Category Archives: Bromocriptine

SERcadian Rhythms

The amino acid L-serine may be the next melatonin. A new study showed administration of 3 grams ~30 minutes before bedtime advanced melatonin onset dramatically, almost instantly. It didn’t increase the concentration of melatonin, just onset (Yasuo et al., 2017). For a higher concentration, you’d need AM sunlight and PM blue blockers or actual mel supps (preferably the former) (eg, Burke et al., 2013).

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Important and interesting caveat in the L-serine story: it only worked if the participants received bright light in the morning.

 

In the figure below, “day 1” is no AM light and “day 2” is yes AM light. In both the L-serine and placebo groups, there is a phase advance on day 2 because of the AM light treatment. The advance is markedly greater when the participants received 3 grams of L-serine:

 

Using rodent models (which mimicked the human effect almost exactly), GABA-A receptors were implicated.

Interesting for a couple reasons.

 

 

GABAnergic agents like benzo’s and alcohol don’t really put you to sleep; they knock you out, which isn’t proper sleep. This suggests a non-circadian effect of L-serine; however: 1) GABA-A prevents light-induced SCN activation; and 2) serine advanced melatonin onset (specifically only when combined with light in the morning).

Anyone gonna try L-serine?

To learn more about this fascinating discovery or if you just like what I do and want to support it, head over to Patreon! Five bucks a month for full access to all articles and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

Also, I’m open to suggestions so feel free to leave a comment or email me directly at drlagakos@gmail.com.

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. I recommend Lion’s Mane for the brain and Reishi for everything else.

 

 

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Two important blog posts which may hint at how this happened: LIGHT timing for circadian entrainment and Melatonin sensitizes the system.

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This study on melatonin supps proves everything about LIGHT is true

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Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening (Rubio-Sastre et al., 2014)

If you like what I do and want to support it, consider becoming a Patron! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

Also, I’m open to suggestions so feel free to leave a comment or email me directly at drlagakos@gmail.com.

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 HERETrueDark is running a pretty big sale HEREIf 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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Breast Cancer Awareness Month

“LIGHT for thought”

There are some things you can control and many more you can’t (eg, circadian disruption, alcohol, BRCA, etc.). It’s impossible to know how much circadian arrhythmia contributes to cancer risk, but the epidemiology is strong and some of the mechanistic work makes sense. It has to do with LIGHT and melatonin.

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Tl;dr: a robust circadian rhythm and proper melatonin peak at night mitigate a lot of other factors. If there’s artificial light at night, then there’s no melatonin, and that’s like, SHIELDS ARE DOWN! And it doesn’t take a lot to shut ‘em down.

There’s also a dietary angle, but it’s borderline one of those things you can’t change (unless you try really really hard) (more on this below), or at least not nearly as fast as you can fix melatonin (see HERE).

 

In 1978, Cohen and colleagues made a few seminal observations (Cohen et al., 1978). In their words,

“(1) Pineal calcification is commonest in countries with high rates of breast cancer and lowest in areas with a low incidence; the incidences of pineal calcification and of breast cancer are moderate among the black population in the United States.

(2) Chlorpromazine raises serum-melatonin; there are reports that psychiatric patients taking chlorpromazine have a lower incidence of breast cancer.

(3) Although information is lacking on breast cancer, the pineal and melatonin may influence tumour induction and growth in experimental animals.

(4) The demonstration of a melatonin receptor in human ovary suggests a direct influence of this hormone on the ovarian function, and possibly oestrogen production.

(5) Impaired pineal secretion is believed to be an important factor triggering puberty (early menarche is a risk factor for breast cancer).”

 

The dark side of light at night: physiological, epidemiological, and ecological consequences (Navara and Nelson, 2007)

 

 

And further observations, for example, that urinary melatonin is prospectively inversely associated with breast cancer (Schernhammer et al., 2008) and total blindness is protective against breast cancer (Flynn-Evans et al., 2009). Total visual blindness is associated with a variety of other problems, but they’re less likely to succumb to artificial light at night-induced melatonin suppression.

 

For the rest of this article or if you just like what I do and want to support it, head over to Patreon! Three bucks a month for access to all articles and there are many other options. There is a limited number of spots left at the $3 level so sign up soon! You can cancel at any time.
And it’s ad-free 🙂

Discounts: still looking for some hot blue-blockers? Carbonshade and Spectra479 are offering 15% off with the coupon code LAGAKOS. And for some delicious organic broths/stocks, Kettle & Fire is 20% off HERE.

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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

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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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