- Optimize Flow of Blood and Oxygen to Peripheral Tissues*
- Helps Maintain Healthy Male Sexual Function*
- Supports Lean Body Mass/Athletic Performance*
- Supports Healthy Dilation of Blood Vessels*
- Supports the Healthy Flow of Blood and Oxygen to the Brain for Healthy Mood, Mind, and Memory*
NOX Rx is Nuley’s newest supplement based on the latest Nobel
Prize-winning research on nitric oxide, a naturally occurring compound
in the body. Nitric oxide is an important messenger that signals a variety
of responses at the cellular level which are beneficial to circulatory,
immune, and nervous system functions. NOX Rx is a refreshing,
effervescent powder that offers therapeutic levels of L-arginine and
L-citrulline, two amino acids the body uses to make nitric oxide.*
Nitric oxide (NO) is produced by various body cells from the amino
acid L-arginine through the enzymatic action of nitric oxide synthase
(NOS). NO has critical roles in regulating the function of organs and
systems throughout the body. It is well known that NO production by
vascular endothelium plays a critical role in blood flow regulation and
that the abnormal production of NO can adversely affect blood flow,
delivery of nutrients and oxygen, and other vascular functions.
L-Arginine is the principal substrate for the family of NOS enzymes
that catalyze the biosynthesis of NO. Some of L-arginine’s benefits
include support of immune response, ammonia detoxification, growth
hormone secretion (during rest), improved exercise performance (at 6
g/d), wound healing, reduced platelet aggregation, and vasodilation.[1,2]
ADMA (asymmetric dimethylarginine) is a newly identified factor
confronting cardiovascular health. As an endogenous NOS inhibitor,
accumulation of ADMA impairs NO formation by competing with
L-arginine for NOS binding. Under these conditions, supplementation
with L-arginine may support maintenance of near-normal levels.[1]
New research also suggests that ADMA accumulation in oxidized lowdensity lipoproteins (OxLDL) may signal vascular smooth muscle cell
(VSMC) migration—which plays a critical role in the etiology of intimal
thickening—and L-arginine markedly blocked ADMA-induced VSMC
migration.[3]
L-Citrulline is a precursor to L-arginine that readily permeates the
intestinal wall and enters the bloodstream. L-citrulline is processed
by the kidney, where it is converted to L-arginine; and oral L-citrulline
supplementation in humans has been shown to increase plasma
L-arginine availability for NO synthesis.[4] In an animal study, oral
supplementation with “L-arginine, L-citrulline, and/or antioxidants
(vitamins C and E) showed marked support of endothelium-dependent
vasorelaxation and blood flow, maintenance of a healthy endothelium,
and decrease in superoxide production and oxidation-sensitive gene
expression …”[5]
Quercetin A major flavonoid naturally occurring in plants, quercetin
has been shown in a study on mice using microarray DNA analyses
and pathway analyses to inhibit LPS-induced expression of IL-1beta,
IL-1alpha, IL-6, TNF-alpha, IL-12, iNOS, VCAM1, ICAM1, COX2, IL-1RA,
TRAF1 and CD40.[6] Experimental models suggest that quercetin
prevents the redox imbalance associated with decreased intracellular
NO levels and superoxide overproduction, and it prevents the
overexpression of inducible NOS (iNOS).[7,8]
Folic Acid Research suggests that homocysteine may decrease
the bioavailability of NO.[9] Therefore, folate’s deleterious effect on
homocysteine may provide the added benefit of increasing NO levels
through enhancing NO bioavailability. Another role of folic acid in
NO production relates to tetrahydrobiopterin (THBP, also known as
BH4)—an essential cofactor for NOS. Inadequate folate may impair
the synthesis of THBP,[10] and 5-MTHF (bioactive folate) may normalize
