Category Archives: Bromocriptine

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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Vasopressin’ me again

Posted on May 25, 2016 | 3 comments

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

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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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Sunlight and the circadian rhythms in your skin

Posted on June 15, 2015 | 32 comments

SUNLIGHT entrains circadian rhythms.  It gives us vitamin D and melanin; it can give us a sunburn, but some evidence suggests that it does NOT cause skin cancer.

“lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma” (Kennedy et al., 2003)

Anecdotally (or so I’ve heard), skin cancer frequently develops in places not regularly exposed to sunlight.  If true, this flies in the face of the dogma which goes something like this (Tl;dr): ultraviolet light from the sun penetrates into the nuclei of skin cells and damages DNA; if the right [wrong] genes are altered/mutated and the mutated cells proliferate, it can develop into a tumor (gross oversimplification).

So, what might explain the discord?

LIGHT entrains the circadian clock; this includes regulating cell cycle genes.  Aberrant cell cycling may lead to out-of-control proliferation in the wrong context, aka cancer.  Interestingly, some evidence suggests that part of the circadian regulation of cell cycle genes includes turning down proliferation when exposure to UV light is expected to be high (daytime); so DNA repair machinery has more time to fix any cell cycle genes that are mutated by UV light before the cell proliferates (Geyfman and Andersen, 2009) = lower chance of creating and propagating a potentially cancerous skin cell.

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Posted in Bromocriptine, chronopharmacology, circadian, melatonin, Vitamin D

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