Friday, March 18, 2016

Intermittent Fasting: Where Are We Now?

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It's been a good while since I last wrote about intermittent fasting. I guess largely because there's only so much to say about the topic and because I feel like I've said most of it. Unless you're going to make inferences based on animal studies, there's only so much you can extrapolate from the human experience and write about.

Another part of it is that I've lost interest. Once your understanding of nutrition is complete, more or less, you reach a point of radically diminishing returns - at this point, expanding your knowledge further in this realm, won't make an iota of difference for your level of fitness. It's much more fruitful to improve your training regimen and understanding thereof. That's my experience.

So for these reasons, I am thankful to Alan Aragon for the aptly titled 'Intermittent fasting: After over a decade of research, where are we today?' in which he writes about the current state of affairs of intermittent fasting. The article appeared in the December edition of the Alan Aragon's Research Review (AARR) which I have been a subscriber of since the first issue.

I asked Alan for permission to publish the article on my site, as I had a few comments on the content therein, and housed no doubts that our readership would be interested in taking part of it all. You'll find that most of my thoughts doesn't have to do with the article itself, but rather with some of the statements and issues raised.

Alan has previously published A Critique of the ISSN Position Stand on Meal Frequency on this site. If you enjoy reading about nutrition and exercise with a scientific twist, check out Alan Aragon's Research Review.

Now enjoy this article, folks. You will find my comments prefixed with MB after the relevant paragraphs below.



Intermittent fasting and body composition: After over a decade of research, where are we today?

By Alan Aragon


Speaking of decades...

The last time I wrote an article about intermittent fasting (IF) was almost a decade ago. A rich body of research on the topic has been published since then. The ongoing interest in IF is not surprising, given its mystique that’s wrapped in ancient spiritual origins, all the way to its modern applications to clinical and aesthetic goals. The aim of this article is to bring the reader up- to-date on the scientific findings, with a particular focus on comparing IF regimes with conventional/linear dieting. After all, the question is not whether IF works – it obviously does, as does any mode of caloric restriction. The question is whether it works better than conventional dieting for improving body composition, and if so, to which contexts can we apply it.


Variations on a theme

Let’s get some labeling/classification aspects out of the way. In the literature, the broad categories that I call linear and non- linear dieting have been called daily caloric restriction and intermittent caloric restriction, respectively. They have also been called continuous energy restriction and intermittent energy restriction. The intermittent category (what we call IF) can be further divided into three subclasses (1):  alternate-day fasting (ADF), whole-day fasting (WDF), and time-restricted feeding (TRF).

Alternate-day fasting


The most extensively studied IF variant is ADF, which typically involves a 24-hour fasting period alternated with a 24-hour feeding period. Complete compensatory intake on the feeding days (to offset the fasting days’ deficit) does not occur, and thus total weight loss and fat loss occurs on ADF. Lean mass- retention has been an intriguing effect of ADF reported by Varady et al (2-4). Lean mass loss in ADF conditions has also been observed by other investigators (5-7). However, the latter effect might be attributable to more severe energy deficits. The more lean mass-friendly The ‘fasting’ period in the Varady model is actually an energy-restricted period (~25% of maintenance requirements, typically in the form of a single meal at lunchtime) alternated with a 24-hour ad libitum (as desired) feeding period.

On the note of alternating fasting and feeding periods of the same length, alternate-week energy restriction (one week on ~1300 kcal/day, one week on the usual diet) has only a single study to-date, but is worth mentioning since it was as effective as continuous energy restriction for reducing body weight and waist girth at 8 weeks and 1 year. (8)



Whole-day fasting


WDF involves one to two 24-hour fasting periods through the week of otherwise maintenance intake in order to achieve the deficit. Of note, not all WDF studies involve zero energy intake in the ‘fasting’ days. Although WDF has been consistently effective for weight loss, Harvie et al saw no difference in bodyweight or body fat reduction between the WDF (2 ‘fasting’ days of ~647 kcal) group and controls when the weekly energy deficit was equated over a 6-month period (9).

