Category Archives: melatonin

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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Keto myths & facts

:::begin rant:::

Trigger warning?  Maybe.

Disclaimer: I’m pro-LC (P<0.05), but not anti-LF because LF works better than LC for some people.  And with the exception of things like keto for neurological issues, I think macros take a back seat to many other factors.

Myths: carbs cause insulin resistance (IR), diabetes, and metabolic syndrome.  Carbs are intrinsically pathogenic.  If a healthy person eats carbs, eventually they’ll get sick.

And the only prescription is more keto.

cowbell

And of course all of this could’ve been prevented if they keto’d from the get-go.

Proponents of these myths are referring to regular food carbs, not limited to things like Oreo Coolattas (which would be more acceptable, imo).  Taubes, Lustig, Attia, and many others have backed away from their anti-carb positions, yet the new brigade proceeds and has even upped the ante to include starvation.  Because “LC = effortless fasting?”

Does this sound sane?

“No carbs ever,
no food often…
otherwise diabetes.”

oreo-coolatta

no one in their right mind would say lentils & beans cause diabetes

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Circadian rhythms and breast cancer

Over the course of human evolution, diets varied widely over time, seasons, geography, etc., ie, we can obviously thrive on many different dietary patterns… but the light/dark cycle was there the entire time.  Why is this not the most important talking/debating point?  Why do people think humans need one particular diet but can ignore circadian rhythms?

Because everyone’s still fussing about carbz and what we are “designed to eat”

*smh*

see also: “Lights Out!” by T.S. Wiley

 

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Circadian timing with REV-ERB and PERIOD

The circadian proteins Bmal and casein kinase (CK) enhance and degrade Period (PER), respectively, by completely different mechanisms.  Both are necessary, but at different times of day… #context

Gross oversimplification: the Bmal party is kicked off in the morning by LIGHT, and acts to increase PER by night (among many, many other things).  As the day progresses, REV-ERB the Repressor slowly shuts down Bmal, so that peak PER occurs in the evening and doesn’t carry over until the next morning.  GSK3b activates REV-ERB the Repressor.  Lithium puts the system in fast forward, leading to phase advance* and ZZZ’s when timed right, at night… I think

 

Lithium GSK3b image

 

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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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