Nutrient Timing Less, Cyclic Dieting & Baseline Microbiome More Important for Fat Loss - Nutrition Science News 02/18

They may have been published in "Obesity" and observed in people w/ weight problems, but the results of these three recent papers are still relevant for lean, metabolically healthy people, too.

Even if you are already way beyond the stage, where "weight loss" is your main interest, I am pretty sure you will appreciate this selection of recent studies from obesity research all around the world. After all, some of the research may actually help you achieve your new goal which should be to lose body fat while keeping or even building lean mass.

In today's research review I am going to discuss three papers that have recently been published in the International Journal of Obesity (after being available online since late 2017, btw). To generalize one could say that the papers deal with the effects of nutrient timing and your microbiome on the efficacy of your fat loss efforts.

Review older articles about the gut - health axis.at the SuppVersity

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

Microbiome <> Bread's H. Effects

• Usefulness of high(er) fiber diet for fat loss depends on your individual microbiome (Hjorth 2017) -- A recent study from the University of Copenhagen found that the pre-treatment ratio of Prevotella to Bacteroides in your gut "determines body fat loss success during a 6-month randomized controlled diet intervention" (Hjorth 2017). 
  
  As Hjorth et al. point out in the introduction of their paper, the human gut microbiota can be divided "into two relatively stable groups that might have a role in personalized nutrition" (Hjorth 2017): Pprevotella and Bacteroids. In their latest RCT the scientists studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets.
  

  

  Figure 1: As the %-ages that indicate the differences between New Nordic and Standard Danish diet indicate, the former is better for everyone. The p-values (change for high vs. low P/B ratios) in the legend, on the other hand, clearly indicate that people with high P/B ratios benefit more from this dietary switch (Hjorth 2017).

  A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/whole grain or an Average Danish Diet (ADD) for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models that yielded interesting insight into the microbiome <> fat loss diet interaction:

  "Among individuals with high P/B the NND resulted in a 3.15 kg (95% confidence interval (CI): 1.55; 4.76, P<0.001) larger body fat loss compared with ADD, whereas no differences was observed among individuals with low P/B (0.88 kg (95% CI: −0.61; 2.37, P=0.25))" (Hjorth 2017)

  If you do the math, you'll realize that this is a statistically significant 2.27 kg difference between subjects with high P/B or low P/B ratios. If you've followed mainstream dietary advice but didn't see the promised (and expected) fat loss benefits, having a relative abundance of Prevotella spp. may be to blame (interested in enterotypes: the basics).

Prevotella have previously been found to be associated with more favorable cardiovascular/metabolic health markers (de Moraes 2017)

Prevotella the vegetarian, the healthy bacteria? If you watched the video I linked above, you will be aware of the link between meat and Bacteroides, on the one hand, and plant foods and Prevotella, on the other hand. Don't subscribe to black-or-white picture they're painting, though. As pointed out later in this article, a low level of the allegedly carcinogenic Bacteroids has also been found to be characteristic of patients with inflammatory bowel disease.

With another study showing a correlation between markers of cardiovascular health and the abundance of Prevotella (e.g. lower BMI, lower 2h blood glucose levels, and waist circumference vs. higher HDL with higher numbers of Prevotella | de Moraes 2017) the latter, i.e. the "vegetarian microbiome", does yet have more scientific back-up to fuel claims about potential health benefits.

• Speaking of "blame", previous studies have shown that the similar results for the health benefits of capsaicin which is likewise particularly pronounced in subjects with a Bacteroides enterotype (Kang 2016). What? Oh right, Bacteroides, alongside Firmicutes account for the majority of human distal gut bacterial flora (~90%) and the presence of these gram-negative bacteria, many of which we know as pathogens, is not generally a bad thing - a recent meta-analysis, for example, found "Lower Level of Bacteroides in the Gut Microbiota Is Associated with Inflammatory Bowel Disease" (Zhou 2016).
  
  Ah, and the good news is that previous research shows that the P/B ratio will remain stable during a 6-month randomized controlled diet intervention with the New Nordic Diet (Roager 2014). It's unlikely that the fat loss benefits will disappear from one day to the next because your microbiome adapted. This does yet also mean that it won't become more effective over time if you've got a low P/B ratio, to begin with :-(
• Yes, you can ... shed body and liver fat and significantly improve your insulin sensitivity no matter if you eat your largest meal early or late in the day (Versteeg 2017) -- The notion that eating a large dinner will have negative health effects that are so potent that they can override the benefits of a caloric deficit has just been disproven (again) in a new RCT from the University of Amsterdam.
  
  The authors, R.I. Versteeg and colleagues, studied if there's any truth to the hypothesis "that during weight loss, consuming most [of one's energy intake] in the morning improves insulin sensitivity and reduces hepatic fat content more than consuming most [of the] energy in the evening" (Versteeg 2018). To this ends, they had twenty-three obese insulin-resistant men (age 59.9±7.9 years, body mass index 34.4±3.8 kg/m²) follow a 4-week hypocaloric diet intervention with either 50% of daily energy consumed in the morning (BF group) or evening (D group).
  

