Intermittent Fasting Increases 24h Energy Expenditure, But Skipping Breakfast Linked to Reduced Metabolic Flexibility

"To eat or not to eat breakfast?" Unfortunately, the scientists geared their research pretty much to this question.
Alright, you all have read my recent Facebook news post about the reduced energy expenditure students reported in a hitherto unpublished paper. Those of you who have (rightly) pointed out that this was at best preliminary evidence (which is, by the way, exactly what I pointed out, as well), will now feel vindicated: Scientists from the German University of Hohenheim report that "when compared with the 3-meal control, 24-h energy expenditure was higher" with a meal-skipping regimen that had a lot of similarity to what many of you will practice and label "intermittent fasting".
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The researchers' main interest was yet not to investigate the effects of "intermittent fasting", but to find out whether the timing of meal skipping "impacts these risks by affecting circadian regulation of energy balance, glucose metabolism, and postprandial inflammatory responses" (Nas 2017).
Figure 1: Schematic overview of the study protocol; note: the interventions were isocaloric and had identical nutrient compositions. *Randomly assigned. BSD, breakfast skipping day; DSD, dinner skipping day (Nas 2017)
To this ends, the researchers had 17 participants [body mass index (in kg/m²): 23.7 6 4.6] participate in a randomized crossover trial comprising three isocaloric 24-h interventions (55%, 30%, and 15% carbohydrate, fat, and protein, respectively), to compare the metabolic effects of
  • breakfast skipping day (BSD) with the first meal at 1 PM and the last at 7 PM, and
  • dinner skipping day (DSD) with the first meal at 7 AM and the last meal at 1 PM
to a conventional 3-meal-structure (smaller meals at 1 AM, 1 PM, 7 PM - total energy and macronutrient intake were identical) on a control day (control).
IF can also help with weight loss in the obese: A recent study also confirms the weight loss benefits of time-restricted feeding showing that obese subjects lose 5% weight, and 4% body fat within 12 weeks when they eat only within an 8h window from 10am-6pm (Gabel 2017 | as discussed in the SuppVersity Facebook News).
In contrast to the previously mentioned graduate research, the scientists offer some insights into how they determined the energy expenditure and the use of a respiration chamber is an important plus of the study.
Figure 2: Fat (A) and carbohydrate (B) oxidation, as well as total energy expenditure (C) during control (light blue), breakfast skipping (pink) and dinner skipping (dark blue) scenario (Nas 2017).
In fact, there's hardly a better way to reliably assess one's subjects energy and macronutrient balance; in conjunction with blood analyses that determined the postprandial glucose, insulin, and inflammatory responses in leukocytes as well as 24-h glycemia and insulin secretion, Nas et al. produced quite a comprehensive dataset which shows the expected null effect on the AUC of the "hunger hormone" glucagon and its opposing peaks and troughs (see Figure 3, left).
Figure 3: While the Ghrelin pattern was reversed, the AUC, i.e. the total ghrelin release did not differ between breakfast and dinner skipping. Furthermore, a closer look at the sign. increased 4h post levels of IL-6 and interferon gamma on the right-hand side of the graph lets us speculate that the high variance could be a result of the previously discussed influence of breakfast(-skipping) habits w/ habitual breakfast skippers seeing lower inflammatory effects (2017)
As well, as the following more surprising effects, the scientists describe in their latest paper in the prestigious "American Journal of Clinical Nutrition" (Nas. 2017):
  • A recent study by Savage, et al. shows conflicting results. In this graduate research, an allegedly likewise isocaloric intermittent fasting diet sign. reduced the energy expenditure (learn more)
    when compared with the 3-meal control, 24-h energy expenditure was higher on both skipping days (BSD: +41 kcal/d; DSD: +91 kcal/d; both P < 0.01), 
  • fat oxidation increased, as it was expected in view of the empty glycogen stores and high AMPK levels in the AM on the breakfast skipping diet (BSD), only (+16 g/d; P < 0.001 | don't forget that this won't translate to increased fat loss if the energy balance is identical)
  • spontaneous physical activity, 24-h glycemia, and 24-h insulin secretion did not differ between intervention days
So far, so good! While the formerly cited results suggest that it doesn't make a difference whether you skip breakfast or dinner, as long as you skip it (=fast intermittently), the blood analyses spoke a different language. In particular, ...
  • the postprandial homeostasis assessment index (+54%) and glucose concentrations after lunch (+46%) were significantly higher on the BSD than on the DSD (both P < 0.05), and 
  • a longer fasting period with breakfast skipping also increased the inflammatory potential of peripheral blood cells after lunch.
That seems to be bad news and confirms the long-standing epidemiologically rooted bias towards eating breakfast and skipping dinner. However, as a SuppVersity reader, you will be aware that previous studies have debunked the myth that eating late and skippin' breakfast was necessarily obesogenic (learn more about breakfast). So what?
If you don't have breakfast and feel fine: Do not start 2017. Here's why!
Is skipping breakfast a true problem, then? Should "Intermittent Fasters" skip dinner? As previously pointed out, the experimental evidence that there was anything special to breakfast is simply not there. Rather than the optimal time to skip a meal for metabolic health appears to be determined by dietary habits (the high variance in the 4h inflammatory response, see Figure 3, right, would support that | learn more about habits and metabolism) and the effects on one's total energy intake. The fact that one's glycogen stores are generally lowered in the AM, as well as a circadian profile in inflammation, may well explain why skipping dinner, i.e. eating breakfast, appears to yield better results, glucose- and inflammation-wise that is.

In the real world, however, differential effects on energy intake make me question the practical relevance of the study at hand - "yes, it's methodologically flawless to use isocaloric diets to isolate the effects of meal skipping/timing", but "no, it's not realistic!" Why's that? Well, 99% of you breakfast skippers out there will probably say that skipping breakfast decreases their daily energy intake. If that's the case, this interacts with both, the glucose and inflammatory response to a meal and - more importantly - the energy expenditure, which may, in fact, have been significantly reduced in the initially referenced graduate study, because the scientists didn't successfully standardize the energy intake... without having the full-text at hand, however, I do not want to further speculate about the reasons for the differences. What I can tell you now, however, is that the study at hand doesn't seem to suggest that a metabolic downside of intermittent fasting exists (note: the "metabolic advantage is too small to translate to fat loss if it wasn't for the reduced energy intake, we'll usually see when people embark on an intermittent fasting regiment). The issue of increased inflammation with breakfast skipping may require further studies | Comment!
  • Gabel, Kelsey, et al. "Effect of 8-Hour Time Restricted Feeding on Body Weight in Obese Subjects." The FASEB Journal 31.1 Supplement (2017): lb274-lb274.
  • Nas, Alessa, et al. "Impact of breakfast skipping compared with dinner skipping on the regulation of energy balance and metabolic risk." The American Journal of Clinical Nutrition (2017): ajcn151332.
  • Savage, Dylan; Yanai, Kaleo; Ketchum, Milton; and Peterson, Janet T., "The Effect of Intermittent Fasting on Resting Metabolism" (2017). Linfield College Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 73.
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