AlanAragonsResearchReviewJuly,2008[BacktoContents] Page1

Copyright July 1st, 2008 by Alan Aragon

Home: www.alanaragon.com/researchreview
Correspondence: [email protected]





2 Creatine has made its mark, and beta-alanine is
scratching for a piece of the action. By Alan Aragon


7 Essential amino acid and carbohydrate ingestion
prior to resistance exercise does not enhance post-
exercise muscle protein synthesis.
Fujita S, et al. J Appl Physiol. 2008 Jun 5. [Epub ahead of
print] [Medline]

8 Water consumption reduces energy intake at a
breakfast meal in obese older adults.
Davy BM, et al. J Am Diet Assoc. 2008 Jul;108(7):1236-9.
[Medline]


9 The effect of meal replacements high in
glycomacropeptide on weight loss and markers of
cardiovascular disease risk.
Keogh JB, Clifton P. Am J Clin Nutr. 2008 Jun;87(6):1602-
5. [Medline]

10 High-protein-PUFA supplementation, red blood
cell membranes, and plasma antioxidant activity in
volleyball athletes.
Malaguti M, et al. Int J Sport Nutr Exerc Metab. 2008
Jun;18(3):301-12. [Medline]



11 The use of a Cissus quadrangularis/Irvingia
gabonensis combination in the management of
weight loss: a double-blind placebo-controlled
study.
Oben JE, et al. Lipids Health Dis. 2008 Mar 31;7:12.
[Medline]
12 Post-exercise ingestion of a unique, high molecular
weight glucose polymer solution improves
performance during a subsequent bout of cycling
exercise.

Stephens FB, et al. J Sports Sci. 2008 Jan 15;26(2):149-54.
[Medline]



13 Touch it.
Shugart C. June 2008. [Testosterone Nation]

















































AlanAragonsResearchReviewJuly,2008[BacktoContents] Page2

Creatine has made its mark, and beta-alanine is
scratching for a piece of the action. By Alan Aragon

INTRODUCTION

In this article

Ill discuss two supplements that are currently being likened to
eachother creatine, which has a vast history of scientific study
(and substantial support for specific purposes), and beta-alanine,
a rookie touted as a future hall-of-famer. Both naturally occur
within the body, and both give athletes hopes of supernatural
performance. Theyre marketed as the dynamic duo of ergogenic
aids, and consumers are scooping them up like hotcakes. Of
course, this is all great motivation for me to investigate and
provide an objective update on the state of the science. If all
youve read is veiled advertising copy about these compounds,
then prepare for a re-education.

The placebo effect works both ways

All supplements can work as long as belief via the power of
suggestion is in place. The term placebo effect is thrown
around frequently to describe an effect, or degree of effect,
occurring independently or in the absence of the presumed
causal agent. An interesting recent example of the placebo effect
happens to fit perfectly with our topic of sports supplements. In
a parallel-arm design, Beedie et al compared the effects of
positive and negative suggestions on subjects who consumed a
placebo (200 mg cornstarch in a gelatin capsule).
1
In the group
told that the placebo was an ergogenic aid, a trend in increased
sprint speed was seen. In the group given negative information
about the placebo, a statistically significant decrease from the
baseline sprinting speed occurred. This data adds strength to the
hypothesis that our pre-conceptions of a supplements
effectiveness can play a measurable role in their effectiveness or
lack thereof.

CREATINE: EFFECTIVE UNDER SPECIFIC CONDITIONS

Occurring naturally in the body; 95% of the bodys creatine pool
is within skeletal muscle. Creatine works via multiple
mechanisms of action. Its primary effect is an increase in
intramuscular phosphocreatine levels, which acts as a pH buffer
as well as a means to recycle the bodys energy currency, ATP.
In this article, I wont delve into further minutia of supplemental
creatines known and proposed mechanisms. For those details
and other interesting trivia, Ill refer you to one of my favorite
review papers on creatine, which also happens to be available in
full text.
2
Most of you reading this already know that creatine
has numerous studies supporting its effectiveness for repeated
short bouts of high-intensity exercise. As such, creatine has
shown relatively consistent effectiveness for enhancing the
performance of sports such as football, soccer, lacrosse, and with
slightly less consistency sprinting. While creatine generally
has improved dynamic and isotonic peak force (this includes
most activities in the weight room), its effect on isokinetc (fixed
speed) peak force is equivocal, and on isometric (static
contraction) force its effects are insignificant.
3
As well, creatine
for the most part has a weak track record for improving
endurance work.
4-6
However, it cant be blanketly assumed that
creatine is useless for endurance sports, since many are a mix of
intensities. Any type of training that combines brief bursts of
energy output with steady-state endurance work can potentially
benefit from creatine supplementation as long as net weight
gains dont neutralize the effectiveness of the anaerobic
enhancement.

Novel forms of creatine for the edge?

Creatine monohydrate (CM) is the most extensively studied
form of the supplement. Other forms have hit the market,
claiming superiority over monohydrate, complete with the
typical barrage of hype and promises. In a cross-over design,
Jager et al compared the plasma concentration curves of CM,
creatine pyruvate (CP), and tri-creatine citrate (CC) over an 8-
hour post-ingestion period.
7
CP elicited the highest blood
concentrations of the three types, and no differences were seen
in the elevations caused by CC and CM. The investigators
concluded that the small differences in plasma creatine
concentrations would not likely have any effect on the increase
in creatine in muscle, since oral creatine bioavailability is nearly
100%. Recently, studies presented at the 4th International
Society of Sports Nutrition (ISSN) annual meeting furthered the
evidence that special forms of creatine are not worth the extra
bucks.
8,9
Tallon and Child demonstrated that Kre-alkalyn,
touted for its resistance to acid degradation, did not reduce the
rate of creatine conversion to creatinine compared to
commercially available CM. The same researchers showed that
creatine ethyl-ester (CEE), hyped for its greater solubility in
lipids and improved absorption, rapidly degrades into creatinine
in stomach acid compared to commercially available CM, which
remained almost completely unaffected.

Moot points & mass gains

I would also add that the quest for a supercreatine is somewhat
pointless since theres a limit to the amount of creatine that can
be loaded into muscle; a saturation point (approximately 160
mmol/kg dry weight) beyond which any extra ingested is simply
excreted. Tactics such as carbohydrate co-ingestion can speed up
the time to saturation, but it does not ultimately increase the
intracellular capacity to store creatine. This is why the timing of
creatine dosing is a secondary concern unless you have a very
limited timeframe (significantly less than a month) to maximally
utilize creatines effects. In the latter scenario, sandwiching the
training bout with immediate pre- and post-workout creatine
(plus carbohydrate and protein) may be the optimal protocol.
10


Traditional creatine dosing involves a loading phase of 20 g for
5-7 days followed by a maintenance phase of 2-5 g. Lean mass
increases of 1-2 kg have been seen in the first 4-28 days using
this method.
2
However, the same degree of intracellular
phosphocreatine saturation as the high-dose loading phase has
been seen with a linear dose of 2-3g/day for roughly 30 days.
3

Although stories of steroid-like size gains from creatine abound,
AlanAragonsResearchReviewJuly,2008[BacktoContents] Page3

longer trials (~12 weeks) have seen roughly a 2 kg greater lean
mass gain than the non-supplemented group.
2
Aside from an
increase in intramuscular water, increases in the diameter of both
fast-and slow-twitch muscle fibers occur as well.

Non-response, safety

Its important to note that the effectiveness of creatine
supplementation varies widely due to individual differences in
training status (highly trained folks may have elevated levels to
begin with and thus see less of a response). Also, non-
responders can simply be closer to their genetic potential for
size, strength, power, and overall performance. Any additional
attempts at forcing ergogenesis or increased lean mass via non-
pharmacological means will yield little to no results. Add to this
that some individuals have higher levels of dietary creatine
intake than others (primarily via red meat consumption), and
will see less results than those who consume less dietary
creatine. The classic profile of a responder to creatine is
someone who has lower starting levels upon supplementation, a
relatively higher proportion of fast-twitch muscle fibers, and
quite a way to go before reaching genetic limits of size and
strength. Non-responders have the opposite profile. Potential
adverse effects of creatine supplementation center on the
excretion of its metabolites, which is regulated by the kidney.
No adverse effects on kidney structure and function (and other
health parameters) in healthy individuals have thus far been
consistently indicated in short- and long-term studies.
11-13


Competition with caffeine?

