Cyclic Dieting (2:2 ON/OFF) Drops 12.3 vs. 8kg of Body Fat in 16 Weeks, Maintains REE During + Fat Loss Post Dieting

It would be nice to see if this form of "long-term"-refeeds or diet-breaks works for leaner men as well.

You will remember that I've previously discussed the advantages of cycling your energy intake in both, classic intermittent fasting or alternative-day fasting contexts, as well as refeeds. Just like the protocol that was used in a recent study from the University of Tasmania (Byrne 2017), all these diets belong to a category of diets that is characterized by what scientists call "intermittent energy restrictions".

The latest RCT by Byrne et al. (2017), which has just been published ahead of print, took a slightly novel approach to energy cycling, though. Compared to IF and ADF, regimen, the energy intake in form of very long intervals (weeks vs. days or hours): more specifically, 8x2 weeks of dieting interspersed by 2 weeks on a maintenance diet.

Despite these differences, the reasoning behind the study design was pretty much the same bodybuilders and physique athletes have been proposing for decades: intermittently returning to eucaloric (energy intake = energy expenditure) diets should improve weight loss efficiency, attenuate compensatory responses associated with energy restriction (reductions in RMR) and thus avert one of several factors that appear to be driving weight regain - hence, the name of the trial: MATADOR, i.e. "Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound".
As previously hinted at, the energy-cycling protocol Byrne et al. used was different from any I've reviewed before. The fifty-one weight-stable, sedentary, healthy, obese male study participants were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total).

Figure 1: Study design - Arrows indicate time points for measurement of body weight, body composition, and resting energy expenditure (REE) in the continuous (CON) and intermittent (INT) groups. Measurements were taken at the start and end of baseline, weeks 4, 8, 12, and 16 or ER, and at weeks 1, 2, 4, and 8 of post-ER energy balance (Byrne 2017).

As Figure 1 tells you, all subjects had to complete a 4-week baseline phase before the intervention (during this phase, four dropouts reduced the number of participants to N=47). After this lead-in, the dietary intake of the remaining subjects was reduced to 67% of their individual weight maintenance requirements.

With one group dieting for 16 weeks straight (CON) and the other accumulating their 16 weeks of dieting in 2-week blocks (INT), the two trials lasted for 28 weeks and 42 weeks, respectively. Body weight, fat mass (FM), fat-free mass (FFM), and resting energy expenditure (REE) were measured reliably at baseline, and repeatedly throughout the diet- and maintenance-phase (see arrows in Figure 1) by air displacement plethysmography (BOD POD) and a properly calibrated ventilated hood system, respectively.

Food was delivered to home - That's a huge strength of this RCT

To improve adherence, the scientists chose to have a commercial kitchen prepare all meals under the direction of a dietician and had the food delivered to the participants’ homes on a weekly basis. To keep their subject's sweet/fast-food/salty teeth in check, the scientists did not keep the diet "100% clean" and included what they call "discretionary items", most fitness junkies would call "treats" or "cheat meals", of which the previously discussed CALERIE study had shown that they will increase subjects' dietary compliance.

Figure 2: Macronutrient composition ( ±2.5 and 5% for fat, protein, and carbs, respectively) of the diet (Byrne 2017).

As far as the "macros" are concerned, the diet looked just like the standard template dietitians still prescribe (despite convincing evidence that this is far from optimal): 25–30% of energy as fat, 15–20% as protein and 50–60% as carbohydrate.
While participants were required to complete daily self-report food diaries for the duration of the study (28 or 42 weeks for CON and INT groups, respectively), the corresponding data have not been analyzed as a measure of dietary adherence; probably because the scientists assumed that, with the food being delivered to the doorstep, subjects who cheated wouldn't record their extra-ordinary food intakes, anyway - which is, in my humble opinion, a questionable assumption.

