Tuesday, July 18, 2017

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.
Learn more about skipping meals at the SuppVersity

Start Havin' Br-eakfast, Get Fat

"Lean Gains" Fast Works

Fasting Better W/ 1 or 3 Meals?

Breakfast Habits Matter

IF + Resistance Training = WIN

ADF Beats Ca-lorie Restriction
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!
  • 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).