Theres only a small amount of data to speculate over, but its
still something to file into the maybes. In the first study showing
this conflict, Vandenberghe et al found that a high dose of
caffeine (5 mg/kg) eliminated the ergogenic effect creatine
supplementation had on isokinetic performance measures, which
included isometric and dynamic strength and fatigability of the
knee extensors.
14
In a subsequent trial by Hespel et al, similar
results were seen in that 3 days of the same caffeine dose (5
mg/kg) increased muscle relaxation time (RT).
15
Since a shorter
RT is important for power production, the lengthening RT can
potentially indicate an increase in fatigue.

Although they provide interesting points to ponder, theres a
couple of notable limitations to these studies. The subjects
abstained from caffeine-containing foods for at least 4 days
before testing, but there was no specification of whether or not
they were habitual caffeine consumers. Caffeines counteractive
effect on creatine may not have occurred to the same degree in
regular users of caffeine, especially if creatine was taken without
any disturbance or lapse in the steady state of caffeine intake.
The latter scenario would more closely represent the real-world
conditions of testing creatines effect during long-standing
caffeine habituation. Also, the small sample sizes (9 participants
in one trial, 10 in the other) leave a lot to be desired in terms of
statistical power.

Another aspect to consider is that both of these trials used lab-
based methods (isokinetic dynamometers) to test the effects of
creatine on force production and fatigue rather than measuring
field-based endpoints such as dynamic and isotonic peak force
such as actual sprint speed/fatigability or various repetition
maximums with free weights (versus fixed-speed isokinetic
machines). Coincidentally, creatine has a history of being hit and
miss with enhancing isokinetic and isometric performance,
3
so
its not too surprising to see caffeine conflict with measures that
creatine hasnt consistently improved in the first place.
Essentially, we need to take it to the field and see what
happens. From an anecdotal standpoint and as any NO-Xplode
bro would attest
16
caffeine and creatine have very little (if any)
conflict in real-world strength, power, or hypertrophy-oriented
training. As with many things, more research is needed to
definitively caution against combining creatine and caffeine. In
fact, an interesting twist of data by Doherty et al indicated that
caffeine was able to increase endurance capacity (time to
exhaustion) despite a 6-day creatine loading phase prior to
testing.
17


BETA-ALANINE: SHOULD ATHLETES JUMP ON IT YET?

To appreciate how it works, a smidge of biochemical
background helps. Carnosine is a di-peptide synthesized from L-
histidine and beta-alanine (BA). Present in high concentrations
in fast-twitch glycolytic fibers as well as nervous tissue,
carnosine is a potent buffer; it neutralizes acidity. BAs
mechanism of action is relatively simple it increases
intramuscular carnosine levels, which act as a buffer against the
accumulation of hydrogen ions (acidity), thus preventing
fatigue. Because of this characteristic, it has been paired with
creatine in tests, presumably for its ability to compliment
creatines short-term power enhancement by filling in the part of
the energy curve where creatines effect diminishes. However,
questions remain of whether this effectiveness is sufficiently
backed by evidence in relevant training situations not to
mention whether or not its relatively safe. The BA industry has
painted it out to be the most significant new breakthrough in
sports supplementation since creatine. Is this hype warranted?
Lets dive into the relevant research.

4-week human performance trials

Take note that this section will be limited to peer-reviewed,
Medline-indexed research. I realize that there are BA study
abstracts that have made their rounds through conferences and
such, but these may or may not make it past peer review and
ultimately into the Medline database. Thus, theres an absence of
12-week studies listed in this article. The current body of BA
research can be divided into shorter-term (~4 weeks) and longer-
term (~10 weeks) studies.

The shorter studies have examined BAs effect on a range of
performance parameters including neuromuscular fatigue,
aerobic power, time-to-exhaustion, and isokinetic measures.
Two of these trials used a combination of BA and creatine, and
demonstrated either equal or further performance benefit when
BA was added.
18,19
In both trials 1.6 g BA was taken 4 times per
day for the first 6 days, then twice a day for the remaining 22
days, along with a typical loading and maintenance dose of
creatine. The other two subsequent short studies used BA as a
sole treatment, and came up with mixed results. Stout et al found
BA ineffective for increasing aerobic power, but it increased
time to exhaustion.
20
Dosing in this study was 3.2g/day for the
first week, and 6.4g/day for the remaining 3 weeks. Derave et al
found that BA improved isokinetic torque but did not improve
isometric endurance or 400 meter race time.
21
Dose began at
2.4g/day and graduated to 4.8g/day by day 8, where it remained
until the end of the trial. In both trials, dosage totals were spread
over 4-6 smaller doses per day. In a more recent trial, Hoffman
et al saw 4.8g BA per day increase the total number of
repetitions throughout trial by 22% over placebo in resistance-
trained men. However, the greater volume of work in the BA
group did not result in greater total body mass, maximal
strength, or peak power.
22


10-week human performance trials

As for the longer (10-week) trials, Hoffman et al examined the
effect of a daily dose of 10.5g creatine plus 3.2 g BA on trained
athletes undergoing a supervised strength training program.
23
As
expected, the creatine-only and creatine plus BA groups
improved maximal strength beyond placebo. Notably, the
greatest improvement in lean mass gain and fat loss occurred in
the BA group. Hill et al investigated a dosing scheme of 4.0g
BA/day that graduated to 6.0g/day over the first 5 weeks of the
trial, and remained at 6.0g/day for the remaining 5 weeks
(divided over 8 doses per day).
24
Subjects were active, but not
trained athletes. BA supplementation significantly increased
total work done on a cycle capacity test. In the most recent
longer-term study, Kendrick et al found no effect of 6.4 g BA
(800mg taken 8 times per day) compared to placebo on any of
the parameters tested (whole body strength, isokinetic force,
high-rep upper-arm curl, body composition).
25

AlanAragonsResearchReviewJuly,2008[BacktoContents] Page4


Side effect & safety issues

Other than perhaps an underweight wallet, BAs most overt side
effect experienced by some but not all individuals is an itchy
histamine reaction (technically called parathesia). Small doses
(400-800mg) might minimize this. According to anecdotal
reports, this prickly sensation occurs within a half hour of
dosing, and can persist for 1-2 hours. The larger the dose, the
more pronounced/prolonged the reaction. The severity of the
response is reduced after roughly 2 weeks of use. The longest
BA trials have not exceeded 3 months, so clearly no long-term
safety data exists. An interesting bit of trivia is that high-dose
BA supplementation was seen to critically deplete taurine levels
in cats, causing brain damage when a dose of 5% of their
drinking water is given over a 20-week period.
26
This translates
to roughly 50 g BA per liter of water consumed, an unlikely dose
for sane humans to consume. Also, BA supplementation hasnt
been seen to affect intramuscular taurine levels in humans.
However, brain biopsies probably wouldnt fly in human trials,
so this question will remain food for thought. So, should athletes
jump on BA supplementation yet? Given the inconsistent results
that beta-alanine has shown, especially in trials using it as a sole
agent, I would rather stand on the sidelines and watch the easily
excitable folks test out the long-term safety and effectiveness of
BA.

There was once a time when creatine was written off by the
medical mainstream as just another scam, but over time, science
proved it safe and effective for its relatively narrow range of use
in athletic pursuits. Will BA find a secure spot on the legit list?
Time will undoubtedly tell, but for now I dont consider it
having yet passed the clutches of needs further scrutiny status.
Given that high-dollar companies such as Abbott Laboratories
(owner of EAS) have their hands in the research on BA, Id say
the chances are better than none that BAs marketability will
continue to flourish. For now, its a matter of watching how the
story unfolds.

Keeping an eye on commerce

A little bit of self-indulgent fun I have with research is following
the money trail. While its true that research has to be funded
somehow, a predominance of industry-sponsored trials in the
world of sports supplements warrants a certain degree of
vigilance. The chart below sums up whos sponsoring the
current body of human performance research on BA
supplementation, as well as an overview of the often
unavoidable tag-teamwork between science and commerce.


































