Benefits:

• Facilitates blood vessel relaxation
• Supports optic nerve and retinal circulation
• May promote healthy erectile function
• May increase blood flow to muscles, supporting athletic performance
• Provides antioxidants; may aid in recovery from intense athletics

This formula contains a blend of ingredients to support production of NO and work synergistically to promote healthy blood vessel function.

• Arginine and Citrulline: Arginine is an amino acid that serves as a precursor to NO. When arginine is made into NO, citrulline is produced and citrulline may be recycled back into arginine, thus supporting continued synthesis of NO. Much of the arginine in food is broken down in the intestine, with only about 50% reaching the circulation. For this reason, supplementing with arginine and citrulline may provide a more reliable supply of these NO building blocks.
• Vitamin C: an antioxidant and also a required factor for building collagen, the primary protein that makes up the physical structure of blood vessels
• Folate: a member of the B-vitamin family and a required cofactor for proper functioning of the enzyme responsible for synthesizing NO
• Taurine: a natural diuretic; it also promotes a healthy heart rhythm and proper functioning of platelets
• Magnesium: a natural blood vessel relaxant
• Grape & Apple Extracts and Glutathione: Polyphenols in grape and apple extracts have potent antioxidant and vasodilating (blood vessel relaxing) properties, partly by facilitating production of NO. Tannins and anthocyanins— polyphenols found in grapes and apples, among other foods—may contribute to the well-known beneficial effects of moderate red wine consumption on cardiovascular health. Glutathione is often called the body’s “master antioxidant,” owing to its powerful ability to help neutralize harmful free radicals.
•  

Preliminary studies show that Nitric Oxide may have some efficacy in both ocular hypertension and glaucoma.*

* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693832/

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Other Ingredients: Natural flavor, citric acid, stevia leaf extract (Stevia rebaudiana).

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Benefits of this formula:

Arginine and Citrulline

Arginine is a critical substrate for the synthesis of NO, a compound that relaxes endothelial cells throughout the cardiovascular system. NO also inhibits platelet aggregation and superoxide radical generation. Arginine supplementation has been shown to reverse the endothelial dysfunction associated with common cardiovascular risk factors and also ameliorates symptoms of certain cardiovascular disorders, including coronary and peripheral arterial disease, ischemia/reperfusion injury and heart failure.1

Supplemental arginine may be beneficial due to high arginase activity in the small intestine, where approximately 40% of arginine is degraded during digestion, and only 50% of dietary arginine enters the systemic circulation.1

Citrulline is included as an adjunct to arginine, as citrulline is converted to arginine in various cells. Unlike arginine, citrulline is not metabolized in the intestine or liver and does not induce tissue arginase. In fact, it inhibits arginase, and citrulline entering peripheral tissues—particularly the kidneys and vascular endothelium—may be readily converted to arginine, thus raising arginine levels and enhancing NO production.2 Studies show that citrulline raises plasma arginine levels significantly higher than arginine itself and has a longer half-life in the body, so citrulline can be thought of as a potent “time-released arginine.”3 Research suggests that one of citrulline’s primary physiological roles is serving as a precursor to arginine in the kidneys.4,5

In regard to the influence of citrulline on increasing NO synthesis and stimulating a positive downstream effect, a study involving men with mild erectile dysfunction demonstrated that 1.5 g/day of citrulline improved erectile function in 50% of participants.3

Cardiovascular health: by increasing NO production, endothelial cell function is improved, which causes blood vessel relaxation; supports normal blood pressure; supports sexual health by maintaining erectile function.

Athletic performance: by increasing blood flow to muscles and enhancing ATP production, exercise can be performed at a higher intensity for a longer duration; muscle contraction may be more efficient, potentially leading to a greater anabolic effect. Additionally, antioxidants in Dr. Berne's Optic Nerve Formula may help aid recovery from intense athletics.

Folate, as 5-MTHF, is included as a precursor to tetrahydrobiopterin (BH4), a required cofactor for activity of the enzyme nitric oxide synthase (NOS).7 Inadequate levels of BH4 result in the generation of superoxide radicals, rather than NO, from endothelial NOS (eNOS).8 When low BH4 bioavailability occurs, oxygen activation is “uncoupled” from arginine oxidation, and NOS produces superoxide instead of NO. NOS-derived superoxide reacts with NO to produce highly reactive peroxynitrite radicals, which rapidly oxidize BH4 and trigger uncoupling of NOS. Depletion of BH4 and uncoupling of NOS may result in hypertension, ischemia/reperfusion injury, overload induced heart failure and atrial fibrillation.9 Sufficient folate is also required for proper metabolism of homocysteine.

