face

13 Gary Taubes’ article, “What Really Makes Us Fat”

By Alan Aragon

15 How much of a calorie surplus is needed for

bulking?
By Alan Aragon

Copyright © May 1st, 2012 by Alan Aragon

Home: www.alanaragon.com/researchreview
Correspondence: aarrsupport@gmail.com

2 What’s the lower threshold of meal frequency for

optimizing muscle gain?
By Alan Aragon

6 Effects of dietary composition on energy

expenditure during weight-loss maintenance.
Ebbeling CB, et al. JAMA. 2012 Jun 27;307(24):2627-34.
[Pubmed]
8 Ketogenic diet does not affect strength
performance in elite artistic gymnasts.
Paoli A, et al. J Int Soc Sports Nutr. 2012 Jul 26;9(1):34.
[Epub ahead of print] [Pubmed]
9 Does metabolic compensation explain the majority
of less-than-expected weight loss in obese adults
during a short-term severe diet and exercise
intervention?
Byrne NM, et al. Int J Obes (Lond). 2012 Jul 24. doi:
10.1038/ijo.2012.109. [Epub ahead of print] [Pubmed]

10 Micronutrient deficiency in obese subjects

undergoing low calorie diet.
Damms-Machado A, et al. Nutr J. 2012 Jun 1;11(1):34.
[Epub ahead of print] [Pubmed]

11 Muscle time under tension during resistance

exercise stimulates differential muscle protein
sub-fractional synthetic responses in men.
Burd NA, et al. J Physiol. 2012 Jan 15;590(Pt 2):351-62.
Epub 2011 Nov 21. [Pubmed]

Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 1


What’s the lower threshold of meal frequency for
optimizing muscle gain?
By Alan Aragon
_________________________________________________________________
Intro & background
A decade ago, intermittent fasting (IF) was still somewhat of an
obscurity to the scientific community, and it was essentially
unknown to the general fitness-oriented public. However, IF – or
reduced meal frequency in general – has been snowballing in
popularity as of the past 5 years or so. Recently, IF has fallen
under scrutiny and criticism by those who feel that a higher
frequency of nutrient-mediated anabolic events throughout the
day optimizes muscle gain. So, whereas meal frequency
reduction shines as an effective means to reduce body fat and
free people from the inconvenience of multiple meals, its ability
to optimize muscle gain has been called into question.
I want to be clear from the outset that this is not going to be an
expository piece on the comprehensive, definitive details of a
given method. It’s more of a speculative romp across a
landscape lacking conclusive data. However, I still feel that there
is enough scientific data and personal observations upon which
useful & meaningful speculations can be made. Another aspect
that needs clarification is that IF comes in several variations, so
instead of assuming or making implications of a universal
definition of IF, I’ll merely be comparing higher and lower meal
frequencies. Without further ado, let’s get into it.
Solid scientific support for muscle retention
In research examining the effects of reduced meal frequency,
reductions in lean body mass have simply not been evident to
any degree of concern. Thus far, the literature on the whole fails
to indicate that lower meal frequencies jeopardize muscle mass
under a variety of conditions. I encourage you to review my
critique of the ISSN position stand on meal frequency if you
need the details on the latter point.1 Nevertheless, I’d like to
touch upon a particularly eyebrow-raising review by Varady
concluding that intermittent caloric restriction (ICR) is just as
effective as daily caloric restriction (DCR) for weight & fat loss,
but might be more effective for retaining lean mass.2 In this
review, Varady reported that 3 of the ICR studies showed no
significant decrease in LBM, while all of the DCR studies
showed an LBM decrease.
However, an important limitation acknowledged by Varady was
that the majority of the ICR trials used bioelectrical impedance
analysis (BIA) to assess body composition. In contrast, the
majority of the DCR studies used dual X-ray absorptiometry
(DXA) and magnetic resonance imaging (MRI). Since the latter
two methods have been shown to have greater accuracy than
BIA,3-5 this casts a shade of doubt upon the conclusions of this
review – especially the idea that ICR might be superior for LBM
retention (as opposed merely being equal).
Unfortunately, there’s a scarcity of long-term trials that directly
compare the effects of differing meal frequency on body
Alan Aragon’s Research Review – May 2012
composition. The few that do exist have been discussed in my
critique of the ISSN position stand.1 To the best of my
knowledge, only one more meal frequency comparison trial that
measured body composition has been published since my
critique. In this latest study, Harvie et al compared continuous
energy restriction (25% daily deficit) with intermittent energy
restriction (75% deficit on 2 days per week) and saw no
significant between-group differences in body composition
change over a 6-month period.6 So, the evidence that meal
frequency reduction is not inherently threatening to lean mass
compared to conventional dieting continues to mount. However,
it’s notable that the current body of work in this area lacks any
structured training protocol or optimization of macronutrition for
athletic purposes.
What about muscle gain?
The research area of optimizing meal frequency for the specific
purpose of muscle gain (in humans) is truly uncharted ground.
There are plenty of hypotheses based on rodent models, but
that’s about it. The traditional, bodybuilding-based approach to
optimizing muscle gains is to eat a protein-rich meal every 2-3
hours, all day long. This practice is rooted in the old myth that a
higher meal frequency raises 24-hour metabolic rate. It’s also
fueled by the notion that more is better when it comes to eating
for muscle gain. So for some, it becomes a default necessity to
be eating around the clock in order to get a massive amount of
total calories down the hatch in a gastrically tolerable way.
This routine is antithetical to any one of the IF variants that
typically involve fasting cycles that last anywhere from 16 to 36
hours. Prior to the relatively recent wave of research in this vein,
less meal frequency was automatically associated with more
muscle loss. We now know that’s not the case, especially in
reference to frequency variations within the course of a single
day. This raises the question of what the lower threshold of daily
meal frequency might be for maximizing muscle anabolism.
Norton et al’s findings & hypotheses
Layne Norton6 has for the past few years been producing data
from rodent models suggesting that the leucine plays a number
of critical anabolic roles that are relevant to the topic of meal
frequency and distribution.7-12 Some of his most notable findings
are as follows:
ƒ A ‘threshold’ amount of dietary leucine is required to
increase plasma leucine and initiate muscle protein synthesis
(MPS). Doubling plasma leucine is needed to stimulate MPS.
ƒ Changes in postprandial plasma leucine predict changes in
muscle weight & body composition.
ƒ Stimulation of MPS may cause nutrient partitioning.
ƒ Leucine content of protein sources predicts protein quality
as related to changes in body composition & muscle mass.
ƒ Egg and whey, but not soy and wheat were able to stimulate
MPS at a small breakfast meal because neither protein souce
contained the threshold amount of leucine.
ƒ Leucine content of complete meals predicts postprandial
MPS outcomes.
ƒ Leucine content and distribution impacts long-term body
composition & muscle mass.
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Norton’s practical recommendations for applying these findings
and maximizing anabolism are as follows:
ƒ Consume multiple leucine-rich protein sources to reach the
leucine threshold in the plasma. This equates to
approximately 2-3 g leucine in humans.
ƒ Distribute protein/leucine relatively evenly through the day.
ƒ Due to the refractory nature of MPS, it may be beneficial to
consume meals every 4-6 hours with leucine/BCAA alone
or in combination with carbohydrate between meals to
optimize MPS.
ƒ Further research is required to clarify optimal meal
frequency.
Regarding protein distribution, Norton’s poster presentation at
the 2012 ISSN Symposium indicated that an even distribution of
protein (30 g per meal at breakfast, lunch, & dinner) caused
greater muscle gains over an 11-week period than the same total
amount of protein distributed unevenly (10 g at breakfast, 20 g at
lunch, 60 g at dinner). The conclusion was that protein
distribution is a critical factor in determining the efficiency of
protein use for muscle anabolism, at least in rats. This supports
Norton’s recommendation of an even distribution of protein at
each meal in order to hit the leucine threshold of 2-3 g (this is
typically contained in about 30-40 g protein from a high-quality
source). I’d make a note that the leucine threshold figure of
2-3 g is lower than reported at a previous ISSN symposium
where he listed the threshold as 3-4 g. Perhaps it would be less
simple, but also more accurate to list it as 0.045-0.06 g/kg.13
Norton also cautions that solid, protein-rich meals should not be
too closely spaced from each other. This is because MPS can
diminish, or become refractory. This idea stems from the
observation in rats that the MPS time course of a meal peaked at
roughly 90 minutes after the meal, and was back to basal levels
at the 3 hour mark. Meanwhile, plasma leucine elevations
peaked at about 45 minutes after the meal, and remained
elevated near peak levels until the 3 hour mark, after which point
leucine levels began to drop. This means that despite the
prolonged elevation in plasma leucine, MPS started to decrease
far before leucine elevations dropped.
Other evidence of the refractory phenomenon is from Bohe et al,
who elevated plasma amino acid levels in humans and saw that
MPS peaked at the 2-hour mark, and rapidly declined thereafter
despite continually elevated blood amino acid levels.14 However,
this wasn’t a feeding study that measured concrete outcomes
over the long term. This was a mechanistic study whose data
was derived via steady intravenous infusion of amino acids. This
type of research is best viewed as a preliminary means to
investigate a small piece of the puzzle. Its usefulness is still
subject to confirmation or refutation by larger, longer trials that
measure relevant endpoints. The authors themselves admit to
this limitation of their study’s applicability. To quote them, “It
may be that amino acids are more efficiently utilized for
maintaining lean body mass and providing substrate for wound
healing when given in divided doses (as occurs with meal
feeding) rather than with continuous application.”
Ultimately, it’s a leap of faith to extrapolate short-term infusion
data to real-world conditions involving orally ingested substrates
and a host of other program variables. An additional bit of
Alan Aragon’s Research Review – May 2012
research that Norton cites to support his protein/BCAA dosing
protocol is research by Paddon-Jones et al, who showed that
MPS could be enhanced by consuming an EAA-carbohydrate
mixture containing 2.8 g leucine between meals spaced 5 hours
apart.15 The main problem with this study was that the
supplemented group had 45 g EAA plus 90 g carbohydrate more
than the control group, which creates an unfair advantage in the
experimental condition. Total protein intake (including
supplemental EAA) in the experimental condition was 109 g,
versus the control group’s 64 g. It thus can be viewed as an
adequate versus inadequate protein dosing study.
Further challenges to Norton et al’s ideas
A recent study by Adechian et al using overweight rats found
that during a 3-week energy deficit following a 5-week high-
energy diet, distributing the intake of a leucine-rich, high-protein
diet over the course of 12 hours does not differently affect
muscle mass compared to the diet consumed within a 3-hour
period.16 I’ll quote their concluding remark:
“Despite the high leucine content of MSP [milk soluble
protein, AKA whey] and the shortness of the post-absorptive
period, there was no difference in the body protein mass
evolution among the groups. Thus, when protein intake is
high, the nature and the timing of protein intake have no
influence on lean body mass changes during energy
restriction.”
The above quote nicely captures an important challenge to
Norton’s ideas on meal frequency (protein frequency in
particular) and protein distribution for maximizing anabolism.
Given a diet with an abundance of high-quality protein from
varying sources, frequency and proportional distribution of
protein doses within day are not likely to make any meaningful
impact unless extremes are pushed. It’s rare for anyone with the
primary goal of muscle growth to eat twice a day (or less). But
even in the case of an IF-type of scenario where only one or two
meals per day are consumed, I would still challenge that any
meaningful compromise in muscular growth is speculative in the
absence of data.
It’s reasonable to hypothesize that consuming a solid, mixed,
protein-rich meal every 4-6 hours while dosing BCAA between
meals could result in a higher rate of muscle growth than getting
all of your protein in a single meal each day. However, I see
quite a grey area when Norton’s protocol is compared with 2-3
meals containing a matched total of high-quality protein (minus
the BCAA or leucine threshold dosing between meals). In the
current literature, lean mass retention has been repeatedly seen
despite sub-optimal total protein intakes with low meal
frequencies in an energy deficit. Therefore, it’s difficult to
imagine that net anabolism would be measurably compromised
with low daily meal frequency in either caloric maintenance or
surplus conditions – especially with an abundant protein intake
combined with a well-designed resistance training program.
A potential counterpoint to the current literature supporting
lower frequencies is that lean mass retention and markers like
nitrogen status do not necessarily represent muscle protein
status. Lean mass consists of tissues aside from muscle, and
nitrogen flux involves a range of non-muscle tissues as well.
[Back to Contents] Page 3
This brings us back to the fact that we can only speculate in the
absence of sufficient data. However, it goes both ways; Norton
would have to admit to the hypothetical nature of his suggested
guidelines as well.
On the note of hypotheses, the next and perhaps most profound
challenge facing Norton’s ideas is that they are based on rodent
research. As I’ve mentioned in previous issues sometimes
facetiously, rodents are not humans. Their handling of BCAA is
fundamentally different from that of humans. As I discussed in
the October 2011 issue, the activity of the enzyme complexes
that regulate BCAA metabolism within the muscle and liver are
highly disparate between humans and rats.17 Therefore, direct
extrapolations can’t be accurately assumed. Similarly,
carbohydrate metabolism is drastically different between our
species since de novo lipogenesis (DNL – the hepatic conversion
of dietary carbohydrate to fat) is about 10-fold more active in
rodents.18
Conclusions & practical considerations
Norton may be on to something with his suggested protocol of
dosing a BCAA solution (containing 2-3 g leucine) between
mixed meals spaced 4-6 hours apart. But, it’s crucial to realize
that the ‘thing’ he may be onto might be miniscule and not worth
the effort or expense for non-competitive populations. In
repeated personal communication, he has admitted to me that
this tactic is done in attempt to clinch a very small edge to win.
As a top-level, drug-free competitor, it’s justifiable to exploit all
hypothetical nutritional means within reason in order to conjure
the last bit of potential.
When applying these hypothetical principles for optimizing
anabolism, I see a continuum of approaches ranging from the
conservative to the optimistic (Norton’s protocol being the
latter). Both would work, but their differential effects remain
unknown. The original question titling this article deals with the
conservative side. So, what’s the lower end of meal frequency
(technically, protein frequency) that would not compromise
maximal rates of muscle gain? I’d speculate that this can be
accomplished by two protein-rich meals ingested within roughly
two hours of both sides of the training bout, along with a third
protein-rich meal consumed elsewhere, whenever it’s convenient
or when hunger calls for it. That’s three daily protein feedings.
Would two protein doses still be able to maximize the rate of
muscle gain? No one knows, but it certainly would protect from
undue muscle loss given the research evidence showing this can
be accomplished with only one meal per day. Nevertheless, I
would error on the safe side and go with three protein-rich meals
as an ‘optimal minimum frequency’ for anabolism. It strikes a
compromise between conservative practicality & exploiting the
hypotheticals. If muscle gain is not the primary goal, and the
trainee is perfectly happy with maintaining, I don’t see going
below 3 meals per day as any sort of threat or compromise.
Also, although reaching the leucine threshold with each meal has
a reasonably sound basis, I have a hunch that even spacing of
meals is less important than Norton holds it to be.
There are plenty of unanswered questions, but one I find
particularly interesting is whether using isolated, free-form
amino acid supplementation is necessary or optimal compared to
Alan Aragon’s Research Review – May 2012
a high-quality, BCAA-rich, whole protein such as whey. A
recent review by Hulmi et al suggests that whey’s beneficial
effects on anabolism are not merely due to its constituent amino
acid content. To quote them,19 “...something other than EAAs
within whey are important for muscle hypertrophy. For example,
it is possible that via the PEPT-1 cotransporters' high capacity,
low specificity rate of transport, and an apparent increased
transport affinity for L-valine bound peptides, that the bound
form of an EAA may be more efficiently utilized than when
delivered in its free-form.”
On a practical note, reaching the leucine threshold through whey
protein is easily accomplished with 30-40 g (1.5-2 scoops,
assuming a 20 g scoop). On a final note, while it makes intuitive
sense that meal frequency reduction can be taken to a degree that
hinders optimal muscle gains, I am highly skeptical that it’s
possible to inhibit muscle gains by protein doses that are too
frequent, supposedly potentiating MPS refraction. I just don’t
see it happening in the real world.
References
1. Aragon AA. A critique of the ISSN position stand on meal
frequency. April 4, 2011. [Leangains.com].
2. Varady KA. Intermittent versus daily calorie restriction:
which diet regimen is more effective for weight loss? Obes
Rev. 2011 Jul;12(7):e593-601. [Pubmed]
3. Bosy-Westphal A, et al. Accuracy of bioelectrical
impedance consumer devices for measurement of body
composition in comparison to whole body magnetic
resonance imaging and dual X-ray absorptiometry. Obes
Facts. 2008;1(6):319-24. [Pubmed]
4. Pateyjohns IR, et al. Comparison of three bioelectrical
impedance methods with DXA in overweight and obese
men. Obesity (Silver Spring). 2006 Nov;14(11):2064-70.
[Pubmed]
5. Neovius M, et al. Bioelectrical impedance underestimates
total and truncal fatness in abdominally obese women.
Obesity (Silver Spring). 2006 Oct;14(10):1731-8. [Pubmed]
6. http://www.biolayne.com/about/
7. Norton LE, et al. Leucine content of dietary proteins is a
determinant of postprandial skeletal muscle protein
synthesis in adult rats. Nutr Metab (Lond). 2012 Jul
20;9(1):67. [Epub ahead of print] [Pubmed]
8. Norton LE, et al. Protein distribution affects muscle mass
based on differences in postprandial muscle protein
synthesis in plasma leucine in rats. 2012 ISSN poster
presentation.
9. Norton LE, et al. Leucine contents of isonitrogenous protein
sources predict changes in body composition and muscle
mass in rats. FASEB J. April 2010 (meeting abstract
supplement) 97.5 [FASEB]
10. Norton LE. Optimal protein intake to maximize muscle
protein synthesis: Examinations of optimal meal protein
intake and frequency for maximizing muscle mass in
athletes. Agro Food Ind. High-Tech. 2009
Mar/Apr;20(2):54-57. [AFI]
11. Norton LE. Leucine content of isonitrogenous protein
sources positivelyt influences body composition and muscle
mass in rats. 2012 ISSN Symposium presentation.
[Back to Contents] Page 4
12. Norton LE, Layman DK. Leucine regulates translation
initiation of protein synthesis in skeletal muscle after
exercise. J Nutr. 2006 Feb;136(2):533S-537S. [Pubmed]
13. Norton LE. Optimal protein intake and meal frequency to
support maximal protein synthesis and muscle mass. 2008
ISSN Symposium presentation.
14. Bohé J, et al. Latency and duration of stimulation of human
muscle protein synthesis during continuous infusion of
amino acids. J Physiol. 2001 Apr 15;532(Pt 2):575-9.
[Pubmed]
15. Paddon-Jones D, et al. Exogenous amino acids stimulate
human muscle anabolism without interfering with the
response to mixed meal ingestion. Am J Physiol Endocrinol
Metab. 2005 Apr;288(4):E761-7 [Pubmed]
16. Adechian S, et al. Spreading intake of a leucine-rich fast
protein in energy-restricted overweight rats does not
improve protein mass. Nutrition. 2012 May;28(5):566-71.
Epub 2011 Dec 20. [Pubmed]
17. Suryawan A, et al. Am J Clin Nutr. 1998 Jul;68(1):72-81..
[Pubmed]
18. Sievenpiper JL, et al. Heterogeneous effects of fructose on
blood lipids in individuals with type 2 diabetes: systematic
review and meta-analysis of experimental trials in humans.
Diabetes Care. 2009 Oct;32(10):1930-7. [Pubmed]
19. Hulmi JJ, et al. Effect of protein/essential amino acids and
resistance training on skeletal muscle hypertrophy: A case
for whey protein. Nutr Metab (Lond). 2010 Jun 17;7:51.
[Pubmed]

Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 5


Effects of dietary composition on energy expenditure
during weight-loss maintenance.
Ebbeling CB, et al. JAMA. 2012 Jun 27;307(24):2627-34.
[Pubmed]
CONTEXT: Reduced energy expenditure following weight loss
is thought to contribute to weight gain. However, the effect of
dietary composition on energy expenditure during weight-loss
maintenance has not been studied. OBJECTIVE: To examine
the effects of 3 diets differing widely in macronutrient
composition and glycemic load on energy expenditure following
weight loss. DESIGN, SETTING & PARTICIPANTS: A
controlled 3-way crossover design involving 21 overweight and
obese young adults conducted at Children's Hospital Boston and
Brigham and Women's Hospital, Boston, Massachusetts,
between June 16, 2006, and June 21, 2010, with recruitment by
newspaper advertisements and postings. INTERVENTION:
After achieving 10% to 15% weight loss while consuming a run-
in diet, participants consumed an isocaloric low-fat diet (60% of
energy from carbohydrate, 20% from fat, 20% from protein;
high glycemic load), low-glycemic index diet (40% from
carbohydrate, 40% from fat, and 20% from protein; moderate
glycemic load), and very low-carbohydrate diet (10% from
carbohydrate, 60% from fat, and 30% from protein; low
glycemic load) in random order, each for 4 weeks. MAIN
OUTCOME MEASURES: Primary outcome was resting
energy expenditure (REE), with secondary outcomes of total
energy expenditure (TEE), hormone levels, and metabolic
syndrome components. RESULTS: Compared with the pre-
weight-loss baseline, the decrease in REE was greatest with the
low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d),
intermediate with the low-glycemic index diet (-166 [-227 to -
106] kcal/d), and least with the very low-carbohydrate diet (-138
[-198 to -77] kcal/d; overall P = .03; P for trend by glycemic
load = .009). The decrease in TEE showed a similar pattern
(mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115]
kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P =
.003; P for trend by glycemic load < .001). Hormone levels and
metabolic syndrome components also varied during weight
maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P
= .005; indexes of peripheral [P = .02] and hepatic [P = .03]
insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P
< .001; non-HDL cholesterol, P < .001; triglycerides, P < .001;
plasminogen activator inhibitor 1, P for trend = .04; and C-
reactive protein, P for trend = .05), but no consistent favorable
pattern emerged. CONCLUSION: Among overweight and
obese young adults compared with pre-weight-loss energy
expenditure, isocaloric feeding following 10% to 15% weight
loss resulted in decreases in REE and TEE that were greatest
with the low-fat diet, intermediate with the low-glycemic index
diet, and least with the very low-carbohydrate diet. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT00315354.
SPONSORSHIP: This study was supported by grants
R01DK072428 and K24DK082730 from the National Institute
of Diabetes and Digestive and Kidney Diseases, Bethesda,
Maryland; grant M01RR02172 from the National Center for
Research Resources, National Institutes of Health, to the
Alan Aragon’s Research Review – May 2012
Children's Hospital Boston General Clinical Research Center;
grant M0102635 from the National Center for Research
Resources, National Institutes of Health, to the Brigham and
Women's Hospital General Clinical Research Center; grant
UL1RR02575801 from the National Center for Research
Resources, National Institutes of Health, to the Harvard Catalyst
Clinical and Translational Science Center; and a grant from the
New Balance Foundation.
Study strengths
This study is innovative since it’s the first to ever compare the
effects of the 3 major diet types on weight loss maintenance –
particularly their effect on total energy expenditure (TEE),
which was measured via stable isotope analysis. Dual X-ray
absorptiometry (DXA) was used to assess body composition.
The measurement of respiratory quotient (RQ) served to verify
the macronutrient compositions of the diets consumed. The
authors specified the crossover design as a methodological
strength, but I see it as just as much of a limitation in this case.
Study limitations
The duration (4 weeks) of the maintenance phases that followed
the 12-week run-in diet was simply too short to foster any
meaningful conclusions. Assessing the maintenance effects of
any diet should at the very least run several months, not one
month – that’s just silly. The authors duly acknowledge this
limitation, although not with the same fervor as I just did.
Impressively, the authors concede several other limitations.
Interestingly, they felt that the low-carbohydrate treatment might
not too extreme in terms of its carb restriction to be considered a
viable long-term solution. Therefore, they caution that the
degree of effects obtainable by carbohydrate restriction seen in
this study stand the chance of being overestimated when applied
to the real world.
An additional limitation that they half-heartedly acknowledge
was the possibility of carry-over effects since a single group of
subjects underwent each of the 3 maintenance conditions in a
cross-over fashion. A final limitation they acknowledge is that
physiological differences (e.g., insulin sensitivity) were not
assessed. This is a bit of a self-deprecating reach, since this is far
from standard procedure; it’s rarely been done in research
comparing dietary effects. A limitation inherent with cross-over
designs that the authors didn’t mention is the potential for order
effects; that is, the order that the treatments were undergone
could have influenced the outcomes. Ideally, a much larger
sample would have been divided into 3 test groups of similar
characteristics, running the maintenance phase for a much longer
duration. A rather glaring limitation was that protein was not
matched across the 3 conditions, which I’ll discuss further. A
final limitation worth noting is that diet trials without a
structured training program have to be viewed with caution,
since exercise can alter the effectiveness of the diet type.
Comment/application
The primary findings were that the decrease in resting energy
expenditure (REE) was greatest in the low-fat diet (-205
kcal/day), followed by the low-GI carb diet (-166 kcal/day), and
[Back to Contents] Page 6
the lowest decrease in REE occurred in the low-carb diet (-138
kcal/day). The diets resulted in the same ranking for total energy
expenditure (TEE), with the high-carb diet having the greatest
decrease (-423 kcal/day), the low-GI carb diet in the middle (-
297 kcal/day), and the low-carb diet yielding the lowest decrease
(-97 kcal/day).
As far as hormonal changes went, serum leptin levels expectedly
mirrored carbohydrate intake, with the low-fat diet yielding the
highest levels, and low-carb diet showing the lowest. 24-hour
urinary cortisol secretion was lowest in the low-fat diet and
highest in the low-carb diet. The latter finding concerned the
authors, since it’s an indicator of metabolic stress. Furthermore,
they specifically stated that, “Higher cortisol levels may
promote adiposity, insulin resistance, and cardiovascular
disease…” However, they merely cited observational research in
support of this concern.1-4
As for metabolic syndrome markers, the differences between
conditions were small and inconsistent, but still mostly in favor
of the low-carb condition. Insulin sensitivity expectedly was
highest with the low-carb & lowest with the low-fat diet.
Another predictable outcome was that triacylglycerol was
highest on the low-fat, and lowest on the low-carb diet, same
occurred with HDL (which again, is expected). A third outcome
favoring the low-carb diet was that it showed the greatest
decrease in plasminogen activator inhibitor 1 (PAI-1) levels,
while the low-fat diet yielded the lowest decrease in PAI-1.
Lowered PAI-1 is favorable because PAI-1 inhibits the
breakdown of blood clots, so lowered levels can be seen as a
good thing in this particular case.
However, another thing concerned the authors – in addition to
the elevated cortisol – was the higher C-reactive protein (CRP)
levels in the low-carb condition compared to the other
conditions. CRP is a biomarker of inflammation, and thus a
potential indicator of atherosclerotic risk. Keep in mind, others
in various media have reported that this study showed an
increase in CRP in the low-carb group, but technically, no
increase in CRP occurred. The low-carb condition simply had
the highest CRP value compared to the other diets. Nevertheless,
the authors voiced concern over this outcome alongside the
cortisol increase.
Plenty of unanswered questions nag at the outcomes of this
study. Although this wasn’t mentioned in the text, the lowest
drop in REE in the low-carb condition can be partially explained
by it containing substantially more protein than the other diets
(151.5 g in the low-carb diet vs. 104.8 g & 105.5 g in the low-fat
& low-GI diets, respectively). This may have better preserved
muscle mass, which is more metabolically active than fat mass.
Unfortunately, body composition results were not reported
(which is a shame since they took the pains to measure it with
DXA), so we’re left guessing. The difference in protein between
the low-carb diet and the others still doesn’t explain the REE
difference between the other diets, whose protein was matched.
The difference in TEE, favoring the low-carb diet, is also a big
question mark since no changes in physical activity were
detected throughout the study. The authors speculate that the
collective differences in energy expenditure might be due to
“intrinsic effects of dietary composition on the availability of
Alan Aragon’s Research Review – May 2012
metabolic fuels.” Specifically, they suggest the possibility that
leptin sensitivity (indicated by the ratio of energy expenditure to
leptin concentration) was greatest in the low-carb, and lowest in
the low-fat diets, and thus imparted the metabolic magic. In
support of this, they cite research by Lustig et al, who admit that
their study was merely correlational, and that the use of the
REE:leptin ratio as a surrogate measure of leptin sensitivity has
not been externally validated.5 The expected outcome of thyroid-