  

  Figure 2: Only the peripheral (e.g. muscle) insulin sensitivity saw a small, but non-significant benefit from meal timing - interestingly enough from having a large dinner, not a large breakfast (Versteeg 2018).

  Insulin sensitivity, measured with a two-step hyperinsulinemic euglycemic clamp using a glucose tracer, intrahepatic triglycerides (IHTG), measured using magnetic resonance spectroscopy, and resting energy expenditure (REE) were assessed before and after the diet intervention and the results were ... quite unambiguous, to be honest: It doesn't make a difference - at least not a statistically significant one! Or, to be more specific:

  "Meal macronutrient composition and weight loss (6.5±1.5% vs 6.2±1.9%, respectively, P=0.70) did not differ between the BF and D groups. Endogenous glucose production (P⩽0.001), hepatic and peripheral insulin sensitivity (P=0.002; P=0.001, respectively) as well as IHTG [intrahepatic triglyceride = liver fat] content (P⩽0.001) all significantly improved with weight loss, but were not different between the BF and D groups. In addition, both groups decreased REE and respiratory quotient equally" (Versteeg 2017).

  In other words: Calories count more than timing and timing the lion's share of your calories later in the day ain't going to hurt your weight loss and health improvement efforts.
• Cyclic dieting (2 weeks in a deficit, 2 weeks on maintenance) shows significant weight and, more importantly, fat loss benefits (Byrne 2017) -- Intermittent fasting is all the rage, but what about "intermittent dieting" or as I would prefer to call it: cyclic dieting? That's probably the question Byrne et al. had in mind when they came up with the subgroup design of the MATADOR study, in which fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total).
  
  In that, it is important to note that both groups had their energy intake reduced to 67% of weight maintenance requirements when they were actively dieting. The total deficit over time was thus identical (assuming perfect adherence).
  
  The body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) data from the forty-seven participants who eventually participated in the study (the others dropped out as early as in the 4-week lead-in), revealed that...

  "weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: −624±557 kJ d−1; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: −360±502 vs CON: −749±498 kJ d−1; P<0.05)" (Byrne 2017).

  Stated simply: The subjects who had bi-weekly "refeeds", which is how some of you may think of the maintenance phases, may not have preserved more muscle mass or higher metabolic rates (if you scrutinize figure 3, you'll see that a residual effect existed on REE, though), ...
  

  

  Figure 3: Changes (absolute) in weight, body composition and resting energy expenditure (in kcal per hour, adjusted for body comp.); p-values for treatment differences (CON vs. INT | Byrne 2017).

  ...but they lost more body fat!  Or, as the scientists put it: "Interrupting ER with energy balance ‘rest periods’ may reduce compensatory metabolic responses and, in turn, improve weight loss efficiency" (Byrne 2017).

Want to lose that blubber in a minimal amount of time? Diet like a bodybuilder and don't forget to refeed, Ladies! A study I discussed three years ago shows that a more conventional "refeed"-ish dieting regimen provides major fat loss advantages, too | more

So what are the take-home messages? Some things matter, other don't. The bacterial composition of your microbiome, or - as scientists would say - your enterotype, which has long been completely overlooked by scientists and dieters alike, does turn out to be the major determinant of the health benefits of what's considered a healthy fiber-rich diet by many researchers.

The often-touted obesogenic and health-disrupting effects of gravitating towards having your largest meal in the PM is - at least in a dieting (=energy reduction) context and if weight + liver fat loss an improvements in glucose metabolism are the primary outcomes - irrelevant; a result that's probably also relevant (needs separate studies, though) for people who skip breakfast and fast intermittently.

And, last but not least. "Cyclic dieting" or whatever you want to call the cycle of 8x2 weeks of dieting at 67% of your maintenance calories interspersed by 7x2 weeks at maintenance seem to support weight and, more specifically and importantly, fat loss, significantly.

So, just as promised: Three studies with practical relevance beyond obesity research. Stay tuned for more research updates in the weeks to come... ah, and let me know if you like the presence of links to the abstracts of papers in the SuppVersity article - usually I stick to references, only; is it worth spending the 3 extra-minutes to implement the links? | Comment!

References: 

• Byrne, Nuala M., et al. "Intermittent energy restriction improves weight loss efficiency in obese men: the MATADOR study." International Journal of Obesity (2017).
• Hjorth, M. F., et al. "Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention." International Journal of Obesity (2017).
• Kang, Chao, et al. "Healthy subjects differentially respond to dietary capsaicin correlating with specific gut enterotypes." The Journal of Clinical Endocrinology & Metabolism 101.12 (2016): 4681-4689.
• de Moraes, Ana CF, et al. "Enterotype may drive the dietary-associated cardiometabolic risk factors." Frontiers in cellular and infection microbiology 7 (2017): 47.
• Roager, Henrik M., et al. "Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet." Applied and environmental microbiology 80.3 (2014): 1142-1149.
• Zhou, Yingting, and Fachao Zhi. "Lower level of Bacteroides in the gut microbiota is associated with inflammatory bowel disease: a meta-analysis." BioMed research international 2016 (2016).