True or False? Losing Your Weight Slowly Will Yield Better (Long-Term) Results Than Rapid Weight Loss - Another Common Weight Loss Myth Debunked by Science?!

With adequ. protein and nutrients "crash"- beats "low and steady" -dieting. In the obese that's almost certain, in athletes more experimental evidence are needed.

You will have heard and read that rapid weight loss will make you lose muscle and set you up for weight regain aka the "Yo-Yo effect". As a SuppVersity reader, you know that things are not as simple as that. While some studies appear to support this urban myth others suggest that the exact opposite may be the case.

A 2014 study by Purcell, Sumithran, and Prendergast that was published in the venerable scientific journal The Lancet for example, showed that rapid weight loss on a very low calorie diet leads to better long-term outcomes than gradual weight loss on a much less restricted diet.

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That's a results of which I feel that it is important enough to re-address ii in its own SuppVersity article. After all, the "slow and steady" advise is still ubiquitous, both in the mainstream and in the health and fitness community. In said study, Purcell et al.

"aimed to investigate whether the rate of weight loss affects the rate of regain, and whether weight lossinduced changes in circulating appetite-mediating hormones and subjective appetite are affected by the rate of weight loss" (Purcell. 2012).

To this end, the researchers from the University of Melbourne conducted a two-phase, non-masked, randomized controlled trial. The study participants were recruited through radio and newspaper advertisements and word of mouth in Melbourne, Australia.

• Inclusion criteria were healthy men and women aged between 18–70 years who were weight stable for 3 months and had a BMI between 30.0–45.0kg/m². 
• Exclusion criteria included use of a very low energy diet or weight loss drugs in the previous 3 months, contraceptive use, pregnancy or lactation, smoking, current use of drugs known to affect body weight, previous weight loss surgery, and the presence of clinically significant disease (including diabetes).

Eligible participants were randomized into 2 different weight loss programs — a 12-week rapid program or a 36-week gradual program —using a computer-generated randomization sequence with a block design to account for the potential confounding factors of age, sex, and body mass index (BMI). Investigators and laboratory staff were blind to the group assignments.

Figure 1: Overview of the study design (Purcell. 2014)

Both, the subjects on the rapid and the gradual weight loss program had the same simple goal: "Reduce your body weight by at least 12.5%." The way the subjects were supposed to achieve this weight loss was yet completely different. For phase 1 of the study (until 12.5% weight loss), the following interventions were prescribed:

• 

  Better ZERO than Some Food? Study Suggest Just That! Learn more.

  Rapid weight loss: Participants in the rapid weight loss group replaced 3 meals a day with a commercially available meal replacement (Optifast, Nestlé Nutrition) over a period of 12 weeks (450–800 kcal/day). 
• Gradual weight loss: Participants in the gradual group replaced 1 to 2 meals daily with the same supplements and followed a diet program based on recommendations from the Australian Guide to Healthy Eating for the other meals over a period of 36 weeks (400–500 kcal deficit per day).

Both groups were given comparable dietary education materials and had appointments every 2 weeks with the same dietician. Participants who achieved 12.5% or greater weight loss were eligible for phase 2. In phase 2, participants met with their same dietician at weeks 4 and 12, and then every 12 weeks until week 144. During appointments, the dietician assessed adherence based on participants' self-reported food intake, and participants were encouraged to partake in 30 minutes of physical activity of mild to moderate intensity. Participants who gained weight were told to reduce their energy intake by 400–500 kcal in order to get back on the weight loss track.

High(er) protein intake (1.2-1.4g/kg) are a way to make very low calorie diets, here fasting vs. protein modified fasting, more effective (Iselin. 1982).

Wait, but what about all the other studies? Well, in their research review, Purcell et al. "found no randomised clinical trials" which even investigated the difference. Practically speaking, this means that the general consensus which is that weight loss should happen gradually and at a rate of 0.5 kg per week is more or less arbitrary (from a science perspective). If you look more closely, though, you will find acute weight loss studies without appropriate follow up you could use as evidence in favor of dieting down slowly - mostly for decreased muscle loss in low (=RDA) protein diet scenarios, though. With adequate protein intakes, said studies yielded very different results - e.g. protein-modified fasts (see Figure | Bistrian. 1977; Iselin. 1982).

To assess the success of the diets, the scientists used the mean weight loss that was maintained at week 144 of phase 2 (primary outcome), the mean difference in fasting ghrelin and leptin concentrations measured at baseline, end of phase 1 (week 12 for rapid and week 36 for gradual), and at weeks 48 and 144 of phase 2, as well as the overall changes in weight, BMI, waist and hip circumferences, fat mass, fat free mass, ghrelin, leptin, and physical activity (secondary outcomes).

Figure 2: Percent of participants achieving the weight loss target in phase 1 completers (left) and all subjects including the losers who didn't complete the full study - that the right figure shows even greater differences actually supports the superiority of the rapid vs. gradual weight loss regimen (p = 0.0001 | Purcell. 2015)

The overall message of the results was clear, the "rate of weight loss does not affect the proportion of weight regained within 144 weeks" (Purcell. 2014). The same goes for the implication that "[t]hese findings are not consistent with present dietary guidelines which recommend gradual over rapid weight loss, based on the belief that rapid weight loss is more quickly regained" (ibid).

Figure 3: Relative changes in measures body composition (left) and activity from pre- to follow up (Purcell. 2015).

