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

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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..

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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.

True or False? 'Low Fat' for the Lean, 'Low Carb' for the Obese and Insulin Resistant - Pilot Study Confirms Often Heard Dieting Advise on a Surface Level , However, ...

True or False? 'Low Fat' for the Lean, 'Low Carb' for the Obese and Insulin Resistant - Pilot Study Confirms Often Heard Dieting Advise on a Surface Level , However, ...

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Low carb, or fat? Left or right?  Which one should you chose and why? Shall you go by your body weight, your insulin sensitivity or your personal food preferences?

"Low Fat for the Lean, Low Carb for the Obese and Insulin Resistant," this quote from the headline sounds like a reasonable advise if you look at the existing evidence on low carbohydrate dieting, which appears to excel whenever the subjects are significantly overweight and insulin resistant. Studies that would do a head-to-head comparison of the two to confirm the accuracy of the hypothesis that "because they are insulin resistant, avoiding carbohydrates will aid people with (pre-)diabetes in losing weight" are non-existent... well, I should probably say they "were" nonexistent; a recent pilot study by Gardner et al does after all just that: compare the weight loss response of insulin sensitive vs. resistant individuals who consume either a low fat or a low carbohydrate diet over 6 months.

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The results of Gardner's study have recently been published ahead of print in the venerable scientific journal  Obesity; and they are... interesting, but as it was to be expected for a pilot study with "only" 61 participants in four groups, more research will be needed to make definite conclusions.

Figure 1: Weight loss (kg) after 6 months on the respective in insulin resistant and sensitive subjects (Gardner. 2015).

If you look at the main study outcome, i.e. the weight loss in Figure 1, for example, it would appear as if the previously cited statement from the headline of today's SuppVersity article was confirmed. Due to the large intra-group (=between individuals in one group) differences in all four diet groups (see error bars in Figure 1, they are about as long as the mean difference, we may speak of a trend or a tendency, that appears to confirm the previously stated hypothesis that an insulin resistant individual is better off avoiding carbs when dieting while an insulin sensitive one should stick to the mainstream low-fat recommendations (remember all subjects were overweight, none of the was athletic).

Figure 2: Proportions of carbohydrates, fats, and proteins for each diet at baseline, 3 months, and 6 months (Gardner. 2015).

This wouldn't be a SuppVersity article, though, if a brief glimpse at the main result was everything it had to offer. Let's first take a look at the reported energy- and macronutrient intakes (Figure 2) of the healthy, premenopausal women and men (age 18-50) with stable (>2 months) BMIs and an age between 28 years and 40 years (aside from the increased number of subjects with metabolic syndrome in the insulin resistant group, there were no noteworthy inter-group differences at baseline).

Limbo-Titrate-Quality: The dietary strategy that was used is quite interesting and actually something worth copying for yourself or your clients. There was the "Limbo" phase where the fat or carb intake had to be cut back drastically to 20 g/day of total fat or digestible carbohydrates. The goal of this phase was, as the scientists point out "to achieve the lowest level of fat or carbohydrate intake within the first 8 weeks" (Gardner. 2015). In the second stage, the scientists labeled as the "Titrate" phase the subjects slowly added fat or carbohydrate back to their diet - in increments of 5 g/day (e.g., from 20 to 25 g/day). With each increase, the intake had to be maintained stable for at least 1, maximally 5 weeks before adding another 5 g/day. The (good) idea was to allow each of the participants (in what the researchers call stage 3 of the intervention, although 2 + 3 appear to depend on each other) to find his or her specific level of fat or carbohydrate intake he / sheh "could be maintained long term, potentially for the rest of their lives" (ibid). The fourth and last stage eventually focused on diet quality. In the "Quality" phase the subjects had to maximize the nutrient density of their foods by selecting whole foods, buying organic, grass-fed, etc.

As you can see significant inter-group differences were observed only for the macronutrient composition; and even though these differences were significant, we are nor talking about a ketogenic vs. no-fat diet. Rather than that, both diets had a relatively balanced macronutrient profile, albeit with different main energy sources (carbs vs. fat). What did not differ for the groups, though was the total energy intake (Figure 2). This is interesting, because, in theory, the subjects were allowed ot eat as much as they wanted; and still, the data in Figure 2 tells you that they restricted their energy intake by noteworthy 30% on average (the ~600kcal-deficit also explains why the subjects even lost weight), with no difference between the subjects on the allegedly more satiating low carb vs. low fat diet.

