Alan Aragons Research Review November 2013 [Back to Contents] Page 1

Copyright November 1st, 2013 by Alan Aragon

Home: www.alanaragon.com/researchreview

Correspondence: aarrsupport@gmail.com

2 Has the last decade of nutrient timing research

reached an anti-climax? By Alan Aragon

5 Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized control trial. Cao JJ, Pasiakos SM, Margolis LM, Sauter ER, Whigham

LD, McClung JP, Young AJ, Combs GF Jr. Am J Clin Nutr.

2013 Nov 27. [Epub ahead of print] [PubMed]

6 Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Witard OC, Jackman SR, Breen L, Smith K, Selby A,

Tipton KD. Am J Clin Nutr. 2013 Nov 20. [Epub ahead of

print] [PubMed]

7 Leucine supplementation of a low-protein mixed

macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. Churchward-Venne TA, Breen L, Di Donato DM, Hector

AJ, Mitchell CJ, Moore DR, Stellingwerff T, Breuille D,

Offord EA, Baker SK, Phillips SM. Am J Clin Nutr. 2013

Nov 27. [Epub ahead of print] [PubMed]

8 Evaluation of the usefulness of a low-calorie diet

with or without bread in the treatment of overweight/obesity. Loria-Kohen V, Gmez-Candela C, Fernndez-Fernndez

C, Prez-Torres A, Garca-Puig J, Bermejo LM. Clin Nutr.

2012 Aug;31(4):455-61. [PubMed]

10 The Meat and Nuts Breakfast of Champions.

By Matt Jones

13 Jonathan Bailor claims slim is simple but finds many ways to overcomplicate it. By Alan Aragon

17 Martial arts meets academia: an interview with Dr.

Brian Jones. By Alan Aragon

Alan Aragons Research Review November 2013 [Back to Contents] Page 2

Has the last decade of nutrient timing research reached an anti-climax?

By Alan Aragon

____________________________________________________

Ivy & Portmans big splash in 2004

Ivy and Portmans book Nutrient Timing: The Future of Sports Nutrition

1 hit publication and ushered in one of the biggest

trends in sports nutrition. I own a copy myself, and youd be hard-pressed to find a sports nutrition-oriented practitioner who

hasnt been influenced by the book, which involves detailed prescriptions for pre-, during-, and post-exercise nutrition. As

stated in the first chapter, specific timing of nutrients enables

trainees to avoid the plateau effect and achieve far greater gains in muscle strength and muscle mass. However, while the authors created an awareness of the potential utility of nutrient

timing strategies, the supporting research was comprised largely

of acute (short-term) studies on subjects taken to glycogen

depletion after an overnight fast.

Hit-and-miss after a standout in 2006

Over the course of the next decade, several chronic (long-term)

studies cropped up, and the results have been equivocal. Perhaps

the strongest research supporting nutrient timing was Cribb and

Hayes famous 2006 finding that timing protein, carbohydrate, and creatine immediately sandwiching both sides of the

resistance training bout resulted in significantly greater lean

body mass (LBM) and strength gains than the same nutrients

positioned far from both sides of the bout.2 From that point

onward, chronic timing studies seemed to be hit-and-miss, yet

the conventional wisdom endured over time. This was despite

research like that of Hoffman et al, which was a similar design to

Cribb & Hayes, but failed to observe significant differences

between the treatments.3

Challenging the paradigm

The anabolic window of opportunity concept became virtually a foregone conclusion. It was presumed to be a matter of fact,

and thus was rarely questioned. To my knowledge, the first peer-

reviewed article to challenge the anabolic window concept was the one I co-authored with Brad Schoenfeld.

4 The reach and

impact of this article has been measurably big. Shortly after its

publication in January of this year, it became the number-one

most viewed article in the history of the Journal of the

International Society of Sports Nutrition (JISSN).

Our paper (full text here) contains an in-depth discussion of the

limitations surrounding the traditional nutrient timing paradigm,

focusing on protein and carbohydrate. An examination of the

literature revealed that the prevailing protein timing tenets lack a

consistent evidence basis, especially in chronic trials. In

addition, the carbohydrate timing rules for maximizing the

anabolic response were on questionable ground as well. To the

latter point, the available data have consistently shown the

failure of additional carbohydrate to augment muscle protein

synthesis given an adequate protein dose both at rest5 and post-

exercise.6,7

An important note about our paper is that it never

claims that the longstanding nutrient timing dogma is useless or

invalid. We never claimed that nutrient timing does not matter.

In fact, the practical applications we outlined for the goal of

maximizing the anabolic response involve specific timing except the anabolic window is considerably larger than that of the traditional dogma. We proposed that there is up to a 4 to 6-

hour peri-workout period in which to dose pre- & post-exercise

protein (with each dose being at least 0.4-0.5 g/kg LBM) and

still maximize the anabolic response to resistance training. The

timing of carbohydrate is left largely to personal preference,

with exceptions being endurance applications where glycogen

depletion occurs more than once per day within close proximity

in the same muscle group. The papers final sentence is an eloquent summation (if I may say so myself):

4 Collectively,

these data indicate an increased potential for dietary flexibility

while maintaining the pursuit of optimal timing.

Quantitative evidence further challenges the paradigm

Conducting a meta-analysis of protein timing studies was the

natural progression of investigation after the publication of our

narrative review. Brad Schoenfeld came up with the idea. He

collaborated with myself and James Krieger on the paper.8 To

our delight, it has become JISSNs #2 most-viewed article of the past year within less than a month of its publication, and its already the #6 most-viewed in the history of the journal. The

popularity of this article and its predecessor shows that there are

many folks in both the academic and public domains with an

open mind to the current data, and a healthy skepticism towards

traditional assumptions.

The aim of our meta-analysis (full text here) was to examine the

available protein timing research on strength and hypertrophy in

a systematic, quantitative fashion. Meta-analyses enable an

increase in statistical power by the pooling of data from several

studies. When done correctly, meta-analyses can provide a big-

picture/aerial view of the data and quantitatively uncover the

weight of the evidence (in whatever direction it might lean, if it

leans at all). We used a multi-level meta-regression that

employed a hierarchical/step-wise reduction process designed to

control for covariates (factors aside from timing that might

influence outcomes). Before delving into this any further, it

should be made perfectly clear that we had no agenda and no

pre-conceived hopes or ideas of what the analysis might find.

The whole point of research is to draw tentative conclusions

based on the data. If done backwards, where the data is cherry-

picked or manipulated to support pre-conceived conclusions,

then the entire purpose is completely lost.

The temporal parameters we chose as inclusion criteria are worth

highlighting because theyre critical for properly interpreting the results. We specifically compared studies where protein was

dosed within an hour of either side of the training bout versus

studies where protein was dosed at least 2 hours away from

either side of the training bout. This framework is based largely

on Ivy and Portmans long-standing, highly influential claim that the post-exercise anabolic window is approximately 45 minutes,

after which point the opportunity to capitalize on nutrient-

mediated anabolism significantly diminishes.1

Alan Aragons Research Review November 2013 [Back to Contents] Page 3

Selected noteworthy details & findings of our meta-analysis

Our analysis had several interesting findings. First of all, there was no significant effect of protein timing on strength or hypertrophy after all covariates were accounted for. This outcome has disturbed and even angered many folks who passionately believe in protein timing near the training bout. However, it must be kept in mind that this result is potentially limited to the parameters we set for comparison, which again, were protein ingested 1 hour pre- and/or post-exercise, versus 2 hours pre- and/or post-exercise. Any effects outside of those parameters were simply not investigated.

Based on the focus of our analysis, we cannot determine whether

or not extended periods of protein neglect beyond 2 hours pre-

and/or post could possibly yield inferior effects on strength

and/or hypertrophy. But once again, our aim was to examine the

proverbial anabolic window of opportunity which is fabled to be a relatively narrow timeframe to slam that shake.

An important finding was that total protein intake (rather than

timing) was the strongest variable associated with hypertrophy.

Average protein intake in the treatment (timed protein) groups

was 1.66 g/kg/day, whereas it was 1.33 g/kg/day in the controls.

Given this, it appears that treatment conditions involved a more

optimized level of protein intake compared to the controls. This

brings us to the issue of the unfair disadvantage of control groups where total protein intake was not matched with that of

the treatment groups. The vast majority of studies simply add a

protein supplement near the training bout and compare that with

a non-protein placebo. We recognized this confounding

imbalance, so we ran a sub-analysis of protein-matched studies,

but still, no significant effect of timing was seen.

It should be noted that of the 23 studies included for analysis,

only 3 of them were protein-matched. This limits the statistical

power of the sub-analysis of true timing studies. Interestingly, 2 of the 3 protein-matched studies did not show a significant

effect of timing. Its also worth mentioning that two frequently cited studies did not meet our inclusion criteria. Esmarck et al

9

didnt make the cut because the protein dose did not contain the minimum of 6 g EAA. Burk et al

10 was excluded because of

insufficient data to calculate effect size. Even if the latter two

studies were included in the analysis, it wouldnt likely alter the outcomes and conclusions, since Esmarck et al saw positive

effects of protein consumed near the end of the training bout

while Burk et al actually saw greater benefits of a protein

supplement timed away from the end of the bout.

