-induced circadian disruptions in modern aging societies (Hatori et al., 2017)
While this article could’ve easily addressed the havoc wreaked on most animals (hibernating, migrating, reproducing, etc.) or even many plants by artificial light, the focus is on humans.
Posted in angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diabetes, Dopamine, melatonin, mortality, sex, sleep, Sun, vasopressin
Tagged circadian rhythm, melatonin, mortality, sleep
I’ve been known to say intermittent fasting is #weaksauce because most of the human studies show little or no effect and people frequently report being hungry (yes, even if LCHF). Human studies, not “n=1’s.”
Well, now we know why. Time-restricted feeding (TRF) only really works when the feeding window is early (eTRF), as demonstrated by the recent Sutton study which showed, miraculously, great benefits achieved sans weight loss. Calories were strictly controlled in that study to prevent weight loss. AND when the participants were on eTRF, they actually reported less hunger in the evening.
We know from the studies by Jacobs and Hirsh that under ad lib AND isocaloric conditions, people lose more weight eating all their food for breakfast than those eating all their food for dinner.
That’s cuz metabolism is gimped at night. Lower metabolic rate and greater propensity to store fat.
Melatonin sensitizes the system, preparing it to optimally partition nutrients in the morning.
For the rest of this awesome article, head over to Patreon! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂
Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!
Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Start your OWN Patreon campaign!
Join Earn.com with this link and get paid to answer questions online.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, Energy balance, Ketosis, melatonin, muscle, sex, sleep, vasopressin
Tagged calories, circadian rhythm, ketogenic, ketones, ketosis, melatonin, nutrition, protein
In Four. EPIC. Experiments (ter Horst et al., 2018)
Tl;dr: sunlight & breakfast in the morning.
Dopamine receptors are downregulated in obese patients and are restored in long-term weight loss patients after bariatric surgery. It’s better to get your dopamine hit via sunlight than sugar duh.
This is some amazing science.
Experiment 1. 50-year old dude with severe OCD gets diagnosed with type 2 diabetes and is only able to get his glucose under control with metformin and 226 IU insulin. At 53, his OCD is treated with deep brain stimulation (DBS). His insulin requirements declined to 180 IU. He didn’t lose weight but went off quetiapine, so maybe coincidence because: 1. quetiapine is diabetogenic; and 2. DBS induces dopamine release.
Two-step hyperinsulinemic euglycemic clamp when DBS is turned off and turned on. BOOM! When it’s on, lower fasting insulin, and better insulin-induced suppression of liver glucose output, free fatty acids, & muscle glucose disposal! DBS improved insulin sensitivity in liver, adipose, and skeletal muscle.
For the rest of the discussion on these super-interesting experiments, head over to Patreon! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂
Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!
Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Start your OWN Patreon campaign!
Join Earn.com with this link and get paid to answer questions online.
Cycloset (bromocriptine)
And #eTRF.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, clamp, depression, diabetes, Dopamine, melatonin, muscle, nicotine, sex, sleep, Sun, testosterone, vasopressin
Tagged diet, energy balance, insulin, melatonin, muscle
From all of the published human studies and “n=1’s” I’ve seen on online forums, intermittent fasting is #nothingsauce. Don’t @ me.
When people lose weight via IF, it’s because of caloric restriction. There’s no metabolic advantage, and if anything, maybe the opposite. Restricting your feeding window to a very short period = metabolic mayhem.
2000 kcals in one sitting?
*smh*
I believe “early Time-Restricted Feeding” #eTRF showed promise in that recent study because of the “early” part; no so much on the “TRF” part. I believe this, in part, because the large majority of our population suffers from some degree of circadian arrhythmia. Social jet lag, too much artificial light at night, skipping breakfast, etc., etc. An EARLIER feeding window is one way to re-align circadian rhythms.
It STARTS with Sleep. Wanna improve body comp and make mindlessly better food choices? Fix your circadian rhythms.
Now onto the one of the weirdest, but potentially most revealing human studies on time-restricted feeding…
For the rest of this article and more, head over to Patreon! Five bucks a month for full access and there are many other options.
Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!
Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Start your OWN Patreon campaign!
Join Earn.com with this link and get paid to answer questions online.
Posted in Advanced nutrition, chronopharmacology, circadian, Dopamine, melatonin, muscle, Protein, strength
Tagged calories proper, circadian rhythm, diet, energy balance, exercise
I feel exonerated!
Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes (Sutton et al., 2018)
Tl;dr: 8 prediabetic men, 5 week crossover study. When on eTRF, the only rule was basically dinner no later than 3 pm and no snacking thereafter. It was isocaloric because: 1) studies on meal timing and weight loss have been done; and 2) they wanted to test meal timing specifically, not confounded by weight loss.
