Category Archives: angiotensin

Circadian rhythms and prostate cancer

Posted on October 20, 2016 | 7 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, Ketosis, Leptin, melatonin, mortality, Sun

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Circadian disruption impairs survival in the wild. Again.

Posted on October 2, 2016 | Leave a comment

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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian

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Circadian rhythms and breast cancer

Posted on September 25, 2016 | 7 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diet, Dopamine, Ketosis, melatonin, sleep, Sun, vasopressin

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Circadian timing with REV-ERB and PERIOD

Posted on August 15, 2016 | Leave a comment

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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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, Dopamine, insulin, melatonin, mortality, Sun, vasopressin, Vitamin D

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LIGHT timing for circadian entrainment

Posted on July 5, 2016 | 13 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, Ketosis, Leptin, melatonin, nicotine, Sun, vasopressin, Vitamin D

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Insulin resistance and obesity

Posted on June 25, 2016 | 32 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, diet, Dietary fat, Dopamine, insulin, Leptin, Protein, TPMC

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Dopamine and breakfast

Posted on June 5, 2016 | 39 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diet, Dopamine, fat, Fish, insulin, Leptin, melatonin, Protein, sex, sleep, Sun, TPMC, Vitamin D

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Social jet lag

Posted on May 5, 2016 | 4 comments

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, diet, Dopamine, Energy balance, Ketosis, Leptin, melatonin, resveratrol, Sun

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LIGHT, Leptin, and Environmental Mismatch

Posted on March 12, 2015 | 13 comments

For a long time, the melanocortin system was basically thought to control the color of skin and hair.  It still does, and many redheads are redheaded due to polymorphisms in one of the melanocortin receptors.

Fast forward to 2015: to make a long story short, melanocortins are HUGE players in circadian biology.

 

POMC ACTH a-MSH

 

Brief background (also see figure above):

Fed state -> high leptin -> a-MSH -> MC4R (the receptor for a-MSH) = satiety, energy production, fertility, etc.

Fasted state -> low leptin -> AgRP blocks MC4R = hunger, energy conservation, etc.

MC4R polymorphisms in humans are associated with obesity.  Melanotan II causes skin darkening (marketed as “photoprotection” [no bueno, imo]), enhanced libido, and appetite suppression.

 

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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, fertility, insulin, melatonin, sleep, Sun

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Meal timing and peripheral circadian clocks

Posted on February 9, 2015 | 54 comments

More on why breakfast in the morning, with light onset is important to avoid circadian desynchrony.

FOOD is excellent at entraining peripheral circadian clocks: if you restrict animals to one meal per day, their peripheral circadian clocks rapidly become entrained to this, regardless of when the meal is administered (Hirao et al., 2010):

 

zeitgeber entraining

ZT0 = “zeitgeber time 0,” or “lights on.” pZT indicates a phase shift coinciding almost exactly with meal timing. Mice normally eat at night, but this doesn’t stop their peripheral clocks from entraining to the day time if that’s when their fed.

This study took it to the next level: they fed 2 meals per day, varying in size, time of day, and duration between meals in almost every conceivable combination.  Actually, it was a quite epic study… some poor grad students working, literally, around the clock, for months…

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Posted in Advanced nutrition, angiotensin, chronopharmacology, circadian, diet, melatonin

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