Sunday, August 26, 2012

Circadian Rhythmicity - "Breakfast" or "Breaking the Fast"? Fasting as Zeitgeber & All About King, Prince & Pauper

Image 1: What would a King say if you served him that for breakfast?
When it comes to the regulation of circadian rhythms by nutrient intakes (and vice versa) the first thing we have to consider is the relation of the day-/night-cycle as discussed in the previous installments of this series and our (historical) ability to hunt and gather food. With our pathetic visual acuity in the dark and our laughable odor sensitivity and sense of hearing, our food intake has always been closely in tune with the light-controlled circadian rhythm. Without the "paleolithic" requirements of gathering and hunting, however, our eating time and frequency is either consciously controlled (e.g. "intermittent fasting") or behaviorally entrained, respectively learned via socialization.

While our sleep/wake cycle is very rigid, our feeding cycle gives us a lot of leeway 

Everyone of you who has ever tried to change a previously learned eating habit or (en-)train a child who is used to be fed whenever it gets hungry to switch to your dietary habits, will be aware of the resistance of these entrained rhythms towards change. Someone, who comes home from his last appointment with his Dr where he was told that "you have to have breakfast", because as we all know "it is the most important meal of the day", is guaranteed to have a hard time switching from coffee-to-go to the "healthy breakfast cereals" his Dr wants him to eat ;-) Mr. Kellog's Honeypops, on the other hand, will certainly be thinking about his beloved breakfast cereals all morning, when his progressive nutrition code wants him to start intermittent fasting.

More than with our sleep cycle which has at least in the broad scope of our evolutionary history always been very stable, the variations in nutrient availability on the large (e.g. seasons), but also on the small scale (e.g. bad luck hunting), are probably the reason that we have a lot more leeway with respect to our eating habits. And still, the well-documented existence of the aforementioned entrainments, and their metabolic and endocrine consequences, of which the correspondence between the release of the "hunger hormone" ghrelin  and our habitual feeding hours is probably the best-established one (suggested read: "Ghrelin Boosting Fats for Intermittent Fasting" for more on why ghrelin is not simply a "hunger hormone").

In a 2008 study, Frecka et al., for example, were able to show that ghrelin rises according to the habitual feeding patterns in both obese and lean subjects (18-50y) - contrary to what the (misplaced) appellation "hunger hormone" would suggest, however, without any significant correlation to subsequent food intake! In other words: While the subjects felt that "it's about time to eat", higher ghrelin levels, as they were observed in those with a lower meal frequency (5.5-6.5h vs. 2.5-3.5h between lunch and breakfast), did not correspond to higher food intakes during lunch - at least as long, as the 2nd meal coincided with the entrained rhythm. What the study does yet not address are the consequences of deviations (short and long term) from this rhythm and the question whether a "natural", i.e. our genetically determined and/or sunlight mediated rhythm exists.

Rise and shine... and eat?

Image 2. Firstly, no king would eat junk like that for breakfast and secondly the saying "have breakfast like a king" should actually read "beak your fast like a king".
When you think about it from an evolutionary perspective, the idea of "having to wait for a meal",  especially the first one of the day, is actually so intuitively logical that it is somewhat tragic that people misunderstand the statement that "breakfast is the most important meal of the day" as an invitation to start binging the very moment the get up, instead of waiting for lunch or even dinner to begin stuffing junk down their pie-holes. Actually this is quite ironic, because if we take a look at the etymological origins of the word "breakfast", it's plain obvious that this is not - as in Germany, where it is called "Frühstück" = "the first piece", the first meal of the day, but the meal that breaks the fast!Unfortunately, though, fasting, has become something, the average TV watching couch-potato of the Western hemisphere is a total foreigner to.