A subsequent study by Harvie et al (10) compared two WDF diets (one with 2 structured energy-restricted ‘fasting’ days and one whose 2 ‘fasting’ days consisted of ad libitum protein and unsaturated fat) with daily energy restriction (DER). Both WDF diets caused greater 3-month fat loss than daily energy restriction. An important detail here is that at 3 months, the 70% of the fasting days were completed in the WDF groups while the DER group achieved their targeted caloric deficit only 39% of the trial.



Time-restricted feeding


TRF typically involves a fasting period of 16-20 hours and a feeding period of 4-8 hours daily. The most studied form of TRF is Ramadan fasting, which involves approximately 1 month of complete fasting (both food and fluid) from sunrise to sunset. Unsurprisingly, significant weight loss occurs, and this includes a reduction in lean mass as well as fat mass (11-12). 

Aside from Ramadan fasting studies, there’s a scarcity of human TRF research in the peer-reviewed literature. Stote et al (13) compared 1 versus 3 meals per day in eucaloric (weight–maintenance) conditions for 8 weeks and surprisingly found 1 meal resulted in fat loss and lean mass gain, while no significant improvements were detected in the 3-meal group. Unfortunately, the use of bioelectrical impedance (BIA) keeps these results questionable. Perhaps the only other longitudinal TRF study was done back in 1971 by Young et al, (14) who found no significant differences in weight loss and body composition change between 1, 3, or 6 meals per day

As for TRF programs in the lay press, Hofmekler’s Warrior Diet (15) published in 2002, was perhaps the first popular diet book to expose the general audience to TRF for weight loss. It involves a 4-6 hour feeding period at night, and an 18-hour “under-feeding” period during the day. The diet draws inspiration and justification from the purported habits of our Stone Age ancestors, as well as other leaps of faith involving the sympathetic and autonomic nervous systems. 

Berkhan’s Leangains system of TRF has a 16-hour ‘fasting’ period and an 8 hour feeding period (16). What separates this protocol from others is its attention to macronutrition, and its administration of branched chain amino acids (BCAAs) during the fasting period. As a matter of trivia that you might enjoy, Hofmekler and Berkhan’s were recently referenced in the peer-reviewed literature (17).



MB: Let me translate that. What Alan means to say is that Hofmekler's Warrior Diet is full of pseudoscientific nonsense and I agree wholeheartedly. 


Article continues...


The most comprehensive systematic review on IF to-date


Seimon et al (18) recently published the largest systematic review of IF research to-date. Importantly, they compared the effects of intermittent energy restriction (IER) to continuous energy restriction (CER) on bodyweight, body composition, and other clinical parameters. Their review included 40 studies in total, 12 of which directly compared an IER with a CER condition.

They found that overall, the two diet types resulted in “apparently equivalent outcomes” in terms of bodyweight reduction and body composition change. In addition, neither IER or CER was superior to the other at improving glucose control/insulin sensitivity. No different effects on thyroid, cortisol, and sex hormones were seen between IER and CER, though the authors concede that there’s insufficient research comparing neuroendocrine effects of the two diet types to draw definitive conclusions in this area.

Interestingly, IER was superior at suppressing hunger. The authors speculated that this might be attributable to ketone production in the fasting phases. However, this effect was somewhat immaterial since it failed to translate into superior improvements in body composition or greater weight loss.



MB: Well, that's not quite true. These studies didn't have a suitable control group, as the participants served as their own controls. Thus, you can't say that it didn't translate into "superior improvements in body composition or greater weight loss" - it might have done so for that that group, even if that conclusion can't be drawn from the collected brunt of data. That's the problem with these systematic reviews Like it says in the paper:


Only 12 of the 40 publications included in this review directly compared IER with CER: the lack of direct comparison makes it difficult to determine whether IER is superior to CER, or for whom.

Seimon, et al. (2015)



Article continues...

Limitations of the review included the standard ones – relatively small sample sizes, relatively short trial durations, and heterogeneous study designs making comparisons outside of the same study difficult. An acknowledged limitation worth highlighting was that 14 of the 40 studies were by the same research group (Varady et al, University of Illinois at Chicago). Ideally, a more diversified and less concentrated set of labs is less likely to repeat the same errors or preserve the same biases.