stimulating hormone being lowest in the low-carb diet and
highest in the low-fat diet merely adds to the mystery of the
outcomes.
The authors concluded that the low-GI diet was the best of the
bunch, since they felt that it came relatively close to producing
the favorable effects of the low-carb diet while avoiding the
latter’s unfavorable effects on markers of inflammation and
stress. Understandably, the low-fat diet got the failing grade. To
quote their most salient point, “These findings suggest that a
strategy to reduce glycemic load rather than dietary fat may be
advantageous for weigh-loss maintenance and cardiovascular
disease prevention.”
This is a fair conclusion based on the results of this study, but
the composition of the diets were far from ideal. As mentioned,
protein intake of the low-fat and low-GI diets were
approximately 1.16 g/kg of the subjects’ post-weight-loss
weight, which isn’t necessarily low, but not necessarily optimal.
The low-carb diet’s protein was 1.67 g/kg, which is much closer
to being ideal for a greater range of health & fitness-related
purposes. A problem that stuck out to me with the low-carb diet
is that it contained 11.2 g fiber. 3 g fiber at each meal were
provided by supplemental means (Metamucil). This indicates a
virtually nonexistent fruit & vegetable intake – unless it was the
unlikely case that low-fiber plant-based foods were specifically
consumed. Coming to mind immediately is a study by Jenkins et
al, who found that a low-carbohydrate, all-plant-based “Eco-
Atkins”diet improved blood lipids better than a low-fat/lacto-ovo
vegetarian diet.6 The plant-based low-carb diet happened to have
28.3 g fiber, which is roughly 2.5 times more than the low-carb
diet in the present study. It would have been interesting to see
how the “Eco-Atkins” diet would have affected hormones &
other metabolic syndrome markers compared to the low-carb
diet of the present study. My hunch is that an abundance of
vegetables (& enough fruit to fulfill the carbohydrate target)
within a low-carb diet would have trumped the present study’s
low-carb diet’s effects on a range of health indexes.
The low-fat diet in the present study had 46.5 g fat, which
simply isn’t realistic for most people in the real world eating a
variety of food within and across the food groups. Interestingly,
the authors never mentioned the potential difficulty in
maintaining such a low fat intake, yet they balked at the
possibility of maintaining the low carbohydrate intake. This
leaves us with the low-GI diet, whose macronutrient targets sat
squarely between the two extremes, and was unsurprisingly the
winner of the group, as least according to the interpretations of
the authors. However, instead of specifically pushing for the
lowering of glycemic load (as opposed to lowering fat), the more
accurate & practical recommendation for the goal of promoting
health or preventing disease would be a push towards moderate
macronutrient targets in general.
[Back to Contents] Page 7
Ketogenic diet does not affect strength performance in
elite artistic gymnasts.
Paoli A, et al. J Int Soc Sports Nutr. 2012 Jul 26;9(1):34. [Epub
ahead of print] [Pubmed]
BACKGROUND: Despite the increasing use of very low
carbohydrate ketogenic diets (VLCKD) in weight control and
management of the metabolic syndrome there is a paucity of
research about effects of VLCKD on sport performance. Ketogenic
diets may be useful in sports that include weight class divisions and
the aim of our study was to investigate the influence of VLCKD on
explosive strength performance. METHODS: 8 athletes, elite
artistic gymnasts (age 20.9 +/- 5.5 yrs) were recruited. We analyzed
body composition and various performance aspects (hanging
straight leg raise, ground push up, parallel bar dips, pull up, squat
jump, countermovement jump, 30 sec continuous jumps) before and
after 30 days of a modified ketogenic diet. The diet was based on
green vegetables, olive oil, fish and meat plus dishes composed of
high quality protein and virtually zero carbohydrates, but which
mimicked their taste, with the addition of some herbal extracts.
During the VLCKD the athletes performed the normal training
program. After three months the same protocol, tests were
performed before and after 30 days of the athletes' usual diet (a
typically western diet, WD). A one-way Anova for repeated
measurements was used. RESULTS: No significant differences
were detected between VLCKD and WD in all strength tests.
Significant differences were found in body weight and body
composition: after VLCKD there was a decrease in body weight
(from 69.6 +/- 7.3 Kg to 68.0 +/- 7.5 Kg) and fat mass (from 5.3 +/-
1.3 Kg to 3.4 +/- 0.8 Kg p < 0.001) with a non-significant increase
in muscle mass. CONCLUSIONS: Despite concerns of coaches
and doctors about the possible detrimental effects of low
carbohydrate diets on athletic performance and the well known
importance of carbohydrates there are no data about VLCKD and
strength performance. The undeniable and sudden effect of VLCKD
on fat loss may be useful for those athletes who compete in sports
based on weight class. We have demonstrated that using VLCKD
for a relatively short time period (i.e. 30 days) can decrease body
weight and body fat without negative effects on strength
performance in high level athletes. SPONSORSHIP: This work
was partially funded by Gianluca Mech SpA, Orgiano (VI), Italy.
Gianluca Mech SpA AP and LC research activity is funded by dept.
of Human Anatomy and Physiology,University of Padova.
Study strengths
This study is conceptually strong. It’s one of the rare few that
have examined the effects of a very low-carbohydrate ketogenic
diet (VLCKD) on athletic performance. Highly trained, elite-
level subjects were used. This eliminates much of the
confounding potential inherent with newbie trainees. Initial
dietary instruction was provided by a dietitian. Intake was
tracked and software-analyzed. The study consisted of two
phases, wherein the subjects served as their own controls. This
minimized inter-individual variations in response, but it also
introduces potential problems (to be discussed next).
Study limitations
The possibility that the subjects’ awareness of the phase changes
(& major differences in protocols) could have influenced the
outcomes. In other words, during the VLCKD phase, subjects
not only ate completely different diets, they also took a plethora
Alan Aragon’s Research Review – May 2012
of supplements, an act which in itself could have imparted a
neuro-psychogenic/placebo-driven advantage.7,8 Although a
parallel-arm design would not have had the advantage of the
subjects serving as their own controls, it would have eliminated
the ‘unblinded’ awareness factor of the programs being
compared. In addition to this, both dietary treatments were not
tightly controlled; they each were consumed ad libitum. As a
result, discrepancies in protein (200.8 g in the VLCKD vs. 83.5
g in the control diet) & energy intake (1972 kcal in the VLCKD
vs. 2274 kcal in the control diet) occurred. Another limitation
was the use of skinfold calipers to assess body composition. A
more ideal method would have been one that minimizes the
possibility for human/technician error, such as dual X-ray
absorptiometry (DXA). Finally, it’s possible that the exercise
performance tests may not accurately reflect or capture all the
strength, power, endurance, and/or specific skills (e.g.,
proprioception) involved with the actual gymnastics routines
presented in competition. A final limitation is the 30-day
duration of the VLCKD. What might occur in a longer treatment
period is open to speculation.
Comment/application
As seen above, the main finding of this study was that a VLCKD
ran for 30 days caused no significant differences in multi-faceted
strength performance testing. The authors point out that this is
the first study to ever show no difference in isometric strength
performance between a VLCKD & a high-carbohydrate diet. In
addition, the VLCKD yielded significant improvements in body
composition, preserving lean mass (despite lower total kcal
intake) & increasing the proportion of lean mass via fat mass
reduction. The body composition results were not surprising
considering the drastic differences in protein consumption,
which were abundant in the VLCKD and rather paltry in the
control diet. What’s actually quite remarkable is how the
subjects were able to maintain their performance capability
during the VLCKD phases despite an average weekly training
volume of 30 hours. This might be explained by the fact that the
performance testing was not particularly endurance-intensive,
thus not placing high demands on glycogen stores which were
undoubtedly compromised during the VLCKD. Another
explanation for the lack of performance testing decrement aside
from the adequate protein & lack of endurance component was
the advanced training status of the subjects, rendering them
resistant to sub-optimal dietary challenges. It would be
interesting to see this study re-done with matched adequate
protein intakes & stricter control of dietary & supplemental
intake. This would likely give the higher-carbohydrate condition
the performance edge, but it wouldn’t impart any weight or fat
loss advantage if total kcal intake was matched.
[Back to Contents] Page 8
Does metabolic compensation explain the majority of
less-than-expected weight loss in obese adults during
a short-term severe diet and exercise intervention?
Byrne NM, et al. Int J Obes (Lond). 2012 Jul 24. doi:
10.1038/ijo.2012.109. [Epub ahead of print] [Pubmed]
OBJECTIVE: We investigated to what extent changes in
metabolic rate and composition of weight loss explained the
less-than-expected weight loss in obese men and women during
a diet-plus-exercise intervention. DESIGN: In all, 16 obese men
and women (41±9 years; body mass index (BMI) 39±6 kg m(-2))
were investigated in energy balance before, after and twice
during a 12-week very-low-energy diet (565-650 kcal per day)
plus exercise (aerobic plus resistance training) intervention. The
relative energy deficit (EDef) from baseline requirements was
severe (74%-87%). Body composition was measured by
deuterium dilution and dual energy X-ray absorptiometry, and
resting metabolic rate (RMR) was measured by indirect
calorimetry. Fat mass (FM) and fat-free mass (FFM) were
