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.
I’m totally cool with keto, honestly! but still don’t really like seeing stuff like the above graphic and people interpreting it to mean “KETO IS MUSCLE-SPARING.”
I came across a recent study on a mouse model of Angelman Syndrome (an epigenetic disorder), and wasn’t surprised to learn there’s a strong circadian component to it. Epigenetics are one of the main ways circadian rhythms are programmed.
In this case, the circadian connection is more direct.
Angelman Syndrome (AS): you inherit 2 pairs of each gene, one from Mom and one from Dad. In some cases, one of the copies is silenced via epigenetics and you’re basically just hoping the other one is in good shape. In the genetically relevant region in AS, the paternal copy is silenced and the maternal copy does all the heavy lifting, but in AS, the maternal copy is mutated or absent, so none of the genes in this region are expressed.
Interestingly, scientists found that one of the genes, Ube3a (an ubiquitin ligase), is involved in regulating Bmal1, a core circadian gene (Shi et al., 2015) . And mice with a silenced paternal Ube3a and mutant maternal Ube3a exhibit many of the same circadian symptoms of children with AS. They don’t mimic all of the symptoms as there are many other genes in this region. But both show circadian abnormalities.
Prader-Willi Syndrome (PWS) is the epigenetic opposite: same region of DNA, but silenced maternal copy and mutant or absent paternal copy. This disorder is characterized by massive obesity and low muscle mass (among other things).
While reading about this disorder, I was taken aback with how the obesity was explained.
“Insatiable appetite” (Laurance et al., 1981), although from what I can gather, these children would develop massive obesity even if they were fed cardboard. Some studies even showed no change in food intake and/or energy expenditure (eg, Schoeller et al., 1988), which led some researchers to publish entire papers about how these children must be lying and/or stealing food (eg, Page et al., 1983) .
Further, other researchers even explained their obesity was due to an inability to vomit (Butler et al., 2007).
THEY’RE OBESE BECAUSE THEY’RE NOT BULEMIC.
AYFKM?
When these kids gain weight, it’s nearly all fat mass; when they lose weight, it’s nearly all muscle [shoulda been a BIG hint]… this even led some researchers (who detected no change in fat mass after significant weight loss) to conclude that their techniques to assess body composition must not be valid in this population because: surely, they must’ve lost some fat mass like normal people do.
THEY FAILED TO CONSIDER THIS IS AN EXTREME CIRCADIAN MISMATCH DISORDER IN NUTRIENT PARTITIONING
It was actually painful to read: these kids are being accused of stealing food and not vomiting because that’s the only way to explain it.
NO IT’S NOT, SCIENCE.
They can be forced into losing fat while maintaining some muscle with an extreme protein-sparing modified fast (eg, Bistrian et al., 1977)…
A few research groups have considered the possibility it’s a hormonal disorder, and some fairly long-term studies with GH replacement have shown promising results (eg, Carrel et al., 1999).
Prader-Willi Food Pyramid. Wait, wut? O_o
Some have even speculated involvement of leptin (eg, Cento et al., 1999), although this hasn’t been followed-up on.
Disclaimer: I don’t know the cure or best treatment modality for Prader-Willi, although given the strong circadian component in its sister condition, Angelman’s Syndrome, I strongly believe this avenue should be explored (in combination with the seemingly necessary hormonal corrections, which have been the only successful interventions yet). “Diet” doesn’t work; these kids aren’t obese because they’re stealing food or failing to vomit. Interventions strictly targeting CICO have massively failed this population.
Side note: in the Angelman Syndrome mouse model, *unsilencing* the paternal copy worked… maybe the same could work in PWS (and/or other forms of obesity)…?
Evidence supporting potential circadian-related treatment modalities for PWS:
A Prader-Willi locus IncRNA cloud modulates diurnal genes and energy expenditure (Powell et al., 2013)
Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells (Devos et al., 2011)
Circadian fluctuation of plasma melatonin in Prader-Willi’s syndrome and obesity (Willig et al., 1986)
And the connection with LIGHT:
Artificial light at night: melatonin as a mediator between the environment and the epigenome (Haim and Zubidat, 2015)
Circadian behavior is light re-programmed by plastic DNA methylation (Azzi et al., 2014)
PWS is much worse than just nutrient partitioning (seriously, just spend a few minutes on any Prader-Willi support forum or this; maybe it is an appetite disorder, but given the data on weight gain [mostly fat mass] and weight loss [mostly muscle mass], it seems far more likely a circadian disorder of nutrient partitioning),
but that component jumped out at me; more specifically, despite the only positive results coming from non-dietary interventions, researchers were still all “#CICO.”
“Lean meat, sugar-free Jello, and skim milk”
FFS
Circadian biology, hormone replacement [where appropriate], and figure out if any specific diets help. PMSF/CR doesn’t work unless “refrigerators and cabinet pantries are locked shut.”
Maybe this applies to other forms of obesity, too.
Maybe.
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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.
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.
Is it possible to improve the amplitude and resiliency of your circadian rhythms? Is this desirable? Yes and yes, I think.
Introducing, the aMUPA mice (Froy et al., 2006). What you need to know about ’em: they have very robust circadian rhythms. How is this assessed? Take some mice acclimated to their normal 12 hour light-dark cycle (LD) and place them in constant darkness (DD). Then take liver biopsies and measure circadian genes to see how well they still oscillate throughout the dark day; this is also known as the free-running clock, and it craps out differently in different tissues depending on a variety of factors. Most of the time, however, it’ll run for a few days in the absence of light. Circadian meal timing also helps to hasten re-entrainment.
