Circadian clocks, entrainment, and health

Summary of a presentation by Orie Shafer titled “Circadian timekeeping and entrainment in neuronal clock networks.”

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From the classic Wever study, which put participants in underground dungeons to study circadian rhythms in the absence of sunlight…

and showed there are multiple inputs, both external and internal zeitgebers.

 

 

In this study, in the absence of sunlight, the human circadian rhythm in locomotor activity, bed movements, and rectal temperature was about 25.8 hours:

The study wasn’t perfect, but still cool.

Most people like to simplify and say light is the input, and while it may be the main one, we now know there are also other important inputs such as food intake for the food-entrainable oscillator and exercise for the skeletal muscle clock.

Behavorial rhythms are driven by molecular rhythms. Molecular  clocks are required in small islands of the brain for behavorial, endocrine, and physiological rhythms.” Search for genetically modified models of virtually any clock gene and it’s going to influence a wide variety of processes. Like, circadian rhythms are important for certain aspects of nearly everything. “60% of the time, it works every time” lol

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Deleterious effects of artificial light at night on health and the environment

Evidence summary on how our increasing exposure to artificial blue light is putting us at risk. And actionable steps on what you can do about it.

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It’s not blue light per se, but rather underexposure to natural sunlight during the day and overexposure to artificial light at night (ALAN). Step 1: Do the opposite of that.

 

 

“Bright light occurs naturally as part of sunlight and moonlight and, like all living things on Earth, we have evolved to respond to the daily cycle of light and dark. There is growing concern that the increased exposure to artificial light at nigh is having an effect on our health, wildlife, and the night sky.”

Your eyeballs are pretty awesome. Rods and cones and these crazy cells that respond specifically to daylight. The crazy cells, ipRGCs, respond to light, particularly in the green/blue range of visible and serve, in part, to entrain the central component of your circadian clock in the SCN. This is important and influences many body functions such as sleep, metabolism, immune system, mood, and even certain disease processes.

If you’re more interested in the environmental impact of artificial light (eg, street lamps), book recommendation: The End of Night: Searching for Darkness in an Age of Artificial Light. If you’re more interested in the human effects: Lights Out: Sleep, Sugar, and Survival.

ALAN-induced clock disruption is said to have “flow-on” negative health effect — there’s no “good news / bad news” to this story (it’s all bad news).

Rock hot blue blockers at night. Use blue light filters on your devices like f.lux and Iris. Sunlight during the day; darkness, moonlight, or firelight at night.

Note those spectral sensitivities – we can see more green/blue than any other colors. Maybe there’s a reason for that?

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The carb/insulin model of obesity was tested again, and it fared better this time.

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial (Ebbeling et al., 2018)

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This is another NuSi study designed to evaluate certain aspects of the carb/insulin model of obesity. Understanding the design of this study is critical to being able to properly evaluate the results.

Very important:

 

1. All food was provided, all the diets were healthy, and most people complied.

2. This was a very expensive study. They used great methods.

Study design: during the “Run-in diet,” everyone followed the same diet (C/F/P: 45%/30%/25%) at 40% caloric restriction in order to lose about 10% of their initial body weight.

Importantly, insulin sensitivity was assessed and this may have influenced what happened next, in the weight maintenance phase. I used to put a lot of weight on this theory — eg, the top 25% most insulin sensitive people will do better on low fat whereas the bottom 25% insulin sensitive people (the most insulin resistant, ie) will do better on low carb — this theory has fared better or worse depending on which study you look at. In this study, it did pretty well.

 

 

In the end, we had 38 people in the entering into the high carb arm of the weight maintenance phase and 43 on low carb.

Remember, they all lost weight on the same diet. Now they’re being fed enough to maintain body weight (low carb, moderate carb, or high carb) and we’re measuring things.

Really exciting stuff!

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The current state of affairs in nutri-Twitter

Rant.

