Tag Archives: circadian rhythm

Efficacy of a wide range of things, from sleep & diet to supps & meds, may depend on timing

Posted on October 22, 2017 | 2 comments

A study on epilepsy was published comparing gene expression in parts of the brain where seizures developed with adjacent healthy tissue (Li et al., 2017). It was in humans, so they couldn’t really have proper controls, because what healthy person would volunteer to have some of their brain chopped out?

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They found the core circadian rhythm gene CLOCK was reduced in epileptogenic regions of the brain compared to healthy nearby tissue. It could be that this is just the way it is in healthy people, or that the seizure itself reduced CLOCK not vice versa. But the researchers followed-up with animal models lacking CLOCK in either inhibitory or excitatory neurons and showed mice lacking CLOCK in excitatory neurons had a lower seizure threshold and a more severe condition (suggests causation). They had worse seizures in the dark phase, similar to the findings in humans.

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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, epilepsy, Ketosis, melatonin, nicotine, sex, Sun, vasopressin, Vitamin D

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

Posted on October 19, 2017 | 15 comments

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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, liver, melatonin, mortality, nicotine, Protein, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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Light & melatonin: timing is everything

Posted on October 13, 2017 | 3 comments

This is kinda like circadian rhythms’ second Nobel Prize. Technically it was LED lights back in 2014, but if you don’t see the connection, I have failed.

Suggest pre-readings: Melatonin sensitizes the system and LIGHT timing for circadian entrainment

Melatonin plays a pivitol role in circadian entrainment. Literally thousands of papers published about it every year.

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THIS IS WHY YOU NEED BLUE BLOCKERS: A single night light exposure acutely alters hormonal and metabolic responses in healthy participants (Albreiki et al., 2017)

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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, muscle, Protein, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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Circadian Rhythms. Nobel Prize.

Posted on October 4, 2017 | 12 comments

18th Century: French astronomer Jean-Jacques d’Ortous de Mairan observed the mimosa plant opened it’s leaves during the day and closed them at night. It would continue to do this even in complete darkness. Thus, a bona fide circadian phenomenon. He didn’t know about circadian rhythms and thought the plants could “sense” when the sun came up, but he was still a genius. He also speculated temperature may have been a factor. Not bad!

 

 

Some of the seminal Nobel Prize-related papers are listed below, but the discovery in brief:

The protein PERIOD (Per) increases over night and decreases during the day. That’s because when another protein, TIMELESS (Tim), reaches a critical threshold, it binds to Per, they enter the nucleus and halt further production of Per. This is the foundation of circadian rhythms. Since these discoveries, made DECADEs ago, we’ve learned it’s WAY more complicated.

 

 

. . .   .     .        .              .

 

 

 

Most of their research was done in fruit flies. You might be thinking, “Yeah, but fruit fly? That’s worse than mouse!”

Polymorphisms in PERIOD cause circadian-related sleeping disorders.

In humans. (eg, Viola et al., 2007, Drake et al., 2015, and Lee et al., 2015.)

 

 

Polymorphisms in many circadian genes mimic certain aspects of self-induced circadian arrhythmia (ie,  skipping breakfast & eating late at night, not getting enough light in the morning & too much in the evening, etc.)… it kills me when I hear about kids playing on their iPads & smart phones late at night. At least get some blue-blockers! (coupon code LAGAKOS is still good for 15% off Carbonshade and Spectra479.)

 

For the rest of this article, 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.

 

also, reminder, can still get 20% off Kettle & Fire’s awesome broths HERE.

 

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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, mortality, sex, sleep, Sun, vasopressin, Vitamin D

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Circadian rhythms & the blues. AND THE GREENS

Posted on September 24, 2017 | 7 comments

Open access for all at Patreon! <- linkage

Approximate wavelengths, in nanometers (nm):

680         red
595         amber
525        green
497         blue/green
470         blue

 

 

[Strongly] suggested pre-reading: Artificial light and circadian rhythms: blocking the blues and The Hot Blue-Blocker Experiment

Patrons can just click here…

Study 1 tested the effects of different wavelengths of light exposure (compared to total darkness) from midnight til 2 AM on melatonin suppression on night 1 and melatonin onset on night 2 (Wright and Lack, 2001). Note: there was no light on night 2.

On night 1, they found that 470 (blue), 497 (blue/green), and even 525 (green) suppressed melatonin, ranging from 65 to 81%.

 

 

However, remarkably, on night 2 those same wavelengths had a carry-over effect, delaying melatonin onset by 27 to 36 minutes!

 

 

This is why lens color of your blue blockers matters. Orange lenses block blue, although blue/green and even green can still have a detrimental impact. Redder lenses more effectively block in the green range.

If you get up to pee or whatever in the middle of the night, it might be prudent to rock your blue-blockers and/or have a lamp with a red bulb.

The following graphs show you how much light is blocked by different lenses – remember, we want as little transmission up to around 525 nm (according to study 1 [above] and study 2 [below]).

However, for a quick and dirty test you can do at home, the people at Spectra479 put this together:

 

 

 

 

Carbonshade and Spectra479 are offering 15% off if you enter the coupon code LAGAKOS at checkout.

 

Normal gray-lensed Ray-Bans block about 85% of all light. Cool for blocking UV, but you’re still getting about ~15% of blue and green light. That’s too much.

 

 

 

 

 

Spectra479s block 99.8% of 450-510nm, which fully encompasses blue to blue-green.

 

 

 

 

 

Carbonshades block 99.8% of 400-570 nm, which fully encompasses blue to green, so the largest range of protection according to study 1 (above) and study 2 (below).

 

 

 

 

I haven’t seen the spectral transmission data on Carbonshades, although they performed the best on Spectra479’s at-home test.

 

The popular orange-lensed Skypers block 98% of blue light and probably not too much green (as per the transmission data below and Spectra479’s at-home test).

 

 

 

 

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 eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS.

For more steps on how to strengthen your circadian rhythms, the potential importance (and relevance) of blocking BLUE/GREEN, and a discussion of the science… head over to Patreon!

Also many more interesting tidbits and some advice, like who might need to upgrade their blue-blockers.

Three bucks a month for access to all articles and there are many other options. And it’s ad-free and you can cancel if it sucks. Don’t hesitate, there are only 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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, mortality, muscle, sex, sleep, strength, Sun, testosterone, vasopressin, Vitamin D

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The importance of entraining skeletal muscle’s circadian clock (and how)

Posted on September 19, 2017 | 9 comments

“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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, Dopamine, melatonin, muscle, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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Artificial light and circadian rhythms: blocking the blues

Posted on September 14, 2017 | 15 comments

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 Skypers … Gunnars … Carbonshades (probably the most effective blue blockers available) … Solar Shields … BLUblox (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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, depression, Dopamine, melatonin, nicotine, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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TRP channels in the Tx of muscle pain & cramps

Posted on September 10, 2017 | 8 comments

https://www.patreon.com/posts/14312822

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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Posted in Advanced nutrition, circadian, glycine, marijuana, muscle, Protein, strength

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How to manage painful muscle cramps

Posted on August 28, 2017 | 11 comments

(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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Posted in Advanced nutrition, circadian, Fish, muscle, sleep, strength

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The Struldbrugs of Luggnag

Posted on August 25, 2017 | 6 comments

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.

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Posted in Advanced nutrition, circadian, TPMC

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