Tag Archives: protein

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

 

 

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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.

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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.

On Patreon, five bucks a month gets you full access. It’s ad-free and you can cancel if it sucks 🙂

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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Brain health: more easy steps

When describing the length of one of his students’ fingers, the great classical guitarist Andres Segovia said “she has more long fingers than anyone else” — he meant longer fingers… English wasn’t his strong suit haha

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Maximize sunlight exposure, minimize artificial light (or at least get some hot blue blockers). Get at least some physical activity. Those are the basics. Moving on…

Tl;dr: Beef heart, calf liver, and maybe some supps 🙂

Coenzyme Q10

Coenzyme Q10 isn’t approved for the treatment of anything, but hear me out.

We have about a gram of CoQ10 in our entire body, concentrated in the mitochondria of highly oxidative tissues (Saini, 2011). It is found at around 60-110 ug/g in heart (eg, Ercan and El, 2011Aberg et al., 1992).

 

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Activate #Nrf2, then optimize: Brussels sprouts

Hahaha What can’t you do, Nrf2?

Remember The Day Almonds Became Interesting? Namely, “the long series of  unlikely events that must occur in order for the bifidogenic effects of almonds to manifest.” Well, it happened again. Or the opposite.

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I’m not a huge fan of antioxidant supps for a variety of reasons, including but not limited to ATBC and CARET. There are certainly some exceptions to this, although your body can handle itself quite well under most circumstances.

I am, however, a pretty big fan of periodically doing things like activating #Nrf2, because anti-cancer. Advantage is that if there’s nothing going on, Nrf2 is degraded pretty quickly (can’t really say the same about antiox supps). If there is something going one, Nrf2 rallies the troops to swiftly restore balance: pathways pathways pathways -> DEAD CANCER CELLS.

 

IT DOESN’T GET ANY EASIER THAN THIS, FAM

 

One of the major ways Nrf2 gets it done is by inducing the synthesis of endogenous protective compounds like glutathione. Glutathione synthesis requires sulfury stuff, particularly (if it’s available), cysteine. Guess what?

 

 

Sulforaphane activates Nrf2 and breaks down to provide cysteine for glutathione synthesis. WEIRD COINCIDENCE, I KNOW RIGHT?

WHAT CAN ANY REMOTELY REASONABLE PERSON CONCLUDE FROM THIS?

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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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Funded by Big ‘Shrooma

Reishi, the mushroom of longevity.

“The goal is to maintain or improve brain function and physical performance. And not get cancer.”

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‘Shrooms-every-day is part of my long-term anti-cancer plan. It’s not always a lot per serving, but I try to do the whole variety thing as much as possible, whatever’s available.

Maybe it’s one of those ice-age fairy tales fallacies, but cultures around the world have attributed a large number of health benefits to ‘shrooms for literally, thousands of years:

Ganoderma [reishi] has a very long history in East Asia as a medicinal mushroom dating back to the Chinese materia medica ‘Shen Nung Ben Cao Jing,’ written between 206 BC and 8 AD. It was considered a superior tonic for prolonging life, preventing aging, and boosting qi.”

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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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Pregnancy dieting and #moderation: just don’t be extreme

“If you can’t absorb B12, no amount of steak will help you” (more on this below)

Just like practically everyone in the field, I’m uncomfortable with the word moderation, in part because one person’s moderation can be wildly different from another’s.

Remember the Motherwell studies? In brief, they asked a group of expecting women to ditch carbs and eat a ton of meat instead (about a pound per day), and compared them with a group not given diet advice. It was designed to compare an extreme diet to an average diet (note: they didn’t assess the opposite extreme, ie, high carb vegan).

Tl;dr: babies were healthy at birth but developed a variety of health problems later in life. Perfect study design? No. Better than ALSPAC? Kinda, yeah.

 

 

In the context of today’s topic, I’ll define moderation as “not extreme” (bear with me here) (unless ALSPAC is retracted or something… which is possible given the study design.)

 

Meat consumption during pregnancy and substance misuse among adolescent offspring (Hibbeln et al., 2017) (aka ALSPAC)

 

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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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