Most of us have become so alienated to the natural 12h+ fast which has once been an obligatory consequence of long winter-nights, food seeking and game that did not willingly surrender to its fate of becoming "breakfast", lunch or dinner, that many of us even have to take specific precautions in order to make sure that they are actually "fasted", when they go to the Dr. to get blood drawn early in the morning. On regular work-days, on the other hand, our tummies, which are designed to work short-time over night, oftentimes haven't even fully digested the remainder from our 16-20h binge of the previous day, in the course of the insufficient 6h of sleep we have gotten before the alarm clock rang. No wonder many people wake up "not feeling like having breakfast" and simply ignore the advice of their doctor has given them, grab a cup of coffee and head to work. Now, this may make their doctors' toenails curl in horror, but it is actually evidence that despite being misaligned (in the eyes of their docs), their feeding pattern does still have some sort of circadian rhythmicity, which would easily be lost once they switch from an early morning fast to the 24/7 binge regimen McDonald's, Burger King & Co are long catering to (see image 2).

When you didn't fast you cannot have breakfast

The answer to the endlessly debated question of whether or not you should have breakfast is - as long as we understand "breakfast" correctly, i.e. as "breaking the fast" - stupidly simple: Without fasting there is no "break(ing the)fast"! Our diurnal metabolic rhythm is geared towards cyclic fasting and feeding patterns, where the feeding hours have always been shorter than the fasting hours.

Figure 1: Are there many ways to Rome? If so, they all have one thing in common achieving an intermediate "fasting state" (green: low energy; orange: medium energy; red: high energy meal)
Obviously, this does not mean that you cannot have breakfast! Rather the opposite is the case, if you recall my hint at the weight loss intervention of the Stadtwerke Cologne (cf. "Carbs Past 6PM"), you will also remember that the most important principle of this dietary intervention is not to have dinner (or at least minimize the energy intake in the evening). And the success obese and chubby and even normal weight bus drivers, administrative officials and all sorts of other employees had with this regimen exemplifies that people can actually have breakfast in the common sense, as long as they've already had their share of (overnight) fasting and are actually breaking a fast.

Did you know that Ratcliff et al. have shown that consuming eggs for breakfast (CHO/fat/protein = 22:55:23) instead of a bagel (CHO/fat/protein = 72:12:16) will reduce the insulin and glucose response, lead to longer satiety and suppress appetite and reduce 24h energy intake (Ratcliff. 2010)? But how can that be? It must be the protein, right? Not really - it's rather the low carbohydrate content which will not totally compromise the increase in FFA levels during fasting, which is characteristic of "being in fat burning mode" - not the least to the morningly rise in cortisol, by the way ;-)
The obese Israeli police officers in the treatment group of the Sofer study (cf. "Carbs Past 6PM"), on the other hand, were just about to begin "fasting" (in the sense of "running" solely on stored fuel), when they woke up at 6AM, after all they did not just have all of their carbohydrates but at the same time ~80%+ of their daily caloric intake less than 12h ago (while the "official" time was past 6PM it is reasonable to assume that dinner was not due before 8PM for most of them). That said, their low calorie, almost-no-carbohydrate "breakfast" was effectively a means to support, not to break the fast. With the caffeine from their artificially sweetened coffee and the slowly digesting combination of fat, small amount of protein and minimal amounts of carbs in the nuts, they kept fueling the lion's share of their metabolic demands from the same stores the Stadwerke employees have tapped into extensively during the evening hours an the night of the previous day.

The "carbohydrate fast", the Israeli police officers were practicing did, if you will, put them in something that would be accurately described as a "semi-fasted" state, where the small and macronutrient specific influx of energy is insufficient to replenish the ATP stores, so that the constant or even slowly declining ADP/ATP ratios will trigger the the same (at least qualitatively) increase in p-AMPK, Sirt1 and downstream PGC1-alpha expression, as regular fasting (cf. Draznin B. 2012).

We are adaptive machines: Many regimens work, as long as they don't lack tact

If thus obviously having, not having or modifying your breakfast can work, it is actually not very surprising that a closer look at the existing research on the issue of whether you fare better or with breakfast, is inconclusive to say the least. Studies such as Astbury et al. with "regular breakfast eaters" as subjects, for example, show that the regular hormonal response was disrupted (stop for a second and think about what "regular" is measured against, here... ok, now go on), when the normalweight healthy men skip their breakfast (Astbury. 2012).
Figure 2: Visual summary of some of the results and weaknesses of the Astbury study.
Unfortunately, the Astbury study is in a way exemplary of much of the research that is / has been done in this area: Many of the studies have either methodological issues / shortcomings and/or present very biased and often even unwarranted interpretations of selected data.

