-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
Effects of a 4-week very low-carbohydrate diet on high-intensity interval training responses (Cipryan et al., 2018)
Relevant study design details: 18 young, healthy, moderately-trained males. First, this was a study on exercise performance. Had it been on glucose management in patients with type 2 diabetes or obesity, this is not the population they would have selected. Second, they needed at least a moderately-trained population otherwise both groups would’ve made big n00b gainz which may have out-weighed any differences incurred by ketoadaptation in 4 weeks.
Third, 4 weeks is a good duration for this kind of study because maximal ketoadaptation occurs in about 3 weeks and doesn’t get stronger thereafter (gains seen beyond 3 weeks are more associated with training effects).
On to the dietary protocols, results, and 2 other relevant new studies… but for that, head on over to Patreon! Five bucks a month gets you full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂
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Posted in Advanced nutrition, diet, endurance, Energy balance, Ketosis, muscle, Protein, strength
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.
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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 🙂
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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…
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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.
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#eTRF
Posted in Advanced nutrition, chronopharmacology, circadian, insulin, melatonin, Sun
Tagged circadian rhythm, ketosis, nutrition, Paleo
There is some overlap between the metabolic effects of calorie restriction (CR) and ketogenic diets (Maalouf et al., 2009). A lot of the underlying mechanisms are related to mitochondrial quality and quantity, anti-apoptotic factors, and neurotrophic factors (eg, BDNF induced by ketosis).
Posted in Advanced nutrition, diet, Dietary fat, insulin, Ketosis, sleep
“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.
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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
Two studies: one on infusion of D-b-hydroxybutyrate at three different level producing up to 2 mM at the highest level (Mikkelsen et al., 2014); and one on ingestion of a ketone monoester (R-3-hydroxybutyl-R-3-hydroxybutyrate) producing ~3.2 mM (Myette et al., 2018). Both studies were relatively small (n = 6 and 20, respectively) yet interesting.
Mikkelsen: mainly justified the use of exogenous ketones in T2DM because of their ability to suppress hyperglycemia and hyperlipidemia. And justified ’em in CNS disorders because adherence is poor in this population and goes downhill with increasing disease severity. They’re anti-ketone salts because: 1) the GI distress and salt load with doses required to get into the 2-3 mM range; and 2) they’re often racemic mixtures of D- and L-b-hydroxybutyrate (“D” is the endogenous one).
As expected, increasing the infusion dose linearly increased plasma bHB:
Further, as expected, brain uptake increased in parallel to plasma levels:
Interestingly, muscle uptake seemed to become saturated and not increase much further… this may be related to the “muscle-sparing effect of fat-derived fuels,” in other words, muscle is sparing ketones for the brain like it does during late starvation.
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.
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Posted in Advanced nutrition, diabetes, Dietary fat, Ketosis
Tagged calories proper, fat, ketogenic, ketones, ketosis, nutrition
“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.
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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