Less Frequent Meals and Eating Most Calories Early in the Day May Prevent Body Fat from Accumulating Over Years

Epidemiologists created the myth of obesity preventing, weight loss promoting effects of increases in meal frequency. Experimental scientists have yet not been able to convince the public that this is bogus... so, studies like Kahleova e al. (2017) may be 'observational bogus', but could actually be more likely to facilitate change than even the best RCTs.

As a SuppVersity reader you know that the commonly heard advice to eat 5-6 smaller vs. 3 larger meals in order to "stoke the metabolic fire" is bullshit ("No Advantage of 6 Meals While Dieting" | read; "Many Small Meals Suck! Especially For Diabetics" | read). Unfortunately, the mainstream media has not caught up to this insight...

... at least not until now. Now you're rightly asking yourselves why this would change, right? Well, you know how mainstream science reporting is obsessed with the impressive number of study participants in often practically worthless epidemiological studies. It is thus not unlikely that they're going to jump on what Hana Kahleova et al. (2017) write in their latest paper in the prestigious Journal of Nutrition, especially because the advice to "eat[...] the largest meal in the morning" confirms at least part of the conventional nutritional advice.

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I believe that I have addressed the issue of having or skipping breakfast at length. Accordingly, I don't think it's necessary to explain once again that the advice to eat breakfast to stay lean is experimentally unsustainable (if you start having breakfast even if you're not hungry in the morning, the opposite will happen, you will gain weight).

That does not refute the assumption that, assuming that you have breakfast, having breakfast like a king and dining like a pauper may still be a valid advice. After all, the mere act of having breakfast - even a small one - will kick you out of a overnight fasting state of which Kahle ova's analysis of data from the 50,660 Canadian and US subjects in the Adventist Health Study II (AHS-2) shows that it is associated with a significant reduction in BMI over an average follow-up period of 7.42 +/- 1.23 years.

Figure 1: That both longer fasting and having breakfast are associated with a negative body-weight trajectory seems confusing. It may yet be easily explained by the mediating effects of dinner times and size (data from Kahleova 2017).

The ostensible contradiction between increased times of overnight fasting and longitudinal reductions in the subjects' BMI, on the one hand (see Figure 1, left), and the link between having breakfast and longitudinal reductions in subjects' BMI, on the other hand (see Figure 1, right), may be mediated by differences in how much and when the subjects dined.

It's not all about breakfast -- Dinner timing and size matter for the length of night fasting, too

How's that? Well, there's a similarly significant trend for reductions in body weight in the diabetic study participants who consumed their largest meal in the morning instead of doing it the "American way", i.e. pigging out in the evening (see Figure 2, right).

Figure 2: More frequent meals (and snacks) are associated with body weight gain, skipping meals and sticking to only 1-2 meals, on the other hand, correlates with body weight loss over 7+-year period (left); having the largest meal in the AM vs. PM is associated w/ an average reduction in BMI of 0.04 kg/m² per year (Kahleova 2017).

Further evidence in favor of the beneficial effects of eating fewer meals comes from the scientists' analysis of the link between the number of eating occasions and the subjects' weight trajectories. As you can see in Figure 2, left, there's a linear increase from weight loss to weight gain from having one to having six or more meals per day.

What's responsible for the timing and frequency effects?

Even with experimental evidence determining the underlying physiological cause of observations like the ones in the study at hand is tricky. You should thus regard the authors' hypothesis about the mechanistic underpinnings of their observations with caution (based on Kahleova 2017):

• satiety hormones, such as leptin or ghrelin, may be involved - Ghrelin is a fast-acting orexigenic hormone, and its concentrations increase pre-prandially and especially at night. Correspondingly, hunger has its intrinsic circadian peak in the evening, promoting the tendency to eat the largest meals late in the day; however, eating a large breakfast reduces hunger, cravings (especially for sweets and fats), and postprandial ghrelin concentrations, thus counteracting weight gain.
• insulin roller coaster with frequent meals - The suppression of the previously mentioned hunger hormone (ghrelin) depends on postprandial insulin release, and frequent eating seems to disrupt this relation similar to other insulin resistant states. Furthermore, our bodies ability to handle glucose is larger in the AM - whether that's due to the lower liver glycogen stores or for circadian rhythms, as Bonham et al. (2017) believe isn't clear, though. Probably both factors contribute to the significantly augmented glucose iAUC in an oral glucose tolerance test, the researchers observed in at night vs. in the morning.

Dopamine and serotonin activity are not on Kahleova's list, but a recent study indicates that they could also be partly responsible for the repeatedly observed benefits of having your largest meal first in the morning: Versteg, et al. observed a sign. increase in serotonin+dopamine receptor binding when subjects consumed 50% of their daily energy intake w/ breakfast (Versteeg 2017).

