Exciting Study on Maintaining Metabolic Rate with Intermittent Kcal Restriction in 2 Week Blocks

(Windmill Tilter) #1

The problem with the CICO model that Dr. Fung made abundantly clear is that it’s a one compartment model. It fails to appreciate that the bodies compensatory mechanisms adapt to calorie restriction by lowering metabolic rate, adjusting hormones, etc in order to confound weight loss and cause weight regain. Even Dr. Fung never said CICO was completely wrong, just that it was inadequate, and doomed to failure because of the compensatory mechanisms of adaptive thermogenisis (decreasing RMR).

The following study is called the Matador study (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound). This study concedes the inadequacy of standard CICO protocol of continual calorie restriction, and focuses on minimizing the compensatory mechanisms the body uses to fight back against weight loss, chief among them adaptive thermogenisis (declining RMR). The hypothesis of the study is that if calorie restriction is done for two weeks, and then calories are brought back to maintenance for two weeks, the body’s adaptive mechanisms will essentially be short circuited, and weight regain will be minimized. That the metabolism can recover to steady state in roughly 2 weeks of refeeding has been shown in prior studies.

The study lasted for 32 weeks with alternating 2 weeks periods of calorie restriction and maintenance calories. Yes, there was a robust control group. Yes, the study was sufficiently powered. Yes, there was a 6 month follow up. Yes, results are absolutely stunning. Seriously, read the study. It’s very encouraging both in the sense that academia is beginning to concede that continuous calorie restriction is asinine, and because of the novel, intuitive approach used (2 weeks on 2 weeks off).

@atomicspacebunny, @OldDoug: This one is right up your alley.

Adjusted RMR at 6 month Follow up
Continuous: -770 +/-523
Intermittent: -255 +/-515

Fat Loss During Study
Continuous: -8.0 +/-4.4
Intermittent: -12.3 +/-4.8

Fat Loss at 6 Month Follow Up
Continuous: -3.0 +/-4.4
Intermittent: -11.1+/-7.4

#2

And no, the study did not include females, sheesh. Studies based in male biology & physiology don’t automatically apply to the other half of the species.

However, interesting!

Intermittent feeding and a degree of randomness is an ancient thing - cortisol levels in relations to overall hormonal balance can vary a lot between males and females though! What is robust can be diverse. The 5 days of feasting, 2 days of IF as a weekly schedule has been studied and Cristian Vlad reviews it in his books. Just 2 IF days per week resulted in similar enhanced recomp compared to daily caloric restriction if I recall correctly.

I really like Naseem Nicholas Taleb’s concept of antifragility as a state beyond robust - cultivated by healthy/primordial randomness.

(Omar) #3

very interesting

I always believed that a permanent metabolic damage is difficult to believe.

an irreversible metabolic trend both way will lead to uncontrollable weight loss or weight gain

(Heather Meyer) #4

It actually makes sense in a way…
If a person is on Keto and losing weight and then takes a Carb laden binge for a day and then weighs on the scale the next day…what happens?
Most people claim they lost weight overnight right? So maybe the jolt of the 2 weeks helps the body let go similar to a binge episode.

(Katie the Quiche Scoffing Stick Ninja ) #5

If anything I think that’s entirely related to the whoosh.
Fat cells filling up with water and holding on until they are ready to be released, when you ‘carb up’, your cells fill with glycogen again and then once full perform the whoosh, regardless of whats in there, glycogen or water. Could be wrong tho.

(Bunny) #6

My comments are not specifically about the study itself, I like to contrast this research for its correlations with other research that are worthy and indicative of being cross-validated with other pre-existing research on this subject:

This looks something like an insulin[3] or glucagon[2] induced thermogenesis[2][3], this study (MATADOR STUDY: Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) also appears to be inducing a slowly progressive leptin like reset or set point[1] stratification in randomly picked obese individuals? Maybe it would work on anyone obese especially those with high T3 thyroid levels indicating a higher predisposition to extreme leptin resistance rather than a moderate, medium to low? See also: Dr. Leo Galland M.D. “The Fat Resistance Diet” “…unlock the secret to the hormone leptin…”

Footnotes:

[1] How to Turn On Your Fat-Burning Switch, Leptin (Your “Starvation Hormone”) How does leptin function in the body and where does the hormone come from? Leptin interacts with areas of the brain that control hunger and eating behavior. (1) The nickname “the starvation hormone” has been given to leptin because levels tend to plummet when someone restricts their calorie intake too much, exercises more and loses body fat. These are all factors involved in what’s called “starvation mode.” (Meanwhile, ghrelin is called a “hunger hormone” that increases your desire to eat.) At your ideal “set point weight,” adipose (fat) cells produce a given amount of leptin, which maintains the internal energy balance needed for necessary cellular function and proper weight management. (2) In most healthy adults, changes in body weight will trigger changes in leptin, causing appetite to either increase when body fat falls or decrease when body fat rises — although in some susceptible individuals this energy-balance system seems to malfunction. When levels of ghrelin and leptin are disrupted, your ability to eat when you are truly hungry and stop when you are full can become severely compromised, leading to changes in body weight and other related consequences. Even though these two hormones have opposite effects, working together in a checks-and-balances type of way, diet and lifestyle changes that help to regulate leptin are also helpful for controlling ghrelin. …” More… …See also: J. Fung et al; ghrelin signaling; hunger comes in waves

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[2] “…Glucagon, a counterregulatory hormone to insulin, serves as a regulator of glucose homeostasis and acts in response to hypoglycemia. …However, it is not known whether endogenous glucagon is involved in the regulation of brown adipose tissue (BAT) function. …” “…In conclusion, in this study, we demonstrated that endogenous glucagon is essential for adaptive thermogenesis and that it regulates BAT function, most likely through increasing hepatic Fgf21 production. …” …More

[3] Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis Published: June 14, 2018

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[4] “…Interestingly, leptin release is modulated in a circadian rhythm manner, which has been correlated with sweet taste recognition? …” (Nakamura et al., 2008)

Summary

[5] Personal Notation: You could also translate this study into a thyroid-hypothalamus-leptin-ghrelin axis reset hypothesis: This may take some experimentation due every persons level of leptin resistance (if you are? high T3 levels are a good indication that you are) and maybe eating a small meal every 3 hours on any given day of the week 5 times (adjusting hours, times and day in sequences) and that does not mean slam down a bunch sugar (although you need some from natural sources like black berries and fruit) or processed foods. What we want do to is heal stubborn hunger signals? This is not THE permanent solution what we want to try to do is trick that leptin and ghrelin starvation switch or set point signal AND also trick it into burning fat while we slowly incorpoarate the ketogenic diet into healing the thyroid and HPA-axis before we graduate to more intense levels of intermittent and extensive fasting including caloric restriction and not shock this very delicate process, what we want is a more progressive and healing transitional relaxed state of feeding for the thyroid and hypothalamus to adapt too and also reducing external sources of stress etc.

3 months in - can't shake ongoing cold. Suggestions?
(Ken) #7

This is the type of cycling that I have done quite a bit of. After my initial 180 pound loss of over a two year period, I experienced a one year stall. I started training again and began cycling carbs. I basically have lost fat since then in increments of between 10 to 20 pounds, with a month or so of slightly higher carb Maintenance periods in between.

I never went back to the NAD during Maintenance, I just ate enough carbs intermittently to only partially recompensate my glycogen.

(Windmill Tilter) #8

This is an important point, and I believe that sex specificity is one of the little details that make this study design so good. In a low powered study where n=25, it makes no sense to mix men and women if there is even a shred of truth the hypothesis that men and women lose weight differently. Unless n=50, you wind up without sufficient statistical power to draw any statistically significant claims about the efficacy of the protocol on either sex.

When you dig into the data on some of these studies, the 3 men in the study lose 10kg of fat and the 15 women in the study gain 2kg of fat, and the conclusion is that on average the weight loss was 0 +/- 4.6kg, when in reality, the correct conclusion is that the diet is demonstrably terrible for women, and insufficiently powered to claim that it was outstanding for the men!

(Doug) #9

Good stuff, Nick. To me, it makes gut-basic sense that there would be an effect, and that “mixing things up” is something to think about for most of us. I’d like to see a comparison with different periods of alternation, i.e. 1 week and 4 weeks versus the 2 weeks of the study.

One thing I can’t figure out is the change in resting energy expenditure, adjusted for changes in body composition.

For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: -624±557 kJ d-1; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: -360±502 vs CON: -749±498 kJ d-1; P<0.05).

The ‘Intermittent’ group lost an average of 14.1 kg. REE went down 502 kJ or 360kJ after adjusting for the loss of 12.3 kg of fat mass and 1.8 kg fat free mass. Makes sense - they lost weight and ended up using less energy, and adjusting for the loss of both fat and other mass means a lesser decline in REE relative to weight.

Yet the ‘Continuous’ group also lost weight, 9.1 kg, and lost both fat mass and fat free mass, 8.0 kg and 1.2 kg, with the REE going down 624 kJ on an absolute basis but then being adjusted upwards to 749 kJ.