SATELLITE VIEW OF BETA-ALANINE SPONSORSHIP

Study Results Sponsor

Derave, et al.
21
Reduced isokinetic fatigue, Not specified
no effect on sprint speed

Hill, et al.
24
Increased cycling work output NAI

Hoffman, et al.
23
Increased maximal strength, EAS
improved body composition

Hoffman, et al.
22
Increased repetition volume Not specified

Kendrick, et al.
25
No effect on any strength Not specified
parameter tested

Stout, et al.
18
Increased neuromuscular EAS
endurance

Stout, et al.
20
Increased neuromuscular NAI
endurance

Zoeller, et al.
19
Increased aerobic power EAS
and endurance
_

____________________________________________________
EAS = Experimental & Applied Sciences, a supplement company
who sells a beta-alanine-containing product, Phosphagen Elite

NAI = Natural Alternatives, Inc., a supplement manufacturer who
holds the patent on CarnoSyn, their patented beta-alanine
product which it supplies to companies such as EAS

AlanAragonsResearchReviewJuly,2008[BacktoContents] Page5

SUMMARY POINTS

P

lacebo perspective
The term placebo effect describes a degree of effect
occurring independently, or in the absence of the presumed
causal agent.
The placebo effect can work both ways, depending upon
whether a persons perception (via suggestion) of a given
supplement is positive or negative.

C

reatine
Creatine has numerous studies supporting its effectiveness
for repeated short bouts of high-intensity exercise.
Training that combines brief bursts of energy output with
steady-state work can benefit from creatine as long as net
weight gains dont neutralize the ergogenic effect.
Novel forms of creatine have thus far failed to show any
significant advantage over creatine monohydrate (CM).
Tactics such as carbohydrate co-ingestion and timing near
training can speed up the time to saturation, but it does not
ultimately increase the intracellular capacity to store creatine.
Traditional creatine dosing involves a loading phase of 20 g
for 5-7 days followed by a maintenance phase of 2-5 g. Lean
mass increases of 1-2 kg have been seen in the first 4-28 days
using this method.
2

However, the same degree of intracellular phosphocreatine
saturation as the high-dose loading phase has been seen with
a linear dose of 2-3g/day for roughly 30 days.
The classic profile of a responder to creatine is someone
who has lower starting levels upon supplementation, a
relatively higher proportion of fast-twitch muscle fibers, and
is far from the genetic limits of size and strength. Non-
responders have the opposite profile.
No adverse effects on kidney structure and function (and
other health parameters) in healthy individuals have thus far
been consistently seen in short- and long-term studies.
A scant number of trials have raised concerns over caffeines
ability to nullify the ergogenic effect of creatine.
Although this is speculative, caffeines counteractive effect
may not have occurred to the same degree in regular users of
caffeine, especially if creatine was taken without any lapse in
the steady state of caffeine intake. More study is needed.

Beta-alanine

4-week trials using a combination of BA and CM have for
the most part shown positive effects of BA beyond CM alone
for delaying fatigue and increasing work volume.
4-week trials using BA as a sole treatment (without CM)
have come up with mixed results. Time-to-exhaustion is
increased, but aerobic power, maximal strength, and sprinting
time is unaffected.
A longer-term (10-week) trial combining BA and CM has
shown positive effects of BA beyond CM alone for
increasing maximal strength.
10-week trials using BA alone have yielded mixed results,
with one study failing to show any improvements in all the
parameters tested (both lab and field tests), while another
study showing an increase in total work output.
Total daily dosage range is roughly 4-6 g, divided over 4-8
mini-doses throughout the day.
BAs most overt side effect experienced by some but not all
individuals is an itchy histamine reaction (technically called
parathesia). Small doses (400-800mg) can help minimize this.
Given that high-dollar companies have their hands in the
research on BA, chances are that BAs marketability will
continue to flourish. For now, its a matter of watching how
the story unfolds.
BA may indeed prove to be a legitimate agent for improving
endurance capacity. But given the mixed results BA has
shown thus far, I would rather watch the easily excitable
folks test out its long-term safety and effectiveness.


REFERENCES

1. Beedie CJ, et al. Positive and negative placebo effects
resulting from the deceptive administration of an ergogenic
aid. Int J Sport Nutr Exerc Metab. 2007 Jun;17(3):259-69.
[Medline]
2. Persky AM, Brazeau GA. Clinical pharmacology of the
dietary supplement creatine monohydrate. Pharmacol Rev.
2001 Jun;53(2):161-76. [Medline]
3. Bemden MG, Lamont HS. Creatine supplementation and
exercise performance: recent findings. Sports Med.
2005;35(2):107-25. [Medline]
4. Balsom PD, et al. Creatine supplementation per se does not
enhance endurance exercise performance. Acta Physiol
Scand. 1993 Dec;149(4):521-3. [Medline]
5. Jones AM, et al. Effect of creatine supplementation on
oxygen uptake kinetics during submaximal cycle exercise. J
Appl Physiol. 2002 Jun;92(6):2571-7. [Medline]
6. Reardon TF, et al. Creatine supplementation does not
enhance submaximal aerobic training adaptations in healthy
young men and women. Eur J Appl Physiol. 2006
Oct;98(3):234-41. [Medline]
7. Jager R, et al. Comparison of new forms of creatine in
raising plasma creatine levels. J Int Soc Sports Nutr. 2007
Nov 12;4:17. [Medline]
8. Tallon MJ, Child R. Kre-alkalyn supplementation has no
beneficial effect on creatine-to-creatinine conversion rates.
Presented at the the 4th International Society of Sports
Nutrition (ISSN) annual meeting. [CR Technologies]
9. Child R, Tallon MJ. Creatine ethyl ester rapidly degrades to
creatinine in stomach acid. Presented at the the 4th
International Society of Sports Nutrition (ISSN) annual
meeting. [CR Technologies]
10. Cribb PJ, Hayes A. Effects of supplement timing and
resistance exercise on skeletal muscle hypertrophy. Med Sci
Sports Exerc. 2006 Nov;38(11):1918-25. [Medline]
11. Poortmans JR, Francaux M. Long-term oral creatine
supplementation does not impair renal function in healthy
athletes. Med Sci Sports Exerc. 1999 Aug;31(8):1108-10.
[Medline]
12. Mayhew DL, et al. Effects of long-term creatine
supplementation on liver and kidney functions in American
AlanAragonsResearchReviewJuly,2008[BacktoContents] Page6

college football players. Int J Sport Nutr Exerc Metab. 2002
Dec;12(4):453-60. [Medline]
13. Kreider RB, et al. Long-term creatine supplementation does
not significantly affect clinical markers of health in athletes.
Mol Cell Biochem. 2003 Feb;244(1-2):95-104. [Medline]
14. Vandenberghe K, et al. Caffeine counteracts the ergogenic
action of muscle creatine loading. J Appl Physiol. 1996
Feb;80(2):452-7. [Medline]
15. Hespel P, et al. Opposite actions of caffeine and creatine on
muscle relaxation time in humans. J Appl Physiol. 2002
Feb;92(2):513-8. [Medline]
16. For those of you just making your way into the inner circle,
I take civil stabs at bros whenever possible.
17. Doherty M, et al. Caffeine is ergogenic after
supplementation of oral creatine monohydrate. Med Sci
Sports Exerc. 2002 Nov;34(11):1785-92. [Medline]
18. Stout JR, et al. Effects of twenty-eight days of beta-alanine
and creatine monohydrate supplementation on the physical
working capacity at neuromuscular fatigue threshold. J
Strength Cond Res. 2006 Nov;20(4):928-31. [Medline]
19. Zoeller RF, et al. Effects of 28 days of beta-alanine and
creatine monohydrate supplementation on aerobic power,
ventilatory and lactate thresholds, and time to exhaustion.
Amino Acids. 2007 Sep;33(3):505-10. [Medline]
20. Stout JR, et al. Effects of beta-alanine supplementation on
the onset of neuromuscular fatigue and ventilatory threshold
in women. Amino Acids. 2007;32(3):381-6. [Medline]
21. Derave W, et al. beta-Alanine supplementation augments
muscle carnosine content and attenuates fatigue during
repeated isokinetic contraction bouts in trained sprinters. J
Appl Physiol. 2007 Nov;103(5):1736-43. [Medline]
22. Hoffman J, et al. beta-Alanine and the Hormonal Response
to Exercise. Int J Sports Med. 2008 Jun 11. [Medline]
23. Hoffman J, et al. Effect of creatine and beta-alanine
supplementation on performance and endocrine responses in
strength/power athletes. Int J Sport Nutr Exerc Metab. 2006
Aug;16(4):430-46. [Medline]
24. Hill CA, et al. Influence of beta-alanine supplementation on
skeletal muscle carnosine concentrations and high intensity
cycling capacity. Amino Acids. 2007 Feb;32(2):225-33.
[Medline]
25. Kendrick IP, et al. The effects of 10 weeks of resistance
training combined with beta-alanine supplementation on
whole body strength, force production, muscular endurance
and body composition. Amino Acids. 2008 May;34(4):547-
54. [Medline]
26. Lu P. Et al. Dietary beta-alanine results in taurine depletion
and cerebellar damage in adult cats. J Neurosci Res. 1996
Jan 1;43(1):112-9. [Medline]








































