• circadian (re-)synchronization with meal timing - Meal frequency and timing can reset and amplify the peripheral circadian clocks and the clock genes that control downstream metabolic pathways, which are perturbed in obesity and metabolic disease. It has been shown in experimental models and in humans that both feeding and fasting change transcription rates and the circadian phase of these genes. Time-restricted feeding seems to improve the circadian oscillations of the key metabolic regulators such as cAMP response element-binding protein, mammalian target of rapamycin, and AMP-activated protein kinase (learn more about meal-timing and the peripheral vs. central circadian clock | Vetter and Scheer (2017) recently wrote about the potential to offset these independent clocks in an editorial in which they discuss the results of a recent paper by Wehrens et al. (2017)).
• improved adipose tissue signaling with fasting -- Experimental data have also suggested that reduced meal frequency (and intermittent fasting) can prevent the development of obesity and is associated with less oxidative damage as well as higher stress resistance through the production of protein chaperones (e.g., heat-shock proteins) and growth factors (such as brain-derived neurotrophic factor), possibly because of improved adipose tissue signaling and subsequent less increase of fat depots.
• having a large breakfast = increased energy expenditure - The increase in energy expenditure scientists have observed in response to high fiber + high protein breakfasts, in particular, may be ascribed to a combination of (a) increased physical activity due to better energy levels and increased thermogenesis. Since this is the exact opposite of what having larger meals in the evening will do, it shouldn't be surprising that having breakfast like a king will yield beneficial metabolic effects in a non-controlled real-world scenario.

Ok, I understand: You would be significantly more excited if we weren't dealing with observational data. Me, too, but as I pointed out in the introduction it is epidemiology that's still shaping the nutritional guidelines all around the world. So, if Kahleova's study can finally convince the stoic members of nutritional advisory boards, it's well worth discussing.

What are the practical implications? The scientists themselves summarize the practical implications quite nicely when they write that their "results suggest that eating less frequently (and eating no snacks), consuming breakfast, and eating the largest meal in the morning may be effective long-term preventive tools against weight gain". One must not forget, though, that the subjects were (mostly sedentary) type II diabetics for whom "eating only 2 meals/d, breakfast and lunch 5–6 h apart", a practice the authors deem "an interesting strategy for weight control" may be more feasible than for highly active individuals.

Moreover, the effect sizes are small. I mean, the avg. weight gain 'due to' eating 6+ vs. 3 square meals per day is only ~1kg for someone who's 1.80 m. We shouldn't forget, though, that obesity doesn't occur over night - for most people in the >30kg/m² region the weight has simply been increasing over years and decades. If proper meal timing and a reduced meal frequency could blunt the nasty weight gain, they could thus be valuable tools in the public fight against obesity.

Bah, epidemiological evidence! Yes, I know: Correlation is not causation. However, when it's seen in line with my previous discussions of experimental evidence on breakfast skipping, fasting and meal-frequency, the study at hand provides observational, but real-world longitudinal evidence with experimental backup.

Just as the authors write, the study's large number of participants and high subject diversity (in terms of age, sex, race, geographic location, and socioeconomic status, enhance, "the relevance of its findings to the North American population" (Kahleova 2017). Furthermore, it is the first large-scale longitudinal study to investigate meal timing precisely, thus enabling the authors to "assess the impact of the duration of the overnight fast and the timing of the largest meal more accurately" (ibid).

This doesn't mean that we can ignore the weaknesses of the study - first and foremost that it is impossible to derive definitive causative links from an observational study like that - especially if it is, like the study at hand, of non-prospective nature (this means that the scientists didn't group subjects into different cohorts according to data at the beginning of the follow-up), which leaves it prone to reverse causations (e.g. fat people skip breakfast hoping to lose weight, but the scientists interpret it as "breakfast skipping makes you fat"). In addition, the previously not discussed linear age-related decline in BMI after the age of 60 y may have messed with the results - at least in the older study participants.  In conjunction with the usual problems of epidemiological studies, i.e. a low response rate (55%), probable errors in self-reported measures of meal frequency and timing (which were
not validated), the lack of detailed information about the meals (e.g. the amount of food and type of food that was consumed consumed per eating episode), as well as residual confounding (the distortion that remains after controlling for confounding in the design and/or analysis of a study), Kahleova's study should rekindle experimental scientists' interest in meal timing and frequency while countering the prevalent phenomenon of confirmation bias towards high(er) meal frequencies | Comment on Facebook!

References:

• Kahleova, et al. "Meal Frequency and Timing Are Associated with Changes in Body Mass Index in Adventist Health Study 2." The Journal of Nutrition. First published ahead of print July 12, 2017 as doi: 10.3945/jn.116.244749
• Versteeg, Ruth I., et al. "Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter binding." The FASEB Journal (2017): fj-201601234R.
• Vetter, Celine, and Frank AJL Scheer. "Circadian Biology: Uncoupling Human Body Clocks by Food Timing." Current Biology 27.13 (2017): R656-R658.
• Wehrens, Sophie MT, et al. "Meal Timing Regulates the Human Circadian System." Current Biology (2017).

DIT: Four Fat-Burning Facts About the Effects of Calories, Macros + Meal Timing on the Thermogenic Effects of Foods

A dream has come true: You can burn more calories by eating more... unfortunately, the so-called "diet-induced thermogenesis" does not fully compensate the increased energy intake - you cannot eat yourself slim as "unfair" as some people think this was.

You all will have read that: eating a high protein meal first thing in the AM kickstarts your metabolic engine. But do you also know that this "kick" is worth - in terms of calories, for example? Do you know how the mix of carbohydrates, fats and proteins will affect your diet-induced thermogenesis? Can you tell if calories matter and whether the meal size and speed at which you consume a given meal will matter?

Well, today's SuppVersity article will not be able to answer all of these questions in a "once and for all" fashion, but being based on the latest systematic review by Quatela et al. (2016), it will still give you a good overview of the individual effects of differing energy intakes, macronutrient compositions, and eating patterns of meals on what scientists call your DIT, i.e. your "diet-induced thermogenesis" (DIT) in response to a std. meal.