I cannot see how this makes sense.

(Windmill Tilter) #10

I’m no scientist that’s for sure, but this is my understanding of it. Hopefully somebody will correct me if I’m wrong.

Continuous adjustment: Their metabolism dropped further than it should have given the small reduction in lean mass, fat mass, etc.

Intermittent adjustment: Their metabolism dropped less than it should have given the large reduction in lean mass & fat free mass.

Think of it this way, if one person lost 1lb and their REE/RMR dropped 250kcal, and another person lost 50lbs and their RMR dropped 250kcal, these events are by no means equivalent. One had an enormous over-response to tiny weight weight loss, and the other had a under-response to a massive weight loss. To normalize them to expected outcomes, RMR predictive equations are used. These guys really went into the weeds to make their calcs accurate, by creating a population specific RMR equation in addition to using the Muller et al equation which was used in Germany to study a similar population of overweight men in an affluent country.

Calculation of predicted REE, and of changes from baseline

Given the contention regarding the best analytical approach to assess and define adaptive thermogenesis,30,31, 32, 33, 34, 35, 36, 37, 38 we examined changes in REE using three approaches:

  1. Comparing REE over the intervention after adjustment for changes in fat mass (FM) and fat free mass (FFM).

  2. Comparing measured REE with REE predicted from the group-specific equations developed using regression analysis of baseline data (see details below).

  3. Comparing measured REE with REE predicted from the reference equation published by Muller et al. 39

It has been suggested32 that the most appropriate analysis uses the study-specific regression equation derived from baseline data (REE, body composition, age, sex). As such, linear regression analyses were performed to develop prediction equations for REE from baseline data (group allocation, age, FM, FFM). Whereas age did not significantly explain any of the variance in REE, group allocation accounted for a significant proportion of variance in REE. Consequently, a separate equation was derived for CON and INT:

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Given the relatively small, homogeneous sample in the present study, it could be argued that the resulting prediction equation may not be robust.35 To overcome this potential weakness, REE was also predicted from the equation developed by Muller et al. 39 on a larger, phenotypically similar cohort (body mass index >30 kgm−2; N =278); where female=0, male=1:

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These equations were used to predict REE at baseline, and after 4, 8, 12 and 16 weeks of ER for the CON and INT groups separately. Changes in REE from baseline for measured and predicted values were then compared.

(Mel Simpson) #11

Sounds so logical
I am on my 2 weeks off now. Probably gaining as I am on vacation. I am really going to try this when I get home.
Thank you for posting this very helpful study!!

(Bob M) #12

Remember, though, that they did not eat ad libitum on their normal refeeding periods; instead, they ate to what they thought their calorie requirements were. That means you’d have to start (or continue) calorie counting.

It’s too bad they didn’t have an arm with intermittent fasting.

(Windmill Tilter) #13

This is a very good point! The diets that they ate were very tightly controlled, and each participant was delivered food at precisely their maintenance level each day. It really was an extremely well controlled, well thought out study. On the down side, to replicate the results, it probably is necessary to revert a tiny bit to CICO thinking and keep an eye on calories on the 2 weeks off… :thinking:

Personally, I still track all my calories anyway, because I cycle between 3 days water fasting, lift heavy, then feast for 3 days. I’m not really trying to restrict so much as I try to keep calories in the range of 3000kcal to 3500kcal in order to increase my metabolism. I’ve lost about 29lbs (264lbs-235lbs) in the 5 weeks since I started cycling mega-feasts and water fasts, and every one of my lifts has gone up, so I think it’s working!

(Doug) #14

Thanks, Nick. I see what you mean. The INT group lost 55% more weight, and had 20% less reduction in absolute REE, so there’s an inverse thing going on. The variance of the two groups resulted in an ‘over/under’ condition with respect to the Müller equation, I guess. The population specific REE equations were extensively curve-fitted, and to compare them to Müller remains questionable, I think. Müller basically says that we should use different formulas for different weight groups when calculating REE; it doesn’t deal with calorie restriction nor with predicted adaptive thermogenesis.

It still bugs me to see the absolute resting energy expenditure adjusted downward for the Continuous group. Weight was lost, and it was both fat and non-fat mass, so REE should have declined. The group lost an average of 8.2% in weight, and had REE decline by 5%. From there, obviously, if weight loss was continued, the decline in REE would have to increase and even surpass the weight loss percentage if weight loss was carried to its maximal conclousion. I do realize that it’s not going to be a linear thing, overall, however.

