Tag Archives: muscle

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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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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We don’t want more or less antioxidants. We want balance. #NRF2

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

Antioxidants

There isn’t a strong case to make for antioxidant supplements. They’ve been shown to do nothing more often than not, and even harm in a few cases when dose & #context were mismatched (eg, ATBC and CARET). This is part of what led to the conclusion that we want an appropriate “reactive oxidative species *tone*” or “antioxidant balance.” Or “landscape.” Or some other catchphrase of the week.

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In line with this, animal models that genetically up- or down-regulate antioxidant pathways are predicted to show negative or no effects because they are, practically by definition, generating a mismatch.

In humans under normal conditions, I believe pro- and anti-oxidants are balanced by our own endogenous processes. If we ingest something that produces a bit too much ROS, they’ll be neutralized. If we ingest something that induces antioxidant processes, they’ll be used if necessary and degraded if not. In other words, as long as you’re not mega-dosing beta-carotene or smoking 2 packs a day, etc., then none of this should matter.

 

 

NRF2

Which brings me to NRF2. I like the concept of periodically inducing our own endogenous detox processes because it seems like they’ll either help or do nothing. Not harm. It’s like, stacking the deck in your favor.

Nrf2: ket target for the treatment of neurodegenerative diseases

 

Bioactive Neutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy

If you ingest something that induces NRF2 and something needs detoxifying (for example, some manifestation of improper ROS tone or inflammation or something), then NRF2 will get it done. Otherwise, NRF2 goes away in about 20 minutes (Kobayashi et al., 2004).

 

Reminders: still looking for a pair of hot blue blockers? Carbonshade and Spectra479 are offering 15% off with the coupon code LAGAKOS. And Kettle & Fire is offering 20% off of their delish broths/stocks HERE.

 

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Project FermenTRP

People have been fermenting food for a long time, all over the world. Different cultures have different traditional fermenting techniques for various foods and beverages (eg, Bell et al., 2017). Many things, ranging from grapes, milk, and cabbages, even meat and fish. For all intents and purposes, it’s practically universally viewed as a beneficial and healthful practice …

for the ‘biome and beyond

#psychobiotics

 

Maybe it’s just because a robust ‘biome lowers the sugar content of your diet! LOL jk I’m sure it’s far more complex than that.

 

Also, the shelf-life of most ferments is forever, so when the zombie apocalypse happens, it’s a good skill to have.

 

Part 2. Project FermenTRP

I started down this rabbit hole because the TRP theory of muscle cramps is interesting. And, well, I got carried away LOL .

 

The idea of a “superfood” is kinda silly, but virtually all TRP agonists are found in so-called superfoods. Fermenting is cool, too, so I decided to combine the two because why not

 

[I know, I know, photography isn’t my specialty]

 

#torched

 

 

Torching habanero peppers does not lessen the burn. To be honest, I’d go with a WAY less hot pepper. And combine with other TRP activators. For synergy. Or something.

 

 

The TRP-theory, in brief:

An interesting theory on the treatment of muscle cramps

Herbs, spices, TRP receptors, and pain

TRP channels in the treatment of muscle pain & cramps

 

Here are some of the more common sources of TRP agonists in the literature:

Hot Peppers (capsaicin) (doesn’t have to be habanero) (DO NOT USE HABANERO)

Involvement of thermosensitive TRP channels in energy metabolism (Uchida et al., 2017)

Targeting nociceptive TRP channels to treat chronic pain: current state of the field (Moran and Szallasi, 2017)

 

Peppercorns (piperine)

Activation of TRPV1 and TRPA1 by black pepper components (Okumura et al., 2010)

 

Ginger (gingerols)

Effects of ginger and its pungent constituents on transient receptor potential channels (Kim et al., 2016)

 

Garlic (allicins & sulfides)

The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin (Macpherson et al., 2005)

Diallyl sulfides in garlic activate both TRPA1 and TRPV1 (Koizumi et al., 2009)

Intragastric administration of allyl isothiocyanaate increases carbohydrate oxidation via TRPV1 but not TRPA1 in mice (Mori et al., 2011)

 

Cinnamon (cinnamonaldehyde)

Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects (Michlig et al., 2016)

 

Mustard & Wasabi (isothiocyanates, I think)

The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil (Everaerts et al., 2011)

Thermosensitive TRP channels and brain function (Tominaga, 2016)

 

Cloves (eugenol)

Oregano, thyme, and clove-derived flavors and skin sensitizers activate specific TRP channels (Xu et al., 2006)

 

There are many more, but those are just some of the ones that made it to part 3.

 

In brassica, speramus.

 

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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.

 

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TRP channels in the Tx of muscle pain & cramps

NSAIDs are OK for muscle pain, but may hinder training progress in the long run (eg, Shoenfeld 2012 and Mackey 2013). The electrolyte theory of muscle cramps has been kinda debunked in some contexts (eg, Braulick et al., 2013, Miller 2014, and McKenney et al., 2015)… although I still recommend all the broths & stocks (homemade, store-bought, chicken, beef, seafood, etc.) for just about everything. 20% of Kettle & Fire broths through this link!

But even when pickle juice works (eg, Miller et al., 2010), it kicks in way sooner than if it worked via replenishing electrolytes – more likely works via the acidity activating specific ion channels.

What do we have left?

Google Image Search came through pretty epic for this…

 

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Herbs, spices, TRP receptors, and pain

The TRP ion channels TRPA1 and TRPV1 have a complicated & interesting relationship with neural activation and pain.

TRPV1 is partly responsible for the pain we feel from eating hot peppers. Capsaicin (or some capsaicinoids or even ginger) bind to this receptor, and we can FEEL IT. The nerves on which TRP ion channels reside become hyperexcited, which has the theoretical effect of feedback inhibition on other afferent nerves in the spinal cord. As far as the TRP-muscle cramp theory goes, this dampens hyperexcited muscle cramp-inducing nerves. So basically, instant resolution of painful muscle cramps.

 

 

Mustard, cinnamon, and garlic hit TRPA1 for a similar effect. Instant muscle cramp-relief… but depending on your taste preferences, could be unpleasant.

 

 

 

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Effects on body recomposition, more on spices, and my personal experience!

 

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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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Exercise & protein, man. Exercise & protein.

-Basically, any beginner can make decent gains upon starting a new exercise regimen… it’s actually hard not to. Noob gainz.

-What’s easier than doubling exercise volume? PROTEIN.

Protein Supplementation to Augment the Effects of High Intensity Resistance Training in Untrained Middle-Aged Males: The Randomized Controlled PUSH Trial (Wittke et al., 2017)

Four groups: 1) high intensity training (HIT); HIT + high protein diet (HIT+P) (1.6 g/kg/d); HIT + high volume (HVHIT); and control. Baseline protein intake was ~1.2 g/kg, so it was about a ~33% increase.

Duration: 22 weeks, which is long enough to actually make some measurable noob gainz.

Results:

 

 

Exercise alone (HIT) wasn’t particularly effective but doubling the volume worked.  What’s easier than doubling the volume?  PROTEIN.  Protein is better than doubling the volume for n00b gainz in LBM.

 

 

More gainz in leg & arm muscle mass and strength.  Doubling the volume was slightly better for fat loss. CICO? Energy intake declined slightly in HIT but remained stable in HIT+P & HVHIT.

My take? Protein is way easier than double-volume high intensity training.

 

 

Protein & exercise, man. Protein & exercise.

 

 

 

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20% off some delish stocks and broths from Kettle and Fire HERE

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