AlanAragonsResearchReviewJuly,2008[BacktoContents] Page7

Essential amino acid and carbohydrate ingestion prior
to resistance exercise does not enhance post-exercise
uscle protein synthesis. m

Fujita S, et al. J Appl Physiol. 2008 Jun 5. [Epub ahead of print]
Medline [ ]

PURPOSE: To investigate the effect that EAA+CHO ingestion
prior

to a bout of resistance exercise on muscle fractional
synthetic rate (FSR) during post-exercise recovery.
METHODS: 22 young

healthy subjects were studied before,
during, and for 2 hr following a bout

of high-intensity leg
resistance exercise. The fasting control

group (FC) did not ingest
nutrients and the EAA+CHO group ingested a solution of
EAA+CHO 1 hr prior to beginning

the exercise bout. Stable
isotopic methods were used in combination

with muscle biopsies
to determine FSR. Immunoblotting procedures

were utilized to
assess cell signaling proteins associated with

the regulation of
FSR. RESULTS: Muscle FSR increased in

the EAA+CHO
group immediately following EAA+CHO ingestion,

returned to
basal values during exercise, and remained unchanged

at 1 hr
post-exercise. Muscle FSR decreased in FC

during exercise and
increased at 1 hr post-exercise.

However, the 2 hr post-exercise
FSR increased by ~50% in both

groups with no differences
between groups. Eukaryotic

elongation factor 2 phosphorylation
was reduced in both groups 2 hrs post-exercise (EAA+CHO:
39%; FC: 47%). CONCLUSION: EAA+CHO ingestion prior to
resistance exercise does not enhance post-exercise FSR as
compared to exercise without nutrients. SPONSORSHIP:
National Institute for Arthritis and Musculoskeletal and Skin
Diseases, National Institutes on Aging, and National Center for
Research Resources.

S

tudy strengths
Pre-test diet was well controlled; each subject was admitted to
the lab the day prior to the exercise study. The subjects were fed
a standard dinner, and a snack at a standardized point before
undergoing the pre-test overnight fast. Dose of the substrates
were proportional to the subjects fat-free mass (FFM) as
determined by DEXA, rather than a flat dose given to all
subjects, as per the norm in similar studies. The EAA dose was
0.35g/kg FFM, carbohydrate (CHO in the form of sucrose) dose
was 0.5g/kg FFM. Novel parameters examined were
immunoblotting and enzyme activity linked to the signaling of
protein synthesis, whereas previous research is for the most part
limited to measuring net protein balance.

S

tudy limitations
This was an acute-effect study rather than a chronic/long-term
study carried out for a period of weeks or months. While its
tempting to extrapolate and draw assumptions based on these
results, chronic trials necessary for more definitive answers. A
articularly odd aspect of this trial was this quote: p

The post-exercise signaling and muscle protein synthesis data
from the Fasting control group have been previously published
and are not included in the results section (9). We have included
previously published Fasting data in all Tables and Figures in
order to provide clear comparisons between groups (9)

Reference 9 in the text is a totally separate trial published in late
2006.
1
The same facility was used, the exercise protocol was
identical, as were the measurement procedures and dietary
control. Still, it strikes me as odd (and pretty much blows it for
me) that the researchers would grab data from a completely
separate trial and superimpose it over the present data as if from
a singular study.

C

omment/application
With the above weirdness aside, this trial produced results
contrary to what the researchers and presumably anyone
would have predicted without examining the small details. Based
on the average FFM of the subjects, 18.1g EAA and 25.8g CHO
was ingested. This EAA dose is greater than the amount used in
the famous Tipton trial, that showed the benefit of a much lower
dose of EAA (6g EAA plus 35g sucrose) taken immediately
preworkout, compared to the same taken immediately
postworkout.
2
Tipton speculated that providing amino acids
during a time of elevated blood flow via exercise enhanced the
substrate delivery to the muscles. In the present trial which saw
no protein-synthetic benefit of the preworkout substrates
compared to fasting conditions, a couple of key aspects (other
than dosage) differed from the Tipton trial. First off, the
substrates were ingested an hour preworkout, as opposed to
immediately preworkout in Tiptons. This might not be an
optimal timing strategy for EAA, whose plasma appearance
curve is much sharper and more temporary than that of whole
protein. Secondly, blood flow during exercise was 44% greater
in Tiptons trial (19.4 versus 13.4 ml/min), which also may have
contributed to its positive results for the preworkout treatment.
The reason for more blood flow is apparent when comparing the
exercise protocols. Tiptons was 10 sets of 8 reps at 80% of
1RM, 2 minutes rest between sets. The present studys was 10
ets of 10 reps at 70% of 1RM, 3 minutes rest between sets. s

Another important difference between the present trial and
Tiptons (again, mainly affected by the timing difference), was a
better-timed insulin response. Tiptons protocol caused
markedly greater insulin elevations during, and at both the 1
hour and 2 hour points postexercise compared to the present
trial. See the chart below comparing the EAA+CHO treatments:







Insulin (U/mL) pre, during, and postexercise

Study 1hr Pre Imm. Pre During 1h Post 2hrs Post


Tipton et al. N/A 79.0 18.5 22.0 6.2
Fujita et al. 20.5 N/A 12.3 7.4 4.6
In 2004, Greehaff et al demonstrated that when plasma amino
acids are kept elevated, insulins ability to suppress protein
breakdown appears to be maximal at 15 U/mL.
3
Notice above
that the postexercise insulin concentrations in the present study
were not only much less than Tiptons (especially 1 hr post), but
at no point postexercise did they reach concentrations that were
much above fasting levels, let alone near or beyond the point of
maximal inhibition of protein breakdown.
Water consumption reduces energy intake at a breakfast
meal in obese older adults.

Davy BM, et al. J Am Diet Assoc. 2008 Jul;108(7):1236-9.
[Medline]

PURPOSE: to determine whether premeal water consumption
reduces meal energy intake in overweight and obese older
adults. METHODS: Twenty-four overweight and obese adults
(body mass index=34.3), mean age 61.3 years, were given an ad
libitum standardized breakfast meal on two randomly assigned
occasions. Thirty minutes before the meal, subjects were given
either a 500-mL water preload or no preload. Energy intake at
each meal was covertly measured. RESULTS: Meal energy
intake was significantly less in the water preload condition as
compared with the no-preload condition (500 vs 574,
respectively, representing an approximate 13% reduction in meal
energy intake. The percentage reduction in meal energy intake
following the water preload was not related to sex, age, body
mass index, or habitual daily water consumption.
CONCLUSION: Given the high prevalence of overweight and
obesity among older adults, future studies should determine
whether premeal water consumption is an effective long-term
weight control strategy for older adults. SPONSORSHIP:
Institute for Public Health and Water Research

Study strengths

Participants were screened to exclude eating disorders or
depression. Premeal water consumptions effect on energy
intake at breakfast instead of lunch or dinner was done to avoid
the potential influence of differences in food intake earlier in the
day on test meal energy intake. Meals were served in individual
cubicles, under standardized laboratory conditions. This
eliminated social and other distractions that could have
influenced food intake. Foods were covertly weighed to the
nearest tenth of a gram, before being served, and again after the
completion of the meal to determine the amount consumed.
Meal energy intake was calculated using current nutritional
analysis software. The researchers also investigated habitual
water and total beverage consumption patterns of each subject to
determine if any of the patterns were associated with the test
meal results.

