Академический Документы
Профессиональный Документы
Культура Документы
By Alan Aragon
[Back to Contents]
Page 1
[Back to Contents]
Page 2
[Back to Contents]
Page 3
4.
5.
3.
[Back to Contents]
Page 4
Study strengths
A novel aspect of this study is the reporting of not just
bodyweight, but also energy expenditure, physical activity (in
METs), appetite hormones, and CLOCK genes, whose single
nucleotide polymorphisms (SNPs) have been associated with
weight loss or obesity depending on within-day timing of food
intake. Sample size was relatively large (420 subjects), and trial
duration was long (~20 weeks). Subjects met with a nutritional
professional every 2 weeks, who counseled them on the range of
dietary and behavioral program aspects. Energy and
macronutrient records were software-analyzed.
Study limitations
The authors acknowledged a couple of limitations. First, the
Harris-Benedict equation was used to predict energy
requirements, and they conceded that this ...is not very accurate
to assess energy expenditure, especially during weight loss.
they also admitted that the groups could have had differences in
resting energy expenditure that went undetected. A solution for
this confounder would be the doubly labeled water technique,
which is a more accurate/objective measure of energy
Alan Aragons Research Review November 2012
Comment/application
A quick perusal could lead many to assume that the over-arching
message is that eating later means getting fatter. However, its
important to note that only the timing of lunch (early as opposed
to late) was associated with a significantly greater loss of
bodyweight. The timing of breakfast or dinner was not found to
have any impact on bodyweight change. This finding deserves
emphasis since it runs contrary to the automatic assumption that
people will make namely, that dinner must be consumed early
in order to effectively lose weight. However, taking a look at the
chart above, the mean weight loss between the differing
breakfast and dinner timing was practically identical. Upon
closer examination of what qualified as a statistically significant
difference in weight loss between the late and early lunch eaters
amounted to a difference of 2.2 kg in 5 months hardly anything
to get overly excited about, considering the potential
confounders discussed. The authors found that late eaters
happened to skip breakfast more frequently than early eaters,
which they felt could be a contributing factor to their lesser
weight loss. Curiously, they posited that the late lunch may
prolong a semi-fasted state and induce glucose metabolism
impairments. However, these speculations have questionable
grounds due to the majority of controlled interventions that do
not support them.3-7 The present findings, although interesting,
dont exactly rock the boat of evidence. Replication with tighter
control would be required. Ill conclude by quoting recent work
by Sofer et al, who found opposite & potentially more relevant
outcomes despite concentrating energy intake later in the day:8
...our studies have demonstrated that manipulation of dietary
carbohydrate distribution led to changes in the daily curves of
leptin, ghrelin and adiponectin that coincided with improved
hunger/satiety status, persistence in the weight loss process,
anthropometric outcomes, insulin sensitivity, metabolic
syndrome parameters and inflammatory status.
[Back to Contents]
Page 5
As seen above, the main findings were that despite the caeindextrose treatment causing a greater initial insulin spike which
accelerated amino acid delivery to muscle during the first 90
minutes after ingestion, amino acid delivery overall was not
greater than the casein-only treatment at the 6-hour mark. This
finding is similar to recent work by Staples et al, who found that
an additional 50 g maltodextrin co-ingested with 25 g whey did
not augment muscle protein balance either at rest or postexercise,10 and also work by Moore et al, who found that 20 g
whole egg protein was sufficient to max-out muscle protein
synthesis & albumin protein synthesis after resistance exercise,
whereas a 40 g dose merely increased amino acid oxidation.11
[Back to Contents]
Study limitations
Page 6
Perhaps the most important outcome was the improvement in 3km time trial performance in SG, since this was a field test
directly related to a real-world race. A similar finding was also
seen by Paavolainen et al,14 who found that concurrent explosive
strength & endurance training improved 5-km time trial
performance despite a lack of change in VO2max. They
speculated that performance was enhanced by explosive strength
training causing improved neuromuscular function, which in
turn translated to improved running economy. The practical
application offered by the authors is for coaches to incorporate
explosive strength training in the endurance programs of welltrained endurance athletes. Based on the weight of the current
evidence,14-17 this looks like a sound recommendation.
