Skipping Breakfast Decreases Energy Intake, Water Before Meal Trick Works, Food Addiction Self-Diagnosis, Eating Speed & Obesity, Chilled Water as a Nootropic & More

Food addiction is a self-diagnosed disease that befalls preferentially those people who spend hours and days on the Internet seeking for an excuse for their inability to lose weight.

It has been a while since I have published the last installment of the short news. Today, however, the publication of the latest edition of the scientific journal Appetite appears to be a good opportunity to finally put out another of the short news potpourris.

I mean, one of the study shows that it may be essential for your well-being to listen to what scientists say and eat healthy, not unhealthy, which is associated with below average well-being in undergraduate students at the Cardiff University (Richards. 2014). But the study by Richards et al. is by no means the only one with highly health-relevant and surprisingly interesting information you will find in today's short news potpourri.

Learn more about the effects of your diet on your body composition at the SuppVersity

Only Whey, Not Soy Works for Wheytloss

Taste Matters - Role of the Taste Receptors

Dairy Protein Satiety Shoot-Out: Casein vs. Whey

How Much Carbs Before Fat is Unhealthy?

5 Tips to Improve & Maintain Insulin Sensitivity

Carbohydrate Shortage in Paleo Land

I mean, who would have guessed that we have a built-in apathy against being too close to obese individuals? No? Well, me neither, but this is just what L.D. Stafford and K. Banks found in their latest study: "[T]he mere proximity effect", which occurs, when normal-weight individuals stand close to obese ones, "can be influenced positively or negatively depending on the perceived status of the non-target individual and that implicit attitudes act to modulate this effect" (Stafford. 2014).

And there is more than just exotic study results in the latest edition of Appetite - examples? Well, here you go:

• 

  Another recent study indicates: Having a small breakfast (118kcal) before morning can benefit 5h post-exercise mood and appetite control in the time between breakfast and lunch and will avoid the cognitive decline associated with consuming a larger breakfast (Vasey. 2014)

  Another breakfast-omitting study (Plekhanova. 2014) shows that high energy intakes at breakfast increase the total daily energy intake compared to both no breakfast and a regular breakfast. Interestingly, though, the energy intake between 9:00-14:00 and 14:00-bedtime was similar between conditions (P>0.05).
  
  Overall, the most important message of the study is thus, the subjects of the UK study at hand indicates that normal- and overweight 2 to 14 year-old girls do not appear to compensate by consuming more energy over the remainder of the day during three days of breakfast omission compared with habitual or high-energy breakfast consumption.
  
  "The lack of compensation in terms of energy intake indicates that energy expenditure may be more important in explaining the higher obesity risk in girls who do not regularly consume breakfast," the scientists who are still analyzing the effects on physical activity point out.
• Scientists find what makes the British fat (Stewart-Knox. 2014) and it's the spit image of the sedentary, meat eating, oil omitting, non-resilient man with higher mood valance and sick relatives. Of these indirect pathways to dietary habits, physical activity level, higher resilience and mood valance were directly related to negative life events, which are thus another determinant of increased waist circumference in middle-aged British adults.
  
  Sounds crazy? Well, but that's exactly what scientists from the University of Bradford found to be associated with increased weight circumference in a representative samples of middle-aged adults aged >43 years were recruited in Great Britain (GB) (n = 1182). 

Think of energy containing foods as fluids... and bang! they become more satiating! A recent study from the University of Sussex (McCrickerd. 2014) confirms once again that satiety is triggered in the brain. In a small scale study the researchers observed that the satiating effects of one and the same calorie containing beverage increased when it was served as a "filling snack" instead of a fluid that was designed to "quench the thirst".

• The water-trick works (Corney. 2014) you all know that common wisdom is commonly bullsh*t, but in the case of the "water-preload reduces food intake" myth, scientists from the Loughborough University have recently been able to show that "consumption of 568 ml water immediately before a meal reduces energy intake in non-obese young males and might therefore be an effective strategy to suppress energy intake in this population."
  
  When the participants arrived at the laboratory fasted (7–10 am) all consumed an ad-libitum porridge breakfast, with either 568 ml water (PRE) or no water (NO-PRE) consumed immediately before the meal. Subjective feelings questionnaires to assess hunger, fullness and satisfaction were completed before (pre-trial) and after (post-trial) the meal in both trials and after the water preload (post-PRE) during PRE.
  
  

  

  Figure 1: Energy intake w/ and w/out water preload (Corney. 2014)

  As you can see in Figure 1, the subjects who didn't receive the water preload consumed statistically significantly more energy than those who didn't.
  
  Immediately after the water preload the subjects in the PRE group also experienced an increase in fullness and satisfaction and a decrease in  hunger compared to pre-trial.
  
  After the meal, on the other hand, the fullness and satisfaction ratings in both groups were identical.
  
  Thus, "[t]his study demonstrates that consumption of 568 ml water immediately before a meal reduces energy intake in non-obese young males and might therefore be an effective strategy to suppress energy intake in this population." (Corney. 2014) Drinking water with the meal, by the way has previously been shown to be not effective to reduce the food intake in lean women (Rollls. 1999); in obese older individuals, on the other hand, it worked (Davy. 2008)

  

  Figure 2: Weight loss (left) and energy intake (right) in a 12-week study investigating the effects of
  pre-meal water intake (500ml) on weight loss (Dennis. 2014)

  Moreover, a study by Dennis et al. shows that consuming 500 ml water prior to each daily meal helped subjects on a hypocaloric diet lose an extra ∼2 kg over the course of a 12-week study (Dennis. 2010).
• We buy & eat the packages we know and like (Gutjar. 2014), study shows. While in a blinded condition liking was the only determinant of food choice in a recent study from the Wageningen University, food choice in the "familiar package session", where the subjects had to pick from a bunch of unhealthy breakfast drinks and dessert products, lay between the blind and naïve package session.

Question: Can advertising make us choose certain foods? At least in preschool children it takes just 30 seconds of ad-exposure to influence their food preferences (Borzekowski. 2001). "Nutritionists and health educators should advise parents to limit their preschooler's exposure to television advertisements," scientists say.

• The scientists interpret their results as being indicative of the guiding effect of extrinsic factors, in this case the packaging, which can have a similar impact on food choices as intrinsic (sensory) properties.

• 

  Figure 3: Previous studies show that chewing your food 40x vs. 15x will significantly reduce the food intake in lean and obese subjects. Sign. effects on hunger and satiety will yet be apparent only in the obese (Li. 2011)

  Fast eaters have higher BMI, waist circumference and body fat! Scientists from the Wageningen University analyzed data from 311 men and 551 women from the Dutch NQplus cohort. What they found was that (a) 17.4% of the women described themselves as being slow, 54.3% as average and 28.3% as fast eaters and that (b) fast eating women had higher weight, BMI, waist circumference and body fat (p<0.05).
  
  Similar results were observed for the male participants of whom 8.7% of reported to be slow, 44.7% average and 46.6% fast eaters. A result that supports previous evidence indicating that a reduction in eating speed / increase in chewing frequency decreases food intake.
• Chilled water as a nootropic! You've read previously that 500ml water can help you lose weight. Interestingly enough the same 500ml chilled water may also help you master your next exams.
  
  According to a study from the University of Reading the consumption of 500ml of chilled water before a set of standardized cognitive tests will improve performance in several of the tests in young and older individuals (Masento. 2014).
• High flavenol cacao drink increases cerebral perfusion in older individuals (Lamport. 2014) One of the latest studies from the University of Reading investigated the effect of a single acute dose of flavanols on cerebral blood flow and fount that the flavenol-rich (494 mg vs. 23mg) drinks  lead to significant increases in regional perfusion across.

• 

  Figure 4: In contrast to whole fruit which increase the risk of diabetes, fruit juices increase T2DM risk sign. (Muraki. 2014)

  If it contains fruits or a lot of water it must be healthy (Bucher. 2014). Parents and children's health perception of beverages are highly susceptible to marketing gabberish. Worst of all, while "water is good", "fruit is even better".
  
  In the eyes of the parents and kids who participated in a recent study at the ETH Zürich fruit content seemed to be a more important criterion specifically for children to rate a certan food as "healthy". Bad news, in view of the fact that fruit juice - in contrast to whole fruit - consumption is associated with an 8% increase in type II diabetes risk according to a 2013 Harvard study (Muraki. 2013).