But this wouldn't be the SuppVersity if we didn't go beyond the mere averages for the main study outcomes. So, let's take a look at the actual changes from the pretest to the follow up in Figure 3. What do you see? Yes, the rapid weight loss group had better (albeit not significantly better) results in everything and that despite the fact that they didn't increase their physical activity (see Figure 2, right). So let's not forget that this information that's missing from the abstract, when we're discussing the "bottom line" to this article in the following paragraphs.

So, fast and furious (weight loss) is always the better choice? I would not necessarily say so, but as Martin et al. point out in a comment on Purcell's study we cannot simply ignore that (a) fewer participants dropped out early in the rapid weight loss group than in the gradual weight loss group, and that (b) during phase 1, more participants in the rapid weight loss group achieved the target weight loss of 12.5% than in the gradual weight loss group (81% vs 62%).

It would be stupid to blindly stick to the mantra that "slow and steady is always better" if evidence from well-designed clinical human trials says the opposite. Specifically, if we also take into account that ...

• 

  Nacker's re-analysis of the TOURS study shows similar results. Subjects who lost weight fasted had the best short+long-term results.

  the subjects who had far less time to achieve the same energy deficit, showed no evidence of relative increases in the adaptational processes like higher levels of the hunger or the "hunger hormone" ghrelin, which are believed to hinder long-term weight loss success
• despite the fact that both groups regained a similar amount of weight, the subjects in the rapid weight loss group, who used a very low calorie diet in phase 1, still had better outcome in both, the short and long run (n.s. difference), compared with those in the gradual weight loss group, who used a moderate caloric deficit.

There's thus no reason to question Purcell's conclusion that very low calorie diets can encourage adherence, weight loss, and retention. In that, it is interesting to point out that...

• very low calorie diets restrict food variety which can actually promote greater satiety and less food intake compared with diets that have more food variety (Rolls. 1984), and
• very low calorie diets are not complex to follow, have simple rules, limit choice,  and essentially eliminate the need for participants to measure or estimate portion size, an endeavour associated with error (Martin. 2007)

In addition, the rapid weight loss success on very low calorie diets is, as Martin et al. rightly point out, "presumably intrinsically rewarding and builds self-efficacy because behaviour change is proximally associated with a large and meaningful reward" (Martin. 2014).

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

If the known and manageable downsides, which are a potential lack of adequate protein and essential micronutrients, or constipation are taken care of and the length and frequency of the interventions is reasonable (e.g. 8-12 weeks depending of the amount of superfluous body fat with 4-6 weeks breaks between cycles), there's no reason to doubt that rapid weight loss on adequately designed very low calorie diets will yield better results than the "slow and steady" approach in the obese. Evidence from studies in athletes is mixed: On the one hand, there are profound detriments from longterm-deficits and no harm from appropriately planned short-term severe calorie restriction. On the other hand there are potential performance decrements (Mero. 2010) without negative effects on body composition and a single study suggesting that deficits of only 9kcal/kg (vs. 15kcal/kg) may allow for muscle gains even while dieting (Garthe. 2011) and thus be superior to taking the "fast track".

So, while it appears quite clear that obese individuals can benefit from losing weight rapidly, there's a paucicity of evidence for athletes and very lean individuals... but even if we had these study, this wouldn't change that what's optimal for you will depend so much on your personal preferences, your lifestyle, your sport, your current body fat levels etc. that there's no general one-size-fits-it-all recommendation. What's important, though, is not to get stuck in the "ONLY SLOW AND STEADY WILL WORK" mantra. Especially if you're not ripped (yet) doing the exact opposite and doing it cyclically may be the better choice | Comment on Facebook!!

References:

• Bistrian, B. R., and Mindy Sherman. "Results of the treatment of obesity with a protein-sparing modified fast." International journal of obesity 2.2 (1977): 143-148.
• Garthe, Ina, et al. "Effect of two different weight-loss rates on body composition and strength and power-related performance in elite athletes." International journal of sport nutrition and exercise metabolism 21 (2011): 97-104.
• Iselin, Hans U., and Peter Burckhardt. "Balanced hypocaloric diet versus protein-sparing modified fast in the treatment of obesity: a comparative study." International journal of obesity (1982).
• Martin, Corby K., et al. "Empirical evaluation of the ability to learn a calorie counting system and estimate portion size and food intake." British Journal of Nutrition 98.2 (2007): 439-444.
• Martin, Corby K., and Kishore M. Gadde. "Weight loss: slow and steady does not win the race." The Lancet Diabetes & Endocrinology 2.12 (2014): 927-928.
• Mero, Antti A., et al. "Moderate energy restriction with high protein diet results in healthier outcome in women." J Int Soc Sports Nutr 7.4 (2010): 1-11.
• Nackers, Lisa M., Kathryn M. Ross, and Michael G. Perri. "The association between rate of initial weight loss and long-term success in obesity treatment: does slow and steady win the race?." International journal of behavioral medicine 17.3 (2010): 161-167.
• Purcell, Katrina, et al. "The effect of rate of weight loss on long-term weight management: a randomised controlled trial." The Lancet Diabetes & Endocrinology 2.12 (2014): 954-962.
• Rolls, Barbara J., P. M. Van Duijvenvoorde, and Edmund T. Rolls. "Pleasantness changes and food intake in a varied four-course meal." Appetite 5.4 (1984): 337-348.

