Nitrate for Muscle+Brain Performance | Walking for Glucose Management | Full Glycogen Stores W/Out Excessive Water Retention | 5x10, 10x10, Cardio How mTOR and Co Respond

If Yap et al. were right and only continuous and not accumulative physical activity mattered, activity trackers like the this would be useless. No one needs a device to remind him of the 30 min of brisk walking he did / skipped today.

In today's installment of SuppVersity "On Short Notice", we're going to take a closer look at a selection of recent papers from the European Journal of Applied Physiology. To be more specific, I will discuss the physiological and psychological effects of dietary nitrate and their potential significance for team athletes. From there we're taking a detour to glycogen resynthesis and its interaction with hydration - a topic that may be highly relevant for bodybuilders and at least interesting for everyone else. Before we then take a departing look at the differential effects of 5x10, 10x10 and endurance exercise on markers of protein synthesis and glucose uptake, we'll spend briefly review the claim that the cumulative physical activity (the one you measure w/ step counters) would lack the characteristic health benefits everyone expects from meeting his daily activity goals.

Read more about exercise-related studies at the SuppVersity

Tri- or Multi-Set Training for Body Recomp.?

Alternating Squat & Blood Pressure - Productive?

Pre-Exhaustion Exhausts Your Growth Potential

Full ROM ➯ Full Gains - Form Counts!

Body Pump, Cardio & Exercise Expenditure

Study Indicates Cut the Volume Make the Gains!

• Dietary nitrate improves sprint performance and cognitive function during prolonged intermittent exercise - While anyone of you should know that nitrate from beetroots can have significant physiological effects, the observations Thompson et al. made in their recent double-blind randomised crossover study are probably real news and above all practically relevant for some of you and/or your clients from various athletic domains (Thompson. 2015).
  
  To investigate the effects of dietary NO3(-) supplementation on exercise performance and cognitive function, the scientists had 16 male team-sport players consume NO3(-)-rich (BR; 140 mL/day; 12.8 mmol of NO3(-)), and NO3(-)-depleted (PL; 140 mL day/1; 0.08 mmol NO3(-)) beetroot juice for 7 days (these are the regular shots you can buy at supplement stores | if you want to drink regular beetroot juice, you need 3-4x the amount). With the nitrate supplement being consumed over a one week period we are thus not talking about the effects of acute, but about the effects of chronic supplementation. Keep that in mind, if you buy one shot and don't feel the results immediately.
  
  On the test day the subjects completed a prolonged intermittent sprint test (IST) protocol (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out" sprint, 100-s active recovery and 20 s of rest) on a cycle ergometer during which cognitive tasks were simultaneously performed.

  

  Figure 1: Comparison of total work during the sprints and reaction times during cognitive decision making tasks designed to emulate the cognitive tasks during team sports (Thompson. 2015).

  As you can see in Figure 1 both, the total work done during the IST, as well as the reaction times that were measured during cognitive tasks in the second half of the IST, were improved in the beetroot vs. placebo trial.
  
  Even though, the scientists didn't find a difference in response accuracy, the findings are highly relevant for any athlete who has to (a) perform at high intensities, while (b) maintaining optimal cognitive performance and decision-making reaction times. Who is that? Well, I'd say almost every team sport athlete of whom previous studies have shown that his / her cognitive acuity suffers during prolonged intermittent exercise. 
• Extra water is not necessary for optimal glycogen replenishment after workouts - In fact, bodybuilders may want to avoid it... Avoid water? No, I am not saying you should not drink water at all, but if you look at the results of Valentín E. Fernández-Elías' recent "analysis of the relationship between muscle water and glycogen recovery after prolonged exercise in the heat in humans" you will see that too much water in the post-workout window may actually give you the 'watery' look some physique athletes like bodybuilders are trying to avoid.
  
  It is usually stated that glycogen is stored in human muscle bound to water in a proportion of 1:3 to 1:4 g. In their latest study, the scientists from the University of Castilla-La Mancha investigated this proportion in biopsy samples that were taken when their trained subjects recovered from prolonged exercise in the heat:

  "On two occasions, nine aerobically trained subjects (VO2max = 54.4 ± 1.05 mL/kg/min; mean ± SD) dehydrated 4.6 ± 0.2 % by cycling 150 min at 65 % VO2max in a hot-dry environment (33 ± 4 °C). One hour after exercise subjects ingested 250 g of carbohydrates in 400 mL of water (REHLOW) or the same syrup plus water to match fluid losses (i.e., 3170 ± 190 mL; REHFULL). Muscle biopsies were obtained before, 1 and 4 h after exercise" (Fernández-Elías. 2015).

  In contrast to what you may have expected, the muscle glycogen replenishment was not impaired by the lack of water in the REHLOW group. Ok, if you look at the data in Figure 2 right, there is a minimal advantage for the adequate water group, but this advantage is not statistically and almost certainly not practically relevant (79 ± 15 and 87 ± 18 g/kg dry muscle; P = 0.20).
  

  

  Figure 2: Muscle water content before and after dehydrating exercise and after 3 h recovery period (a). Muscle glycogen content before and after dehydrating exercise and after 4 h recovery period (b). Data is presented as mean ± SD. *Different from previous time point. †Different from REHFULL (P < 0.05 | Fernández-Elías. 2015).

  The thing that did differ between the adequat (REHFULL) and the inadequate (REHLOW) hydration trial, however, was the muscle water content which was significantly higher in the REHFULL than in the REHLOW trial (3814 ± 222 vs. 3459 ± 324 g/kg dm, respectively; P < 0.05; ES = 1.06).
  
  

  

  SuppVersity Suggested: "Hydrated or Dumb: Dehydration Affects Brain, Muscle and Other Vital Organs - Plus: 15+ Causes of Dehydration + Can the Color of Your Urine Tell You if You Drink Enough?" After reading this SV Classic and my recent article about the link between dehydration and type II diabetes you will probably stop thinking about using dehydration more than just occasionally.

  What's even more striking is that the scientists analysis of the ratio in which water and glycogen were stored in the two groups showed that subjects in the REHLOW trial stored the glycogen at the minimal 1:3 glycogen : water ratio, while their peers who got plenty of water exhibited a glycogen : water ratio of 1:17. Needless to say that this difference in water storage may be very important for bodybuilders during the last days and hours of their contest prep. In view of the importance of optimal hydration for your health, cognition and the hitherto unproven hypothesis that increases in cellular water may be involved in the hypertophy response to exercise (including the efficacy of creatine | Op‘t Eijnde. 2001), (non-)rehydration practices as they were used in the study at hand are nothing I would generally recommend. 
• Study says: Only continuous, not accumulated 30 min of walking will improve your glucose sensitivity - While step counters suggest that all you have to do to improve your health is to take "X" steps per day, the conclusion of a recent study from the DSO National Laboratories in Singapore refutes the simple and beautiful idea that you can distribute the X number of steps you would usually take during 30 minutes of brisk walking over three or more small "exercise servings" and see the same benefits as you'd see with 30 minutes of continuous brisk walking:

  "These findings demonstrate that 30 min of brisk walking is sufficient to improve insulin sensitivity in healthy, young Asians but only continuous and not accumulated walking provides this benefit. " (Yap. 2015).

