Category Archives: Dopamine

Another great camping experiment

In the original Incredible camping experiment, a week-long camping trip was shown to cause people to fall sleep & wake earlier, feel better, and advanced their melatonin secretion.  In the new Camping Experiment, they showed that 70% of this is accomplished within the first 2 days!

 

Some of the #FakeNews headlines attributed the improved sleep quality to sleeping in a tent.  “Cute.”  More likely, this was driven by absence of artificial light.

Proposal: How about fasting from artificial light one day per week?  Or maybe just one night per week?

 

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Metabolism at night

From circadian entrainment to blood glucose management to appetite control to sleep quality:

 

 

We’re really not made to skip breakfast and eat late at night.  Nearly every line of evidence points to this.  And now:

Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study (Bo et al., 2015)

 

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Ketones, NLRP3, and IL-1 beta

Interleukin-1 beta: produced by activated M1 macrophages, classical fever-inducing cytokine, mediates cellular inflammation, and induces COX-2 (target of NSAIDs).  Also involved in autoimmunity.  You don’t want none of it but you certainly don’t want a lot of it.

The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasone-mediated inflammatory disease (Youm et al., 2015)

This is a very specific effect: 1) many structurally similar compounds don’t block NLRP3; and 2) beta-hydroxybutyrate doesn’t block activation of other inflammasomes.

 




 

“In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1b secretion in mouse models of NLRP3-mediated diseases such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome and urate crystal-induced peritonitis. Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.”

 

 

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Specific Absorption Rate

 

I was bored and had a stronger-than-usual espresso, saw the above Tweet, so obviously I decided to read the Health & Safety Guide that came with my cell phone.

The Federal Communications Commission (FCC) set specific limits to Radio Frequency (RF) that any given electronic device can emit.  Theoretically, at or below this level is “safe.”  The actual number comes from the National Council on Radiation Protection and Measurement (NCRP) and Institute of Electrical and Electronics Engineers (IEEE).  The overall tone of this document is grave, ie, they take this RF limit very seriously.

 

The limit: 1.6 W/kg (Specific Absorption Rate [SAR]) or 0.0016 W/g.

 

I checked online at www.fcc.gov/oet/ea, and my phone is rated 0.3 Watts (W) at around 1.5 cm – distance is important: in this case, it’s the difference between squashing the phone between your face and your hand vs. holding it a finger tip’s distance away.

 

So, is my brain safe?  Hard to say; how many grams of brain are within 1.5 cm from my brain? If we’re talking whole head exposure, ~4 kg, that’d be ~6 W.  But I’m more concerned about the 4 grams of brain closest to my ear, within that 1.5 cm range, because brain cancer is pretty scary at any level of brain cancer (ie, whether it affects whole brain or just the 4 grams closest to my ear).

I can’t figure out these maths so I’m sticking with earbuds until I can.

 

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MELATONIN

There are a lot of mysteries involving melatonin, eg, relative importance of gut vs. pineal-derived melatonin.  Does brain melatonin talk to peripheral MT receptors?  Does gut melatonin talk to brain MT receptors?

What we do know: oral melatonin works in people with circadian-related sleep disorders.  This may suggest that oral/gut melatonin talks to brain MT receptors OR that oral/gut melatonin corrects circadian sleep problems by acting in the periphery.  OR a major target of brain melatonin is peripheral MT receptors.  I don’t know.

And as a further testament that melatonin supps aren’t sleeping pills is that they’re non-addictive and can at least temporarily “fix” circadian sleep problems: after prolonged treatment, people report no withdrawal symptoms and still sleep better even up to two weeks after discontinuation (Lemoine et al., 2011)!

 

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LIGHT is a drug

Three stories about LIGHT

One

Carbon monoxide (CO): one of the nasty things in car emissions & cigarette smoke.  Also, a byproduct of the ever-important heme.  Heme, as you may recall, activates Rev-erb:

 

“Food for thought: an endogenous ligand of Rev-erb is heme (the iron-binding element in red blood cells).  Heme is degraded into bilirubin.  Elevated levels of bilirubin cause jaundice.  A treatment of neonatal jaundice is exposure to blue light.  Blue light is a major regulator of circadian rhythms and Rev-erb is an executive-level player in this game.  The primary mechanisms of blue light appear unrelated in these two models (melanopsin activation vs. bilirubin photoisomerization), but seem intertwined, because heme activates Rev-erb.  Cool.”

 

News: Disruption of the body’s internal clock causes disruption of metabolic processes

Science: Reciprocal regulation of carbon monoxide and the circadian clock (Klemz et al., 2016)

Tl;dr: heme degradation occurs on a circadian cycle and produces CO.  CO prevents Clock/Bmal1 from binding to DNA. Inhibiting this process throws off numerous other circadian rhythms in the liver.

SUNLIGHT and food in the morning, and let endogenously produced CO rhythmically tune the clock in the evening.

 

 

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If meat causes cancer…

Disclaimer: I’m meat-cancer agnostic.  *IF* meat causes cancer (and I don’t think it does), it happens extremely slowly and only at very high levels of intake: to get statistically significant risk ratios, researchers usually look to top vs. bottom quartiles, which is quite a large difference in intake.

Meat-cancer studies Tl;dr: some studies show positive associations, some neutral, and none are negative (ie, it’s unlikely meat prevents cancer).