Note in the figure below: 1) there are two distinct lines of aMUPA mice; and 2) both exhibit a greater amplitude in circadian oscillations during free-running, or DD conditions.
Gelatin and glycine have bounced around the blogosphere for quite some time. Coming from a nutrition-centric place: you say gelatin, I think tryptophan (or lack thereof) and glycine. Others think:
Jane Plain discusses positive mental effects of gelatin and pimps Pro-Stat (good source of glycine). Chris Masterjohn discusses glycine and in typical WAP fashion seems to favor bone broth (20% off Kettle & Fire’s awesome broths HERE!). Knox gelatin didn’t help Michael Allen Smith sleep better, and he apparently tracks sleep quality quite well. However, Sondra Rose thinks it improves sleep harmony, and gelatin simply blows Dana Carpender’s mind.
Tryptophan-rich proteins like those found in whey and egg whites will elevate blood levels of tryptophan relative to other large neutral amino acids (Trp:LNAA ratio), leading to higher brain uptake and subsequent serotonin synthesis. Tryptophan-poor proteins like gelatin do the opposite, and impair memory. But the high glycine content in gelatin improves sleep quality.* Glycine powder might be able to get around this, it’s dirt cheap and it seems to have the opposite effect on brain serotonin, albeit at a much higher dose (and in rats).
The most utterly abnormal sleep structure was studied- for 3 weeks, the subjects were subjected to: 1) a 28-hour day; 2) 6.5 hours of sleep per night (equivalent to 5.6 hours in a normal 24-hour day); and 3) dim lighting during the days. This was done to completely destroy circadian rhythms, and accordingly, metabolic calamity ensued: insulin response went down and hyperglycemia went up (compare black to red bars).
B, baseline; SRCD, sleep-restricted circadian-disrupted; R, recovery period
Other notable findings:
1) sleep-restricted subjects ate 6% more
2) their metabolic rate declined 8%
3) body temperature went down 0.09 degrees
All of these things point to one common endpoint: weight gain. Indeed, the authors even concluded that sleep restriction and disrupted circadian rhythms should increase the risk of obesity… except for one thing: everyone in the study lost weight (1.7% of initial body weight).
…suspense…
How, you ask? during the increased waking hours, physical activity actually went up (a LOT). This may have been because the researchers didn’t recruit an average lot, or group of subjects who were generally representative of the population at large. No, this was a highly selective group of “healthy people.” And what do healthy people do when their awake? It’s probably what they don’t do that matters. Healthy people spend less time sitting around (in general). Had the researchers recruited a group of overweight subjects with their X-Boxes, I imagine the increased food intake would not have been adequately balanced by increased physical activity and they would’ve gained weight.
like this guy
I do NOT recommend sleep restriction for weight loss. Even though glucose metabolism was completely restored after 10 days of recovery (gray bars in the figure above), lingering signs of metabolic dysregulation were still apparent (scary).
RMR and leptin
Perhaps not necessarily video game junkies, but those who are otherwise at increased risk of developing obesity do tend to move around less during the day if they sleep less at night (in contrast to the very healthy people mentioned above).
This is not a “very healthy” group of subjects; accordingly, those who slept <6 a night were 27% less physically active and spent over an hour more per day sitting around. In this study, short sleepers weren’t obese [yet]; but they were predisposed to weight gain. (even the media seems to agree with this one).
If you DID want to try sleep restriction for weight loss, and even vowed to decrease food intake (in contrast to the highly active subjects in Buxton’s study), the results still might not turn out so good…
In this study, food intake was intentionally reduced to a similar extent (-10%) in sleep restrictors and non-restrictors, and in agreement with Buxton, metabolic rate declined in sleep restrictors. And although it was only measured at baseline, physical activity during sleep restriction must have increased because weight loss was similar in both groups. But here’s the catch: compared with those who slept 8.5 hours per night, the weight lost by those who slept 5.5 hours per night was primarily fat free mass (which is probably what caused their metabolic rate to go down), whereas it was primarily fat mass in those who got adequate sleep. This finding alone is reason enough to get a good night’s sleep.
In sum:
Exhibit A, Buxton study: sleep-restricted HEALTHY people ate more but moved around WAY more during sleep restriction = weight loss.
Exhibit B, Booth study: those pre-disposed to obesity moved around LESS during sleep restriction = imminent weight gain.
Exhibit C, Nedeltcheva study: the weight lost by sleep restricted overweight dieters was comprised of muscle mass = not good.
In other words, if you think you’re a healthy person who wouldn’t sit around playing video games in your extra waking hours, or even if you promised not to eat more, the effects of sleep restriction on body composition wouldn’t be pretty (no pun intended). Maybe you wouldn’t get fatter, but you’d probably get fattier.
(an epigenetic disorder), and wasn’t surprised to learn there’s a strong circadian component to it. Epigenetics are one of the main ways circadian rhythms are programmed.
(PWS) is the epigenetic opposite: same region of DNA, but silenced maternal copy and mutant or absent paternal copy. This disorder is characterized by massive obesity and low muscle mass (among other things).
(good source of glycine). 
didn’t help 
