Tag Archives: energy balance

Dopamine regulates systemic glucose metabolism in humans

In Four. EPIC. Experiments (ter Horst et al., 2018)

Tl;dr: sunlight & breakfast in the morning.

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Dopamine receptors are downregulated in obese patients and are restored in long-term weight loss patients after bariatric surgery. It’s better to get your dopamine hit via sunlight than sugar duh.

This is some amazing science.

 

 

Experiment 1. 50-year old dude with severe OCD gets diagnosed with type 2 diabetes and is only able to get his glucose under control with metformin and 226 IU insulin. At 53, his OCD is treated with deep brain stimulation (DBS). His insulin requirements declined to 180 IU. He didn’t lose weight but went off quetiapine, so maybe coincidence because: 1. quetiapine is diabetogenic; and 2. DBS induces dopamine release.

Two-step hyperinsulinemic euglycemic clamp when DBS is turned off and turned on. BOOM! When it’s on, lower fasting insulin, and better insulin-induced suppression of liver glucose output, free fatty acids, & muscle glucose disposal! DBS improved insulin sensitivity in liver, adipose, and skeletal muscle.

For the rest of the discussion on these super-interesting experiments, head over to PatreonFive 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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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 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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Cycloset (bromocriptine)

 

 

Go for a walk.

And #eTRF.

 

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Intermittent fasting is homeopathy-level #nothingsauce

From all of the published human studies and “n=1’s” I’ve seen on online forums, intermittent fasting is #nothingsauce. Don’t @ me.

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When people lose weight via IF, it’s because of caloric restriction. There’s no metabolic advantage, and if anything, maybe the opposite. Restricting your feeding window to a very short period = metabolic mayhem.

2000 kcals in one sitting?

*smh*

 

 

I believe “early Time-Restricted Feeding” #eTRF showed promise in that recent study because of the “early” part; no so much on the “TRF” part. I believe this, in part, because the large majority of our population suffers from some degree of circadian arrhythmia. Social jet lag, too much artificial light at night, skipping breakfast, etc., etc. An EARLIER feeding window is one way to re-align circadian rhythms.

 

 

It STARTS with Sleep. Wanna improve body comp and make mindlessly better food choices? Fix your circadian rhythms.

Now onto the one of the weirdest, but potentially most revealing human studies on time-restricted feeding…

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

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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 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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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.

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. 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.

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. 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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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 🙂

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 FireHERE.

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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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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Fixing your rhythms makes everything better. Here’s how.

Full article open to everyone over at Patreon! <- link

What’s more anti-cancer than ‘shrooms and isothiocyanates?

CIRCADIAN RHYTHMS

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.

Caffeine, large meals, and bright light in the evening induce circadian misalignment. That’s why these are better suited earlier in the day.

Caffeine reduces sleep pressure (which is supposed to start low in the morning and peak shortly after sunset) and delays melatonin onset (Burke et al., 2015). After dinner, make it a decaf or just pass.

 

Caffeine is an adenosine antagonist, and the accumulation of adenosine in the brain throughout the day is thought to be a chemical mediator of sleep pressure. Caffeine also delays and reduces melatonin, which increases your sleep needs, or at least time in bed/darkness.

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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!

Three bucks a month for access to all articles and there are many other options. And it’s ad-free.

If you’re on the fence considering it, try it out, you can cancel at any time! Also, there is a limited number of positions remaining at the $3 level.

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

 

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The Struldbrugs of Luggnag

Intermittent fasting (in mice)

Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice.

 

THIS IS BASICALLY THE WORST POSSIBLE OUTCOME

 

The Struldbrugs of Luggnag

 

 

Tl;dr: they’re immortal, but just keep getting older and older and it sucks. It’s basically the exact opposite of what we want, which is something akin to eternal youth.

 

 

This paper was a Giant.

 

Brief background: they were testing a model of intermittent fasting known as EOD, or ad libitum access to food every other day. It’s hard to relate this directly to humans because one mouse day is probably about at least 5 human days… although similar to humans, when chow time comes around, we tend to eat a lot. REFEED MAYHEM.

[rant]
It’s like that dude who takes a pic of 3 big steaks and posts it online, saying “dinner is served, bro” …trying to make it seem like they eat that way normally, ~3x/d, when in reality they’ve been intentionally restricting food intake all day to create a big enough energy deficit to accommodate said steaks… #CICO

P.S. as far as circadian rhythms and dietary protein requirements are concerned, this way of eating isn’t doing you any favors…
[end rant]

 

For the rest of this article, all other articles and much more, head over to Patreon! Five bucks get you all access 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.

Join Earn.com with this link

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