[Back to Contents]
Study limitations
Page 7
25
ngmL-1
respectively). One day of
GTE ingestion did not
affect
markers
of
lipolysis during the exercise
bout. Seven days of GTE
ingestion
significantly
increased plasma glycerol during exercise (P=0.045) and plasma
FAs during exercise (P=0.020) as well as at rest (P= 0.046).
However, fat oxidation did not change in any of the groups.
CONCLUSIONS: There was no effect of 1 day GTE ingestion
on markers of lipolysis or fat oxidation during exercise. Seven
days of GTE ingestion increased lipolysis, indicated by
increased plasma FA and glycerol concentrations, but did not
result in significant changes in fat oxidation. SPONSORSHIP:
This work was supported by a research grant from Unilever Plc.
S.L, D.J and D.M are employees of Unilever. R.R, A.H and A.J
have no professional relationship with the company involved in
this study and have no conflict of interests. N.B was a previous
employee of Unilever however had no conflict of interest at the
time of results interpretation.
This study is the first to measure the effect of green tea extract
(GTE) on fat oxidation rates in humans, while also taking into
account plasma catechin levels. Its also the first to directly
compare the effects of 1 & 7 days of GTE ingestion on fat
oxidation during 60 minutes of moderate-intensity exercise. The
lab provided subjects all of their meals the day before the trial.
To bolster compliance, daily text messages were sent to the
[Back to Contents]
Study strengths
Page 8
[Back to Contents]
Study limitations
Page 9
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
[Back to Contents]
Page 10
Underweight: <18.5
Normal weight: 18.5-24.9
Overweight: 25-29.9
Obesity, Class 1: 30-34.9; Class 2: 35-39.9; Class 3: 40
BMI (kg/m )
FFMI (kg/m )
BFMI (kg/m )
% BF
Men
30.0
27.8
25.0
20.0
18.5
21.7
20.9
19.8
17.5
16.7
8.3
6.9
5.2
2.5
1.8
28.8
25.8
21.7
13.4
10.8
Women
30.0
27.3
25.0
20.0
18.5
18.2
17.5
16.8
15.1
14.6
11.8
9.8
8.2
4.9
3.9
40.0
36.5
33.2
24.6
21.7
*Blue=withinnormal/acceptablelimits
[Back to Contents]
Page 11
So, there it is. Since Noakes is restricting his carb intake to 5075 grams a day, his diet defaults to the exclusion of the
aforementioned foods. The foods he allows himself are eggs,
fish, organic/grass-fed meat, dairy (I was surprised at this), non[Back to Contents]
Page 12
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
[Back to Contents]
Page 13
IreadanarticlecalledCanNicotineSafelyBurnFatand
BuildMusclebyKiefer,andIwaswonderingifnicotine
isaseffectiveforfatlossasitsportrayedtobeinthatarticle.
Thanksinadvance.
That being said, mTOR in that one study was induced in vitro so
there does appear to be a degree of activation there. Whether or
not this is even relevant practically is not known, it is currently
the only study that exists on the topic and at best is preliminary
[Back to Contents]
Page 14
evidence.
The second claim of AMPK activation causing nutrient uptake
was also an in vitro study, where an increase in nitric oxide
caused an increase in peroxynitrate (a free radical) which then
induced AMPK. The study was conducted in immortalized fat
cells, which is again a preliminary study (a nicely conducted one
at that) which needs replication.
The problem here is that mTOR and AMPK have a yin-yang
relationship in all cell lines, when one gets activated it
suppresses the other.7 Reliance on in vitro studies to support
claims made it seem like you can have your cake and eat it too,
but unless a novel pathway suddenly appears in the future that
can prevent crosstalk it seems likely that both of the above are
active. Either one of them will overcome the other, or they will
negate.
