The mission of the International Dark-Sky Association is “to preserve and protect the night time environment and our heritage of dark skies through quality outdoor lighting.” They’re all about stressing the importance of lighting on health, light pollution, and some really interesting stuff.
For more on the topic, check out their website, darksky.org, and Paul Bogard’s book, The End of Night: Searching for Natural Darkness in an Age of Artificial Light
Posted in chronopharmacology, circadian, melatonin, Sun, Vitamin D
Tagged chronopharmacology, circadian, light, melatonin
…just read that huge disasters, ranging from Exxon Valdez to Chernobyl, may have been due, in part, to ignorance of basic principles of circadian rhythms. Gravitas.
Posted in Advanced nutrition, chronopharmacology, circadian, diet, melatonin, mortality, pair-feeding, Protein, sleep, Sun
Tagged circadian rhythm, diabetes, melatonin, mortality, nutrition, protein
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):
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…
Posted in Advanced nutrition, angiotensin, chronopharmacology, circadian, diet, melatonin
Tagged circadian rhythm, diet, melatonin, nutrition, Paleo
“Desynchronization between the central and peripheral clocks by, for instance, altered timing of food intake, can lead to uncoupling of peripheral clocks from the central pacemaker and is, in humans, related to the development of metabolic disorders, including obesity and type 2 diabetes.”
If you haven’t been following along, a few papers came out recently which dissect this aspect of circadian rhythms — setting the central vs. peripheral clocks.
In brief (1): Central rhythms are set, in part, by a “light-entrainable oscillator (LEO),” located in the brain. In this case, the zeitgeber is LIGHT.
Peripheral rhythms are controlled both by the brain, and the “food-entrainable oscillator (FEO),” which is reflected in just about every tissue in the body – and is differentially regulated in most tissues. In this case, the zeitgeber is FOOD.
In brief (2): Bright light in the morning starts the LEO, and one readout is “dim-light melatonin onset (DLMO),” or melatonin secretion in the evening. Note the importance of timing (bright light *in the morning*) – if bright light occurs later in the day, DLMO is blunted: no bueno.
Morning bright light and breakfast (FEO) kickstart peripheral circadian rhythms, and one readout is diurnal regulation of known circadian genes in the periphery. This happens differently (almost predictably) in different tissues: liver, a tissue which is highly involved in the processing of food, is rapidly entrained by food intake, whereas lung is slower.
Starting the central pacemarker with bright light in the morning but skimping on the peripheral pacemaker by skipping breakfast represents a circadian mismatch: Afternoon Diabetes? Central and peripheral circadian rhythms work together. Bright light and breakfast in the morning.
Posted in Advanced nutrition, chronopharmacology, circadian, liver, melatonin, Protein, sleep, Sun
Tagged circadian rhythm, melatonin, nutrition, obesity, protein
Part I: Circadian Mismatch
1. Artificial light at night suppresses melatonin (Lewy et al., 1980); induces “circadian mismatch.”
2. Circadian mismatch is associated with and/or predisposes to breast cancer (eg, He et al., 2014 and Yang et al., 2014).
3. In this epic study, human breast cancer xenografts were exposed to blood taken from healthy, pre-menopausal women during the day (melatonin-depleted), at night (high melatonin), or at night after light exposure (melatonin-depleted) (Blask et al., 2005). They showed that tumors exposed to melatonin-depleted blood exhibited higher proliferative activity than those exposed to melatonin-repleted blood. This has been deemed one of the most “ethical” studies to demonstrate a causal link between circadian mismatch and cancer.
4. And to make matters worse, circadian mismatch also reduces the efficacy of cancer drug therapy (Dauchy et al., 2014). This study showed that, in a rodent model of breast cancer, exposure to light at night (circadian mismatch) enhanced tumor development and induced tamoxifen-resistance, and this was abolished by melatonin replacement.
They also suggested a mechanism: tumors metabolize linoleate into the mitogen 13-HODE. Melatonin
Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin
Tagged chronopharmacology, circadian rhythm
Don’t exacerbate afternoon diabetes with afternoon carbs.
Skeletal Muscle
As discussed previously [at length], insulin sensitivity in skeletal muscle follows a circadian pattern: starts out high in the morning and wanes throughout the day.
Diurnal variation in glucose tolerance and insulin secretion in man (Carroll and Nestel, 1973)
Adipose Tissue
And insulin sensitivity of adipose tissue goes in the opposite direction: starts out low, and increases as the day progresses.
Diurnal variations in peripheral insulin resistance and plasma NEFA: a possible link? (Morgan et al., 1999)
The studies were standardized for a period of fasting, pre-test meal, and exercise… Following insulin, NEFA fell more slowly in the morning (149 uM/15 min) than in the evening (491 uM/15 min).
Diurnal variation in glucose tolerance: associated changes in plasma insulin, growth hormone, and non-esterified fatty acids (Zimmet et al., 1974)
Adipose tissue insulin sensitivity is greater in the evening. FFA are higher, and get shut down more rapidly, after a carb meal in the evening.
