Description
Ingredients
L-Citrulline
L-citrulline is one of three dietary amino acids in the urea cycle responsible for converting ammonia into urea as well as for the production of NO, an important cellular signaling molecule. In this process, L-citrulline is the natural precursor of L-arginine, the substrate used by endothelial nitric oxide synthase (eNOS) to produce NO.
As a signaling molecule, NO has been shown to have a very powerful effect on vasodilation and blood flow.3-5 Because of this, optimizing circulating NO levels has long been a target of aerobic and anaerobic athletes. In fact, numerous clinical trials have been conducted showing that L-citrulline and L-arginine supplementation have a profound effect on exercise performance and power output.
The benefits of circulating NO levels stretch far beyond exercise performance. As a vasodilator, NO improves arterial elasticity, decreases platelet adhesion, scavenges free radicals, and prevents oxidation of LDL cholesterol. Studies show low levels of NO are associated with endothelial cell dysfunction, vasoconstriction, and blood flow challenges. Unfortunately, supplemental L-arginine has a small, transient effect, with no long-term benefit on circulating NO levels, because liver metabolism restricts excess arginine from the blood to avoid long-term physiological consequences.
However, recent research shows that supplementing L-citrulline bypasses liver metabolism, thus making it more bioavailable in the blood stream and allowing it to significantly impact circulating NO levels. In a direct comparison, a recent study showed 3,000 mg of L-citrulline supplementation increased circulating NO levels 1.6-fold higher than 3,200 mg of L-arginine. Another direct comparison study showed L-citrulline supplementation significantly sustained peak plasma NO levels for upwards of four hours, and NO levels in the L-arginine group begin to decline at 1.5 hours.
Quercetin Dihydrate
A flavonoid found in a variety of botanicals, vegetables and fruits, quercetin is a potent antioxidant that inhibits inducible ICAM-1 expression, an important pathway for maintaining normal inflammatory balance. Quercetin has been shown to support normal inflammatory balance by directly inhibiting the activity of NFkB, similar to turmeric. Quercetin is known for its ability to improve endothelial cell dysfunction by maintaining normal inflammatory balance in specific pathways.
MegaNatural® BP Grape Seed Extract
MegaNatural® BP is a premium grape seed extract made in California from a special seed blend extracted with water from a variety of white wine grape seeds. Grapes and grape products contain phenolic compounds found to have health-promoting properties, particularly in cardiovascular wellness. Grape seed extract has a high concentration of phenolic compounds, which have been found to support healthy arterial dilation and blood flow. These polyphenols have been shown to activate NOS, the enzyme that facilitates NO production.
A study examining the effects of MegaNatural® BP grape seed extract in 27 volunteers found that after four weeks of supplementation with either 150 mg or 300 mg, the participants were able to maintain healthy blood pressure levels. The participants taking 300 mg also had a significant reduction in oxidized low-density lipoprotein when compared to placebo.
References
-
- Black PH and Garbutt LD. Stress, inflammation and cardiovascular disease. Journal of psychosomatic research. 2002;52:1-23.
- Tracy R. Emerging relationships of inflammation, cardiovascular disease and chronic diseases of aging. International Journal of Obesity & Related Metabolic Disorders. 2003;27.
- Palmer RM, Ferrige A and Moncada S. Nitric oxide release accounts for the biological activity of endotheliumderived relaxing factor. 1987.
- Furchgott R and Jothianandan D. Endothelium-dependent and-independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Journal of Vascular Research. 1991;28:52-61.
- Vallance P, Collier J and Moncada S. Effects of endotheliumderived nitric oxide on peripheral arteriolar tone in man. The Lancet. 1989;334:997-1000.
- Pérez-Guisado J and Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. The Journal of Strength & Conditioning Research. 2010;24:1215-1222.
- Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG and Jones AM. L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. Journal of Applied Physiology. 2015;119:385- 395.
- Suzuki T, Morita M, Kobayashi Y and Kamimura A. Oral L-citrulline supplementation enhances cycling time trial performance in healthy well-trained males. Journal of the International Society of Sports Nutrition. 2015;12:P52.
- Nagaya N, Uematsu M, Oya H, Sato N, Sakamaki F, Kyotani S, Ueno K, Nakanishi N, Yamagishi M and Miyatake K. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine. 2001;163:887-891.
- Wagenmakers AJ. Amino acid supplements to improve athletic performance. Current Opinion in Clinical Nutrition & Metabolic Care. 1999;2:539-544.
- Cannon RO. Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clinical Chemistry. 1998;44:1809-1819.
- Radomski MW, Palmer RM and Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochemical and biophysical research communications. 1987;148:1482-1489.
- Napoli C and Ignarro LJ. Nitric oxide and atherosclerosis. Nitric oxide. 2001;5:88-97.
- Romero MJ, Platt DH, Caldwell RB and Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovascular drug reviews. 2006;24:275-290.
- Durante W, Johnson FK and Johnson RA. Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clinical and Experimental Pharmacology and Physiology. 2007;34:906-911.
- Pollock JS, Förstermann U, Mitchell JA, Warner TD, Schmidt H, Nakane M and Murad F. Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proceedings of the National Academy of Sciences. 1991;88:10480-10484.
- Morris SM. Arginine: beyond protein. The American journal of clinical nutrition. 2006;83:508S-512S.
- Ryall JC, Quantz MA and Shore GC. Rat liver and intestinal mucosa differ in the developmental pattern and hormonal regulation of carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase gene expression. European Journal of Biochemistry. 1986;156:453-458.
- Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F and Böger RH. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British journal of clinical pharmacology. 2008;65:51-59.
- Morita M, Hayashi T, Ochiai M, Maeda M, Yamaguchi T, Ina K and Kuzuya M. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability. Biochemical and biophysical research communications. 2014;454:53-57.
- Bito T, Roy S, Sen CK, Shirakawa T, Gotoh A, Ueda M, Ichihashi M and Packer L. Flavonoids differentially regulate IFNγ-nduced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. FEBS letters. 2002;520:145-152.
- Min Y-D, Choi C-H, Bark H, Son H-Y, Park H-H, Lee S, Park J-W, Park E-K, Shin H-I and Kim S-H. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-κB and p38 MAPK in HMC-1 human mast cell line. Inflammation Research. 2007;56:210-215
- Sanchez M, Galisteo M, Vera R, Villar IC, Zarzuelo A, Tamargo J, Pérez-Vizcaíno F and Duarte J. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. Journal of hypertension. 2006;24:75-84.
- Plotnick GD, Corretti MC, Vogel RA, Hesslink R and Wise JA. Effect of supplemental phytonutrients on impairment of the flow-mediated brachialartery vasoactivity after a single high-fat meal. Journal of the American College of Cardiology. 2003;41:1744-1749.
- Edirisinghe I, Burton-Freeman B and Kappagoda CT. Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clinical Science. 2008;114:331-337.
- Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F and Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009;58:1743-1746.
Warnings
Always be sure to speak with your healthcare provider before starting any new nutritional supplement when pregnant or nursing. For children, we recommend speaking with your child's pediatrician regarding proper dosing. Store away from children.
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