Indeed, we recognized the scarcity of protein-matched studies as

one of the biggest problems with the literature that traditionally

falls under the nutrient timing umbrella. This scarcity of protein-

matched timing studies is also one of the strongest reasons why

vehemence about the timing of protein immediately near training

is not warranted. The limited statistical power of the small

number of protein-matched studies is also a good reason to not

harbor any strong confidence that protein timing is useless.

Another major limitation of the available research is a lack of

studies that use resistance-trained subjects, since this population

would be most likely to expose any potential benefits of protein

timing. Interestingly, no significant influence of training status

was detected in the full meta-regression model that controlled

for all covariates.

Conclusions, for the time being

So, did nearly a decade of nutrient timing research reach an anti-

climax? It depends on how you look at it, since thats quite a broad claim. Protein timing within a narrow anabolic window

relative to the training bout ( 1 hour pre- and/or post-exercise) appears to take a backseat to total daily protein. This finding

seems to reinforce basic logic. Those who consume enough total

daily protein and energy to maximize strength and hypertrophy

are likely to spend the majority of their day in the postprandial

(fed) state. Furthermore, they are also likely to spend the

majority of their day in a state of hyperaminoacidemia resulting

from multiple protein-rich meals. These conditions collectively

would minimize the effects of temporal variations in protein

intake relative to the training bout.

It bears reiterating that theres a lack of protein-matched timing studies. This makes it possible that the null findings we saw

were due to type II error. In other words, false-negative results

could have occurred from insufficient statistical power to detect

significant differences. Another point to consider is that theres no evidence of an ergolytic effect of protein timed near the

training bout, and there is some evidence of positive effects.

Therefore, scooting the dose(s) close to training is generally a

good idea for maximizing all hypothetical routes toward

muscular size and strength. Avoiding lengthy gaps in protein

feeding relative to the training bout (e.g., significantly more than

2 hours) can also hedge your bets toward maximizing anabolic

adaptations. The degree of timing precision is whats debatable.

People mistakenly debate over nutrient timing importance as if

its a black & white issue. This is a false dichotomy, since it should be viewed as a continuum. I created the chart below to

outline the variable importance of nutrient timing.11

Notice how

the span of applications of nutrient timing diminishes alongside

the increase of nutrient timing importance.

Alan Aragons Research Review November 2013 [Back to Contents] Page 4

References

1. Ivy J, Portman R: Nutrient Timing: The Future of Sports Nutrition. North Bergen, NJ: Basic Health Publications;

2004.

2. Cribb PJ, Hayes A. Effects of supplement timing and resistance exercise on skeletal muscle hypertrophy. Med Sci

Sports Exerc. 2006 Nov;38(11):1918-25. [PubMed]

3. Hoffman JR, Ratamess NA, Tranchina CP, Rashti SL, Kang J, Faigenbaum AD. Effect of protein-supplement timing on

strength, power, and body-composition changes in

resistance-trained men. Int J Sport Nutr Exerc Metab. 2009

Apr;19(2):172-85. [PubMed]

4. Aragon AA, Schoenfeld BJ. Nutrient timing revisited: is there a post-exercise anabolic window? J Int Soc Sports

Nutr. 2013 Jan 29;10(1):5. [PubMed]

5. Hamer HM, Wall BT, Kiskini A, de Lange A, Groen BB, Bakker JA, Gijsen AP, Verdijk LB, van Loon LJ.

Carbohydrate co-ingestion with protein does not further

augment post-prandial muscle protein accretion in older

men. Nutr Metab (Lond). 2013 Jan 25;10(1):15. [PubMed]

6. Staples AW, Burd NA, West DW, Currie KD, Atherton PJ, Moore DR, Rennie MJ, Macdonald MJ, Baker SK, Phillips

SM: Carbohydrate does not augment exercise-induced

protein accretion versus protein alone. Med Sci Sports Exerc

2011, 43(7):1154-1161. [PubMed]

7. Koopman R, Beelen M, Stellingwerff T, Pennings B, Saris WH, Kies AK, Kuipers H, Van Loon LJ: Coingestion of

carbohydrate with protein does not further augment

postexercise muscle protein synthesis. Am J Physiol

Endocrinol Metab 2007, 293(3):E833-842. [PubMed]

8. Schoenfeld BJ, Aragon AA, Krieger JW. The effect of protein timing on muscle strength and hypertrophy: a meta-

analysis. J Int Soc Sports Nutr. 2013 Dec 3;10(1):53. [Epub

ahead of print] [PubMed]

9. Esmarck B, Andersen JL, Olsen S, Richter EA, Mizuno M, Kjaer M. Timing of postexercise protein intake is important

for muscle hypertrophy with resistance training in elderly

humans. J Physiol. 2001 Aug 15;535(Pt 1):301-11.

[PubMed]

10. Burk A, Timpmann S, Medijainen L, Vhi M, Opik V. Time-divided ingestion pattern of casein-based protein

supplement stimulates an increase in fat-free body mass

during resistance training in young untrained men. Nutr Res.

2009 Jun;29(6):405-13. [PubMed]

11. Aragon AA. Continuum of nutrient timing importance (original schematic). NSCA Personal Trainers Conference,

April 2012.

Alan Aragons Research Review November 2013 [Back to Contents] Page 5

Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized control trial.

Cao JJ, Pasiakos SM, Margolis LM, Sauter ER, Whigham LD,

McClung JP, Young AJ, Combs GF Jr. Am J Clin Nutr. 2013

Nov 27. [Epub ahead of print] [PubMed]

BACKGROUND: Although consuming dietary protein above current recommendations during energy deficit (ED) preserves lean body mass, concerns have been raised regarding the effects of high-protein diets on bone health. OBJECTIVE: The objective was to determine whether calcium homeostasis and bone turnover are affected by high-protein diets during weight maintenance (WM) and ED. DESIGN: A randomized, parallel-design, controlled trial of 32 men and 7 women were assigned diets providing protein at 0.8 [Recommended Dietary Allowance

(RDA)], 1.6 (2 RDA), or 2.4 (3 RDA) g kg-1 d-1 for 31 d. Ten days of WM preceded 21 d of ED, during which total daily

ED was 40%, achieved by reduced dietary energy intake (30%) and increased physical activity (10%). The macronutrient composition (protein g kg-1 d-1 and % fat) was held constant from WM to ED. Calcium absorption (ratio of

44Ca to

42Ca) and

circulating indices of bone turnover were determined at day 8 (WM) and day 29 (ED). RESULTS: Regardless of energy state, mean (SEM) urinary pH was lower (P < 0.05) at 2 RDA (6.28 0.05) and 3 RDA (6.23 0.06) than at the RDA (6.54 0.06). However, protein had no effect on either urinary calcium excretion (P > 0.05) or the amount of calcium retained (P > 0.05). ED decreased serum insulin-like growth factor I, increased serum tartrate-resistant acid phosphatase, and 25-hydroxyvitamin D concentrations (P < 0.01). Remaining markers of bone turnover and whole-body bone mineral density and content were not affected by either the protein level or ED (P > 0.05). CONCLUSION: These data demonstrate that short-term consumption of high-protein diets does not disrupt calcium homeostasis and is not detrimental to skeletal integrity. This trial was registered at www.clinicaltrials.gov as NCT01292395. SPONSORSHIP: Supported by the US Army Medical Research and Material Command and the USDA Agricultural Research Service program Bone Metabolism in Obesity.

Study strengths

This study is unique in that its the first to examine the important question of how a high protein intake affects calcium

absorption/retention and markers of bone metabolism during

energetic maintenance and deficit conditions. A thorough set of

protein intake conditions was compared (0.8, 1.6, & 2.4 g/kg)

under weight maintenance as well as a 40% deficit condition

comprised of 30% intake reduction combined with 10% increase

in physical activity. Dietary intake was tightly controlled as the

menu was prepared by research dietitians. A similar intake of

calcium among the conditions was enforced via supplementation

to avoid the confounding effects of varying calcium intakes.

Study limitations

Its possible that the study duration (31 days) was not long enough to reveal potential detriments of the higher-protein

conditions on markers of bone health. Also, there was no

progressive resistance training protocol imposed. Resistance

training has a substantive body of evidence supporting its

beneficial effects on bone mineral density.1-3

Higher dietary

protein has recently been shown to reduce bone turnover in the

long-term (24 months) under dieting conditions.4 In this vein,

higher dietary protein (20% as opposed to 10% of energy) has

also been shown to improve calcium absorption from low-

calcium diet, which offsets urinary losses.5 Its plausible that a

high protein intake in combination with progressive resistance

training and sufficient calcium would constitute a potent effect

on increasing or preserving bone mineral density (in addition to

the protective effect on muscle mass). It would have been useful

(and innovative) to investigate a potential dose-response

relationship between graduated protein intakes and bone status

in the presence of a progressive resistance training program. In

this study, exercise was standardized to be low-intensity and

non-progressive.