The predicted REE, and changes from baseline were calculated using three different approaches to achieve more reliable and comparable (to other studies w/ different results) - Another strength of an interesting paper

As Byrne et al. point out, "the best analytical approach to assess and define adaptive thermogenesis" (Byrne 2017) has been content. Accordingly, they used three approaches:

• Comparing REE over the intervention after adjustment for changes in fat mass (FM) and fat-free mass (FFM).
• Comparing measured REE with REE predicted from the group-specific equations developed using regression analysis of baseline data (see details below).
• Comparing measured REE with REE predicted from the reference equation published by Müller et al. (2004)

Linear regression analysis was used to assess the influence of REE, body composition, age, and sex.  While age did not significantly explain any of the variances in REE, group allocation accounted for a significant proportion of variance in REE. Accordingly, the scientists used a separate equation for the re-analysis of the data and compared their results to the to the ones of Müller's 2004 study, which had a larger, phenotypically similar cohort (for more details on the statistical methods, go to the methods section of the free full-text).

Figure 3: Changes in body weight (kg; mean±s.e.m.) during baseline / 16 weeks of energy restriction (ER) in the continuous (CON; N=19) and intermittent (INT; N=17) groups. (a) Cumulative weight change (kg), (b) individual weight change in INT during each of the blocks, (c) changes in body weight during the individual blocks for both diets, CON and INT - * sign. inter-group (p < 0.05), # sign. intra-group (p < 0.01) differences, diff. indices sign. intra-group differences (Byrne 2017).

Figure 3 shows both, the cumulative weight change (Figure 3.a) in both, and the weight change per dieting block (Figure 3.b) in the intermittently dieting group (INT). As you can see, the subjects in the intermittent diet (INT) group lost significantly more weight than their peers who were chronically restricting their diet for 16 weeks. Here, it is interesting to note that the calories in vs. calories out equation held and the INT dieters gained body weight only during one out of the 7 maintenance blocks (Figure 3.b).

When we compare the course of the weight loss over the whole intervention period, the individual weight loss per block is larger for all blocks but significantly larger only for the first two out of 4 x 4 weeks of dieting (see Figure 3.c).

Weight loss is relevant, but fat loss, or more specifically, permanent fat loss is key!

Now, a cumulative weight loss of >15kg and thus ~1kg of weight per week is impressive. For both, the way they looked and felt (healthwise), however, it was more important how much body fat the subjects lost −8.0±4.4 and −12.3±4.8 kg in the CON and INT diet group, respectively.

Figure 4: Changes in lean and fat mass (in kg) after 16 weeks of dieting and at the subsequent 6-month follow-up; all expressed relative to baseline levels after the 4-wk introduction phase (Byrne 2017) - see Figure 1.

In that, the already impressive INT-advantage (>50% extra fat lost) becomes even more intriguing if you take a closer look at the post-maintenance data I plotted for you in Figure 4. As you can see, the CON dieters regained 17% of the body fat they'd lost - so much, in fact, that the previously significant difference to their baseline body fat levels was no longer significant at the 6-months follow-up. The subjects on the INT diet, on the other hand, maintained 100% of their body fat loss over the course of the 6-mo follow-up.

In the absence of training to trigger lean mass increases in the eucaloric weeks, it is not really surprising that Byrne et al. didn't record similar inter-group differences, as they were observed for the subjects' total body fat mass, for their lean mass, as well.

There are several possible reasons for the efficacy of the INT diet

The most obvious of several reasons why the INT diet was more successful is an increase in dietary adherence. In view of the fact that this just assumed based on the fact that the subjects received ready-made meals, but not rigorously tested/monitored, I wouldn't want to exclude that knowing that the individual dieting phases were only 2-weeks long and related or physiologically induced differences in food cravings could have resulted in different energy intakes in the CON vs. INT groups during the dieting weeks.

The effect of any deviations from the provided diets would yet probably be small and - even if they exist - could not explain the 35% increased fat loss in the INT group during (for the follow-up data in Figure 4, it would be irrelevant, anyway).