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1) It’s almost as if you’re either:

a red meat-eating 110% keto-advocate

or

you think red meat and a ketogenic diet is harmful.

 

If you don’t say the diet is magical, the zealots will try to trick you into, or outright accuse you of saying it’s harmful.

Further,

 

2. And the protein/kidney debate re-surfaced again recently. To be clear: no studies have shown direct harmful effects of protein on kidney function. The studies cited by KDOQI are observational and on end-stage renal disease. Not mild kidney disease or slightly impaired renal function. If I had ESRD, I’d rather play it safe and not enroll in one of Jose Antonio’s high protein diet studies (~4.4 g/kg lol).

I’m pro-LC and HP but not anti-LF. Humans have thrived on a wide variety of diets over time regardless of macronutrient composition. Food quality seems more important in this context.

3. If ketones are muscle-sparing, then…

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CARBOTOXICITY [screaming face emoji]

Noxious Effects of Exaggerated Carbohydrate Intake (Kroemer et al., 2018)

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This blog post is about the above mentioned article. Disclaimer (qualm #1): it is very pro-low carb and refused to include any neutral or negative points about low carb. For example, had it been within the scope of the article, the authors may have said despite excluding the majority of carbohydrate-containing foods, low carb diets actually aren’t restrictive at all. In other words, this is not an unbiased review article.

 

 

Qualm #2: the authors say people have long-recognized the problems of lipid excess and it even has a name, “lipotoxicity.” But these revolutionaries thought the problems of carbohydrate excess need to be recognized so they coined the term “carbotoxicity.” Are we to believe these dorks never heard of “glucotoxicity” even though it was coined before lipotoxicity even was?!

The review is about the molecular, cellular, and neuroendocrine mechanisms that link a prolonged energy surplus to disease and accelerated aging. It doesn’t really distinguish how the energy surplus is established, specifically, but every now and then they throw out there “carbz.” Ignoring that, there are actually some pretty good points.

The history of dietary carbs had three major, transformative steps. The first was the transition from hunter-gatherers to agriculture which shifted the carbs from fruits, seeds, tubers, nuts, roots, and bulbs to a range of cereals (in Europe), rice (in Asia), corn (in Mesoamerica), and potatoes (in South America). And in Weston Price fashion, this was associated with an increase in dental cavities (probably more cause than correlation here).

Acarbose blocks carb digestion, D-glucosamine blocks glycolysis.

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Entrain all of your circadian clocks. Full stop.

Skipping breakfast shifts skin circadian clock and enhances UVB-induced skin aging and cancer (Wang et al., 2017)… ok, that’s not the real title of the paper, but it’s what the research showed. And it’s kind of amazing.

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Regarding skin cancer and wrinkles, there are two basic processes to focus on: proliferation and protection.

 

 

These processes don’t really overlap: you want endogenous protective mechanisms during the day, to protect against UV rays, and you don’t want to be proliferating at this time because that would increase the chances of a malignant mutation being passed on.


Conversely, at night when the risk of UV-induced DNA damage is considerably less, it’s a green light for proliferation of skin cells. This is healthy, anti-aging-like turnover of skin cells.

We’ve discussed the importance of co-entrainment of your circadian clocks in the path: sunlight in the morning to start up the central pacemaker, breakfast in the morning to co-entrain many of the peripheral clocks with the master clock, exercise to get the skeletal muscle clock on board… but now we have another reason for breakfast: to co-entrain the circadian rhythms in your skin!

Consequences of skipping breakfast, going to the gym at night, staying up late, and having a big dinner: increased risk of obesity, diabetes, cardiovascular disease, cancer, etc., etc…

In this study: skin aging and cancer.

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Ketogenic diet as a metabolic therapy for mood disorders

Recent findings and current developments: where do we stand today?