Comment/application

Note that this study was part of a larger study led by Pasiakos et

al that examined varying protein levels on body composition and

muscle protein synthesis.6 They found that both higher-protein

groups lost a significantly higher proportion of fat mass and

lower proportion of lean mass compared to the RDA group,

without any significant differences between the higher-protein

groups (2x versus 3x the RDA). The main findings of the present

study were that despite increases in urinary acidity, diets that are

2 or 3 times the RDA did not significantly alter urinary calcium

excretion, dietary calcium retention, or markers of bone turnover

and bone mineral density when calcium & vitamin D are

consumed at recommended levels.

In addition, what I found interesting was an outcome that wasnt the specific focus of the present study. There was the lack of

significant difference in total weight loss between the groups

during the 21-day energy deficit period. Weight loss was 3.5 kg

for the RDA group, 2.7 kg for 2x RDA, and 3.3 kg for 3x RDA).

The important detail here is that the increased protein intakes in

the weight maintenance (WM) and energy deficit (ED) phases of

each diet were at the expense of carbohydrate:

What we have is further confirmation that under conditions that

tightly control total energy intake, theres nothing inherently advantageous to weight loss about carbohydrate reduction per

se... The authors ultimately concluded that high-protein diets are

not detrimental to calcium metabolism, but also acknowledge the

need for longer-term studies to render more definitive answers to

the question of bone safety of high protein intake.

Alan Aragons Research Review November 2013 [Back to Contents] Page 6

Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise.

Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton

KD. Am J Clin Nutr. 2013 Nov 20. [Epub ahead of print]

[PubMed]

BACKGROUND: The intake of whey, compared with casein and

soy protein intakes, stimulates a greater acute response of muscle

protein synthesis (MPS) to protein ingestion in rested and exercised

muscle. OBJECTIVE: We characterized the dose-response

relation of postabsorptive rates of myofibrillar MPS to increasing

amounts of whey protein at rest and after exercise in resistance-

trained, young men. DESIGN: Volunteers (n = 48) consumed a

standardized, high-protein (0.54 g/kg body mass) breakfast. Three

hours later, a bout of unilateral exercise (8 10 leg presses and leg

extensions; 80% one-repetition maximum) was performed.

Volunteers ingested 0, 10, 20, or 40 g whey protein isolate

immediately (10 min) after exercise. Postabsorptive rates of myofibrillar MPS and whole-body rates of phenylalanine oxidation

and urea production were measured over a 4-h postdrink period by

continuous tracer infusion of labeled [13

C6] phenylalanine and

[15

N2] urea. RESULTS: Myofibrillar MPS (SD) increased (P <

0.05) above 0 g whey protein (0.041 0.015%/h) by 49% and 56%

with the ingestion of 20 and 40 g whey protein, respectively,

whereas no additional stimulation was observed with 10 g whey

protein (P > 0.05). Rates of phenylalanine oxidation and urea

production increased with the ingestion of 40 g whey protein.

CONCLUSIONS: A 20-g dose of whey protein is sufficient for

the maximal stimulation of postabsorptive rates of myofibrillar

MPS in rested and exercised muscle of 80-kg resistance-trained, young men. A dose of whey protein >20 g stimulates amino acid

oxidation and ureagenesis. This trial was registered at

http://www.isrctn.org/ as ISRCTN92528122. SPONSORSHIP:

Supported by GlaxoSmithKline Nutritional Healthcare.

Study strengths

This study breaks new ground by being the first to ever examine

the dose-response relationship of myofibrillar muscle protein

synthesis (MPS) to increasing amounts of whey at rest and after

resistance exercise. Subjects had a minimum of 6 months of

recreational weight-lifting experience. Habitual food intake was

assessed and replicated 48 hours prior to testing. The exercise

protocol was intensive in terms of the work done in the target

muscle group (quads). 16 sets total were done with leg press and

extension at 80% of 1RM with 2-minute rest intervals. A

standout design strength was the assessment of whey-mediated

MPS 3 hours after a standardized high-protein breakfast, in

recognition of the fact that in real world, most people weight-

train in a fed rather than fasted state.

Study limitations

Although the aim of the study was to examine acute response

(which it did a good job of), the very nature of acute response

data is hypothesis-generating in the context of the bigger picture.

Short-term response does not necessarily translate to long-term

adaptation. So, while investigating anabolic response dosing

thresholds provides valuable data, its still preliminary and in need of follow-up by trials examining the influence of these

protocols on endpoints such as hypertrophy and/or strength,

which would require a period of weeks to measure. A final

limitation is a missing intermediate dose between 20 g and 40 g.

It would have been interesting to see the effects of 30 g and 50 g

doses as well, not only to get a finer picture of the response

curve, but also to further exploit where the true plateau is.

Comment/application

The main findings were a lack of significant increase in MPS

with 10 g whey, while MPS significantly increased with 20 g

and 40 g, with a lack of lack of significant difference in MPS

between the latter two doses. However, as seen above, theres an uptrend in MPS that doesnt appear to truly plateau at 40 g, despite the difference between 20 g and 40 g failing to reach

statistical significance. In light of this, the authors diligently

acknowledge the possibility that this small difference could

potentially be meaningful in regards to concrete endpoints in the

long-term:

However, intriguingly, mean postexercise myofibrillar MPS values were ~19% higher in the 20WP than 10WP but only an additional ~10% higher in the 40WP. An additional calculation of the 95% CI for the true difference between the 20WP and 40WP revealed that we could not rule out a 14% increase in the myofibrillar FSR with the ingestion of 40 g whey protein. [...] ...the long-term physiologic impact of a 1014% higher rate of MPS in the 40WP on muscle hypertrophy remains unknown.

The authors astutely mentioned that the dose for maximizing the

anabolic response could potentially vary according to individual

differences in muscle mass. For example, its not known whether someone with 80 kg LBM would have a greater MPS response

to a higher protein dose compared to someone with 50 kg LBM.

Although this hasnt been systematically tested, it intuitively would seem to be true. Knowing that larger individuals require

more total protein, it would be fair to speculate that they also

have a larger capacity for MPS from the constituent doses of

protein that comprise the daily total. In any case, older subjects

have been observed to have a higher protein dosing ceiling for

MPS (35-40 g as opposed to 20 g in younger subjects).7,8

Along

with age comes anabolic resistance. Since most of us dont age in reverse, I would recommend erring toward the higher side of

protein dosing if the main goal is hypertrophy.

Alan Aragons Research Review November 2013 [Back to Contents] Page 7

Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial.

Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ,

Mitchell CJ, Moore DR, Stellingwerff T, Breuille D, Offord EA,

Baker SK, Phillips SM. Am J Clin Nutr. 2013 Nov 27. [Epub

ahead of print] [PubMed]

BACKGROUND: Leucine is a key amino acid involved in the regulation of skeletal muscle protein synthesis. OBJECTIVE: We assessed the effect of the supplementation of a lower-protein mixed macronutrient beverage with varying doses of leucine or a mixture of branched chain amino acids (BCAAs) on myofibrillar protein synthesis (MPS) at rest and after exercise. DESIGN: In a parallel group design, 40 men (21 1 y) completed unilateral knee-extensor resistance exercise before the ingestion of 25 g whey protein (W25) (3.0 g leucine), 6.25 g whey protein (W6) (0.75g leucine), 6.25 g whey protein supplemented with leucine to 3.0 g total leucine (W6+Low-Leu), 6.25 g whey protein supplemented with leucine to 5.0 g total leucine (W6+High-Leu), or 6.25 g whey protein supplemented with leucine, isoleucine, and valine to 5.0 g total leucine. A primed continuous infusion of l-[ring-

13C6] phenylalanine with serial muscle

biopsies was used to measure MPS under baseline fasted and postprandial conditions in both a rested (response to feeding) and exercised (response to combined feeding and resistance exercise) leg. RESULTS: The area under the blood leucine curve was greatest for the W6+High-Leu group compared with the W6 and W6+Low-Leu groups (P < 0.001). In the postprandial period, rates of MPS were increased above baseline over 0-1.5 h in all treatments. Over 1.5-4.5 h, MPS remained increased above baseline after all treatments but was greatest after W25 (267%) and W6+High-Leu (220%) treatments (P = 0.002). CONCLUSIONS: A low-protein (6.25 g) mixed macronutrient beverage can be as effective as a high-protein dose (25 g) at stimulating increased MPS rates when supplemented with a high (5.0 g total leucine) amount of leucine. These results have important implications for formulations of protein beverages designed to enhance muscle anabolism. This trial was registered at clinicaltrials.gov as NCT 1530646. SPONSORSHIP: Supported by Nestec Ltd and the Natural Sciences and Engineering Research Council of Canada (postgraduate scholarship to TAC-V). Study strengths

This is the first study to assess the MPS-stimulating capability of

varying doses of leucine added to a sub-optimal protein dose

(within a mixed macronutrient beverage) at rest and after

exercise. Previous research has looked at supplemental leucine

and EAA effects on protein alone,9 so the present study offers

potentially higher practical value. A comprehensive set of

treatments were compared, including two that involved a higher

leucine fortification bringing the total 5 g, whereas previous

research by the same lab totaled 3 g.9 Prepackaged standardized

diets that were consumed during the 2 days immediately

preceding the trials in order to reduce the confounding potential

of dietary variability.