No evidence exists to support a localized mTOR in skeletal
muscle and AMPK in adipose either (this is a currently unknown
but theoretically plausible nutrient partitioning effect) so touting
these two mechanisms of action for nicotine is, at best, an
unfortunate result of relying too much on in vitro evidence and
not accounting for cellular crosstalk (when one protein or
receptor interacts with another). At worst, its a hasty misuse of
science, resulting in largely irrelevant supporting data.
On the topic of nicotine as a fat burner
There is a lot of research on nicotine that can be found currently,
which dwindles in amount when you control for nicotine per se
(excluding cigarettes) and when you look at studies that induce
weight loss rather than those that prevent weight regain after
smoking cessation the latter of which are fairly common. We
have one (cited by the aforementioned article) that shows an
acute increase in metabolic rate following usage of up to 2 mg
nicotine gum paired with caffeine in otherwise healthy men,8 and
one in otherwise healthy smokers only reporting a thermogenic
response in men,9 and we have one study that noted in nonsmoking using a 15mg patch that 1.6 kg was lost over 91 days,
although after 6 months the difference was no longer apparent.10
The former two studies support the notion that a fat burning
effect may exist (which appears to be mediated via an
acetylcholine-induced release of catecholamines as per the first
study, so I guess it is a good thing that 'adrenaline diabetes'
doesn't exist) and the latter supports the notion of appetite
suppression causing a reduction in weight even when blinded.
Animal studies suggest that the mechanisms of weight loss are
mediated via acetylcholine receptors (as blocking these receptors
block the weight loss), although this implicates both increased
catecholamines as well as appetite suppression.
That is basically it. For the purposes that many people are using
it for (anti-smoking aids ingested with exercise and diet for the
purpose of body fat loss) it is a very underresearched topic.
Misinterpretation of science
At several points in this article, references were cited in support
of the claims. 26 in total, all conveniently hidden behind a Like
this on social media form of pseudo-paywall (where the benefit
is in exposure rather than finances). All citations and their
Alan Aragons Research Review November 2012
Page 15
Citation 18 and 19 do not support the claim of Nicotine restimulates UCP1...so you keep burning fat even if you drop
calories. as neither induced caloric restriction previous to
the experiment.27,28
Citations 20-22 were used to support the appetitesuppressive effect of nicotine, and these citations appear to
be legitimate.29-31
Citation 23 was mentioned as mTOR may also augment
tumor cell growth (context dependent) and the author made
note that Curcumin could negate this effect. It is again an in
vitro study,32 but Curcumin does appear to antagonize the
proliferative effects of nicotine in this cell line (via inhibitin
mTOR activation and the subsequent genomic signalling).
Citation 24 was mentioned in support of how nicotine clears
slower in the evening (despite taking 24 hours to clear the
body, which will always cross over into one evening at
least). The study merely made not of several issues that
could alter the pharmacokinetics of nicotine patches.33
Citation 25 was used in the middle of a paragraph talking
about nicotine dosing, and is a study noting synergism
between nicotine and caffeine.34 It seems out of place here
(possibly being used to recommend 1mg given what the
study and article says), but reappears in the section saying to
stack with caffeine where it makes more sense. There does
appear to be some slight synergy with caffeine and nicotine
in a dose-dependent manner, as assessed by this study using
doses up to a 2mg/200mg nicotine/caffeine combination on
acute thermogenic response. No clue where the claim about
for fat loss and mobilization during training came in,
since there was no training in this study.
Overall, this article offers a number of interesting speculations,
but its also a good example of how citations do not necessarily
mean that the topic on hand is scientific. References in blog
posts are just links, and these links can be poorly directed and
misinterpreted.