Food addicts - what do they say about themselves? A recent study (Ruddock. 2014) found that those who identified as a ‘food addict’ reported frequent food cravings, a preoccupation with food, unhealthy eating patterns, a lack of dietary self-control, and the tendency to eat in the absence of hunger. Furthermore, food addicts reported a problem controlling their intake of foods high in fat and/or sugar. Non-addicts reported the opposite to these behaviours, thus indicating that self- perceived addicts and non- addicts share similar beliefs about what characterizes food addiction.

And last but not least, I want to conclude this installment of the short news with a primer on food addiction. An Internet-based disease... well, sort of. The latest data from the University of Liverpool (Hardman. 2014) would at least suggest that having read on the Internet (or elsewhere) about food addiction and the subsequent belief in the existence of this pathology increases the prevalence of being a “food addict” on both the self-diagnosed measure (57% vs. 27%, respectively, p = .018) and the Yale Scale (16% vs. 0%, p = .02).

As Herbert points out, "[t]hese findings suggest that people readily endorse the concept of food addiction as an explanation for their behaviour." (Herbert. 2014) What will have to be determined in future studies, however, is whether one's belief in his / her own food addiction will also affect the actual food intake -- in other words: Is there a "I am a food addict, so I can't but eat until I die" phenomenon | Comment on Facebook.

References:

• Borzekowski, Dina LG, and Thomas N. Robinson. "The 30-second effect: an experiment revealing the impact of television commercials on food preferences of preschoolers." Journal of the American Dietetic Association 101.1 (2001): 42-46. 
• Bucher, T., M. Siegrist. "If it contains fruits or a lot of water it must be healthy. Parents and children's health perception of beverages." Appetite 83 (2014):347.
• Corney, R.A., C. Sunderland, L.J. James. "Effect of an immediate pre-meal water preload on voluntary energy intake in non-obese young males." Appetite 83 (2014):361.
• Davy, Brenda M., et al. "Water consumption reduces energy intake at a breakfast meal in obese older adults." Journal of the American Dietetic Association 108.7 (2008): 1236-1239.
• Dennis, Elizabeth A., et al. "Water Consumption Increases Weight Loss During a Hypocaloric Diet Intervention in Middle‐aged and Older Adults." Obesity 18.2 (2010): 300-307.
• Gutjar, S., C. de Graaf, G. Jager. "Food choice. The battle between package, taste and consumption situation." Appetite 83 (2014):358 
• Hardman, C.A., H.K. Ruddock, R. Dallas, J. Scott, P.J. Rogers, E. Robinson. "Food addiction, myth or reality? The effects of priming beliefs about food addiction on self-diagnosis and consumption." Appetite 83 (2014): 355.
• Lamport, D., D. Pal, C. Moutsiana, D.T. Field, C.M. Williams, J.P.E. Spencer, L.T. Butler. "The effect of flavanol rich cocoa on cerebral perfusion in older adults during conscious resting state." Appetite 83 (2014):351.
• Li, Jie, et al. "Improvement in chewing activity reduces energy intake in one meal and modulates plasma gut hormone concentrations in obese and lean young Chinese men." The American journal of clinical nutrition 94.3 (2011): 709-716. 
• Masento, N.A., A. John, V. Wilton, V. Benzesin, D.T. Field, L.T. Butler, C.M. van Reekum. "Investigating the effects of acute water supplementation on cognitive performance and mood in young and older adults." Appetite 83 (2014):355.
• McCrickerd, K. L. Chambers, M.R. Yeomans. "Food or fluid? The context of consuming a beverage influences satiety." Appetite 83 (2014):348.
• Muraki, Isao, et al. "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies." BMJ: British Medical Journal 347 (2013).
• Plekhanova, T., J.K. Zakrzewski, Effect of consuming compared with omitting breakfast on free-living energy intake and eating patterns in overweight and non-overweight adolescent girls, Appetite 83 (2014):361.
• Richards, G., A.P. Smith. "Diet and wellbeing in undergraduate students." Appetite 83 (2014): 362.
• Rolls, Barbara J., Elizabeth A. Bell, and Michelle L. Thorwart. "Water incorporated into a food but not served with a food decreases energy intake in lean women." The American journal of clinical nutrition. 70.1 (1999): 448-455. 
• Ruddock, H.K., C.A. Hardman, M. Field. "'I perceive myself to be a food addict'. A qualitative exploration of the ‘food addiction’ concept." Appetite 83 (2014):355.
• Stafford, L.D., K. Banks. "Don't (do) stand so close to me. Mere proximity effects in overweight and underweight contexts." Appetite 83 (2014): 362.
• Stewart-Knox, B., M. Duffy, B. Bunting, D. Almeida, M. Gibney. "Psychological pathways to central obesity in healthy middle-aged British." Appetite 83 (2014):361.

"Breakfast Keeps You Lean" Myth or Mystically True: Hard To Tell With All the Bias, Highly Improper Language Use, Misleading Citations and Unwarranted Causal Implications

We know just one thing about breakfast: Everyone believes it was good for you :-)

Let me first point out that large parts of this article are based on ideas from recently published paper by Brown, Brown and Allison who wrote about the unwarranted and deep rooted believe that skipping breakfast was the first step on the royal road to obesity in a recent issue of the American Journal of Clinical Nutrition (Brown. 2013). Their hypothesis that the conviction that breakfast is the most important meal of the day was so strong that the analyses of experimental and epidemiological data will always fall in line with the (subconsciously) expected outcome, is so appealing that I do not want to deny you this information.

Now, aside from the fact that I know that some of you are not willing to spend the time to read the full-text of the paper, I would not even be allowed to put it up for you to download it. In view of the fact that I also feel that I have one or another thing to add to the discussion, I decided to take compile a brief summary of what I believe are the most important points in Brown et al. 's excellent paper.

I already hinted at the main criteria of biased reporting the researchers used in the title of today's SuppVersity article:

• For the average Joe, scientific bias is only an indirect problem. For him statements like
  

  • "The fact is, when you’re trying to lose body fat, you can’t skip breakfast." (Dr. Oz),
  • "In fact, skipping breakfast actually increases your risk of obesity." (Mayo Clinic),
  • "Want to trim your waist? Try eating breakfast" (Academy of Nutrition and Dietetics),

  or the Surgeon General's assertion "Eating a healthy breakfast is a good way to start the day and may be important in achieving and maintaining a healthy weight" are the real problem (examples from Brown 2013).
  
  Our constant exposure to statements like these from "authorities" and those people in our surrounding who listen to what these "people in the know" say, has the concept of the "healthy" and "anti-obesogenic" breakfast engrained so deeply into our brains that even scientists apparently can't escape the subconscious pro-breakfast bias.
  Biased interpretation of one’s own results. Specifically in the abstracts, findings in favor of the notion that having breakfast will help preventing obesity are emphasized, while findings that are not in line with this hypotheses are either mentioned only as a side-note or simple left out.
• Improper use of causal language in describing one’s own results. Even saying "breakfast has a protective effect against diabetes", would in 99% of the cases qualify as improper use of causal language and that's not just because there is no "may" or "suggest" in here, but simply due to the fact that neither cross-sectional nor longitudinal observational studies (which is what we are dealing with mostly) are actually able to determine causal relationships.
• Misleadingly citing others’ results. Brown et al. identified a pretty impressive example for this practice, when they analyzed the available literature on the matter. It's a study by Schlundt et al. that observed a borderline significant interaction between being assigned to a breakfast condition that differed from the subjects' habitual one, but failed to identify a significant main effect of breakfast consumption on the outcome of their controlled weight loss trial. In other words: "Subjects who were assigned to change from their baseline breakfast frequency lost more weight than did subjects assigned to continue their baseline breakfast frequency" (Brown. 2013). Despite the fact that this does obviously not warrant the conclusion that that breakfast eating would promote weight loss, Brown et al found that of the 46 English language articles that cited Schlundt et al in the context of the proposed effect of breakfast on obesity (PEBO) only 17% of articles cited the results accurately. 29 of them "abused" the results in favor of the "breakfast helps weight loss"-hypothesis and a single article used Schlund et al.'s results to argue against its benefits, which is obviously just as unwarranted.
• Improper use of causal language in citing others’ work. Basically not different from what I have already explained in the context of the interpretation of one's own results, the example Brown et al. use in their paper is a 2002 study by Wyatt et al. that identified a co-occurance (which has not the slightest causal element in it) of weight-loss maintenance and breakfast eating makes it quite clear that it's not just the supplement industry that loves to mask co-occurrences as causal relationships. Only 29% of the papers discussing the results of Wyatt et al. got the difference right, 26% turned it into an association (which was not even tested) and 22% went even one step further and talked about some sort of causal relationship being involved here.

