True Alternate Day Fast Beats Classic Dieting: Max. Fat, Min. Muscle Loss, No 'Metabolic Damage' in 32 Wk Human Study

This is exactly the way your plate will look during true alternate day fasting.
This study is not just about alternate day fasting aka ADF. It is about "true alternate day fasting" - What is that? Well, it's not an official medical term, yet, but if you hadn't read about "alternate day fasting" regimens at the SuppVersity before, you'd probably think that an "alternate day fast" would be a full fast as in "not eating anything" every 48h - like in "Monday, don't eat; Tuesday, eat regularly, Wednesday, don't eat; Thursday, eat regularly..." As of now, only a handful of rodent studies tested (quite successfully, though) these "true alternate fasting" regimen, while human studies often used reduced, but never no energy intakes on the fasting days.

That's until now, though! Scientists from the University of Colorado Anschutz Medical Campus randomized decently healthy, but obese adults BMI 30 kg/m², age 18-55) to either (a) a zero-calorie ADF (n = 14) or chronically energy reduced (CR | -400 kcal/day, n = 12) diet for 8 weeks. Outcomes were measured at the end of the 8-week intervention and after 24 weeks of unsupervised follow-up.
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What is important to understand is that the study diets were not designed to produce comparable energy deficits. Now, at first sight, this may sound stupid, but eventually, this and the 24-week unsupervised follow-up make the study more practically relevant with respect to the actually relevant research question: Is ADF better than a standard-of-care weight loss diet (moderate daily CR)? The existing difference between the two diets which had identical macronutrient profiles (55% carbohydrate, 15% protein, and 30% fat) is described as follows:
  • CR participants were provided a diet that produced a -28% (that was more than intended) deficit from estimated energy requirements (considered a standard-of-care weight loss diet at the time the study was designed). 
  • ADF participants were provided a diet but instructed to fast on alternate days. On fed days, they were provided a diet estimated to meet estimated energy requirements, which was supplemented with ad libitum (as much as they wanted) access to five to seven optional food modules (200 kcal each). ADF participants were permitted to eat as much as they wished on fed days, but were not encouraged to eat all food provided. On fast days, ADF participants were instructed to begin their fast after the evening meal the preceding day, and to consume only water, calorie-free beverages, and bouillon/stock cube soup. 
The subjects' individual daily energy and macronutrient intakes were calculated based on food return
using PROnutra software (Viocare Technologies Inc., Princeton NJ). Estimated energy deficits were calculated by subtracting estimated daily EI from estimated daily energy requirements.
Table 1: Mean daily energy and macronutrient intake on fast and fed days over 8 weeks in ADF (Catenacci. 2016); corresponding data for weeks 9-32 not available.
What about adherence? At least for the first 8 weeks, the subjects' adherence was - within the limits of accuracy values from a non-metabolic-ward study have - excellent. 44.4 kcal/day, that's almost nothing and not really that surprising. After all, studies have shown that, eventually, many people feel it's easier to simply eat nothing than to eat in moderation or less than would be necessary to be satiated. Which leads me to my personal experience (N=1 + friends) that confirms: one of the biggest strengths of any intermittent fasting regimen (ADF or classic IF) is that they are easier to adhere to than regular diets with identical calorie refeeds; and thus eventually back to the study which found the previously hinted at benefits in form of maximal fat, minimal muscle loss and no changes in resting metabolic rate (RMR) only after the not as tightly controlled 24-week weeks of unsupervised follow-up - the real-world part of the study, as I would like to call it.
When the scientists say that the subjects in the fasting (ADF) group "achieved a 376 kcal/day greater energy deficit" (Catenacci. 2016) we thus have every reason to be skeptical of the accuracy of this value. Providing a range of 200-500 kcal would probably be more "accurate" - and if we further assume that the real value is on the lower side, it's also not surprising that "there were no significant between-group differences in change in weight (mean +/- SE; ADF 28.2 +/-  0.9 kg, CR 27.1 +/-  1.0 kg)" (ibid.)
Figure 1: Changes in body composition (%) during the initial tightly controlled 8 weeks and at the end of the subsequent "real-world" uncontrolled 24 weeks, i.e. at the end of the 32 weeks (Catenacci. 2016).
With that being said, who cares if the relevant real world results, i.e. the reduction in fat mass and the ill effects on lean mass after the 24 weeks of unsupervised follow-up speak a clear language: ADF kicks CR's ass, or, in non-acronym English, if you simply don't eat every other day, this is a highly effective real-world compatible weight loss tool, one that will have sign. better effects on your body composition (fat to lean mass ratio) than regular dieting where you reduce your energy intake by the same X% every day!
Figure 1: Absolute (see below for explanation) advantage in changes of body composition in the ADF group (left) and changes in resting metabolic rate (in kcal/d) in the controlled early and uncontrolled follow-up (Catenaccio. 2016).
And the best is yet to come: Not only did the subjects in the ADF group lose more fat and less muscle (the values in Figure 2, left are absolutes, i.e. the fat mass values are extra percent body fat loss, while the lean mass value is an extra percent gained in the latter 24 weeks, the "real-world" phase), the subjects in the ADF group also experienced sign. increases in BDNF, the brain-derived neurotrophic factor, which decreased in the CR group who thus could not longer benefit of its beneficial effects on brain health and its ability to regulation the subjects' energy balance (Xu. 2003; Bariohay. 2005; An. 2015); and these effects on the energy balance, respectively the resting metabolic rate (RMR), show: Unlike the subjects in the CR group, the ADF subjects didn't suffer the statistically significant RMR decrease of -111.6 +/- 36.9 kcal/day reduction we see in the CR group (ADF: -16.2 6 +/- 36.6 kcal/d).