Study limitations

The main limitation was the acute (short-term) nature of the study. While it provides valuable data, it still leaves open question about whether any of these differences in acute response would influence long-term adaptations in strength and/or hypertrophy. Another limitation was that the results may be limited to the exercise protocol, which consisted of only 8 sets of knee extensions at 80% of 1 RM (this was half the volume of work done by Witard et al,

10 which I reviewed on the

previous page). Another limitation was the use of subjects who werent necessarily trained. No training age was specified, nor were any minimums or maximums imposed for training status.

Comment/application

Depicted above are the MPS results in the early and late test periods in the resting (A) and post-exercise condition (B). Below A & B are the combined results of the entire test periods in the resting (C) and post-exercise conditions (D). The notable findings were that MPS increased significantly in all conditions, but MPS in the 25 g whey (W25) and the sub-optimal whey dose plus the higher leucine fortification amounting to 5 g leucine (W6+High-Leu) was greater than the MPS in the other treatments, with no significant differences in MPS between those two treatments. These results are not in full agreement with previous research by the same lab,

9 where 25 g whey was the

most effective treatment for sustaining increased rates of MPS post-exercise even more so than the sub-optimal whey dose fortified with an equivalent leucine dose to 25 g whey. However, the present study included a higher leucine fortification (amounting to 5 g instead of 3 g). Another difference was the inclusion of carbohydrate (35 g) and fat (5.68 g).

Interestingly, there were no significant differences in MPS between the resting and post-exercise conditions. The latter finding does not align with what Yang et al observed in older subjects, who experienced greater MPS post-exercise with 40 g whey than with 20 g,

8 suggesting a saturable response to lower

protein doses in younger subject despite the more sensitized post-exercise conditions.

Alan Aragons Research Review November 2013 [Back to Contents] Page 8

Evaluation of the usefulness of a low-calorie diet with or without bread in the treatment of overweight/obesity.

Loria-Kohen V, Gmez-Candela C, Fernndez-Fernndez C, Prez-Torres A, Garca-Puig J, Bermejo LM. Clin Nutr. 2012 Aug;31(4):455-61. [PubMed]

BACKGROUND & AIMS: Despite the lack of scientific evidence, bread is one of the most restricted foods in popular hypocaloric diets. The aim of this study was to compare two nutrition strategies (with or without bread) designed to promote weight loss in overweight/obese women. METHODS: A clinical, prospective and randomised study in which 122 women >18 years, BMI 25 < 40 kg/m(2) were divided into two groups: intervention group (BREAD, n = 61) and control group (NO BREAD, n = 61). Both groups received a low-calorie diet (with or without bread), nutrition education and physical activity guidelines, and were monitored for 16 weeks. RESULTS: 104 women completed the study (48.4 9 years, 29.8 3.5 kg/m(2)). Anthropometric and biochemical markers improved after the intervention without significant differences between groups. BREAD group significantly increased total cereal consumption (3.2 1.3 to 3.7 0.5 servings/day, P < 0.05) and the percentage of energy from carbohydrates (41.2 6.4 vs. 45.9 5.0% P < 0.001) and reduced fat (39.0 6.6 vs. 32.7 5.1% P < 0.001). In contrast, NO BREAD group increased the discrepancy with recommended consumption. NO BREAD group had the most dropouts (21.3% vs. 6.6%, P < 0.05). CONCLUSIONS: The bread inclusion in a low-calorie diet designed for weight loss favoured a better evolution of dietetic parameters and greater compliance with the diet with fewer dropouts. Registered under ClinicalTrials.gov Identifier #NCT01223989. SPONSORSHIP: This study was made possible thanks to a research project funded by the Pan cada da (Daily Bread) open call promoted by the Scientific Committee of Bread and by Incerhpan (Interprofessional Agrifoods of the Cereals-Flour-Bread Chain). Study sponsors had no involvement in the study design, in the analysis and interpretation of data, in the writing of the manuscript or submit it.

Study strengths

This study is quite unique and interesting. Its also relevant in light of the recent wave of anti-grain propaganda by various fad

diet authors and their followers. This is the first study to ever

compare the specific inclusion and exclusion of bread in

overweight and obese subjects. The authors make the interesting

point that due to this diet lore, the Spanish population has

decreased its consumption of bread from 368 g/day in 1964 to

134 g/day in 2006,11

yet adult obesity prevalence steadily

increased from 17.4% in the 1990s to 24% in the 2000s.12 Subjects received group counseling/education sessions. Physical

activity was imposed (although rather loosely) to at least 3 times

per week for 30 minutes of moderate to intense physical activity.

Study limitations

I would prefer to have seen dual X-ray absorptiometry (DXA)

instead of bioelectrical impedance analysis (BIA) to assess body

composition. Pimentel et al observed BIA to not only

overestimate percent body fat (%BF) in overweight subjects by

14.2%, but also underestimate %BF in obese subjects by

10.9%.13

Also, LaForgia et al found BIA to have poor individual

accuracy compared to the four compartment model,14

which is

the most comprehensive method of assessing body composition,

accounting for fat mass, bone mineral mass, total body water,

and residual mass. The authors of the present study

acknowledged that its unknown how their results might have panned out beyond the 16 weeks. They also acknowledged that

the results might be limited to the all-female subject sample.

Comment/application

\ The main findings of this study were 3-fold. First, there was a

lack of significant in body composition change between groups.

The bread group lost 4.3 kg while the no-bread group lost 4.0 kg.

As for body fat, the bread group lost 2.5% while the no-bread

group lost 2.1%. Both groups lost muscle mass (0.9 & 0.7 kg in

the bread & no-bread groups, respectively). This shouldnt be a major surprise considering that total energy and macronutrition

was similar between groups. Secondly, there were no significant

between-group differences in blood lipids, glucose control, and

other biochemical measures. Finally, the chart above shows

where the effects of each treatment diverge: program adherence.

A significant increase in transgressions (lapses in dietary

compliance by 150 kcal) was seen in the no-bread group, while

no significant increase in transgressions was seen in the bread

group. Furthermore, in the self-reported adherence ratings, the

bread group scored higher than the no-bread group (64.3%

versus 55.6%), and dropout was markedly lower in the bread

group compared to the no-bread group (6.6% vs 21.3%).

Although the reasons for dropping out varied, exclusion of bread

was found to be a significant factor.

This is one of those studies that strongly challenges the anti-

bread/anti-grain movement, specifically in the important realm

of alleviating obesity. Heres an excerpt from the conclusion, which sums things up well:

This study may be of significant scientific interest since it may represent an advance in understanding nutrition problems in overweight/obese people and provides understanding about how these can influence weight control. It can also help dispel myths about bread being a dangerous or caloric food by highlighting the usefulness of a balanced low-calorie diet within a nutrition education programme as part of patient treatment.

Alan Aragons Research Review November 2013 [Back to Contents] Page 9

1. Bemben DA, Bemben MG. Dose-response effect of 40 weeks of resistance training on bone mineral density in older adults Osteoporos Int. 2011 Jan;22(1):179-86. [PubMed]

2. Guadalupe-Grau A, Fuentes T, Guerra B, Calbet JA. Exercise and bone mass in adults. Sports Med. 2009;39(6):439-68. [PubMed]

3. Suominen H. Muscle training for bone strength. Aging Clin Exp Res. 2006 Apr;18(2):85-93. [PubMed]

4. Jesudason D, Nordin BC, Keogh J, Clifton P. Comparison of 2 weight-loss diets of different protein content on bone health: a randomized trial. Am J Clin Nutr. 2013 Nov;98(5):1343-52. [PubMed]

5. Hunt JR, Johnson LK, Fariba Roughead ZK. Dietary protein and calcium interact to influence calcium retention: a controlled feeding study. Am J Clin Nutr. 2009 May;89(5):1357-65. [PubMed]

6. Pasiakos SM, Cao JJ, Margolis LM, Sauter ER, Whigham LD, McClung JP, Rood JC, Carbone JW, Combs GF Jr, Young AJ. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013 Sep;27(9):3837-47. [PubMed]

7. Pennings B, Groen B, de Lange A, Gijsen AP, Zorenc AH, Senden JM, van Loon LJ. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab. 2012 Apr 15;302(8):E992-9. [PubMed]

8. Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr. 2012 Nov 28;108(10):1780-8. [PubMed]

9. Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012 Jun 1;590(Pt 11):2751-65. [PubMed]

10. Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am J Clin Nutr. 2013 Nov 20. [Epub ahead of print] [PubMed]

11. Varela-Moreiras G, Avila JM, Cuadrado C, del Pozo S, Ruiz E, Moreiras O. Evaluation of food consumption and dietary patterns in Spain by the food consumption survey: updated information. Eur J Clin Nutr 2010 Nov;64(Suppl. 3):S37e43. [PubMed]

12. Salas-Salvad J, Rubio MA, Barbany M, Moreno B, Grupo Colaborativo de laSEEDO. SEEDO 2007 consensus for the evaluation of overweight and obesityand the establishment of therapeutic intervention criteria. Med Clin (Barc) 2007 Feb 10;128(5):184e96. [PubMed]

13. Pimentel GD, Bernhard AB, Frezza MR, Rinaldi AE, Burini RC. Bioelectric impedance overestimates the body fat in overweight and underestimates in Brazilian obese women: a comparison with Segal equation 1. Nutr Hosp. 2010 Sep-Oct;25(5):741-5. [PubMed]

Alan Aragons Research Review November 2013 [Back to Contents] Page 10

The Meat and Nuts Breakfast of Champions.

