From circadian entrainment to blood glucose management to appetite control to sleep quality:
We’re really not made to skip breakfast and eat late at night. Nearly every line of evidence points to this. And now:
Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study (Bo et al., 2015)
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, muscle, Sun, Uncategorized, Vitamin D
Tagged circadian rhythm, melatonin
Interleukin-1 beta: produced by activated M1 macrophages, classical fever-inducing cytokine, mediates cellular inflammation, and induces COX-2 (target of NSAIDs). Also involved in autoimmunity. You don’t want none of it but you certainly don’t want a lot of it.
The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasone-mediated inflammatory disease (Youm et al., 2015)
This is a very specific effect: 1) many structurally similar compounds don’t block NLRP3; and 2) beta-hydroxybutyrate doesn’t block activation of other inflammasomes.
“In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1b secretion in mouse models of NLRP3-mediated diseases such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome and urate crystal-induced peritonitis. Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.”
Polish Mayor @jmmajchrowski takes steps to protect citizens from rising electromagnetic radiation; wifi, smartmeters https://t.co/Ywg0Jr7Xqw
— Dr Maryanne Demasi (@MaryanneDemasi) January 12, 2017
I was bored and had a stronger-than-usual espresso, saw the above Tweet, so obviously I decided to read the Health & Safety Guide that came with my cell phone.
The Federal Communications Commission (FCC) set specific limits to Radio Frequency (RF) that any given electronic device can emit. Theoretically, at or below this level is “safe.” The actual number comes from the National Council on Radiation Protection and Measurement (NCRP) and Institute of Electrical and Electronics Engineers (IEEE). The overall tone of this document is grave, ie, they take this RF limit very seriously.
The limit: 1.6 W/kg (Specific Absorption Rate [SAR]) or 0.0016 W/g.
I checked online at www.fcc.gov/oet/ea, and my phone is rated 0.3 Watts (W) at around 1.5 cm – distance is important: in this case, it’s the difference between squashing the phone between your face and your hand vs. holding it a finger tip’s distance away.
So, is my brain safe? Hard to say; how many grams of brain are within 1.5 cm from my brain? If we’re talking whole head exposure, ~4 kg, that’d be ~6 W. But I’m more concerned about the 4 grams of brain closest to my ear, within that 1.5 cm range, because brain cancer is pretty scary at any level of brain cancer (ie, whether it affects whole brain or just the 4 grams closest to my ear).
I can’t figure out these maths so I’m sticking with earbuds until I can.
Posted in chronopharmacology, circadian, Dopamine, melatonin, sex, Sun
Tagged circadian rhythm, melatonin
There are a lot of mysteries involving melatonin, eg, relative importance of gut vs. pineal-derived melatonin. Does brain melatonin talk to peripheral MT receptors? Does gut melatonin talk to brain MT receptors?
What we do know: oral melatonin works in people with circadian-related sleep disorders. This may suggest that oral/gut melatonin talks to brain MT receptors OR that oral/gut melatonin corrects circadian sleep problems by acting in the periphery. OR a major target of brain melatonin is peripheral MT receptors. I don’t know.
And as a further testament that melatonin supps aren’t sleeping pills is that they’re non-addictive and can at least temporarily “fix” circadian sleep problems: after prolonged treatment, people report no withdrawal symptoms and still sleep better even up to two weeks after discontinuation (Lemoine et al., 2011)!
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, Sun, vasopressin, Vitamin D
Tagged circadian rhythm, melatonin
Study: 12 weeks, obese men, very high fat low carb (VHFLC) vs. low fat high carb (LFHC) (Veum et al., 2016) #FATFUNC
Pictorially:
It wasn’t explicitly AD LIB, but pretty close. I say this because that is the magnitude of appetite decline we might expect when people go on The Hunger Free Diet(s), eg,
^^^ GOOD IDEA
Posted in Advanced nutrition, circadian, diet, Dietary fat, Energy balance, Exercise, fat, insulin, Ketosis, muscle, Protein, Sugar, TPMC
Tagged body composition, calories proper, carbs, diet, insulin, ketosis, nutrition, processed food, protein, soda
Three stories about LIGHT
One
Carbon monoxide (CO): one of the nasty things in car emissions & cigarette smoke. Also, a byproduct of the ever-important heme. Heme, as you may recall, activates Rev-erb:
“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.”