While fasting will obviously not trigger DIT, it relates to the effects of meal frequency on DIT

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The previously hinted at review comprised 26 papers - all with a randomized crossover design capable of comparing the effects of two or more eating events on DIT. And here's what the authors found:

Higher energy intake increased DIT; in a mixed model meta-regression, for every 100 kJ increase in energy intake, DIT increased by 1.1 kJ/h (p < 0.001 | Quatela. 2016). 

There's, for example, the 1990 study by Kinabo and Durnin who found no effect of the macronutrient composition of the test meals they served either high-carbohydrate-low-fat (HCLF) with 70%, 19% and 11% of the energy content from carbohydrate, fat and protein, respectively, or a low-carbohydrate-high–fat (LCHF) with 24%, 65% and 11% to sixteen adult, non–obese female subjects.

Figure 1: Studies like Kinabo & Durnin (1999) show that low carb vs. low fat does not make a difference - what does matter for DIT (and that's statistically and practically sign.) is the total energy intake per meal.

Accordingly, the two scientists concluded that "[t]he present study suggests that TEF is significantly influenced by the energy content of a meal but not by meal composition" (Kinabo. 1990) - very similar observations, albeit not always with meals differing in their macronutrient composition, have been made by Hill et al. (1984), and Segal et al. (1990).

There's a 50% difference in the thermogenic response to a std. meal (720kcal; the other meal was 35% of the RMR and thus not identical for both groups) in lean vs. obese men - in fact, the obese don't show any stat. sign. DIT (Segal. 1990).

Beware of becoming obese - It will impair your DIT: Even if the last-mentioned study by Segal et al. (1990) confirms that higher energy intakes will yield higher degrees of post-prandial diet-induced thermogenesis (DIT), it is far more important that this study is the first in a recently expanding line of studies that shows that this effect of high-energy meals is blunted in the obese (see Figure on the left). And there's more: With a 9-10% increase in thermogenesis in lean men, the 5% increase in the obese subjects is small and statistically and practically non-significant enough to count as one of the many reasons why obese individuals cannot get away with occasional binges as easily as those who are still lean.

With 100 kcal extra producing on average a thermogenic effect of only 1 kcal/h you got to be careful, though. Eating more is not going to burn body fat! What the research does suggest, however, is a possible explanation for the efficacy of intermittent fasting, where you can consume at least one really satiating, highly thermogenic high energy meal per day.

Meals with a high protein or carbohydrate content had a higher DIT than high fat, although this effect was not always significant (Quatela. 2016). 

The next take home message takes us back to my claim from the introduction: you all will have heard about the beneficial metabolic effects of high protein breakfasts. And in contrast to what the take home message says about carbohydrates, the evidence that high(er) protein intakes yield higher levels of diet-induced thermogenesis has been found consistently (see green lines in the Table 1) .

Table 1: Colored version of an overview from the review by Quatela, et al. (2016) - yellow = study shows advantage for CHOs; gray = study didn't find effect of high carb vs. high fat; green = study shows advantage for protein.

The effects of eating high carb and low carbohydrate meals on thermogenesis, on the other hand, is less clear. While there are studies showing that "low carb = more DIT" (see yellow lines in Table 1), there are also studies which observed identical effects for both, high fat and high carb meals (see gray lines in Table 1). a certain amount / percentage of protein, that's what the data in Table 1 tells us, is not enough for an optimal DIT to occur.

What should also be mentioned, though, is the fact that there's ZERO evidence to the opposite, i.e. an acute increase in thermogenesis to high fat intakes, when the meal size / energy content is standardized and the protein content is kept the same... and no, the study by Riggs et al. (2007) is not an example that this statement was wrong. After all, the "high fat" group in Riggs' study also received increased amounts of protein. The effects on DIT the scientists observed may thus well be ascribed to the extra 10% protein, not to the increased fat and/or reduced carb content.

You better don't starve yourself either! While the previous red box has thought you about the ill consequences being obese will have on your body's ability to burn off extra calories, the previously mentioned study by Riggs et al. shows that being too thin, i.e. underweight (starved), appears to have the same effect. In their study a higher protein intake lead to an increase in DIT only in the normal- yet not in the under- and overweight women; and that the exact same lack of thermogenesis can be observed in weight-reduced formerly obese subjects has been observed by Schutz et al. (1894) more than 40 years ago.

Simply distinguishing between calories and macros, alone, however, is not sufficient to predict the real-world DIT effect of a given meal. This (hopefully) unsurprising revelation takes us right to the last two take home messages that relate to the DIT effect of certain micronutrients and the importance of meal frequency.

Meals with medium chain triglycerides, and meals high in PUFA had a significantly higher DIT than other fats (meta-analysis, p = 0.002 | Quatela. 2016). 

Yes, it is true MCT oils are not just rapidly metabolized, there's also good evidence that they can increase the diet-induced thermogenesis in mouse and, more importantly, man (Kasai. 2002a,b; Clegg. 2013 | discussed => here).

Figure 2: The thermogenic effect of a meal does also depend on the type of fat in it (Casas-Agustench. 2009)

In a similar vein, the likewise comparatively easily oxidized PUFAs have been found to increase DIT compared to both MUFAs, i.e. monounsaturated, and - even more so - SFA, i.e. saturated fats (Piers. 2002; Casas-Agustench. 2009)

Consuming a meal as a single bolus eating event compared to multiple small meals or snacks was associated with a significantly higher DIT (meta-analysis, p = 0.02 | Quatela. 2016).