The biased, sometimes false reporting, as well as the focus on studies that were designed to produce the desired result "Breakfast is good for you!" must not hide the fact that we actually still don't know if eating breakfast will have beneficial, neutral or maybe even negative on our metabolism, body weight and body fat levels.

Now, what's actually true? What can you believe?

As Brown et al. point out, "there have been very few RCTs that investigated breakfast and weight change." (Brown. 2013) Consequently, researchers' overview of the currently available literature does not allow for a definitive answer to the litmus question "Is skipping breakfast good or bad for you?"

Figure 1: Randomly selected long(er) term studies on weight gain / loss of having / not having breakfast.

I know that some of you will now jump at the results of those trials that suggest that skipping breakfast is beneficial, surf over to whatever "anti-breakfast"-facebook group they are in and start celebrating the corresponding articles as evidence that they've been right all along... don't do that! In view of the intriguing observations Schlundt et al. made in their previously cited stud, it may simply be that switching from one meal pattern to the other may have brought about the beneficial effects.

Food timing can also influence our biological clock | learn more

How simply changing the system may facilitate weight loss : You just have to look the success people have with the guru-esque "you must not eat"-approaches you will find plastered all over the Internet (and costly ebooks) - if your favorite foods are not on the "you are allowed to eat"-list (which is almost always the case with these 5-10 item lists), you will automatically lose weight (* it is important to point out that the beneficial weight loss effects do not depend on the "quality" of the system - you may switch from a bad diet to an even worse one - as long as you break with your habits and can't overeat on your favorite foods, you'll loose weight)

A similar effect as with the contemporarily increasingly popular "you must not eat this" diets will obviously also occur, if you are a breakfast eater who loves his tons of cereals and bagels or your truckloads of bacon and eggs. Once you simply skip on those, it's not very likely that you will compensate on other foods later in the day, so that it is not surprising if you lose weight - you simply consume less energy than before!

Incidentally, intermediate endpoint studies would support the notion that behavioral mechanisms play a much larger role in the etiology of the purported link between breakfast consumption and obesity. The often heard hypothesis that having breakfast will reduce subsequent energy intake in the course of the day and thus result in an overall reduced food intake, however, is not supported by the currently available evidence.

Figure 2: Selection of controlled studies investigating the effect of breakfast eating / skipping on total energy intake.

Things look different for observational studies, though. The majority of these usually cross-sectional assessments of the temporary relationship of breakfast consumption and obesity, indicates that there is "a clear link between breakfast omission and excess weight" (Brown. 2013) - what these analyses don't tell us, though, is that this is a causal relationship.

" Cardio on Empty is Fatiguing. Fasting Without Exercise, However, is Nootropic" | read more

Bottom line: In the end, there are only three things we know for sure. There is a major bias in favor of a desirable (=preventive) effect of breakfast on obesity in the general public, the authorities and even among the scientists. This bias is reflected in the currently available literature in form of improper language use, misleading citations and unwarranted causal implications.

As long as we don't get rid of this built-in bias, we are left with a host of observational evidence, tons of flawed reviews and no answer to the (imho not even important) question whether you should or shouldn't have breakfast if you want to lose or maintain your current body weight.

References:

• Ask AS, Hernes S, Aarek I, Johannessen G, Haugen M. Changes in dietary pattern in 15 year old adolescents following a 4 month dietary intervention with school breakfast–a pilot study. Nutr J 2006;5:33.
• Astbury NM, Taylor MA, Macdonald IA. Breakfast consumption af fects appetite, energy intake, and the metabolic and endocrine re sponses to foods consumed later in the day in male habitual breakfast eaters. J Nutr. 2011;141:1381–9. 
• Brown AW, Bohan Brown MM, Allison DB. Belief beyond the evidence: using the proposed effect of breakfast on obesity to show 2 practices that distort scientific evidence. Am J Clin Nutr. 2013 Nov;98(5):1298-308.
• Crepinsek MK, Singh A, Bernstein LS, McLaughlin JE. Dietary effects of universal-free school breakfast: findings from the evaluation of the school breakfast program pilot project. J Am Diet Assoc 2006;106: 1796–803.
• Geliebter A, Yahav E, Forbes G, Hashim SA. Lunch meal intake folowing high and low glycemic breakfast cereals. FASEB J. 1999;13: A871–A. 
• Geliebter A, Yahav E, Biase B, Hashim SA. Lunch meal intake folowing high and low fiber breakfast cereals. Obes Res 1999;7:44S.
• Geliebter A, Yahav E, Haq S, Hashim SA. Cholesterol and weight change following daily high or low fiber breakfast cereals. Obes Res 2000;8:25S. 
• Hirsch EHE, Halberg F, Goetz FC, Cressey D, Wendt H, Sothern R, Haus E, Stoney P, Minors D, Rosen G, et al. Body weight change during 1 week on a single daily 2000-calorie meal consumed as breakfast (B) or dinner (D). Chronobiologia 1975;2(suppl 1):31–2.
• Jakubowicz D, Barnea M, Wainstein J, Froy O. High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013 Mar 20.
• Kral TV, Whiteford LM, Heo M, Faith MS. Effects of eating breakfast compared with skipping breakfast on ratings of appetite and intake at subsequent meals in 8- to 10-y-old children. Am J Clin Nutr 2011;93: 284–91. 
• Leidy HJ, Racki EM. The addition of a protein-rich breakfast and its effects on acute appetite control and food intake in ’breakfast-skipping’ adolescents. Int J Obes 2010;34:1125–33. 
• Levitsky DA, Pacanowski CR. Effect of skipping breakfast on sub sequent energy intake. Physiol Behav 2013;119:9–16. Taylor MA, Garrow JS. Compared with nibbling, neither gorging nor a morning fast affect short-term energy balance in obese patients in a chamber calorimeter. Int J Obes Relat Metab Disord 2001;25:519–28.
• Powell CA, Walker SP, Chang SM, Grantham-McGregor SM. Nutrition and education: a randomized trial of the effects of breakfast in rural primary school children. Am J Clin Nutr 1998;68:873–9.
• Rosado JL, del R Arellano M, Montemayor K, Garcı´a OP, Caaman˜o Mdel C. An increase of cereal intake as an approach to weight re duction in children is effective only when accompanied by nutrition education: a randomized controlled trial. Nutr J 2008;7:28.
• Wyatt HR, Grunwald GK, Mosca CL, Klem ML, Wing RR, Hill JO. Long-term weight loss and breakfast in subjects in the National Weight Control Registry. Obes Res 2002;10:78–82.

8x Increase in "Mitochondria Building" Protein PGC1-Alpha W/ Medium Intensity Exercise in Glycogen Depleted Elite(!) Cyclists: Training Revolution or Recipe for Disaster?

With only 2-7x increases in PGC1-alpha expression HIIT seems to lag behind compared to this "eat low, train low, gain high" strategy, but not every protein essay that glitters in the petri dish will turn into Olympic Gold in the real world ;-)

As a diligent student of the SuppVersity you should by now have at least a preliminary understanding of how the adaptive machine you call your "body" adapts to the various nutritional and physical challenges most people subsume under the all-encompassing and pretty nondescript terms "diet" and "exercise". Against that background it should not really come as a surprise that researchers from the The Swedish School of Sport and Health Science are soon going to publish the data of an experiment that shows that even (you could probably also say, in particular, although respective evidence is still missing) highly trained athletes can benefit from exercising in a glyocogen depleted state - at least if the yardstick you use to measure the "benefits" is an increase in mitochondrial biogenesis (Psilander. 2012).

Train high, eat low (carb), train low and...?

To elicit the differential effects of 6x10 min bouts of cycling at 60% of the individual VO2max (4min of active rest in between) with normal vs. depleted skeletal muscle glycogen stores, Psilander et al. had their 10 highly trained male national elite level competitive road cyclists and mountain bikers (27.8±1.6 years, 74.7±2.0 kg, 183±2 cm, and 4.9±0.1 l/min VO2Max) perform an 8x4min interval training at 88% of their individual VO2Max ~16.5h before they had to report back at the laboratory on the actual testing day (the intervals were seperated by 4min of active rest, i.e. cycling at 100W+).