  In said study, twenty-five healthy participants (12 males) participated in an oral glucose tolerance test (OGTT) the morning after: (i) accumulating three 10 min bouts of walking the previous evening; (ii) walking continuously for 30 min the previous evening or; (iii) resting the previous evening. Blood samples were taken in the fasted state and for 2 h post-OGTT. The subjects' insulin sensitivity was estimated from fasting blood glucose and insulin using the quantitative insulin sensitivity check index (QUICKI) and in response to the OGTT using an insulin sensitivity index (ISI-Matsuda).
  

  

  Figure 3: Changes in fasting glucose, insulin and insulin sensitivity (QUICKI) the morning after accumulated walking, continuous walking or a rest day; values expressed rel. to sedentary control (Yap. 2015).

  Now, as you've read a few lines above, the scientists say: Only the continuous walking is beneficial. Well, I don't know about you, but if I look at the study results in Figure 1, I wouldn't say that the data suggests that only continuous brisk walking would be beneficial. In fact, the early morning glycemia, which is by the way a pretty stupid measure of glucose tolerance anyway (cortisol rises in the AM and ruins the results), is very similar and the OGTT data in Figure 2 shows no practically relevant effect or difference either.
  

  

  Figure 4: Glucose (a), insulin (b) and insulin sensitivity index (ISI-Matsuda) (c) calculated from an oral glucose tolerance test the morning after three 10 min bouts of accumulated brisk walking, a 30-min continuous brisk walk or resting the previous evening. Values are mean (SD) (n = 25). Main effect of time for glucose (a) and insulin (b) (both P < 0.001). Main effect of trial for ISI-Matsuda (c) with Bonferroni post hoc t tests: accumulated walking vs. continuous walking (P = 1.000); accumulated walking vs. rest (P = 0.204); continuous walking vs. rest (P = 0.081 | Yap. 2015)

  With that being said, you can still rely on your step counter as a guide to a health-relevant amount of activity. What is important is that you get your physical activity in; and not that you do it in a continuous matter (even though that may offer small benefits in the study at hand). Plus, you will remember: Especially for those with some extra-weight on their hips "Increasing Physical Activity Just as Effective as Strength, Endurance or Combined Exercise to Lose Fat and Build Muscle" | re-read the SV article.

Figure 5: Summary of exercise-induced responses in signaling proteins and their selected signaling pathways investigated in the present study. The figure is simplified, and not all the possible connections between the proteins are shown. Signaling proteins are marked according to the present findings of changes from pre-exercise to 30 min post-exercise within the group (Ahtiainen. 2015).

Are you missing something? Yes, the -TOR study. The one with the different exercise types and volume and the effects on the signaling pathways regulating skeletal muscle glucose uptake and protein synthesis after workouts. So why did this interesting paper not get more room? Well, the answer is simple: If you determine only markers of protein synthesis, glucose uptake & co in response to 5 × 10 repetition maximum (RM) resistance exercise (RE) with leg press device (5 × 10 RE; n = 8), 10 × 10 RE (n = 11), and endurance exercise (strenuous 50-min walking with extra load on a treadmill; EE; n = 8) you generate results with little practical relevance. After all, we know that an increase in mTOR phosphorylation does not tell us that the actual protein synthesis let alone the long-term gains increases, as well - since those were not assessed in the Ahtiainen paper, their results are rather of educational than practical value.

The educational value is thus also the reason I still mention the study. I mean, I didn't want to deny you the opportunity of looking at the scientists' excellent "summary of exercise-induced responses in signaling proteins and their selected signaling pathways" in Figure 5 - even though, the cause-and-effect relationships are still 'hypothetical' in parts ;-) | Comment on Facebook!

References:

• Ahtiainen, Juha P., et al. "Exercise type and volume alter signaling pathways regulating skeletal muscle glucose uptake and protein synthesis." European journal of applied physiology (2015): 1-11.
• Fernández-Elías, Valentín E., et al. "Relationship between muscle water and glycogen recovery after prolonged exercise in the heat in humans." European journal of applied physiology (2015): 1-8.
• Op‘t Eijnde, B., et al. "Effect of creatine supplementation on creatine and glycogen content in rat skeletal muscle." Acta physiologica Scandinavica 171.2 (2001): 169-176.
• Thompson, Christopher, et al. "Dietary nitrate improves sprint performance and cognitive function during prolonged intermittent exercise." European journal of applied physiology (2015): 1-10.
• Yap, Mei Chan, Govindasamy Balasekaran, and Stephen F. Burns. "Acute effect of 30 min of accumulated versus continuous brisk walking on insulin sensitivity in young Asian adults." European journal of applied physiology (2015): 1-9.

Is the "Fat Kid" Doomed to Stay Fat Forever? What's the Role of Physical Activity Within a Window of Opportunity?

How large is the impact of not being active on childhood, adolescent and adult obesity. Plus: Are there critical time periods in gestation, infancy childhood and adolescence?

You may have heard the claim that "fat cells form during childhood and puberty and stay forever" before, right? Well, if that's the case it would be logical to assume that our childhood may be a critical developmental windows in which we have the time-limited opportunity to shape or help shape our own or our kids body composition for the rest of our or their lives.

Scientists from Mater Health Services South Brisbane, the University College of London, and the Griffith University have now reviewed the relatively scarce experimental and abundant observational pertinent research in order to examine "the role of physical activity during periods of risk to reduce the probability of obesity onset and maintenance in adulthood" (Street. 2015).

Reduced obese individuals and other things related to "metabolic damage"

Chronic Dieting Can Make You Skinny Fat

Nasty insights into the YoYo-Effect

Is There Diet-Induced Metabolic Damage?

Energy Deficits Can Make Athletes Fat

Fat Cell Size, NAFLD & Reduced Obesity

Metabolic Damage - What's the Evidence?

Unfortunately, but not surprisingly, most of the experimental evidence comes from rodent studies. If we tried to summarize the results of these studies in a half-sentence it would say that they demonstrate general positive effects of early exercise on the outcomes for all animals irrespective of maternal obesity status or post-weaning diet.

"Although high-fat post-weaning diets resulted in generally fatter animals, the body composition, endocrine and immune system profiles of these animals were healthier than non-exercising high-fat diet animals and comparable to standard chow non-exercising animals" (Street. 2015).

Interestingly, these effects do not disappear when the animals stop exercising. Rather than that studies indicate that exercise at an early age can protect animals against obesity onset for 5 weeks following exercise cessation (Caruso. 2013) - that's quite impressive if we take into account that rodents have a much shorter lifespan and a rapid early development period compared to humans (five rodent weeks in the early life are similar to several human years).