The last of our four take home messages is one you have read in previous SuppVersity articles about the advantages and disadvantages of fasting and/or a lower meal frequency, before. If you compare the effects of consuming a standardized meal as a bolus event versus splitting the same meal into two (Kinabo. 1990), three (Vaz. 1995), four (Allirot. 2013) or six (Tai. 1991) smaller equal meals or snacks to be consumed throughout the morning, the bolus administration will always produce the highest thermogenic response.

Figure 3: Mean differences in DIT between bolus vs. frequent smaller meals (e.g. snacking | Quatela. 2016)

This effect, however, is not significant in the two small meals and three small meals conditions. And still, Quatela's meta-analysis of all four studies (see Figure 3) shows that "[t]he overall mean of the difference is positive, which means that the DIT was lower in the smaller frequent meals event trials compared to the bolus trial" (Quatela. 2016).

The degree of processing will likewise affect the thermogenic response to food (Barr. 2010).

And there's still more: Unprocessed foods are more thermogenic than processed foods (Barr. 2010). The same goes for eating fast vs. slow (slow increases DIT compared to fast eating). It should be mentioned though that at least for the latter variable, as well as the effect of and palatability the evidence is either insufficient, unclear or contradictory. That's why I would agree that only "the energy intake, macronutrient compo-sition, and eating pattern of the meal" (Quatela. 106) have a sufficiently proven practically relevant effect on DIT.

With that being said, I cannot let you go without reminding you that neither the extra 10kcal/h you expend if you add another 1000kcal to your meal nor 17% increase in DIT you can get from increasing a meal's protein content will strip an inch off your waist or decrease your body fat percentage by 0.1% - and comprehensive evidence on the long-term effects is still warranted (for meal frequency there's some; the same goes for high protein). Optimizing your DIT should thus be only one (and not the most important) strategy in your dieting toolbox  | Comment.

References:

• Barr, Sadie B., and Jonathan C. Wright. "Postprandial energy expenditure in whole-food and processed-food meals: implications for daily energy expenditure." Food & nutrition research 54 (2010).
• Casas-Agustench, Patricia, et al. "Acute effects of three high-fat meals with different fat saturations on energy expenditure, substrate oxidation and satiety." Clinical Nutrition 28.1 (2009): 39-45.
• Clegg, Miriam E., Mana Golsorkhi, and C. Jeya Henry. "Combined medium-chain triglyceride and chilli feeding increases diet-induced thermogenesis in normal-weight humans." European journal of nutrition 52.6 (2013): 1579-1585.
• Kasai, Michio, et al. "Comparison of diet-induced thermogenesis of foods containing medium-versus long-chain triacylglycerols." Journal of nutritional science and vitaminology 48.6 (2002a): 536-540.
• Kasai, Michio, et al. "Comparison of diet-induced thermogenesis of foods containing medium-versus long-chain triacylglycerols." Journal of nutritional science and vitaminology 48.6 (2002b): 536-540.
• Kinabo, J. L., and J. V. G. A. Durnin. "Thermic effect of food in man: effect of meal composition, and energy content." British Journal of Nutrition 64.01 (1990): 37-44.
• Kinabo, J. L., and J. V. Durnin. "Effect of meal frequency on the thermic effect of food in women." European journal of clinical nutrition 44.5 (1990): 389-395.
• Hill, James O., et al. "Meal size and thermic response to food in male subjects as a function of maximum aerobic capacity." Metabolism 33.8 (1984): 743-749.
• Piers, L. S., et al. "The influence of the type of dietary fat on postprandial fat oxidation rates: monounsaturated (olive oil) vs saturated fat (cream)." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 26.6 (2002): 814-821.
• Quatela, Angelica, et al. "The Energy Content and Composition of Meals Consumed after an Overnight Fast and Their Effects on Diet Induced Thermogenesis: A Systematic Review, Meta-Analyses and Meta-Regressions." Nutrients 8.11 (2016): 670.
• Riggs, Amy Jo, Barry D. White, and Sareen S. Gropper. "Changes in energy expenditure associated with ingestion of high protein, high fat versus high protein, low fat meals among underweight, normal weight, and overweight females." Nutrition journal 6.1 (2007): 1.
• Schutz, Yves, et al. "Decreased glucose-induced thermogenesis after weight loss in obese subjects: a predisposing factor for relapse of obesity?." The American journal of clinical nutrition 39.3 (1984): 380-387.
• Tai, Mary M., Peter Castillo, and F. Xavier Pi-Sunyer. "Meal size and frequency: effect on the thermic effect of food." The American journal of clinical nutrition 54.5 (1991): 783-787.
• Thyfault, JOHN P., et al. "Postprandial metabolism in resistance-trained versus sedentary males." Medicine and science in sports and exercise 36.4 (2004): 709-716.
• Vaz, Mario, et al. "Postprandial sympatho-adrenal activity: its relation to metabolic and cardiovascular events and to changes in meal frequency." Clinical Science 89.4 (1995): 349-357.

Regular Meals Promote Thermogenic Effect of Food - 22% to 50% Higher Postprandial Thermogenesis in Healthy Women

While the ads for many fat burners tell you just that, thermogenesis is not the #1 determinant of whether you're lean or fat. It is just one of a bazillion factors that influence your energy balance which in turn controls your weight.

Thermogenesis is (falsely) treated like the holy grail in fat loss supplement ads. When all is said and done, though, even a 100% increase in thermogenesis, which has nothing to do with a 100% increase in total energy expenditure, is usually easily compensated for by increased energy intakes in the average and extraordinary male or female dieter.