Metabolic Effects of Total Fasting Suggest: You Better Eat "Nothing" Than "Some" If You Want to Make Weight - The Metabolic Adaptation to Dieting is Yet Not All That Counts

It is hard and it will cost you muscle, but dieting as in simply eating nothing for a few days won't kill your metabolism and it will shed a lot of weight (assuming you're as obese as the subjects in a new study).

Common sense dictates: The more you reduce your energy intake, the more your resting and total energy expenditure will decline. That's a normal adaptational process, right? Right, at least in the short run, however, the equation isn't that easy.

Scientists from the from the Newcastle University just published the results of an interesting experiment, in which they aimed to investigate whether three groups of obese men, exposed to different levels of negative energy balance (fasting, very low calorie diet (VLCD, 2.5MJ/day) and low-calorie diet (LCD, 5.2MJ/day)) in experimental controlled conditions, were characterised by distinct changes in resting and total EE after losing a similar amount of body weight (5% and 10%WL).

As the scientists point out, "[t]he study also provided the opportunity to test if the rate of WL and weight lost as FFM [fat free mass] were associated with the level of adaptive thermogenesis" (Siervo. 2015). The significance of the results for athletes and wanna-be athletes should thus be obvious.

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To collect the necessary data, the scientists recruited 18 obese men who were randomly assigned to one out of three groups. Group 1 did a total fast for 6 days (=no food!). Group 2 was meant to achieve a 5% weight loss in 3 weeks on a very low calorie diet containing only 2.5MJ/day (that's only 597.51kcal/day). Group 3 had an "easier" (?) job, as they were meant to lose 10% of their body weight in six weeks during which they consumed a low calorie diet containing 5.2MJ/day (that's 1 242.83 kcal/day).

Figure 1: Macronutrient intake in grams in the 3 diet groups (Siervo. 2015)

"[D]uring the 6-day baseline period subjects consumed a fixed maintenance diet (13% protein, 30% fat and 57% carbohydrate). After the 7-day baseline period, each group followed the specific diet to lose 5% and 10% of their baseline body weight. However, the duration of the fasting was of 6 days as ethical constraint allowed to fast subjects to lose 5% of their baseline body weight. The duration of the WL phases to achieve a 10%WL was of 3 and 6 weeks for the VLCD and LCD groups, respectively. Throughout the study, participants were residential in the Human Nutrition Unit at the Rowett Institute of Nutrition and Health (RINH), Aberdeen, UK.

All food and drinks consumed by each participant during the study were supplied by the dietetics staff in the Unit. The participants were requested not to undertake any other strenuous physical activity during the study and they were asked to record their individual exercise sessions" (Siervo. 2015).

The actual energy intake (EI) of the subjects was measured daily. While the participants in the starvation group had access to water only, the diets of the other groups contained 32% of the energy as protein, 35% as carbohydrate and 33% as fat. More specifically,

• the LCD weighed 1260g, with an energy content of 5.2kJ/g coming from protein 50.3g (17%), carbohydrate 155.7g (50%), and fat 45.4g (33%), while
• the VLCD weighed 642g, with an energy concent of 2.55kJ/g coming from protein 49.4g (32%), carbohydrate 52.8g (35%), and fat 23.1g (33%) and was thus - in science terms - a high "protein diet", because it contained >30% of the energy from protein.

The resting energy expenditure (REE) was measured at baseline and at the end of each WL phase (5% and 10%WL) by indirect calorimetry over 30–40 min using a ventilated hood system (Deltatrac II, MBM-200, Datex Instrumentarium Corporation, Finland).

Figure 2: Changes in body composition in the three diet groups according to weight loss (Siervo. 2015).

If we take a look at the changes in body composition in Figure 1, we'll see that the Weight loss in the fasting group was 6.0 kg over 6 days. The VLCD group, who dieted far longer, lost 5.2 and 9.2kg over 11 and 21 days and the LCD group lost 7.2 and 12.6 kg over 21 and 42 days, respectively. Thus, the "[m]ean rates of WL during the 5% WL period were different between the fasting (-1.01 kg/d), VLCD (-0.52 kg/d) and LCD (-0.35 kg/d) groups" (Siervo. 2015).

Women watch out! It is not just possible, but in view of the association between the magnitude of daily energy deficit and the frequency of menstrual disturbances (Williams. 2015), women may see significantly more more side effects on harsh (fasting) diets.

What is far more important, though, is the fact that the allegedly "sanest" way of dieting, i.e. the LCD (=moderate deficit), produced the most significant fat mass loss. Accordingly, the "slow" diet had the upperhand in terms of fat free mass (FFM) losses, as well:

"The fraction of FFM to total WL after 5%WL was 46, 30 and 18% for the fasting, VLCD and LCD groups respectively. At 10% WL, the VLCD losses were 20% FFM and 80% FM compared with 9% FFM and 91% FM in the LCD group (Siervo. 2015).

Against that background it's quite surprising that (a) the VLCD and LCD showed a similar degree of metabolic adaptation for total EE (VLCD=-6.2%; LCD=-6.8%) and that (b) the metabolic adaptation for resting EE was greater in the LCD (-0.4MJ/day, -5.3%) compared to the VLCD (-0.1MJ/day, -1.4%) group.