By Matt Jones

____________________________________________________

Introduction

The suggestion made by Charles Poliquin within the articles and

multimedia section of the Poliquin Groups website reads as follows: rotating meat and nuts breakfast increased mental acuity and focused energy allows for a slow and steady rise in blood sugar to remain stable for an extended period of time what you eat for breakfast sets up your entire neurotransmitter

production for the day.

All of these suggestions are made relative to popular breakfast

choices that are generally higher in carbohydrate, including oats,

cereal, and bread.

For those unaware, Charles Poliquin is a well-respected, highly

successful strength and conditioning coach. But as is known

globally, a good strength coach does not necessarily make a

good nutritionist. It is not the aim of this article to openly

criticise Poliquins practices or question his motives or intentions, nor will I launch an outright tirade on him. That

would be too easy. However, it is necessary to discuss the

application of this much-famed breakfast.

As with all AARR articles, the extravagant claims will be

examined meticulously, and honestly with frequent reference to

the existing evidence base. In this case, Ill examine the claims of optimised neurotransmission and neurotransmitter production

for the day.

Neurotransmitter basics

A neurotransmitter is a chemical signal that allows for

transmission of signals from one neuron to another, across a

synapse. Neurotransmission allows for, and control muscle fiber

contraction, bodily actions, emotions and feelings. The most

significant neurotransmitters in the human body are

acetylcholine, norepinephrine, dopamine, Gamma Amino

Butyric Acid (GABA), glutamate, serotonin and endorphins.

There is a substantial body of evidence to support the notion that

nutrition has a significant influence on the appearance of blood

and brain neurotransmitters.1-3

Neurotransmitters and cognitive function

Research has demonstrated that serotonin is a known sleep-

inducing agent,4 with human research indicating that serotonin

reduces subjective alertness, objective performance, and

increases feelings of relaxation and lethargy.5 The

neurotransmitter dopamine on the other hand is associated with

pleasurable reward, behavior, cognition, mood, memory,

movement, attention and learning. Interestingly, dopamine is

critically involved in the drug addiction process by inducing

pleasant states or by relieving distress.6 Acetylcholine has a

number of physiological functions; it is a widely distributed

excitatory neurotransmitter that in the central nervous system

and is involved in wakefulness, attentiveness and memory.

Interestingly, Alzheimers disease is characterized by a significant reduction in acetylcholine concentration and

function,7 highlighting its importance in human health

performance.

Neurotransmitters and nutrition

Neurotransmitters are primarily synthesized from amino acids,

particularly the branched chain amino acids (BCAAs), tyrosine and tryptophan. The rates at which neurotransmitters are

synthesized depends upon the availability of the amino acid

precursor. Research from rodent studies in the 70s and early 80s demonstrated that increased concentrations of tryptophan resulted in an elevation in serotonin synthesis, and increasing

concentrations of tyrosine resulted in elevations in dopamine and

certain catecholamines.8

This was supported by earlier research indicating that the

administration of a single dose of tryptophan elevated brain

tryptophan levels, and thus the levels of serotonin and its major

metabolite 5-hydroxyindole acetic acid (5-HTP). The

administration of tyrosine, elevated brain tyrosine levels, and

thus catecholamine increased in the central nervous system

(CNS), while the consumption of lecithin or choline (found in

fat) increased brain choline levels and neuronal acetylcholine

synthesis.9 Ultimately concluding that tryptophan was the

precursor for serotonin, tyrosine was the precursor for dopamine

and choline the precursor for acetylcholine.

All of these early studies utilised both observational and knock-

out rodent models, using a single dose of the precursor, although

similar effects have been seen following the consumption of

dietary sources, real-food. Again using a rodent model, Wurtman

& Fernstrom9 demonstrated that the consumption of a single

protein-free high-carbohydrate meal elevated brain tryptophan

levels. Similarly, the consumption of a single 40% protein meal

accelerated brain catecholamine synthesis through increased

availability of tyrosine. Fernstrom10

concluded that a minimal

change of delta 0.07 in the tryptophan to large neutral amino

acid ratio is required to influence mood following protein

consumption, so a considerable shift in the ratio is required to

have an effect on subsequent cognition.

These data clearly demonstrate that the neurotransmitters

serotonin, dopamine and the catecholamines are under specific dietary control. Essentially this is the data Poliquin has built his

meat and nut breakfast on, and in that regard he is correct. The

acute effects of a high-carbohydrate protein-free meal, atypical

of a modern Western diet breakfast (think oatmeal and cereals)

does induce marked increases in serotonin synthesis, and thus

may result in increased feelings of lethargy.

However, is the absolute avoidance of carbohydrate justifiable

based on the current evidence? Is the process irreversible as

Poliquin suggests, does breakfast dictate the neurotransmitters

for the entire day? If Poliquin had read a little further instead of

cherry-picking the juiciest data, he would have realized that this

is not the case.

Interestingly, in the same research by Wurtman & Fernstrom9

found that the addition of protein to an otherwise protein-free

Alan Aragons Research Review November 2013 [Back to Contents] Page 11

high-carbohydrate meal suppressed the increases in brain

tryptophan and serotonin synthesis, because protein contributes

to the blood plasma considerably larger amounts of the other

neutral amino acids (e.g., BCAAs, phenylalanine) than of tryptophan. Tryptophan and other large neutral amino acids,

most notably the BCAAs leucine, isoleucine and valine share the same specific transporter across the blood-brain barrier and

thus compete for uptake.11

Therefore, brain 5-HTP synthesis will

increase when there is an increase in the ratio of free tryptophan

to BCAAs in the blood. This explains why the addition of protein to an otherwise protein-free high-carbohydrate meal can

suppress serotonin synthesis.

This theory has also been confirmed in humans. Using 20 men,

Lieberman et al13

administered single oral doses of tryptophan

(50 mg/kg) and tyrosine (100 mg/kg) in a double-blind,

crossover study. Tryptophan increased subjective fatigue and

decreased self-ratings of vigor and alertness, but did not impair

performance on any of the tests. Compared to placebo there was

no difference in performance with tyrosine, although tyrosine

administration did reduce reaction time relative to tryptophan.

Lieberman et al concluded that tryptophan has significant

sedative-like properties, but unlike other sedatives this may not

impair performance in a series of cognitive tests. However, it is

extremely unlikely probably impossible in fact that a human would ever consume 50 mg/kg tryptophan in a single dose from

a dietary source, and thus would not necessarily have to worry

about the negative mental effects of isolated tryptophan

consumption.

Poliquins strong recommendation to avoid carbohydrate at breakfast, in fear of neurotransmitter malfunction, mental

breakdown and impaired performance has only a handful of

cherry-picked studies to support it. In reality, the brain

neurotransmitters are influenced by the ratio of free tryptophan

to large neutral BCAAs,14 so a mixed meal that is able to maintain a balance in that ratio is more likely to optimize

neurotransmitter synthesis. Furthermore, an increase in the ratio

of free tryptophan to large neutral amino acids following a high-

carbohydrate protein-free meal is reversible through the addition

of protein to that meal, ultimately balancing the ratio again. This

invalidates Poliquins suggestion that the first meal of the day dictates brain neurotransmitter production for that entire day.

Worth mentioning is an intricate study by Fischer et al.14

They

examined the cognitive effects of isoenergetic meals consisting

of three carbohydrate ratios, a carbohydrate-rich meal (4:1), a

balanced meal (1:1), and a protein-rich meal (1:4) in 15 healthy

subjects, in an attempt to elucidate which breakfast combination

is most suitable in a school environment. Unsurprisingly,

attention and decision times were improved in the first hour with

the high carbohydrate meal, due to the provision of and greater

rise in glucose metabolism. However, during the first hour it was

both the balanced and higher protein meals that resulted in

improved performance. In addition, overall reaction times in a

central task were fastest after both the balanced and high-protein

meal, thus suggesting a high-protein meal or a balanced meal

appear to result in better overall cognitive performance. The

results also revealed participants subjective measures of tasty and pleasant were greater in the balanced meal than in the

high-protein meal, which suggests this would be the most

effective in a practical/dietary adherence sense.