Study limitations

Although subjects were instructed on how to accurately record
their food and beverage intake, the fact that they were
responsible for this presents inherent inaccuracy. Since the
subjects were obese, they stand a greater chance of
underreporting their intake than normal-weight subject would. In
fact, research by Lichtman et al showed that obese subjects
underreported their dietary intake by an average of 47%.
4
The
degree of coaching/supervision to ascertain the participants
accuracy throughout the trial was not explicitly described. The
saving grace here is that this wasnt a heterogeneous sample, so
at least one can assume that the tendency to underreport intake
would be uniform.
AlanAragonsResearchReviewJuly,2008[BacktoContents] Page8


Comment/application

This study is interesting from the standpoint that much of the
dieting population is more attracted to following simple/general
guidelines rather than sticking strictly to a very specific,
complex regimen. In this case, drinking a couple of glasses
of water (500 mL, about 16 oz) a half-hour before breakfast lead
to a 13% reduction in energy intake of the test meal. This
translated to roughly 74 kcal less in the water preload treatment.
The authors suspect that delayed gastric emptying contributed to
satiety and thus reduced intake.

Interestingly, the caloric reduction was not associated with sex,
classification of overweight vs obese, age, body mass index, or
habitual fluid intake. This means that downing 2 cups of water
30 minutes prior to breakfast is likely to be a universal tactic for
reducing calories at that meal, at least for people fitting the
profile of this sample (older, overweight/obese). In a previous
study with the same protocol used on nonobese adults, these
investigators saw a 60 kcal reduction in breakfast intake after a
water preload.
5
Notably, the younger adults in that trial (21-
35yrs vs 60-80yrs) didnt exhibit a decreased caloric intake in
spite of the water preload. However, the age-dependent effect in
normal-weight folks is less relevant than the results of the
present trial on the overweight and obese.

The million-dollar question now is whether or not these acute
results can be applied across a chronic period where the ultimate
variable body composition flux can be detected. Its possible
that energy intake reduction may diminish over time as subjects
become adapted to the water preload. Its also not impossible
that the water preload could lead to a progressive reduction in
caloric intake via progressive decreases in stomach capacity
causing progressively sooner satiety signals. For those unaware,
reduction in stomach capacity by dieting (non-surgical) means is
not an urban myth. Geliebter et al saw a 27-36% reduction in
stomach capacity in obsess subjects who lost 9 kg over a 4-week
period on a 600 kcal diet.
6


I find it somewhat humorous that something as simple as water
is being tested as a weight loss supplement, and the implications
are very significant if you extrapolate the results to 3 meals per
day. Lets imagine that an overweight individual used this water
preload tactic 3 times per day. Thats 74 kcal x 3 = 222 kcal
reduction for the day. Per month, thats 6660 kcal, which
translates to roughly 1.9 lbs (0.86 kg) per month, almost for free,
with no harmful side effects. When you compare this
hypothetical treatment to two popular weight loss supplements,
you have to chuckle a little:









3 daily water preloads vs popular weight loss supplements

Compound Monthly weight loss Study


Ephedrine/caffeine 0.88 kg Boozer, et al.
7




Plain H
2
O 0.86 kg Hypothetical
CLA 0.20 kg Whigham, et al.
8



AlanAragonsResearchReviewJuly,2008[BacktoContents] Page9


The effect of meal replacements high in
glycomacropeptide on weight loss and markers of
cardiovascular disease risk.

Keogh JB, Clifton P. Am J Clin Nutr. 2008 Jun;87(6):1602-5.
[Medline]

PURPOSE: To examine whether greater weight loss could be
achieved and sustained with a Glycomacropeptide (GMP)-
enriched whey powder supplement compared with a skim milk
powder supplement. METHODS: In a double-blind,
randomized, parallel-design study using meal replacements,
weight, body composition (determined by dual-energy X-ray
absorptiometry), blood pressure, fasting lipids, glucose, and
insulin were measured at baseline, 6, and 12 mo. Meal
replacements contained 15 g protein from GMP-enriched whey
protein isolate (GMP-WPI) or skim milk powder (SMP) and 900
kJ/sachet. Volunteers consumed 2 sachets/d instead of 2 meals
for 6 mo and 1 sachet/d for a further 6 mo. Of the 127
participants (95 women, 32 men, 95.5 kg, body mass index
33.4kg, 50.0 y), 82 completed the 6-mo study and 72 of those
completed the 12-mo study. RESULTS: At 6 mo, weight loss
was 9.5 kg in GMP-WPI versus 11.0 kg in SMP, and 9.9 kg in
GMP-WPI versus 10.8 kg in SMP at 12 mo with no differences
between treatments. Total and LDL cholesterol, triacylglycerols,
glucose, insulin, and systolic and diastolic blood pressure
decreased at 6 and 12 mo compared with baseline with no
difference between treatments. HDL cholesterol increased at 12
mo compared with baseline. CONCLUSION: Meal
replacements containing GMP had no additional effect on the
overall sustained 12-mo weight loss of 10 kg. There were
improvements in cardiovascular disease risk markers.
SPONSORSHIP: Murray Goulburn Nutritionals, Victoria,
ustralia. A

S

tudy strengths
82 subjects completed the study. This is a large number
compared to the typical sample size in weight loss supplement
research, which typically consists of low double-digit totals with
single-digit treatment arms. Another strength was the 12-month
duration. Body composition was measured via dual-energy X-
ray absorptiometry (DEXA), the gold standard of assessment.
Subjects had a consultation with a dietitian at baseline, 3, and 24
wk and attended the clinic every 4 wk for a weigh-in and to
collect meal replacements. Compliance with taking the
supplements was assessed by a daily checklist and by the
accounting of the empty packets returned. Although food aside
from the meal replacements was the responsibility of the
subjects, the regime was relatively simple and effective for
eight loss (and maintenance of weight loss): w









Study limitations

Incorporating a structured/supervised exercise program would
have been ideal, but with large sample sizes and limited budgets,
this isnt a common occurrence in supplement weight loss
research. Another problem with this study was in a lack of
reporting. It would have been helpful to see a complete
breakdown of macronutritional intake based upon food records
interpreted by dietary analysis software, but this was not the
case. Aside from this, and perhaps the gray area of the self-
reported food intake, this trial was well designed.

Comment/application

This study is yet another example of the vindication of the low-
tech. No differences in blood pressure, lipids, glucose, insulin, or
weight loss. Both groups lost roughly 10kg in 6 months and kept
it off for the remaining 6 months of the study, regardless of the
fortification of glycomacropeptide (GMP) in one of the
treatments. GMP has been observed to stimulate the satiety
hormone CCK, whose mechanism for this purpose is thought to
be a slowing of gastric emptying. Since no differences in weight
loss occurred, the authors speculate that perhaps 27g/day was an
insufficient GMP dose to accomplish the fat loss they previously
observed in rats consuming a much higher dose.
9

In a trial that undoubtedly contributed to the expectations of the
present study, Hall et all showed that a 48g whey protein preload
significantly decreased ad libitum meal intake compared to an
equivalent casein preload.
10
This was contrary to what I would
expect, given the more slowly digested nature of casein. The
whey treatment increased CCK levels by 60% compared to
casein, and this partially explains why the whey treated group
reported less feelings of hunger and greater satiety. More
recently, Bowen et al compared the effect of 4 preloads ( 55g
whey, 55g casein, 56g glucose, and 56g lactose) on subjective
satiety rating, energy intake, CCK, and ghrelin (a hunger-
associated hormone). Inspite of a higher CCK and lower ghrelin
output from the protein preloads compared to the carb preloads,
energy intake did not differ between groups. Contrary to the
speculations of the authors of the present study, Bowen et al did
not find gastric emptying to contribute to appetite control at
least in the short-term confines of the trial. Clearly, this is an
area that needs further investigation with longer trials in order to
raw meaningful conclusions. Right now, its one big hmmm. d