Against that background you may be asking yourselves why the latest study from the School of Life Sciences at the University of Nottingham even made the "SuppVersity newsworthy"-cut. Well, the answer can be seen in Figure 1, which tells you that modulating the eating patterns in said randomized crossover trial didn't just affect the extent of postprandial thermogenesis, but also the weight, body fat and, in particular, the 'waist trajectory' of the subjects, 9 obese women (mean ± SD BMI: 33·3 ± 3·1 kg/m²).

You can learn more about meal frequency at the SuppVersity

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To ascertain whether modulating the regularity of meal pattern over two weeks would affects the thermogenic response to a test meal and anthropometric measurements in obese women, Alhussain et al. had their subjects follow irregular and regular meal patters for 2 weeks, each:

• regular meal pattern - 6 meals/day
• irregular meal pattern -  varying from 3 to 9 meals/day

In that, it is important to note that "[i]n the two intervention periods, identical foods were provided in amounts designed to keep body weight stable" (Alhussain. 2016). For the testing sessions, the participants attended the laboratory after an overnight fast pre and post each intervention period.

"On arrival, measurements were made of body weight, body composition, waist circumference and waist to hip ratio. Resting energy expenditure was then assessed by using indirect calorimetry, fasted and during the 3 h period after consumption of a milkshake, test drink (50 % CHO, 15 % protein and 35 % fat of energy content)" (Alhussain. 2016).

As already hinted at, the scientists observed significant changes in the postprandial thermogenic response and non-significant effects on the subjects body composition.

Figure 1: Changes in markers of body composition during the two 2-week periods (Alhussain. 2016).

More specifically, the regular meal pattern that allowed for weight and body fat stability and even triggered a non-significant decrease in waist circumference. The irregular pattern, on the other hand, produced an albeit statistically non-significant increase in body weight and body fat - a change, of which we can hypothesize that it would reach statistical significance in the weeks to come.

A 2004 study in lean women shows: This is not a "fat-girl thing". TEF of lean women suffers even more (Farshchi. 2004).

This is not a "fat girl-thing"! In case you think 'Well, that's not me, I am lean and for me these results are irrelevant', you may want to take a look at a 2004 study by Farshchi et al. in which the researchers observed a similar effect in perfectly lean women. If you take a look at the figure on the left, I've copied right from the full text of said study, you will even notice that the decline in energy expenditure in the lean women is significantly more pronounced than in the obese women in the study at hand.

In view of the lack of strict dietary control outside of a metabolic ward, it is hard to say whether the effects on body composition (Figure 1) were triggered solely by the decrease in thermogenesis (Figure 2) due to the irregular meal pattern. As I've pointed out in countless previous SuppVersity articles these effects may just as well be caused by increases in food intake, which are never (or at least rarely ;-) 100% accurately reported by subjects of clinical trials.

Figure 2: Postprandial extra energy expenditure due to thermogenesis (kcal/3h) before and after 2-weeks on regular or irregular meal pattern in 9 obese women [mean ± SD BMI: 33·3 ± 3·1 kg/m² | Alhussain. 2016).

Eventually, the lack of dietary control must not necessarily be a disadvantage. After all, there's no strict dietary control in the real world, either. Therefore, any study that tightly controls their subjects food intake will fail to portray a correct picture of its subjects real lives - lives in which the average subject shows a very low adherence to his/her (self-)prescribed diet and will thus (just as it may have been the case in this study) simply eat, when he/she is hungry, even if his/her meal plan tells him/her not to do so - and regular meal patterns certainly help avoiding hunger pangs.

Previous research clearly indicates that it would be a "fat mistake" to believe that a reduced meal frequency on some of the 14 days on the irregular pattern was behind the non-sign. weight and fat gain in this study.

Bottom line: It should be obvious that it would be a mistake to consider the study at hand "convincing evidence" that irregular meal patterns promote weight and, more importantly, fat gain. An effect on thermogenesis, on the other hand, appears to exist - at least in women.

In spite of the paucity of evidence, the way many people in today's society are "always on the run" and hardly able (or willing) to stick to regular meal patterns, it does seem at least "likely" that irregular meal patterns are part of the reason our hectic life-styles lead to ever-increasing obesity rates. How important the impact of regular meal-patterns on our thermogenic response to meals actually is, though, will have to be evaluated in future studies | Comment!

Addendum: No, this is not your average meal timing article. I am not saying you have to eat at a specific time, or you have to eat 6, 3 or 5 meals a day. The one and only thing the study suggests (and this is in line with previous studies on skipping breakfast) that you should eat at the same time (roughly) everyday. The mechanism behind the benefits is probably related to the ability of timed meals to entrain a stable circadian rhythm and optimize the way your body handles the food you consume (e.g. stable insulin and glucose levels => no release of glucocorticoids, etc.).

References:

• Alhussain, et al. "Deleterious effects of irregular meal pattern on dietary thermogenesis in obese women." Proceedings of the Nutrition Society 75 (2016): OCE1, E6.
• Farshchi, H. R., M. A. Taylor, and I. A. Macdonald. "Decreased thermic effect of food after an irregular compared with a regular meal pattern in healthy lean women." International journal of obesity 28.5 (2004): 653-660.

Are Six Meals Better Than Two? Recent Study Shows Lean Mass Gains on Std. Energy-Reduced Diet W/Out Differences in Fat Loss W/ 6 vs. 2 Meals/Day - Do You Have to React?

Do the results of the latest randomized controlled cross-over study from the California State University mean that you have to change your eating habits? Find out in today's SuppVersity Article!

