Intermittent Fasting Beats Isocaloric Continuous Dieting (Fat Loss & Health) | New Study + Research Update 12/18

Is intermittent dieting the better form of dieting? Results are promising, but far from conclusive - even in 2018. Check out the latest study in Obesity and selected research from '18, now!
Let's get this straight, right away. The lion's share of the currently available literature on intermittent fasting vs. continuous dietary restriction suggests that "[i]ntermittent energy restriction [is] comparable to continuous energy restriction for short-term weight loss in overweight and obese adults" (Harris 2018).

And yes, there are numerous studies suggesting that intermittent (IER) is even superior to regular, continuous energy restriction (CER).
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However, with the plethora of different regimen and other essential differences in study design, such as subject characteristics, the in-/exclusion of exercise, or the nutritional composition of the diets the existing evidence is yet so heterogeneous that a general statement about the comparative efficacy of intermittent vs. continuous dietary restrictions seems unwarranted.

Just another promising study?

Against that background it will also hardly surprise you that the latest investigation to compare intermittent fasting (IF) versus continuous energy intakes at 100% or  70%  of  calculated  energy  requirements  on  insulin  sensitivity,  cardiometabolic  risk,  body  weight,  and  composition ends on the following conclusion:
"When prescribed at matched energy restriction,  IF reduced weight and  fat mass and improved total and low-density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss" (Hutchinson 2018). 
And guess what, with their results, the researchers from the Adelaide  Medical  School are in good company. Only recently, Antoni et al. identified potentially life-saving differences in the effects of intermittent vs. continuous dietary restrictions. In their study, the scientists from the University of Surrey, observed significantly more pronounced improvements in blood pressure, as well as the postprandial C-peptide (part of the glucose metabolism) and triacylglycerol response in the IF group who dieted for only 2/7 days of the week (Antoni 2018a).
What? Oh yes, there's this impressive 2014 study I discussed in detail - it's worth checking out if you haven't done so already | read it!
Is refeeding "intermittent fasting"? With no clear-cut definition of what constitutes an intermittent fasting regimen, it makes sense to include the results of a recent review in "Obesity Reviews" in this research update. In the eponymous paper, the authors outline a "[r]ationale for novel intermittent dieting strategies to attenuate adaptive responses to energy restriction" (Sainsbury 2018) and report that of the five randomized controlled trials in adults with overweight or obesity that have tested the effects of "refeeding" (=energy balance or absence of energy restriction), two reported greater weight loss than CER, whereas three reported similar weight loss between interventions.
Figure 1: Markers of postprandial lipid (left) and glucose metabolism before and after 5 % weight loss via intermittent energy restriction (IER, black circles) and continuous energy restriction (CER, black squares) in Antoni 2018.
Researchers from the same group have also been able to show that time-restricted feeding aka "intermittent fasting" (feeding window ≥3 h reduced vs. baseline) triggers significant reductions in energy intake in overweight subjects on an ad-libitum (=eat as much as you want) diet (Antoni 2018b).

On the other hand, studies like Schübel et al. (2018) failed to demonstrate significant inter-group differences between continuous and intermittent dietary restriction in their recent 50-week-study (Schübel 2018). Others even report that "in normal-weight subjects have shown detrimental effects of intermittent diets on fat distribution and metabolic homeostasis, raising safety concerns and the need for further investigation" (Brinia 2018). Moreover, another 1-year study found that subjects in the IF group reported greater hunger - that's in contrast to the general consensus among practitioners, but it's what Sundfør et al. report in their recent paper in NMCD (2018).
Table 1: As a review of Ganesan et al. (2018) illustrates, "intermittent fasting" can be effective in form of various regimens. 
There are multiple ways to shed that body fat w/ intermittent fasting: As the tabular overview on the left goes to show you, the studies in Ganesan et al's (2018) review of studies showing statistically highly significant reductions in body fat (p < 0.01) used very different iterations of an "intermittent fasting"-diet, ranging from alternative day fasting to refeeding.

