Meal timing and peripheral circadian clocks

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):

 

zeitgeber entraining

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…

Experiment 1. Every combination of big breakfast / small dinner, medium breakfast; medium dinner; and small breakfast / big dinner was tried.

I feel guilty summarizing so much research so briefly, but for the sake of our sanity, the major finding of this part was: 1) bigger meals entrained peripheral circadian clocks better than smaller ones; and 2) they became more entrained to the time of the biggest meal.

N.B. regardless of peripheral circadian clock timing, the central clock is entrained by light in the morning ergo, bigger meals should be timed earlier in the day.

 

Experiment 2. They next tested various fasting intervals. For example, feeding meal #2 either 6, 12, or 18 hours after meal #1.

 

 

They showed that meals consumed after longer periods of fasting were more powerful at entraining the peripheral clock, which became entrained to the time of the meal after the longest fast.  For example, consider these 2 relatively extreme scenarios:

A) breakfast at 8am, fast for 8 hours, dinner at 4pm, fast for 16 hours, then breakfast again at 8am.

B) breakfast at 8am, fast for 16 hours, dinner at midnight, fast for 8 hours, breakfast again at 8am.

In scenario A, breakfast occurred after the longer fasting window (16 hours vs. 8 hours), and the peripheral circadian clock phase shifted earlier, in line with breakfast and LIGHT, in the morning.  In scenario B, dinner occurred after the longer fasting window, and the peripheral clock phase shifted later, in line with dinner in the evening.

 

Remember: regardless of the peripheral circadian clock timing, the central clock is entrained by LIGHT in the morning… ergo, a longer fasting period should occur prior to breakfast in the morning (ie, scenario A).

 

 

Combine the findings from experiments 1 & 2, and you get: a big breakfast, early dinner, and the longest fasting interval between dinner & breakfast.  All of these findings are incredibly consistent with avoiding Afternoon Diabetes.

 

Part 2.

Humans aren’t big mice.  Mice are nocturnal, which means they eat at the night.  FACT.

 

mice eat at night

 

Sooo…

 

carb back-loading flow chart

 

WHO’S THE MOUSE DOCTOR NOW?! 😛
jk

 

Part 3.

Before you come at me, claiming that “skipping breakfast, hunting all day, and feasting at night” is how our ancestors must have evolved

 

I, for one, think Hunter-Gatherers were capable of planning ahead: having leftovers? that could be breakfast (in the morning).  And even if this wasn’t the case, and every HG who ever existed only had big dinners… there’s a theory that these folks were very good at fattening due to intermittent periods of famine/starvation.  In fact, it likely saved their lives during periods of low food availability.  Do you think they would only eat at night if it wasn’t the best way to store calories as adipose?

“Why do people think HG was such a retard?” -Craig Zielinski

 

calories proper

 

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  • Jason

    Thanks for the info mouse doctor 🙂 Is the jk for “just kidding” or is that somebody’s initials…

    • just kidding 🙂

      • Eric – Golden, CO

        I know when he said it, it was supposed to be a jab at you, but I think it is actually a rather good nickname given your day job. Wear it with pride Yankee Doodle!

  • Jill

    My circadian and bio clocks seem to be mismatched, and I will sometimes wake up ravenous in the middle of the night and have to eat a considerable number of calories in order to fall asleep [which I then have to factor in to the following day’s count]. How does one fix this? I’m taking Mg before bed, but eating earlier/later in the day makes no difference. Low carb, so the bad effects are minimized, but still, bad effects.

    • TechnoTriticale

      Anyone who might provide suggestions is probably going to want to know:
      – bright light at night?
      – blue light at night?
      – lights in bedroom?
      – live near busy road?

      • “- bright light at night?
        – blue light at night?
        – lights in bedroom?
        – live near busy road?”

        No, no, no, and that’s unfortunate 😛

        • Jill

          lol

          How about all factors kept constant, sleep unpredictable? I’ve got the funky glasses.

          • Kasha

            So you’re eating in the middle of the night or you feel like eating in the middle of the night? What time?

        • Sky King

          No lights at night, Dr. Bill delights!
          No/low lights in the morning, Dr. Bill gives us fair warning! 🙂

    • Evan Hobbs

      I would like to know this also as I’ve experienced the same for years and years. It sucks… I often eat right before bed thinking this will help but I still wake up hungry and have to eat carbs to be able to fall back asleep…

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  • Jack Kruse

    A big breakfast……..sounds familiar. Leptin Rx 101. Now Bill consider this with your mice data: The naked mole rats possess lower levels of natural antioxidants than mice and accumulate more oxidative damage to their tissues at an earlier age than other rodents. Yet paradoxically, they live virtually disease-free until they die at a very old age. They are the oldest living rodent. Might this be evidence of what you currently believe about antioxidants is just not factual?