Figure 1: Graphical outline of the experimental protocol and its effect on the glyocogen stores of the from the vastus lateralis muscle (based on Psilander.. 2012)

The protocol (see figure 1) was repeated twice, with adequate time in-between and in random order, with the subjects consuming water only and low carbohydrate meals

• low carb meals (LC) were eggs and bacon (0.02 g CHO, 0.6 g protein and 0.8 g fat/kg bw) for dinner and breakfast, providing a total of of <0.04 g CHO, 1.2 g protein and 1.6 g fat/kg bw

before the glycogen depleted trial (LC) and high carbohydrate beverages (maltodextrin-dextrose powder Carbo 134 w/ 1.0g CHO/kg bw) + high carbohydrate meals

• high carb meals (HC) were pasta with meat sauce and lemonade for dinner (1.83 g CHO, 0.53 g protein and 0.14 g fat/kg body weight bw) and oatmeal and orange juice (1.54 g CHO, 0.31 g protein and 0.12 g fat/kg bw) for breakfast and additional bananas with beverage 3,5,7 and 8 for a total of 12.6 g CHO, 0.9 g protein and 0.3 g fat/kg bw

before the glycogen repleted trial (HC).

... get impressive increases in PGC1-alpha, but no AMPK response at all!

As the data in figures 1 & 2 goes to show you the nutritional intervention was not without effect the factual glycogen levels (figure 1, right) and the glucose, insulin and fatty acid levels before and after the workout (figure 2) - and, as you would expect it, the corresponding changes in gene and protein expression in the muscle samples the researchers collected approximately 15 min before the depletion (S1) and test exercise (S2), as well as 3 h after the test exercise:

Figure 2: Free fatty acid levels before depletion (S1) and before (S2) and after (S3) exercise trial, as well as PGC1-alpha and p-AMPK expression (data calculated based on Psilander. 2012)

Now what you probably won't have anticipated, though is the absence of the expected p-AMPK response to exercise in the low glycogen (LC) trial.

"The mRNA content of the master regulator of mitochondrial biogenesis (PGC-1a) was not changed 14 h after depletion exercise (pre-test exercise) but was significantly increased 3h after the test exercise in both conditions (Fig.2). The increase was, however, much more pronounced in LG than in NG (8.1-fold vs. 2.5-fold, P<0.01). The mRNA content of two other regulators of mitochondrial biogenesis (PRC and Tfam) also increased significantly but with no difference between conditions (time-dependent effect, Py0.01; [not shown in my graph]). The mRNA content of genes for oxidative metabolism enzymes (PDK4 and COX I) only increased after LG with a significant difference between the two conditions. The mRNA content of CS, Sirt1, NRF1 and PPAR[-delta] did not change under any conditions." (Psilander. 2012)

Almost 8x elevated levels of PGC-alpha but no change in the "fat burning, GLUT-4 pomoter" AMP-activated protein kinase? How can that be? The answer to this question is actually pretty simple: If the phosphorlyation of AMPK changes in response to changes in the ATP to ADP ratio (the name is misleading, here as scientists have initially believed that the main determinant was the ATP to AMP ratio, which is yet not the case), it should be obvious that it won't change, if the ATP levels are already so low that at most the ADP to AMP, but not the already rock bottom ATP do AMP ratio will be changing.

What happens if your body senses that it cannot fuel his energetic demands with glucose?

In the presence of borderline hypoglycemic glucose levels (the normal range starts at 4.4 mmol/L; after the depleted test the subject were at 4.3 mmol/L!) your body would be ill advised to increase glucose uptake. So if this is not an option the only way to make up for the lack of energy are fatty acids. Unfortunately the amount of fatty acids your skeletal muscle can oxidize is strictly rate-limited by your mitochondrial capacity ... now, I am asking you what's the "natural", the logical and in the case of the 10 cyclists in the study at hand also the factual reaction that will get you out of this mess? Right! To build more powerful mitochondria and thus widen the "bottle neck"! And what's going to do just that? Yeah! The ~8x increase in PGC-1alpha expression you see in figure 2. 

Practical implications: From protein essays to results?  

 Now that we have gotten the mechanisms straight, there is but one question we have to answer - what does that mean for you? When and for whom does it make sense to train with depleted gycogen stores? And in an even broader context - what does that tell us about low-carbing and (intermittent) fasting?

1. 

   Before you even consider making this a staple of your regimen, I would encourage you to read the whole SuppVersity Athlete's Triad Series

   Even (or especially?) for trained athletes competing in largely aerobic sports, training in a state of depleted glycogen store can serve as a viable tool to elicit even higher (2-7x; cf. Gibala. 2009, Nordsorg. 2010. Psilander. 2010) increases in increases (8x!) PGC1-alpha and (allegedly) mitochondrial biogenesis as you would see them in response to high intensity interval training at much lower intensities (but correspondingly longer durations). 
2. Training in a fasted state does not per se guarantee / put you at risk of being glycogen depleted, neither does intermittent fasting and or "training on empty". As long as you replete your glycogen stores after your workouts you won't see similarly pronounced increases in PGC1-alpha in response to "regular" aerobic training at a low intensity. You will, on the other hand, still see increases in AMPK and, what's even more important, you will be able to perform at much higher intensities! A fact that is particularly important for the strength trainees out there.
3. While it may make sense on occasion, and merely based on it's beneficial effects on purported  mitochondrial biogenesis (I don't have to remind you that we don't have any information on whether the increase in PGC1-alpha did even translate into an increase in mitochondrial biogenesis in the absence of adequate glycogen / ATP levels!), I want to reemphasize the scientists very hint that "[l]ongitudinal studies examining protein levels and performance are required" before it can be recommended to include this practice as a staple into your routine!

4. 

   Life is to complex for black-and-white thinking, and so are AMPK, mTOR & co! Learn more in the Intermittent Thoughts.

   Long-term exercise in a glycogen-depleted state without adequate carbohydrate intake and thus glycogen repletion is not for nothing one of the causative factors of the athlete's triad (see Part I & II of the SuppVersity Athlete's Triad Series). I would therefore be very surprised if the long-term outcomes of low-carbing + (intermittent) fasting w/out regular glycogen repletion would be anything but negative, regardless of its beneficial effects on PGC1-alpha. After all, the study at hand clearly shows that you will also be missing out on the benefificl effects of increased p-AMPK expression of which you know based on what you have read in the Intermittent Thoughts on Intermittent Fasting Series that it is one of the, if not the central argument in favor of intermittent fasting.

The practical take home message of this study is therefore that exercise + diet induced targeted glycogen depletion before a workout (not via an overnight fast, only; that would leave your muscle glycogen stores largely intact, while your body is burning fat and tapping into your hepatic glycogen reserves) can become one among a whole host of tools in your workout-toolbox. You can use it sporadically, but you should not need another study to be able to predict that the downsides of chronic use are going to outweigh (purported - again, we are measuring markers only, here!) short term benefits.

On a last note: I guess you know that the SuppVersity is the place where you will hear about respective longitudinal data first, right? To make sure you don't miss that I suggest you go to www.facebook.com/SuppVersity like the page or register for updates at twitter.com/ProfDrAndro!

References:

• Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol. 2009 Mar;106(3):929-34.
• Nordsborg NB, Lundby C, Leick L, Pilegaard H. Relative workload determines exercise-induced increases in PGC-1alpha mRNA. Med Sci Sports Exerc. 2010 Aug;42(8):1477-84.
• Psilander N, Wang L, Westergren J, Tonkonogi M, Sahlin K. Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise. Eur J Appl Physiol. 2010 Oct;110(3):597-606. Epub 2010 Jun 23.
• Psilander N, Frank P,  Flockhart M, Sahlin K. Exercise with low glycogen increases PGC-1agene expression in human skeletal muscle. Eur J Appl Physiol. 02 Oct 2012 [ahead of print]

Intermittent Fasting Ramadan Style: Lose More Than 3% Body Fat Off an Already "Lean" 31" Waist in 28 Days. Plus: Why Do the "Fast / Starve Two Times à Week" Diets Work?

Feasting and a wasp waist? Does bring the two together?