That said, if meat does cause cancer, here is how it might happen:

1. The “Maybes:” AGEs, leucine/mTOR, methionine, etc., but only in combination with numbers 2 & 3.  Not by themselves.

2. Circadian arrhythmia and cancer: potential mechanisms

3. Most animal foods have a lot of linoleate 18:2n6 or at least a lot more n6 than n3 (grass-fed is usually a little better in this context).  More on this below.

 

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Circadian rhythms and cancer: potential mechanisms

Humans are incredible omnivorous beasts that can thrive on a great variety of diets, but crumble if you mess with their sleep.

Circadian arrhythmia is thought to be a driving force behind a few types of cancer.  But how, exactly, does seemingly harmless things like artificial light, skipping breakfast, or jet lag actually promote tumorigenesis?  There are many potential mechanisms, and I’d bet different circadian disruptions promote different cancers in different #contexts.

In some cell types, circadian disruptions which dampen amplitude increase proliferation.  This has led to some researchers to believe a robust circadian rhythm per se is tumor-suppressive.  In agreement with this, many tumor suppressors are direct targets of circadian transcription factors.  As was observed in some skin cancers, you may want suppressed proliferation at some times of the day but not others, so the tissue can renew properly.  But you don’t want, for example, skin cells to be proliferating while they’re being exposed to UV light, so this process happens at night (in circadian fashion).

Circadian transcription factors also directly interact with endogenous antioxidant systems.

 

circadian-image

 

Cancer clocks out for lunch: disruption of circadian rhythm and metabolic oscillation in cancer (Altman, 2016)

 

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Circadian rhythms and prostate cancer

Observations:

Incidence of prostate cancer is higher among pilots, flight attendants, and rotating shift workers than the general population (RR as high as 3.0 in some cases!).

Circadian rhythms of androgens is absent & clock genes are disrupted in prostate cancer; the latter of which is reversible with melatonin which also suppresses prostate cancer progression.

Interestingly, radiation treatment is significantly more effective before 5pm than after.  I don’t know why this is; could be a spurious correlation.  Or not.

 

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Discordant insulin sensitivity on a high protein diet

So, we have another “high protein” weight loss study (Smith et al., 2016).  Or really, a “low (0.8 g/kg) vs. moderate (1.2 g/kg) protein weight loss study.”  In brief, it took ’em about 6 months to lose 10% of their starting body weight, then were given 4 weeks of weight stability before “after” measurements were taken.

Important: this was not a contest to see who would lose more weight; they kept going and adjusting food intake until both groups lost 10%.  Not really ad lib, but otherwise a good study design imo.  The intervention was relatively weak (eg, protein 0.8 vs. 1.2 g/kg), but on the plus side, that’s realistic and very “do-able.”  If you’re interested in super-high protein diets (3-4 g/kg), check out research by Jose Antonio.

 




 

Big yet not unexpected finding: the low protein group lost about twice as much muscle than the normal protein group.

 

fat-free-mass

 

The isocaloric normal protein group lost more fat and less muscle than the low protein group.

But then everyone freaked out because the low protein group experienced a significant improvement in muscle/liver insulin sensitivity whereas the normal protein group didn’t:

 

glucose-rate-of-disappearance

 

-The headlines were hilarious, like, “high protein makes weight loss not work anymore.”

-Then some critics jumped the shark and blamed it on “liquid calories,” because whey protein shakes are totes non-Paleo, and #JERF.

-TBH, I found more interesting the changes in adipose insulin sensitivity

The normal protein group had the most insulin sensitive adipose of all groups… yet they lost more fat mass despite eating just as much or even slightly more than the other groups.

 

adipose-insulin-sensitivity

 

Does this mean they’re doomed to regain the weight?  I don’t think so, as high dietary protein is one of the strongest predictors of weight loss success long-term.

HERESY!  the low protein group had: 1) lower basal insulin than the normal protein group; 2) lower adipose insulin sensitivity; 3) ate less (NS); yet lost less fat mass.

 




 

In other words, the normal protein group had higher basal insulin, more insulin sensitive adipose tissue, and slightly higher food intake (NS).  According to the insulin model, they should’ve lost less fat mass than the low protein group, but they didn’t.

Is this another chink in the armor of the insulin model?

The truth seems to be: people lose weight on both LC and LF diets by giving up junk food.  On LC, this is accomplished by giving up carbs; on LF, this is accomplished by switching to better carbs.  Some people adhere better to one diet or the other.  Maybe insulin sensitivity has something to do with it.

Insulin from high protein: not bad?
Insulin from good carbs: not bad?
Junk food: no bueno.
So maybe just maybe it’s not just ze insulin…

 




 

Back to the protein…

This was not sorcery; it’s been seen before in a variety of different paradigms: dietary protein has a profound impact on nutrient partitioning.

Yes, even when it’s liquid calorie insulinogenic whey protein isolate bro-shakes.

Yes, even when it’s not crazy-high levels of protein…  seriously, 1.2 g/kg is not “high”

 

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Past blog posts on [the non-sorcery of] dietary protein:

Holiday feasts, the freshman 15, and damage control

Dietary protein, ketosis, and appetite control.

Nutrient Partitioning: …a *very* high protein diet.

Protein “requirements,” carbs, and nutrient partitioning

Cyclical ketosis, glycogen depletion, and nutrient partitioning

Meal frequency, intermittent fasting, and dietary protein

Muscle growth sans carbs

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