converted into energy equivalents using constants 9.45 kcal per g
FM and 1.13 kcal per g FFM. Predicted weight loss was
calculated from the EDef using the '7700 kcal kg(-1) rule'.
RESULTS: Changes in weight (-18.6±5.0 kg), FM (-
15.5±4.3 kg) and FFM (-3.1±1.9 kg) did not differ between
genders. Measured weight loss was on average 67% of the
predicted value, but ranged from 39% to 94%. Relative EDef
was correlated with the decrease in RMR (R=0.70, P<0.01), and
the decrease in RMR correlated with the difference between
actual and expected weight loss (R=0.51, P<0.01). Changes in
metabolic rate explained on average 67% of the less-than-
expected weight loss, and variability in the proportion of weight
lost as FM accounted for a further 5%. On average, after
adjustment for changes in metabolic rate and body composition
of weight lost, actual weight loss reached 90% of the predicted
values. CONCLUSIONS: Although weight loss was 33% lower
than predicted at baseline from standard energy equivalents, the
majority of this differential was explained by physiological
variables. Although lower-than-expected weight loss is often
attributed to incomplete adherence to prescribed interventions,
the influence of baseline calculation errors and metabolic
downregulation should not be discounted. SPONSORSHIP:
None listed.
Study strengths
There is a huge grey area in our knowledge of how to accurately
predict weight loss based on current ‘standard’ calculation
benchmarks. Much of it is a jumble of educated guesses. This
study tackles the question of just how much we might miss the
mark when estimating the outcomes of a weight loss program. In
rare fashion, this study included a supervised, structured exercise
program (2 resistance training sessions & 4 aerobic sessions per
week, both types were progressive). Body composition was
assessed via dual X-ray absorptiometry (DXA), and total body
water was assessed via isotope deuterium. Five different
approaches were used to predict weight loss.
Study limitations
Perhaps the most glaring limitation was the use of a very-low-
energy diet (565-650 kcal per day). While this bolsters the
simplicity of execution, it excludes a large portion of the general
population for whom this protocol would be inappropriately low.
Alan Aragon’s Research Review – May 2012
Another limitation was that the diet was not completely lab-
provided, despite its low energy content. Subjects were still
responsible for fulfilling one of the three main meals of the day,
which consisted of lean meat and non-starchy vegetables. A
more ideal design would have provided the subjects with this
meal in order to prevent lapses in compliance or underestimation
errors in meal construction that impinged upon the intended
energy deficit. A limitation acknowledged by the authors was
that diet-induced thermogenesis (DIT) was predicted, rather than
directly measured. Another limitation I would add is that the
protein target (0.94 g/kg for males & 0.90 for females) was not
optimized. This is a frustratingly common design flaw in the diet
literature. If you refer back to my review of protein requirements
in the Editor’s Cut of the January 2011 AARR issue, roughly
1.5 g/kg appears to be the minimum daily protein dose necessary
to prevent lean body mass loss in non-athletic populations in an
energy deficit, undergoing resistance training. The present study
fell significantly short of that, despite imposing a severe energy
deficit.
Comment/application
Comment/application
The primary finding was that weight loss was 33% less than
predicted by a collection of standard/traditional methods.
Nevertheless, this discrepancy was in large part accounted for by
drops in RMR, DIT, overestimation of lean mass loss. RMR
decreased 228 kcal/day (11%). The estimated drop in DIT was
an additional 236 kcal/day, yielding an estimated total energy
expenditure decrease of 464 kcal/day. This represents 60% of
the discrepancy between the predicted and actual weight loss.
Another roughly 30% of the remaining discrepancy can be
explained by an underestimation by the Wishnofsky constant
(7700 kcal per kg of bodyweight), which assumes that the
composition of weight loss is likely to be 79% fat mass, and
21% lean mass.9 In the present study, a lower proportion of lean
mass was lost than predicted. As seen in the chart above, 3-3.1
kg of lean mass out of 16.1-16.3 kg of total mass was lost (an
18.8% loss). These losses account for approximately 90% of the
discrepancy, so it’s reasonable to speculate that the remaining
10% could easily be attributable to imperfect compliance by
subjects to the prescribed meal construction.
[Back to Contents] Page 9
 complete nutrient status (it’s possible that the inclusion of other
tissue levels may provide a more comprehensive estimate). I
Micronutrient deficiency in obese subjects undergoing would add to this that although 800 kcal/day was prescribed, the
low calorie diet. macronutrient breakdown of the diet was not reported, nor were
the ingredients of the product (Optifast 800) listed in the
Damms-Machado A, et al. Nutr J. 2012 Jun 1;11(1):34. [Epub manuscript. A bit of digging revealed that the daily totals of this
ahead of print] [Pubmed] product (five 160 kcal servings) amounts to 70 g protein, 100 g
carbohydrate, and 15 g fat. Funny enough, this formula is
BACKGROUND: The prevalence of micronutrient deficiencies is described as “protein-rich” when in reality, it just happens to
higher in obese individuals compared to normal-weight people, have more protein that traditional formulas, which can
probably because of inadequate eating habits but also due to
accurately be described as protein-poor. Another interesting
increased demands among overweight persons, which are
detail is that the primary carbohydrate sources in the shake
underestimated by dietary reference intakes (DRI) intended for the
general population. We therefore evaluated the dietary
product are lactose & fructose (stats & ingredients here).
micronutrient intake in obese individuals compared to a reference
Comment/application
population and DRI recommendations. Furthermore, we determined
the micronutrient status in obese subjects undergoing a standardized
DRI-covering low-calorie formula diet to analyze if the DRI meet
the micronutrient requirements of obese individuals. METHODS:
In 104 subjects baseline micronutrient intake was determined by
dietary record collection. A randomly assigned subgroup of subjects
(n = 32) underwent a standardized DRI-covering low-calorie
formula diet over a period of three months. Pre- and post-
interventional intracellular micronutrient status in buccal mucosa
cells (BMC) was analyzed, as well as additional micronutrient
serum concentrations in 14 of the subjects. RESULTS: Prior to
dietetic intervention, nutrition was calorie-rich and micronutrient-
poor. Baseline deficiencies in serum concentrations were observed
for 25-hydroxyvitamin-D, vitamin C, selenium, iron, as well as SZ-
carotene, vitamin C, and lycopene in BMC. After a three-month
period of formula diet even more subjects had reduced
micronutrient levels of vitamin C (serum, BMC), zinc, and
lycopene. There was a significant negative correlation between
lipophilic serum vitamin concentrations and body fat, as well as
between iron and C-reactive protein. CONCLUSIONS: The
present pilot study shows that micronutrient deficiency occurring in
obese individuals is not corrected by protein-rich formula diet
containing vitamins and minerals according to DRI. In contrast,
micronutrient levels remain low or become even lower, which might
be explained by insufficient intake, increased demand and As seen in the above chart, baseline deficiencies already existed
unbalanced dispersal of lipophilic compounds in the body. Trial for vitamin D3, vitamin C, selenium, & iron. After the 12-week,
registration The study was registered at ClinicalTrials.gov 800 kcal formula diet designed to meet 100% of the dietary
(NCT01344525). The study protocol comprises only a part of the reference intakes (DRI), deficiencies remained in selenium &
approved trial protocol. SPONSORSHIP: This work was supported iron. Vitamin C deficiency increased, and new deficiencies
by the “Competence Network of Obesity“, research group “Obesity occurred in zinc and calcium. Not shown above, lycopene
and the GI tract, “funded by the Federal Ministry of Education and deficiency at baseline remained uncorrected after the dieting
Research, Germany (No.FKZ 01GI0843 to SCB), and by Nestlé period. Clearly, the micronutrient-fortified formula diet did not
HealthCare Nutrition GmbH, Munich, Germany. succeed in preserving, let alone correcting multiple
micronutrient deficiencies. Of particular concern were the
Study strengths increased deficiencies and newly developed deficiencies as a
Although several studies have observed an association between result of the dieting protocol. It’s notable that 86% of the
obesity and a range of micronutrient deficiencies, this study subjects were on regular medication, which likely influenced
fulfills the need to directly measure the effect of large-scale micronutrient bioavailability or usage. An interesting outcome
weight loss on micronutrient status despite an attempt at was that all of the status of the fat-soluble vitamins improved by
covering potential deficiencies through a micronutrient-fortified the end of the trial. This makes sense, since these nutrients get
diet. Orally-derived buccal mucosa cell samples, as well as ‘trapped’ within fat tissue and thus rendered less available in
serum micronutrient levels were assessed. circulation. Ultimately, risking further micronutrient deficiency
to alleviate a dangerous state of obesity is probably a worthy
Study limitations trade. However, preventing nutrient deficiency could be a matter
of not dieting as drastically, which would enable a greater intake
The authors acknowledge two main limitations. First off, the of contextually correct nutrients within the matrix of whole
dietary recording method might be biased due to estimations foods. An alternative to this would be to simply increase the
instead of direct food weighing. A second limitation was that the dose of micronutrient supplementation (or fortification) to well
measurement of blood nutrient levels might not reflect the beyond 100% of the DRI.
Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 10