In spite of the fact that we don't know for sure for how long these protective effects will last in humans, there's little doubt that the same up-regulation of markers associated with increases in the skeletal muscle mitochondrial function, of which scientists believe that they protect the young rodents from obesity, will occur in humans as well (Shindo. 2014). Luckily, this is not the only thing we already know about rodents and assume for humans. Here's more:

• 

  Figure 1: If rodents are exercise in "childhood" (3WK), already, they will be significantly leaner - irrespective of whether they are fed an obesogenic HFD or the regular SMD diet (Wagener. 2012).

  the earlier, the better - the earlier young rodents are exercised (e.g. in the rodent equivalent of childhood), the more pronounced the protective effect against adult obesity (Wagener. 2012) - as you can see in Figure 1 earlier exercise will also yield significantly reduced body fat levels on standard rodent chow (SMD - 3WK);
• muscle & brain are involved - next to changes in the mitochondria, the "stay lean" effect is also mediated by changes in structure and/or function of brain regions involved in appetite regulation in mouse & man (Street. 2015); 
• males benefit more than females - the benefits of early exercise appear to be more pronounced for male vs. female animals (Schroeder. 2010); whether that's due to the higher muscle mass remains to be elucidated

In view of the fact that corresponding studies in human beings are not just time-consuming and expensive, but could also be unethical (think of kids being randomly assigned to non-exercise groups getting fat and sick as adults), it is not surprising that most of the evidence from human studies is of observational nature. Much in line with the findings from rodent studies, it has been suggested that three critical periods are important for obesity onset before adulthood: gestation and early infancy, the adiposity rebound and adolescence.

"Each period is characterized by substantial yet qualitatively different changes in growth and maturation. The culmination of each period represents a milestone in development and a subsequent reduction in the developmental plasticity of the maturing system. Given the inherently greater plasticity of earlier periods, obesity risk later in the life course is greater if the pre-conditions for obesity are established and maintained early. Disrupting the trajectory of obesity during development is likely to pay dividends in adulthood with a healthier body composition and metabolic profile. The disrupting effect of physical activity is less well understood in relation to obesity risk during and following critical periods" (Street. 2015).

Let's briefly recap what we know about these periods and how exercise during gestation (obviously in this case the mother would exercise), early infancy and adolescence influence our obesity risk as adults:

• 

  Figure 2: Body fat levels according to quartiles of physical activity in late pregnancy (Harrod. 2014).

  Gestation - Physical activity during pregnancy has been associated with reduced odds of a large-for-gestational age (LGA) infant, as well as reduced risk of small-for-gestational age, which are both linked to increased obesity risks later in life. In addition, there is evidence of reduced body fat levels, but identical lean mass and a significantly reduced risk of macrosomia (=excessive body weight) in babies born to mothers with higher levels of physical activity during pregnancy.
  
  Overall, however, the existing evidence - specifically for strength training - is conflicting and we are far from fully understanding the complex interactions between physical exercise, nutrition during gestation and the weight and body composition of the newborn baby (a usual more does not necessarily help mor). What appears to be certain though is that if beneficial effects occur, those will last for at least 12-24 months (Mattran. 2011; Chu. 2013). In one study scientists even found significantly reduced obesity risks up to age 5 even if the physical activity of the mother was the only significant difference between the kids (Clapp. 1996)

• 

  Figure 3: Observational data shows that there is an inverse linear association between infant activity scores and body fat percentages as early as in year 1 (Li. 1995).

  Infancy - Although it is correct that our body composition in infancy is still largely influenced by our mother's physical activity during gestation, there's good evidence that an earlier achievement of gross motor milestones (sitting, crawling, etc.) gives us the activity headstart we need to stay lean. Based on the correlation between earlier motor milestones and lower subscapular and triceps skin-folds measurements of 12 month-old kids Street et al. conclude that  "more active infants depose less fat over the first year [...] because active energy expenditure has resulted in increased metabolic capacity".
  
  In contrast to rodents, the "early activity bonus" does not last long in humans. With 5 years "early active" children are no longer significantly leaner than their peers, unless they were continuously more active and/or were fed different diets.
  
  In spite of the fact that early life activity does not provide life-long protection against obesity, though, the experimental and observational evidence of an inverse relationship between physical activity and body fat levels in infancy (Li. 1995) highlights the importance of leading an "active life" - in the most general sense - as early as possible. This is also relevant, because activity builds, while inactivity "kills" muscle, which is in turn associated with a further reduction in physical activity: Overweight infants, for example, have been shown to reach motor milestones later than leaner counterparts (Slining. 2010). Now you've just learned about the link between these milestones and staying lean in a previous paragraph. Accordingly, you will know that this means that the "sweet", chubby babies and toddlers may be caught in a vicious cycle of "obesity > low activity > lower muscle > lower activity > more obesity > lower activity ... "even before the know what the word "activity" means.

  

  Figure 4: Normal body fat development during infancy (Street. 2015).

  This does not mean that babies have to be "ripped", but I guess we all have seen kids with body fat levels way beyond the normal ~30% at 6 months (see Figure 4). The real problem, however, occurs thereafter, when the slow and steady decline in body fat should be driven by increases in a kid's activity energy expenditure (AEE). The latter takes the role of the energetic needs of growing which have previously been every toddler's #1 energy consumer. If the growth process slows and "activity", which does by the way include "vocalization primarily in the form of crying [which] is the next greatest pre-ambulatory energy cost after the energy cost of growth" (Street. 2015), does not take it's place, obesity ensues.
  
  Obviously, you could counter that by calorically restricting your toddler, but this is (a) unhealthy and (b) the exact opposite of what the mums and dads do. In fact, way too many of them are priming their kids to become obese sugar addicts by giving their kids a sugar-sweetened beverage (a "healthy baby tea" *rofl*), whenever the kids utter a sound just to make them shut up do. It is thus no wonder that studies have linked infant temperaments that are characterized by negative affectivity/emotionality and a more frequent use of vocal signals such as crying and thus more frequent maternal feeding responses to increased fat gain (Baughcum. 1998; Darlington. 2006). That's alarming, even if it has not yet been conclusively shown that the two are causally and not just corollary related.

• 

  Does the Optimal Meal Frequency Depend on Age? Study Suggests: Kids Better Eat Often, Adolescents Rather Step Away From Their Sugary Sins - Quality Counts! Read more!

  Childhood - An important feature of childhood development, particularly in terms of its association with increased obesity risk, is a fall in body mass index (BMI) until about 5–7 years of age, which is followed by the so-called "adiposity rebound" (AR).
  
  The earlier this rebound occurs, i.e. the earlier kids start to become fat again, the higher their risk of obesity as late as adulthood (Whitaker. 1998; Taylor. 2004). More specifically, studies like Whitaker et al. (1998) show that "early gainers" have a 20% higher obesity risk later in life and an extra 20% risk if they were already overweight - or I should say "over-fat" - at the age of 5-7 years.
  