Summation
In sum, Nicotine is a promising anti-obesity drug, and the antiinflammatory effects of it can theoretically confer more benefit
to obese persons than classical stimulants. The aforementioned
claim needs to be studied though, as studies on nicotine and
inducing weight loss are surprisingly scarce. There is no
evidence to currently support nicotine as a muscle building agent
beyond a single in vitro study of questionable practical
significance, and the fat burning effects of nicotine do not appear
to be greater than that of classical stimulants such as ephedrine
or caffeine. The concept of adrenaline diabetes most likely
does not exist, and especially not the same degree as chronic
insulin resistance, and as such nicotine is unlikely to exert more
weight loss to athletes than classical stimulants (mentioned
before).
Nicotine is another possible option to add to a supplement
regimen or to throw into your minds database; it does not
currently revolutionize anything pertaining to fat loss or musclebuilding.
[Back to Contents]
Page 16
18.
19.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Kiefer J. Can Nicotine Safely Burn Fat and Build Muscle? The
Surprising Facts. Accessed November 21, 2012. [Dangerously
Hardcore]
Bawa-Khalfe T, Altememi GF, Mandyam CD, Schwarz LA,
Eikenburg DC, Standifer KM. The presence of beta2adrenoceptors sensitizes alpha2A-adrenoceptors to desensitization
after chronic epinephrine treatment. BMC Pharmacol. 2007 Dec
20;7:16. [PubMed]
Astrup A, Lundsgaard C, Madsen J, Christensen NJ. Enhanced
thermogenic responsiveness during chronic ephedrine treatment in
man. Am J Clin Nutr. 1985 Jul;42(1):83-94. [PubMed]
Tran TM, Friedman J, Baameur F, Knoll BJ, Moore RH, Clark RB.
Characterization of beta2-adrenergic receptor dephosphorylation:
Comparison with the rate of resensitization. Mol Pharmacol. 2007
Jan;71(1):47-60. [PubMed]
Bergman BC, Perreault L, Hunerdosse D, Kerege A, Playdon M,
Samek AM, Eckel RH. Novel and reversible mechanisms of
smoking-induced insulin resistance in humans. Diabetes. 2012
Dec;61(12):3156-66. [PubMed]
Chajek-Shaul T, Scherer G, Barash V, Shiloni E, Caine Y, Stein O,
Stein Y. Metabolic effects of nicotine on human adipose tissue in
organ culture. Clin Investig. 1994 Jan;72(2):94-9. [PubMed]
Xu J, Ji J, Yan XH. Cross-talk between AMPK and mTOR in
regulating energy balance. Crit Rev Food Sci Nutr.
2012;52(5):373-81. [PubMed]
Jessen AB, Toubro S, Astrup A. Effect of chewing gum containing
nicotine and caffeine on energy expenditure and substrate
utilization in men. Am J Clin Nutr. 2003 Jun;77(6):1442-7.
[PubMed]
Perkins KA, Sexton JE, DiMarco A. Acute thermogenic effects of
nicotine and alcohol in healthy male and female smokers. Physiol
Behav. 1996 Jul;60(1):305-9. [PubMed]
Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E,
Pfaff A, Wilkins H, Howard D, Levin ED. Neurology. 2012 Jan
10;78(2):91-101. [PubMed]
Lefkowitz RJ, Pitcher J, Krueger K, Daaka Y. Mechanisms of betaadrenergic receptor desensitization and resensitization. Adv
Pharmacol.1998;42:416-20. [PubMed]
Sears MR. Adverse effects of beta-agonists. J Allergy Clin
Immunol. 2002 Dec;110(6 Suppl):S322-8. [PubMed]
Premont RT.Once and future signaling: G protein-coupled receptor
kinase control of neuronal sensitivity. Neuromolecular Med.
2005;7(1-2):129-47. [PubMed]
Bawa-Khalfe T, Altememi GF, Mandyam CD, Schwarz LA,
Eikenburg DC, Standifer KM.
