Can an Alternate-Day High Fat Diet Turn You into a Fat Burning Machine (Boost Your Muscles' Oxidative Capacity)?

Can an Alternate-Day High Fat Diet Turn You into a Fat Burning Machine (Boost Your Muscles' Oxidative Capacity)?

alternate day fasting fasting fat burning fatty acid oxidation high fat

Whether the "alternate-day high fat diet" is in fact an alternative to "training low and competing high", which you can also tweak like this, appears questionable to me, but it is certainly interesting.

If you take a look at the contemporary "low carb"-hype, one of the often-heard arguments in favor of high(er) fat and low carbohydrate intakes is the notion that this would increase your cells' ability to bur fat... or, as some people phrase it: "A high fat diet will turn you into a fat burning machine!"

Believe it or not, this is not totally wrong. What is wrong, though, is that the increase in mitochondrial fatty acid oxidation capacity, which is an adaptive response to the lack of other energy sources, will translate into direct fat loss. Eventually, you will still only lose weight and body fat if you are in a caloric deficit: high carb, low carb or no carb - personal preferences and parameters may determine which one works best for you, but eventually both work.

Until further studies have been done, you better stick to real fasting?

Breakfast and Circadian Rhythm

Does Meal Timing Matter?

Habits Determine Effects of Fasting

Fasting Works - It Does, Right!?

Does the Break- Fast-Myth Break?

Breakfast? (Un?) Biased Review

But I am getting off an a tangent. The actual question in today's SuppVersity article is after all not, whether a high fat diet allows for easier, faster or more reliable fat loss than a balanced or high carb diet. No, the question for today's SuppVersity article is: "Can an Alternate Day High Fat Diet Provide Turn You into a Fat Burning Machine?"

A hilarious idea, right? Well, I would probably have said the same before I had read a recent study from the Waseda University in Japan (Li. 2016). In said study, Li et al. tried to elucidate whether they would be able to get the same improvements in mitochondrial enzyme activity and protein content others have observed in rodents on high fat diets without the concomitant long-term intra-abdominal fat accumulation, and ever-increasing insulin resistance, and obesity. Put simply, Li et al. wanted to know if a small tweak to the diet would be able to "induce increases in mitochondrial oxidative capacities in skeletal muscle without intra-abdominal fat accumulation and body weight gain," as it would "offer many advantages" to endurance athletes (Li. 2016). Their hypothesis was that

• feeding a high fat diet every other day would trigger the increase in free fatty acids (FFA) that's necessary to produce the desirable increases in mitochondrial capacity, while
• feeding a regular (low fat) diet on the other day would help to ameliorate (or even better block) the accumulation of intra-abdominal fat mass. 

Accordingly, the scientists conducted a study in which male wistar rats were fed an alternate-day high-fat diet, with a lard, corn oil, sucrose, and casein based HF diet (32%, 18%, 27%, and 23%, respectively, of total calories | 5.1 kcal/g) on one and standard rodent chow (59% carbohydrate, 12% fat, and 29% protein | 3.4 kcal/g) on the other day.

Figure 1: Visceral (epididymal) fat mass, plasma glucose, fatty acid and insulin levels and relative difference to control (above bars); mind the multiplicators that were necessary to plot all data in a single graph (Li. 2016).

As you can see in Figures 1 & 2 the scientists achieved their goal. The visceral fat gain was sign. ameliorated. In spite of identical body weights, the rodents who had been fat high fat diets on alternate days were yet still fatter than their peers on the control diet.

Figure 2: Levels of markers of mitochondrial oxidative capacity after the treatment period (Li. 2016).

To know whether this increase in visceral fat was worth it, one would need to know whether the increases in citric acid synthetase (CS), beta-HAD, PGC-1a and LCAD activity actually pay off in form of increased endurance and/or performance gains due to an increased oxidative capacity.

Figure 3: Effects of alternate‐day high‐fat diet feeding on glycogen concentration (A) and GLUT‐4 protein content (B) in rat skeletal muscle. Values are mean ± SEM of 6 animals per group // If we go by the effects on glycogen, GLUT-4 and insulin (see Figure 1), the ALT diet should not impair the use of CHOs in athletes and would thus allow for CHO fueling during competition, but that's, as much about ALT, in theory!