  It is thus only logical that studies show that obese pre-schoolers often become obese adults (Nader. 2012). Next to the Western junk-food diet, research findings in the recent decades support a relationship between increased obesity risk, low physical activity and high sedentary pursuits during childhood (Reilly. 2010).
  

  

  Figure 5: Risk increase / decrease of becoming an obese teenager for weight status at AR, maternal and paternal BMI during; I think it's quite telling that even the "medium" weight (=average kids) already have increased obesity risks, these days (data from Whitaker. 1998).

  A recent study by Schuster et al., for example, shows that "overweight fifth-graders were more likely to become obese if they had an obese parent (P < .001) or watched more television (P = .02)" (Schuster. 2014); and that's only the last in a series of studies suggesting that children who engage in more vigorous physical activity are at reduced risk of obesity, while children who are more sedentary are at a significantly greater risk of becoming obese in adolescence, which happens to be the next and last developmental step we're going to discuss in today's SuppVersity obesity feature.
• Adolescence - Adolescence is a critical phase in the development of our fat stores. While the years before puberty are characterized by both fat cell hypertrophy (the fat cell size increases), hyperplasia (more fat cells are formed) and apoptosis (fat cells die), most experts agree that the number of apoptotic processes in our adipose tissue declines rapidly as we approach puberty.
  
  

  

  Figure 6: Difference of total fat mass of girls at age 10, 11, 12, 13; all values relative to girls who had a low and maintained a low activity levels (LL) - HH: high activity at baseline, low later, LH: low activity at baseline, high later, HL: high activity at baseline, low later (Völgyi. 2011).

  This decline in the adipose tissue turnover is really bad news and one of the reasons why scientists believe that the "critical window" from the headline of today's SuppVersity article closes during puberty:

  "It is generally thought that alteration in the size of fat cells in adulthood is achievable but maintenance of reduced fat cell size is likely to be difficult because of the mechanisms that may include, e.g. decreased leptin production. Furthermore, while an increase in adipo-cyte number is possible during adulthood, reversal of fat cell number does not occur. Consequently, adolescence represents an additional critical window when physical activity may affect obesity risk (reducing fat cell accretion) in ways it can-not during adulthood (reducing established fat cell number). " (Street. 2015)

  Since adolescence is also associated with an increase in lean mass, including skeletal muscle and bone, it is thus high time to start being, or - better - being even more active. After all, both muscle and bone mass are positively correlated with physical activity levels (Bailey. 1999; Völgyi. 2011).

A 2005 study by D'Andrea et al. shows significant increases in resting energy expenditure after large volume liposuction (all values expressed rel. to baseline). This is the exact opposite of what would happen if the same 4-5% of body fat had been lost by dieting and thus evidence that surgery may help people lose weight without setting them up for the yoyo effect even after the "window of opportunity" closed. 

Liposuction to the rescue! I am usually not a fan of cosmetic surgery, but in view of the fact that D’Andrea et al. (2005) were able to show that large-volume liposuction results in "a significantly improved insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels" in a clinical study conducted with 123 obese women, it is hard to ignore that the surgery knife may help even if the "Window of Opportunity" has closed, already. The reduction in REE in reduced obese individuals is after all one of the main reasons they regain weight (or struggle with weight regain for the rest of their life). If this problem is in fact triggered by the high amount of emptied fat cells that are left behind after losing more than 40lbs, it's only to assume that the surgical removal of fat cells would not lead to the same "pro-weight gain" problems.

• If you take a look at the data in Figure 6 it's yet not too late to start being active in puberty. The previously sedentary girls in Völgyi's study (Figure 6 | LH) who started to exercise regularly during puberty, for example,  were similarly lean as their "always active" peers (HH). Probably because they expended more energy, but also because their exercise left them less hungry than their sedentary peers ... that sounds like bogus? Well, take a look at the reduced 24h energy intake Thivel et al. measured in youths who were locked in a metabolic chamber in response to high intensity exercise vs. sitting around (Thivel. 2012 | Figure 7)  - exercise does not make you hungry.
  

  

  Figure 7: Much in contrast to what you may expect, obese kids actually eat less, when they are forced to work out. In that, doing high intensity exercise (HIE) is more "satiating" than low intensity (Thivel. 2012).

  Now, if exercise curbs your appetite, while being sedentary increases it and its obesogenic consequences, which in turn reduce your willingness and ability to exercise, it is obvious what Street et al refer to when they are talking about "a two way street" (Street. 2015). It's the previously hinted at vicious cycle in which lower physical activity predisposes to obesity, while obesity in turn predisposes to even greater reductions in physical activity.
  
  In view of the previously referenced physiological peculiarities, adolescence appears to be the last stage in our development, where increased activity, alone, can go a long and consequential way. It is thus all the more important to break the cycle of being sedentary <> getting fatter before the transition into adulthood takes place. After all, the currently available research leaves little doubt that physical activity during adolescence will promote an adult body composition and metabolic profile that is associated with a reduced obesity risk, and reduced morbidity: Adult women who were more active adolescents, for example, are 50% less likely to be abdominally obese - even if all covariates are controlled for (da Silva. 2015). Physical activity interventions in adults, on the other hand, yield very ambiguous results. In most cases, however, being more active alone will not make a significant enough difference to trigger fat loss and instigate health improvements. 

Shi et al. conducted an interesting experiment that highlight the role of low leptin in weight regain. They fattened rodents up, dieted them down and found that the weight reduced rodents whose weight loss had stagnated after 3 weeks had the same low leptin levels as the normal-weight significantly leaner rodents. The hypothesis is that this is due to having more, but empty fat cells that produce way too little leptin for the total amount of body fat, because the amount of leptin that's produced depends in a non-linear way on the level of fat in the cells. Rodent bogus? Well several human studies showing a reversal of neurological, endocrine and metabolic abnormalities in reduced obese indiv. with leptin (Rosenbaum. 1997, 2005 & 2008) suggest that this may actually be happening in man & woman, too.

So what? With the vicious cycle of being sedentary, getting fat, being even more sedentary and getting even fatter, we are back to our original question which was whether you'd have to stay fat forever if you end up being fat at the end of puberty. I wouldn't go so far as to say that your fate is determined, but it's hard to ignore the evidence that our kids can at least avoid adding additional fat cells and thus increase their chance of life-long leanness by leading an active lifestyle. We, on the other hand are in a very compromised situation. In contrast to studies in adolescents, many studies in adults show that even combined aerobic and resistance training, may effectively shed our love-handles once we are adults (Willis. 2012).

Dieting, on the other hand, may successfully reduce our body weight, but the risk of "refilling" the fat cells we've created as babies, children and adolescents, when the body fat turnover and the natural "apoptotic death" of fat cells stagnates, increases with every pound of extra body fat we've "acquired" as babies, children and teens. Why exactly this is the case has not been fully elucidated, yet. I personally find that Shi's 2009 hypothesis that says (generally speaking) that the high number of small fat cells in people who have gained a lot of fat before adulthood are left with after a diet won't produce enough leptin to signal the body that they've achieved a new steady state. Constant hunger and rapid and easy fat gain even from consuming the "exact" amount of energy they should need are the nasty consequences some of you may have experienced first-hand | Comment!

