GLUCONEOGENESIS

I get asked about this a lot. Gluconeogenesis. The brain uses the equivalent of 120 g glucose/d. During starvation, brain still uses glucose, but less (because ketosis) and a bit differently (less oxidation, more lactate release).

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The brain and the obligatory glycolytic tissues always use at least some glucose.  During starvation, this glucose comes from gluconeogenesis.

The substrates for gluconeogenesis are primarily lactate, pyruvate & alanine, glycerol, propionate, and some amino acids (not leucine or lysine). The relative proportions change depending on #context, eg, the duration since your last meal, diet composition (keto, LF, etc.), etc.

Recommended textbook: Stipanuk or Gropper.

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For more on renal gluconeogenesis, see HERE.

The Fates of Pyruvate

As mentioned in the previous blog, obligatory glycolytic cells lack the apparatus (eg, mitochondria) to fully oxidize fuels down to CO2 and water. Thus, they can’t run on fatty acids, ketones, or beta-hydroxybutyrate. During prolonged starvation, there’s always some glucose in the blood, so they survive.

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Recommended textbook: Stipanuk or Gropper.

Glucose -> glycolysis -> pyruvate: then to lactate or the mitochondria, depending on the context. Skeletal muscle has mitochondria, but if you’re exercising hard, glycogen to lactate produces more energy faster than glycogen to pyruvate to mitochondria. Blood lactate increases in this context. During prolonged starvation, lactate is a valuable precursor for gluconeogenesis, so many tissues release lactate instead of oxidizing pyruvate.

To get the rest of this article (it doesn’t suck, I promise) or if you just like what I do and want to support it, head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

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If you have no idea what I’m talking about, read this then this.

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

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Obligatory glycolytic cells

Some cells lack mitochondria; they need glucose. And they don’t stop working during starvation because #gluconeogenesis.

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Red blood cells, renal medullar cells, and certain cells in the retina. Now do you see why it would be a problem if they stopped working during starvation? Hint: You’d die rather quickly.

Recommended textbook: Stipanuk or Gropper.

 

 

Those cells are unable to use conventional oxidative metabolism like the TCA cycle, ß oxidation of fatty acids, oxidation of ketone bodies and most amino acids, and the electron transport chain are all mitochondrial pathways absent from those cells.

To get the rest of this article (it doesn’t suck, I promise) or if you just like what I do and want to support it, head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

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If you have no idea what I’m talking about, read this then this.

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. recommend Lion’s Mane for the brain and Reishi for everything else.

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Glucose dynamics during prolonged fasts

This is a somewhat complicated level of metabolism. Which tissues are producing what & how much, what are they burning & how much, etc., etc…

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After a few weeks, things begin to level out — we’ll pick it up there. Much of this is from a class I TA’d for in grad school, this book, and all the Cahill studies.

 

 

“The rate of glucose use at this time is around 90-100 g per day [remember, this is starvation, so all of that glucose comes from gluconeogenesis]. Of that, about 40 g is recycled via the Cori and glucose-alanine cycles and the remainder is ‘new’ glucose, ~18 g from glycerol and ~45 g from amino acids.”

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Starvation ketosis and “priority” of brain fuels

“Priority” is a funny concept the fields of nutrition, metabolism, etc. For the brain, it is said to be glucose. It’ll use ketones when glucose is low and ketones are really high, like during starvation, but otherwise it’s just glucose. Why is this? One of my mentors had some great insights…

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“It seems that the loss of some energy as ketones in the urine is the price we pay to provide the brain with a suitable fuel. But there are a number of unanswered questions about brain fuel use. Why does the brain not use free fatty acids? The usual answer given is that they are not transported across the blood-brain barrier fast enough to be used as a major fuel and this is probably true. However, why did the brain not develop a suitable transport system, or localized store of glycogen for that matter.”

WHY NOT FATTY ACIDS?

Textbook: Biochemical, Physiological, and Molecular Aspects of Human Nutrition

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Affiliate links: still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon codeLAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.

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. recommend Lion’s Mane for the brain and Reishi for everything else.

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Metabolism of starvation/fasting =/= low carb diet

The Biology of Starvation (intro)

The Biology of Starvation: Renal Gluconeogenesis

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One of the major [obvious] differences in metabolism between fasting and low carb dieting is nitrogen metabolism… because you’re eating protein on a low carb diet, not so much while fasting. During fasting/starvation your body tries to downregulate the urea cycle because you can’t really afford to be ‘wasting’ amino acids/protein. I bet you never thought about the muscle-sparing effect of fat-derived fuels like that!

 

 

“Glucose production in starvation” is important because you need to make all of it and reduce the use of it.

 

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If you have no idea what I’m talking about, read this then this.

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, RealMushrooms makes great extracts. 10% off with coupon code LAGAKOS. recommend Lion’s Mane for the brain and Reishi for everything else.

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7 Worst Heart Health Sins (Page 20)

I read this on a magazine cover and my level of impending disappointment rapidly increased as I approached page 20. Aaaaand….

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It wasn’t horrible! Could use some tweaking, but hit a lot of important points and didn’t say “NO RED MEAT EVER.”

1/ You sneak a smoke.

DUH. Smoking cigarettes is the worst way to get your nicotine hit imaginable. Use a patch, chew nicotine gum, suck on a lozenge. Just. Don’t. Smoke. It also ages your skin faster.

 

 

2/ You skip your walk.

BOOM! We all know the power of a good walk, amirite? Get sunlight and fresh air, get off your butt as often as possible!

For the rest of this article, head over to Patreon! Five bucks a month for full access and there are many other options.

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Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

Affiliate links: still looking for a pair of hot blue blockers?  Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.

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.

calories proper

 

 

 

Low carb diet. NAFLD.

An integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans (Mardinoglu et al., 2018)

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Critique and analysis.

They did two very small (n=10 & n=7) 2-week long studies of low carb, high protein. Carb/fat/protein was 4/72/24 compared to 20/42/18 at baseline. There was no control group, so the results were compared to baseline.

 

 

Lots of pro’s and con’s on this one… but for that, 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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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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Cracking into the Food-Entrainable Oscillator (FEO)

Scheduled meals and scheduled palatable snacks synchronize circadian rhythms: consequences for ingestive behavior (Escobar et al, 2011)
Big hat tip to Robb Wolf for bringing this to my attention. If you’ve been following my more circadian-related stuff, I’ve done a lot of tip-toe’ing around the FEO (food-entrainable oscillator). Tl;dr: sunlight entrains the master clock in the SCN via well-known mechanisms; food entrains peripheral clocks (riddle wrapped in a mystery inside an enigma). 
Ideally, to ensure co-entrainment of the central and peripheral clocks, breakfast and sunshine in the morning, around sunrise.
We know bad things happen when you do the opposite and why you Shouldn’t. Do. OMAD (one-meal-a-day).
For the rest of this article, 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 at any time.
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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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Diet X DESTROYS Diet B in Protein-Matched Ad-Lib Feeding Study

DESTROYS!

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With language like that, you’d expect to see a pretty big difference between the two diets. I mean like, really big difference.

So I clicked the link. Aaaaand #nothingsauce.

 

?(????)?

This study was similar to: “Carbs: Low vs. Lower” where it was shown that many people do just as well losing weight on a low carb diet as they do on a ketogenic diet.

The study was actually quite good, but “destroys” is not the word I would’ve used, especially since the destroyer dieters lost only about 25% more fat mass (P=0.083) and FOUR TIMES MORE FAT-FREE MASS (P=0.054).

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If you have no idea what I’m talking about, read this then this.

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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