Category Archives: nicotine

Intermittent Fasting and Goalposts

I may come across as harsh on Intermittent Fasting (IF) and I’d like to be clear about something. I’m not saying IF will make you gain body fat or die a slow and painful death. I am saying the quality of evidence presented in human studies suggesting it will benefit you somehow is #weaksauce. Further, I don’t really like the idea of huge refeeds. Like, how can 2000 kcals in one sitting be remotely healthy?

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Metabolic. Mayhem.

 

 

You may have noticed many guru’s sliding away from “intermittent fasting” and “skipping breakfast” and toward promoting a more circadian-appropriate feeding pattern. That’s because it’s about when you eat, not the precise duration of the feeding window.

The studies have been done:

 

Which brings me to the current IF study #weaksauce du jour and it’s implications. But for that you’re gonna have to head on over to Patreon! Five bucks a month gets you access to all articles 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 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. 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.

[FULL ARTICLE ON PATREON]

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 🙂

Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!

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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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.

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

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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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).

Free full article on Patreon!

 

 

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])

 

For full access to all articles and much more (or if you just like what I do and want to support it), become 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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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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We don’t want more or less antioxidants. We want balance. #NRF2

“The goal is to maintain or improve brain function and physical performance. And not get cancer.”

Antioxidants

There isn’t a strong case to make for antioxidant supplements. They’ve been shown to do nothing more often than not, and even harm in a few cases when dose & #context were mismatched (eg, ATBC and CARET). This is part of what led to the conclusion that we want an appropriate “reactive oxidative species *tone*” or “antioxidant balance.” Or “landscape.” Or some other catchphrase of the week.

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In line with this, animal models that genetically up- or down-regulate antioxidant pathways are predicted to show negative or no effects because they are, practically by definition, generating a mismatch.

In humans under normal conditions, I believe pro- and anti-oxidants are balanced by our own endogenous processes. If we ingest something that produces a bit too much ROS, they’ll be neutralized. If we ingest something that induces antioxidant processes, they’ll be used if necessary and degraded if not. In other words, as long as you’re not mega-dosing beta-carotene or smoking 2 packs a day, etc., then none of this should matter.

 

 

NRF2

Which brings me to NRF2. I like the concept of periodically inducing our own endogenous detox processes because it seems like they’ll either help or do nothing. Not harm. It’s like, stacking the deck in your favor.

Nrf2: ket target for the treatment of neurodegenerative diseases

 

Bioactive Neutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy

If you ingest something that induces NRF2 and something needs detoxifying (for example, some manifestation of improper ROS tone or inflammation or something), then NRF2 will get it done. Otherwise, NRF2 goes away in about 20 minutes (Kobayashi et al., 2004).

 

Reminders: still looking for a pair of hot blue blockers? Carbonshade and Spectra479 are offering 15% off with the coupon code LAGAKOS. And Kettle & Fire is offering 20% off of their delish broths/stocks HERE.

 

If you like what I do and want to support the show, consider becoming a Patron!

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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LIGHT timing for circadian entrainment

Basically, this much is pretty obvious now: LIGHT and food in the morning + darkness after sunset = proper circadian entrainment.  But the how is pretty cool; LIGHT affects different biochemical pathways at different times of the day, which is how it can either advance or delay your circadian phase.

LIGHT entering the eyes is perceived by ipRGCs which then dish out glutamate and PACAP.  These mediators go on to activate receptors in the SCN (the “Master Clock”).

Depending on the time of day, glutamate and PACAP affect different pathways.

 

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Protein dilemma ~ sleepy or smart. #Gelatin

Gelatin and glycine have bounced around the blogosphere for quite some time.  Coming from a nutrition-centric place: you say gelatin, I think tryptophan (or lack thereof) and glycine.  Others think:

Jane Plain discusses positive mental effects of gelatin and pimps Pro-Stat (good source of glycine).  Chris Masterjohn discusses glycine and in typical WAP fashion seems to favor bone broth (20% off Kettle & Fire’s awesome broths HERE!).  Knox gelatin didn’t help Michael Allen Smith sleep better, and he apparently tracks sleep quality quite well.  However, Sondra Rose thinks it improves sleep harmony, and gelatin simply blows Dana Carpender’s mind.

bones

 

Tryptophan-rich proteins like those found in whey and egg whites will elevate blood levels of tryptophan relative to other large neutral amino acids (Trp:LNAA ratio), leading to higher brain uptake and subsequent serotonin synthesis.  Tryptophan-poor proteins like gelatin do the opposite, and impair memory.  But the high glycine content in gelatin improves sleep quality.*  Glycine powder might be able to get around this, it’s dirt cheap and it seems to have the opposite effect on brain serotonin, albeit at a much higher dose (and in rats).

 

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