References:

• Bailey, D. A., et al. "A six‐year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskatchewan Bone Mineral Accrual Study." Journal of Bone and Mineral Research 14.10 (1999): 1672-1679.
• Baughcum, Amy E., et al. "Maternal feeding practices and childhood obesity: a focus group study of low-income mothers." Archives of Pediatrics & Adolescent Medicine 152.10 (1998): 1010-1014.
• Caruso, V., H. Bahari, and M. J. Morris. "The Beneficial Effects of Early Short‐Term Exercise in the Offspring of Obese Mothers are Accompanied by Alterations in the Hypothalamic Gene Expression of Appetite Regulators and FTO (Fat Mass and Obesity Associated) Gene." Journal of neuroendocrinology 25.8 (2013): 742-752.
• Chu, Lisa, et al. "Impact of maternal physical activity and infant feeding practices on infant weight gain and adiposity." International journal of endocrinology 2012 (2012).
• Clapp, James F. "Morphometric and neurodevelopmental outcome at age five years of the offspring of women who continued to exercise regularly throughout pregnancy." The Journal of pediatrics 129.6 (1996): 856-863.
• D’Andrea, Francesco, et al. "Changing the metabolic profile by large-volume liposuction: a clinical study conducted with 123 obese women." Aesthetic plastic surgery 29.6 (2005): 472-478.
• da Silva Garcez, Anderson, et al. "Physical Activity in Adolescence and Abdominal Obesity in Adulthood: A Case-Control Study Among Women Shift Workers." Women & health ahead-of-print (2015): 1-13.
• Darlington, Anne-Sophie E., and Charlotte M. Wright. "The influence of temperament on weight gain in early infancy." Journal of Developmental & Behavioral Pediatrics 27.4 (2006): 329-335.
• Harrod, Curtis S., et al. "Physical activity in pregnancy and neonatal body composition: the healthy start study." Obstetrics & Gynecology 124.2, PART 1 (2014): 257-264.
• Li, Ruowei, et al. "Relation of activity levels to body fat in infants 6 to 12 months of age." The Journal of pediatrics 126.3 (1995): 353-357.
• Mattran, Kelly, et al. "Leisure-time physical activity during pregnancy and offspring size at 18 to 24 months." Journal of Physical Activity and Health 8.5 (2011): 655.
• Nader, Philip R., et al. "Next steps in obesity prevention: altering early life systems to support healthy parents, infants, and toddlers." Childhood Obesity (Formerly Obesity and Weight Management) 8.3 (2012): 195-204.
• Reilly, John J. "Low levels of objectively measured physical activity in preschoolers in child care." Medicine and science in sports and exercise 42.3 (2010): 502-507.
• Rosenbaum, Michael, et al. "Effects of Weight Change on Plasma Leptin Concentrations and Energy Expenditure 1." The Journal of Clinical Endocrinology & Metabolism 82.11 (1997): 3647-3654.
• Rosenbaum, Michael, et al. "Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight." Journal of Clinical Investigation 115.12 (2005): 3579.
• Rosenbaum, Michael, et al. "Leptin reverses weight loss–induced changes in regional neural activity responses to visual food stimuli." The Journal of clinical investigation 118.7 (2008): 2583.
• Schroeder, Mariana, et al. "Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity." Hormones and behavior 57.4 (2010): 496-505.
• Schuster, Mark A., et al. "Changes in obesity between fifth and tenth grades: A longitudinal study in three metropolitan areas." Pediatrics 134.6 (2014): 1051-1058.
• Shi, Haifei, et al. "Diet‐induced Obese Mice Are Leptin Insufficient After Weight Reduction." Obesity 17.9 (2009): 1702-1709.
• Shindo, Daisuke, Tomokazu Matsuura, and Masato Suzuki. "Effects of prepubertal-onset exercise on body weight changes up to middle age in rats." Journal of Applied Physiology 116.6 (2014): 674-682.
• Slining, Meghan, et al. "Infant overweight is associated with delayed motor development." The Journal of pediatrics 157.1 (2010): 20-25.
• Street, S. J., J. C. K. Wells, and A. P. Hills. "Windows of opportunity for physical activity in the prevention of obesity." Obesity Reviews (2015).
• Taylor, Rachael W., et al. "Rate of fat gain is faster in girls undergoing early adiposity rebound." Obesity research 12.8 (2004): 1228-1230.
• Thivel, David, et al. "The 24-h energy intake of obese adolescents is spontaneously reduced after intensive exercise: a randomized controlled trial in calorimetric chambers." PloS one 7.1 (2012): e29840.
• Wagener, A., A. O. Schmitt, and G. A. Brockmann. "Early and late onset of voluntary exercise have differential effects on the metabolic syndrome in an obese mouse model." Experimental and Clinical Endocrinology and Diabetes 120.10 (2012): 591.
• Whitaker, Robert C., et al. "Early adiposity rebound and the risk of adult obesity." Pediatrics 101.3 (1998): e5-e5.

Phosphatidic Acid Reduces Whey-Induced Acute Protein Synthesis - Rodent Study Appears to Suggest Antagonism Not Synergism Between PA & Whey - What's the Verdict?

If we take the study at hand as a bench-mark, it appears as if you cannot really recommend PA supplements to serious gymrats. Due to a bunch of short-comings and a lot of open questions, I have to caution you not to jump to preliminary & potentially flawed conclusions.

If you are a "regular" here, at the SuppVersity, you will have heard about the mTOR-promoting effects of Phosphatidic Acid (PA) before (learn more). If you've also been following the SV News on Facebook, you will also know that I have repeatedly highlighted that we need studies that go beyond the mere provision of phosphatidic acid to mouse or man and assess whether adding PA to whey will ameliorate the whey-protein induced increases in protein synthesis, muscle and strength gains. Why would that be important if we do have studies that indicate that PA is effective? Well, anyone who even remotely considers paying the $$$ for a PA product will already be taking whey protein. If adding PA on top of his whey protein shake does not yield extra benefits (or worse), he would - and I would even say he should - not spend extra cash on phosphatidic acid... but before we get to any conclusions, let's take a close look at the latest research.

Today, I must suggest you stick to the tried and proven, protein supplements

Are You Protein Wheysting?

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Protein: Food or Supplement?

Protein Timing DOES Matter!

Less Fat, More Muscle!

To understand why one may even expect that there was a synergism between whey protein (or leucine) and phosphatidic acid, one has to be aware of the fact that both trigger mTOR, albeit via different pathways: While leucine activates mTOR through RAG GTPase, PA is thought to independently activate mTOR through competitive binding with the mTOR inhibitor FKBP38. As Mobley et al. point out in the introduction to their latest paper in the Journal of the ISSN it does thus "stand[...] to reason that whey protein could synergistically activate mTOR if co-ingested with PA" (Mobley. 2015). Accordingly, ...