Back to our study Each meal replacer only had 15g protein. At
900 kJ (215 kcal) per packet, This roughly the equivalent of 2
cups of low-fat milk (actually even that has more protein). In the
racy world of fitness and bodybuilding nutrition, meal
replacements have about 3 times more protein than those in the
present trial. Last month I reviewed a study by Arciero et al,
who used meal replacement products by Experimental and
Applied Sciences (EAS).
11
Subjects in that trial lost roughly 6 kg
during a 12 week trial. Apparently, the subjects in the present
trial ate less overall calories, judging from the greater weight
loss they experienced. However, both groups in the present trial
lost lean mass (~2 kg), whereas subjects in the Arciero trial did
not, and its likely due to a lack of protein intake combined with
the absence of a resistance training program. What could easily
be done to alleviate the protein deficiency is substitute one of the
meal replacements with 2-3 scoops (40-60g) of whey.
Volunteers were advised to consume 2 sachets/day to
replace 2 meals and to consume one energy-restricted meal
containing 120 g raw weight meat/fish/chicken. They were
also advised to eat 2 servings (300g) of fruit/day, 2 cups
cooked and 1 serving raw (salad) vegetables/day, 250 mL
reduced-fat milk, and 30 g high-fiber cereal during the day.
Bran or psyllium supplements were recommended to relieve
constipation.
AlanAragonsResearchReviewJuly,2008[BacktoContents] Page10

High-protein-PUFA supplementation, red blood cell
membranes, and plasma antioxidant activity in
volleyball athletes.

Malaguti M, et al. Int J Sport Nutr Exerc Metab. 2008
un;18(3):301-12. [ J Medline]

PURPOSE: To evaluate the role of a high-protein, low-calorie,
polyunsaturated fatty-acid (PUFA)-supplemented diet on
anthropometric parameters, erythrocyte-membrane fatty-acid
composition, and plasma antioxidant defenses of
nonprofessional volleyball athletes. METHODS: The athletes
were divided in two groups: One (n = 5) followed the
Mediterranean diet, and the other (n = 6) followed a high-
protein, low-calorie diet with a 3-g/day fish-oil supplementation.
All the athletes had anthropometric measurements taken, both at
the beginning and at the end of the study, which lasted for 2
months. RESULTS: Body-mass index and total body fat were
significantly diminished in the second group, while they
remained unchanged in the first. Plasma total antioxidant activity
(TAA) was significantly increased in the plasma of both groups,
with no differences between the groups, suggesting that physical
activity, not the different diets, is the main contributor to the
increase of plasma TAA. The second group showed a significant
increase in erythrocyte-membrane PUFA content and in the
unsaturation index value (UI) because of the fish-oil
supplementation. CONCLUSION: A high-protein, low-
carbohydrate, fish-oil-supplemented diet seems to be useful only
when the aim of the diet is to obtain weight loss in a short-term
period. The significant increase in the UI of erythrocyte
membranes indicates the potential for harm, because a high
intake of PUFA might increase susceptibility to lipid
peroxidation not counterbalanced by a higher increase in TAA.
Adherence to the Mediterranean diet seems to be the better
choice. SPONSORSHIP: Not specified.

Study strengths

Something Ive grown to appreciate through reading countless
studies is the ability of the investigators to not just report and
interpret the results of the experiment, but also describe the
background/basis of the question, including an overview of the
related literature. This trial does a thorough job of this.
Furthermore, the content is engaging because the authors seem
to have a subtle flair for attacking the pop diet book The Zone.
Although diet was not lab-provided (it rarely is), the subjects
filled out a validated food frequency questionnaire at 3 points
during the study in addition to daily detailed food records.
Subjects were given pictures of food servings in order to develop
the skill of recognizing proper portion sizes. Finally, although
they werent professional or specifically described as highly
trained, the subjects were competitive athletes as opposed to
couch potatoes, who as a population only reflect one or two of
the AARR readership.

Study limitations

The sample size was small: 5 participants in the lower carb
group, and 6 in the Mediterranean diet group. This makes for
what statisticians would regard as grossly underpowered, and
thus prone to not being sensitive enough to detect small but
clinically meaningful differences (but as well see, it turns out
that a few differences were indeed detected). Another limitation
was the use of calipers (biceps, triceps, subscapular, and
suprailiac skinfolds) to measure bodyfat percent. While a given
technician can be quite skilled at the caliper technique, theres
still a certain unavoidable margin of human error that could have
been reduced with a hands-off method such as hydrostatic
weighing, air displacement plesythmography (Bod Pod), and
certainly DEXA. Its rare to see calipers used in recent studies,
o I was surprised to see these researchers stuck in a time warp. s

Comment/application

Fish oil has been repeatedly praised as the must-use supplement
by both authoritative and unauthoritative sources for a good part
of the last decade, during which time an abundance of positive
fish oil research has surfaced. However, Ive remained skeptical
and perhaps overly careful about recommending anything
beyond 6g of normally concentrated fish oil (about 30% EPA &
DHA content) for most healthy individuals who dont regularly
consume fish. In some clinical cases more is warranted, but in
most cases, it isnt. Last months issue discussed the potential
adverse oxidative effects of overconsuming eggs fortified with
omega-3 fatty polyunsaturated fatty acids (n-3 PUFA) cooked
under high heat. The present study is one of the minority of
studies that show a potential downside that clicks with one of my
eservations about indiscriminate fish oil supplementation. r

The authors acknowledge that n-3 PUFA consumption has been
shown to reduce triacylglycerol, have anti-inflammatory effects,
improve glucose and insulin metabolism, and reduce risk of
cancer and cardiovascular disease. However, they also point out
that their greater number of double bonds leaves them more
vulnerable to oxidation. This opens up the possibility for an
actual reduction in antioxidant capacity and increased depletion
of antioxidants in the body. Contrary to this concern,
Thorlaksdottir et al recently found a positive correlation between
plasma antioxidant capacity and n-3 PUFA in red blood cells,
and a negative correlation between antioxidant capacity and n-6
PUFA.
12
But as always, correlational research should be
cautiously interpreted due to its lack of control of many
variables. In contrast to the latter study, Yaqoob et al found that
daily supplementation of 3.2g (9 capsules) fish oil-derived
EPA/DHA had no effect on total antioxidant activity.
13
In the
present study, 3g fish oil containing an 86% EPA/DHA
concentration caused a significant increase in the unsaturation
index (UI) of the red blood cells of the athletes which raised
concerns that, following the high-protein fish-oil-supplemented
diet also indicates the potential for harm, because a high intake
f DHA might increase susceptibility to lipid peroxidation. o

Although the authors conclude that the high-protein, low-
carbohydrate diets seem to be useful only when the aim is to lose
weight in a short-term period, they failed to discuss the impact
of the caloric treatment imbalance on the results. The higher-
protein, fish oil-supplemented group consumed a diet composed
of 40% carbohydrate, 30% protein 30% fat, and a total of 2,450
kcal. The Mediterranean diet group consumed 55%
carbohydrate, 15% protein, and 30% fat, and a total of 2,450
kcal per day. This 300 kcal difference would explain the 1-point
drop in BMI in the high-protein fish oil group compared to the
Mediterranean group, whose BMI didnt budge.


AlanAragonsResearchReviewJuly,2008[BacktoContents] Page11

The use of a Cissus quadrangularis/Irvingia
gabonensis combination in the management of weight
loss: a double-blind placebo-controlled study.