Likewise noteworthy: The resting EE did not decrease after short-term fasting and no evidence of adaptive thermogenesis (+0.4MJ/day) was found after 5%WL. The rate of WL was inversely associated with changes in resting EE (n=30, r=0.-42, p=0.01).

Figure 3: Metabolic Adaptation - Percent of total and resting energy expenditure not accounted by changes in body composition (FFM and FM) after 5% and 10% weight loss (WL) in obese assigned to three different WL interventions (Siervo. 2015).

So what to make of these study results? If you scrutinize the results in Figures 2 & 3 and, most importantly, the ratio of fat free mass to fat mass loss, it's quite astonishing that the study confirms the common wisdom that slow weight loss will allow for a greater fat-specificity than fast weight loss. After all, the subjects losing 5% of their total body weight lost 88% of it in form of lean muscle (I wonder how much glycogen and thus water loss this was) in the total fast group, 42% in the very low calorie diet group (VLCD) and only 20% in the "moderate" = low calorie diet group. In this context, it's also noteworthy that "biggest losers", i.e. those who lost weight most successfully (cf. Tremblay. 2013) and achieved a 10% weight loss in the VLCD group had a sign. better fat free / fat mass ratio (23% vs. 42%) than those who managed to lose only 5% in three weeks.

Eventually, it may thus seem that the study at hand would confirm what we already know: Slow and steady is best, ... and that's true, but the fact that "slow and steady" produces the greatest reduction in resting metabolic rate makes me question whether the weight rebound after longer, but less severe dieting phases is actually smaller or not. Previous studies suggested there's no difference, but these studies used different protocols and stand in contrast to a plethora of studies like Sénéchal et al. (2012 | learn more). Whether it would be the same for the study at hand is thus questionable | Comment on Facebook! 

References:

• Siervo, Mario, et al. "Imposed rate and extent of weight loss in obese men and adaptive changes in resting and total energy expenditure." Metabolism (2015): Accepted Article.
• Sénéchal, Martin, et al. "Effects of rapid or slow weight loss on body composition and metabolic risk factors in obese postmenopausal women. A pilot study." Appetite 58.3 (2012): 831-834.
• Tremblay, A., et al. "Adaptive thermogenesis can make a difference in the ability of obese individuals to lose body weight." International journal of obesity 37.6 (2013): 759-764.
• Williams, Nancy I., et al. "Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction." American Journal of Physiology-Endocrinology and Metabolism 308.1 (2015): E29-E39.

High Energy Flux, A New Determinant of Successful Weight Loss? Eat More, Train More, Lose More? Increased Resting Metabolic Rate & Satiety, Decreased Hunger While Dieting!

Always hungry? Can't lose weight? "Train more and eat more" (not less!) could be the solution.

A recent thesis from Rebecca Foright, highlights that a high energy flux state characterized by high daily energy expenditure (resulting from increased physical activity) with matching high energy intake (high-calorie throughput) may attenuate the weight-loss-induced energy gap by reducing hunger and ameliorate the otherwise diet-related reduction in resting metabolic rate.

Foright recruited eleven obese study participants from the Colorado State University community and surrounding areas to test her "exercise more, eat more, lose more (easily)" hypothesis.

The enrollment criteria included: BMI between 30-43 kg/m², age 18-55 years, weight stable over the prior 12 months, desire to lose weight, and ability to exercise as assessed by electrocardiogram (ECG), resting blood pressure and a normal incremental exercise test to exhaustion with simultaneous ECG. Exclusionary criteria included: pregnancy or breastfeeding, smoking, use of medication known to affect appetite or metabolism (including but not limited to antidepressants and statins), or prior surgery for weight loss. In short, most of the participants were what we today call "healthy obese."
"The approach used in this study was a within-subjects cross-over experimental design to test the effect of high and low flux states following weight loss on resting metabolic rate and perceptions of hunger and satiety."

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The study protocol was divided into four distinct phases: (1) baseline testing phase prior to weight loss; (2) weight loss phase induced by a hypocaloric diet over the course of several months; (3) weight maintenance phase in which subjects were maintained at the reduced weight for 3 weeks; and (4) experimental phase in which measures were obtained of subjects’ resting metabolic rates, fasting and post-prandial perceived hunger and satiety, fasting and post-prandial circulating glucose, insulin, and PYY concentrations, and ad libitum food intake on the 5th day following low flux and high flux phase conditions, respectively, completed in random order with a three-day washout period in between (see Figure 1).

Figure 1: Experimental Timeline | #Order of Low Flux and High Flux were randomly assigned (Foright. 2014).

During the low flux condition subjects remained sedentary for four consecutive days. All food was provided so that energy intakes were adjusted to maintain energy balance.

• resting metabolic rate (RMR) measurements on day 1-4 of the low flux phase
• caloric intake was adjusted according to RMR everyday
• subjects were fed standardized meals with a macro composition of 50/35/15 (carbohydrate/fat/protein) and an energy intake that was 1.3x the RMR
• subjects had to refrain from physical activity (>3,000 steps per day)
• at the end of day 5, the subjects completed a hunger/satiety questionnaire used to assess general feelings of hunger/satiety over the prior four days of the low flux condition

During the high flux condition subjects exercised on four consecutive days (approximately 500 net exercise kcal expenditure at 60% V02 max) and were fed additional food necessary to maintain energy balance.