"the purpose of this study was to examine if PA acutely increases anabolic signaling markers and muscle protein synthesis (MPS) in gastrocnemius with and without whey protein concentrate (WPC) supplementation" (Mobley. 2015).

In view of the fact that previous studies did not do a detailed analysis of the skeletal muscle transcriptomic response to PA and considering the fact that the latter may be important with respect to finding explanations for any - positive or negative - findings, Mobley et al. ran detailed analysis of the skeletal muscle mRNA response to PA and/or WPC, as well. Their goal was to assess whether PA or PA + whey would affect key genes involved in muscle mass maintenance (myostatin (Mstn) and p21Cip1), metabolism (PGC-1α and GLUT-4), and skeletal muscle atrophy (Atrogin-1 and MuRF-1). To get this data, the researchers randomly assigned male Wistar rats to four different treatments groups groups in which they were gavaged with one of the following "supplements":

• control (CON) - 1 ml of tap water
• phosphatidic acid (PA) - 0.029 g soy-derived PA (S-PA, Mediator®, ChemiNutra, Austin, TX, USA) suspended in 1 ml of tap water; this being a human equivalent dose of 1.5 g per the species conversion calculations of ReaganShaw et al. (learn more)
• whey protein concentrate (WPC) - 0.193 g WPC (standardized to 80 %, donated graciously by C.M.L.) suspended in 1 ml of tap water; this being a human equivalent dose of 10 g 
• combined (PA + WPC) - 0.029 g soy-derived PA + 0.193 g WPC suspended in 1 ml of tap water

Three hours post-feeding, the gastrocnemius muscle was removed and analyzed for markers of Akt-mTOR signaling, gene expression patterns related to skeletal muscle mass regulation and metabolism, and muscle protein synthesis (MPS) analysis (note: there was no training involved!).

Why is it important that there was no training involved? With training we'd have a third factor that affects protein synthesis and net muscle gains via the mTOR cascade. It is well possible that it does not make much of a difference and the results would be similar. In view of the fact that it is yet also possible that the results would be reversed, no athlete should make his supplement choices based on studies that do not involve a form of physical exercise that's at least remotely similar to his / her own training.

Figure 1: Effects of PA with or without the co-ingestion of WPC on skeletal muscle mRNA expression patterns. Legend: Data are presented as means ± standard error. Bars not sharing similar superscript letters are significantly different (p < 0.05 | Mobley. 2015).

In our discussion of the results, I'd like to start with the less controversial data (if there is any) in Figure 1. The figure depicts the 6 graphs that illustrate the skeletal muscle mRNA expression in response to the four different treatments. If you know something about reading graphs like this you will realize that the PA+WPC combo had a potentially anabolic advantage in terms of myostatin suppression. Just like the increase in glucose transporter GLUT-4, where the PA+WPC group shows significantly higher levels than any other group, this would be a clear sign of the expected beneficial synergism. However, no relevant differences were found for the potentially "atrophic" proteins MuRF-1 and atrogen-1 (learn more), and the mitochondria builder PGC-1a (for a discussion of the potential relevance of the significant increase of the cell-cycle arrest protein p21Cip1 in the PA only group see blue box).

Learn how satellite cells, domain sizes, myonuclei and myostatin limit the growth potential of your muscle in this SV Classic!

What do we make of the large increase in P21Clp1 mRNA? In view of the fact that the p21Cip1 gene is thought to promote satellite cell differentiation (Hawke. 2003a,b), one could argue that its increase in the PA group could be a harbinger of the reduced muscle protein synthesis in the whey condition. After all, any protein that goes to the myogenic precursor cells in the sarcoplasm is diverted away from the myoplasm and the myoblasts the scientists extracted from the rodents. If that's in fact case, it would be even more interesting to see a long-term study on PA + WPC. Eventually it would mean that PA may increase the recruitement of satellite cells. That's important not just for muscle repair, but also for growth.

In fact, a lack of new satellite cells which can form myonuclei will cause the domain sizes to increase to a critical level, where mostatin will stop further growth in order to prevent the muscle from becoming disfunctional, until new myonuclei have been formed from satellite cells.

So, if this process of muscle "restructuring" was triggered, promoted or enforced by PA this could be a huge plus. One that would be especially valuable for experienced athletes for whom the increase in domain sizes may in fact become a growth limiting factor. Unfortunately, all this remains speculative, until corresponding human long-term studies W/ will have been conducted.

If we think of the p21Cip1 elevation (see discussion in the blue box) as the "standby" for muscle gains, look at the increased myostatin levels and even the mTOR response in Figure 2 everything looks as if the study had hardly been necessary and the expected synergism was there. Unfortunately, the most straight forward marker of real-world benefits, the skeletal muscle protein synthesis (it's not a real-world benefit in and out of itself), tells us a very different story.

Figure 2: Effects of PA with or without the co-ingestion of WPC on mTOR-related signaling markers (a-f) and acute factional muscle protein synthesis (right hand side | Mobley. 2015).

If there was a synergism between whey and PA it does - and the data in Figure 2 leaves no doubt about that - not translate into increases in muscle protein synthesis. In fact, the addition of phosphatidic acid appears to blunt, not increase the acute influx of protein into the muscle. That may be a "shocking" revelation for some of you, but if you've been following the SuppVersity articles for a couple of month you will know that there's a disconnect between the increases in allegedly anabolic signalling molecules like mTOR & co and the actual rate of protein synthesis. That does not change the simple truth, though, that the data in Figure 2 (right) suggests that the provision of PA on top of whey protein impairs the protein anabolic effect of whey.

So, does this mean that phosphatidic acid is a supplemental non-starter? Let's not jump to conclusions we may regret, here. We are not only dealing with a preliminary rodent study, here, we are also dealing with a study without practically relevant study outcomes. Why's that? Well, you should remember that there are two disconnects when it comes to measuring mTOR, protein synthesis and actual muscle size & strength gains. I've already mentioned the first one: Increases in mTOR and related signalling proteins don't necessarily translate to increases in protein synthesis.

From previous SuppVersity articles you should yet also remember that increases in protein synthesis don't necessarily translate into significantly increased muscle gains, either (Burd. 2012 | learn more). Why's that? Well, I guess the answer is more complex than that, but one thing everyone should understand is that muscle gains are the difference between protein synthesis and breakdown. Whether the protein breakdown did in fact increase, though, is something the mere elevation of an allegedly catabolic signalling protein, i.e. MuRF1 (see Figure 1), in the study at hand cannot tell us reliably. What we'd really have to measure would be the net protein accrual (in sarcoplasm and myoplasm | see blue box) over 24h or more - a value that has not been determined in the study at hand. If we had this value and it was significantly lower with PA  + WPC, this would be a reason to be concerned.

On it's own PA has already proven that it works - even in humans, where it doubled the lean mass gains triggered albeit non-significant reductions in body fat at 50% of the dosage used in the study at hand. So, if anything, we may use this study to argue that adding PA to whey could be useless.

