Nutrient/Meal Timing: A Dozen Examples of Its Purported Impact on 'Ur Health, Weight Management & Body Comp.

Everyone will know somebody who managed to build an impressive physique with meal-timing. The question you cannot answer, however, is whether that's due to the timing or rather his/her mindful eating habits, healthy food choices and overall controlled energy intake.
Originally, people thought about dieting quite mechanistically. With health and fitness becoming more important than religion to many people, this has changed significantly and we've seen various trends ranging from the low-fat fad in the 1980s to the anti-fructose movement of the early 2000s and the ketogenic revival 10 years later. Eventually, the transient nature of all these trends did yet confirm one thing: the macronutrient of your diets may influence if and how much fat/muscle weight you lose or gain, but it's only one out of several parameters that determine the way(s) in which your diet will affect your health and body composition.

Another factor that has been recognized to do just that is nutrient timing, i.e. the ingestion of food or specific foods and nutrients at specific, purportedly "optimal" time-points. In the fat-o-phobic 1980s, the mantra was: eat small quantities of low GI high carb foods every 2h. The result was a snacking culture that has probably contributed to the exponential rise of obesity rates over the past decade.
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I've written about the problems that are associated w/ eating 24/7 in previous articles (e.g. "Many Small Meals Suck! Especially For Diabetics", "Are Six Meals Better Than Two?" or "Prevent Body Fat Gain by Eating Most of Your Calories Early in the Day")  - just as I've addressed the potential benefits of the frequent ingestion of high protein meals as it is also suggested in the ISSN's position stand on nutrient timing (read it). With 2018 being only a few days away, I decided to use the holidays to take another look at the potentially relevant new evidence on meal/nutrient timing which is (and always has been) one of the five most frequent topics of e-mail and Facebook questions I get.

