Nitric Oxide scientifically known as arginine-alpha-keto-glutarate
(AAKG) is a relatively new product to the sports nutrition industry.
Although there is now brief conclusive evidence as to the effect
of the product, the range of findings is significantly less than
that of other supplements such as creatine and BCAA's. The common
theory behind nitric oxide is that it increases blood flow to
the muscles which in turn helps to deliver and transport blood
and nutrients more adequately to these working muscles. This
is then thought to be an effective way to enhance skeletal muscular
hypertrophy as well as increasing ones recovering capabilities,
all which have been theorized to enhance human performance. Technically,
nitric oxide is a free form gas that is produced in the body
and is used to communicate with other cells. To produce this
gas, enzymes in the body break down the amino acid Arginine.
The production of Nitric Oxide occurs when the amino acid, L-arginine
is converted into L-citruline through an enzyme group known as
Nitric Oxide Synthase.
A recent study at Baylor University's (Texas) Exercise and Sports
Nutrition Lab examined the effects of AAKG supplementation during
training on body composition and training adaptations in experienced
gym rats (16). Thirty-five resistance-trained males were matched
according to fat-free mass and randomly assigned to ingest supplements
containing either a placebo or commercial AAKG supplement in
a double blind manner. Subjects took four grams of the supplements
three times daily (12 grams per day) for eight weeks during standardized
training. There were no significant changes in body mass or body
composition. However, there were significant changes in strength
levels. The bench press one repetition maximum (1RM) was greatly
increased over the eight week period for the AAKG group. Specifically,
AAKG supplementation helped subjects add an average of 13 pounds
to their bench press max over the placebo group during the eight
week testing period.
It may be interesting to note that, although body composition
did not change during the study, a longer duration experiment
may have shown an increase in lean muscle mass for the AAKG group.
In fact, muscle mass is often accompanied by changes in strength
as seen in most studies, but may take as long as 12-16 weeks
to fully maximize physiological responses and processes in terms
of muscular hypertrophy (18). This study shows that AAKG supplementation
may augment 1-RM strength in response to training, but does not
appear to significantly affect body composition. However, it
could be argued that such a significant increase in strength
levels would eventually lead to increased muscle hypertrophy
if the testing period would have continued for an extended period
For over a decade now, arginine, which is a critical ingredient
for nitrous oxide, has been hypothesized as having a positive
effect on growth hormone in the human body. Suminski et al (82)
sought to discover the legitimacy of these claims. In this particular
study, 16 men were randomly assigned to four different groups
using varying combinations of exercise and arginine. It was concluded,
based on the ending research of this study, that the amino acid
formula containing high amounts of arginine had a positive effect
on increasing basal levels of growth hormone. Since arginine
is the foundational element of nitric oxide, it can be safely
theorized that arginine may have an anabolic effect on the human
body by increasing levels of nitric oxide and growth hormone.
One of the oldest studies related to nitric oxide was done by
Elam et al (19) in which subjects who received a form of nitric
oxide supplement produced greater total gains in strength and
lean body mass while on a high intensity strength training program
compared to a placebo group on the same exercise regime over
the same five week period. Of further interest in this study
was that nitric oxide also enhanced recovery from chronic stress
by decreasing tissue breakdown as shown by lower urinary hydroxyproline
(UH) levels. It also appears that from certain studies done by
Friedl et al (20), higher levels of nitric oxide in the body
are correlated with enhanced immune function.
In another study by Nagaya et al (21), the supplementation protocol
required that each subject consume 1.5 g of arginine per 10 kg
of body weight per day for 7 days. A significant increase in
peak oxygen consumption was observed. A possible mechanism to
describe this increase in performance is the role that arginine
has in augmenting nitric oxide. An increase in nitric oxide bioavailability
results in coronary vessel vasodilatation and flow, which in
turn, may positively influence coronary function.
Another interesting fact to note as reported by numerous supplement
companies is that nitric oxide acts to reduce inflammation. This
should be of great interest to bodybuilders as it has the potential
to reduce the pain associated with subjecting muscles to extreme
stress. It has also been reported that nitric oxide may also
affect the release of adrenaline from the adrenal medulla. However,
many of these claims have not been negated or proven under scientific
methods. Therefore, more research is needed to help finalize
From the proceeding findings, it can be seen that AAKG supplementation
holds some promise for bodybuilders and other strength-power
athletes. AAKG appears to augment 1-RM strength in response to
training. Furthermore, AAKG does not appear to adversely affect
general markers of health. Again, more research is needed before
firm conclusions can be drawn.
The problem with AAKG, is that excessive production of Nitric
Oxide, whether through the exogenous use of one or more of arginine,
and nitrates/nitrites may depress endogenous
testosterone production since nitric oxide inhibits Leydig
cell steroidogenesis (22-25).