Speaking of the potential for bias, Varady has published a lay- directed book titled, The Every-Other-Day Diet (19). I’m not claiming that Varady is destined to make sure her ADF study results will always square up with her book, but it’s one of the potential caveats nevertheless. I would add to these limitations that there’s a severe lack of IER (and IER vs CER) studies that include a structured training component.


MB: I agree wholeheartedly. I'm glad Alan brought this up. The opportunities for fuckery in the scientific literature are endless. Usually, industry is the culprit - you know, studies praising the benefits of snacks or breakfast (sponsored by Kellogg's or General Mills) or studies on the tremendous muscle-building effects of protein powders (sponsored by supplement companies) and the like.

These studies can't fully be trusted and needs to be scrutinised more than the rest. They're suspect, because their funding comes from a source that would benefit from a positive result, and the results should always be taken with a grain of salt. And very often, almost always in fact, these studies arrive at a positive result.

Studies sponsored by the food industry were far more likely to reach conclusions that favored the industry. They seemed more like marketing than science.
Of the 152 industry-funded studies she has examined, 140 boast results that favor the funder. That's more than 90 percent.

Food companies distort nutrition science. Here's how to stop them.


If you want to read more about this topic as it pertains to nutritional science, check out Marion Nestle and her writings. She's quite brilliant.





Why Calories Count by Marion Nestle. I found this book in a large box of bullshit that I ordered from Amazon two years ago. It was the only thing worth scavenging and I intend to read it after I'm done with a few horror novels. I figure that I'd be properly warmed up by then. A book about food politics and marketing shenanigans can get quite dark and depressing no doubt.


But food companies are as unlikely to fund research on intermittent fasting, as Coca Cola is unlikely to fund research on ketogenic diets. What Alan brings up is the potential for bias on the researcher's part, Krista Varady to be specific. Aside from researching intermittent fasting, she is also involved in selling books, namely books based off of the research she is doing. What gives?

Well. While I haven't read The Every-Other-Day Diet, but I have mixed feelings about Krista Varady. She does try a bit too hard for my liking. I covered her work* before in "Intermittent Fasting For Weight Loss Preserves Muscle Mass?" back in the days and found several problems. Note that I'm wrongfully referring to Varady as "he" in that article. In short, she published a pretty shitty review of the subject, but then again, there weren't that many data points around in 2011. Five years later, it's gotten a little better, but there's still not enough good data around to draw any definitive conclusions - and like Alan says, a lot of that data comes from the same lab (Varady's).

It's worth mentioning that Varady appeared in a laughable infomercial documentary called "Eat, Fast and Live Longer" on BBC Horizon. In it, Michael Mosley - the show host and soon-to-be-author, interviews researchers working in the field of intermittent fasting and Varady is one of them. After rewatching the segment she appeared in, I found her to be matter of fact and professional even though she dutifully suffered through all the TV show gimmicks thrown at her - they gorged on hamburgers and fries to show that you could stuff your face and still lose weight on ADF, for example.

By the way, this "documentary" served as a launching pad for Michael Mosley's worthless book The FastDiet. Seems like there was some kind of falling out between Varady and Mosley after that. Anyway. Don't waste your money. If you want a book on intermittent fasting, pick up Eat Stop Eat.

Now, speaking of Varady, there's nothing wrong with pushing your agenda, but don't shove it down peoples throats by publishing bad research and doing shady shit like failing to disclose your conflicts of interest, because that makes you suspect in my eyes.

That said, there's nothing fishy about her recent work, as far as I can tell. It's entirely possible that Varady and her colleagues got together one night and decided amongst themselves to doctor the results, but I find that very unlikely.





It's kind of spooky, but a client just sent me this two minutes ago. I'm mentioned on the same page as Mosley and Varady, and I'm reading it just as I finish up this paragraph. I believe he was reading a book by his doctor, Robin Willcourt. I'll have to ask about the title, so I'll add it here later for those interested. Update: Name of the book is  Chasing Antelopes: Why All This Caused All That


When fuckery strikes in science, it's usually a lot more subtle and sinister. I would know, because years ago, I approached Alan with this subject. See, I had uncovered some sophisticated tampering with the results of a study that received a lot of spin on social media and the mainstream news. I was slightly distressed over the fact that he had missed it - the studies appeared in the AARR, not only once, but twice - and presented my findings. I needed a second opinion, because maybe I was making a hen out of a feather.