Next, to the previously referenced ISSN position stand, a cursory review of previous research overviews produces, among other results, the following insights:
  • meal timing (MT) may inhibit the growth of cancer (vs. ad-libitum intake | Li 2010) - most likely by reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition
  • Figure 1: A conceptual model of the mammalian circadian system. A circadian pacemaker located in the retinorecipient suprachiasmatic nucleus (SCN) in the hypothalamus generates circadian rest-activity, feeding, body temperature and other rhythms that entrain to environmental light-dark (LD) cycles. The daily feeding rhythm provides time cues that entrain circadian oscillators elsewhere in the brain and in most peripheral organs and tissues | Patton 2013 and Vetter 2017
  • meal timing (MT) influences and, ideally, synchronizes the central and peripheral clocks of your body to ensure optimal endocrine, metabolic and immune function by making sure that corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1 are released/metabolized at optimal intervals 
  • Table 1: Summary of human studies of eating frequency (Kaczmarek 2017b)
    the evidence that (intermittent) fasting (for 16h+) can have profound health benefits has been accumulating over the years (Mattson 2014; Patterson 2015) - the mechanisms involve a metabolic shift to fat metabolism and ketone production and stimulation of adaptive cellular stress responses that prevent and repair molecular damage
  • the notion that "one size/timing fits them all" is flawed for having/skipping breakfast and meal frequency, in general - more specifically, previously discussed studies by Thomas et al. (read up on it) and LeCheminant et al. (read up on it) suggest that you better stick to what has been working for you in the past instead of forcing or depriving yourself of breakfast all of a sudden
  • the observed benefits and detrimental effects of increased meal frequency, eating a large dinner, eating before bed, etc. have been shown to be mediated (at least partly) by their impact on people's total daily energy intakes -- in multivariate analyses controlling for age, sex, sleep duration, and timing, eating more frequently, later timing of the last meal, and a shorter duration between last meal and sleep onset predicted higher total caloric intake (Reid 2014); other confounding factors are results of the still prevalent advice not to skip breakfast or to eat breakfast like a king and dinner like a pauper or rather the fact that people who live a health-conscious life and eat healthy diets tend to adhere to this recommendation (Leech 2015).
    Figure 2: During weight loss, consuming the most energy in the AM does not improve weight loss, insulin sensitivity and reduces hepatic fat content more than consuming the most energy in the PM (Versteeg 2017).
    In experimental studies where a potential influence on energy intake is effectively precluded by standardizing the subjects food intake (energy deficit as it was the case in Versteeg 2017), food timing does, as you'd expect it, not affect weight loss and or its health benefits (in Versteeg 2017 on the liver).
  • while there is quite a number of studies, the study quality is generally low - with small sample sizes, short-term interventions, a lack of clear-cut definition of "an eating occasion" and a severe lack of several key outcomes such as physical activity, adherence to assigned EF, and hunger (Palmer 2009)
Unfortunately, the last-mentioned lack of long-term tightly controlled experimental data from human studies is still an if not the main problem when we're talking about the effects of meal timing. That doesn't mean, though that more recent studies (published between Jan 2017 and Dec 2017) wouldn't have anything to bring to the table, such as...
  • the "carbohydrate-last"-principle which was posited by Shukla et al. (2017) based on the observation that a "carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes" (Shukla 2017) -- in fact, the scientists' data showed significant reductions in the incremental areas under the curve for glucose (iAUC0-180) and incremental glucose peaks of 53% and 54%, respectively, when carbohydrate was consumed last compared with carbohydrate consumed first and by 44% and 40%, respectively, compared with the all components together condition
    Figure 3: Changes in incremental areas under the curves (iAUCs) (0–180 min) in healthy subjects after consuming carbohydrate first, followed 10 min later by protein and vegetables versus protein and vegetables first, followed 10 min later by carbohydrate, expressed relative to control meal where all components were served together in form of a sandwich (Shukla 2017).
    In that, it may be worth pointing out that, compared to protein preloads, "the carbohydrate-last meal pattern lead to lower glycemic and insulin excursions but higher glucagon-like peptide-1 response" (Shukla 2017) - in other words, improved blood sugar control, reduced levels of insulin and higher levels of the satiety hormone GLP-1 were observed with the "carbohydrate-last" pattern.
  • Figure 4: Circadian Align- vs. Misalignment (Poggiogalle 2017).
    novel insights into the way(s) the circadian system regulates glucose, lipid, and energy metabolism suggest it's all about healthy habits - insights of which a recent says that the patterns peak in the biological morning or early afternoon, implicating earlier in the daytime as optimal for food intake" (Poggiogalle 2017).

    As the overview in Figure 4 illustrates, controlled light exposure, healthy sleep habits and timed eating may help avoid or at least ameliorate health problems related to circadian misalignment.
  • the fat difference between consuming almonds as a snack vs. preload that was observed only recently in healthy, young Korean adults between 20-39 - while all followed the same high-carb diets (isocaloric) all subjects were instructed to consume 56 g of almonds per day, one group did that as a preload before meals, while the other snacked between meals; with profound differences in health-relevant outcomes over the 16 week study period: "Almond consumption as a preload modified body fat percentages, whereas snacking on almonds between meals improved blood lipid profiles" (Liu 2017).
  • further evidence that our tolerance to carbohydrates, even low GI carbohydrates, deteriorates from AM to PM (Leung 2017)- more specifically, when healthy test subjects consume a low GI meal (3.3 MJ, 48% energy (E) from carbohydrate, 40%E from fat and 11%E from protein, 22 g fiber) at 0800h, 2000h and 0000h (midnight), they will display higher postprandial glucose iAUC over 3h after the meal both, in the evening and at midnight (p = 0.008, p = 0.021 | no significant difference between evening and midnight (p = 0.594) was observed); similar observations were made for the postprandial insulin iAUC which was also higher in the evening and at midnight compared to the morning (p = 0.008 for both).
  • evidence that our microbiome has its own biological clock comes from the University of Illinois at Urbana-Champaign (Kaczmarek 2017a) - if we are honest, we do, however, not really know if that's even relevant and what we could do with these new insights
Meal Timing Crucial for Fat Loss? Is WHEN You Eat More Important for Losing Weight Than HOW MUCH You Eat? | Learn more about a study that seems to suggest just that!
The verdict is still out there: Even with the more recent research and reviews like Beccuti, et al. (2017) that conclude "that eating time is relevant for obesity and metabolism", the hard evidence that the purported benefits of meal timing are not ultimately only results of changes in total energy intake is - in my humble opinion - not yet convincing. With that being said, though, we cannot ignore that (irrespective of the mechanism) "observational and experimental studies found an association between meal timing, weight gain, hyperglycemia and diabetes mellitus with benefits deriving from an early intake of food in the day in a wide range of individuals" (Beccuti 2017) - that may be the result of changes in ad-libitum food intake, but would still favor advising average Joes to eat early, btw.