Against that background, it is also not surprising that the study at hand suggests that ADF dieting is also less likely to cause / promote the dreaded yo-yo effect: With the total fat mass (%) declining and the lean mass (%) inclining only in the ADF, yet not in the CR group where the body composition kept deteriorating in the 24 weeks of unsupervised follow-up, I previously called "the real-world phase".
Chronic Energy Deficits Make Athletes Fat - The Longer You Starve, the Fatter You Get. No Matter What the Calories-in-VS-Calories-Out Equ. Says - With true alternative day fasting (this is what the study at hand suggests but only future studies will prove), the dreaded decline in RMR and increase in body fat (in the study at hand that's +1.2 kg total and +0.8kg trunk fat in the CR group) hopefully won't happen.
The subjects lost only 2.4% body fat, why's that so exciting if they started at >40%? Well, what is exciting is that even though the ADF diet was clearly not optimally designed (e.g. way too little protein on both fasting and feasting days), there was a fundamental difference in the diets' effects on the subjects' body composition during the "real-world test", i.e. the 24 weeks of unsupervised. A difference that tells you a lot about which regimen is going to yield the better results for the majority of you and your clients: the alternative day fast.

Follow-up studies will now have to (a) identify the underlying mechanism that explains the ADF advantage (of which I personally believe that it is mostly an increased adherence to ADF | remember: the best diet won't help you lose weight if you can't adhere to it), and (b) modify the fasting regimen (e.g. protein modified fast with say 150g protein on the fasting day + the little fat and carbs that come from the protein source and optional veggies) and/or the macro-nutrient profiles on the feasting days and in the CR group from being simply stupid (namely 55% carbohydrate, 15% protein, and 30% fat) to a ratio that would promote fat loss and lean mass retention | Comment on Facebook!
  • An, Juan Ji, et al. "Discrete BDNF neurons in the paraventricular hypothalamus control feeding and energy expenditure." Cell metabolism 22.1 (2015): 175-188.
  • Bariohay, Bruno, et al. "Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex." Endocrinology 146.12 (2005): 5612-5620.
  • Catenacci, Victoria A., et al. "A randomized pilot study comparing zero‐calorie alternate‐day fasting to daily caloric restriction in adults with obesity." Obesity 24.9 (2016): 1874-1883.
  • Xu, Baoji, et al. "Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor." Nature neuroscience 6.7 (2003): 736-742.
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