• resting metabolic rate (RMR) measurements on day 1-4 of the low flux phase
• caloric intake was adjusted according to RMR everyday
• subjects were fed standardized meals with a macro composition of 50/35/15 (carbohydrate/fat/protein) and an energy intake that was 1.7x the RMR
• subjects were given pedometers and had to achieve at least 7,500 steps per day
• subjects exercised at 60% of their VO2max to burn 500kcal
• at the end of day 5 the subjects completed a hunger/satiety questionnaire used to assess general feelings of hunger/satiety over the prior four days of the low flux condition

Overall, a testing week consisted of two baseline days and 5 high/low energy flux days. In that, three identical experimental days were used to examine possible differences in perceptions of hunger and satiety, blood glucose, insulin, and PYY in response to breakfast preload, and ad libitum intake from a meal buffet.

Note: The caloric deficit that was designed to produce a 7% weight loss over the course of the 12-16 week long weight loss phase was identical in the undulating high and low energy flux phases of the study. The results are thus not a consequence of the increase in energy intake during the high flux phase (in fact the opposite was the case in some subjects, anyway). The extra calories were after all burned again during the four exercise days.

"Now what is particularly interesting about the study is that the researchers did not content themselves with measuring the acute effects of high vs. low energy fluxes. They also investigated what happened after the 12-16 week weight loss phase.

To minimize the acute effects attributable to the dynamic phase of weight loss on metabolic rate and on hunger and circulating appetitive hormone concentrations, subjects were maintained at the seven percent lower body weight for a three-week period prior to the start of the low and high flux conditions. During these three weeks subjects reported to the KANC every three days to monitor weight and minimize weight fluctuations. Subjects were instructed to consume a slightly increased kcalorie intake compared to the weight loss phase to maintain weight" (Foright. 2014).

Put simply, the scientists wanted to know, whether the effects of high vs. low energy flux dieting would influence a dieters ability to lose weight and maintain the newly achieved weight.

Figure 2: Weight loss and energy flux where exactly as the scientists had planned (Foright. 2014)

As you can see, the average weight loss was almost identical to the targeted 7% (de facto "only" 6.9%). Similarly,

[...a]s designed, the energy intake for high flux (x±SD: 3,191±587 kcal/d) was significantly greater (p < 0.001) than for low flux (x±SD: 2,449±406 kcal/d) (Figure 2, right). In accord with the study design, there was no difference in macronutrient composition between the two conditions (data not shown)" (Foright. 2014).

Now all that would be pointless if both groups lost weight similarly effortlessly. In reality, though, On the subjects were significantly more hungry and felt less satiated at the end of each of the days during low flux.

Figure 3: As you see, the mean difference was already huge. It was more than huge in in
the subject who saw the greatest benefit (Foright. 2014).

On the other hand, they were significantly more full at the end of each of the days during high flux (p=0.015). There was a strong trend for the subjects to exhibit greater hunger throughout the day during low compared to high flux (p=0.09).

RMR increases sign. in trained but not untrained subjects in a high energy flux state - no training, no difference between the two groups - the energy balance was identical in both conditions (Bullough. 1995)

No, this is not an outlier study: In 1995 Bullough et al. were already able to show that the resting metabolic rate on diet + exercise regimen that established an identical energy balance was greater in trained than in untrained subjects only when trained subjects were in HF. As Bullough et al. point out "[t]hese data indicate that RMR is influenced by exercise, energy intake, and their interaction and suggest that higher RMR in trained vs untrained individuals results from acute effects of HF rather than from a chronic adaptation to exercise training." (Bullough. 1995) Bell et al. on the other hand found that "[m]aintenance of high energy flux via regular exercise may be an effective strategy for maintaining energy expenditure and preventing age-associated obesity" (Bell. 2013).

And Goran et al. (1994) found that "RMR can be elevated during a state of energy balance when energy flux is increased," and that the "magnitude of adaptive change in RMR is similar in response to increased EI [energy intake] and/or PA [physical activity]." 

Figure 4: The subject who saw the greatest satiety benefit in the high flux phase was also the one that consumed the most energy on the low flux condition - even more than on the high flux condition (Foright. 2014)

Interestingly, the subject who saw the largest benefit (see Figure 3) was also the guy or gal who consumed the most energy in the low flux condition (orange line in Figure 4).

So what about the health markers?

The  fasting insulin decreased following weight loss and was significantly lower on the LF (8.3±1.1 µU/ml) and HF (6.4±0.8 µU/ml) experimental days compared to the pre-weight loss baseline (11.8±0.6 µU/ml). In other words, while both groups saw significant increases in insulin sensitivity due to dieting, the effects were (unsurprisingly) significantly more pronounced during the high energy flux (=exercise phase).

In contrast to what the significant differences in hunger ratings would suggest, there were no general differences in fasting PYY (the satiety hormone) concentrations among pre-weight loss, low and high flux conditions respectively.

Figure 5: Insulin and PYY levels of the subjects in the high and low flux phases over the course of the day (2014).

If you look at the data in Figure 5, it's obvious that the PYY levels were, in fact, lower in the high flux condition - from 180-360 minutes in the high flux condition compared to the baseline (pre-weight loss) and low flux, to be precise.

Figure 6: Average resting metabolic rate at baseline and across 5 days of low and high flux (Foright. 2014)

So what? Beneficial, not beneficial, or not sure? In spite of the absence of significant differences in PYY ("hunger hormone"), the subjects' post-diet response clearly indicates that the energy deficit was easier to tolerate in the high flux phases.

