Category Archives: circadian

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 disruption impairs survival in the wild. Again.

We evolved on Earth, with regular 24-hour “circadian” cycles; abandoning them is incompatible with survival.  Natural Selection does not look upon this favorably.

Natural selection against a circadian clock gene mutation in mice (Spoelstra et al., 2016)

 

The first time this was discussed, HERE, they ablated the master circadian clock, the SCN, which made the animals arrhythmic with a bollixed circadian period:

 

scn-lesion-activity-image

 

scn-lesion-period-image

resulting in significantly increased predation in the wild:

 

scn-lesion-activity-survival

 




 

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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 arrhythmia in different types of obesity

This study was pretty interesting.

Three groups of women:

1) normal weight

2) gynoid obesity (stores more fat in hips & butt), defined by WC/HC < 0.85

3) android obesity (stores more fat in belly, which is rare in women), defined by WC/HC > 0.85

 

First, we get confirmation that insulin sensitivity (IS) is better in morning than evening.  But then we get these interesting glucose tolerance curves:

 

circadian-glucose-tolerance

 

Fat stored in your hips & butt is thought to be healthier than that stored in your belly region.  This is confirmed here.  Gynoid obesity, while exhibiting an attenuated AM/PM difference, was able to restore euglycemia by the end of the experiment at both time points.  Ie, gynoid obesity selectively improved IS in the evening.

 




 

Android obesity, which is more nefarious than gynoid (also confirmed here), had a similar though not as robust effect in the evening but deteriorated IS in the morning.

One potential interpretation: it’s better to have a little extra fat stored in your hips and butt than to be lean or have belly fat.  However, I have a qualm with that interpretation.  Healthy people show a robust circadian difference in glucose tolerance.  Just as insulin resistance (IR) is an accepted physiological phenomenon observed in some ketogenic dieters, I view this circadian difference, also, as physiological.

 

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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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Insulin resistance and obesity

Some people believe insulin resistance (IR) causes obesity, and they are not pleased when I say this is actually a controversial topic in the field…

“Bill isn’t toeing the company line.  Again.”

So I asked a simple question: if IR causes obesity, how?

 

 

The Common Response: 1) IR -> 2) hyperinsulinemia -> 3) more insulin = more fat mass.

However, this is flawed.

Easiest rebuttal (somewhat of a strawman, but whatevs): Barbara Corkey and her group has done a lot of work showing that insulin hypersecretion (caused by dietary additives, preservatives, weird chemicals, etc.) may actually precede & causes IR… not enough insulin hypersecretion to induce hypoglycemia, just enough to induce IR.

So that basically breaks the 1st step in the Common Response, but doesn’t really disprove the possibility that IR still causes obesity (or can cause obesity).

In any case, check out Corkey’s 2011 Banting Lecture.  Highly recommended, a lot of food for thought.

 

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Dopamine and breakfast

T.S. Wiley wrote a lot about the protein-rich breakfast; here’s my understanding of her take on it.

N.B. I highly recommend her book, Lights out: sleep, sugar, and survival.

Quotes are mainly taken from the text. I’ve tracked down some of the cites; the rest are in the back of the book, albeit somewhat unorganized :/

Part 1. We naturally have a cortisol spike first thing in the morning, known as the Cortisol Awakening Response (CAR).  This peak, which can be screwed up by artificial light at night or a big evening dinner, helps support morning light-induced dopamine.

CAR

Dopamine is great, but may induce impulsivity if it’s unfettered.

Enter: the protein-rich breakfast. It provides tryptophan and a bit of insulin to promote serotonin synthesis (eg, Manjarrez-Gutierrez et al., 1999).

Not enough serotonin to make you crazy, just enough to balance the dopamine = impulse control.

~ circadian balance achieved ~

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Vasopressin’ me again

I’ve been following the links between blood pressure modulatory hormones and circadian rhythms for a while now — and while it’s a fascinating overall picture, this nut hasn’t been cracked [yet].  A paper published in Science may have brought us one step closer.  (And some potential biohacks.)

Background reading (probably important, because my thoughts on this aren’t very coherent [yet]):

LIGHT, Leptin, and Environmental Mismatch (skip down to Part 2)

Circadian phase delays and metabolism

Circadian biology: jet lag, mood, & potential role of BP regulatory peptides

 

The new study: Changes in the composition of brain interstitial ions control the sleep-wake cycle (Ding et al., 2016)

It was a study on mouse brain, but the #context is very relevant here.

Tl;dr: they showed that changes in extracellular ions, independent from neuronal activity, can induce sleep or wakefulness.  “Independent from neuronal activity” was accomplished by silencing the neurons with tetrodotoxin.

 

Pufferfish

 

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Social jet lag

Social jet lag is basically a general term that refers to circadian arrhythmia.  Sort of like insulin resistance, it’s rampantly abundant — some have estimated a prevalence of up to 75%!  Social jet lag can be induced by shift work, East/West travel, late meal timing, artificial light at night, sleeping late, not enough sunlight in the morning, etc., etc.  And while any of the above insults, by themselves, may not really screw up your circadian rhythms, you can see how easy it is for one person to fall prey to nearly of them:

Eat a late dinner, stay up late using artificial light (eg, computer, smart phone, etc.), sleep late the following day so you skip breakfast and don’t get any sunlight in the morning.

CIRCADIAN MISMATCH ACCOMPLISHED

This increases your risk for a wide variety of ailments, ranging from cancer to diabetes to bipolar disorder: no bueno.

One key mediator of the effects of LIGHT is melatonin.  Artificial light at night suppresses melatonin.  Sunlight in the morning can blunt the impact of this!  It all ties in together.  Gravitas.

Great review article here.

 

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