Category Archives: Advanced nutrition

Research studies, hypotheses, data, etc.

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?].

 

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

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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.

[Patron link]

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.

 

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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.

[Patrons click here]

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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Pregnancy dieting and #moderation: just don’t be extreme

Posted on October 10, 2017 | Leave a comment

“If you can’t absorb B12, no amount of steak will help you” (more on this below)

Just like practically everyone in the field, I’m uncomfortable with the word moderation, in part because one person’s moderation can be wildly different from another’s.

Remember the Motherwell studies? In brief, they asked a group of expecting women to ditch carbs and eat a ton of meat instead (about a pound per day), and compared them with a group not given diet advice. It was designed to compare an extreme diet to an average diet (note: they didn’t assess the opposite extreme, ie, high carb vegan).

Tl;dr: babies were healthy at birth but developed a variety of health problems later in life. Perfect study design? No. Better than ALSPAC? Kinda, yeah.

 

 

In the context of today’s topic, I’ll define moderation as “not extreme” (bear with me here) (unless ALSPAC is retracted or something… which is possible given the study design.)

 

Meat consumption during pregnancy and substance misuse among adolescent offspring (Hibbeln et al., 2017) (aka ALSPAC)

 

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The *other* spicy things

Posted on October 7, 2017 | 3 comments

Wasabi, horseradish, mustard, radish, etc., etc.

 

The Isothiocyanates (ITCs) (for example, allyl isothiocyanate [AITC])

 

It’s basically cancer’s second worst enemy (just after ‘shrooms). Also an enemy of anything that tries to eat AITC-containing plants (it’s even harmful to the plant itself!). Actually, AITC is stored in a harmless form, as a glucosinolate. The enzyme myrosinase is stored separately. When the cell walls are broken (something bites into it), and myrosinase comes in contact with glucosinolate, AITC is formed. In the animal kingdom, it’s kinda like tear gas. It’s even harmful to the plant, but better a little chemical burn than eaten alive.

 

 

Side note: store-bought wasabi is usually horseradish and maybe some mustard, but for the #context of this article, it doesn’t really matter because they all contain isothiocyanates. If you want to get the right thing, try and find the actual plants; they’re not easy to confuse:

Wasabi:

 

 

 

Remember NRF2?

Wasabi does that, too!

 

Horseradish:

 

 

 

 

Isothiocyanates

For us, it’s what drives the mouth-burning, sinus-clearing, and eye-watering sensations.

Unlike capsaicin (the *other* spicy things; eg, from hot peppers), the burn is much shorter in duration because AITC is water soluble. Try eating a habanero and putting out the fire with ice water.

YOU’RE MAKING IT WORSE

Capsaicin is fat-soluble; it doesn’t dissolve in water (especially cold water) – so you’re basically just spreading it all around your mouth. Try something with a little fat instead.

 

Mechanisms of action of isothiocyanates in cancer chemoprevention (Navarro et al., 2011)

chemoprevention > chemotherapeutic

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 and 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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Circadian rhythms & the blues. AND THE GREENS

Posted on September 24, 2017 | 7 comments

Open access for all at Patreon! <- linkage

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

Patrons can just click here…

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.

For more steps on how to strengthen your circadian rhythms, the potential importance (and relevance) of blocking BLUE/GREEN, and a discussion of the science… head over to Patreon!

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.

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, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, mortality, muscle, sex, sleep, strength, Sun, testosterone, vasopressin, Vitamin D

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The importance of entraining skeletal muscle’s circadian clock (and how)

Posted on September 19, 2017 | 9 comments

“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.

 

For the rest of this article (including my interpretation and advice), 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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, Dopamine, melatonin, muscle, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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TRP channels in the Tx of muscle pain & cramps

Posted on September 10, 2017 | 8 comments

https://www.patreon.com/posts/14312822

NSAIDs are OK for muscle pain, but may hinder training progress in the long run (eg, Shoenfeld 2012 and Mackey 2013). The electrolyte theory of muscle cramps has been kinda debunked in some contexts (eg, Braulick et al., 2013, Miller 2014, and McKenney et al., 2015)… although I still recommend all the broths & stocks (homemade, store-bought, chicken, beef, seafood, etc.) for just about everything. 20% of Kettle & Fire broths through this link!

But even when pickle juice works (eg, Miller et al., 2010), it kicks in way sooner than if it worked via replenishing electrolytes – more likely works via the acidity activating specific ion channels.

What do we have left?

Google Image Search came through pretty epic for this…

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Posted in Advanced nutrition, circadian, glycine, marijuana, muscle, Protein, strength

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Herbs, spices, TRP receptors, and pain

Posted on September 5, 2017 | 2 comments

The TRP ion channels TRPA1 and TRPV1 have a complicated & interesting relationship with neural activation and pain.

TRPV1 is partly responsible for the pain we feel from eating hot peppers. Capsaicin (or some capsaicinoids or even ginger) bind to this receptor, and we can FEEL IT. The nerves on which TRP ion channels reside become hyperexcited, which has the theoretical effect of feedback inhibition on other afferent nerves in the spinal cord. As far as the TRP-muscle cramp theory goes, this dampens hyperexcited muscle cramp-inducing nerves. So basically, instant resolution of painful muscle cramps.

 

 

Mustard, cinnamon, and garlic hit TRPA1 for a similar effect. Instant muscle cramp-relief… but depending on your taste preferences, could be unpleasant.

 

 

 

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Effects on body recomposition, more on spices, and my personal experience!

 

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An interesting theory on the treatment of muscle cramps

Posted on August 31, 2017 | 17 comments
Being the nerd I am, after experiencing a few days of painful muscle cramps (which I wrote about here), I went to Google like a madman.
Here’s what I learned from the experience and subsequent Googling.
Most things I wrote in the original post still stand. But there are a ton of completely different types of muscle cramps; those associated with cirrhosis, MS, pregnancy, dialysis, idiopathic nocturnal, etc.
Number 1 mandatory advice: do all the long-term stuff like broths, (20% off Kettle & Fire!) potassium, mag, etc (even though all of these things have mixed findings; they might work for your specific type of cramp and are unlikely to cause harm). But for immediate management of painful cramping, you may need to bite the bullet and take a muscle relaxer or benzo or something.
A lot of this post is inspired by a crazy theory touted by a new anti-cramp product (targeted at yet another type of cramp, “exercise-associated muscle cramp” [EAMC]), but the explanation of it’s mechanism is super-interesting.

I still stand by the previous interventions, except according to a few case studies and a lot of anecdotes, pickle juice can work within 1-2 minutes! That observation was part of the basis of developing this product. Some people think the acidity in pickle juice activates gastrointestinal TRP receptors (see below), and I’m totally cool with all kinds of vinegar…
But I digress.

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 and all prior & future articles, head over to Patreon! Three bucks a month for access to all content. It’s ad-free and you can quit if it sucks.

There are a limited number of spots left at the $3 level, so join soon! You can cancel at any time.

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

 

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Posted in Advanced nutrition, diet, Exercise, strength

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