The slightly, but significantly higher resting metabolic rate during the high flux phases further underlines that there is a benefit of eating more and training more. The fact that this didn't show in the hormonal markers the scientists analyzed may simply be a consequence of choosing the wrong markers. Acetylated ghrelin, for example, would be such an alternative marker... and seeing the cortisol and testosterone would also have been interesting.

The way it is, we still have the decreased subjective hunger, increased subjective satiety, and increased RMR which speak in favor of the high flux state dieting. What we do not know, though, is whether the effects will be the same in athletic (vs. sedentary) subjects [based on my personal experience we will!] and whether they can be maintained for say 4 weeks instead of four days | Comment on Facebook!

References:

• Bell, Christopher, et al. "High energy flux mediates the tonically augmented β-adrenergic support of resting metabolic rate in habitually exercising older adults." The Journal of Clinical Endocrinology & Metabolism 89.7 (2004): 3573-3578.
• Bullough, Richard C., et al. "Interaction of acute changes in exercise energy expenditure and energy intake on resting metabolic rate." The American journal of clinical nutrition 61.3 (1995): 473-481.
• Foright, Rebecca. A high energy flux state attenuates the weight loss-induced energy gap by acutely decreasing hunger and increasing satiety and resting metabolic rate. Diss. Colorado State University, 2014.
• Goran, Miachel I., et al. "Effects of increased energy intake and/or physical activity on energy expenditure in young healthy men." Journal of Applied Physiology 77.1 (1994): 366-372.
• Rarick, Kevin R., et al. "Energy flux, more so than energy balance, protein intake, or fitness level, influences insulin-like growth factor-I system responses during 7 days of increased physical activity." Journal of Applied Physiology 103.5 (2007): 1613-1621.

Thyroid Issues? Low Energy Intake Triggers Low T3 / High rT3 Syndrome in Exercising Women >19kcal/kg LBM Avail. Energy Required. Low Carbing Worsens the Impact of ED

It's not your thyroid, but your behavior that's to blame for your low T3 levels, the fatigue and being "unable to lose weight". If you exercised less and ate more, you could fix it without medical intervention or thyroid madness using Lugol's or other junk ;-)

It's something I am facing on a daily basis - on Facebook, in Emails and private messages: Women with self-induced thyroid issue who wonder that their body does everything to conserve lean and fat mass. Women who are working out on a daily basis, dieting like crazy and (in their words) "still not losing weight".

It does not take a thyroid expert to identify the reason for their problems: They are training too much and eating too little. Just like the 27 women in seminal experiment that was conducted at the Ohio University in the early 1990s. A study I am going to elaborate on in today's SuppVersity article, although I personally believe it shouldn't take experimental evidence to convince people (yes, this is true for men, as well) to stop run themselves into the ground.

Low T3 syndrome is also a part of the (Female) Athletes Triad.

Female Athletes' Body Comp Suf- fers From Dieting

Female Athlete's Triad is not ex- clusively female

Female Athlete's Triad - A Vicious Cycle

Female Athlete's Triad - Recovery Part 1/3

Female Athlete's Triad - Recovery Part 2/3

Female Athlete's Triad - Recovery Part 3/3

Said study was conducted by Anne B. Loucks and Edward M. Heath who worked at the Derpartment of Biological Sciences and the College of Osteopathic Medicine at the Ohio University back in 1994. The purpose of their study was to characterize the functional relationship between energy availability and thyroid metabolism to gain insight into the extent of he dietary reform that might be necessary. The scientists expected to find a proportional relationship that would prove the necessity of dietary compensation for exercise energy expenditure to prevent reductions in T3 levels, scientists call "low T3 syndrome".

To this ends, Loucks & Heath recruited 28 healthy, non-obese, nonsmoking women (18-29 years old) with no recent history of dieting or weight loss were recruited from the university and surrounding community. All received a detailed verbal and written description of the study and signed an informed consent document. The participants had to keep a prospective diet records for seven consecutive days a measure that was necessary to determine their baseline energy intake and
Subjects were assigned to four groups in a monotonic experimental design of energy availability treatments.

Figure 1: Overview of the experimental design (Loucks. 1994)

"The experimental manipulation of dietary energy intake, exercise energy expenditure, and, thereby, energy availability (defined as dietary energy intake minus energy expenditure during exercise) is shown in Fig. 1. All four experimental groups expended ~30 kcal kg LBM of energy in daily exercise at 70% of aerobic capacity for four consecutive days beginning on day 2, 3,4, or 5 of the menstrual cycle. All exercise was performed under continuous supervision on treadmill and cycle ergometers in a sequence of 30-min bouts interrupted by lo-min rest periods."  (Loucks. 1994)

During the first exercise bout, heart rate at 70% aerobic capacity was determined by monitoring oxygen uptake. Thereafter, heart rate was monitored continuously by means of a Uniq HeartWatch model 8799 (Computer Instruments, Hemstead, NY) and maintained at the previously measured level by adjusting treadmill speed and slope or cycle work load.

I know you will be asking, but aside from simply eating more there is no way to cure low T3 symptom. In fact the worst thing you can do is to get a script for T4 from your doc, because this will only elevate the inactive thyroid hormone (=break) rT3.