Not a big deal, I think, in the end, and I’m quite impressed with the Intermittent group’s weight loss of 12.8% while only having a 4.2% reduction in REE, adjusted to an effective decline of 3%. Compared to the ‘horror stories’ of metabolic slowdown, I’m thinking, “Oh Yeah - we can work with that.” :slightly_smiling_face:

(Windmill Tilter) #15

Calculating adaptive thermogenesis is a tricky business for sure. Just using a standard equation like Harris Benedict is done sometimes, but that fails to take into account that your sample population may have begun with above normal REE to start with. I’m not sure I’m 100% on board with how they did it, but they definitely didn’t take the lazy way out! They went above and beyond to follow current best practices, and displayed the REE results using their own curve-fit equations as well as Muller. I’ll be poking around to see if there is another methodology.

I agree 100%. Not a perfect study or a perfect strategy, but the results are really encouraging. I’m looking forward to the follow up study!

Two weeks is completely arbitrary obviously. I think the ideal strategy is to measure RMR more frequently so that you can calculate the curve of the RAR decline towards the daily caloric intake. It makes little sense to wait to reverse direction when you’re 50kcal above the caloric intake, it makes more sense to do it while the curve is still steep. The same is true in the opposite direction.

Once you’ve done this, it’s possible to compare the curve of the decline of RMR during calorie restriction and the incline of the curve during refeeding to other cycles. Maybe 17 days restriction and 12 days for one person and 12 day restriction and 17 days refeeding is ideal for other.

The other more important factor is that the human metabolism is a very, very clever little beast. The first time you do a 2 week restriction it may react very slow downwards. The 16th time you do it, it may drop all the way down in 72 hrs. If you’re not measuring daily, you don’t get that data.

I just bought a Korr calorimeter so I can run that experiment on myself. :grinning:

#16

It makes sense to study both sexes from the get-go, separately, because of compelling biological and hormonal realities apart from statistical methods.

However the fact that male-based studies have been an inherent scientific bias involving straightforward prioritization of males as study subjects in a context where females are not only the other half of a 99% dimorphic speices, but also are the ones who often gestate and birthe the species, and then directly impact critical infant brain development & health of future generations - to delay or sideline female studies is unconscionable and/or backwards.

Really, it’s a human rights issue when we look at various disasters for women & children’s public health and food access created by male bias in science. I’m 50+ years old and have observed the glacial pace of medical research reform in this regard for three decades.

Nina Teicholz does an excellent job digging in to this issue of sex-based research bias in her book The Big Fat Surprise - the research methods are connected to a pernicious delay of science on behalf women’s health. Regardless of less than n=50 statistics, the deprioritization of females by medical science can and does delay sexual parity in medicine and elsewhere. It also can and does delays certain lifesaving public health reforms. There is the fundamental issue of persistent sexism in science, and many decades of male-centered statistics. (Dr. Phinney & Jeff Volek do a good job in acknowledging sex-based difference in their writing, as does the excellent film LCHF/keto film Run On Fat, where the petite female Meredith Loring outlasted large framed Finnish superman Sami Inkinen who bonked out for a day - and rowed them all by herself during that time - on their shared vessel for their record-setting row from Cali to Hawaii).

IMHO, studies both large and small should prioritize females as research subjects considering the history and the fundamental bias, or at least politely acknowledge the societal nonsense/injustice of not doing so.

For those of us who are females, it can be really bizarre to notice new studies with headlines portending info on “human metabolic facts” based on male subjects as the so-called humans of our dimorphic species :rofl::joy::open_mouth: :crazy_face::rage: Quite absurd! So, I suppose that a basic protocol or helpful remedy when exciting studies are conducted and published but are male-centered, involves acknowledging the issue straight on, so as to advance structured change on behalf of actual public health and expedient generational health.

(Windmill Tilter) #17

Could be. I’ve read hundreds of counterproductive and poorly designed weight loss studies for both sexes, and I haven’t kept particularly close tabs on which were more useless. Would another DASH diet study done exclusively with women really advance the cause of women’s health and women’s rights? I’m not so sure.

I’m just glad that a half decent study of weight loss came out for anybody. I think this one was exciting and it represents progress.

#18

We’ll have to agree to disagree then, in terms of the overarching issues that inform western medical science’s male bias. It’s more a human rights issue from a global health perspective. For many informed females, male-centered studies are tiresome, and certainly don’t appeal as progressive - and we shouldn’t have to explain it at length.

I think Dr. Phinney & Jeff Volek do a great job at implementing a certain kind of empathy and respect about this context in their research & writing, and as Nina Teicholz has so articulately written of, there is much to be done in terms of sexual parity in nutrition research and medical science.