Tag Archives: ketosis

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.

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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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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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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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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.

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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.

calories proper

 

 

 

Is gluconeogenesis demand-driven? answer: it depends (#context strikes again!)

Context #1. The easiest way to explain gluconeogenesis (GNG) is how it relates to starvation. If you’re not eating food, your brain still needs a steady supply of fuel. Mostly glucose at first (ketones come later), but since you’re not eating anything, glucose comes from hepatic GNG (huge potential supply*) or glycogenolysis (limited supply). *One of the precursors for GNG, glycerol, comes from stored fat (which you’ll die of something else before you run out of stored fat bc GNG).

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In this case, it is mostly true that GNG is demand-driven.

 

If you’re interested in this, more HERE.

 

Context #2. Protein (which also contains GNG precursors) doesn’t acutely increase glucose. But you might think protein does convert to glucose via GNG but protein also induces a splash of insulin which is why blood glucose doesn’t rise. Read this blog post at least up to the awesome Fromentin study: “8% of the blood glucose produced under optimal gluconeogenic conditions came from dietary protein.” But also check out the Conn & Newburgh studies. And Gannon.

 

 

This is usually the reason recreational keto dieters say they can be high protein, which either ends up looking like PSMF or it’s probably not very ketogenic (which doesn’t really matter in this #context; protein is restricted in therapeutic ketogenic diets).

#BenignDietaryKetosis #BDK

 

 

For the rest of this article (or if you just like what I do and want to support it) head over to Patreon! Full access for a measly five bucks a month and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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Affiliate links: still looking for a pair of hot blue blockers? Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERETrueDark is running a pretty big sale HERE.  BLUblox just upped their game with their 550‘s.
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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Context #3. the mouse doctor is in 🙂

Context #3b. Chronic high protein.

Context #4. Random thoughts on animal foods.

Intermittent fasting is nothingsauce

So Twitter got supermad when I said the human studies on intermittent fasting are not compelling. Not the anecdotes or n=1’s. The actual human studies.
And instead of “not compelling,”
I may have said “nothingsauce.”

Hilarity ensued. I was bombarded with
ALL.
THE.
ANECDOTES.

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Someone was kind enough to send me all the proof that I was wrong. Here are the 5 non-Varady studies, reviewed.

Tl;dr: as long as you’re not eating like a child, “Eating > not eating. QED.”

 

 

Alternate day calorie restriction (ADCR) improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma (Johnson et al., 2006)

Study design: n=10, 8 weeks, NO CONTROL GROUP. Every other day they ate 20% of normal and ad lib the other days. This would’ve been much cooler if they included a 40% caloric restriction and weight maintenance (WM) control groups. The former to see if ADCR was superior to a similar reduction in energy intake and the latter because people behave differently when their being observed (regardless of which group they’re in) (few studies include a WM control group).

Result: body weight declined by 8%. Is that worth having nothing but a snack every other day? How about compared to 40% CR? Nothingsauce?

Oh yeah, uric acid increased and BDNF decreased. So, gout, kidney stones, and cognitive deterioration. Yummy nothingsauce.

 

The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women (Eshghinia et al., 2013)

Study design: similar to the above, and also lacking a control group.

Result: BW declined by 7%.

Critique: same. No control group. Would this have been better than CR or anything else? They basically just say “it’s relatively safe;” but it’s not, really… and some forms of intermittent fasting can have harmful side effects.

 

For the rest of this article (including some LOLZ & facepalming), head over to Patreon! It gets better (or worse, depending on how you look at it): metabolic mayhem, rebound hyperglycemia, some circadian chicanery #eTRF, and much more.

And stay tuned: since BDNF actually declined in the Johnson study, I’m following up with a review of intermittent fasting vs. various aspects of cognition, memory, mood, sleep, etc.

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UPDATED 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.

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Isocaloric MCT-supplemented ketogenic diet may improve cognition in Alzheimer’s patients

Two-thirds of the time, it works half of the time 🙂

Yes, we all pretend to know the mechanism how ketones may improve cognition in MCI/Alzheimer’s, but we don’t. Nobody does.

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-Preferred fuel? kinda meaningless

-Niacin receptor? if so, where are the studies on niacins or even nicotinamide riboside (the latter is kind of unrelated, but should yield some niacin in vivo) (P.S. blog post on NR in the works).