    • Thomas Hemming Larsen

      Jack, please remind me. Didn’t you say that once you’re leptn sensitive, high protein consumption should happen in the evening (like Bill is also suggesting)?

      • Jack Kruse

        When youre LS and ubiquitin is coupled to the other two cycles then you can use high protein……..but here is the caveat: It has to be low exercise at the same time. If not……only way to limit mTOR activation is chronic cold exposure which is why my CT protocol is designed to work with the Leptin Rx. Leptin is about light not food, which is why me and Jane dont see eye to eye on leptin. She will come around eventually especially if she keep following Peter’s bread crumbs.

  • Thomas Hemming Larsen

    Very good article Bill. Its quite interesting with not only meal timing but also meal sizing depending on the time of day. Should one actively aim for scaling down the meals as the day progresses? Should dinner just be eaten as early as possible?
    I still believe most of the success on CN/CBL is due to eating real/nutritious food 90% of the time and limiting the crap.

    • “Should one actively aim for scaling down the meals as the day progresses?”

      that seems like a good idea

      “Should dinner just be eaten as early as possible?”

      doesn’t have to be *too* early — just not right before bed..?

      “Does working out entrain the circadian clock?”

      Here is what I know: Daytime is for activity. Working out in the evening can disrupt circadian rhythms. So, I’d say it’s “prudent” to exercise during sunlight hours.

      • Thomas Hemming Larsen

        Thanks Bill. Is the reason for breakfast being the biggest meal that after the 16h fast you would be more insulin sensitive, compared to a shorter fast?
        Does post workout meal sizes play a role? I.e. could working out before dinner but having a small dinner hinder progress?

        • 1) in one experiment, they tried longer periods of fasting before breakfast, lunch, & dinner (at any time of day). In every case, longer fasting = better entrainment of peripheral clocks to next meal.

          2) insulin isn’t necessary for entrainment of peripheral clocks http://bit.ly/18ANwHN

          3) exercise & biggest meal *at night* seems like it would phase delay both central & peripheral clocks = no bueno

          • Thomas Hemming Larsen

            Sorry, for some reason I had missed that post. That is a really interesting article (may I add that your posts have become better lately). I was going to ask if it is calories and/or macro nutrients which entrain the clock, it seems like its manily calories.
            What you’re more or less saying in that link is what Dr. Panda also showed in the wonderful infographic, and something I think most people is capable of.

          • Thanks, Thomas!

          • Thomas Hemming Larsen

            I came to think that protein should be eaten in the evening to have the amino acids in the body for the overnight fast. I just saw in another comment that you agree with that.
            Is there also a ‘circadian’ reason for this or is it simply to avoid going catabolic?

          • Catabolic stuff.

            See the notorious Alves’ study: whether it’s due to avoiding carbs at night, or having protein at night, that group maintained the most lean mass.

          • Thomas Hemming Larsen

            Thanks Bill. Sorry to drag this out but I came to think of another thing. If training in the afternoon, wouldn’t it be beneficial to also have a good amount of protein prior to that? My thinking is to have some protein already in the body instead of backloading all/most of them.

          • I’m pretty sure you already know my answer to this 😛

          • Thomas Hemming Larsen

            Hehe, Bill 🙂 I know what you mean. But it was an honest question in terms of ‘optimal’ circadian rhythm. Maybe should have been how to balance the protein between lunch and dinner.

      • Jack Kruse

        Your clock pays attention to its height……..did you know that? How much do you know about altitude and where you live? You might want to bio hack that……………http://jackkruse.com/ubiquination-1-bio-hacking-altitude-suicide-loss-muscle-mass/

        • Dan Ordoins

          Jack – Another great one. Another lesson for moving towards optimal. ????

  • Did a little 2 post response on the Kruse forums after reading this post. I like the premise of backloading protein or carbs, and I give a possible protocol and explanation of it here:

    * http://forum.jackkruse.com/index.php?threads/reverse-electron-flow.12744/page-2#post-155437

    * http://forum.jackkruse.com/index.php?threads/reverse-electron-flow.12744/page-2#post-155438

    • Thanks!

      I liked this quote, in particular: “Using food at sunrise to force peripheral clocks to signal strongly
      together with the natural light stimulus setting the central clock is
      the basic idea.”