Figure 5: Unadjusted and adjusted (for fat-free mass and fat mass) changes in REE (kcal/d) measured relative to post-baseline diet after the dietary intervention and the 6-months follow-up (Byrne 2017).

It is, accordingly, more likely that the observed differences in terms of fat loss and fat loss maintenance are results of the differential changes in resting metabolic rate (REE | Figure 5) which reached statistical significance at the end of the dieting phase, when the scientists adjusted the measured REEs for the changes in fat-free (FFM) and fat mass (FM) - a statistically significant and practically highly relevant advantage for the INT dieters who experienced 52% and 67% smaller reductions in REE after the intervention and the follow-up phase, respectively.

After 12-wks the reduction in REE was sign. larger than predicted w/ continuous dieting

In that, it is interesting to note that the more efficient INT regimen showed a better congruence with the model predictions than the regular dieting regimen (CON) the predictive equations were made for (see Figure 6) - and that irrespective of whether the scientists' own linear regression equation or the potentially more accurate equation from Müller et al (2004) was used:

Figure 6: Comparison of the measured and predicted changes in non-adjusted (left) and adjusted (right) REE in KJ/d, based on the equation developed based on the study at hand (top) and a potentially more accurate equation from the larger-scale study by Müller et al. (bottom); * denotes statistically significant differences p < 0.05 (Byrne 2017).

One of the many take-home messages from the study at hand is thus that common REE-estimations lose their accuracy as the duration of caloric restriction increases. Even though this is the case for continuous and intermittent dieting, the predictions were found ...

• to overestimate the adaptative reduction in REE for the early phase and to underestimate the adaptation in the late phase of dietary intervention in the CON group, and
• to underestimate the adaptative reduction in REE for the early phase and to overestimate the adaptation in the late phase of the dietary intervention in the INT group.

Keep in mind, though, while there are opposing trends, the INT regimen does not fully protect you from reductions in metabolic rate. In the long term, these changes are, however, significantly less pronounced than what you'd see with an equal amount of dieting weeks without maintenance phases.

Wait, why were previous "intermittent fasting" studies not that promising?

As the authors point out in the discussion of their results, this is not the first diet that interpreted "intermittent fasting" as 'block fasting'. Previous studies with 5:5 or 1:1-week blocks over 25 and 8 weeks, respectively (Arguin 2012; Keogh 2014) yielded different results, reporting no advantage of intermittent ER (although the energy deficit in the latter study was not matched between groups).

Whether these differences can be explained due to the fact that the study at hand is the only one to actually hit the "maintenance energy requirements" during the 4x2 weeks on the eucaloric diets isn't clear (also because the scientists didn't actually measure the total EE and body composition during the 4x2 energy balance blocks in the INT group. Furthermore, something as simple as the subjects' sex could also make all the difference: the subjects in both previously cited studies were, after all, women, and you've previously read at the SuppVersity that the female hormonal and metabolic system reacts more sensitive to energy restrictions.
References:

• Arguin, Hélene, et al. "Short-and long-term effects of continuous versus intermittent restrictive diet approaches on body composition and the metabolic profile in overweight and obese postmenopausal women: a pilot study." Menopause 19.8 (2012): 870-876.
• Byrne, et al. "Intermittent energy restriction improves weight loss efficiency in obese men: the MATADOR study." Int J Obes (Lond). Aug 17 (2017) [Epub ahead of print].
• Keogh, Jennifer Beatrice, et al. "Effects of intermittent compared to continuous energy restriction on short‐term weight loss and long‐term weight loss maintenance." Clinical obesity 4.3 (2014): 150-156.
• Müller, Manfred J., et al. "World Health Organization equations have shortcomings for predicting resting energy expenditure in persons from a modern, affluent population: generation of a new reference standard from a retrospective analysis of a German database of resting energy expenditure." The American Journal of Clinical Nutrition 80.5 (2004): 1379-1390.