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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Artificial light and circadian rhythms: blocking the blues

Check out the above image of the electromagnetic (EM) spectrum. Different biohacking eyewear have different purposes, and it largely depends where on the EM spectrum they act.

If you stare at a computer screen (or iPad, smart phone, etc., etc.) all day, the specialized glasses you may want to look into block out light just south of the visible light wavelengths. These will help with eye strain, headaches, etc. You could use bona fide blue blockers for this, as they block blue and everything south, although it’d be overkill and probably annoying due to visual disturbance. Pixels  and Gunnars are good for this, but they’re not especially great at blocking blue light (with the possible exception of the amber-tinted Gunnars).

Warning: there’s an article floating around on the internet saying it’s useless to block blue light because those computer glasses don’t preserve melatonin secretion. This is a STRAWMAN. Computer glasses aren’t designed to block blue light.
The truth: it’s still important to block blue light at night. If you get eye strain or headaches staring at a computer screen, than computer glasses may be appropriate.

 

 

 

Blocking blue light at night is key for proper melatonin secretion and preservation of circadian rhythms.

Most smart devices emit LED light which has a particular spike in the blue range:

 

If you need to light at night: moonlight or candles > amber or red-tinted bulbs  > low watt incandescent bulb. They should be positioned below eye level as light entering the eyes from above more effectively suppresses melatonin than light from below (with the exception of moonlight LOL) (Glickman et al., 2003).

 

Amber lenses to block blue light and improve sleep: a randomized trial (Burkhart and Phelps, 2009)

 

Wearing blue light-blocking glasses in the evening advances circadian rhythms in the patients with delayed sleep phase disorder: an open-label trial (Esaki et al., 2016)

 

Uvex SkypersGunnarsCarbonshades (probably the most effective blue blockers available) … Solar ShieldsBLUblox (less expensive and pretty cool-looking, too) … Spectra479

 

Spectra479 and Carbonshade are offering a 15% discount with the coupon code LAGAKOS!

 

Circadian misalignment augments markers of insulin resistance and inflammation independently of sleep loss (Leproult et al., 2014)

 

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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.

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 (which is the type I think I had), etc.
Number 1 mandatory advice: do all the long-term stuff like broths, 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 pain management, you may need to bite the bullet and take a muscle relaxer.
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.

 

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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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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]

 

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Meal timing and the circadian regulation of nutrient partitioning.

Breakfast [in the morning] strengthens circadian rhythms and reduces postprandial glucose excursion after lunch (Jakubowicz et al., 2017)

 

 

 

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Surviving is not thriving. You need robust circadian rhythms for both.

Worded another way, we strive for optimal, not merely survival.

We’ve seen it time & time again in various experimental models. Most recently in Antelope Ground Squirrels and Mice with disrupted master circadian clocks. In humans, we see mood disorders, impaired nutrient partitioning, increased cancer risks, et cetera, et cetera.

 

 

 

 

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Sunlight, Meal Timing, and Circadian Rhythms

Hey fam, remember this? Sunlight and the circadian rhythms in your skin

Tl;dr: During the day, when potential DNA damage from UV light is higher than at night, the circadian rhythms in your skin upregulate expression of enzymes which protect & repair DNA. They also downregulate proliferation because the last thing you want is for a harmful DNA mutation to be rapidly spread. All of this thanks to a robust circadian rhythm.

 

NEW STUDY

 

Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage (Wang et al., 2017)

 

In general, LIGHT entrains the central circadian clock and FOOD entrains peripheral clocks. That’s why we try to get a big breakfast and go outdoors in the morning (or mimic this as closely as possible).

 

 

And from the aforementioned blog post, there is a bona fide circadian rhythm in skin, too. Well it appears this one, similar to other peripheral tissues, is regulated in part by FOOD but is also influenced by LIGHT.

 

 

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Part 2 is up now!

 

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