Oben JE, et al. Lipids Health Dis. 2008 Mar 31;7:12. [Medline]

PURPOSE: To evaluate the effects of two formulations, Cissus
quadrangularis-only and a Cissus quadrangularis/Irvingia
gabonensis combination, on weight loss in overweight and obese
human subjects. METHODS: 10 week randomized, double-
blind, placebo-controlled design involving 72 obese or
overweight participants (45.8% male; 54.2% female; ages 21-44;
mean age = 29.3). The participants were divided into three equal
groups: placebo, Cissus quadrangularis-only, and Cissus
quadrangularis/Irvingia gabonensis combination. Capsules
containing the placebo or active formulations were administered
twice daily before meals; no major dietary changes nor exercises
were suggested during the study. A total of six measurements
(body weight, body fat, waist size; total plasma cholesterol, LDL
cholesterol, fasting blood glucose level) were taken at baseline
and at 4, 8, and 10 weeks. RESULTS: Compared to the placebo
group, the two active groups showed a statistically significant
difference on all six variables by week 10. The magnitude of the
differences was noticeable by week 4 and continued to increase
over the trial period. CONCLUSION: Although the Cissus
quadrangularis-only group showed significant reductions on all
variables compared to the placebo group, the Cissus
quadrangularis/Irvingia gabonensis combination resulted in even
arger reductions. SPONSORSHIP: Not specified. l

S

tudy strengths
The sample size (72 subjects total, 24 per treatment arm) was
relatively large for a non-pharmacological intervention. Subjects
were examined once a week for a fairly wide range of
assessments including body weight, percent body fat, and waist
circumference, subjective impressions of well-being.

S

tudy limitations
There wasnt the slightest attempt made to control or assess
dietary factors, which is a big minus in a weight loss supplement
trial. Bio-electrical impedance analysis (BIA) as used measure
for body composition. This method is subject to error based on
hydration flux. Optimally, DEXA should have been used, or at
the very least, hydrostatic weighing.

C

omment/application
I was alerted to this study by an AARR subscriber (his alias is
Conciliator on the forums). Shortly after the abstract of this
trial was posted in the Supplement Science subforum of
bodybuilding.com, he found a few fishy details surrounding this
study and thought it would be interesting to expose them. Of
course I jumped at the chance. The studys principal
investigator, Julius Oben, is also the Chief Scientific Officer of
Gateway Health Alliances Inc., based in Fairfield, California.
Furthermore, Oben holds the patent on the use of supplement
formulations containing Cissus quadrangularis (CQ) as a weight
loss aid, and the assignee is none other than Gateway Health
Alliances, Inc. Heres the link to the official record, which was
filed in August of 2000, outlining each of the claims made for
his invention. Here are the key claims of United States patent
7175859: #














The invention claimed is:

1. A method of promoting weight loss in a mammal in need
thereof comprising: providing a composition containing an
aqueous extract of stems or leaves or stems and leaves of
one or more Cissus quandragularis plants to promote weight
loss; wherein the composition provided is administered to
the mammal to promote weight loss.

9. The method of claim 1, wherein the composition
promotes weight loss by providing one or more benefits
selected from the group consisting of: (a) reducing fats
adsorbed by the body, (b) increasing fat in the feces, and
(c) reducing carbohydrate breakdown.

The proposed mechanisms in claim #9 have for the most part
failed to materialize in the literature thus far. For example, a
systematic review on chitosan (a purported fat blocker)
determined that weight loss results in high-quality trials have
been minimal and unlikely to be of any clinical significance.
14

As for carb-blockers, white kidney bean extract (phaseolus
vulgaris - PV) has had its 15 minutes of lackluster in the
scientific literature as well, but research is ongoing. PVs
mechanism is the inhibition of alpha-amylase, which breaks
down carbohydrate, making its calories usable by the body. Its
generally present in supplements that are a proprietary blend of
other ingredients, so its difficult to determine its specific
contribution to study results. In general, shotgun cocktails of
supposed fat-burning ingredients end up being overpriced
caffeine supplements. Thus far, the bulk of the research on PV-
containing supplements shows no statistically significant effects
on weight loss,
15,16
with the exception of perhaps a single recent
study published in a recently established open-access online
journal that will accept studies from any corner of the planet for
a $1200 publication fee.
17
Unsurprisingly, most if not all of the
research is industry-funded, and dietary control is minimal to
onexistent. n
In the present study, the authors
mention Cylaris (a CQ-based
product branded by Gateway
Health Alliances, Inc.) as an
example of combining different
phyto- ingredients for a potential
synergistic effect. In this case,
the heightened weight loss effect
is due to the combining of CQ
with Irvingia gabonensis (IG),
the other component tested. As it
turns out, the combination of
CQ and IG caused the greatest
weight loss among the treatments. I smell a new diet product
ooking, do you? To quote Conciliator, c

This doesn't mean that Oben's research is necessarily bogus,
but can you tell me why an American corporation is having an
obscure university in a poor West African country do the
research on their products, while simultaneously employing the
lead researcher? Smells like bad fish to me.
AlanAragonsResearchReviewJuly,2008[BacktoContents] Page12

Post-exercise ingestion of a unique, high molecular
weight glucose polymer solution improves performance
during a subsequent bout of cycling exercise

Stephens FB, et al. J Sports Sci. 2008 Jan 15;26(2):149-54.
[Medline]

PURPOSE: To determine the effect of post-exercise ingestion
of a unique, high molecular weight glucose polymer solution,
known to augment gastric emptying and post-exercise muscle
glycogen re-synthesis, on performance during a subsequent bout
of intense exercise. METHODS: On three randomized visits, 8
healthy men cycled to exhaustion at 73.0% (s = 1.3) maximal
oxygen uptake (90 min, s = 15). Immediately after this,
participants consumed a 1-L solution containing sugar-free
flavored water (control), 100 g of a low molecular weight
glucose polymer (LMW) or 100 g of a very high molecular
weight glucose polymer (HMW), and rested on a bed for 2 h.
After recovery, a 15-min time-trial was performed on a cycle
ergometer, during which work output was determined.
RESULTS: Postexercise HMW resulted in faster and greater
increases in blood glucose and serum insulin concentrations than
LMW, and greater work output during the 15-min time-trial
(164.1 kJ, s = 21.1) than both the sugar-free flavoured water
(137.5 kJ, s = 24.2; P < 0.05) and the low molecular weight
glucose polymer (149.4 kJ, s = 21.8; P < 0.05) solutions.
CONCLUSION: These findings could be of practical
importance for athletes requiring rapid re-synthesis of the
muscle glycogen store during recovery following prolonged sub-
aximal exercise. SPONSORSHIP: Not specified. m

S

tudy strengths
The small sample size (8 subjects) was somewhat alleviated by
having each subject take all 3 tests on randomized occasions
separated by at least one week. An endurance performance time-
trial was completed after a glycogen depletion protocol (cycling
to the point of exhaustion at 75% of VO
2
max, and depleting any
remaining glycogen by repeating a work rest protocol until no
longer able to maintain a pedal frequency of 70 revolutions per
minute for more than more than 2 min). The importance of doing
exercise performance (maximal amount of work possible in a
fixed duration in this case 15 minutes) instead of measuring
time to exhaustion is that the former better resembles real-life
racing. On the track, its not a matter of who can keep going the
ngest distance, its who can make it to the finishing line first. lo

Stu

dy limitations
Doing the tests first thing in the morning is necessary to
eliminate the confounding influence of previous meals.
However, this limits the applicability of the results to trainees
who train first thing in the morning. Those who train later in the
day after a few meals will be within varying degrees of the fed
state, and might not necessarily benefit. Another limitation was
the 2-hour duration between glycogen depletion and
performance testing. This is not to say that some competitive
athletes dont have to perform to exhaustion within 2 hours after
depletion, but these results may not apply to those who have
ignificantly longer recovery intervals at their disposal. s