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Great “Tl;dr:” figure ->

 

 

 

There is most definitely a multi-level bidirectional relationship between mood disorders and diet/lifestyle habits. Can diet cause or cure mood disorders? Can mood disorders cause you to eat/behave a certain way? Yes, yes, and yes. #Context.

That said, diet interventions present a unique and potentially useful treatment avenue for mood disorders.

Mood disorders are a significant source of mental capital loss with high rates of treatment resistance, in part, because we have no clue about the causes, full influence of their spectrums, or how exactly the effective pharmacotherapies work.

The ketogenic diet: why it should be explored ->

  1. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including glutamate/GABA transmission, monoamine levels, mitochondrial quantity and quality, neurotrophism, oxidative stress, insulin signaling, inflammation, etc., etc…
  2. Benign dietary ketosis is a very exclusive diet, immediately cutting out many of the potentially offensive foods.
  3. Malign dietary ketosis, while still technically ketosis, is full of unhealthy n6- and trans fat-rich oils, insufficient protein and fibre, etc. It’s basically the bacon-wrapped cheese dog version of keto.

Domains of depressive symptomatology of interest: anhedonia, rumination, suicidality, sleep disruption, appetite dysregulation, among others.

In this context, it may be perfectly legitimate to supplement a low carb diet with exogenous ketones or coconut oil.

BDNF BDNF BDNF!

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Scientifically, high protein breakfast FTW

It wasn’t even *that* high in protein (30g) but relative to skipping breakfast, everything got better (Gwin and Leidy, 2018).

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At 7 days, this study was longer than some but shorter than others. Breakfast was provided by the researchers. Participants were on their own for lunch and dinner. Ad lib, although 7 days isn’t really long enough to influence body weight and this wasn’t even a goal of the researchers. Their goals were hunger, satiety, fullness, and sleep quality.

RANDOMIZED CROSSOVER. BOOM.

 

 

Small sample size (n = 13), although based on previous findings & expected effect sizes, they needed 12 participants for an 80% chance of detecting a statistically significant difference if one truly existed. Bigger sample sizes are usually better, but when those resources can be better spent elsewhere, researchers use these power calculations to determine the fewest participants required…

moving on

On day 7, they assessed some brain stuff before lunch and then sent them home with party boxes loaded with an assortment of pre-weighed foods & snacks. The participants were instructed to eat as much of whatever they wanted, ad lib, and return the boxes the following day.

The brain stuff:

Just like #eTRF

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The Current Status of the Ketogenic Diet in Psychiatry

Here’s when it’s important to measure your ketones (Bostock et al., 2017). Actually, this is one of the cooler aspects of keto: you don’t need to rely on FFQ’s or diet diaries or other unreliable methods to determine adherence. You just measure ketones directly — if they’re there, you’re adhering to the diet. And while this isn’t really important for body recompositioning purposes, it may matter for neuropsychiatric applications where the ketones themselves may be part of the MOA directly.

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Major limitations in the published studies on this: NOT MEASURING KETONES. If keto didn’t work and they didn’t report ketones, it’s hard to know if keto really didn’t work or adherence failure.

One more point before diving into the studies: rigid, strict adherence is very important here. One study showed efficacy in mild cognitive impairment, but adherence worsened with disease severity. In other words, the people who potentially stood to benefit the most were the least able to stick to the diet. This is why I’m open to coconut oil or medium chain triglyceride-supplemented low(ish) carb diets or even ketone supplements.

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“The Danger of Being an Owl” — sounds scary, right?

^^^ from a recent Vox article. It’s brief, and relatively in line with what I’ve slowly come to think is true about chronotypes. That is, they’re a species-level property. For example, there are morning larks and night owls. There aren’t morning owls.

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Virtually every human study on chronotypes is remarkably consistent: humans aren’t a night-species.

Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals (Lucassen et al., 2013)

They basically put all of the results in the title lol. People who stayed up late and skipped or delayed breakfast had higher stress hormones, lower HDL, and were of generally poorer health.

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