      • I hope the points we’re missed 🙂

        * potential benefits of delaying eating to 2 hours post sunrise

        * importance of high protein dinner in the 2 hours prior to sunset

        • I agree with the second point.
          Not 100% sure about the first one, though 🙂 I’m thinking peripheral clocks should be started at the same time as the central clock, with light onset, for better circadian alignment… what do you think?

          • Here’s the train of thought that led to the conclusion for breakfast 2 hours after sunrise.

            (1) Assuming that the ideal is to have food together with sunrise, does delaying food for 2 hours cause any harm?

            Not likely, you’re still eating early in the day, and pretty close to sunrise.

            —-

            (2) Is there benefit to delaying eating?

            Most likely, because cortisol tends to drop off pretty quickly within 2 hours post sunrise, and cell volumes are lower, and cell signalling is more efficient, allowing for better handling of food stimulus.

            —-

            (3) Is there any harm to eating too early?

            Possibly. High cortisol (which is needed in the morning), together with a food stimulus is a possible way to generate more fat cells.

            —-

            (4) How do we define “circadian alignment”, and why is it important?

            This gets to my question in the forum posts, asking what does “better circadian alignment” really mean.

            I elaborated on my speculative thoughts on the Kruse forums — http://forum.jackkruse.com/index.php?threads/reverse-electron-flow.12744/page-2#post-155438

            The underlying point there is that you need circadian alignment to deal with stress.

            “Stress” means anything that requires components of the body to react to external environmental changes.

            Being awake means dealing with stress — the sleep state is the default if you believe a lot of what Kruse says. I also brought up the case of the virus to show an entity that has life potential, but manages to isolate itself from stress (and thus is not living) until the appropriate conditions are met.

            Eating involves stress, therefore liver signalling increases. Eating at night involves even more stress. Eating at any time is still stress though ….

            The question becomes “when are the rest of the components of the body best capable of dealing with the stress that eating places”, and the answer for humans is when sunlight is present.

  • Scenario A – this is basically what I’ve been doing for almost a year now…sometimes disrupting the cycle by a prolonged fasting. for my n=1, this seems to fit in very nicely. Your research on circa rhythms are very insightful Bill. Keep doing what you’re doing! 😉

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  • Ryan

    Bill another great post! I couldn’t agree more from the data I have seen. This seems to go along with the other previous data you had mentioned about a recent study that looked at eating before training vs after training. Likely if you have a big breakfast as in this case you also optimize that component if you train after, etc. More and more research seems to be supporting this idea of larger breakfasts. Great work

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  • “The body tends to turn more food into fat at night, while turning it into fuel during the day…”

    http://bit.ly/1M17JD4

    • Thomas Hemming Larsen

      Is that the study with the awesome infographic?

  • Paleo Osteo

    leptin reset alert

  • daz

    here’s another recently published (Mar 2015) ‘breakfast skipping’ study;
    http://onlinelibrary.wiley.com/doi/10.1002/oby.21049/abstract

    Suppversity did a review on it here;
    http://suppversity.blogspot.com.au/2015/03/latest-study-on-breakfast-skipping.html

    May be worth a look & possible future post (or just some comments)…

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  • Paul

    This essay I wrote is relevant, I think.

    Evidence
    against the warrior diet being conducive to normal human circadian rhythm
    optimization

    Based on the
    physiology of the light entrainable oscillator (LEO) of the suprachiasmic
    nucleus (SCN) of the human brain, we are night time sleepers. During the day, sunlight entering our eyes
    causes a decrease of melatonin production in our brains. Melatonin is a chemical that promotes
    sleepiness, so when it is low during the day we are more alert and awake. During the dark hours, melatonin increases in
    our brains and we get sleepier.

    Another
    effect of a normal circadian cycle is core body temperature (CBT)
    oscillation. CBT peaks during the day
    and troughs during the night. The bigger
    the amplitude of CBT the higher one’s sleep quality is. The architecture of higher quality sleep
    includes higher percentages of slow wave sleep (SWS) and rapid eye movement
    (REM) sleep.

    There is a
    food entrainable oscillator (FEO) in the peripheral tissues of the body as well. The intake of food is the zietgeber or time
    giver for the FEO, and the FEO can be in synchrony with the LEO, or it can be
    out of synch depending on the timing of said food intake.