You are among the couple of thousand people who have been following the Intermittent Thoughts on Intermittent Fasting Series, here at the SuppVersity you will be aware that despite "fasting windows", "feasts" and "breakfast skipping" a religious fast as it is performed by Muslims all around the world may share several key elements with what fitness fanatics think about, when they hear the words intermittent fasting". There are however a couple of key differences of which you should be aware.

• rising before sunrise and having breakfast will minimize the fasting window - While most people I know personally don't do this, there are families, where everyone gets up before the sun rises to have breakfast. With the huge dinner before bed and a (usually smaller) breakfast right after you stand up in the early AM, the fasting window which would otherwise be up to 18h wide can become pretty narrow.
• not drinking during the fast - It is religious practice, so I am not in the position to criticize it, but for anyone fasting for health purposes not drinking anything during the fasting hours is absolutely not advisable.
• food / diet quality - The average Westerner will probably assume that the food quality sucks during Ramadan, after all the family-get-togethers are not exactly occasions to eat chicken, rice and broccoli, but compared to the regular diet of the inhabitants of the Western obesity belt the self-prepared meals from real food ingredients will probably still entail an improvement in overall diet quality for many people who are fasting for religious reasons.

I guess I could enumerate at least 3 additional factors you may want to keep in mind, when you take a look at the results of the Shruthi, Hassan and Reddy, three scientist from the Bhaskar Medical Colleg in Andhra Pradesh, India, report in a paper that has recently been published in the International Journal of Recent Trends in Science And Technology (Shruthi. 2013).

31" waist as a starting value? Obviously not a US study*

Ramadan fasting increases fatty acid oxidation: In 1995 Jalila El Ati and her colleagues were able to show that the respiratory quotient, i.e. the ratio of carbs / fats that are being burned as fuel decreases by ~10% in healthy 25-39 year old women (El Ati. 1995).

The study was conducted at the research lab of Department of Physiology Bhaskar Medical College during the month of Ramadan in the year 2011 (Aug - Sept). The subjects were 50 young adults in the age group 18-24yrs - with 6 dropouts (personal reasons) that leaves us with data on the changes in body composition, blood pressure, and heart rate from 44 subjects, whose baseline BMI (24kg/m²) was very different from that of the "average" American and whose 31.5" waist is a clear indicator that they were in pretty good shape (compared to those who are currently totally digging alternate day fasting after they have failed with the South Beach, the Weight Watchers and the rest of the "I am a stupid lazy ass and don't want to make the appropriate lifestyle changes" diets in the past.

* Health alarm: Did you know that the average US teenager had a 34" waist, in 2004? That was already 2" more than 5 years before (Li. 2006; data based on NHANES 2004). If we extrapolate a yearly increase of 0.25"  this means we should have arrived at 35.25" today.

You will often hear the proponents of the the idea that some people are simply "naturally lean" state that this is usually a result of the fact that they are eating "frequent small meals" to satiety. So, based on that argumentation you would actually expect that the subjects in the study at hand, who would probably qualify as "naturally lean", may have jeopardized this "natural leanness" by robbing themselves of the opportunity to keep "grazing".

Figure 1: BMI, waist and hip circumference and body fat % before and after 28 days Ramadan fasting (Shruti. 2013)

As the data in figure 1 goes to show you this obviously did not hurt the results of the 44 subjects in the study at hand, who lost an everage of 3.1% body fat within 28 days. Given the fact that all the initially mentioned factors should reduce the efficacy of Ramadan fasting for improvement in body composition compared to that of a fast in the (meanwhile) classic "lean gains" style, this appears pretty damn impressive, right?

If you take into account that the scientists measured only subcutaneous fat (this is a necessary result of using the skinfold method), which is usually comparably slow to respond, it certainly argues for the cosmetic advantage of timed feasting over uncontrolled all-day snacking - whether the same would yet be true if we standardized the caloric and macronutrient intake is questionable (see my comment on the 2-day a week fast in the box below, as well).

---

Why do the fast 2x per week diets work? It's easy the main working principle is a reduction in calorie intake. If you assume you have a 2,400kcal intake and cut back to 800kcal (some prescribe 500kcal) on 2 days that's a 66% (80%) reduction in energy intake. Interestingly, though the compensation effect is much less pronounced than you would expect and occurs usually only on the days after the fast. So, 10% more on the days after the fasting days leaves us with a caloric deficit that will still amount to 2.720kcal (3320kcal for the 500kcal variety) or 10% (20%) per day.

Impressive it is, but in the end it's still basic mathematics: As impressive as it may be, the underlying reason - and this is something all previous Ramadan studies appear to support a simple reduction in energy intake that is, at least in some cases, supported by improvements in diet quality, reductions in carbohydrate and increases in protein intake that are brought about by the elaborate cooking, the absence of snacks and sugar sweetened beverages and the mere fact that you simply cannot stomach the same amount of food you would usually consume in three main meals and two snacks within one or two meals... no matter how huge those meals may be.

Does that exclude that "having AMPK come to its right", sirtuins, increased fatty acid oxidation and the whole fastin' hoopla may figure here, as well? No it does not, but even the significant reduction in systolic and diastolic blood pressure in the study at hand, as well as the improvements in glycemia and lipid metabolism in previous Ramadan studies are, when all is said and done, eventually brought about by the downstream effects of a reduced calorie intake. And this, is by the way also true for the "eat whatever you want all week long and cut back to 800kcal (or 500kcal) mainly from protein on two out of seven days" diets as well (see infobox to the right for an example calculation).

References:

• el Ati J, Beji C, Danguir J. Increased fat oxidation during Ramadan fasting in healthy women: an adaptative mechanism for body-weight maintenance. Am J Clin Nutr. 1995 Aug;62(2):302-7. 
• Li C, Ford ES, Mokdad AH, Cook S. Recent trends in waist circumference and waist-height ratio among US children and adolescents. Pediatrics. 2006 Nov;118(5):e1390-8.
• Shruthi B, Hassan A, Reddy BV. The Effect of Ramadan Fasting on the Body Composition, Blood Pressure, Heart Rate of Healthy Young Adults. International Journal of Recent Trends in Science And Technology, ISSN 2277-2812 E-ISSN 2249-8109, Volume 8, Issue 1, 2013 pp 31-35.

Glycogen-Free Muscle Growth - Erratum: Differences in P70K-Phosphorylation Between Glycogen De- and Repleted Leg Even Less Significant Than Previously Reported.

Image 1: For the SuppVersity Super-Student Duong Nguyen, training in the semi-fasted state worked wonders. Want to know more? Read his guest-post and visit his blog.

This is post #713 and another premier. It's the first time that I have to go back (at least partly) on something I posted three weeks ago in a post about the myth that well-stocked muscle glycogen stores would be necessary to induce an anabolic growth response in skeletal muscle. Those of you who read the respective blogpost probably remember that I had to rely on the little information there was in a short abstract that had been published in the program of the 2011 ISSN conference, because a full paper with all the information on the study had (and still has) not been published.

Now, three weeks and a long and interesting email-correspondence with the author, Donny Camera from the RMIT University in Melbourne, Australia, later, I have to admit that (my interpretation of) the abstract was not completely correct. In the abstract it says (Camera. 2011):

p70S6K^Thr389 phosphorylation in LOW [glycogen depleted leg] increased in both nutrient (15-49 fold) and placebo (∼8 fold) groups 1 h and 4 h post-exercise compared to rest (P <.05) but was only different from rest 1 h post-exercise in NORM in the nutrient group (∼36 fold, P <.05).

Back then (and to be honest, even now that I know what Donny actually meant), my understanding of "but was only different from rest 1h post-exercise in NORM in the nutrient group" was that there was no additional benefit from exercise in the normal leg, unless a post-workout drink consisting of 20g Whey + 20g maltodextrin was consumed. While I found that initially surprising I assumed that the absolute p70S6K response (remember the abstract provides information about the relative changes, only) in the non-depleted leg [NORM] would have been much higher than in the glycogen depleted leg, so that the addition of a protein + carbohydrate post-workout shake would not really make a difference.

Figure 1: This graph depicting the p70k response in the glycogen depleted and the normal leg is of merely illustrative nature the data is not identical with the original material from the study (Camera. 2011), but was made up to adequately represent the most important findings.