Mechanisms

Fischer et als research14 might lead one to presume carbohydrate-rich foods contain significant amounts of

tryptophan, thus increase free tryptophan concentrations after

ingestion, elevating tryptophan uptake and stimulating serotonin

synthesis. However, this is not the case. A bowl of oats for

example porridge or oatmeal depending which side of the pond you are a common staple of many a Western breakfast, vilified by Poliquin for the potential negative effects on

neurotransmission and mental performance. Well, the amino

acid profile of 100g oats indicates a tryptophan concentration of

234 mg, compared to 694 mg isoleucine, 1284 mg leucine, and

937 mg valine, which collectively make up the BCAAs.15

So, a

high-carbohydrate breakfast does not contain that much

tryptophan, although it accelerates serotonin synthesis through

an increase in tryptophan uptake by the brain.

It would appear that although the carbohydrate meal alone does

not contain much tryptophan, the insulin secreted following the

carbohydrate meal results in a rapid removal and significant

decrease in plasma levels of the large neutral amino acids

(tyrosine, phenylalanine, BCAAs and methionine) that would ordinarily compete with tryptophan for uptake by the brain.

Tryptophan then crosses the blood-brain barrier and is converted

to serotonin.5 It thus appears that it is not actually the

carbohydrate that causes the problem; it is the insulin response

to that carbohydrate that drives the large neutral amino acids out

of the bloodstream, leaving tryptophan free to pass the blood

brain barrier, with no competition.

Logic

The insulin index formulated by Holt et al15

clearly demonstrates

that beef, the food favored by Poliquin in his infamous meat and

nut breakfast, elicits an insulin response of 7910 2193

pmol/min/L (expressed as area under the curve, or AUC). Grain

bread, a food demonized by Poliquin in fear of it frying all brain

cells has an insulin AUC of 6659 837 pmol/min/L. The insulin

index clearly indicates beef is more insulinogenic than many of

the carbohydrate-rich foods tested. This suggests that the net

effect in regards neurotransmitter synthesis of a high-protein

carbohydrate-free meal may be similar to that of a mixed meal.

The greater insulin response to beef consumption will lead to a

reduction in the BCAAs and other neutral amino acids, leaving free tryptophan to be taken up by the brain. Interestingly, 100 g

steak contains more tryptophan than the same portion of oats

(288 mg versus 234 mg).16

Logic, intuition and a basic understanding of the insulin index

suggests this could be true, although a number of rodent studies

have disproved the hypothesis, where Rouch et al17

revealed a

high-protein diet significantly reduced serotonin concentrations

for 2-hours, and Wurtman & Fernstrom9 reported similar

findings. Interestingly, the reduction in serotonin following

protein feeding is thought to be among the reasons why protein

is more satiating that carbohydrate.

Alan Aragons Research Review November 2013 [Back to Contents] Page 12

As discussed previously, research has demonstrated that

Poliquins suggestion that the first meal of the day dictates that whole days brain neurotransmitter activity is false. The process is reversible and easily altered. Looking at more of the evidence

to disprove this claim, Fernstrom and Fernstrom analyzed the

brain tryptophan concentrations and rates of serotonin synthesis

in fasted rats fed a high-carbohydrate meal followed 2-hours

later by a protein-containing meal.18

They demonstrated that

when the high-carbohydrate meal was fed first, brain tryptophan

concentrations increased as did serotonin synthesis, and these

changes were reversed at 4 hours if the second meal contained

protein. Interestingly the authors went on to conclude, quote:

brain tryptophan concentrations and serotonin synthesis are thus responsive to the sequential ingestion of protein and

carbohydrate meals if there is a sufficient interval between

meals.

Rouch et al19

reported the plasma ratio of free tryptophan to

large neutral amino acids was increased by a carbohydrate meal,

and remained high for 2-hours, a subsequent casein (protein)

meal reversed this change. In an intriguing twist, a first casein

meal reduced the ratio, and was not increased again by a

subsequent carbohydrate meal. This finding actually supports

Poliquins claims in that an initial high-protein carbohydrate-free meal is more favorable than a high-carbohydrate protein-free

meal in regards neurotransmitter synthesis.

The reversible nature of neurotransmitter synthesis is supported

by the central fatigue hypothesis in humans, which predicts that

the ingestion of BCAAs during exercise will raise plasma BCAA concentration and hence reduce transport of free

tryptophan into the brain; subsequently reducing the formation

of serotonin and alleviating sensations of fatigue and therefore

improve endurance performance.20

To-date, this hypothesis is

still controversial despite many years of research. Nevertheless,

it highlights the reversible nature of neurotransmitter synthesis.

Conclusion and recommendations

My recommendation based on this evidence is that a single

macronutrient meal can have a significant impact on the brain

neurotransmitters. A protein-free high-carbohydrate meal typical

of the meals consumed at breakfast by many Westerners think oatmeal, etc can increase serotonin synthesis, and thus increase feelings of fatigue as Poliquin claims. However, a high-protein

high-fat carbohydrate-free meal can increase dopamine and

catecholamine synthesis. The latter can be favorable, but with

your daily macronutrient requirements in mind, combined with

the fact that eating single-macronutrient meals would be

extremely tasteless and boring, it would be more appropriate for

most to consume mixed meals than to focus on meals free from

certain macronutrients in fear of a surge of sleep-inducing

neurotransmitters. Furthermore, the current evidence does not

consistently indicate decrements in mood, cognitive

performance, or alertness from a protein-rich meal that also

includes carbohydrate.

In conclusion, the exclusive promotion of low-carbohydrate,

high-protein, high-fat meat and nut breakfast is largely

unsubstantiated, but has minimal support by a few cherry-picked

studies. A mixed meal consisting of protein, carbohydrate and

fat is adequate, and in a practical sense is likely to be optimal.

______________________________________________________________________________

Matt is the lead performance nutritionist at Nutrition Condition. He holds an MSc in Nutrition Science, and a BSc in Sports Science. Matt coaches world-class athletes, large corporations and personal clients. Matt employs strong scientific principles within his practices and has is a great proponent of the evidence-based approach. Matt can be contacted at matt@nutritioncondition.co.uk or on twitter @MattJonesNC

References

1. Wurtman, R., & Fernstrom, J. (1974). Nutrition and the Brain. Scientific American, 230, 84- 91. [The Wurtman Lab]

2. Growdon, J., Cohen, E., & Wurtman, R., (1977). Treatment of brain diseases with dietary precursors of neurotransmitters. Annals of Internal Medicine, 86, 337 339. [PubMed]

3. Gelenberg, A., & Gibson, C., (1984). Tyrosine for the treatment of depression. Nutrition & Health, 3, 163 173. [PubMed]

4. Hartman, E., & Spinweber, C., (1979). Sleep induced by L-tryptophan. Effect of dosages within the normal dietary intake. The Journal of Nervous and Mental Disease, 167, 497 499. [PubMed]

5. Spring, B., (1984). Recent research on the behavioural effects of tryptophan and carbohydrate. Nutrition & Health, 3, 55 67. [PubMed]

6. Le Foll, B., Gallo, A., Le Strat, Y., Lu, L., & Gorwood, P., (2009). Genetics of dopamine receptors and drug addiction: a comprehensive review. Behavioural Pharmacology, 20, 1 17. [PubMed]

7. Francis, P., (2005). The interplay of neurotransmitters in Alzheimers disease. Central Nervous Systems Spectrums, 10, 6 9. [PubMed]

8. Wurtman, R., Hefti, F., & Melamed, E., (1980). Precursor control of neurotransmitter synthesis. Pharmacological Reviews, 32, 315 335. [PubMed]

9. Wurtman, R., & Fernstrom, J., (1975). Control of brain monoamine synthesis by diet and plasma amino acids. The American Journal of Clinical Nutrition, 28, 638 647. [PubMed]

10. Fernstrom, J., (1994). Dietary amino acids and brain function. Journal of the American Dietetic Association, 94, 71 77. [PubMed]

11. Maughan, R., (2000). Nutrition in sport. Blackwell Science, United Kingdom

12. Chaouloff, F., Kennett, G., Serrurrier, B., Merino, D., & Curzon, G. (1986). Amino acid analysis demonstrates that increased plasma free tryptophan causes the increase of brain tryptophan during exercise in the rat. Journal of Neurochemistry, 46, 1647 1650. [PubMed]

13. Lieberman, H., Corkin, S., Spring, B., Wurtman, R., & Growdon, J., (1985). The effects of dietary neurotransmitter precursors on human behaviour. American Journal or Clinical Nutrition, 42, 366 370. [PubMed]

14. Fischer, K., Colombani, P., Langhans, W., & Wenk, C. (2002). Carbohydrate to protein ratio in food and cognitive performance in the morning, Physiology & Behaviour, 75, 411 423. [PubMed]

15. Holt, S., Miller, J., & Petocz, P., (1997). An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods. American Journal of Clinical Nutrition, 66, 1264 1276. [PubMed]

16. http://nutritiondata.self.com/ 17. Rouch, C., Nicolaidis, S., & Orosco, M., (1998). Determination, using

microdialysis, of hypothalamic serotonin variations in response to different macronutrients. Physiology & Behaviour, 65, 653 657. [PubMed]

18. Fernstrom, M., & Fernstrom, J. (1995). Brain tryptophan concentrations and serotonin synthesis remain responsive to food consumption after the ingestion of sequential meals, The American Journal of Clinical Nutrition, 61, 312 319. [PubMed]

19. Rouch, C., Meile, M., & Orosco, M., (2003). Extracellular hypothalamic serotonin and plasma amino acids in response to sequential carbohydrate and protein meals. Nutritional Neuroscience, 6, 117 124. [PubMed]

20. Gleeson, M., (2005). Interrelationship between physical activity and branched-chain amino acids. The Journal of Nutrition, 135, 1591 1595. [PubMed]

Alan Aragons Research Review November 2013 [Back to Contents] Page 13

Jonathan Bailor claims slim is simple but finds many ways to overcomplicate it.

