Thursday, January 16, 2014

Eating by the Clock Overrides Natural Regulation of Energy Intake: Is the Circadian Rhythm More Important Than Energy Availability?

Is it true? Are we slaves to our internal clock? Is time really the only determinant of whether we are or aren't hungry?
As a SuppVersity student you are well aware of the far-reaching effects our internal clock has on our metabolism (if you ain't aware of this, I'd suggest you review the Circadian Rhythm Series | click here). And if you are honest with yourself, you are probably also aware of the fact that it does not really matter if you eat 500kcal or 1,000kcal for breakfast, at 1:00pm - when you usually have launch - you're hungry... hold on! Are you actually hungry? If we define hunger as the urge to eat, the answer will probably be: Yes, you are! It would however be incorrect to assume that this "hunger" correlates in a predictable way with your current energy needs - otherwise obesity shouldn't be a problem, right?
Burn more, eat ... the same - don't we know that from previous studies?

Exercise: Does It Really Make You Hungry?!

HIIT, LISS ↺ Appetite & Satiety

Carbs Past 6PM Reloaded make you ... lean!

HIT the Cravings, Reduce Hunger W/ Intense Cardio

No-Carb Foods, Artificial Swee- teners & Cravings

he Fallacy of Working Out To "Burn Calories"
The insight that overeating shouldn't be a problem if we were able to adjust our energy intake to our energy expenditura was probably also in the back of of Elizabeth C. Wuorinen's and Katarina T. Borer's heads, when the researchers from the Norwich University and the University of Michigan devised two experiments that would allow them to investigate the human urge to eat (the thing we call hunger) and its obvious correlation with regular eating times (Wuorinen. 2013). In that, the scientists were particularly interested, ...
  • whether a central neural circadian oscillator activates hunger during the wakeful period of the day to produce a hunger acrophase at mid-day, and 
  • if the hormonal consequences of meal eating and digestion and mechanical sequelae of digestive food processing inhibit this central hunger drive and thus provide cues for ultradian meal entrainment.
If you reread the hypothesis you will realize that there is a reciprocal relationship between the rhythmicity of your food intake and the expression of hunger-related hormones. When the clock says "Eat!" your Hunger hormones go up, you eat and you reinforce the already existing urge to eat in regular intervals (for most people approx. every 6h) or at fixed time points.

The clock controls when you're hungry. It's the master, the hormones are the slaves.

If that's correct, the magnitude of hunger of the 10 normal-weight post-menopausal women who participated in the Wuorinen study should be determined primarily by the circadian time of day and ultradian interdigestive episodes, and only secondarily, or even not at all by the inter-meal energy expenditure or the concentrations of ghrelin, leptin, or insulin. To verify that you have to collect hunger ratings in a realistic non-energy-deprived scenario and express them as function of time of day, interdigestive periods, the magnitude of energy deficit experienced since the previous meal, and plasma concentrations of ghrelin, leptin, and insulin.
Figure 1: Illustration of the experimental setup during the 2 trials (Wuorinen. 2013)
The illustration of the experimental protocol in Figure 1 goes to show you that Wuorinen & Borer used exercise (120min treadmill walking in study 1;  10 x 15min slow walking, 5-min rest (LOW) 10 x 7.5 minutes fast walk, 10min rest (HIGH)) as a means to modulate the energy expenditure.

On the day before each trial, a standardized meal consisting of 60% carbohydrates, 25% fat, and 15% protein containing 33% of weight maintenance calories was provided at 19 h. As the scientists point out, ...
"[...a]ll trial meals also had this macronutrient composition. Caloric intake during the trials was assessed from measurements of food provided and any food left uneaten. The inter-meal intervals (IMIs) were: IMI1 from the dinner at 19 h prior to the start of the trial day to breakfast on the day of the trial, IMI2 from the breakfast to lunch at 13 h, and IMI3, from the lunch to the dinner at 17 h. No adjustments in the quantity of food provided were made for energy expended during exercise." (Wuorinen. 2013)
The amount of food was standardized only in experiment 2 ("study 2" as the scientists called it). In experiment 1, the women were free to eat as much as they wanted.
Figure 1: Energy expenditure and intake (kcal) during study 1, total energy balance (middle) and hunger ratings (right) expressed in relative to of maximal score on the scale (Wuorinen. 2013)
A brief glance at the data in Figure 1 does yet suffice to see that working out did not compensate b any means for the exercise-induced extra-energy expenditure. If we do the math, this left the women in the exercise group with a -370kcal energy deficit, while the ladies who had been sitting around all day have already consumed 159kcal more than they would need.
Results #1: What the researchers were interested in was not the energy balance, though. For Wuorinen & Borer, the identity of the hunger-ratings and energy intakes before and after Meal 2 in the presence of significant differences in leptin (see small Figure to the left) was the actual relevant result (see Figure 1).
In spite of the fact that the results of study 1 did already confirm the research hypothesis, the experiment in study 2, which had a longer study duration and standardized energy intakes, is probably of greater significance with with respect to the original research question.

