Category Archives: Sun

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?

In you’re interested consultations with me, reach out: drlagakos@gmail.com.

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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

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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.

Brain Health, Easy Steps

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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 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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This study on melatonin supps proves everything about LIGHT is true

Open to everyone on Patreon!

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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Ketones, Cancer, and the NLRP3 Inflammasome

“Check ‘em all. Do the work. There’s no room for cherry-picking here.

LOOK THE GIFT HORSE IN THE MOUTH”

A few years back, researchers discovered the pseudo-ketone beta-hydroxybutyrate suppressed the NLRP3 inflammasome (Youm et al., 2015). NLRP3 is notorious for aggravating gout symptoms, so it was like: “Yay! A potentially clinically relevant use for ketone supps!” (I think there might be other applications as well, but that’s for another blog post).

Ketones, NLRP3, and IL-1b

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It’s thought that NLRP3 is around during active flares, so gout sufferers would stay on their regular meds and take ketone supps as needed – this is important because from what I understand, gout flares really suck, some people get them frequently, and ketone supps aren’t covered by insurance [yet?].

 

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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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