The presence of beta2adrenoceptors sensitizes alpha2A-adrenoceptors to desensitization
after chronic epinephrine treatment. BMC Pharmacol. 2007 Dec
20;7:16. [PubMed]
Sztalryd C, Hamilton J, Horwitz BA, Johnson P, Kraemer FB.
terations of lipolysis and lipoprotein lipase in chronically nicotinetreated rats. Am J Physiol. 1996 Feb;270(2 Pt 1):E215-23.
Andersson K, Arner P. Systemic nicotine stimulates human adipose
tissue lipolysis through local cholinergic and catecholaminergic
receptors. Int J Obes Relat Metab Disord. 2001 Aug;25(8):122532. [PubMed]
Bergman BC, Perreault L, Hunerdosse D, Kerege A, Playdon M,
Samek AM, Eckel RH. Novel and reversible mechanisms of
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
[Back to Contents]
Page 17
Muscle Strength & Hypertrophy in Chronic Nutrient Timing Studies Compiled by Brad Schoenfeld & Alan Aragon
What follows is an update of the collection of chronic nutrient timing studies first presented in the September 2012 issue of AARR. Two
studies are added, and the chart is not a pasted image file like the previous (its now intrinsically part of this document), so it should be
more clearly visible.
_____________________________________________________________________________________________________
KEY: yellow = significant benefits from timing nutrients near training; no background color = no significant benefits from timing nutrients near training;
blue = total protein (including supplementation) was matched between experimental & placebo/control conditions. Note that the baseline/habitual
protein amounts listed are the average of the groups compared.
Total Protein
intake
habitual or
baseline vs
with supp
Protein
Matched
with
Control?
10 g milk/soy protein
combo consumed
either immediately or 2
hours after exercise
1.05 g/kg
(supplement
increased this
to 1.18 g/kg)
32
untrained
young
men
6% CHO solution, 6 g
EAA mixture, combined
CHO + EAA
supplement or placebo
consumed during
exercise
Cribb and
Hayes,
2006
23 young
recreation
al male
bodybuilders
Willoughby
19
untrained
young
males
Study
Subjects
Supplementation
Esmarck
et al, 2001
13
untrained
elderly
males
Bird et al,
2006
et al, 2007
Measurement
Method
Training Protocol
Strength Results
Body
composition
Results
Yes
MRI and
muscle
biopsy
Progressive resistance
training consisting of
multiple sets of lat
pulldown, leg press
and knee extension
performed 3 days/wk
for 12 wks
Significant
increase in
muscle CSA with
immediate vs.
delayed
supplementation
Not specified,
but a range
was
listed:15% of
9.8-13.7 MJ;
87.8-122.7g.
No
DXA
Progressive resistance
training consisting of 3
sets of 8-10 repetitions
for all the major
muscles performed 2
days/wk for 12 wks
Immediate intake
increased both
dynamic and
isokinetic
Strength, whereas
delayed intake only
improved
dynamic strength.
Immediate pre-post
supplementation
caused greater
increases in 1RM in 2
out of 3 exercises
1 g/kg of a supplement
containing 40 g whey
isolate, 43 g glucose,
and 7 g creatine
monohydrate
consumed either
immediately before and
after exercise, or early
morning & late evening
20 g whey-dominant
protein or 20 g
dextrose consumed 1
hour before and after
exercise
1.01 g/kg
(supplement
increased this
to 2.01 g/kg)
Yes
DXA and
muscle
biopsy
Progressive resistance
training consisting of
exercises for the major
muscle groups
performed 3 days/wk
for 10 wks
Immediate pre-post
supplementation
caused greater
increases in 1RM in 2
out of 3 exercises
2.27 g/kg
(supplement
increased this
to 2.76 g/kg)
No
Hydrostatic
weighing,
muscle
biopsy,
surface
measurements
DXA, CT,
and
muscle
biopsy
Progressive resistance
training consisting of 3
sets of 6-8 repetitions
for all the major
muscles performed 4
days/wk for 10 wks
Protein
supplementation
caused greater
increases in relative
strength (maximal
strength corrected for
bodyweight) in bench
press & leg press
1RM leg press & leg
extension strength
increased, with no
significant difference
between groups
No significant
differences in
muscle CSA
increase
between groups
No significant
differences in
total body mass
or lean body
mass between
groups.