If you are a SuppVersity reader you know that the scientific evidence that eating four meals instead of two when dieting is scarce. More recently, there have actually been more studies to suggest that eating very frequently like 6+ meals per day may eventually ruin your dieting efforts because (a) the constant grazing won't allow your insulin levels to drop and (b) people tend to eat "a little too much" with each of these meals, so that - eventually - they are missing their target energy intakes. Now, an ahead of print article in the peer-reviewed scientific journal Nutrition Research suggests that, in a tightly controlled scenario and with significantly overweight, not to say obese women as subjects, an increase in food frequency from two to six meals per day can have beneficial effects on their weight loss success.

You can learn more about meal frequency at the SuppVersity

Grazin' Bad For the Obese!

Breakfast Keeps You Lean?!

Frequent Protein Consumption

Myth: Few Meals More Bodyfat

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Int. Fasting & Exercise

More specifically, Michelle Kulovitz Alencar et al. (Alencar. 2015) set out to deterimine whether
either a two meal (2MF) or six meal frequency (6MF) regimen can improve body composition and blood-based markers of health while consuming a portion-controlled equihypocaloric diet.

Figure 1: Overview of the study design (Alencar. 2015) | Explanation of the indices: (a) resting metabolic rate, (b) blood pressure (c) visual analogue scale, (d) area under the curve

The study was a randomized-controlled cross-over trial. Thus, the researchers who randomly assigned their N = 11 obese women (52 ± 7 years, 101.7 ± 22.6 kg, 39.1 ± 7.6 kg/m²) who had been to either of the treatment conditions (2MF or 6MF) for two weeks, ensured that by having a washout after the initial two weeks and another two-week intervention phase thereafter, none of the meal frequency patterns had an "unfair" advantage of being "the first" while. Here is an overview of the key facts directly from the research paper:

• 

  SuppVersity Classic: Grazin' Study Shows: Increased Eating Frequency Bad For Obese and Lean Men. Reduced Diet-Induced Thermogenesis and Blunted Lipolysis Could Promote Future Weight Gain | read more.

  The 2MF pattern participants were instructed to consume allocated meals every 5-6 hours while awake. 
• The 6MF pattern participants were instructed to consume allocated meals/snacks every 2-3 hours while awake. 
• Meals provided to participants were defined as an eating occasion with a caloric intake between 200 and 300 kcals, while a snack was defined as an eating occasion with a caloric intake between 100 and 200 kcals. 
• Throughout all treatment conditions, food products were identical and participants received the identical assortment of pre-packaged food products containing 1,200kcal/day with ~75g/day of protein and a macronutrient ratio of 52% carbohydrates, 27% protein, and 21% fat. 
• Participants consumed their designated meal pattern eating only Nutrisystem® meal products which were supplied to the participant. Participants also supplemented this diet with a limited selection and quantity of Nutrisystem®-approved fresh fruits and vegetables. The additional fresh items added accounted for only approximately 187 kcals/day, or 15% of daily caloric intake of the participants’ daily total of ~1200 kcals per day. 
• The participants consumed identical food products throughout the study.

Participants followed their respective MF pattern for the two weeks of Phase I. They the
At the same time a cross-over design like this "virtually" doubles the number of subjects. The same obviously goes for the data Alencar et al. could use to compare the effects of the two meal frequency patterns on body composition, glucose, insulin and lipid components by their individiual responses to a test meal.

Why four meals during the "washout"? During the washout phase participants were instructed to consume the allocated meals and snack (a total of four occasions per day) every 3-4 hours while awake. The washout phase was chosen as 4MF because it was the average number of eating occasions of the participants prior to participation.

Speaking of the effects. As you may have guessed from my preliminary remarks in the introduction, both groups successfully lost (p≤0.05) body mass (=total weight | 2MF: -2.8 ± 1.5 vs. 6MF: -1.9 ± 1.5 kg) - in fact with a slight but highly non-significant "advantage" for the two-meal pattern.

Figure 2: Changes in body composition and resting metabolic rate in both groups (Alancar. 2015).

Since differences in the effects of dieting on glucose, insulin, total-cholesterol, or LDL-C (p>0.05) between the two groups were not observed, one could falsely conclude that the two-meal strategy was in fact minimally more effective.

Figure 3: The fact that we are dealing with body impedence data should make you question the significance of the alleged "lean mass boosting" effects of a 6-meal pattern in people on a calorically reduced diet who are consuming only 75g/day protein total (figure from Alancar. 2015).

It may look like both meal patterns were equally effective... at first sight, at least. If we consider the average fat-free mass (FFM) loss, as well, it is quite obvious that the 6-meal pattern which produced an average increase in fat free mass of 1.2 ± 1.7% (vs. a fat free mass loss of -3.3 ± 2.6% in the two-meal pattern), there is little doubt that in this particular study with this particular subject group, six eating occasions were the superior choice.

A corresponding difference in resting metabolic rate, which reduced by only 4% by the way was yet absent. In addition, the lean body mass benefits were obtained by the means of rather unreliable body impedence analyses (Böhm. 2013; Romero-Corral. 2008) and stands in contrast to the results of several previous studies, which often show different results.