Something similar can be said about what I consider one of the most important research contributions of the last year: the "carbohydrate-last"-principle and the previously largely ignored metabolic effects of a principle that you could file under "intra-meal-nutrient-timing". In contrast to "inter-meal-nutrient-timing", which failed to produce really relevant results, that's an area of research of which I believe that it will reappear on my and thus your radar in 2018 | Comment!
  • Beccuti, G. et al. "Timing of food intake: Sounding the alarm about metabolic impairments? A systematic review." Pharmacological research (2017).
  • Dhurandhar, Emily J., et al. "The effectiveness of breakfast recommendations on weight loss: a randomized controlled trial." The American journal of clinical nutrition 100.2 (2014): 507-513.
  • Li, Xiao-Mei, et al. "Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing." Cancer Research 70.8 (2010): 3351-3360.
  • Mattson, Mark P., et al. "Meal frequency and timing in health and disease." Proceedings of the National Academy of Sciences 111.47 (2014): 16647-16653.
  • Kaczmarek, Jennifer L., Salma MA Musaad, and Hannah D. Holscher. "Time of day and eating behaviors are associated with the composition and function of the human gastrointestinal microbiota." The American journal of clinical nutrition (2017a): ajcn156380.
  • Kaczmarek, Jennifer L., Sharon V. Thompson, and Hannah D. Holscher. "Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health." Nutrition reviews 75.9 (2017b): 673-682.
  • Leech, Rebecca M., et al. "Understanding meal patterns: definitions, methodology, and impact on nutrient intake and diet quality." Nutrition research reviews 28.1 (2015): 1-21.
  • Leung, Gloria KW, Catherine E. Huggins, and Maxine P. Bonham. "Effect of meal timing on postprandial glucose responses to a low glycemic index meal: A crossover trial in healthy volunteers." Clinical Nutrition (2017).
  • Liu, Yanan, et al. "The effects of daily intake timing of almond on the body composition and blood lipid profile of healthy adults." Nutrition research and practice 11.6 (2017): 479-486.
  • Patton, Danica F., and Ralph E. Mistlberger. "Circadian adaptations to meal timing: neuroendocrine mechanisms." Frontiers in neuroscience 7 (2013).
  • Patterson, Ruth E., et al. "Intermittent fasting and human metabolic health." Journal of the Academy of Nutrition and Dietetics 115.8 (2015): 1203.
  • Poggiogalle, Eleonora, Humaira Jamshed, and Courtney M. Peterson. "Circadian Regulation of Glucose, Lipid, and Energy Metabolism in Humans." Metabolism (2017).
  • Reid, Kathryn J., Kelly G. Baron, and Phyllis C. Zee. "Meal timing influences daily caloric intake in healthy adults." Nutrition Research 34.11 (2014): 930-935.
  • Shukla, Alpana P., et al. "Carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes." BMJ Open Diabetes Research and Care 5.1 (2017): e000440.
  • Thomas, E. A., Higgins, J., Bessesen, D. H., McNair, B. and Cornier, M.-A. (2015), Usual breakfast eating habits affect response to breakfast skipping in overweight women. Obesity. doi: 10.1002/oby.21049
  • Vetter, Celine, and Frank AJL Scheer. "Circadian Biology: Uncoupling Human Body Clocks by Food Timing." Current Biology 27.13 (2017): R656-R658.
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