the activity of NOS in THBP-depleted endothelial cells.[11] In a placebocontrolled study of patients receiving 400 mcg/d of folic acid for seven weeks before coronary artery bypass grafting, improved vascular
function was observed and attributed to improved availability of THBP
for NOS and reduced vascular oxidative stress.[12]
Vitamins C and E Free-radical injury reduces NO availability, and
antioxidants appear to preserve NO. In addition, healthy endothelial
function is associated with low oxidative stress, particularly decreased
superoxide production and reduced oxidized LDL (OxLDL), which, if
elevated, can reduce endothelium-derived NO activity. Vitamins C
and E administration can reduce both superoxide and OxLDL, thereby
improving NO activity.[13] According to Heller et al, “The effect of alphatocopherol seems to be dependent on tissue saturation with ascorbic
acid, and both vitamins may act synergistically to provide optimal
conditions for endothelial NO formation.”[14]
References
Böger RH. The pharmacodynamics of L-arginine. J Nutr. 2007 Jun;137(6 Suppl
2):1650S-55S. [PMID: 17513442]
Bailey SJ, Winyard PG, Vanhatalo A, et al. Acute L-arginine supplementation
reduces the O2 cost of moderate-intensity exercise and enhances highintensity exercise tolerance. J Appl Physiol. 2010 Nov;109(5):1394-403. [PMID:
20724562]
Sun L, Zhang T, Yu X, et al. Asymmetric dimethylarginine confers the
communication between endothelial and smooth muscle cells and leads to
VSMC migration through p38 and ERK1/2 signaling cascade. FEBS Lett. 2011
Sep 2;585(17):2727-34. [PMID: 21821030]
Sureda A, Cordova A, Ferrer MD, et al. Effects of L-citrulline oral
supplementation on polymorphonuclear neutrophils oxidative burst and nitric
oxide production after exercise. Free Radic Res. 2009 Sep;43(9):828-35. [PMID:
19585317]
Hayashi T, Juliet PA, Matsui-Hirai H, et al. l-Citrulline and l-arginine
supplementation retards the progression of high-cholesterol-dietinduced atherosclerosis in rabbits. Proc Natl Acad Sci U S A. 2005 Sep
20;102(38):13681-86. [PMID: 16157883]
Qureshi AA, Tan X, Reis JC, et al. Inhibition of nitric oxide in LPS-stimulated
macrophages of young and senescent mice by delta-tocotrienol and quercetin.
Lipids Health Dis. 2011 Dec 20;10(1):239. [Epub ahead of print] [PMID:
22185406]
Kostyuk VA, Potapovich AI, Suhan TO, et al. Antioxidant and signal modulation
properties of plant polyphenols in controlling vascular inflammation. Eur J
Pharmacol. 2011 May 11;658(2-3):248-56. [PMID: 21371465]
Zhang ZJ, Cheang LC, Wang MW, et al. Quercetin exerts a neuroprotective
effect through inhibition of the iNOS/NO system and pro-inflammation gene
expression in PC12 cells and in zebrafish. Int J Mol Med. 2011 Feb;27(2):195-
[PMID: 21132259]
Tawakol A, Forgione MA, Stuehlinger M, et al. Homocysteine impairs coronary
microvascular dilator function in humans. J Am Coll Cardiol. 2002 Sep
18;40(6):1051-58. [PMID: 12354427]
Crabtree MJ, Channon KM. Synthesis and recycling of tetrahydrobiopterin in
endothelial function and vascular disease. Nitric Oxide. 2011 Aug 1;25(2):81-88.
[PMID: 21550412]
McCarty MF. Coping with endothelial superoxide: potential complementarity of
arginine and high-dose folate. Med Hypotheses. 2004;63(4):709-18. [PMID:
15325022]
Shirodaria C, Antoniades C, Lee J, et al. Global improvement of vascular
function and redox state with low-dose folic acid: implications for folate therapy
in patients with coronary artery disease. Circulation. 2007 May 1;115(17):2262-
[PMID: 17420345]
Carr A, Frei B. The role of natural antioxidants in preserving the biological
activity of endothelium-derived nitric oxide. Free Radic Biol Med. 2000 Jun
15;28(12):1806-14. [PMID: 10946222]
Heller R, Werner-Felmayer G, Werner ER. Alpha-Tocopherol and endothelial nitric
oxide synthesis. Ann N Y Acad Sci. 2004 Dec;1031:74-85. [PMID: 15753135]
*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