Now, that I have the absolute data available, I see that this is not the case (cf. schematic illustration in fig. 1). The absolute p70S6K response to exercise was within the statistical margin of error identical in both groups regardless of whether post-workout nutrients were or were not supplied. Still, the addition of the whey + maltodextrine combination increased the p70S6K response in the "anabolic" 1h window roughly 4-fold above the increase that was seen with exercise alone. In that, the increase in the NORMAL leg may have been greater; more importantly, however, the maximal degree of phosphorylation at t=1h post exercise was identical in both legs. Furthermore, the absolute data underlines the aforementioned importance of post-workout nutrient supply (in this case in the form of fast digesting protein + carbohydrate sources), as the provision of the whey + maltodextrine formula quadrupled the already pronounced increase in p70S6K phosphorylation irrespective of the glycogen status of the trained leg.

Thus, it turns out the relative values from the abstract, on which I based my previous blogpost, did provide an initial impression, but not the whole picture oft what happens on the cellular level when you train a "fasted muscle" (which is why I usually do not even bother with abstracts, if I do not have access to the full text, but in this case, there simply was no fulltext, and the results were too interesting to keep them back). Contrary to the researchers initial hypothesis was there not only more than enough "gas in the tank" of the LOW leg even after selective glycogen depletion to for the protein synthetic cascade to be put into motion, the absolute degree of p70S6K phosphorylation and (this is only a reasonable assumption) exercise and nutrient induced protein (re-)synthesis were also identical.

Image 2: Glycogen stores (magenta staining) in liver cells (A. Gunin)

Did you know that the rate of glycogen depletion in the human liver upon fasting (no exercise) is about 0.3mmol/kg liver tissue per minute? If we assume that, in a fed state, the average human being stores roughly 300mmol/kg glycogen in his/her liver, a 16-hour fast, as Martin Berkhan from leangains.com suggests them, would use roughly 96% of your liver glycogen stores (calculations based on Nilsson. 1973) - probably no coincidence that we are seeing the first detrimental effects on resting energy expenditure after this time-span, what do you think?

Personally, I was not surprised by this result, partly because I still think that this way of selective glycogen depletion is not representative of whole body starvation, the one and only state of which I would assume that you would see profound decreases in the anabolic response to exercise. And since I know you would be asking: I assume you will see identical results if you train (intermittently) fasted (and Duong is the living testimony to this hypothesis ;-), although your whole body (and especially liver) glycogen levels will probably be lower than the ones of the study participants.

Want to Clean Up Cellular Garbage? Train Fasted! Fasted Training Boosts Cellular Housekepping (=Autophagy) & Forms the Basis of Structural Adaptations to Exercise

Want to promote muscular and overall health? Do this after an 8h+ fast.

Exercise is a stressor. It modifies the intra and extracellular millieu, impairs the energetic status and stretches, sometimes even over-stretches the membranes. That certainly sounds as if you want to avoid it at all costs, but as nature had it, it is this eustress (good stress) that is absolutely essential for the remodeling of the muscle we are all working out for to happen - no stress no reason to adapt. It's that simple and does still have one major caveat: Too much stress and the adaptation turns into a constant and often insufficient repair process.

But who wants to "deconstruct" muscle, anyway?

Now, from the gymbro perspective the most important aspect of the training induced adaptation processes would probably be protein synthesis. And while you can actually argue that this was the case if things were just about "growing", a different picture emerges, when you look at health benefits and the actual remodeling process which does necessarily begin with "demodeling", or rather the demolution of old muscle tissue - when that's happening in a controlled self-induced (by the cell) manner, scientists call this process autophagy.

Autophagy is one of the main reasons fasting is good for you

Now, when cells "kill" themselves, they usually do that for a reason. In fact, the process of autophagy must be seen as part of the general housekeeping - a part with enormous importance, as one of the possible consequences  of its failure is cancer. Moreover, it has been demonstrated only recently that autophagy is also an essential process for muscle adaptation:

Suggested read: "If a High Fat Diet was a Pill, the Lay Press Would Celebrate it as 'Exercise in a Pill'" | read more

"Autophagy is activated in skeletal muscle by numerous catabolic stimuli such as food deprivation, denervation or sepsis. However, evidence for the necessity of basal autophagy level in the maintenance of myofibrillar integrity has counterbalanced the vision of a system only implicated in muscle wasting. Very recently, the activation of the autophagy-lysosomal pathway has emerged as an essential process for skeletal muscle adaptation after endurance training (Lira. 2013)." (Jamart. 2013)

That being said, a group of researchers from the Université catholique de Louvain in Belgium set out to study whether the two major pro-apoptotic mechanisms in our lives, i.e. working out and fasting would complement each other so that their effects add up and you get the double dose of healthy - and as you have learned today "muscle (re-)building" cell death.

Can you combine it? Yes you can!

As you can see in figure 1 the answer is clear: Yes, you can - meaning you can combine fasting and exercise and achieve an even greater activation of the autophagy-lysosomal pathway .

And what about humans? Do we have reason to believe this would not happen in human beings? Of course we do, but it is actually very unlikely that there will be major differences in the intra-muscular response to fasting. Plus, we do have human studies showing related benefits that are exclusive to fasted training, already (see "bottom line").

The data in figure 1 arose from the observations the researchers made, when they had a group of rodents perform a 90 min run at a speed of 10m/min (I did not plot the increases in markers of autophagy like Gabarapl1-II, Atg12, Lc3b, Gabarapl1 and p62/Sqstm1, simply because I don't think they are useful for you - take it for granted that those were only increased in the fasted state).

Figure 1: Comparison of selected markers of celluar and mitochondrial autophagy (mitophagy) in mice before and after 90min run in the fasted or fed state (Jamart. 2013)

 For the mice half of whom had been food deprived for 8h that's actually the normal speed of locomotion and would equal a low intensity walk/jog for a human being (about 55% of VO2max). The reason the scientists picked this protocol was that it has previously been shown to be sufficient to arrive at a plateau phase when no further increases in the accumulation of autophagosome number in different skeletal muscle groups of mice submitted to exercise running can be observed (He. 2012).

---

But is this even a good thing? Now, I can already see you struggling with the idea of voluntarily inducing "catabolism" - that's stupid right? Yes, you are right, it is in fact stupid to think about autophagy this way. This is not a non-selecive process that kills valuable muscle tissue like sarcopenia, it's a necessary prerequesite for the structural integrity of your muscle (get rid of the junk, build new stuff in place) and your whole body. The ability to boost local the systemic activation of the autophagy-lysosomal pathway is thus in fact a definitive plus you don't want to miss, but don't want to overtax, either (don't do it everyday, don't do it in combination with a high caloric deficit, don't forget to refuel after the workout).

Suggested read: "3x30s High Intensity Intervals Increase mTOR & Ramp Up Marker of Protein Synthesis - Even in a Fasted State!" | read more

In 2011 van Proeyen et al. observed that training fasted does not only increase the intramuscular fatty acid oxidation in 20 healthy young volunteers, it did also and this may come as a surprise, prevent "the development exercise-induced drop in blood glucose concentration" (Van Proeyen. 2011) - the same drop in blood sugar that will make you feel exhausted and is a potential risk factor for an acceleration of the metabolic downregulation that occurs, whenever you are dieting. One year before van Proeyen et al. had already established that in times of high fat overfeeding (+30%kcal; 50% fat) only fasted training was able to increase the AMPK levels (=anti-cancer, anti-diabetic, anti-obesity effect) in young men (van Proyen. 2011).

Said study by van Proyen was by the way the first to prove that fasted training is more potent than fed training to facilitate adaptations in muscle and to improve whole-body glucose tolerance and insulin sensitivity during hyper-caloric fat-rich diet. So, I suggest you remember it, when you wake up tomorrow and think about whether you should go for a run now or rather after filling up your belly with some delicious eggs or whatever it is that you have for breakfast.

References:

• He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q,
  Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby
  R, Scherer PE, and Levine B. Exercise-induced BCL2-regulated autophagy is required
  for muscle glucose homeostasis. Nature481: 511-515, 2012. 
• Jamart C, Naslain D, Gilson H, Francaux M. Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state. Am J Physiol Endocrinol Metab. 2013 Aug 20. [Epub ahead of print]
• Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, Hoehn KL, and Yan Z. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J, 2013. 
• Van Proeyen K, Szlufcik K, Nielens H, Pelgrim K, Deldicque L, Hesselink M, Van Veldhoven PP, Hespel P. Training in the fasted state improves glucose tolerance during fat-rich diet. J Physiol. 2010 Nov 1;588(Pt 21):4289-302.
• Van Proeyen K, Szlufcik K, Nielens H, Ramaekers M, Hespel P. Beneficial metabolic adaptations due to endurance exercise training in the fasted state. J Appl Physiol. 2011 Jan;110(1):236-45. doi: 10.1152/japplphysiol.00907.2010. Epub 2010 Nov 4.