If the heart rate began to drift monotonically, suggesting a thermoregulatory effect, then oxygen uptake was measured directly by gas analysis. Heart rate and Borg scores of per- ceived exertion were recorded at the fourth and fifth minutes of each exercise bout.

Figure 2: Energy intake and expenditure (kcal/lbm) during the study period in all four grous (Loucks. 1999)

As you can see in Figure 2 the amount of available energy ranged from ~10kcal/kg lean body mass (LBM) in the group who had been assigned to the lowest amount of Ensure, a liquid food product that was the only food source the subjects received during the treatment period to ~40kcal/kg lean body mass in the group with the highest intakes.

Table 1: Thyroid hormone concentrations before treatment and changes in concentrations resulting from 4 days of controlled energy availability | Tq, thyroxine; fT4, free T,; T3, triiodothyronine; rT3, reverse T3; ff3, free T3 (Loucks. 1999)

As you can see in Table 1 the thyroid hormone concentration in the two lower groups (10kcal and 19kcal/kg lbm) dropped significantly. With a 10% decrease in free T3 only the changes in the 10.8kcal /kg lbm group were physiologically significant.

Bottom line: In a previous experiment (12), the scientists had been able to show that energy availability, rather than dietary energy intake or exercise energy expenditure separately, is the behavioral factor affecting thyroid regulation in exercising women. It is thus not exactly surprising that 4 days on an energy deficient diet in the study at hand were enough to induce a low T3 syndrome in the female participants of the study at hand.

Figure 3: Mean T3 thyroid hormone levels after 20 days of total fasting, 800kcal diet without carbohydrates and 800kcal diet consisting almost exclusively of carbs (Spaulding. 1976)

In this context it's important to point out that the effect occured only, when the dietary inake fell below 50% of the dietary requirement and that the changes in thyroid hormone levels are restricted to T3 and won't show up on tests that evaluate TSH and T4, only.

In studies of the effects of dietary restriction on thyroid metabolism in sedentary obese patients, T3 levels declined only when dietary energy intake fell below a particular threshold and the carbohydrate con- tent of the diet influenced the location of this threshold. T3 levels fell when energy intake was reduced to 800 kcal/day if carbohydrate content was <200kcal/day. Previous studies also highlight that a reduction of carbohydrate intake, will reduce the amount of free T3 by increasing the conversion of T4 to the inactive thyroid metabolite rT3.

Irrespective of the fact that a high(er) carbohydrate diet can help women maintain normal thyroid function on a diet, studies indicate that there is an energy threshold below the amounts of carbs in the diet become irrelevant and the T3 levels crash as a simple consequence of a lack of energy in the diet (Spaulding. 1976) | Comment on Facebook!

References:

• Loucks, Anne B., and Edward M. Heath. "Induction of low-T~ 3 syndrome in exercising women occurs at a threshold of energy availability." American Journal of Physiology 266 (1994): R817-R817. 
• Spaulding, Stephen W., et al. "Effect of caloric restriction and dietary composition on serum T3 and reverse T3 in man." The Journal of Clinical Endocrinology & Metabolism 42.1 (1976): 197-200.

More Than -2kg Body Fat in 4 Days? Manic Exercise and a 4-Day x 5,000kcal Energy Deficit on Whey or Sucrose Based Starvation Diet Yield Astonishingly Long-Lasting Fat Loss

Actually, even cherry tomatoes were not allowed in the first 4 days ;-)

Wow! If that's what you thought, when you read the figure in the headline you know what I thought, when I spotted the latest paper from the University of Las Palmas de Gran Canaria in the "ahead of print" section of the Scandinavian Journal of Medicine & Science in Sports (Calbet. 2014).

I mean, the title of the study, "a time-efficient reduction of fat mass in 4 days with exercise and caloric restriction", sounds pretty harmless. Too harmless for what happened to the 15 subjects the researchers recruited for an experiment that was almost as extreme as its astonishing results.

Wake up, work out, starve and sleep

I would say the above summarizes pretty well what I was referring to, when I said "something happened to the subjects" in the first 4 days of the study, the 15 not exactly lean study participants (mean BMI ~30kg/m²; body fat 31%) started their days with 45min of an arm cranking exercise (at 15% maximal intensity; see Figure 1).

Figure 1: Schematic overview of the different phases of the diet + exercise intervention (Calbet. 2014)

When they were done, they spend most of the remaining waking hours day walking - 8 h of walking at 4.5 km/h (35 km/day) 4 days in a row and on a diet delivering meager 3.2 kcal/kg body weight from a shake that contained either pure whey protein or pure sucrose.

This can't really be the whey to go? Right?

What sounds like some mad survival program did, as you can see in Figure 1, produce quite impressive weight loss effects. Unfortunately, this is "weight", as in fat and muscle and that at an almost 1:1 ratio - certainly not the type of "weight loss" any of you should strive for.

Figure 2: Lean mass (left) and fat mass (right) development during the four phases of the intervention (Calbet. 2014)

Now, the fat rebound in the sucrose group would initially suggest that your gut feeling was right. Eventually, it's yet unlikely that this was more than a mere coincidence and the shocking loss in lean mass that occurred during the 4-day of manic dieting + walking, normalized withing days, when when the subjects returned to their regular energy intakes (+ obligatory 10,000 steps a day).

The latter obviously suggests that most of the "muscle loss" was actually water + glycogen and thus easy to restore (see Figure 3, right, as well).

