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It were the nightly binges, not the fasting that made the rodents fat... and it's not news that starving and bingeing is obesogenic, is it?

Recently, Kara L. Kliewer and her colleagues, probably tried to do something good, when they conducted a study to "capture intraday oscillations in lipid stores and adipose tissue gene expression in gorging mice and to identify metabolic consequences of gorging precipitated by food restriction during weight regain" (Kliewer. 2015). Whether what came out of it, i.e. articles saying that "Skipping Meals Promotes Belly Fat Storage, Increases Risk For Insulin Resistance" (MedicalDaily), however, will help people avoid help you lose body or belly fat appears to be highly questionable, though. After all, the mainstream interpretation of the study is rigid with respect to its implications.
Before we delve further into the details, however, let's briefly take a look at what the researchers from the Ohio State University actually did: As you can see in Figure 1 we are - and this is by no means clear whence you're reading only the press-release "copy-and-paste"-jobs online - actually dealing with a feeding regimen that looks pretty similar to what people usually think of when they are talking about intermittent fasting.

Figure 1: Feeding and fasting cycles and metabolic states in 24h feeding cycle (Kliewer. 2015).

So, basically, we are talking about a ~15h fast with that is followed by a 7h feeding window. But there are significant differences to intermittent fasting in humans:

1. Gorging is not allowed on IF-regimen - Usually people who follow intermittent fasting regimens are somewhat anal about their nutrition. A binge like the one that occurred in the mice during the feeding phase is therefore representative mostly of the obese who don't "fast" in the sense of "intermittent fasting", but try to starve themselves for 24h failing only to fall victim to their own cravings late at night (remember: mice are active at night, so their biological clock is inverted compare to ours).
2. Feeding does not occur at the wrong time on IF-regimen - Since we are already talking about "falling victim to [one's] cravings late at night," someone doing a real IF-regimen would never feed at night. He would do it in the early to late afternoon to avoid messing with his cicrcadian rhythm. The mice in the study at hand, however, were fat one-third into the "light period", which is their night and according to the rodents' biological clock not a proper time to "gorge".

Against that background I would be more than hesitant to use the study at hand as evidence of the adipogenic effects of intermittent fasting.

Figure 2: Yes, there's an increase in body weight (albeit not to the same weight as in the control group) and there is an increase in body fat, but both are due to "binging" not due to fasting (Kliewer. 2015).

Rather than that, you will probably see increases in visceral body fat as they are shown in Figure 2 (right hand side) in the previously mentioned "failed self-starvers" who starve all-day and gorge at night - none of my previous intermittent fasting suggestions involved either of these practices (i.e. starving and gorging).
I am thus pretty sure that you have not ruined your body composition if you've been skipping breakfast or even breakfast and launch recently; and that's even more true, if you have followed my advice to use intermittent fasting as a short-term program to lose fat by combining timing and energetic restriction to your advantage.

If you have don just that, you don't have to care about the idiots who are still trying to propagate the myth of "frequent meals for fat loss". If they (a) knew the difference between intermittent fasting and starving and (b) had not relied on an already messed up press release, but had read the study, they would have been aware that  the researchers themselves state that the mechanism for the increased fat gains still has to be elucidated:

"Future studies should determine whether changes in adipose tissue gene expressions, lipid stores, and whole-body metabolism in our study can be attributed to the initial food restriction, circadian disturbances, and/or gorging eating pattern" (Kliewer. 2015).

And let's be honest, do you really think it's the meal skipping, not gorging at a (internal clock-wise) totally wrong time that made the mice fat? If so, you have probably been exposed to too much "frequent meal propaganda" in the past years.
References:

• Kliewer, Kara L., et al. "Short-term food restriction followed by controlled refeeding promotes gorging behavior, enhances fat deposition, and diminishes insulin sensitivity in mice." The Journal of nutritional biochemistry (2015).

Don't eat unless this brunette,... ah, I mean her clock tells you to eat. That's intermittent fasting (IF) - well, at least one out of at least three versions of eating by the clock people call "intermittent fasting". Needless to say that this doesn't make it much easier to decide if IF works or not.