Because of the lack of findings of proper dosages for AAKG, the
temporary recommendations are 2000mg-6000mg per day are generally
accepted by scientists and physiologists. However, it should
be noted that with any amino acid containing product, overdose
is a possibility. Dosing with too much arginine can lead to diarrhea,
weakness and nausea. Clear dosing guidelines have not been established,
so it is best to do what is known as "tolerance mapping"
(26). Begin with small dosages and slowly increase the amount
to build up tolerance while at the same time taking note of any
improvements, plateauing, or
Summary and Recommendation
Nitric oxide has received positive feedback from several scientific
studies. Nitric oxide (AAKG) offers increased levels of strength,
increased levels of growth hormons, enhanced blood flow to the
working muscles, and enhanced immune function. There is little
evidence to substantiate a valid argument for increasing muscle
hypertrophy through AAKG supplementation.
Dr Mauro Di Pasquale MD summarizes (27):
So while dramatically increasing nitric oxide in the body
has some benefits, and provides more of a pump when training
giving the impression that it's a potent ergogenic aid, its detrimental
effects on testosterone makes the use of nitric oxide supplements
containing one or more of large amounts of L-arginine, L-arginine
precursors, nitrates and nitrites counter productive for muscle
hypertrophy, body composition and athletic performance.
Dosage recommendations vary widely for AAKG due to a lack
of standardized supplementation routines among scientists. However,
the common recommendations range anywhere from 3-30 grams a day.
AAKG is best absorbed on an empty stomach and split up 2-4 times
throughout the day before or after meals. Morning, pre, and post
workout are also quality times to consume AAKG. Large doses of
30 grams or more have not shown any negative side effects or
toxicity and have even shown positive attributes.
According to consumerlab.com and other sources, some of the higher
quality forms of nitric oxide on the market include: BSN Nitrix,
NxLabs Vaso XP, Syntrax Nitrous, CytoSport Fast Twitch, Xyience
XNO, Progressive Laboratories Arginine, Nature's Harmony L-Arginine,
Controlled Labs White Flood, and Gaspari Nutrition SuperPump250.
16. International Society of Sports Nutrition Conference Proceedings.
Sports Nutrition Review Journal, 1: S1-11, 2004.
17. Manninen, H. Supplement Performance: Nitric Oxide Boosters.
Cutting-Edge Data from ISSN Conference Proceeding. 2005.
18. Baechle, T., Earle, R., Essentials of Strength Training
and Conditioning. National Strength and Conditioning Association.
19. Elam RP, Hardin DH, Sutton RA, Hagen L. Effects of arginine
and ornithine on strength, lean body mass and urinary hydroxyproline
in adult males. J Sports Med Phys Fitness. 1989 Mar; 29(1): 52-56.
20. Friedl R, Moeslinger T, Kopp B, Spieckermann PG. Stimulation
of nitric oxide synthesis by the aqueous extract of Panax ginseng
root in RAW 264.7 cells. Br J Pharmacol. 2001 Dec; 134(8): 1663-70.
21. Nagaya N, Uematsu M, Oya H, Sato N, et al. Short-term
oral administration of L-arginine improves hemodynamics and exercise
capacity in patients with precapillary pulmonary hypertension.
Am J Respir Crit Care Med. 2001; 163: 887-891.
22. Drewett JG, Adams-Hays RL, Ho BY, Hegge DJ. Nitric oxide
potently inhibits the rate-limiting enzymatic step in steroidogenesis.
Mol Cell Endocrinol. 2002 Aug 30;194(1-2):39-50.
23. Panesar NS. Is steroid deficiency the cause of tolerance
in nitrate therapy? Med Hypotheses. 2000 Oct;55(4):310-3.
24. Panesar NS, Chan KW. Decreased steroid hormone synthesis
from inorganic nitrite and nitrate: studies in vitro and in vivo.
Toxicol Appl Pharmacol. 2000 Dec 15;169(3):222-30.
25. Andric SA, Janjic MM, Stojkov NJ, Kostic TS. Testosterone-induced
modulation of nitric oxide-cGMP signaling pathway and androgenesis
in the rat Leydig cells. Biol Reprod. 2010 Sep;83(3):434-42.
Epub 2010 May 12.
26. Bodybuilding.com. NO Nitric Oxide Info And Products. 2006.
27. MauroMD.com, Questions & Answers. 2011.
82. Suminski RR, Robertson RJ, Goss FL, Arslanian S, Kang
J, DaSilva S, Utter AC, Metz KF. Acute effect of amino acid ingestion
and resistance exercise on plasma growth hormone concentration
in young men. Int J Sport Nutr. 1997 Mar; 7(1): 48-60.