-Epigenetics? Idk. Of those, I’d say probably all contribute somehow.

Ketogenic Diet Retention and Feasibility Trial #KDRAFT (Taylor et al., 2017)

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Ketone supps and physical performance

We’ve had a couple more studies on the various ketone supps: two esters (D-b-hydroxybutyrate-R 1,2-Butanediol Monoester and R,S-Butanediol Diacetoacetate) and one beta-Hydroxybutyrate sodium and potassium salts (KetoForce). We’ll call them Clarke, Burke, and Stewart so I don’t get Carpal Tunnel Syndrome typing them out each time. Technically, b-hydroxybutyrate isn’t really a ketone, but whatevs.

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“Clarke”

 

“Burke”

 

“Stewart” (this is actually a blend of the sodium “Na” and potassium “K” [not shown] salts)

 

Two studies on Stewart

Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males (O’Malley et al., 2017)

“Ten healthy, recreationally active men.” The participants did a brief warm-up then a 150 km cycling time trial after receiving 24 g Stewart or salt-matched placebo.  Controlling for salt was cool, but Stewart has about as 5 kcal/g, so the placebo could’ve controlled for that somehow, with either fat or carb, or something… (probably wouldn’t have mattered anyway)

Results: blood beta-hydroxybutyrate reached about 1 mM, power output declined 7% and it took the keto group about 45 seconds longer to complete the time trial.

Oral beta-hydroxybutyrate salt fails to improve 4-minute cycling performance following submaximal exercise (Rodger et al., 2017)

“Highly trained cyclists.” Similar study design as McSwiney’s — drain the tank with 90 minutes cycling at 80% max then 4 minute maximal performance test. Same dose as above in 2 divided doses. Same issue with the control group.

Results: blood beta-hydroxybutyrate reached ~0.6 mM and there was a trivial (non-significant) increase in power. This is actually in line with my interpretation of McSwiney regarding the decline in power output before and after draining the tank; ketoadaptation and all that jazz.

 

One study on Burke

Ketone diester ingestion impairs time-trial performance in professional cyclists (Leckey et al., 2017)

“Internationally competitive elite cyclists.” Two doses of 20 g Burke then a 20-minute warm-up followed by a 31 km time-trial. Non-caloric placebo control, whereas Burke is estimated 4.7 kcal/g. They were well-fed and caffeinated.

Results: beta-hydroxybutyrate reached ~1.1 mM, time-trial took 2% longer, and power was reduced 3.7%.

 

One study on Clarke

Nutritional ketosis alters fuel preference and thereby endurance performance in athletes (Cox et al., 2016)

“High performance athletes.” This study was different: one group got a drink that was 40% Clarke and 60% carbs (by calories), the other drink was 100% carbs. Calorie-controlled. They cycled for an hour at 75% max (to drain the tank), then 30-minute time trial.

Results: this is the first one that worked. beta-hydroxybutyrate reached 2-3 mM and they made it 2% further during the time-trial.

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade  is 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.

For my interpretation of these studies and an  explanation why I think the different keto supps had different effects (or if you just like what I do and want to support it), 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 🙂

Also, I’m open to suggestions so feel free to leave a comment or email me directly at drlagakos@gmail.com.

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERETrueDark is running a pretty big sale HEREIf 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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I’m not anti-keto, but I’m not anti-science.

The ketogenic diet inhibits mTOR but spares muscle. Wait, wut?

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mTOR is a key mediator of skeletal muscle growth. Primarily via stimulating protein synthesis, although some researchers are even looking for ways to activate it to prevent atrophy (eg, Dyle et al., 2014) (eg, ursolic acid & tomatidine).

Role of skeletal muscle mTOR in mechanical load-induced growth (Goodman et al., 2011)

Signaling pathways mediating muscle mass in aging skeletal muscle: role of mTOR (Sandri et al., 2013)

Mechanisms regulating skeletal muscle growth and atrophy (Schiaffino et al., 2013)

mTOR is necessary for proper satelite cell activity and skeletal muscle regeneration (Zhang et al., 2015)

 

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

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 🙂

Also, I’m open to suggestions so feel free to leave a comment or email me directly at drlagakos@gmail.com.

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERETrueDark is running a pretty big sale HEREIf 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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