Circadian Rhythmicity - "Breakfast" or "Breaking the Fast"? Fasting as Zeitgeber & All About King, Prince & Pauper

Image 1: What would a King say if you served him that for breakfast?

When it comes to the regulation of circadian rhythms by nutrient intakes (and vice versa) the first thing we have to consider is the relation of the day-/night-cycle as discussed in the previous installments of this series and our (historical) ability to hunt and gather food. With our pathetic visual acuity in the dark and our laughable odor sensitivity and sense of hearing, our food intake has always been closely in tune with the light-controlled circadian rhythm. Without the "paleolithic" requirements of gathering and hunting, however, our eating time and frequency is either consciously controlled (e.g. "intermittent fasting") or behaviorally entrained, respectively learned via socialization.

While our sleep/wake cycle is very rigid, our feeding cycle gives us a lot of leeway 

Everyone of you who has ever tried to change a previously learned eating habit or (en-)train a child who is used to be fed whenever it gets hungry to switch to your dietary habits, will be aware of the resistance of these entrained rhythms towards change. Someone, who comes home from his last appointment with his Dr where he was told that "you have to have breakfast", because as we all know "it is the most important meal of the day", is guaranteed to have a hard time switching from coffee-to-go to the "healthy breakfast cereals" his Dr wants him to eat ;-) Mr. Kellog's Honeypops, on the other hand, will certainly be thinking about his beloved breakfast cereals all morning, when his progressive nutrition code wants him to start intermittent fasting.

More than with our sleep cycle which has at least in the broad scope of our evolutionary history always been very stable, the variations in nutrient availability on the large (e.g. seasons), but also on the small scale (e.g. bad luck hunting), are probably the reason that we have a lot more leeway with respect to our eating habits. And still, the well-documented existence of the aforementioned entrainments, and their metabolic and endocrine consequences, of which the correspondence between the release of the "hunger hormone" ghrelin  and our habitual feeding hours is probably the best-established one (suggested read: "Ghrelin Boosting Fats for Intermittent Fasting" for more on why ghrelin is not simply a "hunger hormone").

In a 2008 study, Frecka et al., for example, were able to show that ghrelin rises according to the habitual feeding patterns in both obese and lean subjects (18-50y) - contrary to what the (misplaced) appellation "hunger hormone" would suggest, however, without any significant correlation to subsequent food intake! In other words: While the subjects felt that "it's about time to eat", higher ghrelin levels, as they were observed in those with a lower meal frequency (5.5-6.5h vs. 2.5-3.5h between lunch and breakfast), did not correspond to higher food intakes during lunch - at least as long, as the 2nd meal coincided with the entrained rhythm. What the study does yet not address are the consequences of deviations (short and long term) from this rhythm and the question whether a "natural", i.e. our genetically determined and/or sunlight mediated rhythm exists.

Rise and shine... and eat?

Image 2. Firstly, no king would eat junk like that for breakfast and secondly the saying "have breakfast like a king" should actually read "beak your fast like a king".

When you think about it from an evolutionary perspective, the idea of "having to wait for a meal",  especially the first one of the day, is actually so intuitively logical that it is somewhat tragic that people misunderstand the statement that "breakfast is the most important meal of the day" as an invitation to start binging the very moment the get up, instead of waiting for lunch or even dinner to begin stuffing junk down their pie-holes. Actually this is quite ironic, because if we take a look at the etymological origins of the word "breakfast", it's plain obvious that this is not - as in Germany, where it is called "Frühstück" = "the first piece", the first meal of the day, but the meal that breaks the fast!Unfortunately, though, fasting, has become something, the average TV watching couch-potato of the Western hemisphere is a total foreigner to.

Most of us have become so alienated to the natural 12h+ fast which has once been an obligatory consequence of long winter-nights, food seeking and game that did not willingly surrender to its fate of becoming "breakfast", lunch or dinner, that many of us even have to take specific precautions in order to make sure that they are actually "fasted", when they go to the Dr. to get blood drawn early in the morning. On regular work-days, on the other hand, our tummies, which are designed to work short-time over night, oftentimes haven't even fully digested the remainder from our 16-20h binge of the previous day, in the course of the insufficient 6h of sleep we have gotten before the alarm clock rang. No wonder many people wake up "not feeling like having breakfast" and simply ignore the advice of their doctor has given them, grab a cup of coffee and head to work. Now, this may make their doctors' toenails curl in horror, but it is actually evidence that despite being misaligned (in the eyes of their docs), their feeding pattern does still have some sort of circadian rhythmicity, which would easily be lost once they switch from an early morning fast to the 24/7 binge regimen McDonald's, Burger King & Co are long catering to (see image 2).

When you didn't fast you cannot have breakfast

The answer to the endlessly debated question of whether or not you should have breakfast is - as long as we understand "breakfast" correctly, i.e. as "breaking the fast" - stupidly simple: Without fasting there is no "break(ing the)fast"! Our diurnal metabolic rhythm is geared towards cyclic fasting and feeding patterns, where the feeding hours have always been shorter than the fasting hours.

Figure 1: Are there many ways to Rome? If so, they all have one thing in common achieving an intermediate "fasting state" (green: low energy; orange: medium energy; red: high energy meal)

Obviously, this does not mean that you cannot have breakfast! Rather the opposite is the case, if you recall my hint at the weight loss intervention of the Stadtwerke Cologne (cf. "Carbs Past 6PM"), you will also remember that the most important principle of this dietary intervention is not to have dinner (or at least minimize the energy intake in the evening). And the success obese and chubby and even normal weight bus drivers, administrative officials and all sorts of other employees had with this regimen exemplifies that people can actually have breakfast in the common sense, as long as they've already had their share of (overnight) fasting and are actually breaking a fast.

Did you know that Ratcliff et al. have shown that consuming eggs for breakfast (CHO/fat/protein = 22:55:23) instead of a bagel (CHO/fat/protein = 72:12:16) will reduce the insulin and glucose response, lead to longer satiety and suppress appetite and reduce 24h energy intake (Ratcliff. 2010)? But how can that be? It must be the protein, right? Not really - it's rather the low carbohydrate content which will not totally compromise the increase in FFA levels during fasting, which is characteristic of "being in fat burning mode" - not the least to the morningly rise in cortisol, by the way ;-)

The obese Israeli police officers in the treatment group of the Sofer study (cf. "Carbs Past 6PM"), on the other hand, were just about to begin "fasting" (in the sense of "running" solely on stored fuel), when they woke up at 6AM, after all they did not just have all of their carbohydrates but at the same time ~80%+ of their daily caloric intake less than 12h ago (while the "official" time was past 6PM it is reasonable to assume that dinner was not due before 8PM for most of them). That said, their low calorie, almost-no-carbohydrate "breakfast" was effectively a means to support, not to break the fast. With the caffeine from their artificially sweetened coffee and the slowly digesting combination of fat, small amount of protein and minimal amounts of carbs in the nuts, they kept fueling the lion's share of their metabolic demands from the same stores the Stadwerke employees have tapped into extensively during the evening hours an the night of the previous day.

The "carbohydrate fast", the Israeli police officers were practicing did, if you will, put them in something that would be accurately described as a "semi-fasted" state, where the small and macronutrient specific influx of energy is insufficient to replenish the ATP stores, so that the constant or even slowly declining ADP/ATP ratios will trigger the the same (at least qualitatively) increase in p-AMPK, Sirt1 and downstream PGC1-alpha expression, as regular fasting (cf. Draznin B. 2012).

We are adaptive machines: Many regimens work, as long as they don't lack tact

If thus obviously having, not having or modifying your breakfast can work, it is actually not very surprising that a closer look at the existing research on the issue of whether you fare better or with breakfast, is inconclusive to say the least. Studies such as Astbury et al. with "regular breakfast eaters" as subjects, for example, show that the regular hormonal response was disrupted (stop for a second and think about what "regular" is measured against, here... ok, now go on), when the normalweight healthy men skip their breakfast (Astbury. 2012).

Figure 2: Visual summary of some of the results and weaknesses of the Astbury study.