Arginine and Citrulline

Arginine is a critical substrate for the synthesis of NO, a compound that relaxes endothelial cells throughout the cardiovascular system. NO also inhibits platelet aggregation and superoxide radical generation. Arginine supplementation has been shown to reverse the endothelial dysfunction associated with common cardiovascular risk factors and also ameliorates symptoms of certain cardiovascular disorders, including coronary and peripheral arterial disease, ischemia/reperfusion injury and heart failure.₁

Supplemental arginine may be beneficial due to high arginase activity in the small intestine, where approximately 40% of arginine is degraded during digestion, and only 50% of dietary arginine enters the systemic circulation. ₁

Citrulline is included as an adjunct to arginine, as citrulline is converted to arginine in various cells. Unlike arginine, citrulline is not metabolized in the intestine or liver and does not induce tissue arginase. In fact, it inhibits arginase, and citrulline entering peripheral tissues—particularly the kidneys and vascular endothelium—may be readily converted to arginine, thus raising arginine levels and enhancing NO production. ₂ Studies show that citrulline raises plasma arginine levels significantly higher than arginine itself and has a longer half-life in the body, so citrulline can be thought of as a potent “time-released arginine.” ₃ Research suggests that one of citrulline’s primary physiological roles is serving as a precursor to arginine in the kidneys. _4,5 In regard to the influence of citrulline on increasing NO synthesis and stimulating a positive downstream effect, a study involving men with mild erectile dysfunction demonstrated that 1.5 g/day of citrulline improved erectile function in 50% of participants. ₃ NOx SynergyTM includes glutathione as an adjunct to citrulline. The combination of these compounds has been shown to increase plasma levels of NO in humans in vivo. It may be particularly beneficial for recovery from intense physical activity and may enhance muscle protein synthesis after resistance training.6

Grape (Vitis vinifera) and Apple (Malus pumila) Extracts
A proprietary combination of apple and grape polyphenols are included for their potent antioxidant and vasodilating properties. These polyphenols have been shown to enhance vasodilation by increasing the activation of the eNOS enzyme. Animal models and in vitro research have shown that polyphenols (including those from grapes and apples) are effective for increasing NO synthesis and availability by enhancing eNOS activity.11-14 Studies in humans confirm the health benefits of wine and grape polyphenols.15,16 This formula also includes vitamin C for its role in supporting healthy blood vessels. This nutrient is a required cofactor for building collagen, which is a key structural component of blood vessels. Additionally, working synergystically with the antioxidant compounds in grape and apple extracts, vitamin C exerts vasoprotective benefits, including helping to maintain capillary integrity.

Phloretin, a polyphenol most commonly found in apples, has been shown to inhibit the expression of inflammatory cytokine- induced adhesion molecules in aortic endothelial cells. It has also been demonstrated to reduce platelet aggregation, suggesting that phloretin could be protective against the onset and progression of cardiovascular disease.17 Other apple polyphenols inhibit expression of pro-inflammatory genes in human cells in vitro in a dose dependent manner.18

Taurine

This sulfonic acid derivative of cysteine has been shown to affect cardiovascular function through multiple mechanisms. It is anti-arrhythmic, hypotensive, and may decrease platelet aggregation.19 It also has a normalizing effect on cardiac muscle function with regard to calcium status, as it may strengthen contraction at low calcium levels, and beneficially relax the force of contraction at high calcium levels.20 Human and animal studies have shown taurine to reduce intimal thickening, arteriosclerosis, oxidative stress, and inflammation associated with diabetes, hypertension, and smoking-induced vascular events. Taurine supplementation in hypertensive patients has been shown to alleviate hypertension symptoms, as well as reverse arterial stiffness in type 1 diabetics.21 Taurine may also have a direct effect on NO by increasing eNOS expression, increasing plasma arginine concentration, and reducing synthesis of asymmetric dimethylarginine (ADMA), a NOS inhibitor.22

Chelated Creatine/Magnesium Complex

The combination of creatine and magnesium is a synergistic pairing of two compounds with powerful effects on cardiovascular health and muscle performance. The production of ATP involves the transfer of a phosphate group from creatine to ADP, and this transfer is dependent on the availability of magnesium ions. The chelated creatine/magnesium complex in this formula provides a stable, highly effective form of creatine with the presence of magnesium, wherein magnesium repletion facilitates the anabolic activity of creatine.

Magnesium is well-regarded for its hypotensive and relaxing effects, and a magnesium deficiency is associated with several conditions related to blood vessel function and blood flow.23 Creatine has long been recognized for its beneficial effects on muscle performance and lean body mass.24-27 Supplemental creatine stimulates strength and muscle mass, but its efficacy is limited by the lactamation reaction, which transforms some creatine into anabolically inert creatinine. Pairing creatine with magnesium inhibits this conversion, thus increasing the amount of creatine available for supporting muscle cells.

Supplementing with this creatine/magnesium chelate helps increase muscle strength as well as the speed of muscle mass growth, since larger amounts of ATP may facilitate greater force stimuli and muscle contraction. Creatine has also been demonstrated to increase muscle anaerobic capacity and aerobic recovery by stimulating mitochondrial activity.28 According to research, the effects of a combined magnesium/creatine chelate are significantly more potent than the administration of creatine and magnesium from separate sources.29,30 The effect of the anthocyanins in this product on NOS and oxidative stress may offer additional benefits for athletic performance as an ergogenic aid and to facilitate recovery.31,32

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

References

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3. Cormio L, De Siati M, Lorusso F, Selvaggio O, Mirabella L, Sanguedolce F, Carrieri G. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011 Jan;77(1):119-22.

4. Moinard C, Nicolis I, Neveux N, Darquy S, Bénazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62.

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