Noteworthy: The alternative day fasting studies were conducted in normal-weight individuals who likewise saw improvements in their body composition.
And the study at hand seems to support the hunger-increasing effects of intermittent fasting (see Figure 2) - interestingly enough, in both IF groups and thus irrespective of the total energy intake:
Thus having returned from a short overview of the latest and greatest in IER vs. CER (or IF vs. CD) returned, it's about time to take a closer look at the initially introduced study by Hutchinson et al. (2018). In said study, the subjects, women with overweight (n = 88;  50 ± 1  years,  BMI  32.3 ± 0.5  kg/m2) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks:
"IF groups fasted for  24 hours after breakfast on three nonconsecutive days per week.  All foods were  provided and diets matched for macronutrient composition  (35%  fat,  15%  protein,  50%  carbohydrate).  Insulin sensitivity by a hyperinsulinemic-euglycemic  clamp,  weight, body composition, and plasma markers were assessed following a “fed” day (12-hour fast) and a 24-hour fast (IF only)" (Hutchinson 2018).
But how exactly did that work? Well, on fed days, IF70 participants were provided with ~100% and IF100 with ~145% of energy requirements.
"IF groups consumed breakfast before 8 am on fasting days (~32% of energy requirements at breakfast on fasting days in IF70 and ~37% in IF100), and then commenced a ~24-hour 'fast' until 8 am the following day on three nonconsecutive weekdays per week. During the fast, participants were allowed water, small amounts of energy-free foods (e.g., 'diet' drinks, chewing  gum/mints),  black  coffee,  and/or  tea  and  were  provided  with  250 mL of very-low-energy broth (20 kcal/250 mL, 2.0 g protein, 0.1 g fat, 3.0 g carbohydrate) for lunch or dinner" (Hutchinson 2018). 
As previously pointed out, the diets were matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). How adherent the subjects actually were, though, is difficult to tell, even though the scientists delivered free foods every 2 weeks to their home - I mean, the "few" cookies at the office and the White Hot Chocolate (worth 590kcal) from Starbucks can easily ruin any dieting effort without appearing on ashamed subjects' 7-day food logs.
Figure 3: Changes in anthropometric outcomes following 8 weeks of intermittent or continuous intake at 70% and 100% of daily energy requirements.  (A)  Weekly weights;  (B)  change in body weight, (C)  fat mass and (D) fat-free mass (all as mean ±  SEM). Pairwise comparisons: *P  <  0.05 vs. control; ^P < 0.05  vs.  IF100; ‡P  <  0.05 vs. DR (Hutchinson 2018)
In view of the fact that this is not an IF-specific problem, though, it raises no general doubts about the most relevant results in Figure 3: the subjects on the F70 protocol displayed greater reductions in weight and fat mass.

The lean mass issue: an intermittent fasting specific problem?

In that, we cannot ignore, though, that the IF70 subjects also recorded the greatest reduction in fat-free mass (=muscle + organs). With ~1.4kg FFM per 4kg FM, the fat-to-organ (including muscle) weight loss ratio was yet worse than the one in the DR70 group, i.e. those subjects who cut their calories by 30% every day (35% in F70 vs. 20% in DR70) - a lean mass sparing effect as it was reported by Varady et al. in both 2009 and 2013.
Figure 4: Pooled effect sizes (Weighted Mean Difference) of secondary outcomes, calculated as difference between the reductions in IER vs. CER, i.e. intermittent vs. continuous energy restriction (Harris 2018)
Whether the greater lean mass losses were a result of the ~30g/d lower protein intake in the IF70 vs. DR70  group (~70 vs. 100g/d that's 0.78g/kg body weight and ~1.3g/g in the intermittent and continuous dieting group, respectively | see Figure 6 in the bottom line, too) is not clear - to me, however, it doesn't sound unrealistic to assume that a mere lack of total daily protein may have been driving these changes in body composition which were not observed with a more intense protocol (alternating every 24-h between consuming 25% or 125% of energy needs), which found that...
"[t]he FFM:total mass ratio increased in both ADF (0.03 ± 0.00) and CR (0.03 ± 0.01) compared to the control group (P < 0.01), with no differences between the intervention groups" (Trepanowski 2018).
In fact, a recent effort to pool and compare the data on IER and CER for a meta-analysis by Harris et al. (2018) found no difference in muscle and a significantly higher reduction in waist circumference (-2.14 cm | p = 0.002) and fat mass (-1.38kg | p = 0.014) - with only six studies and the previously described methodological heterogeneity in study design it would yet be premature to subscribe to any claims about the fat loss specificity of either form of dieting (see Figure 4).
Would more protein help? A study by Harvie was conducted to vary the protein intake and see its effects on body composition and metabolism, but failed to induce relevant intake differences in 2013; overall resistance training and increased protein intakes are yet going to slow down muscle loss when dieting (Hector 2018) - on every diet. If you scrutinize the results of Harris' meta-analysis in Figure 3 you will see that the changes in the subjects' insulin levels were likewise among the handful of statistically significant differences between IER and CER - again with an advantage for the intermittent dieting groups. With 70g
This leads us back to the latest contribution and actual subject of today's article, Hutchinson's recent study in Obesity and its non-aesthetic (ok, body fat is also health-relevant) outcomes, where significant improvements in markers of glucose metabolism (see Figure 5)...
Figure 5: Changes in markers of insulin sensitivity and biochemical markers following 8 weeks of intermittent or continuous intake at 70% and 100% of daily energy requirements. (A) Change in insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamp; completers analysis (DR70 n = 22;  IF70 n = 18;  IF100 n = 19;  C n = 10);  (B) change in fasting blood glucose; (C) change in fasting insulin; (D) change in HOMA-IR; (E) change in nonesterified fatty acids (NEFA); (F) change in aspartate transaminase; (G) change in fibroblast growth factor-21; (H) change in beta-hydroxybutyrate. Data are shown as mean ±   SEM. Filled bars: change from baseline to fed visit; open bars: change from baseline to fasted visit. Pairwise comparisons: *P < 0.05 vs. C; ^P < 0.05  vs.  IF100; ‡P   <   0.05 vs. DR70 (Hutchison 2018).
as well as reductions in total and LDL cholesterol and triglycerides were observed only in the IF70 group, i.e. those subjects who reduced their energy intake by 30% by intermittent fasting (lipids not shown in Figure 5) and hence, ultimately, to the claim from the headline of this article: "Intermittent Fasting Beats Isocaloric Continous Dieting" - an article that turned out to be more of a research update than the analysis of Hutchinson's latest results.
Figure 6: You can hardly argue that the real-world nutrient intakes (in g/d) in the IF70 group come close to what we know would be optimal for lean mass retention (Hutchinson 2018).
So what's the verdict, then? Even though Hutchinson et al. are not the first to diagnose clinically relevant advantages of intermittent vs. isocaloric continuous dieting interventions, we'll need a  lot more research to be able to understand important confounding variables such as protein intake, concurrent exercise, the mere type of IF protocol that is used, subject-specificity...