Bottom line: In view of unaltered glycogen levels and slightly, but non-significantly increased levels of glucose transporter 4 (GLUT-4 | see Figure 3) levels in the muscle tissue of the ALT rats, it is likely that these performance changes would have been observed, but Li et al. don't have the data to prove that they exist.

For the average endurance athlete of whom the scientists rightly write that he does not adopt a high fat diet, even though it may increase the mitochondrial enzyme activities and decrease the utilization of glycogen during endurance exercise, Li's study is thus of very limited value, because future studies are necessary to prove the practical efficacy and relevance of an "alternate-day high fat diet" that has been tested only in rodents and how it compares to "training low and competing high" (Burke. 2010) | Comment!

References:

• Burke LM. Fueling strategies to optimize performance: training high or training low? Scand J Med Sci Sports. 2010 Oct;20 Suppl 2:48-58. doi: 10.1111/j.1600-0838.2010.01185.x.
• Li X, Higashida K, Kawamura T, Higuchi M. Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle. Nutrients. 2016 Apr 6;8(4). pii: E203.

Ramadan Fasting Studies Showing Fat, but no Muscle Loss Support Benefits of 'Lean Gains'-Style Intermittent Fasting

Ramadan Fasting Studies Showing Fat, but no Muscle Loss Support Benefits of 'Lean Gains'-Style Intermittent Fasting

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Remember, Ramadan fasting is not about eating healthy or dieting, after sundown most Muslims consume at least as much energy as on a non-fasting day.

While scientists usually refer to alternate-day fasting as "intermittent fasting", the average fitness enthusiasts will think of Martin Berkhan's "lean gains" protocol, when he or she hears the words "intermittent fasting" - a protocol that involves fasting for minimally 16h and eating for maximally 8h and is thus somewhat similar to the "eat only after sundown" protocol Muslims follow during Ramadan.

Against that background, it makes sense to assume that the two dozen of peer-reviewed Ramadan fasting studies from the Middle East and the Muslim part of Asia provide an (albeit often uncontrolled) model for intermittent fasting.

Do you have to worry about fasting when your're dieting!?

Breakfast and Circadian Rhythm

Does Meal Timing Matter?

Habits Determine Effects of Fasting

Breaking the Fast & the Brain

Does the Break- Fast-Myth Break?

Breakfast? (Un?) Biased Review

If we assume that this premise is true, a recent study from the Dr. Cipto Mangunkusumo General Hospital at the Universitas Indonesia, provides intriguing insights into the lean mass conserving effects of "intermittent fasting".

The study aimed to evaluate the effect of Ramadan fasting on body composition in healthy Indonesian medical staff. To this ends, Ari Fahrial Syam et al. (2016) recorded the body composition of healthy medical staff  members of the Dr. Cipto Mangunkusumo General Hospital before, during and after Ramadan fasting in 2013 (August to October).

Figure 1: Changes in body composition during the 28-day Ramadan fast (Syam. 2016).

In conjunction with data on the energy intake of the forty-three subjects, the data the scientists gathered appear to confirm what the proponents and followers of the "lean gains" variety of intermittent fasting say: You will lose body fat, but not muscle and that without significant reductions in energy intake.

According to 24h food recalls, the subjects didn't change their energy intake during Ramadan. The fat loss can thus not be explained by the induction of a caloric deficit.

Yes, the body composition was assessed by BIA, but ... while body impedance analysis (BIA) may not the best method to assess the %fa and % lean mas of trained athletes, but has been shown to have a high accuracy and reliability in "normal" people. Similarly, the 24-hour food recalls that were used to evaluate the subjects' dietary intake are often a bit off, but that's the case for both pre- and post-assessments, which is why it is reasonable to assume that there was indeed no significant change in total energy intake. This doesn't change, though that it's a pity that the scientists don't provide information about individual nutrients intakes. Previous studies suggest increased protein intakes during Ramadan fasting (Frost. 1987; El Ati. 1995) - a potentially highly relevant increase, obviously.

One thing Syam's study adds to the table, however, is that (a) the weight you will lose is not just body fat, it's also a lot of water and even bone (see Figure 1) and that (b) your (fat) weight will bounce back, within 4-5 weeks when you return to your usual eating habits.

Table 1: Overview of pertinent research comparing the results of the study at hand to previous studies (Syam. 2016).

