metabolism at night

Recently, when the topic of breakfast came up, I got something like this: “correlation isn’t causation, and anyway, it’s because people aren’t eating bacon & eggs at night, they’re having cake & alcohol.”

OK, you can’t say “correlation isn’t causation” and then suggest a cause, literally, in the same sentence.

But anyway, yeah, that actually is a plausible cause. Cake & alcohol are mainly consumed at night.

Also, metabolism is gimped in the evening: 1) skeletal muscle insulin resistance; 2) adipose tissue insulin sensitivity; and 3) impaired diet-induced thermogenesis.

Continue reading →

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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diet, Dopamine, Energy balance, melatonin, muscle, Protein, sex, sleep, strength, Sun, vasopressin, Vitamin D

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Eating in the absence of hunger

Posted on March 4, 2017 | 20 comments

Good idea? Bad idea? … a bit of a rant

Some gurus swear by the “only eat when hungry” mantra.  I’m neutral on the issue.  In my opinion, it can work for people who are good planners because if you wait until you’re hungry and haven’t planned or prepared a meal yet, then it might be a while until you finally get to eat.  Maybe you’re an hour from home: unlucky => by the time you start cooking, you’re famished and end up overeating.  So you try to repent by skipping breakfast the following morning but fall into the same trap.  Of course, however, it’s not gonna be like this for everyone.

 

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Posted in Advanced nutrition, diet, insulin, Ketosis, muscle, Protein, strength, TPMC

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LCHF negates performance benefit of training. O_o

Posted on January 8, 2017 | 16 comments

It takes about 3 weeks to become fully ketoadapted and you don’t really get more ketoadapted thereafter, at least as per max fat oxidation rates (which seems a pretty good surrogate, imo).

Important point: “Athletes who drop carbs cold turkey suddenly suck.”  And performance usually recovers by around week 3.  This has been confirmed in nearly every proper study on the subject, in a variety of contexts.

 




 

Which brings me to the latest alleged slam on keto & physical performance:

Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit of intensified training in elite race walkers (Burke et al., 2016)

 

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Posted in Advanced nutrition, diet, Dietary fat, Energy balance, Exercise, fat, insulin, Ketosis, muscle, Protein, strength, TPMC

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