Brain Health, Easy Steps

Posted on November 9, 2017 | 1 comment

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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Posted in Advanced nutrition, chronopharmacology, circadian, diet, Dietary fat, Dopamine, Exercise, melatonin, Sun, wine

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Yet another study showing low carb doesn’t impair performance +

Posted on November 6, 2017 | 1 comment

and by some metrics, at least in this study, might even improve it.

Ketoadaptation enhances exercise performance and body composition responses to training in endurance athletes (McSwiney et al., 2017)

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Advantage of this study over previous ones: 12 weeks. I believe the choice to opt for self-selection over randomization was to improve adherence (which was pretty good for this 12 week-long study). Downside is, well, it’s not randomized. Crossover RCT is best but it’s always a trade-off: sample size, duration, tools, etc., everything has a price. Literally.

Tl;dr: Ketoadaptation doesn’t diminish performance at high intensity even after “draining the tank.”

The study: we aren’t told much about the diets, just high carb vs. ketogenic. And keto group was advised to drink broths for salts, mins, electrolytes, etc.* Speaking of which 🙂 Kettle & Fire is offering 20% off their delish broths/stock HERE.

*I don’t think this qualifies as cheating in this #context.

Before and after the 12-week dietary intervention, a battery of tests were performed: a six second all-out bicycle sprint (SS), immediately followed by a 100 km time trial (TT), immediately followed by a 3-minute sprint (CPT).

These were well-trained, healthy individuals who continued their training throughout the study. This & duration are two important nuances of this study (more on this below).

The biggest finding …*drumroll* … significantly greater fat loss in the keto group and this wasn’t even a weight loss study. They also jacked up protein intake so they didn’t lose muscle mass. Protein declined in the high carb group, but they were able to maintain muscle because carbs increased.

 

WHERE HAVE WE SEEN THIS BEFORE

HINT: HERE

 

 

Whether they knew it or not, this study was designed to test peak power output before (SS) and after (CPT) exhaustively draining the tank (TT). The theory is that ketoadaptation: 1) spares glycogen so there’s some juice left in the tank for the second peak power test, although racing 100 km is pretty tough so there couldn’t have been much juice left in either group; and 2) ketoadaptation relies more on fatty acids at every level of output, as evidenced by the RER figure (below). Fuel usage comes close at high levels of output (both groups rely more heavily on glucose), but ketoadapted is always a little lower (eg, see the right-most point in the figure below). And fat stores are basically limitless whereas glycogen is not. This may or may not have been a factor here.

 

PEAK PERFORMANCE

I don’t know why the authors reported peak power relative to body weight. I could understand lean mass, maybe, but keto lost a lot of weight via body fat. If peak power remained the same (as has previously been shown), it would [falsely] appear to increase in this study.

For a more nuanced interpretation of this study (which is good, I promise!), head over to Patreon! 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 HERE. TrueDark is running a pretty big sale 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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Posted in Advanced nutrition, diet, Dietary fat, insulin, Ketosis, muscle, Protein, strength

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TRP activation indicates an assassination attempt

Posted on November 3, 2017 | 1 comment

Whether it’s a noxious odor or burning sensation, TRP channels are there to let you know something’s up. They’re why we feel sting, burn, itch, etc., etc.

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TRPV1 lights up just as much if you bite into a burning hot food as it does a hot pepper. It responds to physical heat and capsaicin.

The infamous wasabi receptor, TRPV1:

TRPA1 in the lungs reduces respiration because it’s activated by poisonous gases… so you end up breathing in less of the poisonous gas. Actually, respiratory TRPA1 activation will make a sleeping mouse wake up and flee!

And yet for some reason, TRPs are anti-cancer in a wide variety of #contexts.

New insights into pharmacological tools to TR(i)P cancer up (Gautier et al., 2014)

If you’re exposed to a TRP activator and escape, cool, if not, you die (jk). Unless it’s a false assassin, in which case that smarty TRP will be downregulated.

I’m happy to have not participated in this study:

Oral irritation by mustard oil: self-desensitization and cross-desensitization with capsaicin (Simons et al., 2003)

Jab a mouse with a large enough dose of capsaicin, early enough in life, and they’re virtually permanently desensitized (Gamse et al., 1980). Under no circumstances should you do this.

 

 

TRPA1 is actually upregulated in lung cancer cells (Schaefer et al., 2013). It’s unknown why, but given the chemopreventive nature of TRPs and the ability to modulate them, might a spicy meal or 2 be prudent?

For the rest of this article (and much more) head over to Patreon! 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 HERE. TrueDark is running a pretty big sale 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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Posted in Advanced nutrition, cancer

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This study on melatonin supps proves everything about LIGHT is true

Posted on October 31, 2017 | Leave a comment

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 HERE. TrueDark is running a pretty big sale 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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, insulin, melatonin, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

Breast Cancer Awareness Month

Posted on October 28, 2017 | 6 comments

“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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, sex, sleep, Sun, vasopressin, Vitamin D

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Ketones, Cancer, and the NLRP3 Inflammasome

Posted on October 25, 2017 | 4 comments

“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?].

 

Continue reading →

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Posted in Advanced nutrition, circadian, Ketosis, liver, melatonin, mortality, Sun

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Efficacy of a wide range of things, from sleep & diet to supps & meds, may depend on timing

Posted on October 22, 2017 | 2 comments

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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, epilepsy, Ketosis, melatonin, nicotine, sex, Sun, vasopressin, Vitamin D

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Fixing your rhythms makes everything better. Here’s how.

Posted on October 19, 2017 | 15 comments

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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, liver, melatonin, mortality, nicotine, Protein, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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We don’t want more or less antioxidants. We want balance. #NRF2

Posted on October 16, 2017 | 5 comments

“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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Posted in Advanced nutrition, circadian, diet, muscle, nicotine, smoking

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Light & melatonin: timing is everything

Posted on October 13, 2017 | 3 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, muscle, Protein, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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