Also, I think the results are due to meal timing, not fasting duration per se, because of the studies by Jacobs & Hirsh. In brief, they tested meal timing with similar fasting durations and showed people who ate one-meal-a-day all at breakfast lost more weight than people who ate one-meal-a-day all at dinner. First they showed this in an ad lib context and then again in an isocaloric context. Metabolism is gimped at night.
For a discussion of these exciting new data, head over to Patreon! Five bucks a month for access to all articles and there are many other options.
Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!
Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Start your OWN Patreon campaign!
Join Earn.com with this link and get paid to answer questions online.
#eTRF
Posted in Advanced nutrition, chronopharmacology, circadian, insulin, melatonin, Sun
Tagged circadian rhythm, ketosis, nutrition, Paleo
“The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock systems (Heyde et al., 2018)”
Sleep disruption and circadian arrhythmia induce metabolic, cognitive, and immunological impairments. Is it causal? YES.
Sleep is highly conserved across the animal kingdom, since the dawn of time.
Interesting comparison: unlike hibernation or a coma, sleep is highly reversible. Lots of rebound regulation: lots of wakefulness makes you tired; lots of sleep leads to increased wakefulness.
Studies have shown improved memory performance after naps and extended sleep durations. Imo, you don’t need to go from 6 to 9.5 hours overnight, but keep that “9.5” on your radar.
Diet is easy, just eat like an adult. You can go 10 days without even eating! Try that with sleep. No, don’t try that. Most definitely incompatible with survival. Sleep deprivation impairs cognitive functions.
As a marker of health: cognitive function >>> how many reps you can do at the gym.
For the rest of this article (it doesnt suck, I promise!), head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.
Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.
Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!
Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Start your OWN Patreon campaign!
Join Earn.com with this link and get paid to answer questions online.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diabetes, Dopamine, Energy balance, insulin, Leptin, melatonin, sex, sleep, Sun, testosterone, vasopressin, Vitamin D
Tagged circadian rhythm, insulin, melatonin, mortality, nutrition, Paleo, sleep
“Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep-wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance (Goel et al., 2013).”
Acute and chronic sleep restriction degrade neurobehavioral functions, attention, cognitive speed, and memory. Strictly according to the studies (not your n=1), < 5.5 hours is bad, < 7 hours is suboptimal, and ~ 9.5 hours may be optimal. Seems like a lot; who has time to sleep 9.5 hours?!
Above image shows cerebral blood flow (orange) in the same person’s brain during a Psychomotor Vigilance Test performed in the morning and afternoon. Interestingly, most participants perform better in the afternoon and this is associated with more blood going to a different part of the brain.
“Sleep is a ubiquitous biological imperative that appears to be evolutionarily conserved across species.” Mandatory for optimal attention and cognitive performance.
To get the rest of this article (it doesn’t suck, I promise) or if you just like what I do and want to support it, head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.
Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.
Affiliate links: still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Posted in angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diabetes, Dopamine, Exercise, fertility, melatonin, mortality, nicotine, sex, sleep, Sun, testosterone, vasopressin
Tagged circadian rhythm, exercise, melatonin, mortality
Another comprehensive review article: Chronobiological theories of mood disorders (Zaki et al., 2017)
Here is my summary and opinions about it.
Tl;dr: the authors cautiously explored the bidirectional and/or causal effect of sleep & circadian disorders vs. mood disorders. I appreciated their caution but a lot of the evidence presented suggested circadian arrhythmia as a causal agent.
Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) don’t address underlying circadian and seasonal rhythm dysfunctions, so patients are usually prescribed these meds indefinitely.
In the future, they see light therapy and melatonin receptor agonists as better treatments. I’d say an outdoor walk sunlight exposure after breakfast in the morning, blue blockers or nix artificial light at night, and instead of melatonin agonists, consider serine.
“The master clock controlling chronophysiological rhythms of theand body organs is located in the SCN…” VIP and AVP are abundant in the SCN! I knew it! LOL
“Humans’ endogenous rhythmic activity has a period slightly longer than 24 hours, hence, it needs daily entrainment to 24 hours with zeitgebers.”
Translation: SUNLIGHT AND BREAKFAST IN THE MORNING
Evidence favoring circadian and sleep disorders as causal agents in mood disorders:
For the rest of this article (or if you just like what I do and want to support it), head over to Patreon! Five bucks a month gets you full access and there are many other options.
It’s ad-free and you can quit if it sucks 🙂
Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.
UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, sleep, Sun, Vitamin D
Tagged circadian rhythm
In Nedeltcheva’s notorious weight loss study, those assigned to shorter sleep duration (5.5 hours) lost more muscle and less fat mass than those assigned to adequate sleep duration (8.5 hours). Same diet + same calories + circadian arrhythmia = no bueno.
*I’d say 8.5 hours can be called in this context. I like saying, seasonally, 8-9.5 hours of darkness, most of which should be spent sleeping. Others say 7-9 hours is adequate and <7 is inadequate. I agree with that, too*
Similar outcomes are seen in any number of sleep restriction studies. Figuratively, everything goes down the toilet. But that’s only half of the story.
There are a couple randomized intervention studies on intentional sleep extension and the results are very cool.
The effects of extended bedtimes on sleep duration and food desire in overweight young adults: a home-based intervention (Tasali et al., 2014)
They recruited habitual under-sleepers (<6.5 hours), recorded their sleep behaviors for a week, then gave them individualized behavioral counseling on sleep hygiene with the goal of extending their sleep duration to 8.5 hours. It worked: they were less sleepy, felt more vigorous, and spontaneously ate less sugar and fewer calories. Had the intervention lasted longer than 2 weeks, we would’ve seen body comp improvements as per Nedeltcheva’s study results. IT STARTS WITH SLEEP.
Beneficial impact of sleep extension on fasting insulin sensitivity in adults with habitual sleep restriction (Leproult et al., 2015)
Similar set-up as above: 2 weeks initial monitoring, then 6 weeks where they slept about an hour longer. It worked. Total sleep time positively correlated with indices of insulin sensitivity.
Feasibility and emotional impact of experimentally extending sleep in short-sleeping adolescents (van Dyk et al., 2017)
Kids who normally slept 5-7 hours a night increased that by ~70 minutes for 5 weeks. It worked: reduced symptoms of sleepiness, anger, and confusion! Seriously?
Seriously.
Most of these studies basically just told the participants to go to bed earlier (in evening chronotypes) or sleep a little later (in morning chronotypes). It was individualized and not pharmacological. That means you can do it.
Check it: Blocking nocturnal blue light for insomnia: a randomized control trial (Schecter et al., 2018) CROSSOVER STUDY. Tl;dr: it worked. Blue blockers, FTW.
If you like what I do and want to support it, check out my Patreon campaign!
UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Join Earn.com with this link. Get paid to answer questions!
Hey team, remember when I was making wild predictions about REV-ERB alpha?
“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.” (From HERE)
and statements:
“Pharmaceutical-grade circadian augmentation = unwittingly better-timed meals? Improved body composition? …they were eating more and moving less. … One possible mechanistic explanation comes from mice lacking Rev-erb in skeletal muscle (Woldt et al., 2013). Mitochondrial biogenesis was impaired and exercise tolerance was reduced in these mice. Spontaneous physical activity was lower; thus, it stands to reason that Rev-erb agonism may improve skeletal muscle mitochondrial function. This isn’t entirely consistent with the drug study, but pretty close.” (From HERE)
REV-ERB is really really good for skeletal muscle.
Beta-hydroxybutyrate inhibits activation of the NLRP3 inflammasome.
Well, so does REV-ERB alpha! In a new study, knocking down REV-ERB alpha jacked up NLRP3 and pharmacologically enhancing it attenuated NLRP3 (Pourcet et al., 2017). The consequence of this in REV-ERB KO mice injected with LPS was hyper-inflation. No bueno. Mice given the commercially-available REV-ERB alpha agonist “Stenabolic” were protected.
I’m geeking out about REV-ERB alpha & SR9009. And fwiw, I don’t think anything will actually fully replace the benefits from actual physical activity and/or exercise, although it’s very hard for some people; eg, COPD, CHD, etc. In those populations, if they can’t exercise enough to really improve their condition, something like this might help. But I’m sure perfectly healthy people are going to try it. If you do, let us know in the comments!
For more about this fascinating research and how it can work for you (or if you just like what I do and want to support it), head over to Patreon! Five bucks a month gets you full access and there are many other options.
It’s ad-free and you can quit if it sucks 🙂
Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.
UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.
Regulation of Circadian Behavior and Metabolism by Synthetic Rev-erb Agonists (Solt et al., 2013)
Rev-erb alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy (Woldt et al., 2013)
“Seriphos“
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, depression, Dopamine, Exercise, melatonin, muscle, sex, sleep, strength, Sun, vasopressin
Tagged body composition, circadian rhythm, energy expenditure