Unfortunately, the Astbury study is in a way exemplary of much of the research that is / has been done in this area: Many of the studies have either methodological issues / shortcomings and/or present very biased and often even unwarranted interpretations of selected data.

Image 3: Another day at the SuppVersity and yet another thing learned, right? Come on, don't tell me you knew that it was the US nutritionist Adelle Davis who coined the (in-)famous advice to "breakfast like a king, lunch like a prince and dine like a pauper"...

In the Astbury study, for example, the provision of a 2nd breakfast-like liquid "preloading" meal before the launch is a major drawback to the real-world significance of their results. Serving their subjects Kellog's Krispies with skim milk, on the other hand, may be representative of the "fly-by" junk breakfast many people consume in the misplaced believe that it would be a "healthy breakfast", but has eventually little to do with the "long-term satiating breakfast of the kings", Adelle Davis (image 3) probably had in mind when she advised people to...

"BREAKFAST LIKE A KING, LUNCH LIKE A PRINCE, DINE LIKE A PAUPER" - Adelle Davis (1904-1974)

Moreover most of the promoters of this approach recommend to get at least (!) 25% of your day’s calories from breakfast - enough to keep you going right through till lunchtime, both physically and mentally". The sugary junk breakfast in the Astbury study, however, was not just fat free (something Adelle's milk in image 3 certainly wasn't!), it contained also no more than 10% of the daily energy requirements and was thus 40% beyond the minimal prescription for a "king's breakfast".

"To say that obesity is caused by merely consuming too many calories is like saying that the only cause of the American Revolution was the Boston Tea Party." - Adelle Davis

What's even more hilarious, though, is that the scientists explicitly measure the statistically already hardly significant changes in hormonal patterns, specifically highlight the the +17% increase in caloric intake upon lunch, and don't waste a single word on the important fact that the the overall caloric intake in both conditions was identical, and the increased food intake during lunch did not even fully compensate for the calories the subjects missed during breakfast in the abstract to their paper.

Eating vs. not-eating and quantity over quality

Note: The aforementioned "calories don't cause obesity" statement is only valid within a relatively narrow margin of total caloric intake and there is NO - and I repeat NO - debating that a healthy human being can maintain it's body weight, let alone lose weight, when he or she is eating more than 50% above his / her maintenance threshold!

With the second of the afore-cited statements from Adelle Davis, who was incidentally also among the first prominent nutritionists to support the necessity of exercise, the dangers of vitamin deficiencies, and the imperative need to avoid hydrogenated fat and excess sugar consumption, we are getting back on track, now: "Obesity is not caused by consuming too many calories!"

If you look at the current "answers" to the ensuing question: "If it's not calories that cause obesity, what is it then?" You will find answers that range from insulin over leptin resistance to fructose and general carbohydrate overconsumption, right into the too much omega-6 fats argument and the whole litany. Each "expert" has his / her own hobbyhorse in his stable... they are like pieces to a puzzle, some of which do, some of which don't go well together.

Eating a high protein diet (40%+ from protein), while trying to reap the benefits from a "ketogenic diet", for example, is impossible, and one of the reasons people "just can't lose weight". To "breakfast like a king" and still adhere to the underlying principles of a "Berkhan-esque" Lean Gains regimen, on the other hand, is not as mutually exclusive as it may sound. After all, the "intermittent fast" which is at the heart of Berkhan's protocol does not have to take place in the morning (click here and read more about intermittent fasting).

Figure 3: The good old saying of the king, prince and pauper could actually become important again, when you break the fast early and thus stop eating "early". Why you want to do that at all? Well if you want your diet to have any priming effect on your circadian rhythm fasting is the best (and most natural) way to induce the zeitgeber gene response - here exemplified by the Per2 expression of mice in response to 8h (red) and 16h (green) fasts (data based on Hirao. 2010)

Compared to the "early fast" (=skipping breakfast and even lunch), which comes totally naturally as an extension of the (ideally) growth hormone mediated nightly shift into the fasted state, the "late fast" (=skipping dinner) does simply require some more tweaking on your part (see figure 3), because you will have to modulate your food intake in a way that allows for a similarly smooth transition into the fasted state, as the going to bed after a satisfactory last meal of the day and letting your body take care of the rest.

Low GI, low carb, damn ... didn't we hear that before?

Image 4: "If you had told me that this is all about low GI or low carb diets before I had taken a nap right away! Much better for my circadian rhythm than this!"

This is also, where macronutrient ratios come into play. The aforementioned egg breakfast from the Ratcliff study (see red box above), for example, would provide the advantage of minimizing the glucose and insulin spike compared to a "breakfast" with Rice Krispies, for example, and thus minimize the subsequent drop in blood glucose. That the latter is one of the fundamental determinants of our ability to appropriately control our food intake, was one of the findings of a 2002 study by Westerterp-Plantenga et al. who report that the frequency and extent of these events added significantly to the explanatory value of the meal frequency data they had collected from 20 healthy young (18-31 y) normal weight (BMI: 22.8+/-1.9 kg/m²) men.

Yet despite the fact that the conclusion the researchers from Maastricht University in the Netherlands make based on their data

"[h]abitual meal frequency is based upon a cluster of related factors including macronutrient composition of the food, sweetness perception, hunger suppression, blood glucose declines and average baseline blood glucose levels." (Westerterp-Plantenga. 2002)

may sound like yet another recitation of the "good" reasons why you should eat a low GI or low carb diet, the most important word, at least in the context of this series, is probably "habitual"!

Eating by the clock or setting the clock by eating?

Figure 4: Light is the master regulator, and integrated only via the suprachiasmatic nucleus; fasting and calorie restriction can strengthen or weaken this superordinate or central rhythmicity, of greater practical importance is yet probably their role in the subordinate system and specifically the peripheral organs, e.g. liver, muscle, fat, etc. (illustration based on Froy. 2007)

Exactly this previously mentioned habituation or "entrainment" effect, however, is a significant problem, when we are trying to interpret the already scarce research on "optimal" circadian feeding patterns: Imagine you invite a group of 8 breakfast eaters for two testing sessions into your lab, give them breakfast in one, let them "starve" in another. Two weeks later, you repeat the same experiment with Adelfo Cerame and 7 other people who fast for 16h+ every day... I guess I don't have to tell you that you cannot expect the breakfast eaters to show the same hormonal, metabolic and epigenetic response as the intermittent fasters.

Instead of following up on the exact timing questions, the next episode will therefore deal with the lower right part of figure 4, the few established effects of individual macro- and micronutrients, and just to make sure you come back next week, I'll drop three of them: glucose, caffeine and vitamin A

References:

• Astbury NM, Taylor MA, Macdonald IA. Breakfast consumption affects appetite, energy intake, and the metabolic and endocrine responses to foods consumed later in the day in male habitual breakfast eaters. J Nutr. 2011 Jul;141(7):1381-9. 
• Draznin B, Wang C, Adochio R, Leitner JW, Cornier MA. Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res. 2012 Aug;44(9):650-5.
• Frecka JM, Mattes RD. Possible entrainment of ghrelin to habitual meal patterns in humans. Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G699-707.
• Froy O. The relationship between nutrition and circadian rhythms in mammals. Front Neuroendocrinol. 2007 Aug-Sep;28(2-3):61-71. Epub 2007 Mar 24.
• Halsey LG, Huber JW, Low T, Ibeawuchi C, Woodruff P, Reeves S. Does consuming breakfast influence activity levels? An experiment into the effect of breakfast consumption on eating habits and energy expenditure. Public Health Nutr. 2012 Feb;15(2):238-45.#
• Hirao A, Nagahama H, Tsuboi T, Hirao M, Tahara Y, Shibata S. Combination of  starvation interval and food volume determines the phase of liver circadian rhythm in Per2::Luc knock-in mice under two meals per day feeding. Am J Physiol Gastrointest Liver Physiol. 2010 Nov;299(5):G1045-53.
• Ratliff J, Leite JO, de Ogburn R, Puglisi MJ, VanHeest J, Fernandez ML. Consuming eggs for breakfast influences plasma glucose and ghrelin, while reducing energy intake during the next 24 hours in adult men. Nutr Res. 2010 Feb;30(2):96-103.
• Westerterp-Plantenga MS, Kovacs EM, Melanson KJ. Habitual meal frequency and energy intake regulation in partially temporally isolated men. Int J Obes Relat Metab Disord. 2002 Jan;26(1):102-10.