Muscle time under tension during resistance exercise
stimulates differential muscle protein sub-fractional
synthetic responses in men.
Burd NA, et al. J Physiol. 2012 Jan 15;590(Pt 2):351-62. Epub
2011 Nov 21. [Pubmed]
BACKGROUND/PURPOSE: We aimed to determine if the
time that muscle is under loaded tension during low intensity
resistance exercise affects the synthesis of specific muscle
protein fractions or phosphorylation of anabolic signalling
proteins. METHODS: Eight men (24 ± 1 years (sem), BMI =
26.5 ± 1.0 kg m(-2)) performed three sets of unilateral knee
extension exercise at 30% of one-repetition maximum strength
involving concentric and eccentric actions that were 6 s in
duration to failure (SLOW) or a work-matched bout that
consisted of concentric and eccentric actions that were 1 s in
duration (CTL). Participants ingested 20 g of whey protein
immediately after exercise and again at 24 h recovery. Needle
biopsies (vastus lateralis) were obtained while fasted at rest and
after 6, 24 and 30 h post-exercise in the fed-state following a
primed, constant infusion of l-[ring-(13)C(6)]phenylalanine.
RESULTS: Myofibrillar protein synthetic rate was higher in the
SLOW condition versus CTL after 24-30 h recovery (P <
0.001) and correlated to p70S6K phosphorylation (r = 0.42, P
= 0.02). Exercise-induced rates of mitochondrial and
sarcoplasmic protein synthesis were elevated by 114% and 77%,
respectively, above rest at 0-6 h post-exercise only in the SLOW
condition (both P < 0.05). Mitochondrial protein synthesis rates
were elevated above rest during 24-30 h recovery in the SLOW
(175%) and CTL (126%) conditions (both P < 0.05). Lastly,
muscle PGC-1α expression was increased at 6 h post-exercise
compared to rest with no difference between conditions (main
effect for time, P < 0.001). CONCLUSION: These data show
that greater muscle time under tension increased the acute
amplitude of mitochondrial and sarcoplasmic protein synthesis
and also resulted in a robust, but delayed stimulation of
myofibrillar protein synthesis 24-30 h after resistance exercise.
SPONSORSHIP: This research was supported by a research
grant from Natural Sciences and Engineering Research Council
of Canada to S.M.P.
Study strengths
This study investigates the controversial battle between what’s
more important for promoting muscle protein synthesis –
maximal fiber activation (by prolonging time under tension) or
intensity-dependent contraction volume (i.e., lifting heavier
weights that are closer to maximal strength capacity). Muscle
protein synthesis was measured at the fraction-specific level
(myofibrillar, sarcoplasmic, and mitochondrial), which is a more
sophisticated approach than merely measuring mixed muscle
protein synthetic response. To quote the authors in a moment of
eloquence, this methodology is able to “underpin the true acute
phenotypic response during exercise recovery.” Recreationally
resistance-trained subjects were used, minimizing the
confounding variability of newbie effects. 3-day diet records
were taken in order to have a model for diet replication in the
subsequent testing & recovery period. Subjects served as their
own controls via each leg performing the opposing protocol.
Alan Aragon’s Research Review – May 2012
This unilateral model helps control the problem of inter-
individual response differences.
Study limitations
A limitation acknowledged by the authors is that an assumption
must be made that a small sample of fibers represents what’s
occurring in the entire muscle (the vastus lateralis). I would also
add that that the small number of subjects (8) inevitably
compromises statistical power, and thus the ability to generalize
the results. Another limitation was that long-term effects were
not measured. While the assessment methods were state-of-the-
art, chronic effects are still open to speculation. Ideally, a
follow-up experiment would be carried out over a period of
weeks or months so further measures of hypertrophy (& strength
performance) can be compared. Perhaps the study’s biggest
limitation was the nature of the exercise tests. More on that in
the following discussion.
Comment/application
Technically, this study accomplished what it set out to do, which
was to compare the effect of different time under tension
protocols on muscle protein synthesis, using low load. However,
the practical implications are questionable, mainly because of
the nature of the protocols tested. First of all, training with 30%
of 1RM has very limited applicability beyond injured, frail
elderly, and diseased populations. A case can be made for using
such light loads to focus on building local muscular endurance,
but this has limited transfer toward building maximal strength,
power, and hypertrophy. Secondly, the repetition tempos
compared were somewhat unrealistic and impractical, especially
the slow treatment with 6-second concentric & eccentric phases
of each repetition.
The 3 sets in the slow protocol lasted 198, 119, & 90 seconds,
respectively. The control treatment, with 1-second repetition
phases instead of 6-second phases, matched the slow treatment’s
number of repetitions per set (12, 7, & 6 reps respectively). The
3 sets in the control protocol lasted 24, 14, and 11 seconds,
respectively. The slow protocol took substantially longer to
complete than the control protocol. So, imagine 3 sets, including
the 2-minute rest intervals between sets, taking 10.8 minutes to
complete. In contrast, the 3 sets in the control treatment with fast
reps took 4.8 minutes to complete. But perhaps the most
important confounder – which was unavoidable because
repetition number was matched – was the fact that only the slow
condition was taken to failure, but not the control. It’s not
unrealistic to assume that the sets in the control condition were
only taken half-way to the point of fatigue. So, it’s really not
surprising that muscle protein synthesis and anabolic signaling
were greater in the slow condition than the control condition.
Previous research still challenges the relevance & applicability
outcomes of the present study, since higher intensities were
used, and a traditional tempo (rather than a 1-second concentric
& eccentric tempo) is compared with a slow tempo. Importantly,
this research examined long-term effects, and measured concrete
outcomes such as exercise performance and body composition
change. With little exception,10 traditional strength training has
shown superior effects in a range of adaptations than slow tempo
training which necessitates lighter loads.11-14
[Back to Contents] Page 11
1. Adam TC, et al. Cortisol is negatively associated with
insulin sensitivity in overweight Latino youth. J Clin
Endocrinol Metab. 2010;95(10):4729-35. [Pubmed]
2. Holt HB, et al. Cortisol clearance and associations with
insulin sensitivity, body fat and fatty liver in middle-aged
men. Diabetologia. 2007;50(5):1024-32. [Pubmed]
3. Purnell JQ, et al. Enhanced cortisol production rates, free
cortisol, and 11beta-HSD-1 expression correlate with
visceral fat and insulin resistance in men: effect of weight
loss. Am J Physiol Endocrinol Metab. 2009;296(2):E351-
57. [Pubmed]
4. Vogelzangs N, et al. Urinary cortisol and six-year risk of
all-cause and cardiovascular mortality. J Clin Endocrinol
Metab. 2010;95(11):4959-64. [Pubmed]
5. Lustig RH, et al. Obesity, leptin resistance, and the effects
of insulin reduction. Int J Obes Relat Metab Disord. 2004
Oct;28(10):1344-8. [Pubmed]
6. Jenkins DJ, et al. The effect of a plant-based low-
carbohydrate (“Eco-Atkins”) diet on body weight and blood
lipid concentrations in hyperlipidemic subjects. Arch Intern
Med. 2009 Jun 8;169(11):1046-54. [Pubmed]
7. Pollo A, et al. The top-down influence of ergogenic
placebos on muscle work and fatigue. Eur J Neurosci. 2008
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8. Faria V, et al. Imaging the placebo response: a
neurofunctional review. Eur Neuropsychopharmacol. 2008
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9. Wishnofshy M. Caloric equivalents of gained or lost weight.
Am J Clin Nutr. 1958 Sep-Oct;6(5):542-6. [Pubmed]
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11. Keeler LK, et al. Early-phase adaptations of traditional-
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Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 12

