-induced circadian disruptions in modern aging societies (Hatori et al., 2017)
While this article could’ve easily addressed the havoc wreaked on most animals (hibernating, migrating, reproducing, etc.) or even many plants by artificial light, the focus is on humans.
Posted in angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diabetes, Dopamine, melatonin, mortality, sex, sleep, Sun, vasopressin
Tagged circadian rhythm, melatonin, mortality, sleep
“The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock systems (Heyde et al., 2018)”
Sleep disruption and circadian arrhythmia induce metabolic, cognitive, and immunological impairments. Is it causal? YES.
Sleep is highly conserved across the animal kingdom, since the dawn of time.
Interesting comparison: unlike hibernation or a coma, sleep is highly reversible. Lots of rebound regulation: lots of wakefulness makes you tired; lots of sleep leads to increased wakefulness.
Studies have shown improved memory performance after naps and extended sleep durations. Imo, you don’t need to go from 6 to 9.5 hours overnight, but keep that “9.5” on your radar.
Diet is easy, just eat like an adult. You can go 10 days without even eating! Try that with sleep. No, don’t try that. Most definitely incompatible with survival. Sleep deprivation impairs cognitive functions.
As a marker of health: cognitive function >>> how many reps you can do at the gym.
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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diabetes, Dopamine, Energy balance, insulin, Leptin, melatonin, sex, sleep, Sun, testosterone, vasopressin, Vitamin D
Tagged circadian rhythm, insulin, melatonin, mortality, nutrition, Paleo, sleep
Some important points: there is a lot of evidence that low melatonin mediates the carcinogenic effects of circadian arrhythmia. One of the classical observations was that melatonin-depleted blood from women exposed to bright light promoted tumor growth in a model of human breast cancer and rat liver cancer (Blask et al., 2005). This is also the study that elucidated one possible mechanism: tumors take-up the n6-fatty acid linoleic acid and convert it to 13-HODE, which drives proliferation. Melatonin inhibits this (and more).
There are also data in both humans and rodents that bright light exposure during the day protects nighttime melatonin secretion against artificial light-induced suppression (eg, Kozaki et al., 2016).
This was confirmed by showing bright daytime light exposure protected sleep quality in people exposed to artificial light at night (Rangtell et al., 2016).
FYI Rodents exposed to light at night are screwed (Blask et al., 2014):
So, daytime light preserves & protects nighttime melatonin secretion. Melatonin-replete blood inhibits tumor growth. And to connect all the dots: daytime light exposure inhibits tumor growth in some pre-clinical models cancer (eg, Dauchy et al., 2015).
And for all you Walburgers, melatonin inhibits aerobic glycolysis in tumors (eg, Hevia et al., 2017 AND Mao et al., 2016)!
This isn’t a free pass for you to use artificial light at night. Ideally, you should use no artificial light at night. Or dim red ones. Or at least rock some hot blue blockers.
Nocturnal light pollution and underexposure to daytime sunlight: complementary mechanisms of circadian disruption and related diseases (Smolensky et al., 2015)
Doxorubicin resistance in breast cancer is driven by light at night-induced disruption of the circadian melatonin signal (Xiang et al., 2015) (same for tamoxifen [Dauchy et al., 2014])
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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.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, Dopamine, melatonin, nicotine, sex, sleep, Sun, testosterone, vasopressin, Vitamin D
Tagged circadian rhythm, melatonin, nutrition, sleep
Reishi, the mushroom of longevity.
“The goal is to maintain or improve brain function and physical performance. And not get cancer.”
‘Shrooms-every-day is part of my long-term anti-cancer plan. It’s not always a lot per serving, but I try to do the whole variety thing as much as possible, whatever’s available.
Maybe it’s one of those ice-age fairy tales fallacies, but cultures around the world have attributed a large number of health benefits to ‘shrooms for literally, thousands of years:
“Ganoderma [reishi] has a very long history in East Asia as a medicinal mushroom dating back to the Chinese materia medica ‘Shen Nung Ben Cao Jing,’ written between 206 BC and 8 AD. It was considered a superior tonic for prolonging life, preventing aging, and boosting qi.”
Open to everyone at Patreon! <- link
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.
Tl;dr: sleep, sunlight, seafood, and exercise. Maybe some others. No industrial foods.
Brain-derived neurotrophic factor (BDNF) comes up a lot, so I’ll just tell you now, it’s like brain-fertilizer.
Sunlight promotes dopamine synthesis in your brain (eg, de Lima et al., 2011). Dopamine, via D5 receptor, has a lot of direct effects on memory and learning, but also stimulates BDNF (Perreault et al., 2013). Take a walk outside after breakfast and/or lunch. Bonus: vitamin D is also good for the brain and exercise after meals promotes +nutrient partitioning.
At night, you need melatonin, and for that, you need darkness. In my experience, it’s harder to control sleep onset & duration than time in darkness. T.S. Wiley recommends 9.5 hours of darkness. That’s a lot, I know, but I have a lot of respect for Wiley and she explains it well in Lights Out!
The studies on melatonin supps are mixed (eg, 1, 2, 3, 4) but those on crappy sleep aren’t (eg, 1, 2, 3), so come on fam, at least get some blue blockers (if you choose Carbonshade or Spectra479, use coupon code LAGAKOS for 15% off).
The positive influence of exercise on brain health seems to have many mechanisms, BDNF being one of them (Seifert et al., 2010). Myokines from exercising muscles have a part in this (Philips et al., 2014), so does beta-hydroxybutyrate (eg, Sleiman et al., 2016 and Marosi et al., 2016). Possible role for exogenous bHB supps?
Niacin boosts BDNF (eg, Fu et al., 2014). Fortunately, it’s fairly abundant in the diet, but if you wanna try something new, nutritional yeast can add cheesy deliciousness to just about anything.
Niacin is also a precursor to NAD+, and this company really REALLY thinks NAD+ is the bomb (see their website for a round-up of the science). Rodent studies have suggested nicotinamide riboside is better at boosting brain NAD+ than niacin (eg, Collins and Chaykin, 1972), but as mentioned above, niacin isn’t hard to find via diet.
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.
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Posted in Advanced nutrition, chronopharmacology, circadian, diet, Dietary fat, Dopamine, Exercise, melatonin, Sun, wine
Tagged circadian rhythm, ketones, melatonin, sleep
Full article open to everyone over at Patreon! <- link
What’s more anti-cancer than ‘shrooms and isothiocyanates?
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.
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, liver, melatonin, mortality, nicotine, Protein, sex, sleep, Sun, testosterone, vasopressin, Vitamin D
Tagged body composition, circadian rhythm, energy balance, melatonin, mortality, muscle, sleep
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.)
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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, mortality, sex, sleep, Sun, vasopressin, Vitamin D
Tagged circadian rhythm, melatonin, sleep
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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
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.
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.
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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
Tagged body composition, circadian rhythm, melatonin, obesity, Paleo, sleep
“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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, Dopamine, melatonin, muscle, sex, sleep, Sun, testosterone, vasopressin, Vitamin D
Tagged body composition, circadian rhythm, diet, dopamine, energy balance, energy expenditure, melatonin, muscle, sleep
We evolved on Earth, with regular 24-hour “circadian” cycles; abandoning them is incompatible with survival. Natural Selection does not look upon this favorably.
The first time this was discussed, HERE, they ablated the master circadian clock, the SCN, which made the animals arrhythmic with a bollixed circadian period:
resulting in significantly increased predation in the wild:
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian
Tagged circadian rhythm, melatonin, mortality, Paleo, sleep