Category Archives: vasopressin

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

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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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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Light & melatonin: timing is everything

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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Circadian Rhythms. Nobel Prize.

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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Circadian rhythms & the blues. AND THE GREENS

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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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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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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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)

 

 

 

Freebie over at Patreon.

 

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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!
(plus, it’s ad-free)

update: part 2 is up now!

 

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Scheduled Meals for Circadian Entrainment

Scheduled Meals for Circadian Entrainment

This one’s for Patrons!

For $3 a month, Patron’s have access to all articles.  I still plan on 4-5 new ones per month and I’ll post at least one of ’em here.  Join up! Thanks.

 

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