As the research overview in Table 1 shows, some, but not all of the (side) effects are actual news. Hossini et al. (2013), for example, didn't observe changes in mineral or water content. The initially highlighted lack of protein / muscle loss, on the other hand, was observed in all three studies in which the exact body composition was measured. It is thus not unreasonable to assume that this is a characteristic feature of pertinent "intermittent fasting" protocols.

Fears about fat gain are likewise unwarranted | learn more

Bottom line: Don't get all excited, even if the 24h food recall were accurate and the fat loss occurred in the absence of reductions in food intake, the fat loss was statistically significant, but with less than 500g practically negligible.

The more important message of the study at hand is thus that intermittent fasting doesn't trigger a loss of muscle mass - a fear that is still prevalent, especially in male members of the fitness community | Comment!

References:

• El Ati, Jalila, C. H. I. R. A. Z. Beji, and J. A. B. E. R. Danguir. "Increased fat oxidation during Ramadan fasting in healthy women: an adaptative mechanism for body-weight maintenance." The American journal of clinical nutrition 62.2 (1995): 302-307.
• Frost, G., and S. Pirani. "Meal frequency and nutritional intake during Ramadan: a pilot study." Human nutrition. Applied nutrition 41.1 (1987): 47-50.
• Hosseini, Seyyed Reza Attarzadeh, et al. "The effect of ramadan fasting and physical activity on body composition, serum osmolarity levels and some parameters of electrolytes in females." International Journal of Endocrinology and Metabolism 11.2 (2013): 88.
• Faris Mohammed Ahmed, et al. "Impact of Ramadan Intermittent Fasting on Oxidative Stress Measured by Urinary 15-F2t-Isoprostane." Journal of Nutrition and Metabolism 2012 (2012).
• Norouzy, A., et al. "Effect of fasting In Ramadan on body composition and nutritional intake: a prospective study." Journal of Human Nutrition and Dietetics 26.s1 (2013): 97-104.
• Sadiya, Amena, et al. "Effect of Ramadan fasting on metabolic markers, body composition, and dietary intake in Emiratis of Ajman (UAE) with metabolic syndrome." Diabetes, metabolic syndrome and obesity: targets and therapy 4 (2011): 409.
• Syam, Ari Fahrial, et al. "Ramadan Fasting Decreases Body Fat but Not Protein Mass." International Journal of Endocrinology and Metabolism 14.1 (2016).

Overeating = Natural Response to Strict Dieting That Occurs Despite Increased Satiety Hormone Response to XXL-Meal

Overeating = Natural Response to Strict Dieting That Occurs Despite Increased Satiety Hormone Response to XXL-Meal

fasting hunger lose fat satiety satiety hormones starvation

This is not a photo from the full-text of the study, but it could be. After all the energy deficient diet was >90% below the maintenance intakes of the subjects. That's unfortunately much more severe than the average dieter's approach, but some of the things the scientists observed still have very general applications.

If you've ever dieted to make the cut in a sports with weight classes, you will know this insatiable hunger which climaxes on the last two days when you are down to a handful of  calories per day. It's a hunger that won't be satisfied even if you eat an extra 1000 kcal above maintenance.

Athletes competing in sports with weight classes may need to accept the post-dieting binge, but what about average Joes and Janes? Will a fasting day ruin the average dieters dieting efforts by making them eat more extra-calories on day 2 than they've economized the day before? A recent study from the US Army Research Institute of Environmental Medicine, in which scientists have attempted to stimulate and simulate this insatiable hunger in a tightly controlled experimental environment, may hold the answer.

Do you have to worry about fasting when your're dieting!?

Breakfast and Circadian Rhythm

Does Meal Timing Matter?

Habits Determine Effects of Fasting

Fasting Works for Obese, Too!?

Does the Break- Fast-Myth Break?

Breakfast? (Un?) Biased Review

As Kristie L O'Connor et al. point out an altered secretion of appetite-mediating hormones is the #1 candidate to explain the common tendency for weight regain (Sumithran. 2013 | see Figure 1). This hypothesis is supported by several studies that have reported decreases in circulating leptin and insulin concentrations in response to weight loss that are disproportionately greater than contemporaneous reductions in fat mass (Mars. 2005; Blom. 2006; MacLean. 2006; Pasiakos. 2011; Sumithran. 2011). Other studies have documented blunted postprandial gastroenteropancreatic hormone responses after weight loss (Chan. 2004).