Nope. Alan agreed, it was some shady shit. In fact, it was a case study in deceit. Career-ending, if you ask me. But to this day, no one has debunked the findings, and the researcher is still active; polluting the journals with more bullshit for every new study that gets published. Who knows, maybe one day I'll put an end to it.

The key point of all this, is that science can't be trusted for shit, unless you do your due diligence and read the fine print. But in this particular case, concerning Krista Varady, I'm not worried.


Article continues below...


This limitation also plagues the body of research comparing various within-day meal frequencies. Readers familiar with my work know that Brad Schoenfeld, James Krieger, and I did a meta-analysis on the effect of meal frequency on body composition, and found that higher meal frequencies were associated with greater losses of fat mass and greater retention of lean mass (20). However, sensitivity analysis revealed that the removal of a single study (21) completely eliminated the significant effect of meal frequency on changes in body composition.

It’s worth noting that the studies in our analysis (and in this entire body of literature) lacked sufficient protein. An exception was Arciero et al (22) who found that 6 meals per day at 35% of total kcal as protein was superior to 3 meals per day for reducing total body fat and abdominal fat. Furthermore, 6 meals per day increased lean mass despite hypocaloric conditions.


MB: Sure thing. Something like that only happens in a study sponsored by EAS, Alan.


Article continues below...

What about muscle gain? 


The retention of lean mass in IF studies has been seen repeatedly. However, the question of muscle gain via IF remains unanswered since the investigative focus of IF research has been on weight/fat loss and accompanying clinical effects. No IF studies in the current literature have focused on the goal of gains in muscle size and/or strength. As such, No IF studies to-date (at least none that have passed peer review) have included a structured, progressive resistance training program.

This is untreaded ground fresh for the taking by researchers with the desire to do so. With that said, a poster presentation by Tinsley et al (23) at the The 12th ISSN Conference and Expo provided a summary of their study that compared the effects of TRF (on non-training days, all calories consumed in a 4-hour period) and progressive esistance training (RT) 3 days a week for 8 weeks – versus an RT group presumably on their usual diet. No between-group differences were seen in body composition, but interestingly, TRT+RT outperformed the RT in leg press maximal strength and in bench press endurance. The full text of this will be interesting to dig into if/when this study makes it into publication.


MB: Very interesting indeed. Reading the paper behind this presentation, the sentence "Noticeable differences in individual responses to the programs were noted." caught my eye. I spoke to the lead author, Grant Tinsley, and here's what he had to say about that.


Me:

Care to elaborate on this part? 
"Noticeable differences in individual responses to the programs were noted."

How did this present itself? In what group did these high/low-responders reside?


Grant:

Thanks for the email. I’m familiar with your work online, and I read a good number of your articles as my interest in intermittent fasting developed a few years ago. In regards to the abstract, that individual variability data wasn’t the focus, but I did want to mention it. That data is the focus of an abstract we wrote which will be presented at the Texas chapter of the American College of Sports Medicine in early March (and at the national conference in Boston this summer). Although we had a statistician look at the data a few different ways, I think that the descriptive information about percent changes seen during the study were most interesting.

Here are some of the major ones which we included in the upcoming abstract: For the TRF + RT group, percent changes ranged from -5.5 to +2.6% for body weight, -22.1 to +9.4% for fat mass, -7.7 to +4.6% for lean body mass, +3.4 to +30.4% for bench press 1-RM, and +10.1 to +67.6% for leg press 1-RM. 

For RT alone group, percent changes ranged from -6.6 to +2.1% for body weight, -14.4 to +12.6% for fat mass, -4.1 to +3.9% for lean body mass, +4.9 to +12.9% for bench press 1-RM, and +14.3 to +37.7% for leg press 1-RM. 

There were individuals who responded favorably and unfavorably in both groups. Based on our interviews of subjects (discussed more in the full manuscript, which should be submitted this week), I believe that the intermittent fasting positively influenced some individuals food choices, but negatively influenced others (i.e. some individuals “felt healthier” and thus made better food choices, which likely improved their body composition results, while others felt that they would eat anything and everything in sight whenever they were allowed to eat).