C

omment/application
This is the first study comparing the performance effect of high-
molecular weight carbohydrate (HMW) with low-molecular
weight carbohydrate (LMW). Previous research has found that
the speed of gastric emptying and glycogen resynthesis is
significantly faster with HMW. In fact, Piehl-Aulin et al saw
muscle glycogen synthesis rates after glycogen depletion were
70% greater over 2 hours (50 vs. 30 mmol/kg/hr) compared with
a commercially available solution glucose and glucose polymers
with a lower molecular weight.
18
Heres an interesting bit of
trivia this isnt the fastest rate of glycogen resynthesis ever
recorded. Recently, Pederson et al showed that after glycogen
depletion, a single high dose of caffeine (8mg/kg) along with a
carbohydrate intake totaling 4g/kg by the end of a 4 hour
recovery period resulted in the fastest rate of glycogen synthesis
ever recorded in orally administered conditions in humans: 60
mmol/kg/hr, as opposed to 50 mmol/kg/hr seen in the present
trial. The all-time highest rate was accomplished via a mixed bag
of carbohydrate sources (bars, gels and sports drinks). This is not
to say that an even higher rate could be achieved with HMW
arbs plus caffeine, but this is yet to be demonstrated. c

Glucose in the HMW treatment peaked at 8.1 mmol/L at 30
minutes, and LMW peaked at 7.3 mmol/L at 50 minutes after
ingesting a 1 liter solution containing 100g of either
carbohydrate type. Insulin peaked at 80.6 U/mL 70 minutes
after ingesting HMW, and it peaked at 68.7 U/mL at 40
minutes after ingesting LMW. In contrast to the results seen
here, previous research by Piehl-Aulin et al saw no differences
in glucose and insulin response when comparing HMW with
LMW, and there are a few plausible explanations. This likely
due to a number of distinct differences in the testing methods.
First of all, the present study used arterialized-veinous sampling,
which is a more sensitive method that the veinous sampling used
by Piehl-Aulins team. Secondly, the present study had a higher
frequency of blood sampling (every 10 minutes in the present
trial vs every 30 minutes), Finally, its possible that the subject
in the earlier study had large variations in glucose and insulin
response, that when combined with the repeated feeding bouts
post-depletion (every 30 minutes), made it difficult for them to
accurately track the glucose and insulin curves. In the present
study which used a more accurate technique and less
confounding variables, peak glucose levels in HMW was 10%
igher than LMW, and occurred 20 minutes sooner. h

The HMW carb source used in this study was Vitargo (a waxy
maize starch-derived product by Swecarb), which is a very high-
molecular weight glucose polymer. Its counterpart in this trial
was Maxijul (by SHS Intl), the equivalent of maltodextrin in
terms of molecular weight and metabolic behavior. The HMW
group had 10% greater work output than the LMW group during
the 15-minute time trial, and furthermore, an increase in
performance was seen in every subject. Given these results,
HMW carbohydrate such as those derived from waxy maize
starch might be worth a try for athletes with multiple glycogen
depletion bouts in a single day. For all other cases, its just an
empty-calorie carb source that offers no advantage over other
sources, since complete glycogen resynthesis will happen within
24 hours after depletion, regardless of carb source or presence of
other macronutrients even large amounts of fat.
19, 20



AlanAragonsResearchReviewJuly,2008[BacktoContents] Page13

Editors note for those of you who might open this at work or
in the presence of your mother-in-law, please be warned that
theres barely-clad models in the Testosterone Nation link.

Touch it.
Shugart C. June 2008. [Testosterone Nation]

Okay, lets begin by thanking AARR member Ryan Z for
alerting me to this article. And by the way, those of you who
come across anything you want me to discuss in the Lay Press
section or any other section for that matter dont hesitate to
send me the link at [email protected].

As of this writing, I have no idea who Chris is. I know that he
writes for T-Nation (thanks to bodyrecomposition.com). I have
no idea what he does for a living or what hes accomplished in
this field. Im simply gonna free-flow my thoughts strictly on the
content of this article. And Ill be as civil as possible.















I guess this puts part of our philosophies at odds right off the bat.
Ive NEVER liked the idea of touching a hot stove. While I
believe that experience is valuable, I also think that experience
can screw you up good. I have a tendency to be overly careful
and analytical. While I realize the potential disadvantages of it, I
also dont get burned a whole lot. No sizzling flesh, no glory? I
wouldnt know; maybe Chris will inspire me to explore my
adventurous side!











I can see how the stove-touching concept can apply to program
adjustments that dont necessarily have acute/adverse
consequences. However, I would caution anyone whos been
living in one extreme of either low- or high-carb for a lengthy
period to avoid a 180-degree turn right off the bat. I would take
things incrementally, or at least institute a transitional period,
however brief. This sensible bit of caution will allow the
necessary adaptations to occur in order to avoid misery, rebound,
nd general failure. a












I'm not against doing some reading and research, but I
believe that everyone is different. Or more accurately, there
are at least two different types of people that fit into each
concept. Genetics, hormonal predispositions, environmental
factors, muscle fiber types, natural enzymes, etc. etc. make
us all respond differently.

Some can build their chests with bench press only; others
can't. Some gain muscle rapidly eating in the middle of the
night; others just get fat. Some respond to creatine; others
don't..
It seems like folks who are prone to the leap-before-you-look
approach are just being lazy when it comes to the reading and
researching. Now, I agree with the point that the researching part
can be taken so far out of balance that the practical trials never
get done. However, I think its not only irresponsible to avoid
knowledge, but it can be downright boring (for me personally,
anyway) to not have a logical inkling of the whys behind what
Im spending my time, effort, and resources doing day in and
day out. To use creatine as an example, if people arent aware of
the realistic rate of mass gain achievable by creatine, or if
theyre not aware of its rather narrow specificity of use, theyll
automatically label themselves non-responders, and then move
on to the next supplement on the list From that point you can
just picture someone hoping beta-alanine will do wonders for
their maximal strength in the 5x5 Ripp Zone.
Touch It By Chris Shugart, June 2008

I've always liked the idea of touching a hot stove. What I
mean is, I think that real life and hands-on experience are
always the best teachers, although often the most brutal.

The old analogy about touching a stove is perfect: You can
tell a child not to touch a hot stove all you want. Teach him,
warn him, threaten him, provide him with a colorful
informational pamphlet, whatever. He won't truly know
about the dangers of touching a hot stove until he... touches a
hot stove.

Then he knows. He really knows.











Here are some examples of the different "stoves" I've
ouched in the last few months: t

1) Peanuts and peanut butter as allergic and detrimental to
fat loss and muscle building goals.
2) Eccentric-only training for injured (torn) muscles.
3) Coconut oil as a healthy saturated fat source.
4) Training over 90 minutes per session when supplementing
with specific aminos, proteins, and carbs.
5) HCL therapy
1) On what basis? Did some tan buff guy with shaved loins say
so? See, this just isnt good enough for me. If Im gonna give up
my peanut butter, there better be a damn good reason for it.
"Touching the stove" is also a fast and efficient teacher.
People spend years debating certain issues and wrestling
mentally with different concepts and ideas. Why? Just spend
a few weeks or months trying the new thing and then you'll
know how it works for you.

For example, some people thrive on low-carb diets and some
people don't do well on them at all. Which one are you? Do
both and find out. You'll know in a few months. Easy.
2) Im no expert on injury rehab, but blanketly issuing eccentric-
only training for TORN muscles sounds about as sensible as
taking a straw and sniffing a line of red ants for that pre-workout
rage. Eccentric exercise done correctly can be beneficial for
treating Achilles tendonopathy, but not for speeding up the
healing process of a pec tear.
3) Im aware of the research showing positive health effects of
coconut oil. However, I think its incorrect to deify (or
demonize) any single source of food, when in the end its the net
macronutrition that matters more than anything else. Getting an
obsession for hemp oil will come next as soon as the buff guy
says its the bomb.
4) Oh lordy.
5) HCL therapy? I think thats the wrong kind of therapy to seek
at this point. Try the Blood Type Diet with a dash of witchcraft.
Whatever you decide, do not I repeat DO NOT get wrapped
up in scientific research.


AlanAragonsResearchReviewJuly,2008[BacktoContents] Page14

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This is easily one of the most priceless video clips Ive ever
seen. Forget about ignorance, contest prep is bliss! Credit goes
to AARR member Quinton for alerting me to this clip.






Thanks once again for getting your wits filled with another
AARR issue. If you have any questions, comments, suggestions,
bones of contention, cheers, jeers, any feedback at all, send it
over to [email protected]. All suggestions are taken very
seriously. I want to make sure this publication continues to stand
alone in its excellence.