News: Disruption of the body’s internal clock causes disruption of metabolic processes
Science: Reciprocal regulation of carbon monoxide and the circadian clock (Klemz et al., 2016)
Tl;dr: heme degradation occurs on a circadian cycle and produces CO. CO prevents Clock/Bmal1 from binding to DNA. Inhibiting this process throws off numerous other circadian rhythms in the liver.
SUNLIGHT and food in the morning, and let endogenously produced CO rhythmically tune the clock in the evening.
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, Protein, sleep, Sun, vasopressin
Tagged circadian rhythm, melatonin
Disclaimer: I’m meat-cancer agnostic. *IF* meat causes cancer (and I don’t think it does), it happens extremely slowly and only at very high levels of intake: to get statistically significant risk ratios, researchers usually look to top vs. bottom quartiles, which is quite a large difference in intake.
Meat-cancer studies Tl;dr: some studies show positive associations, some neutral, and none are negative (ie, it’s unlikely meat prevents cancer).
That said, if meat does cause cancer, here is how it might happen:
1. The “Maybes:” AGEs, leucine/mTOR, methionine, etc., but only in combination with numbers 2 & 3. Not by themselves.
2. Circadian arrhythmia and cancer: potential mechanisms
3. Most animal foods have a lot of linoleate 18:2n6 or at least a lot more n6 than n3 (grass-fed is usually a little better in this context). More on this below.
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, mortality, muscle, Protein, sleep, Sun
Tagged circadian rhythm, melatonin, mortality, processed food, protein
Humans are incredible omnivorous beasts that can thrive on a great variety of diets, but crumble if you mess with their sleep.
Circadian arrhythmia is thought to be a driving force behind a few types of cancer. But how, exactly, does seemingly harmless things like artificial light, skipping breakfast, or jet lag actually promote tumorigenesis? There are many potential mechanisms, and I’d bet different circadian disruptions promote different cancers in different #contexts.
In some cell types, circadian disruptions which dampen amplitude increase proliferation. This has led to some researchers to believe a robust circadian rhythm per se is tumor-suppressive. In agreement with this, many tumor suppressors are direct targets of circadian transcription factors. As was observed in some skin cancers, you may want suppressed proliferation at some times of the day but not others, so the tissue can renew properly. But you don’t want, for example, skin cells to be proliferating while they’re being exposed to UV light, so this process happens at night (in circadian fashion).
Circadian transcription factors also directly interact with endogenous antioxidant systems.
Cancer clocks out for lunch: disruption of circadian rhythm and metabolic oscillation in cancer (Altman, 2016)
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, sex, sleep, vasopressin, Vitamin D
Tagged circadian rhythm, dopamine, melatonin, mortality
Caloric restriction (CR) activates autophagy. Intermittent fasting (IF) is basically kind-of-like the opposite of CR. I’m not knocking IF. The animal studies of autophagy, based on “chronic nutrition depletion,” more accurately reflect CR which results in decreased body weight or metabolic rate. IF generally includes refeeds, resulting in weight maintenance. Also, in the few human studies on it, weight loss (CR) but not fasting (IF) has been shown to induce autophagy.
If you’re actually losing weight over the long-term with an IF protocol, and thus are CR by definition, then I suspect you may be autophaging, too (yeah yeah, I know, that’s not really how autophagy works, but you get the picture).
Disclaimer: I’m relatively autophagy-agnostic; not really confident racing to maximize it is a great thing based on Human Studies.
Book: Autophagy in Health and Disease
Exhibit A: autophagy in skeletal muscle
Tl;dr: “a little exercise is a better than a lot of fasting”
A1) Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle (Moller et al., 2015)
The protocol: participants either fasted for 36 hours or received a glucose infusion before and during exercise (cycling at 50% max for an hour).
“In the present study, we demonstrate that short-term aerobic exercise activates autophagic signaling through ULK1 in human skeletal muscle, independently of nutrient background.”
They really should’ve stressed that the deck was stacked to show fasting activated autophagy… 36 hours of fasting is pretty long but it had no effect.
Posted in Advanced nutrition, circadian, endurance, Exercise, insulin, liver, muscle
Tagged calories, calories proper, diet, energy balance, energy expenditure, exercise, insulin, nutrition
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.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, Ketosis, Leptin, melatonin, mortality, Sun
Tagged calories proper, carbs, circadian rhythm, insulin, ketosis, mortality, nutrition