I hope that information is somewhat helpful.

....


Article continues...


The Editor’s Cut of the May 2012 issue of AARR pondered the question of what might be the lower threshold of meal frequency for optimizing muscle gain. I concluded that this threshold, based on what we knew at the time, was probably 3 protein-rich meals. I contended that a lower daily meal frequency than that would compromise maximal rates of muscle gain. Since that time, a replication of well-controlled studies has shown the superiority of 4 doses of 20 g whey eliciting a stronger anabolic response during a 12-hour period than 2 doses of 40 g or 8 doses of 10 g (24, 25). These findings made me re-think my position of a 3- meal minimum. It’s plausible that folks with the goal of maximizing rates of muscle gain should look to a minimum of 4 daily doses of protein at of at least 20-40 g (older subjects require 35-40 g to maximize the anabolic response). (26-28)



MB: This is all nice and dandy in theory, if it weren't for the fact that...

1. The studies that made Alan "re-think" his position of a 3-meal minimum are all funded by Néstle - a controversial company who likes to be addressed as the “world’s leading nutrition, health and wellness company.” The former Néstle-owned supplement company Musashi supplied the whey protein used in at least one of the two studies Alan cites.

Remember the quote from Marion Nestle - no relation to the company Nestlé - earlier in the article? Here it is again:

Studies sponsored by the food industry were far more likely to reach conclusions that favored the industry. They seemed more like marketing than science.
Of the 152 industry-funded studies she has examined, 140 boast results that favor the funder. That's more than 90 percent.

If you think the supplement industry is any different, you're batshit crazy. I'm willing to go out on a limb and say that it's closer to a 100% when it comes to the supplement industry.


2. The results obtained in these studies are unlikely to be relevant for real-world eating habits and real-world results.

However, it is important to note that this response was characterised when protein was ingested alone, and as the authors acknowledge, this finding cannot be evaluated in the context of a mixed meal. Indeed, it is commonplace to consume protein in the form of a mixed-macronutrient meal. Therefore, it is reasonable to postulate that macronutrient co-ingestion could alter intestinal transit, thus influencing amino acid absorption kinetics () and perhaps MPS. Moreover, this study used high-quality whey protein
With regard to the notion of applicability to the ‘real-world’ setting, it also may be significant that the participants entered the experimental trial in the fasted state. As a result the authors are unable to identify whether a pre-exercise meal would influence the MPS response to RE and various feeding strategies. This point becomes more relevant when considering the impact of insulin on MPB with regard to the true growth response and therefore the long-term applicability of the findings.

Pattern of protein ingestion to maximise muscle protein synthesis after resistance exercise. Commentary by McGlory, Wardle & Macnaughton (2013).


3. Grant Tinsley, previously mentioned, showed that there were no major differences in lean body mass gain between one group maintaining a standard meal frequency and one group adhering to a 4-hour feeding window while performing weight training thrice a week for 8 weeks. In fact, less frequent eating lead to superior results overall, as the intermittent fasting group outperformed the other group in measures of leg press strength and bench press endurance.

How is that possible? Well, perhaps it's only possible without a supplement company as your funding source, as you're not dependent on delivering results that favour an approach which entails gobbling down protein shakes between your meals. Because that's what this is really about in the end - supplement companies fund studies that will tell people to eat more frequently to maximise muscle growth, because that means they profit. No one really eats more than three cooked meals a day - so if you can throw out some gobbledygook about how you must spike muscle protein synthesis every few hours, in comes the protein shakes = profit.



Article continues....


Of course, the big limitation is that acute studies can measure protein synthesis but they can’t measure changes in body composition. Recent work by MacKenzie-Shalders found no significant difference in lean mass increase between a high protein intake (2.6-2.7 g/kg) spread across 4 vs 6 meals in elite rugby players. This findings are interesting, but once again, 3 meals per day remains a gray area in the question of a minimum for maximizing muscle growth. Perhaps future studies will compare 3 meals versus 5 or 6 for this purpose – while imposing an energy surplus and a progressive resistance training program. Seems like just a matter of time before someone in the current or newer generation of researchers attacks this gap in the literature.