Figure 1: Selected pathways involved in body weight regulation (left) and tabular overview of physiological changes after diet-induced weight loss and their effect on energy intake and storage (right | Sumithran. 2013).

Scientists have speculated that these ill effects may be countered by eating diets with a low energy density and thus putting equivalent stress on the gastric mechanoreceptors in our guts. Unfortunately, this alone has turned out to be as ineffective as other attempts to minimize the adaptive response to energy restriction. On the other hand, the existing effects the volume of what we have will have on our satiety is something that has been overlooked in previous studies.

Figure 2: Study design. EB, energy balance; ED, energy deprivation; EE, energy expenditure; EI, energy intake; RMR, resting metabolic rate; TDEE, total daily energy expenditure; VAS, visual analogue scale (O'Connor. 2016).

Overall, our understanding of the complex relationship between what and how much we eat and how this affects our subjective satiety and corresponding hormone response is still very limited. To address this knowledge gap O'Conner et al. created 2 isovolumetric diets that differed in energy density but were otherwise comparable in taste, texture, and appearance that were fed to healthy young adults during a period of energy balance (EB) and a period of 90% energy deprivation (ED), in oder to "examine the physiologic effects of short-term ED on appetite-mediating hormones and appetite independent from reductions in diet volume" (O'Connor. 2016 | see Figure 2).

It is a common misunderstanding that you "must" lose your weight slowly: While most mainstream diet advise involves the recommendation that you shouldn't reduce your energy intake too significantly and that you must lose your weight slowly, the existing peer-reviewed experimental and observational evidence does not support the notion that (a) slow eight gain would support greater lean mass retention or (b) prevent weight regain. Learn why that's the case.

Figure 3: Overview of energy intake, deficits and macronutrient composition in the two study groups (O'Connor. 2016).

As the scientists had expected the energy deficit that was induced over two seperate 48-h periods during which the energy intake was matched to energy expenditure to maintain energy balance (EB) (-44 +/- 92 kcal/d) or yield less than 10% of the energy the subjects required (ED).

In conjunction with the low-to-medium intensity exercise regimen (0–65% VO2peak for 187 6 +/- 21 min/d) that burned an extra 1683 +/- 329 kcal/d, the ED group did thus end up having a whopping -3696 +/- 742-kcal/d deficit on each of the two days (!).

It is thus no wonder that the scientists observed a whole host of significant differences in the hormonal response to the "diet" (diet vs. fasting). One difference you probably know much better however, is depicted in Figure 4, which shows that the subjects in the ED group consumed not simply the amount of energy they needed on the subsequent ad-libitum meal condition, but an extra 811 kcal - and they still felt a significantly greater desire to eat right after and 180 minutes after the meal.

Figure 4: Energy intake on an ad-libitum (eat as much as you want) meal before and after the intervention (left)
and the corresponding desire to eat before and after the meal (right); the dotted line at 20 min in the right graph
indicates the time at which the ad-libitum meal was served (O'Connor. 2016).

Unfortunately, the complexity of the hormonal changes does not allow us to identify this one parameter we could target to counter this effect. With significantly reduced fasting insulin (256% 6 42%) and acyl ghrelin (260% 6 17%) concentrations, as well as leptin concentrations that decreased more during ED compared with EB (-47% 6 +/- 27% compared with -20% +/- 27%; P-interaction = 0.05), we have two three (expected) candidates that could explain the increased hunger and desire to eat before the ad-libitum meal. The increased postprandial insulin (57% +/- 63%; P < 0.001), GLP-1 (14% 6 28%; P = 0.04), and PP (54% +/- 52%; P < 0.001) areas under the curve (AUCs), as well as the reduced acyl ghrelin increase (-56% +/- 13%; P < 0.001) after ED compared with after EB, on the other hand, appear to contradict the lack of satiating effect of the 1834 kcal lunch in the 18–39 year-old healthy men and nonpregnant women who participated in the study at hand.

Intermittent Fasting Works, But is It Better Than "Regular" Dieting? What Do the Latest Reviews / Meta-Analyses Say? Find out in this SuppVersity Classic!

So what can be done? Well, the increase in appetite and desire to eat is probably a generally unavoidable effect of "starvation diets" and since this is what the study at hand focuses on, it is difficult to predict how pronounced the effect would have been if the ~3500kcal energy deficit, the subjects in the study at hand reached within just one day, would have been induced over the course of 3-5 days. A dieting approach like that would after all been much closer to what the average dieter does over the course of 3-5 days only to then overeat and fall off the wagon on the weekend. In addition, a lower calorie deficit may have (a) made it easier to identify what exactly it is that causes the rebound effect and may (b) have been insufficient to compensate for the binge.