Study 2 confirms the results of study 1 in a longer-term scenario w/ stand. energy intake

This time the subjects remained at the lab for a complete day, they performed two bouts of exercise at different intensities and received standardized meals and yet neither the exercise intensity, nor the inability to compensate for energy that was expended during the workouts had any effect on hunger-ratings - and that in the presence of increased ghrelin (=hunger hormone) levels.
Result #2: Neither the exercise intensity, nor the extend of the energy deficit or the rise in ghrelin the scientists observed when the energy intake on the three mails of experiment 2 was fixed had an effect on hunger ratings.
All that would obviously suggest that the one thing that counts is and the entrained eating-frequency, if we did not know from previous SuppVersity articles that Taubesian "Exercise just makes you hungry"-hypothesis is fundamentally flawed.

For us, Wuorinen's & Borer's conclusion, which implies that the only thing that counts is that you eat, when it's time to eat, irrespective of how your energy balance looks like, is intriguing, but not bulletproof. There is after all one major caveat, somebody without our understanding of the effects of exercise on hunger and satiety (such as Wuorinen & Borer ;-) would not realize: If the exercise induced modulation of the energy balance (calories in vs. calories out) have no orm as the reduced neuronal response in brain regions in response to endurance exercise (cf. Evero. 2012) would suggest, a negative effect on hunger-ratings and ad-libitum food intake, you cannot use an exercise intervention to modulate the energy balance in an experiment that's designed to identify the influence of circadian rhythms on individual hunger ratings.
The central clock still matters The only thing the study at hand does not prove is the fact that it is the primary, let alone only factor that controls when you're hungry and much energy you will consume before you feel satiated. If you remember the SuppVersity "Circadian Rhythm" Series you will be ware of the link between central and peripheral clock, i.e. the interactions between the master circadian clock(s) in the hypothalamus, the suprachias- matic nucleus (SCN), and the brain areas< implicated in the control of feeding, on the one hand, and the rest of your organs, on the other hand (learn more).
There is good evidence that the "alarm times" of this clock can be (re-)set by the adherence to habitual meal times which entrain an ultradian inter-meal-interval hunger rhythm - a phenomenon those of you who stick to intermittent fasting regimens should be very familiar with. If it wasn't for your bodies ability to adjust, you would after all run around as hungry as on day 1 of the switch to a 6-8h feeding window forever.
Bottom line: Against that background we do have to be very careful with our interpretation of the results of this, and the previous studies on the effects of exercise on hunger and ad-libitum food intake. Why? Well, we cannot really tell, if...
  • the well-established absence of increases in energy intake in response to exercise has little to do with the interaction between working out and hunger-ratings and is simply a necessary consequence of the primary of the circadian rhythm (= people being conditioned to eat X1 amount of food at time-point T1, or...
  • the fact that the ladies in the study at hand did not report increased hunger ratings in the exercise condition is a necessary consequence of the fat that exercise does not make you hungry as Mr. Taubes postulated on the Dr. Oz Show
Based on the results of the study at hand, we thus cannot decide, if "the circadian rhythm is more important than energy availability" (see title), with respect to the questions (a) "When do we eat?" and (b) "How much do we eat?" if we simply follow our natural urges (="hunger"). To do that it would require the modulation of the energy intake alone and without the use of exercise interventions that will have their own effects on satiety (cf. Evero. 2012).
  • Evero, Nero, et al. "Aerobic exercise reduces neuronal responses in food reward brain regions." Journal of Applied Physiology 112.9 (2012): 1612-1619.