Image 3: Another day at the SuppVersity and yet another thing learned, right? Come on, don't tell me you knew that it was the US nutritionist Adelle Davis who coined the (in-)famous advice to "breakfast like a king, lunch like a prince and dine like a pauper"...
In the Astbury study, for example, the provision of a 2nd breakfast-like liquid "preloading" meal before the launch is a major drawback to the real-world significance of their results. Serving their subjects Kellog's Krispies with skim milk, on the other hand, may be representative of the "fly-by" junk breakfast many people consume in the misplaced believe that it would be a "healthy breakfast", but has eventually little to do with the "long-term satiating breakfast of the kings", Adelle Davis (image 3) probably had in mind when she advised people to...
Moreover most of the promoters of this approach recommend to get at least (!) 25% of your day’s calories from breakfast - enough to keep you going right through till lunchtime, both physically and mentally". The sugary junk breakfast in the Astbury study, however, was not just fat free (something Adelle's milk in image 3 certainly wasn't!), it contained also no more than 10% of the daily energy requirements and was thus 40% beyond the minimal prescription for a "king's breakfast".
"To say that obesity is caused by merely consuming too many calories is like saying that the only cause of the American Revolution was the Boston Tea Party." - Adelle Davis
What's even more hilarious, though, is that the scientists explicitly measure the statistically already hardly significant changes in hormonal patterns, specifically highlight the the +17% increase in caloric intake upon lunch, and don't waste a single word on the important fact that the the overall caloric intake in both conditions was identical, and the increased food intake during lunch did not even fully compensate for the calories the subjects missed during breakfast in the abstract to their paper.

Eating vs. not-eating and quantity over quality

Note: The aforementioned "calories don't cause obesity" statement is only valid within a relatively narrow margin of total caloric intake and there is NO - and I repeat NO - debating that a healthy human being can maintain it's body weight, let alone lose weight, when he or she is eating more than 50% above his / her maintenance threshold!
With the second of the afore-cited statements from Adelle Davis, who was incidentally also among the first prominent nutritionists to support the necessity of exercise, the dangers of vitamin deficiencies, and the imperative need to avoid hydrogenated fat and excess sugar consumption, we are getting back on track, now: "Obesity is not caused by consuming too many calories!"

If you look at the current "answers" to the ensuing question: "If it's not calories that cause obesity, what is it then?" You will find answers that range from insulin over leptin resistance to fructose and general carbohydrate overconsumption, right into the too much omega-6 fats argument and the whole litany. Each "expert" has his / her own hobbyhorse in his stable... they are like pieces to a puzzle, some of which do, some of which don't go well together.

Eating a high protein diet (40%+ from protein), while trying to reap the benefits from a "ketogenic diet", for example, is impossible, and one of the reasons people "just can't lose weight". To "breakfast like a king" and still adhere to the underlying principles of a "Berkhan-esque" Lean Gains regimen, on the other hand, is not as mutually exclusive as it may sound. After all, the "intermittent fast" which is at the heart of Berkhan's protocol does not have to take place in the morning (click here and read more about intermittent fasting).
Figure 3: The good old saying of the king, prince and pauper could actually become important again, when you break the fast early and thus stop eating "early". Why you want to do that at all? Well if you want your diet to have any priming effect on your circadian rhythm fasting is the best (and most natural) way to induce the zeitgeber gene response - here exemplified by the Per2 expression of mice in response to 8h (red) and 16h (green) fasts (data based on Hirao. 2010)
Compared to the "early fast" (=skipping breakfast and even lunch), which comes totally naturally as an extension of the (ideally) growth hormone mediated nightly shift into the fasted state, the "late fast" (=skipping dinner) does simply require some more tweaking on your part (see figure 3), because you will have to modulate your food intake in a way that allows for a similarly smooth transition into the fasted state, as the going to bed after a satisfactory last meal of the day and letting your body take care of the rest.

Low GI, low carb, damn ... didn't we hear that before?