Suggested Read: "Cell Swelling Keeps Muscles "Pumped" For More Than 52h - Could It Even Help You Build Muscle?" | read more

Lean mass can be tissue, water and glycogen: Early "muscle loss" is mostly water + glycogen (esp. on low carb diets; Kreitzman. 1992). In view of older studies on the muscle-building mechanisms of creatine (Persky. 2001) and the latest research on the involvement of muscular (hyper-)hydration in skeletal muscle hypertrophy Ribero et al. (2014), the loss of water and glycogen - as benign and as far as the glycogen goes, even metabolically beneficial (leaves room to store glucose ➲ improves insulin sensitiviy) as it may be - could hamper your gains.

What I cannot explain - at least not without telling you that my answer is of hypothetical nature and would thus require experimental confirmation - are the impressive long(er)-term weight loss effects.
Usually you would expect the subjects to jojo back up, right away - in the worst case to body fat levels that are higher than those nasty 31%, where they were initially coming from. If you take a look at Figure 3, it's yet plain to see that the opposite was the case.

Figure 3: Progressive changes in body fat and lean mass (in kg) over the course of the study period (Calbet. 2014)

In spite of the fact that the subjects returned to their regular energy intakes, they lost an additional body fat - at quite an impressive rate, by the way. Now, an as previously mentioned hypothetical explanation for these observations is the use of body fat as a substrate and energy source to refill the previously mentioned glycogen stores in muscle and liver.

Even if we take into consideration that the release (lipolysis) and oxidation of fats and the storage of glucose from dietary carbohydrates (it's not impossible (Kaleta. 2012), but unlikely that the stored body fat is used as an energy source for glyconeogenesis) in form of glycogen are energetically costly, the 2,000kcal would equal no more than max. 300g of stored body fat, which is more than the additional 450g even the whey protein group dropped during the 4-day aftermath.

That's quite astonishing: Would you have expected that this "4-days of madness" diet would generate a total fat loss of -3.8kg (2.8kg of those from the potentially life-threatening trunk fat) and thus produce an outcome of which the researchers rightly say that it "is better than several interventions combining low-calorie diets and exercise lasting from 12 weeks to 1 year (Garrow. 1995; Shaw. 2009)" and bet the largest randomized control trial for the response to 8-month resistance training, aerobic training, or combined aerobic and resistance training (Willis et al., 2012)? Certainly not, right?

Figure 4: Weight loss (not fat loss!) maintenance in Calbet et al. and the average US dieter according to a meta-analysis by Anderson et al. (2001)

Well, considering the fat that the mean fat loss here is greater than that achieved by the latest pharmacological intervention, i.e. the administration of glucagon-like peptide-1 (GLP-1) agonists for 20 weeks (which gave a weighted mean loss of 2.9 kg in 21 trials involving 6411 participants; Vilsboll. 2012), I am actually happy that there was a one year follow up to show that a short-term intervention can never replace permanent life-style changes... although, when you look at the whey protein group, who regained a meager 1.09kg in Phase V and thus significantly less than the 50-80% the average subject on a medically supervised weight loss diets (Anderson. 2001; see Figure 4), I do have to admit this is not just surprising.

This is damn impressive, even if the comparison is unfair, due to longer follow ups in the average study in Anderson's meta-analysis. Still, there is one thing I would like to see before I'd recommend this type of diet to anyone who doesn't have to lose another 2kg of fat before a physique show or photoshoot at the end of the week: A comparison of the health benefits of successful whey-based(!) crash dieting.

References:

• Anderson, James W., et al. "Long-term weight-loss maintenance: a meta-analysis of US studies." The American journal of clinical nutrition 74.5 (2001): 579-584.
• Calbet, J. A. L., et al. "A time-efficient reduction of fat mass in 4 days with exercise and caloric restriction." Scandinavian Journal of Medicine & Science in Sports. (2014). Accepted Manuscript. doi: 10.1111/sms.12194 
• Garrow, J. S., and C. D. Summerbell. "Meta-analysis: effect of exercise, with or without dieting, on the body composition of overweight subjects." European journal of clinical nutrition 49.1 (1995): 1-10.
• Kaleta, Christoph, Luís F. de Figueiredo, and Stefan Schuster. "Against the stream: relevance of gluconeogenesis from fatty acids for natives of the arctic regions." International journal of circumpolar health 71 (2012).
• Kreitzman, Stephen N., Ann Y. Coxon, and Kalman F. Szaz. "Glycogen storage: illusions of easy weight loss, excessive weight regain, and distortions in estimates of body composition." The American journal of clinical nutrition 56.1 (1992): 292S-293S.
• Persky, Adam M., and Gayle A. Brazeau. "Clinical pharmacology of the dietary supplement creatine monohydrate." Pharmacological Reviews 53.2 (2001): 161-176.
• Ribeiro, Alex S., et al. "Resistance training promotes increase in intracellular hydration in men and women." European journal of sport science ahead-of-print (2014): 1-8. 
• Shaw, K., et al. "Exercise for overweight or obesity." Cochrane Database Syst Rev 4 (2006).
• Vilsbøll, Tina, et al. "Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials." BMJ: British Medical Journal 344 (2012).
• Willis, Leslie H., et al. "Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults." Journal of Applied Physiology 113.12 (2012): 1831-1837.