 least efficiently, and thus has the highest thermic effect, with 25-
30% of its calories being required for its utilization within the
Gary Taubes’ article, “What Really Makes Us Fat”” body. The thermic effect of carbohydrate comes in second place,
at 6-8%, and fat is in the lowest spot, at 2-3%.
By Alan Aragon
_________________________________________________________________ But why does Taubes assume that ignorance or denial of the
aforementioned describes the scientific community? And why
does he assume that anyone would believe that what we eat is
“relatively unimportant”? My guess is that he’s setting up the
perfect scenario to destroy these ludicrous notions. The problem
is, no one with a remotely solid foundation of nutritional
knowledge holds those beliefs in the first place. So who is
Taubes railing against? He’s merely creating a straw man – or in
this case, a straw building – to burn down.
Based on direct feedback I’ve received, my Taubes article But then he gets into the sticky part, where he begins to slickly
critiques have been perennially popular with AARR subscribers. imply that a hypocaloric state is not conducive to fat loss, and a
Luckily, I quite enjoy Taubes articles since they provide plenty hypercaloric state is not conducive to fat gain. So, Taubes offers
of food for thought. They also provide plenty of cannon fodder. the following entertainment – I mean, wisdom:
Apparently, recent research by Ebbeling et al1 excited Gary
Taubes into writing another widely exposed carbophobic article The obvious mechanism: carbohydrates stimulate secretion of 
in the New York Times.2 While I can appreciate Taubes’ the  hormone  insulin,  which  works,  among  other  things,  to 
courage in tacking difficult questions, I always end up face- store fat in our fat cells. At the time, though, the conventional 
palming at his empty justifications and wild claims. But, this wisdom  was  beginning  its  shift:  obesity  was  becoming  an 
makes for good discussion – and hopefully an opportunity to energy  issue.    Carbohydrates,  with  less  than  half  the  calories 
clear up some misconceptions. I’ll interject my responses to his per  gram  as  fat,  were  beginning  their  official  transformation 
most interesting and outrageously baseless claims. And here – into  heart‐healthy  diet  foods.  One  reason  we’ve  been  told 
we – GO. since to eat low‐fat, carbohydrate‐rich diets is this expectation 
that they’ll keep us thin. 
A CALORIE is a calorie. This truism has been the foundation of 
nutritional  wisdom  and  our  beliefs  about  obesity  since  the  As I read the above passage, my head automatically starts
1960s. What it means is that a calorie of protein will generate  shaking in a “no” fashion. Just...no. The way he calls
the  same  energy  when  metabolized  in  a  living  organism  as  a  carbohydrates the obvious cause of obesity is perhaps the crux of
calorie  of  fat  or  carbohydrate.  When  talking  about  obesity  or  why he’s famous. In the current day and age of nutritional
why  we  get  fat,  evoking  the  phrase  “a  calorie  is  a  calorie”  is  voodoo, if you’re just plain crazy enough, people will take
almost  invariably  used  to  imply  that  what  we  eat  is  relatively  notice, and many will believe you. The main problem I see with
unimportant. We get fat because we take in more calories than  Taubes’ position is his selective and purposeful denial of the fact
we  expend;  we  get  lean  if  we  do  the  opposite.  Anyone  who  that you can put any adult on a diet consisting of 6 slices of
tells  you  otherwise,  by  this  logic,  is  trying  to  sell  you  white bread per day, and watch him dwindle to an emaciated pile
something.  of bones in a matter of months (or for some, a matter of weeks).
Why would this preposterous all-bread diet do this? It’s almost
Taubes swings open his article with a big, bodacious straw man all carbohydrate; refined carbohydrate, at that. Better yet, put
fallacy. He misrepresents the side of the opposition on several any adult on a diet consisting of 10 tablespoons of pure, white
fronts. First of all, the expression “a calorie is a calorie” can be table sugar (sucrose) per day. There you go, it’s even more
taken literally, in which case it’s self-evidently true since a unit refined, and half of it consists of fructose. Would the same rapid
of measure is what it is – it’s unchanging. A calorie is a calorie weight loss occur? Of course it would. And we obviously know
just as a gram is a gram, a meter is a meter, or a minute is a that this is because a caloric deficit would be imposed. But,
minute. It’s the figurative interpretation that Taubes assumes is would anyone in his right mind advocate or undergo such a diet?
the belief held by enough people to get up in arms over. I don’t know. Maybe this is something Taubes would do in his
Essentially, he’s assuming that the prevailing wisdom in the deepest, darkest fantasies.
scientific mainstream is that the macronutients all have the same
thermic effect and lack different physiological roles within the On a less facetious note, the line of logic that carbs are
body. Further, he’s assuming that conventional nutritional insulinogenic and thus cause obesity is incomplete and incorrect.
wisdom says that the quality of the diet does not matter. There is One thing that the proponents of this idea are not capable of
not a single educated person I’ve ever known who would agree doing is supporting this stance with a consistent body of well-
with any of those premises. designed/well-controlled research showing that a higher
proportion of dietary carbohydrate drives fat gain more than an
In the scientific community (even in the conservative & isocaloric, protein-matched comparator over the long-term. And
relatively backward sectors), it’s well-known that dietary that’s not even asking to show that this would be the case in
macronutrients have different metabolic costs of processing.3 physically active people whose protein-sufficient diets are
Protein is the most energetically expensive; it’s processed the predominated by whole & minimally refined foods.
Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 13
Taubes’ use of Ebbeling et al’s recent study (which I reviewed Taubes was tempted to report that subjects consumed a
earlier in this issue) to support his position exemplifies how conventional, starch-dominant diet containing 229 g
desperate people can get. It also shows how selective and carbohydrate per day. And Taubes thinks you can’t lose weight
unobjective people can get when defending their anti-carb on a high-carb diet. The authors conclusions are far less
religion. Let’s have a look at what he highlights. glorifying than Taubes’ are toward the low-carb diet. To quote
the authors, “...this restrictive regimen may increase cortisol
On  the  very  low‐carbohydrate  diet,  Dr.  Ludwig’s  subjects  excretion and CRP. The low–glycemic index diet appears to
expended 300 more calories a day than they did on the low‐fat  have qualitatively similar, although smaller, metabolic benefits
diet  and  150  calories  more  than  on  the  low‐glycemic‐index  to the very low-carbohydrate diet, possibly without the
diet.  As  Dr.  Ludwig  explained,  when  the  subjects  were  eating  deleterious effects on physiological stress and chronic
low‐fat diets, they’d have to add an hour of moderate‐intensity  inflammation.”
physical  activity  each  day  to  expend  as  much  energy  as  they 
So, what really makes us fat? It’s not carbohydrates, or any
would  effortlessly  on  the  very‐low‐carb  diet.  And  this  while  single macronutrient, for that matter. It’s too many total calories
consuming the same amount of calories. If the physical activity  in, and not enough calories out. This is not to imply that
made  them  hungrier  —  a  likely  assumption  —  maintaining  everyone should be on a high-carbohydrate diet (or any specific
weight on the low‐fat, high‐carb diet would be even harder.   diet in particular). It all depends on the individual situation.
Individual circumstances, preferences, tolerances, & total energy
While there differences in energy expenditure were detected requirements vary. As such, individual carbohydrate
between the diets, the low-carb diet had the unfair advantage of requirements will vary from low to high, and every point in
containing roughly 44% more protein than the other diets. between. It’s wise to put the emphasis on personal preference,
Perhaps more importantly, these measured differences in energy since preference fosters the consistency of adherence. Relatively
expenditure are potentially inconsequential in the face of the recent research by Alhassan et al lent support to what should be
concrete outcomes. Aside from the study design limitations I intuitive: long-term weight loss was greatest in subjects who
discussed earlier, there were no weight differences or even any were most adherent, regardless of diet type.4 The authors thus
trends between the groups during the maintenance phase that concluded that, “...strategies to increase adherence may deserve
would point to the clinical relevance of these expenditure more emphasis than the specific macronutrient composition of
differences. In fact, during the test diet phase, the subjects’ the weight loss diet itself in supporting successful weight loss.”
bodyweight was nearly identical during each condition.
Why is the idea of individually tailoring carbohydrate intake so
Furthermore, I find it humorous that Taubes thinks that hard for seemingly smart people like Taubes to grasp? Maybe he
maintaining weight would be most difficult on the low-fat/high- does understand this concept – but is uninterested in its utter lack
carb diet, because the authors themselves expressed concern of journalistic excitement.
with how realistic the low-carb diet might be to live with. They
specifically stated that the low-carbohydrate diet “...involved References
more severe carbohydrate restriction than would be feasible for
many individuals over the long term.” Taubes was pretty good 1. Ebbeling CB, et al. Effects of dietary composition on energy
about reporting the tidbits from the study that fit his pre-existent expenditure during weight-loss maintenance. JAMA. 2012
beliefs, but left out the opinion of the authors that run contrary to Jun 27;307(24):2627-34. [Pubmed]
his anti-carb doctrine. 2. Taubes G. What really makes us fat. New York Times
Sunday Review. June 30, 2012. [NY Times]
3. Jéquier E. Pathways to obesity. Int J Obes Relat Metab
If  we  think  of  Dr.  Ludwig’s  subjects  as  pre‐obese,  then  the 
Disord. 2002 Sep;26 Suppl 2:S12-7. [Pubmed]
study  tells  us  that  the  nutrient  composition  of  the  diet  can  4. Alhassan S, et al. Dietary adherence and weight loss success
trigger  the  predisposition  to  get  fat,  independent  of  the  among overweight women: results from the A TO Z weight
calories consumed. The fewer carbohydrates we eat, the more  loss study. Int J Obes (Lond). 2008 Jun;32(6):985-91.
easily  we  remain  lean.  The  more  carbohydrates,  the  more  [Pubmed]
difficult.  In  other  words,  carbohydrates  are  fattening,  and 
obesity  is  a  fat‐storage  defect.  What  matters,  then,  is  the 
quantity  and  quality  of  carbohydrates  we  consume  and  their 
effect on insulin. 