It has been some time since I wrote about "Intermittent Fasting" ("lean gains"-style, i.e. eat in a 6h-8h window everyday), "Fasting" (don't eat at all) and "Alternate Day Fasting" (eat very little / usually ~800kcal one day / and normal the next one, repeat). Against that background it is worth devoting a whole waredownloadsoft Research Update to the latest studies and reviews of IF and ADF.

In the corresponding papers, Tinsley and La Bounty review the "effects of intermittent fasting on body composition and clinical health markers in humans", Varady et al. discuss "the determinants of weight loss success with alternate day fasting" and Seimon et al. address the question whether "intermittent diets provide physiological benefits over continuous diets for weight loss?", as part of a short report in form of a systematic review of clinical trials.

So, where do I start? I guess it would be best to build the article around the most extensive and for many of you probably most interesting analysis by Seimon et al. that's about to be published in one of the next issues of Molecular and Cellular Endocrinology: "Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials" (Seimon. 2015)
Usually I don't do this, but in view of the tons of articles I have already written about Intermittent Fasting, I feel like it is possible to start with the conclusion which says that "[i]ntermittent fasting thus represents a valid – albeit apparently not superior – option to continuous energy restriction for weight loss." Accordingly, the question I still owe you an answer to is "WHY?", i.e.: "What makes intermittent fasting 'a valid' weight loss strategy?", and "Why is it 'valid - albeit nor superior'?" Well, the answers to these questions are neither straight forward nor can they be answered objectively. As every review and/or meta-analysis, Seimon's paper ends with the researchers' subjective interpretation of selected, objective data. Data from a total of 40 publications involving humans of any age or body mass index that had undergone a diet involving intermittent energy restriction, 12 with direct comparison to continuous energy restriction. What all of these studies have in common is that they measured one or more of the following variables: Body weight, body mass index, or body composition before and at the end of energy restriction.

Table 1: The Aguin study is one out of many that shows that both intermittent and chronic energy restriction work and produce statistically (see p-values) identical changes in body composition, size and relevant markers of lipid and glucose metabolism (Arguin. 2012)

What they did not share, though, was the type of "Intermittent Fasting". Practically speaking, this means that 31 of the 40 publications "involved ‘intermittent fasting’ of 1-7-day periods of severe energy restriction" - were thus rather "fasting" or "alternate day fasting" than classic "intermittent fasting" studies. More specifically: Seimon et al. also included studies like Arguin et al. (2012) in which the subjects were either dieting for 15 weeks at a moderate energy restriction or for 3 cycles of 5 week at higher energy deficits were interspersed by 3 cycles of 5 weeks on a calorically sufficient diet and the results were compared after each intervention, as well as one year thereafter. These obviously more important parameters are summarized in Table 1, and they don't show any inter-group differences.
Now, while the Arguin study is not correctly summarized in the tabular overview of all studies they reviewed, the most important information, i.e. the fact that the cyclic diet does not provide any significant advantages or disadvatages over continuous dieting is true. Based on the meta-analysis by Seimon et al., the following take-home messages can be stated:

• The drop out rates were comparable for interventions involving intermittent energy restrictions (IER) and continuous energy restrictions (CER).
• Significant reductions in body weight, size (waist, hip, etc.) and adiposity can be achieved with both intermittent energy restrictions (IER) and continuous energy restrictions (CER).
• If we go by weight loss which happens to be the most frequently measured study outcome in Seimon's selection of studies, the results are comparable for IER and CER.

• Study suggests: Your goals may determine whether a low or high fat diet is the better basis for your alternate day fasting fat loss diet | more

  A reduced drive to eat, on the other hand, appears to be a unique advantage of intermittent energy restrictions, where eating very little for a fixed time period appeared to be easier to handle for the subjects then the grazing that's part of many CER interventions.
  
  This is an important results, after all, one of the mainstream arguments against intermittent or alternate day fasting is that they will trigger an overcompensation on the (re-)feeding day - a phenomenon that was not observed.
  