By Alan Aragon

Background

According to his LinkedIn profile, Jonathan Bailor is a self-

proclaimed nutrition and exercise expert and former personal trainer who specializes in using high-quality food and exercise

to simplify wellness. However, his profile reveals that his main day-job since 2005 is at Microsoft. His current position is Senior

Program Manager. This immediately reminds me of Dave

Asprey, a computer programmer-turned-health guru with a

pseudoscientific slant and a flair for gimmickry. Bailors book is called The Calorie Myth, which Im assuming has gotten a healthy amount of publicity through the marketing might of

publishing giant HarperCollins. Heres his promotional video thats making the social media rounds. In the clip, Bailor delivers a summary of the obesity problem, as well as his

solution. Thus far, I havent seen any research-based critiques of it, and boy, is it begging for one. My commentary will follow

key excerpts from the video, and end off with discussion of his

questionable training methods.

Today more of us are dieting and exercising than ever, and yet more of us are overweight and diabetic than ever.

While the second part is true, the first part is false. We are not

dieting and exercising more than ever. The latest data shows that

were consuming about a full meals worth of calories (445 kcal) more than we did in 1970,

1 while reducing our energy

expenditure by the equivalent of 30 minutes of walking (142

kcal) since 1960.2 So, contrary to Bailors claim, were actually

eating more and moving less.

Its been proven that on average we are consuming about 300 more calories per person per day than we were in the late 70s. Between then and now, that adds up to well over 3 million more calories per person, which if the starvation is healthy, count your calories, and metabolism works like math premise were true, means the average American today should weigh well over 1000 pounds.

The above statement makes no sense at all. If the typical adult

consuming 2500 kcal/day added 300 kcal/day to that, he or she

would eventually plateau at a bodyweight whose maintenance

requirement is 2800 kcal and this is certainly not going to be what sustains a 1000-lb person. Who knows where Bailor got

that figure from (Im assuming he did some wonky math on progressively increasing intake by 300 kcal each day), but it

makes a good attention-grabber for audiences with zero

knowledge in this area.

Just like no quantity of clean water will ever clog a sink, no quantity of the high-quality, clean foods we were designed to eat will ever clog our body. Eat smarter, not less, problem solved.

Here Bailor is claiming that reducing calories-in is not the

solution to weight loss. This is another oversimplification, since

for many folks who are overweight or obese from overeating, a

caloric deficit (via reduction of calories-in and/or increase of

calories-out) is precisely what needs to be sustained in order to

reverse the condition. Intake reduction can be achieved a number

of ways. You can reduce the portion size of the foods you

currently consume. Or, you can eat more energy-sparse foods

that end up displacing the amount of energy-dense foods (which

is what Bailor is recommending). Or, you can do a combination

of both. The thing is, all of those options are paths toward

reducing the intake of metabolizable energy. So, its utterly misleading to say that eating less is not the solution when thats exactly what ends up happening terms of energy intake when

these tactics are employed.

Compounding the falsehoods, he also claims that increasing

intake will not cause weight gain if its comprised of high-quality foods. According to Bailor, food quality is determined by

4 factors: 1) satiating capacity, 2) aggression, or how likely

those foods are to be stored as body fat, 3) nutrient density, and

4) efficiency, or how many calories can be stored as body fat.

The latter factor is a reiteration of #2, but then you wouldnt be able to build a catchy acronym (SANE). He then goes on to

outline 3 factors that determine the sanity of foods: 1) water, 2) fiber, and 3) protein. Whats already apparent is that in Bailors attempt to simplify getting slim, he stacks sets of rules that complicate and cloud the real objective, which again is to

impose and sustain a caloric deficit. This can and should be

achieved on an individual basis that respects personal preference

and tolerance (and athletic goals when applicable). But lets go on to see Bailors justification of the latter set of rules.

Water, protein, and fiber-rich foods are sane. On the other hand, dry, relatively low-fiber and low-protein foods are insane. Starches and sweets such as cookies and bread, pasta and potatoes are some of the insane foods that will contribute to a hormonally clogged sink.

This leaves a huge gray area of unaddressed permutations. There

are plenty of high-protein, low-fiber foods like meats. What

about protein powders, which are water-free and low-fiber?

Bailor is just fine with protein powder despite its failure to meet

2 of the 3 criteria for sane foods. There are also plenty of low-protein, high-water, high-fiber foods. According to Bailor,

combining the latter two makes it okay in some cases. To quote

him in the Frequently Asked Questions page of his website,

When it comes to achieving optimal athletic performance, right before, during, and right after the event, we need to quickly get

Alan Aragons Research Review November 2013 [Back to Contents] Page 14

our muscles glucose and amino acids. The most SANE option

Ive found for doing this is blending fruits with whey protein powder and consuming these shakes before, during, and after

the event. For on-the-go protein he approves of protein bars, as long as they contain a minimum of 4 times more protein than

sugar. Nevermind that protein bars, like protein powders, are

typically low in fiber, and of course water-free. Along these

lines of irony, Bailor says that the more natural a food is, the

more sane it is. Yet, he recommends consuming low-fat or fat-

free versions of dairy products, as well as consuming egg whites

mixed with whole eggs in order to increase the proportion of

protein and decrease fat intake. Harp on insanity but give a free pass to logical incoherence... Got it.

Bailor calls for the avoidance of starches including potatoes. He apparently is in denial that potatoes are rich in

micronutrition, water, and fiber. A recent scientific review by

Weaver and Matt describes the misunderstanding and injustice

leveled at potatoes:3

Potatoes are often left out of the vegetable category in food guidance because of their purported association with higher fat diets. Yet white potatoes are a good source of several shortfall nutrientspotassium, magnesium, fiber, and vitamin B-6, and as consumed, provide 3%-4% of total energy. [...] Potatoes should be counted as a vegetable in food guidance systems. In fact, they had their own category in the 1933 USDA food guidance system because of their important contribution to nutrient intake.

Its also ironic that Bailor bashes potatoes while harping on the importance of satiety. Holt et al found that potatoes were far

more satiating than all 38 common foods tested, including

protein-dominant foods.4 Its tough to talk about potatoes

without mentioning Chris Voigt, the head of the Washington

State Potato Commission. This brave man went on a 60-day

potato-only diet and lost 21 lbs while improving his blood lipid

profile and reducing his fasting glucose levels.5

Another fun factoid challenging Bailors stance is that the top 10 countries with the lowest obesity rates unanimously consume a

starch-dominant diet.4 In light of this, its amusing how Bailor

advises to skip the rice when eating Asian dishes, since 8 of the

top 10 countries that lead the world in low obesity rates are

Asian.6 Its given that correlation does not automatically equal

causation, so observational evidence should be viewed with

caution. However, the fact that a low-carb diet is not the

common thread among the leanest (or the healthiest) populations

on the planet strongly suggests that starch avoidance is likely to

be a trivial factor at best in the war against obesity.

As for the controlled interventions, research comparing high

versus low-carb diets rarely matches protein intakes between

groups. Therefore, the higher-protein condition typically yields

more favorable results. This isnt surprising considering the positive effects of protein on satiety, thermogenesis, and lean

mass preservation. However, studies that do match adequate

protein intake fail to show a weight loss or fat loss advantage of

the low-carb condition.7,8

Eat way more non-starchy vegetables, way more sea food and nutritious meats, more low-sugar fruit, and more nuts and

seeds. Get so full and satisfied from eating as many sane foods as you want, whenever you want, that youre too full for dessert. So go ahead, double the portion of your nutritious high-protein main dish, triple that side of non-starchy veggies.

These are the words of someone without a lot of dietary

counseling experience. Granted, you cant really expect that from someone whose formal background involves computer

software development and management. Heres the problem. Any push towards filling up on a strict set of foods and strictly

avoiding another set of foods is at best, a short-term solution. At

worst, it can backfire and lead to excessive fat gain and all of the

accompanying problems.

Bailor repeatedly mentions that we need to repair our broken

hormonal systems in order to lower our bodyweight set-points.

Im wondering how he plans to achieve that with dietary recommendations which combine a fiber fetish with fat-phobia

and carbo-phobia. This is an ideal recipe for decreasing

testosterone9,10

and triiodothyronine (T3) production.11,12

Thats a double-whammy for compromising muscle gain and fat loss

efforts.