Training produced a
significant increase in
1RM strength both in
the bench press &
squat, no differences
between groups.
Significant
increase in fatfree mass
occurred with
the time-divided
regimen,
whereas no
change was
evident with the
time-focused
regimen.
Verdijk et
al, 2009
28
untrained
elderly
males
10 g casein hydrolysate
or placebo consumed
immediately before and
after exercise
1.1 g/kg
(supplement
increased this
to 1.2 g/kg)
No
Hoffman
et al, 2009
33 welltrained
young
males
1.60 g/kg
(supplement
increased this
to 2.22 g/kg)
Yes
DXA
Burk et al,
2009
13
untrained
young
males
Supplement containing
42 g protein
(milk/collagen blend)
and 2 g carbohydrate
consumed either
immediately before and
after exercise, or early
morning & late evening
Two casein-dominant
protein doses (35 g
each) consumed either
in the morning &
evening away from the
afternoon training bout
- or - consumed in the
morning, and then
again immediately prior
to the resistance
training bout
Placebo
condition
consumed
1.05 g/kg,
protein
condition
consumed
1.37 g/kg
Yes
DXA
Progressive resistance
training consisting of
multiple sets of leg
press and knee
extension performed 3
days/wk for 12 wks
Progressive resistance
training consisting of
3-4 sets of 6-10
repetitions of multiple
exercises for the entire
body peformed 4
days/wk for 10 wks.
Progressive resistance
training consisting of
3-4 sets of 6-10
repetitions of multiple
exercises, each
muscle group trained
2x/wk, totaling 4
days/wk for 8 wks
[Back to Contents]
CHO + EAA
caused the
greatest gains in
fat-free mass
and muscle fiber
CSA relative to
placebo
Significant
increases in lean
body mass and
muscle CSA of
type II fibers in
immediate vs.
delayed
supplementation
Significant
increase in total
body mass, fatfree mass, and
thigh mass with
protein vs. carb
supplementation
Page 18
Hulmi et
al, 2009
31
untrained
young
males
15 g whey isolate or
placebo consumed
immediately before and
after exercise
1.43 g/kg
(supplement
increased this
to 1.53 g/kg)
No
MRI,
muscle
biopsy
Progressive,
periodized total body
resistance training
consisting of 2-5 sets
of 5-20 repetitions
performed 2 days/wk
for 21 wks
Strength increased
similarly in the protein
& placebo group, but
only the protein group
increased isometric
leg extension strength
vs the control group
Wycherly
et al, 2010
34
untrained,
older men
& women
w/type 2
diabetes
Yes
DXA,
waist girth
Progressive resistance
training 8-12
repetitions of multiple
exercises, total
sessions 3 days/wk
for 16 wks
Not measured
Erskine et
al, 2012
33
untrained
young
males
20 g whey protein or
placebo consumed
immediately before and
after exercise
1.35 g/kg
(supplement
increased this
to 1.56 g/kg)
No
MRI
Weisgarber
9
untrained
young
adults (5
men, 4
women)
1.35 g/kg
(supplement
increased this
to 1.56 g/kg)
No
DXA,
ultrasound
No significant
differences in maximal
isometric voluntary
force or 1 RM strength
between groups
No significant
differences in 1 RM
strength increase
between conditions
et al, 2012
Significant
increase in CSA
of the vastus
lateralis but not
of the other
quadriceps
muscles in the
protein group vs
placebo
Fat mass, fatfree mass, and
waist
circumference
decreased with
no significant
differences
between groups
No significant
differences in
muscle CSA
between groups
No significant
differences in
muscle size or
lean mass
increase
2.
3.
4.
5.
6.
7.
8.
Page 19