Tag Archives: fat

The influence of ketones on intermediary metabolism

Two studies: one on infusion of D-b-hydroxybutyrate at three different level producing up to 2 mM at the highest level (Mikkelsen et al., 2014); and one on ingestion of a ketone monoester (R-3-hydroxybutyl-R-3-hydroxybutyrate) producing ~3.2 mM (Myette et al., 2018). Both studies were relatively small (n = 6 and 20, respectively) yet interesting.

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Mikkelsen: mainly justified the use of exogenous ketones in T2DM because of their ability to suppress hyperglycemia and hyperlipidemia. And justified ’em in CNS disorders because adherence is poor in this population and goes downhill with increasing disease severity. They’re anti-ketone salts because: 1) the GI distress and salt load with doses required to get into the 2-3 mM range; and 2) they’re often racemic mixtures of D- and L-b-hydroxybutyrate (“D” is the endogenous one).

 

 

As expected, increasing the infusion dose linearly increased plasma bHB:

Further, as expected, brain uptake increased in parallel to plasma levels:

Interestingly, muscle uptake seemed to become saturated and not increase much further… this may be related to the “muscle-sparing effect of fat-derived fuels,” in other words, muscle is sparing ketones for the brain like it does during late starvation.

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ketones inhibit lipolysis

 

 

 

Ketosis in an evolutionary context

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, 2003Hayes et al., 2012).

 

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The Omega-3 Index: Eat Seafood

“Need” is a funny concept.  You don’t need to eat seafood.  You don’t need an appendix or legs, either.

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For example, Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease (Farzaneh-Far et al., 2010)

Telomere length is believed to be a biomarker of aging: the shorter your telomeres, the faster you’re aging.  In the study, they measured telomere length in white blood cells and EPA+DHA in whole blood at baseline and again 5 years later.

omega-3 intake and telomerase

Quartile 1: EPA+DHA = 2.3% of the fatty acids in whole blood.

Quartile 2: 3.3%

Quartile 3: 4.3%

Quartile 4: 7.3%

Potential confounders: quartile 4 was comprised of educated rich white old non-smokers with low levels of inflammation, but the statisticians assure us those variables were controlled for… so there’s that.

 

 

You might be thinking: Bill-man, I don’t feel like getting my Omega-3 Index tested, how much seafood will put me in that fourth quartile?

 

omega-3 index

 

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On the impact of diet on circadian phase setting

We’ve seen that meal size and frequency can influence circadian rhythms, but here are some examples of how nutrients can, too.

Circadian phase advance: going to bed earlier, waking up earlier.  Blue blockers at sunset, bright light at sunrise.  Flying east.  Autumn.

Circadian phase delay: staying up late, sleeping in.  Flying west.  Spring.  Using smart phones, tablets, and iPads in bed at night.  Light pollution.

Relative to adolescents, infants and children are circadian phase advanced.  This is part of what is fueling the movement to delay high school start times.  Kids are mentally better prepared to work later in the day.  With early school start times, performance is down in the morning, but they kill it on video games after school.  Delaying start time by an hour won’t totally fix this, but could help.

 

 

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Low carb, low glycemic index, or something else entirely

Why Low Carb?

OmniCarb (Sacks et al., 2014)

Study design & results in a nutshell:

5 weeks, low(ish) vs. high carb (40 vs. 58%) with the calorie difference split between protein (23 vs. 16%) and fat (37 vs. 27%).  In other words, the low(ish) carb diet was higher in protein and fat.  And there was 2 versions of each diet —  a high and low glycemic index.  Lots of crossing over; all in all, weak intervention but decent study design & execution.

Aaaand nothingsauce nothingburger.  Goal was insulin sensitivity, not weight loss.

 

glucose and insulin

 

 

 

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Endurance Performance Doesn’t Decline on a Low Carb Diet

The new study by Zinn and colleagues doesn’t debunk ketoadaptation. And the authors agree!

In brief, it was 5 ~50-year old recreational endurance athletes. They’ve been training a lot for a very long time. In other words, one way to view this study is the opposite of n00b gainz. Experienced exercisers don’t typically make gains in 10 weeks without drastically changing their training program or increasing protein intake – neither of which occurred in this study.

 

 

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Long-term fat adaptation.

Ketoadaptation

More on physical performance and ketoadaptation

A timeline of ketoadaptation.

 

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FOOD PROFILE

Hey Fam, announcement: I’m moving to Patreon soon — will still post about 4-5 articles per month with at least 1 open to the public. The rest will be for Patrons. I’m still trying to figure it out and I’m open to suggestions!

 

I loved this – when describing the two study diets, which differed markedly in carb content (10% vs. 53%), the authors said they were similar in energy, protein, and “FOOD PROFILE,” meaning low-processed, lower-glycemic foods.

Non-industrial foods.

Hunger-free Diet(s).

BOOM!

Visceral adiposity and metabolic syndrome after very high-fat and low-fat isocaloric diets: a randomized controlled trial (Veum et al., 2016)

 

What happens when you give up industrial foods and start following a Hunger-free Diet (regardless of carbz)?

 

 

EVERYBODY LOSES WEIGHT

 

 

And le saturated fat? Industrial foods are the problem, not saturated fat. One group went from 48 to 31 grams per day (LFHC), the other group went from 42 to 81 (VLCHF): all metabolic parameters improved in both groups.

 




 

Even their livers shrank:

 

 

My only qualm: everyone lost a bit of muscle. NOT SURPRISING when you cut calories & protein and don’t exercise. Protein dropped by about ~25 grams in both groups. When you cut calories, you need to up protein or start lifting heavy shit otherwise you’ll lose muscle. The ketonez won’t help.

 

 

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Exercise & protein, man. Exercise & protein.

-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.

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

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That’s SOME olive oil!

Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy (Lauretti et al., 2017)

I think the whole point of this study was to show-off their swanky EVOO.

“The EVOO was from the olive growing area of Apulia region (Torremaggiore, Foggia, Italy). Olive fruits from the cultivar “Peranzana” were processed immediately after harvesting and EVOO obtained by crushing the olives under mechanical cold pressure to preserve all the nutritional components, and meet the stringent criteria of the premium quality level (free acid content < 0.3 g%, peroxide value < 7 mEq/Kg, K232 < 1.85).”

 

 

Which may or may not be from this company.

Peranzana: it’s a single varietal olive oil, meaning it’s made from only one type of olive – similar to buying varietal wines, eg, malbec – it specifies the grape, but not the location, producer, wine’s name, etc., etc. You can actually get a Peranzana EVOO or olives online.

 

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High Meat, Low Carb During Pregnancy

The Motherwell Studies

Around 50 years ago a group of expecting mothers were asked to increase their meat intake to about a pound a day and cut out the carbs (Campbell et al., 1996). They assessed a variety of traits of the infants and again when they were all grown up.

The babies were healthy, but as adults they tended to have higher blood pressure (Shiell et al., 2001), higher cortisol response to stress especially if the diet was also low in green vegetables (Reynolds et al., 2007), and modestly worsened glucose tolerance (Reynolds et al., 2007).

 

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