Tag Archives: melatonin

Global rise of potential health hazards caused by blue light

-induced circadian disruptions in modern aging societies (Hatori et al., 2017)

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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.

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Watch the Clock, Not the Scale

I’ve been known to say intermittent fasting is #weaksauce because most of the human studies show little or no effect and people frequently report being hungry (yes, even if LCHF). Human studies, not “n=1’s.”

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Well, now we know why. Time-restricted feeding (TRF) only really works when the feeding window is early (eTRF), as demonstrated by the recent Sutton study which showed, miraculously, great benefits achieved sans weight loss. Calories were strictly controlled in that study to prevent weight loss. AND when the participants were on eTRF, they actually reported less hunger in the evening.

 

 

We know from the studies by Jacobs and Hirsh that under ad lib AND isocaloric conditions, people lose more weight eating all their food for breakfast than those eating all their food for dinner.

 

 

That’s cuz metabolism is gimped at night. Lower metabolic rate and greater propensity to store fat.

Melatonin sensitizes the system, preparing it to optimally partition nutrients in the morning.

For the rest of this awesome article, head over to PatreonFive bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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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 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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Dopamine regulates systemic glucose metabolism in humans

In Four. EPIC. Experiments (ter Horst et al., 2018)

Tl;dr: sunlight & breakfast in the morning.

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Dopamine receptors are downregulated in obese patients and are restored in long-term weight loss patients after bariatric surgery. It’s better to get your dopamine hit via sunlight than sugar duh.

This is some amazing science.

 

 

Experiment 1. 50-year old dude with severe OCD gets diagnosed with type 2 diabetes and is only able to get his glucose under control with metformin and 226 IU insulin. At 53, his OCD is treated with deep brain stimulation (DBS). His insulin requirements declined to 180 IU. He didn’t lose weight but went off quetiapine, so maybe coincidence because: 1. quetiapine is diabetogenic; and 2. DBS induces dopamine release.

Two-step hyperinsulinemic euglycemic clamp when DBS is turned off and turned on. BOOM! When it’s on, lower fasting insulin, and better insulin-induced suppression of liver glucose output, free fatty acids, & muscle glucose disposal! DBS improved insulin sensitivity in liver, adipose, and skeletal muscle.

For the rest of the discussion on these super-interesting experiments, head over to PatreonFive bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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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 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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Cycloset (bromocriptine)

 

 

Go for a walk.

And #eTRF.

 

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Mutual influence of sleep and circadian clocks on physiology and cognition

“The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock systems (Heyde et al., 2018)”

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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.

For the rest of this article (it doesnt suck, I promise!), head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

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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 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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It STARTS with Sleep.

 

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Circadian rhythms, sleep deprivation, and human performance

“Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep-wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance (Goel et al., 2013).”

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Acute and chronic sleep restriction degrade neurobehavioral functions, attention, cognitive speed, and memory. Strictly according to the studies (not your n=1), < 5.5 hours is bad, < 7 hours is suboptimal, and ~ 9.5 hours may be optimal. Seems like a lot; who has time to sleep 9.5 hours?!

Above image shows cerebral blood flow (orange) in the same person’s brain during a Psychomotor Vigilance Test performed in the morning and afternoon. Interestingly, most participants perform better in the afternoon and this is associated with more blood going to a different part of the brain.

“Sleep is a ubiquitous biological imperative that appears to be evolutionarily conserved across species.” Mandatory for optimal attention and cognitive performance.

To get the rest of this article (it doesn’t suck, I promise) or if you just like what I do and want to support it, head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

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

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It STARTS with Sleep.

Social jet lag.

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Poor sleep, “dietary disinhibition,” and weight gain

“Dietary disinhibition”

In school, the concept was taught like this: recruit a bunch of people and tell them it’s for a cookie taste-testing project. Give them a form with a bunch of questions about cookie quality (taste, texture, sweetness, etc.) and a plate of cookies.

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SWITCHAROO!

They aren’t there for a cookie taste-test. It turns out that some people experience “dietary disinhibition” wherein if they eat one cookie, they think something like “well, I’ve blown my diet for the day, so might as well just eat the whole plate of cookies” (actually, I’m pretty sure it’s way more complicated than that, but I learned it in a nutrition class, not a psychology class).

It’s not a lot of people — most would just take a bite and fill out the questionnaire — but it’s been replicated in enough settings that it’s probably a real phenomenon.

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Sunlight is anti-cancer: get some

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).

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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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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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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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Brain Health, Easy Steps

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.

For the rest of this article (which includes advise on foods & supps), 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 content and there are many other options. Sign up soon as the number of spots at the $3 level is limited. It’s ad-free and you can cancel at any time.

 

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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.

 

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