While reading the dreamy hypothesizing Taubes is doing in the

above passage, I wonder if he realizes that the authors ultimately
did not give the low-carb diet the top spot when ranking the
three conditions. The authors ended up awarding the low-GI diet
as the winner of the bunch. The low-carb diet contained 50.1 g
while the low-GI diet contained 206.1 g. Again, no differential
effect on bodyweight was seen. During the initial 12-week run-
in phase of the study, subjects lost an average of 14.3 kg (31.5
lbs), which is a substantial loss by any standard. I doubt that

Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 14

 1000 kcal daily surplus, it was found that an average of 432 kcal
was stored, and 531 kcal was burned. Two-thirds of the latter
How much of a calorie surplus is needed for bulking? was dissipated through an increase in non-exercise activity
By Alan Aragon thermogenesis (NEAT). This consists of unconscious activities
such as fidgeting, maintaining posture, muscle contraction, and
 
             How much of a calorie surplus do I need for bulking?   other instances of spontaneous activity during both sleeping and
             I’ve  seen  all  kinds  of  different  recommendations  and  waking hours. The range of NEAT increase was rather large (-98
don’t know where to start. Is there a solid guideline I can go by,  to +692 kcal/day), but the upper end of NEAT being at 692
or is it just a matter of adding 500 cals a day and seeing what  kcal/day can easily explain why some folks feel like they’re
happens?   “weight gain-proof” or “hard-gainers” despite substantially
increased food intakes. In reality, although they attempted to
create a caloric surplus, unconscious caloric expenditure
The caloric surplus you program into your diet can be quite nullified it.
different from the ACTUAL surplus that occurs. This largely
depends on how much spontaneous/non-exercise activity Back to the original question, just how much of a caloric
increases alongside the purposefully increased intake. It helps to increase is required for a bulking (muscle-gaining) phase? This
get a bit of background on this concept to fully appreciate and will vary individually, and this is why some gain sufficiently on
understand its magnitude, so I’ll take the liberty to bring a 200-300 kcal increase, while others need to increase their kcals
research into this casual conversation. by 700-800 to make a dent (due to NEAT & other non-volitional
expenditure eating up their surplus). Even a seemingly drastic
A classic study by Levine et al fed non-obese adults (aged 25-36 increase of 1000 kcal might actually be necessary for some
years) 1000 kcal above their maintenance needs for 8 weeks.1 individuals. Refer back to the chart and notice that the range of
The study was methodologically strong. Body composition was total weight gained in the 8-week period was as low as 1.4 kg
assessed via dual X-ray absorptiometry (DXA). Energy (3.1 lb). The person who gained this little weight could be a
expenditure was assessed via doubly labeled water. Both are good candidate for the 1000 kcal increase if his goal was to gain
considered gold-standard methods for their intended purposes. weight. Ultimately, you’ll have to just trial & error this one out
Their findings were rather fascinating. Here’s a snapshot of how to find the sweet spot. I’d start on the lower or mid range
the variables were affected during the 8 weeks: (depending on how easily you feel you gain fat), and then ratchet
up from there as needed. And also, for most non-newbies, an
average gain of 2-3 lbs a month is plenty. Otherwise, you’ll just
be piling on excess fat.

References
1. Levine JA, et al. Role of nonexercise activity thermogenesis in
resistance to fat gain in humans. Science. 1999 Jan
8;283(5399):212-4. [Pubmed]
2. Byrne NM, et al. Does metabolic compensation explain the
majority of less-than-expected weight loss in obese adults
during a short-term severe diet and exercise intervention?
Int J Obes (Lond). 2012 Jul 24. doi: 10.1038/ijo.2012.109.
[Epub ahead of print] [Pubmed]

The conventional belief is that increasing intake by 500 kcal/day

would allow a gain of 1 pound per week, and the converse is
presumed to occur with weight loss, but many of us know from
experience or observation that neither are very reliable. In this
very issue, I reviewed a study by Byrne et al showing that the
amount of weight loss was only 67% of what was predicted by This 5-minute clip highlights a guy’s first year of practicing the
standard methods.2 Or, you could think of it as being an art of parkour/free running, which takes me back to a simpler,
overprediction of weight loss by 33%. more reckless era of my youth. Watch for the foot fracture at
2:27. Don’t worry, it’s not graphic.
In the present case of weight gain, a traditional model might
predict a gain of 2 pounds per week given a 1000 kcal/day
surplus, which in 8 weeks would amount to 16 pounds.
However, in the case of Levine et al’s carefully controlled study, If you have any questions, comments, suggestions, bones of
an average of 4.7 kg (10.34 lbs) was gained. Our traditional contention, cheers, jeers, guest articles you’d like to submit, or
model over-predicted weight gain by 54.7 %. Strikingly, of the any feedback at all, send it over to aarrsupport@gmail.com.

Alan Aragon’s Research Review – May 2012 [Back to Contents] Page 15