In some cases this may be a consequence of a less rigorous dietary control and the previously hinted at collateral damage due to using each of the six or more eating occasions to eat a little more than ones diet would allow, but that must not necessarily be all. Furthermore, weight and fat loss is not everything. Specifically for obese subjects like the ones in the study at hand, the insulin lowering effects of eating less frequently which are also responsible for the general tendency to be less hungry on energetically reduced diets, can provide another advantage: An increase in heart-healthy HDL cholesterol that was observed in the study at hand only when the subjects were consuming the two-meal pattern. Against this background and evidence from other studies, I caution you against wholeheartedly subscribing to conclusion that this single study would demonstrate, let alone "prove" that a six-meal strategy is the way to go for everyone willing to shed body fat. Higher protein intake, or exercise for example could be game changers. Moreover, for the already lean, the repeated elevations of insulin in response to the frequent meals which were - to my surprise - not observed in the study at hand, but other studies (Fogteloo. 2004 | read more) - may actually hinder the loss of the last slabs of body fat and in the absence of caloric deficits, increased meal frequencies have been linked to increase liver fat and an overall higher obesity risk (Koopman. 2014 | learn more) | Comment on Facebook!

References:

• Alencar, Michelle K., et al. "Increased meal frequency attenuates fat-free mass losses and some markers of health status with a portion-controlled weight loss diet." Nutrition Research (2015).
• Böhm, A., and B. L. Heitmann. "The use of bioelectrical impedance analysis for body composition in epidemiological studies." European journal of clinical nutrition 67 (2013): S79-S85.
• Fogteloo AJ, Pijl H, Roelfsema F, Frölich M, Meinders AE. Impact of meal timing and frequency on the twenty-four-hour leptin rhythm. Horm Res. 2004;62(2):71-8.
• Koopman, Karin E., et al. "Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: A randomized controlled trial." Hepatology 60.2 (2014): 545-553.
• Romero-Corral, Abel, et al. "Accuracy of body mass index in diagnosing obesity in the adult general population." International journal of obesity 32.6 (2008): 959-966.

Less Frequent Large(r) Meals & Caffeine - Proven Ways to Increase Your Energy Expenditure & Conserve Your Resting Metabolic Rate While Dieting | Part I of A Multipart Series

Whether you want to lose or gain weight, never forget to "Eat to live!"

To lose weight, you must create a negative energy balance.It is however unrealistic to expect your body not to do everything it can to conserve energy, when you've been eating 50% below maintenance for weeks (e.g. you need 2,000kcal, but eat only 1,000). Not to reduce your energy intake by more than 40% (for max. 2 weeks) and going with 20-25% if you plan to diet for 4-6 weeks would thus qualify as rule #1; a rule of which I can only say that I highly recommend you stick to it, because if you don't even the five tips below are not going to save your metabolism from crashing (learn more about the nine rules that can help avoiding metabolic shut-down).

There is evidence of effects of coffee & CGA on your gut microbiome (Jaquet. 2009)

Fiber for Female Fat Loss

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet

Ah, and before I forget to mention it. If you don't control your dietary energy intake, chances that any of the following tricks (in that case magically) help you lose weight without the need to diet are anywhere between "slim" and "zero".

• Eat large meals less frequently: It may go against the longstanding recommendation, but due to the fact that meal size, not macro composition is the main determinant of the post-meal increase in thermogenic effect.

  

  Figure 1: Increase in metabolic rate above basal metabolic rate (BMR) (kJ/min) after ingestion of
  four different test meals by human subjects (Kinabo. 1999)

  And considering the fact that the latter lasts for 5h+ (see Figure 1) the idea that you have to eat a small meal every hour "to stoke the furnace" is fundamentally flawed. No wonder, people all over the world are successfully using weight by intermittent fasting.

Thermic effect of food (in kcal/3h), when it's consumed at rest or after a workout in lean vs. obese (fat, not just heavy) subjects (Segal, 1985)

The thermic effect of food is reduced with obesity: A review of 49 pertinent studies by researchers from the Pennington Biomedical Research Center clearly indicates "the reduction of TEF in obesity is related to the degree of insulin resistance, which may be influenced by a low level of sympathetic activity." (Jonee. 1997). A study by Segal et al. measured a difference of 42% at rest and 64% if the meal was consumed after a workout (see figure on the left). Accordingly those of you who are still carrying more than "some" extra weight should be careful not to overestimate the benefits of food induced increases in thermogenesis. Don't misinterpret this as "you got to eat more often", though! This could make things even worse.

• You have to be careful, though, long arduous workouts during the fast or fasting for more than 12-16h could nullify the thermogenic benefit of being able to eat to satiety once or twice a day. And no! The Kinabo study is not a statistical outlier, it's just like a study with almost identical results by Tai et al. (1991) real vs. broscience which dictates that you "got to stock the furnace" - a practice of which the latest controlled studies show that is has "no significant effect on 24-h fat oxidation, but may increase hunger and the desire to eat." (Ohkawara. 2013)

• Use 4mg/kg caffeine per day - You will certainly have expected to see caffeine on the list of agents that help. Unfortunately, caffeine is significantly more effective for lean vs. overweight individuals. In a study from the Institute of Physiology at the University of Lausanne, David Bracco and colleagues were able to show that the thermogenic effect of caffeine coffee (4mg/kg body weight) was 35.6% more pronounced in the lean vs. obese female subjects (Bracco. 1995) - similar results have been reported by Belza et al. (2007), Hollands et al. (1981) increases of 15% in the two hours after the ingestion of caffeinated vs. decaffeinated coffee.
  