The lack of data on the net protein accrual is directly related to another problem Mobley et al. call the "limited post-feeding time point interrogation" and mean that you cannot tell what happens in days / weeks by measuring protein synthesis for a very short period at a "random" point after the ingestion of a supplement. Since we (b) also don't have data on the intramuscular PA levels and are (c) lacking data on different dosages of PA and/or WPC dosages as well as an exercise group (which could be a game changer), the only thing we can tell for sure is that future long-term human studies with relevant outcome markers, i.e. strength and muscle gains, as well as a resistance training component are needed before we can safely conclude that PA joins the ranks of the dozens of supplemental non-starters that have been celebrated in the absence of relevant scientific evidence as "the next best thing" in the past decades | Comment!

References:

• Burd, Nicholas A., et al. "Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men." British Journal of Nutrition 108.06 (2012): 958-962.
• Hawke, Thomas J., Nan Jiang, and Daniel J. Garry. "Absence of p21CIP rescues myogenic progenitor cell proliferative and regenerative capacity in Foxk1 null mice." Journal of Biological Chemistry 278.6 (2003a): 4015-4020.
• Hawke, Thomas J., et al. "p21 is essential for normal myogenic progenitor cell function in regenerating skeletal muscle." American Journal of Physiology-Cell Physiology 285.5 (2003b): C1019-C1027.
• Mobley, C. Brooks, et al. "Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle." Journal of the International Society of Sports Nutrition 12.1 (2015): 32.

Paleo Goes "Real Science" - First Meta-Analysis of Available RCTs Shows Improvements in Health + Body Composition

The good thing about paleo is that you can eat a broad range of foods. An advantage that makes paleo versatile and tasty enough to adhere to.

I know that I will probably have annoyed some of you by implicitly calling "paleo" non-scientific. If we are honest, though, the whole paleo concept is based on extrapolating data from modern hunter gatherer populations, infusing them with a minimal amount of real evidence of what our ancestors ate and mixing that with the intrinsically flawed assumption that the way our ancestors ate (which was 100% opportunistic and 0% "optimized") was the optimal way for us to eat... and no, I am not going to apologize for what some of you may consider an assault on respected scientists who have published more than a dozen of papers which constitute the theoretical backbone of an experimentally still mostly unverified, but promising approach to "healthy dieting".

Meat is an essential part of the "paleo diet" | Learn more about meat at the SuppVersity

You May Eat Pork, too!

You Eat What You Feed!

Meat & Prostate Cancer?

Meat - Is cooking the problem

Meat Packaging = Problem?

Grass-Fed Pork? Is it Worth it?

Just to make sure there's no confusion. I am not saying that everything that Eaton, Cordain and others wrote is bogus. I am just saying that their papers are above everything else the material based on which others have formulated research hypothesis and done experimental research. Research that has been reviewed in a soon-to-be-published paper in the influential American Journal of Clinical Nutrition, by Eric W Manheimer, Esther J van Zuuren, Zbys Fedorowicz, and Hanno Pijl. A paper that leaves its readers with a generally positive conclusion, but state that "[t]he available data warrant additional evaluations of the health benefits of Paleolithic nutrition" (Manheimer. 2015). Now that does not sound like much, but in view of the scarcity of evidence it is more than you'd usually expect from a review that was partly financed by the National Center for Complementary and Alternative Medicine of the US.

When they decided on the methodology, inclusion and exclusion criteria, Manheimer et al. began with the simple, but important question "Does paleo-nutrition improve risk factors for chronic disease more than other dietary interventions in people with the metabolic syndrome?" To answer this question, the authors searched the following bibliographic databases for reports of controlled trials without any language restriction (likewise included were relevant results from the following ongoing trials databases):

• 

  Figure 1: Details of the selection process in January 2015 (Manheimer. 2015).

  The Cochrane Central Register of Controlled Trials (CENTRAL) 2014
• MEDLINE via OVID (from 1946)
• EMBASE via OVID (from 1974)
• LILACS (Latin American and Caribbean Health Science Information database, from 1982)
• Science Citation Index (from 1988 to the present).
• The metaRegister of Controlled Trials 
• The U.S. National Institutes of Health Ongoing Trials Register
• The Australian and New Zealand Clinical Trials Registry 
• The World Health Organization International Clinical Trials Registry platform 

The reference lists of all identified RCTs and key review articles were also reviewed and squared with the following selection criteria:

"Randomised controlled trials will be included. Any other study design will be excluded. We will only include cross-over trials if we are able to extract the relevant data from the first phase (i.e., before the crossover occurred) because we consider the risk for carryover effects to be prohibitive" (Manheimer. 2015).

In addition, the scientists looked for dietary interventions which were designed to emulate as much as possible, for the modern time, the diet of plants and animals eaten by human beings during the Paleolithic era. More precisely, Manheimer et al. included only studies with diets with...

• large amounts of vegetables (including root vegetables), 
• fruits (including fruit oils e.g., olive oil, coconut oil, palm oil), 
• nuts, fish, meat, and eggs

To make sure to get relevant data, the duration of the dietary intervention had to be at least one week. Studies showing only acute improvement in blood pressure, glucose levels or whatever from eating more veggies and fruit and calling that "the paleo diet" were thus not included in the meta-analysis. The same goes for two uncontrolled clinical trials, as well as all studies where the dietary protocols included one or several of the following "paleo-nono-foods": dairy, grain-based foods, legumes, extra sugar, nutritional products of industry (including refined fats, refined carbohydrates).

This is the macronutrient composition (in g/day) of what Eaton describes as the "paleo diet" in his 1985 seminal paper - needless to say that this is based solely on hypothetical extrapolations of sample data from modern hunter gatherer populations and the little actual evidence we have of what our ancestors ate (Eaton. 1985).

So what's paleo, and what was it compared to? For those who are too lazy to read the full article, here's the gist. The "paleo diets in the four RCTs that were analyzed in Manheimer's meta-analysis used diets that were high in vegetables (including root vegetables), fruits (including "fruit oils", i.e. olive oil, palm oil, coconut oil) and nus, fish, meat and eggs. Dairy, grains, legumes, extra-sugar and processed foods were a no-go in all studies Manheimer et al. included in their analysis. The control diets in all 4 RCTs that were concluded in the meta-analysis were based on distinct national nutrition guidelines, but still broadly similar. Obviously that's interesting, because the results of this meta-analysis are thus going to be a comparison of the "paleo diet" and the recommended "healthy diet" according to what experts on certain advisory boards think would be the one and only way for us to eat.

Important side note: I would like to use the chance to highlight that this diet - if it was not for the (imho) unnecessarily rigid exclusion of dairy and legumes - is actually very similar to what fitness experts have been suggesting for decades. If you do the math on the macros in Eaton's recommendation you end up with 32.5% protein, 22.8% fat, 43.7% carbohydrates and the rest of the energy in form of fiber. With this common macro ratio from the fitness community and the requirement to "get all of that from whole foods" you end up eating almost the same diet.