    The effects
    on sleep of asynchrony between the LEO and FEO were illustrated in a study
    titled “Sleep during Ramadan intermittent fasting” by Roky et al. In the study, they observed a decrease in
    sleep quality and CBT amplitudes of the subjects during the night time only
    eating period of Ramadan. Night time
    eating interfered with night time sleeping.

    http://www.ncbi.nlm.nih.gov/pubmed/11903862

    Another
    study titled “Alterations of internal circadian phase relationships after
    morning versus evening carbohydrate rich meals in humans” by Krauchi et al, observed
    that the evening carb rich meal caused a significant decrease of the CBT
    amplitude resulting primarily from an increased night time trough. That means poorer sleep after the evening
    meal.

    http://www.ncbi.nlm.nih.gov/pubmed/12164252

    Another
    study, more pertinent to the warrior diet’s central premise concerning the
    autonomic nervous system, is titled “Effect of insulin and glucose infusions on
    sympathetic nervous system activity in normal man”. In it, Rowe et al show evidence that
    increased plasma insulin causes an increase in SNS activity. Eating carbs (and eating in general) causes
    an increase in plasma insulin which causes an increase in SNS activity,
    whereas, fasting and carb restriction stimulates parasympathetic nervous system
    activity via a reduction of plasma insulin.
    This is the opposite of warrior diet theology.

    http://diabetes.diabetesjournals.org/content/30/3/219.abstract

    So, eating a
    majority of one’s calories at night before bed time is antagonistic to night
    time sleep quality and optimal circadian rhythms.

    Why should
    anyone care? Circadian rhythm disruption
    is associated with a host of diseases of civilization including cancer and
    cardiovascular disease, the two leading causes of mortality and morbidity in
    the U.S.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521792/

    http://www.heartandmetabolism.com/download/44/3.pdf

    With all of
    this in mind, I believe that eating during a morning restricted feeding window
    is best for circadian rhythm optimization. I eat one meal per day in the morning before I
    go to work. It is a grand, high fat,
    ketogenic affair. I can easily ingest
    4000+ Kcal within a one hour feeding window, and then I am set for the
    day. I do not get hungry until the
    evening after work, usually. Then I
    anticipate the fat burning that will happen when I go to bed with an empty
    stomach. If I am slightly hungry at bed
    time, I know that I will not be hungry when I wake up the next morning. That is one of the effects of being a keto
    adapted fat burning beast.

    Hunger,
    while in a keto adapted state, is low key and mellow. It is very different from the panic filled,
    hormonal hunger that carbohydrate addicts experience when they are going
    through the withdrawls that occur every two to three hours. My ketone breath, which increases every
    evening, lets me know that I have plenty of fuel coursing through my blood even
    though my stomach is flushed empty.

    Also,
    because my sleep is of a much higher quality now than it used to be, I only
    need around six hours of unconsciousness per night. When I wake up at 0430 to 0500, I am ready to
    go. My body temperature is noticeably
    cooler at bed time than it was before I started restricting my feeding window
    to the mornings, as well. Lower night
    time CBT is indicative of higher circadian amplitudes.

    On workout
    days, I still eat only one morning meal with no snacking and no obsessive
    compulsive pre and post workout calorie ingesting. If I want to do a gut buster, then I will
    workout before the meal to avoid hurling.
    If the emphasis of the workout is to be on stimulating hypertrophy, then
    doing it after the meal is fine.

    I believe we
    should be doing this bodybuilding lifestyle business primarily for improved
    health. The meal timing of the warrior
    diet is antagonistic to optimal circadian rhythms and is therefore antagonistic
    to optimal health.

  • TechnoTriticale

    Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans
    http://www.pnas.org/content/early/2015/04/09/1418955112

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  • Nicolas Tav?an

    Incredible! So following a 18hr fast, 6hr feeding window, eating the main meal later in the day, would shift clock to later in the day?

    I wonder if this accounts for my sleep issues the past few years, where I switched to: No breakfast, small lunch (2pm) and large dinner (6pm).

    One way to find out . . . shift meal timing!

    • “So following a 18hr fast, 6hr feeding window, eating the main meal later in the day, would shift clock to later in the day?”

      yes — this would most likely induce some degree of circadian phase delay & deteriorate sleep quality

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  • bearowsley

    Seth Roberts (n=1) wrote that too early breakfast would wake him up too early.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964443/
    others
    http://blog.sethroberts.net/2011/12/19/poor-circadian-entrainment-cured-by-meal-timing/

    I myself made a similar observation, that postponing breakfast at least 2 hours would let me sleep through the night, whereas earlier breakfast or eating late would disrupt my sleep and wake me up at 4-5 o clock on the next day.

    So I read that there is a 2 hour period in mice, called food anticipatory activity. (e.g. PMID:23010662)

    My question is: When only eating once per day, and standing up at 7 o clock, which scenario would you prefer: eat at 7 o clock, eat at 9 o clock, eat at 12 o clock.
    In other words: how long is the food anticipatory period for humans?