Niteworks™ is based on the research of Nobel Laureate Dr. Louis Ignarro. Niteworks™ is a powder drink mix dietary supplement containing amino acids L-arginine and L-citrulline, as well as fat and water-soluble vitamins E, C, plus folic acid, alpha-lipoic acid and taurine. It is recommended for nighttime administration based on the rationale that nitric oxide levels are lowest during sleep due to inactivity, lack of food and low blood pressure (Guerrero et al., 1996; Sherwood et al, 2002). Ingredients in Niteworks™ (L-arginine, Vitamin C, and Vitamin E) promote a healthy cardiovascular system by supporting enhanced nitric oxide production. Nitric oxide formation is further increased due to the recycling effect of L-citrulline to L-arginine and the fact that L-citrulline is taken up into cells by an uptake mechanism independent of that for arginine (Miller, 2006; Rytlewski et al., 2005; Oka et al., 2005; Smith et al., 2006; Woollard et al., 2002; Gokce et al., 1999; Desideri et al., 2002; Rydlewicz et al., 2002; Daly et al., 2002).
L-arginine and L-citrulline are primary driver ingredients in Niteworks™, included as precursors to drive the production of nitric oxide. Folic acid is to support a healthy cardiovascular system, while vitamins C and E have been shown to provide a synergistic effect on nitric oxide (NO) production when used in combination with L-arginine. The formula also includes alpha-lipoic acid, taurine and lemon balm as supporting ingredients.
A two-arm, prospective randomized double blind placebo-controlled three week clinical study investigating the efficacy of Niteworks™ supplementation in sixteen elderly male cyclists was published (Chen et al, 2010). One group received Niteworks™ while the other group received a placebo product, which was taken at night time, according to the Niteworks™ label recommended usage. Measurements were taken at baseline, and again at one and three weeks. There were no differences between the two groups in exercise parameters at baseline or VO2 max over the course of the study. Results showed that there was no change in anaerobic threshold in the placebo group, while the group receiving Niteworks™ had a significantly higher anaerobic threshold than the placebo group at weeks one and three. The authors concluded that the arginine and antioxidant-containing Niteworks™ supplement increased the anaerobic threshold at both week one and three, as well as watts of power output, in elderly cyclists.
The physiological changes observed in the Niteworks™ group could be associated with prolonged exercise and a higher work rate. This study indicated a potential role for the combination L-arginine and antioxidant supplement in improving exercise performance in the elderly (Chen et al, 2010).
A pilot study investigating the effect of L-arginine supplementation on functional capacity assessed 0, 3, 6 or 9 grams of L-arginine daily in three divided doses over a 12 week period (Oka et al, 2005). Treadmill testing was conducted using the Skinner-Gardner protocol, and community-based walking was assessed using the walking impairment questionnaire. The study reported a trend for a greater increase in walking distance at an arginine dose of 3 grams per day, and a trend for improvement in walking speed in individuals receiving L-arginine. While this was a pilot study intended to document safety and provide information for a power calculation and dosing protocol, the results suggest that 3 grams of supplemental L-arginine may help combat reduced bioactivity and/or synthesis of endothelium-derived NO that impairs walking in a study model using select population (Oka et al, 2005).
Another double-blinded, randomized, placebo-controlled cross-over study investigated the pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine on NO metabolism in 20 healthy volunteers over 1 week (Schwedhelm et al, 2007). A dose-dependent increase in area under the curve (AUC) and Cmax (peak serum concentration) of plasma L-arginine was observed with L-citrulline supplementation. This study was the first to show that oral L-citrulline supplementation raises plasma L-arginine concentration and augments NO-dependent signaling in a dose-dependent manner (Schwedhelm et al, 2007). This evidence supports the inclusion of L-citrulline in Niteworks™, to ultimately support increased plasma levels of L-arginine and consequently, increased NO production.
In a placebo-controlled study involving 61 subjects, either 3 grams of arginine or placebo was orally given for 3 weeks. Subjects were also placed on a reduced nitrate diet for one week before, as well as one week after, the treatment with L-arginine. The study assessed the biochemical effects of exogenous L-arginine, plasma levels of selected amino acids as well as plasma levels and 24-h excretion of nitrite/nitrate in urine. Urine or plasma nitrite/nitrate levels reflect global NO production in human body. After three weeks of treatment, 24-h urinary excretion of nitrite/nitrate was significantly elevated in the groups of subjects taking L-arginine, but the difference did not reach statistical significance. Also, after three weeks of treatment, mean plasma levels of L-citrulline were higher in subjects receiving L-arginine (Rytlewski et al., 2005).
A study has demonstrated that coronary endothelial dysfunction in humans is characterized by increased coronary and circulating endothelin, and decreased production of the second messenger of NO, cGMP. Lerman et al. (1998) tested to see if a long-term oral L-arginine supplementation for 6 months could reverse coronary endothelial dysfunction in response to acetylcholine in humans with nonobstructive coronary artery disease. 26 patients were blindly randomized to either oral L-arginine or placebo, 3g three times a day for 6 months. L-arginine supplementation improved coronary blood flow compared with the placebo.
Researchers have studied the recycling of citrulline to arginine in various conditions. According to Solomonson, upon stimulation of NO production by biochemical stimulus, bradykinin, recycling is co-stimulated to the extent that more than 80% of the citrulline produced is recycled to arginine. They also compared the effect of exogenous citrulline with the effect of exogenous arginine on NO production and the levels of intracellular arginine following bradykinin activation. Surprisingly, added arginine did not cause as great an increase in endothelial NO production as did added citrulline (Solomonson et al., 2003). The same researchers also studied the degree of citrulline being recycled to arginine. The preliminary results suggest an efficient caveolar complex for the regeneration of arginine directed to receptor-mediated production of NO in endothelial cells an efficiency of greater than 80% for the recycling of citrulline to arginine under conditions of maximum stimulation of production.
In vivo L-citrulline supplementation has been shown to reduce blood pressure in salt-sensitive hypertensive rats, which is presumably achieved by an increase in NO production. Hecker et al. (1990) investigated the mechanism by which cultured endothelial cells generate L-arginine. When arginine-depleted endothelial cells were incubated in Krebs’ solution for 60 minutes, L-arginine levels were significantly (9.7-fold) elevated. Arginine-depleted endothelial cells did not form urea or metabolize L-ornithine but converted L-citrulline to L-arginine. In another in vivo study, the researchers evaluated the influence of ingested L-arginine, L-citrulline, and antioxidants (vitamin C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in the vascular system of rabbit. Rabbits were treated orally for 12 weeks with L-arginine, L-citrulline, and/or antioxidants. L-arginine plus L-citrulline, either alone or in combination with antioxidants caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression (Hayashi et al., 2005).
Vitamin C and E are supporting ingredients in Niteworks™. Vitamin C’s main function is quenching super oxides and reactive oxygen species thereby preventing NO inactivation, by inhibiting LDL oxidation and this preserve more NO (which is affected negatively by oxidized LDL) and it might enhance eNOS activity an important co-enzyme of NO synthesis.