Figure 3: Fiber, added sugar and saturated fat intake in g/1000kcal (Gardner. 2015).

Visible differences existed, obviously, for the intake of fiber, added sugars and saturated fats (Figure 3). These differences, which are characteristic of low fat vs. low carb diets, may also be the reason a recent study by Mansoor et al. (see red box below) found differences in the effects on triglycerides (increases with high CHO and even more so sugar intake), HDL and LDL (both increase w/ high saturated fat intakes) when they compiled the results of the contemporary low fat vs. low carb trials.

So, what's healthier, then? Low carb or low fat? To answer this question, researchers from the University of Oslo have recently conducted a meta-analysis that yielded quite interesting results, when the individual findings from the studies were pooled as weighted mean difference (WMD) using a random effect model: Compared with participants on LF diets, participants on LC diets experienced a greater reduction in body weight (WMD –2·17 kg; 95 % CI –3·36, –0·99) and triglicerides (WMD –0·26 mmol/l; 95 % CI –0·37, –0·15), as well as a greater increase in HDL-cholesterol (WMD 0·14 mmol/l; 95 % CI 0·09, 0·19) - that's good. Unfortunately, they also saw signficant increases in LDL-cholesterol. With 0·16 mmol/l, the mean difference in LDL was larger than the mean HDL increase, which could suggest an increase in CVD risk and has the authors conclude that their "findings suggest that the beneficial changes of LC diets must be weighed against the possible detrimental effects of increased LDL-cholesterol" (Mansoor. 2015). Personally, I would say, though, that for the mostly obese subjects in the studies, the weight loss and reduction in triglycerides (likewise a marker of CVD risk) are more important than the increase in LDL-C - future studies should try to elucidate if the particle size and LDL oxidation worsened as well and what the actual long-term (years, not months) effects are.

It is thus no wonder that the data from  blood analysis of the study at hand (Figure 4) mirrors the results of the studies Mansoor et al. (2015) analyzed for their meta-analysis that is about to be published in the British Journal of Nutrition (see red box):

Figure 4: Changes in LDL-C, HDL-C, Trigs and fasting glucose after 3 & 6 months (Gardner. 2015).

With the most significant differences being observed for triglycerides and LDL, the situation is very similar to the one the Mansoor et al. describe in their review. In this regard, it is also worth mentioning that the differences between the groups were reduced, when the subjects started to increase their fat or carbohydrate intake by 5g on a 1-4 week basis to eventually end up at their individual "that's how I could eat for the rest of my life"-level (compare the 3 months with the 6 months data).

This doesn't solve the dilemma we're in, though: without further data on particle sizes and oxidative status of the LDL molecules, etc. it is virtually impossible to make a reliable prediction which of the two diets is going to have the higher long-term health benefits. What may be even more important, though, is that we must not forget that it is not debatable that both diets triggered significant weight loss and measurable health improvements, especially in the subjects with pre-existing insulin resistance (blue and orange bars in Figure 4).

Figure 5: Changes in the prevalence of metabolic syndrome after 3 and 6 months (Gardner. 2015).

Bottom Line: So, it doesn't matter how you diet as long as you diet? Well, as previously pointed out, the absolute weight-loss values in Figure 1 appear to confirm the hypothesis that "low carb" is for the sick, while "low fat" for the healthy overweight individuals.

The significant intra-group differences, however, tell us that whether you are or aren't insulin resistant is not the only determinant of your response to the different diets. Especially for healthy individuals experimentation and finding what suits you, your lifestyle and sports best does therefore still appear to be the way to go.

In those with pre-existing metabolic syndrome (which is more than just insulin resistance, by the way), the generally higher relative reduction in MetSyn prevalence Gardner et al. observed in their study (Figure 5) do yet appear to confirm the general trend towards low-carbohydrate diets for people with serious metabolic issue; and maybe that's actually the main take-home message of a study that must be seen as a first attempt to identify one of the variables that determine whether an individual thrives on a low carb, a low fat or maybe just a completely balanced diet | Comment!

References:

• Gardner, et al. "Weight Loss on Low-Fat vs. Low-Carbohydrate Diets by Insulin Resistance Status Among Overweight Adults and Adults with Obesity: A Randomized Pilot Trial" Obesity (2015): Ahead of print.
• Mansoor, et al. "Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials." British Journal of Nutrition (2015): First view article.