Category Archives: angiotensin

Scheduled Meals for Circadian Entrainment

Scheduled Meals for Circadian Entrainment

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Light and food in the morning

Suggested pre-reading: Metabolism at night

Recently, when the topic of breakfast came up, I got something like this: “correlation isn’t causation, and anyway, it’s because people aren’t eating bacon & eggs at night, they’re having cake & alcohol.”

OK, you can’t say “correlation isn’t causation” and then suggest a cause, literally, in the same sentence.

But anyway, yeah, that actually is a plausible cause. Cake & alcohol are mainly consumed at night.

Also, metabolism is gimped in the evening: 1) skeletal muscle insulin resistance; 2) adipose tissue insulin sensitivity; and 3) impaired diet-induced thermogenesis.

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Carb early but not often

*if you’re going to carb, that is



The Sofer study was uniquely insightful in that they compared 3 carb-rich meals per day with the same amount of carbs but restricted to 1 meal.  Both groups ate 3 times per day.  Tl;dr: one carb meal is modestly better than three even when total carbs are controlled.  Since the carb-meal happened to be dinner, #fakenews reported that “carbs at night” are superior… but we saw right through that – the real conclusion was carb frequency not carb timing.


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What or When to Eat

Artificial light at night, crappy sleep, and skipping breakfast are major contributors to poor circadian rhythms.  Some bro’s insist WHAT you eat is infinitely more important than WHEN you eat.  I beg to differ, at least in part – nix the refined & processed foods and it doesn’t really matter if you prefer low fat or low carb (P<0.05).  Evidence: Hunger-free diet(s).


Exhibit A.  On the other hand, feed two people identical diets but induce circadian disruption in one and whammo – big difference in outcome.



Significantly less fat loss and more muscle loss in the circadian disrupted group.

Interindividual variability? Yes.  Statistical significance? YES.


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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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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


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.




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


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