This leads us directly to the most important result of the study at hand: As suboptimal as the diet may be, one significant and probably mostly underappreciated result of the study at hand is that - once again - the energy deficit you accumulate during a quasi-fast was not fully compensated for over the 36h follow up period. A fact that adds to the existing evidence in favor of cyclic diets as every-other-day fasting, where you cycle hunger and ad-libitum diet days | Comment!

References:

• Blom, Wendy AM, et al. "Fasting Ghrelin Does Not Predict Food Intake after Short‐term Energy Restriction." Obesity 14.5 (2006): 838-846.
• Chan, Jean L., et al. "Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects." The Journal of Clinical Endocrinology & Metabolism 89.1 (2004): 335-343.
• Egecioglu, Emil, et al. "PRECLINICAL STUDY: FULL ARTICLE: Ghrelin increases intake of rewarding food in rodents." Addiction biology 15.3 (2010): 304-311.
• MacLean, Paul S., et al. "Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290.6 (2006): R1577-R1588.
• Mars, Monica, et al. "Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake." The American journal of clinical nutrition 81.3 (2005): 570-577.
• O'Connor, et al. "Altered Appetite-Mediating Hormone Concentrations Precede Compensatory Overeating After Severe, Short-Term Energy Deprivation in Healthy Adults." Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions (2016).
• Pasiakos, Stefan M., et al. "Appetite and Endocrine Regulators of Energy Balance After 2 Days of Energy Restriction: Insulin, Leptin, Ghrelin, and DHEA‐S." Obesity 19.6 (2011): 1124-1130.
• Sumithran, Priya, et al. "Long-term persistence of hormonal adaptations to weight loss." New England Journal of Medicine 365.17 (2011): 1597-1604.
• Sumithran, Priya, and Joseph Proietto. "The defence of body weight: a physiological basis for weight regain after weight loss." Clinical Science 124.4 (2013): 231-241.

Alternate Day Fasting (ADF) Cuts 50% Body Fat and Boosts Lean Mass by 12-13% - In Fat Rodents on Low Fat ADF Diet

Alternate Day Fasting (ADF) Cuts 50% Body Fat and Boosts Lean Mass by 12-13% - In Fat Rodents on Low Fat ADF Diet

alternate day fasting fasting high fat IF intermittent fasting lose fat low fat

When you're alternate day fasting your plate will look as empty or almost as empty as this every other day.

In the scientific literature, the term "intermittent fasting" is used inconsistently. Often, however, it refers to an every-other-day-fasting-regimen, in which you eat on day A and don't eat (or eat almost nothing) on day B. This was also the case of Juliet D. Gotthardt's latest study, where "intermittent fasting" therefore meant eating an ad-libitum diet (eat as much as you want and when you want) on day 1 and starving on day 2 (Gotthardt. 2015). What the scientists from the State University of New Jersey already knew was that this would protect male C57BL/6 from weight gain, what they didn't know and wanted to find out was whether the macronutrient content of the diet would modulate this effect..

Do you have to worry about muscle loss and metabolic damage, when you're fasting?

Breakfast and Circadian Rhythm

Does Meal Timing Matter?

Habits Determine Effects of Fasting

Fasting Works - It Does, Right!?

Does the Break- Fast-Myth Break?

Breakfast? (Un?) Biased Review

Accordingly, 64 mice were purchased from The Jack son Laboratory (Bar Harbor, ME, USA) and fattened up on an ad libitum, high fat diet (HFD; 4.73 kcal/g, 45% fat, 20% protein, 35% carbohydrate; D12451) for 8 weeks (note: this means all mice were already overweight, when the actual "intermittent fasting" began).

Figure 1: Energy content (kcal/100g) of the high and low fat diets the rodents were fed over the course of the 4-week experimental phase either ad-libitum or on an every-other-day-fasting regimen (Gotthardt. 2015).