Image 4: "If you had told me that this is all about low GI or low carb diets before I had taken a nap right away! Much better for my circadian rhythm than this!"
This is also, where macronutrient ratios come into play. The aforementioned egg breakfast from the Ratcliff study (see red box above), for example, would provide the advantage of minimizing the glucose and insulin spike compared to a "breakfast" with Rice Krispies, for example, and thus minimize the subsequent drop in blood glucose. That the latter is one of the fundamental determinants of our ability to appropriately control our food intake, was one of the findings of a 2002 study by Westerterp-Plantenga et al. who report that the frequency and extent of these events added significantly to the explanatory value of the meal frequency data they had collected from 20 healthy young (18-31 y) normal weight (BMI: 22.8+/-1.9 kg/m²) men.

Yet despite the fact that the conclusion the researchers from Maastricht University in the Netherlands make based on their data
"[h]abitual meal frequency is based upon a cluster of related factors including macronutrient composition of the food, sweetness perception, hunger suppression, blood glucose declines and average baseline blood glucose levels." (Westerterp-Plantenga. 2002)
may sound like yet another recitation of the "good" reasons why you should eat a low GI or low carb diet, the most important word, at least in the context of this series, is probably "habitual"!

Eating by the clock or setting the clock by eating?

Figure 4: Light is the master regulator, and integrated only via the suprachiasmatic nucleus; fasting and calorie restriction can strengthen or weaken this superordinate or central rhythmicity, of greater practical importance is yet probably their role in the subordinate system and specifically the peripheral organs, e.g. liver, muscle, fat, etc. (illustration based on Froy. 2007)
Exactly this previously mentioned habituation or "entrainment" effect, however, is a significant problem, when we are trying to interpret the already scarce research on "optimal" circadian feeding patterns: Imagine you invite a group of 8 breakfast eaters for two testing sessions into your lab, give them breakfast in one, let them "starve" in another. Two weeks later, you repeat the same experiment with Adelfo Cerame and 7 other people who fast for 16h+ every day... I guess I don't have to tell you that you cannot expect the breakfast eaters to show the same hormonal, metabolic and epigenetic response as the intermittent fasters.

Instead of following up on the exact timing questions, the next episode will therefore deal with the lower right part of figure 4, the few established effects of individual macro- and micronutrients, and just to make sure you come back next week, I'll drop three of them: glucose, caffeine and vitamin A

  • Astbury NM, Taylor MA, Macdonald IA. Breakfast consumption affects appetite, energy intake, and the metabolic and endocrine responses to foods consumed later in the day in male habitual breakfast eaters. J Nutr. 2011 Jul;141(7):1381-9. 
  • Draznin B, Wang C, Adochio R, Leitner JW, Cornier MA. Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res. 2012 Aug;44(9):650-5.
  • Frecka JM, Mattes RD. Possible entrainment of ghrelin to habitual meal patterns in humans. Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G699-707.
  • Froy O. The relationship between nutrition and circadian rhythms in mammals. Front Neuroendocrinol. 2007 Aug-Sep;28(2-3):61-71. Epub 2007 Mar 24.
  • Halsey LG, Huber JW, Low T, Ibeawuchi C, Woodruff P, Reeves S. Does consuming breakfast influence activity levels? An experiment into the effect of breakfast consumption on eating habits and energy expenditure. Public Health Nutr. 2012 Feb;15(2):238-45.#
  • Hirao A, Nagahama H, Tsuboi T, Hirao M, Tahara Y, Shibata S. Combination of  starvation interval and food volume determines the phase of liver circadian rhythm in Per2::Luc knock-in mice under two meals per day feeding. Am J Physiol Gastrointest Liver Physiol. 2010 Nov;299(5):G1045-53.
  • Ratliff J, Leite JO, de Ogburn R, Puglisi MJ, VanHeest J, Fernandez ML. Consuming eggs for breakfast influences plasma glucose and ghrelin, while reducing energy intake during the next 24 hours in adult men. Nutr Res. 2010 Feb;30(2):96-103.
  • Westerterp-Plantenga MS, Kovacs EM, Melanson KJ. Habitual meal frequency and energy intake regulation in partially temporally isolated men. Int J Obes Relat Metab Disord. 2002 Jan;26(1):102-10.