Category Archives: Vitamin D

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)

 

For the rest of this article or if you just want to support the show, 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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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.

 

 

Head over to Patreon, where for three bucks a month you get access to the rest of this article, all previous articles, and much more! Go soon because there’s only a limited number of spots at the $3 level. It’s ad-free and you can cancel at any time.

 

Part 2 is up now!

 

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A robust circadian rhythm is the key to good aging

That’s basically everything.

 

 

Aging predisposes you to pretty much every single disease. We all die eventually, and no one wants the last 10 years to be low quality of life. We used to say “healthspan,” now people say they “want to die as young as possible, as old as possible.” That is, to live a long life but remain healthy and active until the end.

Couple recent studies suggest a robust circadian clock (both centrally & peripherally) may be the key.

LIGHT is the primary zeitgeber which entrains the central clock. Food entrains the peripheral clock. Both in the morning, to co-entrain both clocks and prevent desynchrony.

DARKNESS and decreased food intake in the evening is just as important. Being young helps, too (von Gall and Weaver, 2006)

 

 

 

For the rest of Part 1, all of Part 2, and more, head over to Patreon!
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update: part 2 is up now!

 

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Light and food in the morning

Suggested pre-reading: Metabolism at night

Recently, when the topic of breakfast came up, I got something like this: “correlation isn’t causation, and anyway, it’s because people aren’t eating bacon & eggs at night, they’re having cake & alcohol.”

OK, you can’t say “correlation isn’t causation” and then suggest a cause, literally, in the same sentence.

But anyway, yeah, that actually is a plausible cause. Cake & alcohol are mainly consumed at night.

Also, metabolism is gimped in the evening: 1) skeletal muscle insulin resistance; 2) adipose tissue insulin sensitivity; and 3) impaired diet-induced thermogenesis.

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Carb early but not often

*if you’re going to carb, that is

 

 

The Sofer study was uniquely insightful in that they compared 3 carb-rich meals per day with the same amount of carbs but restricted to 1 meal.  Both groups ate 3 times per day.  Tl;dr: one carb meal is modestly better than three even when total carbs are controlled.  Since the carb-meal happened to be dinner, #fakenews reported that “carbs at night” are superior… but we saw right through that – the real conclusion was carb frequency not carb timing.

 

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What or When to Eat

Artificial light at night, crappy sleep, and skipping breakfast are major contributors to poor circadian rhythms.  Some bro’s insist WHAT you eat is infinitely more important than WHEN you eat.  I beg to differ, at least in part – nix the refined & processed foods and it doesn’t really matter if you prefer low fat or low carb (P<0.05).  Evidence: Hunger-free diet(s).

 

Exhibit A.  On the other hand, feed two people identical diets but induce circadian disruption in one and whammo – big difference in outcome.

 

 

Significantly less fat loss and more muscle loss in the circadian disrupted group.

Interindividual variability? Yes.  Statistical significance? YES.

 

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Metabolism at night

From circadian entrainment to blood glucose management to appetite control to sleep quality:

 

 

We’re really not made to skip breakfast and eat late at night.  Nearly every line of evidence points to this.  And now:

Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study (Bo et al., 2015)

 

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MELATONIN

There are a lot of mysteries involving melatonin, eg, relative importance of gut vs. pineal-derived melatonin.  Does brain melatonin talk to peripheral MT receptors?  Does gut melatonin talk to brain MT receptors?

What we do know: oral melatonin works in people with circadian-related sleep disorders.  This may suggest that oral/gut melatonin talks to brain MT receptors OR that oral/gut melatonin corrects circadian sleep problems by acting in the periphery.  OR a major target of brain melatonin is peripheral MT receptors.  I don’t know.

And as a further testament that melatonin supps aren’t sleeping pills is that they’re non-addictive and can at least temporarily “fix” circadian sleep problems: after prolonged treatment, people report no withdrawal symptoms and still sleep better even up to two weeks after discontinuation (Lemoine et al., 2011)!

 

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