The mice were then equally divided by bodyweight and transitioned to one of four experimental groups:

• HFD - an ad libitum high fat diet 
• IMF-HFD - an every-other-day fasting high fat diet
• LFD - ad libitum low fat diet
• IMF-LFD - an every-other-day fasting low fat diet

The mice in the IMF group were food deprived every other 24-hour period beginning at 9:00 AM (fasting day), 2 hours into the light cycle. On fasting days, all animals were weighed, food in take was recorded, cages were changed.

The alternative-day fasting induced a sign. reduction in food intake.

What's the mechanism, here? As the food intake data on the left shows, the effect is at least partly mediated by a significant reduction in food intake. In other words, just as it has been observed in humans, there's no full compensation for the lack of energy intake on the fasting day. This is intriguing, because the increase in norepinephrine (NE | 50-60%) in the hypothalamus and the expression of NPY in the arcuate nucleus ( 65–75%) in both IMF groups would suggest that the rodents were not immune to the regular compensatory stress response to fasting.

After four weeks, the mice on the IMF-HFD ( 13%) and IMF-LFD ( 18%) had significantly lower body weights than those who continued on the HFD.

Figure 2: Body composition as assessed by EchoMRI in all groups at the end of 4 weeks of the diet intervention. Data are represented as means SEM. A: Fat mass (g). B: Lean body mass (g). *** indicates difference from HFD (P .001); * indicates difference (P < .05) from HFD; $ indicates difference (P < .05) from IMF-HFD (Gotthardt. 2015).

As you can see in Figure 2, the body fat of the mice was also significantly reduced - in all four groups by 40–52%. The significant lean mass increases I hinted at in the headline, however, were observed only in the intermediate fasting low fat diet group (IMF-LFD | 12–13%).

Figure 3: Oral glucose tolerance tests in all groups at the end of 4 weeks of the diet intervention. Data are represented as means SEM. A: Blood glucose (mg/dl) response to an oral bolus of glucose (2 g/kg) over 180 minutes. Values for IMF-HFD and LFD overlap. B: Area under the curve (AUC) of glucose tolerance test (Gotthardt. 2015).

As Figure 3 goes to show you, the low fat alternative-day fasting (IMF-LFD) group also had the highest oral glucose tolerance with almost no increase in glucose during the glucose tolerance test. Whether that's due to the increase in lean mass is yet as questionable due to the mere extent of the reduction in glucose AUC. If the latter was simply due to an increase in muscle mass, you'd furthermore expect that the insulin levels of the IMF-LFD rats would have been lower as well. Insulin, as well as leptin, however, decreased to a similar extent in all treatment groups (compared to the high fat diet, obviously).

Figure 4: Cause and consequences of the low-fat exclusive increase in dopamine (DA) in the anterior hypo-thalamus of the fasted rodents are two things researchers don't yet fully understand (Gotthardt. 2015).

What do we make of this study? While I have to admit that the headline suggests that the lean mass increase was a result of the reduced fat intake, a hypothesis that would explain why there should be a mechanistic link between alternate-day-fasting, low fat dieting and increases in lean mass is not in sight. That's disappointing, but with the low-fat exclusive significant increase in anterior hypothalamus dopamine expression (see Figure 4) and the previously mentioned extreme increase in glucose sensitivity (cf. Figure 3), Gotthardt's study provides starting points for future research and it confirms that alternate day fasting does not cost you muscle mass... in this respect previous human trials showed similar results, by the way.

One thing you have to keep in mind is that the high fat diet (HFD) in the study at hand was after high in fat, but it was not low in carbohydrates. Accordingly, it would be really interesting to see, how a true low-carb diet would have affected rodents - and obviously humans, of whom a 2013 human study by Klempel et al. that used a similarly messed up "high fat diet" (45% fat, 40% carbs, 15% protein) shows that they lose the same amount of weight and body fat on "high" and "low fat" diets. Whether that's a species-dependent difference to the study at hand or a result of "too much fat" in Klempel's diet (25% fat is significantly more than in the Gotthardt study) will yet have to be determined in future studies; studies that will hopefully also use an actual high fat alternate-day-fasting regimen instead of the the high fat + high carb Western diet clone that was used in both, the study at hand, and the previously cited human study by Klempel et al. | Comment!

References:

• Gotthardt, Juliet D., et al. "Intermittent Fasting Promotes Fat Loss with Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice." Endocrinology (2015): en-2015.
• Klempel, Monica C., Cynthia M. Kroeger, and Krista A. Varady. "Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet." Metabolism 62.1 (2013): 137-143.