And yet again, we see how Bailor complicates a simple concept

like eating more fruit by setting rules about the type of fruit

allowed. Demonizing certain foods while deifying others is a

false perceptual framework that can lead to adverse

psychological effects. Hes also putting the evil/off-limits stamp on dessert, thereby creating a platform for obsessiveness and

food neuroticism. An all-or-nothing, rigid approach to dieting

has actually been associated with overeating, increased

bodyweight, and eating disorder symptoms, while flexible

dieting has shown a stronger association with lower bodyweight

and the absence of depression and anxiety.13,14

Its clear that Bailors simplifications are anything but simple. Neither are they logical or grounded in science.

Bailors eccentricity doesnt end with diet

Bailor is strongly enamored with eccentric resistance training

(focusing on the negative phase of the repetition) to the point of claiming its the best way to train. In fairness, theres an interesting body of research on the benefits of eccentric training

on strength and hypertrophy. A relatively recent meta-analysis

by Roig et al15

found that eccentric training is more effective at

increasing total and eccentric strength than concentric training.

However, a subgroup analysis of 3 studies that equated intensity

as a percentage of 1RM showed no major differences between

eccentric and concentric training in promoting strength gains.

The authors repeatedly stress that strength gains from eccentric

exercise are highly specific to the mode of contraction and

velocity of movement. One of their caveats is worth quoting

directly:

Because total strength was calculated as the average of eccentric, concentric and isometric strength gains, we must consider that excessively weighted gains in eccentric strength could have influenced the measure of total strength.

Now, heres where things go awry. Bailor claims that the eccentric phase should last 10 seconds. His reasoning is to

Alan Aragons Research Review November 2013 [Back to Contents] Page 15

maximally stimulate the type IIB fibers, and thus evoke the most

profound hormonal response possible in terms of making inroads

into fat loss and setpoint-lowering. I sent this video of Bailor

coaching a bodyweight squat to my friend and colleague Brad

Schoenfeld, who I consider to be one of the top researchers in

area of exercise science. Heres his feedback:

1. From a strength perspective, there is certainly a transfer from eccentric training to concentric training, but optimal concentric strength is achieved through training concentrically.

2. Eccentric seems to be at least as effective as concentric exercise for hypertrophy. But optimal hypertrophy would seem to require that both modes of action be included. There is some evidence that eccentric training has a preferential effect on fast twitch fibers and thus the slow-twitch fibers would not be adequately stimulated. What's more, there appear to be different "types" of hypertrophy associated with each action: eccentric training has an effect on "in series" hypertrophy while concentric has more of an effect on 'in parallel' hypertrophy. It's a highly complex topic that requires more research (limitations are in the training experience of subjects, time course of study, and others). Bottom line is that there current evidence indicates that both modes of actions are important.

3. Humans don't possess type IIb fibers--these are exclusive to rodents; we possess the IIx isoform.

4. There is no evidence that a 10-second slow eccentric is optimal for hypertrophy. In fact, there is evidence that faster eccentrics are actually more hypertrophic than very slow eccentrics (although there are some methodological issues with this research as well).

5. The knees-over-toes myth of squats is something I've covered extensively. His point should have been that you should not force the knees into forward translation but rather sit back into the squat; whether the knee goes past the toes or not is irrelevant.

On the note of Brads final point, Fry et als examination of the knees-over-toes issue warrants mention.

16 They found that

although restricting forward movement of the knee past the toes

(as Bailor recommends) decreases stress on the knees, it also can

transfers stress to the hips and lower back. This picture from

their paper is worth a thousand words:

Fry et al concluded that allowing the knees to go beyond the toes

may be necessary to optimally distribute forces on all of the

joints involved with the squat. Bailors claim that the knee should never pass the toe is thus a load of grass-fed baloney.

Concluding thoughts

Im not quick to criticize anyone who makes a diligent effort to disseminate high-quality information that considers the full

range of scientific evidence. There is a growing number of folks

in this industry who indeed produce excellent, research-based

work. In contrast, Bailors relatively short video clip is just so crammed with misleading and plain-false information, that it

quickly rustled me into myth-slaying mode. The clip is so well-

produced, that its immediately intriguing and engaging to those without any solid understanding of physiology. Sure, there are

moments of good information, but those moments are

consistently interspersed with hogwash. For example, many

people do need to eat more vegetables, but then he imposes the

non-starchy vegetable rule. Also, many do need to eat more

fruits, but then he imposes the low-sugar fruit rule. On a final

note, its difficult to tell who is lucidly sheisting the public, and who sincerely believes their own fairy tales with the best of

intentions. Bailor appears to lean toward the latter, but that

doesnt exempt his material from meeting my red pen.

References

1. United States Department of Agriculture. Food Availability (Per Capita) Data System. Summary Findings: Food Patter Equivalents and Dietary Trends. Updated Sep 16, 2013. [ERS/USDA]

2. Church TS, Thomas DM, Tudor-Locke C, Katzmarzyk PT, Earnest CP, Rodarte RQ, Martin CK, Blair SN, Bouchard C. Trends over 5 decades in U.S. occupation-related physical activity and their associations with obesity. PLoS One. 2011;6(5):e19657. [PubMed]

3. Weaver C, Marr ET. White vegetables: a forgotten source of nutrients: Purdue roundtable executive summary. Adv Nutr. 2013 May 1;4(3):318S-26S. [PubMed]

4. Holt SH, Miller JC, Petocz P, Farmakalidis E. A satiety index of common foods. Eur J Clin Nutr. 1995 Sep;49(9):675-90. [PubMed]

5. http://20potatoesaday.com/ 6. Central Intelligence Agency. A Spotlight on World Obesity

Rates. Updated Apr 30, 2013. [CIA] 7. Soenen S, Bonomi AG, Lemmens SG, Scholte J, Thijssen

MA, van Berkum F, Westerterp-Plantenga MS. Relatively high-protein or 'low-carb' energy-restricted diets for body weight loss and body weight maintenance? Physiol Behav. 2012 Oct 10;107(3):374-80. [PubMed]

8. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, Sears B. Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets. Am J Clin Nutr. 2006 May;83(5):1055-61. [PubMed]

9. Anderson KE, Rosner W, Khan MS, New MI, Pang SY, Wissel PS, Kappas A. Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man. Life Sci. 1987 May 4;40(18):1761-8. [PubMed]

Alan Aragons Research Review November 2013 [Back to Contents] Page 16

10. Volek JS, Kraemer WJ, Bush JA, Incledon T, Boetes M. Testosterone and cortisol in relationship to dietary nutrients

and resistance exercise. J Appl Physiol (1985). 1997

Jan;82(1):49-54. [PubMed]

11. Mathieson RA, Walberg JL, Gwazdauskas FC, Hinkle DE, Gregg JM. The effect of varying carbohydrate content of a

very-low-caloric diet on resting metabolic rate and thyroid

hormones. Metabolism. 1986 May;35(5):394-8. [PubMed]

12. Pasquali R, Parenti M, Mattioli L, Capelli M, Cavazzini G, Baraldi G, Sorrenti G, De Benedettis G, Biso P, Melchionda

N. Effect of dietary carbohydrates during hypocaloric

treatment of obesity on peripheral thyroid hormone

metabolism. J Endocrinol Invest. 1982 Jan-Feb;5(1):47-52.

[PubMed]

13. Stewart TM, Williamson DA, White MA. Rigid vs. flexible dieting: association with eating disorder symptoms in

nonobese women. Appetite. 2002 Feb;38(1):39-44.

[PubMed]

14. Smith CF, Williamson DA, Bray GA, Ryan DH. Flexible vs. Rigid dieting strategies: relationship with adverse

behavioral outcomes. Appetite. 1999 Jun;32(3):295-305.

[PubMed]

15. Roig M, O'Brien K, Kirk G, Murray R, McKinnon P, Shadgan B, Reid WD. The effects of eccentric versus

concentric resistance training on muscle strength and mass

in healthy adults: a systematic review with meta-analysis. Br

J Sports Med. 2009 Aug;43(8):556-68. [PubMed]

16. Fry AC, Smith JC, Schilling BK. Effect of knee position on hip and knee torques during the barbell squat. J Strength

Cond Res. 2003 Nov;17(4):629-33. [PubMed]

Alan Aragons Research Review November 2013 [Back to Contents] Page 17

Martial arts meets academia: an interview with Dr. Brian Jones. By Alan Aragon

____________________________________________________

____________________________________________________

Dr. Brian Jones has a PhD in exercise science and is currently a

full time faculty member at Georgetown College in Kentucky. He

teaches courses in anatomy and physiology, exercise physiology,

and research methods among others. Dr. Jones has written three

books, authored two textbook chapters, and has written for

numerous print and online periodicals. He has extensive

experience in strength and conditioning/personal training with

clients ranging from professional athletes to clinical special

populations. Dr. Jones is the current state director of the NSCA

and holds the CSCS certification. He is a fellow and faculty

member in the Institute of Marti