Summary: to minimize blood glucose excursions and proclivity for fat storage, eat more calories earlier in the day; this is circadian nutrient timing. And according to the Alves study, a low-carb protein-rich dinner best preserves lean tissue during weight loss.
Posted in Advanced nutrition, circadian, clamp, diet, Energy balance, insulin, Ketosis, melatonin, Protein
Tagged body composition, calories proper, carbs, circadian rhythm, energy expenditure, insulin, ketosis, melatonin, nutrition, protein
Remember the “jet lag-resistant” mice? Guess what: screw with circadian biology and metabolism pays the price.
In brief, vasopressin was classically thought of as an anti-hypotensive hormone. The vasopressin analog Desmopressin is used to treat bed-wetting. But vasopressin biology is much more interesting than that: mice lacking both vasopressin receptors require very little time adapting to large circadian phase changes. And as with many fundamental concepts in chronobiology, this is intimately linked with metabolism.
People with certain polymorphisms of the vasopressin receptor, V1A, exhibit elevated blood glucose levels and are at greater risk for diabetes (Enhorning et al., 2009):
This risk is strongest in men in the highest quartile of fat intake, and is statistically more significant after adjusting for age and physical activity:
This study wasn’t designed to be a very powerful indicator of diet-disease relationships, but a little speculation: some think higher fat [and lower carb] intake should be protective against diabetes… which may be true, for people who can tell time. Alter one nucleotide in the vasopressin 1A receptor gene and the game changes.
Posted in Advanced nutrition, angiotensin, circadian, clamp, Dietary fat, Energy balance, insulin, liver, melatonin, muscle, vasopressin
Tagged body composition, calories proper, carbs, circadian rhythm, diet, energy balance, fat, insulin, melatonin, obesity
Carb Back-Loading (CBL) redux, part I
Step 1: eat little in the morning (maybe some fat+protein; definitely no carb)
Step 2: exercise in the afternoon/evening
Step 3: eat the carbs, all of them. Preferably high glycemic carbs.
Other: no dietary fat post-workout; protein periodically throughout the day.
What makes CBL different from its predecessors is the stress on the timing – exercise and carbs in the evening. John Berardi’s “Massive Eating” dietary guidelines are similar: protein+fat meals all day except pre- and post-workout, which are protein+carb meals. Martin Berkan’s “LeanGains” is fasting most of the time (including pre-workout), exercise in the afternoon, then a big post-workout meal (quite similar to CBL). My only tweak, as discussed below (and previously here and here), would be a pre- rather than post-workout meal [in some contexts].
There’s a summary of this blog post at the bottom… it might be helpful to read that first (see: “Tl;dr:”). Also, please note that much of this post is about the fringe of theoretically optimizing nutrient partitioning, like improving from 85 to 90%, or 40 to 45%, not 40 to 90%… I’m not that deluded.
My initial take, in general, is that this book is loaded with gems about nutrition, exercise, biochemistry, and physiology. It’s also very readable and has a lot of good recommendations. In this post, I want to discuss one specific aspect of CBL: tissue-specific circadian regulation of metabolism.
Posted in Advanced nutrition, circadian, diet, Energy balance, Exercise, fat, insulin, melatonin, muscle, Protein, strength, TPMC
Tagged body composition, calories proper, carbs, circadian rhythm, diabetes, diet, energy balance, exercise, melatonin, muscle, nutrition
From the best I can gather, one of the more immediate players in circadian biology is the coenzyme nicotinamide adenine dinucleotide (NAD), which participates in a variety of redox reactions. Fasting increases the intracellular NAD/NADH ratio, setting off a cascade of events involving epigenetics and the regulation of metabolism.
NAD activates sirtuins, a family of deacetylase enzymes. This is epigenetics.
SIRT1 regulates the activity of BMAL1 and CLOCK, two circadian transcription factors, which target NAMPT, an enzyme that synthesizes NAD. And in a curious feed-forward mechanism, CLOCK and BMAL1 enhance SIRT1 expression… genetic deletion of any of these players induces insulin resistance (Zhou et al., 2014), and this can be recapitulated with constant darkness: reduced BMAL1 and SIRT1, hepatic insulin resistance; the latter can be reversed with resveratrol
Posted in Advanced nutrition, circadian, Energy balance, Exercise, melatonin, muscle, resveratrol, TPMC, wine
Tagged body composition, calories proper, circadian rhythm, energy balance, energy expenditure, exercise, insulin, melatonin, obesity
Melatonin is secreted from the pineal gland, the seat of the soul, the third eye. Pinealectomy induces circadian arrhythmia and has interesting effects on adipose tissue biology.
Exhibit A. In 2004, Alonso-Vale and colleagues showed that 6 weeks after pinealectomy, [melatonin-deficient] rats subjected to fasting exhibited an impaired energy conservation response. That is, they lost more weight and significantly depleted their adipocytes:
Posted in circadian, empty calories, Energy balance, Leptin, melatonin, TPMC
Tagged body composition, calories, calories proper, carbs, circadian rhythm, diet, energy balance, insulin