Tag Archives: diet

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 🙂

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  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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The power of a good walk.

I walk a lot. Usually after meals; sometimes for sunlight & exercise, other times just because it’s a habit and I like doing it. Sometimes even twice a day (eg, after breakfast and lunch).

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But seriously, it’s way healthier than I thought. This has been in-and-out of the news a few times over the years, but I was always like, “duh,” until I finally looked at the numbers. In some cases glucose & insulin excursions are down 20, 30, even 50%! (mostly depending on the distance covered, but also speed) (but mostly distance).

LOL there are like, a million studies titled “breaking up prolonged sitting improves everything” haha

And since the effects are acute, a lot of well-controlled RCTs — the flipside of that is you have to do it every day… my opinion is that total glycemic exposure over the course of your life is an important metric (more on the MOA below); and with the rise of continuous glucose monitoring systems, this will be proven true.

Exhibit A. The biggest intervention (VERY long walks, 5-6 hrs/d), but most profound results (Manohar et al., 2012)

 

 

 

Exhibit B. Prolonged sitting vs. a 30-minute walk vs. 1.5 minutes walking every 30 minutes throughout the day (Peddie et al., 2013). Both of these interventions are very doable, imo.

In this study, the total daily exposure was 49, 47, and 30 mM / 9 h. 90 seconds of walking every 30 minutes cut glucose by almost half. HALF. Insulin also dropped precipitously. If you work a sedentary job, MAKE TIME FOR THIS. EVERY DAY. GO NOW.

For the rest of this article (it’s good, I promise!) and much more (or if you just like what I do and want to support it), head over to Patreon! Five bucks a month for all 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 please don’t hesitate to leave a comment or contact 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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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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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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The importance of entraining skeletal muscle’s circadian clock (and how)

“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.

 

For the rest of this article (including my interpretation and advice), head over to Patreon!

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An interesting theory on the treatment of muscle cramps

Being the nerd I am, after experiencing a few days of painful muscle cramps (which I wrote about here), I went to Google like a madman.
Here’s what I learned from the experience and subsequent Googling.
Most things I wrote in the original post still stand. But there are a ton of completely different types of muscle cramps; those associated with cirrhosis, MS, pregnancy, dialysis, idiopathic nocturnal, etc.
Number 1 mandatory advice: do all the long-term stuff like broths, (20% off Kettle & Fire!) potassium, mag, etc (even though all of these things have mixed findings; they might work for your specific type of cramp and are unlikely to cause harm). But for immediate management of painful cramping, you may need to bite the bullet and take a muscle relaxer or benzo or something.
A lot of this post is inspired by a crazy theory touted by a new anti-cramp product (targeted at yet another type of cramp, “exercise-associated muscle cramp” [EAMC]), but the explanation of it’s mechanism is super-interesting.

I still stand by the previous interventions, except according to a few case studies and a lot of anecdotes, pickle juice can work within 1-2 minutes! That observation was part of the basis of developing this product. Some people think the acidity in pickle juice activates gastrointestinal TRP receptors (see below), and I’m totally cool with all kinds of vinegar
But I digress.

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 the taste, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS.

There are a limited number of spots left at the $3 level, so join soon! You can cancel at any time.

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

 

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How to manage painful muscle cramps

(I think)

disclaimer: to the best of my knowledge, the causes and cures of painful muscle cramps are unknown. Researchers have studied nearly every electrolyte & metabolite in people who don’t get cramps, people who get cramps, people who get cramps while they’re actively experiencing a painful muscle cramp, and when they’re not.

Conclusion:

¯\_(?)_/¯

 

This is about idiopathic painful muscle cramps. Pregnancy, dialysis, and cirrhosis-related cramps may be completely different.

 

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