  

  Figure 2: Relative increase in resting metabolic rate, energy expenditure during exercise and sleep in lean and obese women in response to the ingestion of 4mg/kg of caffeine (vs. placebo | Bracco. 2014)

  In addition to the overall effect size, the data in Figure 2 does also indicate that an "over night" effect, as well as the increase in energy expenditure during workouts were likewise only observed in the lean, not in the obese women (since the lack of thermogenesis has been associated with decreased insulin sensitivity using 300-500mg of alpha lipoic acid, as I have suggested in a recent article, may ameliorate the reduction in postprandial thermogenesis).

Remember not to go overboard on caffeine (here's why): Stick to 600mg/day and take it in three to four doses of 200mg or 150mg respectively; and, if possible, get some of it from coffee, for the added benefits of chlorogenic acid & co (McCarty. 2005). In fact, a recent study from the Technische Universität Kaiserslautern shows that coffee consumption 250ml 3x per day (vs. decaffeinated coffee as placebo) will even induce body fat loss(es) in the absence of deliberate restrictions of food intake in 84 healthy subjects... and on top of it, the coffee consumption protected the study participants DNA (Bakuradze. 2014).

• Now 4mg/kg may seem like quite a high dosage for some of you. In contrast to the usual SuppVersity mantra that "more won't help more", those 4mg caffeine per kg of body weight are yet well necessary. In a 1999 study from the University of Geneva, for example, the administration of only 50mg of caffeine had no effect on the resting energy expenditure of 10 healthy male volunteers (Dullo. 1999).
  
  

  

  Figure 3: Substrate utilization (mg/min) before (filled bars) and after (empty bars) the ingestion of a complex test meal with either coffee (4mg/kg caffeine) or decaffeinated coffee (Acheson. 1980).

  Furthermore, caffeine has also been shown to increase the thermic effects of a meal and to shift the fuel utilization towards fatty acids (Acheson. 1980; see Figure 3). The latter will not necessarily help you to burn more body fat, but it will spare liver and muscle glycogen, when you're dieting and reduce the chances that your liver resorts to amino acids from your musculature to cover the glucose requirements of your body.
  
  In conjunction with the net increase in energy expenditure Dullo et al. quantify in the range of 150 kcal in lean volunteers and 79 kcal as a response to the bi-hourly consumption of 100mg of caffeine in the post-obese subjects, there is little doubt that
  

  "Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity." (Dullo. 1989)

  Studies by Yoshida et al. support this notion and confirm that the addition of caffeine to the weight loss equation will be particularly effective in overweight individuals with reduced baseline metabolic rate (Yoshida. 1995) and more recent experimental data from the University of Maastricht confirms that high caffeine intakes are associated not just with increased weight loss through thermogenesis and fat oxidation, but also with reduced fat mass, and waist circumference in overweight and moderately obese subjects (Westerterp‐Plantenga. 2005).

Suggested: Many Small Meals Suck - Especially for Diabetics | more

You already knew those two? Well in that case you've probably been following my articles here at the SuppVersity for quite some time, now. I have, after all, written about caffeine, coffee, intermittent fasting and meal frequencies, before. And in case you didn't find at least a couple of additional new figures, you haven't seen before, I can comfort you: There will be follow ups in the course of the next weeks.

It would thus be a stroke of bad luck if you didn't find at least one new agent or trick in one of the next installments of this series or spend your time commenting on Facebook!

References:

• Acheson, K. J., et al. "Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals." The American journal of clinical nutrition 33.5 (1980): 989-997. 
• Bakuradze, Tamara, et al. "Four weeks coffee consumption affects energy intake, satiety regulation, body fat, and protects DNA integrity." Food Research International (2014).
• Bracco, David, et al. "Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women." American Journal of Physiology-Endocrinology and Metabolism 32.4 (1995): E671. 
• Dulloo, A. G., et al. "Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers." The American journal of clinical nutrition 49.1 (1989): 44-50.
• Dulloo, Abdul G., et al. "Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans." The American journal of clinical nutrition 70.6 (1999): 1040-1045.
• Hollands, Marjorie A., J. R. Arch, and M. A. Cawthorne. "A simple apparatus for comparative measurements of energy expenditure in human subjects: the thermic effect of caffeine." The American journal of clinical nutrition 34.10 (1981): 2291-2294.
• Jonee, Lilian, and George A. Bray. "The thermic effect of food and obesity: a critical review." Obesity research 5.6 (1997): 622-631.
• Kinabo, J. L., and J. V. G. A. Durnin. "Thermic effect of food in man: effect of meal composition, and energy content." British Journal of Nutrition 64.01 (1990): 37-44. Segal, Karen R., et al. "Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight." Journal of Clinical Investigation 76.3 (1985): 1107.
• McCarty, Mark F. "A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk." Medical hypotheses 64.4 (2005): 848-853.
• Ohkawara, Kazunori, et al. "Effects of increased meal frequency on fat oxidation and perceived hunger." Obesity 21.2 (2013): 336-343.
• Segal, Karen R., et al. "Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight." Journal of Clinical Investigation 76.3 (1985): 1107.
• Tai, Mary M., Peter Castillo, and F. Xavier Pi-Sunyer. "Meal size and frequency: effect on the thermic effect of food." The American journal of clinical nutrition 54.5 (1991): 783-787. 
• Westerterp‐Plantenga, Margriet S., Manuela PGM Lejeune, and Eva MR Kovacs. "Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation." Obesity research 13.7 (2005): 1195-1204.
• Yoshida, T., et al. "Relationship between basal metabolic rate, thermogenic response to caffeine, and body weight loss following combined low calorie and exercise treatment in obese women." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 18.5 (1994): 345-350.