The number of studies all these search efforts brought to light was - as you, as someone who's heard about all the pertinent trials on www.facebook.com/SuppVersity, already, will know - not exactly extensive. All in all, only four RCTs that involved 159 participants were included. This were four RCTs with very similar results, as the researchers' meta-analysis revealed:

"In this systematic review and meta-analysis of 4 RCTs, Paleolithic nutrition resulted in greater short-term pooled improvements on each of the 5 components of the metabolic syndrome than did currently recommended guideline-based control diets. However, the greater pooled improvements did not reach significance for 2 of the 5 components (i.e., HDL cholesterol and fasting blood sugar). For each metabolic syndrome component, the quality of the evidence for the pooled estimate for improvement was moderate" (Manheimer. 2015).

I guess what these results mean is much easier to grasp if you take a look at the plot of the data I've created for you. Keep in mind: What you see in Figure 1 are the differences compared to the allegedly "optimal" recommended diets in the respective studies, not differences to the habitual diets of the subjects which were probably significantly more pronounced.

Figure 2: Improvements in  triglycerides, HDL, fasting blood sugar, waist circumference, systolic and diastolic blood pressure with "paleo" diets vs. nationally recommended diets (Manheimer. 2015).

The most significant and probably practically relevant benefits of the paleo diet can be seen in the graph on the right hand side: Compared to the relatively small (and practically probably almost irrelevant, if not already stat. non-significant) advantages in terms of blood lipids and glucose, the improvements in blood pressure and waist circumferences are what I would use to argue in favor of paleo-esque dietary recommendations in front of any expert panel.

Meat vs. beans - what's more satiating? A recent study from the University of Minnesota did a "paleo-relevant" comparison of the satiety effects of meat- and bean-based meals. More specifically, Bonnema and her colleagues compared the satiety response to a beef meal providing 26 g of protein and 3 g of fiber to a bean meal providing 17 g of protein and 12 g of fiber. What they found may surprise the non-paleo-lovers out there: "[The] beef-based meal with high protein and [the] bean-based meal with moderate protein and high fiber produced similar satiety, while the bean-based meal resulting in higher, yet moderate, gas and bloating" (Bonnema. 2015). Since both lead to a reduced energy intake on subsequent meals, both the anti-paleo legume-based and the paleo meat-based meal "could equate to weight loss and/or management over time" (ibid.).

After all, more than 50 million people in the US alone are suffering from full-blown hypertension (high blood pressure). In view of the fact that even pre-hypertension is associated with an 80% increased risk of cardiovascular morbidity (learn more), the consumption of a paleo-esque diet could thus save the lives of millions of people. In view of the fact that this would also save us billions of dollars that are spent on managing hypertension every year, this is probably the strongest argument in favor of the "paleo diet" (Note: It's not an exclusive advantage, though. The DASH diet with a similar if not higher vegetable and fruit content has similar effects).

Figure 3: Increase in all-cause mortality risk among 48 500 men and 56 343 women, 50 years or older, in the Cancer Prevention Study II Nutrition Cohort according to BMI and waist circumference (Jacobs. 2010).

A bit less convincing for the average panel member, but practically as relevant are the significant decreases in waist circumference. With studies showing a 2-fold elevated all-cause mortality risk in average American men and women with WC ≥120 cm (compared with <90 cm) and WC ≥110 cm (compared with <75 cm), respectively (see Figure 3 for details), there's yet little doubt that an improvement in this often overlooked health-marker is just as important as the reduction in blood pressure.

Bottom line: Even though we have to rely exclusively on the evidence of the four studies (Lindeberg. 2007; Jönsson. 2009; Boers. 2014; Mellberg. 2014), there's little doubt that paleo-esque diets are superior to many of the recommended "low fat + whole grain, ..."-diets. Unfortunately, the number of pertinent studies is small and the existing studies have short-comings the critics will always bring up as an objection when someone dares questioning the current recommendations:

• Three out of the four existing RCTs, i.e. Lindeberg, Jönssen and Boers, either didn't account for inter-group differences at baseline or didn't report whether they did that or didn't do it (you can safely assume that they didn't, so that everyone can easily say that the paleo group had an unfair advantage and we cannot tell if this was or wasn't the case).
• Adverse events were assessed only in one out of the four existing RCTs (in the Boers study) and otherwise completely ignored (in view of the accusations against "paleo" from the proponents of the current guidelines that's an important shortcoming).
• The quality of life was not assessed by any of the studies (I don't say that the quality of life will suffer, but it is unquestionably important to assess it, also in view of the likeliness that people will adhere to the diet in the long run).

These issues, as well as the short the duration of three out of the four existing studies (only the Mellberg study lasted 2 years) are problems the "paleo research" will still have to overcome before any of the governing bodies / councils will say "paleo is the new recommended diet for XY" (insert "the average citizen of the European Union", "the average US citizen", etc. for XY).

No, there are not neg. side effects of high protein intakes. On the contrary, the major source of acids in the Western diets are grains which are obviously not allowed on "paleo diets" | more

In view of the fact that the analysis of secondary outcomes, like body weight development [subjects on paleo lost 2.69 (0.52-4.87) kg more], inflammation [subjects on paleo reduced their CRPs by 0.28 (0.21-0.76) mg/L more], fasting insulin [subjects on paleo had 13.03 (6.52-32.59) pmol/L lower levels], and total cholesterol [subjects on paleo had 0.24 (0.09- 0.56) mmol/L levels], yielded similar "pro-paleo" results, I personally think that it is very unlikely that future trials that avoid these problems would find very fundamentally different results and/or ill health effects of a liberal paleo-esque dietary template.

The fact that longer-term studies that account for baseline differences, measure adverse events and assess the quality of life of their subjects are not available, yet, is still holding "paleo" back from greater acceptance within the medical / research community. Plus: What I would like to see are studies that compare the different paleo varieties, as in "strict paleo" vs. "paleo + dairy" or "paleo + legumes"... but who knows, maybe someone is already working on one or several of these studies at the very moment today's SuppVersity article is published. | Comment on Facebook!

References:

• Boers, Inge, et al. "Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study." Lipids Health Dis 13.1 (2014): 160. 
• Eaton, S. Bovn, M. Konner, and N. Paleolithic. "A consideration of its nature and current implications." N Engl j Med 312.5 (1985): 283-9.
• Jacobs, Eric J., et al. "Waist circumference and all-cause mortality in a large US cohort." Archives of internal medicine 170.15 (2010): 1293-1301.
• Jönsson, Tommy, et al. "Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study." Cardiovasc Diabetol 8.35 (2009): 1-14.
• Lindeberg, Staffan, et al. "A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease." Diabetologia 50.9 (2007): 1795-1807.
• Manheimer, et al. "Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis." American Journal of Clinical Nutrition (2015): Ahead of print.
• Mellberg, Caroline, et al. "Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a 2-year randomized trial." European journal of clinical nutrition 68.3 (2014): 350-357.