MB: Yes, and preferably someone without ties to a supplement company.


Article continues....

Concluding perspectives & applications 


IF has proven itself to be an effective approach to dieting, and has outperformed conventional dieting in some cases. In the interest of cohesion to the topic, this article didn’t delve into IF’s effect on athletic performance. However, it’s important to keep in mind that IF protocols can compromise performance goals if careful modifications are not made. In general, IF is best applied to goals oriented toward altering body composition and clinical markers that occur alongside body fat reduction. This is not to say that muscle gain cannot occur with IF – it’s just that the rates of gain will not likely be maximised.

As for which IF variant to chose (ADF, WDF, TRF, etc) if one decides to try IF, the good news is that they all have demonstrated effectiveness in the literature, and therefore can be chosen on the basis of personal preference. Just remember that there is no special metabolic magic in IF, just like there’s no stoking the metabolic furnace with 6 meals a day.


Article ends.



Alan ends by reminding the audience that there is no special metabolic magic in IF, just like there's no stoking the metabolic furnace with 6 meals a day. He's right on both accounts, but loses credibility by pushing for something that seems equally ludicrous; the assumed fact that a higher meal frequency, specifically "a minimum of 4 daily doses of protein", is superior for muscle gain. There is not one good independent study in support of this claim - the ones he cites are either sponsored by Nestlé or EAS, and most of them doesn't measure real-world results.

It's unfortunate to see that Alan has fallen for this. At the very least, I would like him to exercise his critical thinking skill and question the validity of the studies he forms his opinion on.

Meanwhile, he discounts the studies not backed by supplement companies that does measure real world results - and these all show that there's either no difference between between low or high meal frequencies when weight training is involved, or a slight edge to be obtained by a lower meal frequency.

I don't think Alan is in cahoots with the supplement industry nor do I think he's wilfully misleading his audience. What I do think, is that he doesn't see all cards on the table, and that he would do well to reflect more on possible conflicts of interests in the papers that he reads and presents in Alan Aragon's Research Review.

That's all folk. Thank you all for reading. Special thanks to Alan Aragon for a large part of the content and for the willingness to participate in this open "peer review" of his article.

P.S. For those of you who aren't aware, I am no longer on hiatus. I am actively working with and accepting new clients. People who sign up during the month of March or April get a $50 discount. If you're looking to get beach ready, get in touch.

P.S.S. I will be competing at Eleiko Sportscenter in Halmstad on March 20th and starting 11.30-12.00 GMT, you will be able to livestream the event on YouTube. The link will be up on www.rga.nu, so stay tuned for that. Don't hesitate to swing by and say hi if you're in the vicinity. 

P.S.S.S. One last thing, I've fixed the PayPal donation button at the bottom of my page. It was broken for the longest amount of time. :( If anyone wants to donate, I highly appreciate it.

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24. Moore DR, Areta J, Coffey VG, Stellingwerff T, Phillips SM, Burke LM, Cleroux M, Godin JP, Hawley JA: Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males. Nutr Metab (Lond) 2012, 9:91.

25. Areta JL, Burke LM, Ross ML, Camera DM, West DW, Broad EM, Jeacocke NA, Moore DR, Stellingwerff T, Phillips SM, et al: Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol 2013, 591:2319-2331.

26. Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr. 2012 Nov 28;108(10):1780-8.

27. Pennings B, Groen B, de Lange A, et al. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am. J. Physiol. 2012; 302:E992–9.

28. Kim IY, Schutzler S, Schrader A, Spencer H, Kortebein P2, Deutz NE, Wolfe RR, Ferrando AA. Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults. Am J Physiol Endocrinol Metab. 2015 Jan 1;308(1):E21-8.

29. MacKenzie-Shalders KL, King NA, Byrne NM, Slater GJ. Increasing Protein Distribution has no Effect on Changes in Lean Mass During a Rugby Preseason. Int J Sport Nutr Exerc Metab. 2015 Jul 1. [Epub ahead of print]





My name is Martin Berkhan and I work as a nutritional consultant, magazine writer and personal trainer.

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