I could continue this list forever, but instead of doing so, I will tell you this: If skipping breakfast "lean gains"-style allows you to effortlessly reduce your energy intake by 500kcal/day - do it!

Don't fret, though, if intermittent fasting just doesn't seem to work for you even after you've given it enough time (2 weeks+) for your circadian rhythm to adjust.

If there's one thing we seem to be able to tell for sure it's that the main driver of (intermittent fasting-induced) weight loss is the calorie deficit you're generating - add heavy resistance training and sufficient protein 2g/kg to the mix and watch your progress in the mirror. Much better progress than the subjects in the Hutchinson study who didn't skip breakfast, but reduced their energy intakes by 500kcal/d without either working out or eating close to sufficient amounts of protein (see data in Figure 5) | Leave a comment on Facebook!
  • Antoni, Rona, et al. "Intermittent v. continuous energy restriction: differential effects on postprandial glucose and lipid metabolism following matched weight loss in overweight/obese participants." British Journal of Nutrition 119.5 (2018a): 507-516.
  • Antoni, Rona, et al. "A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects." Journal of Nutritional Science 7 (2018b).
  • Brinia, M. E., et al. "The effects of intermittent energy restriction on metabolic and cardiovascular function and overall health." Arch. Hell. Med 35 (2018): 1-17.
  • Ganesan, Kavitha, Yacob Habboush, and Senan Sultan. "Intermittent Fasting: The Choice for a Healthier Lifestyle." Cureus 10.7 (2018).
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  • Hutchinson, et al. "" Obesity  27 (2019): 50-58. Ahead of print.
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  • Schübel, Ruth, et al. "Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial." The American journal of clinical nutrition 108.5 (2018): 933-945.
  • Smith, Gordon I., et al. "Effect of Protein Supplementation During Diet‐Induced Weight Loss on Muscle Mass and Strength: A Randomized Controlled Study." Obesity 26.5 (2018): 854-861.
  • Sundfør, T. M., M. Svendsen, and S. Tonstad. "Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial." Nutrition, Metabolism and Cardiovascular Diseases (2018).
  • Trepanowski, John F., et al. "Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: secondary analysis of a randomized controlled trial." Clinical Nutrition 37.6 (2018): 1871-1878.
  • Varady, Krista A., et al. "Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults–." The American journal of clinical nutrition 90.5 (2009): 1138-1143.
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