  On the contrary, "participants only consuming an average of 95% of their calculated energy needs on feed days" (Seimon. 2015). This is particularly noteworthy because "this apparent suppression of the drive to eat occurred despite decreased circulating levels of the appetite-reducing hormone, leptin, following IER" (Seimon. 2015). Whether this is related to an increase in ketone bodies in the IER studies that was non-existent or less pronounced in the CER trials will still have to be elucidated, though.
• A trend towards mood disturbance, tension, anger and confusion was observed in only one study. A study by Hussin et al. (2013) that was done in aging normal-weight men and the results of which stand in contrast to what Johnson et al. found in overweight subjects in 2007.
  

  Figure 1: Intermittent energy restrictions (IER) appear to be better suited for the obese, whose mood improves during th fast, while the mood of lean subjects decreases sign. (Hussin, 2013 & Johnson. 2007).

  In conjunction with the increased drop-out rates in Hussin's study, we may argue that a lack of triglyceride and FFA releasing adipose tissue may make IER interventions harder to adhere to - probably, because of a simple lack of available energy during the fast.

• So, "Intermittent Fasting Does Now Make You Fat"? Do the Facebook Posts Lie? Not Necessarily, but Many People Forget that IF Works Only if it Reduces Your Energy Intake | more

  In view of the sign. reductions in leptin in IER interventions it is hardly surprising that Seimon et al. didn't find convincing evidence that IER would ameliorate the reduction in resting metabolic rate that's an inevitable (temporary) side effect of any dieting regimen.
  
  One (de Groot. 1989) out of three studies that made a direct comparison between the two even found a further reduction in resting metabolic rate (RER) in the IER group, the others found no difference (Hill. 1989; Harvie. 2011; Arguin. 2012). Overall, it would yet appear as if any potentially existing difference was negligible.
  
  Other metabolic adaptations such as a reduced IGF1 production were observed only in trials where the subjects fasted with liquid meals (Kroeger. 2012).
• No difference and on average comparable improvements in glucose homeostasis were observed in the 20 studies that tested respective parameters in detail. While there are individual studies that suggest advantages for one or another method, the overall picture that emerges is that there are no systematic differences - a conclusion that would also explain the - in parts - contradictory results from pertinent studies.
• Lastly, it must not go unmentioned that the addition of exercise to IER will make it - just as it is the case for CER, by the way - more effective and will thus shed more fat (and maintain more lean mass) than IER alone.
  

  Figure 2: The combination of alternate day fasting and exercise reduces uncontrolled and emotional eating in 64 obese subjects over the course of a 12-week study (Bhutani. 2013).

  Somewhat surprising, but in view of the overall anti-appetite effect of fasting not impossible is that the combination of exercise with IER also reduced the subjects' craving for uncontrolled and emotional overeating (Bhutani. 2013).

In view of the fact that only 12 of the 40 publications included in Seimon's review directly compared IER with CER, it is yet important to remember that we are far from being able to tell who will benefit most and who least from "intermittent fasting" (in the broadest sense). If you review the above summary of the results, you will yet have to agree that it would appear as if men and women who still have a ton of weight to lose could fare better with intermittent or alternate day fasting, while lean individuals may, but don't necessarily have to struggle with the lack of readily available energy during the fast.

Figure 3: While race matters and Caucasians appear to do much better on alternate day fasting regimen, the baseline body weight (and BMI | not shown) doesn't make a difference in the 4 ADF trials Varady et al. reviewed (2015).

At least in the 8-week ADF studies Varady et al. reviewed in their previously mentioned short report in Obesity Research and Clinical Practice, however, the initial body weight was not a good predictor of weight loss success. Rather than that, "[s]ubjects aged 50—59 y achieved greater (P = 0.01) weight loss than other age groups" and "Caucasian subjects achieved greater (P = 0.03) weight loss than other races" (Varady. 2015) with the alternate day (ADF) version of "intermittent fasting".

With only 5 out of the 40 studies in Seimon's review having a follow-up and no follow-up in any of the ADF studies in the previously cited short report by Varady et al. (2015), the long-term benefits or detriments must be considered largely under-researched, at the moment, too.