It comes down to nutrient timing. We feel that NO products are best taken 15 minutes prior to workouts and creatine taken 1 hour prior to working out. Taking them together to us seems like a much less effective way to take these cool supplements.
In a nutshell Persky showed that creatine takes 40-50 minutes to get into the muscle and also that creatine mixed with carbohydrates may take even longer supporting our theory that 60 minutes is probably optimal and buttressing our internal testing.
It would seem that L-Arginine products suffer a similar fate that things like Prohormones do. Arginase is expressed in the liver and seems to deactivate Arginine before it can become a NO precursor as demonstrated in the studies of intravenous arginine vs. oral arginine. IV Arginine showed promise yet oral didn't which leads me to believe co-factors like Quercetin that can inhibit liver based Arginase should really help increase the efficacy of the product.
Pharmacokinetics of intravenous and oral l-arginine in normal volunteers by Oranee Tangphao shows that a peak concentration of oral L-Arginine occurs at about 60 minutes after ingestion, but the graph shows around 15 minutes significant L-Arginine is circulating and peaks at 60 minutes where it is then at a pretty steady state for about 100 minutes. So, right about when you hit the gym you are getting an infusion of Arginine at active levels and peaks during your workout.
J Clin Pharmacol. 2003 Jan;43(1):29-37.
Single- and multiple-dose pharmacokinetics of oral creatine.
Persky AM, Müller M, Derendorf H, Grant M, Brazeau GA, Hochhaus G.
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Supplementation with exogenous creatine (Cr) has shown physiological benefits in humans, but little is known about the pharmacokinetics of Cr in humans. Six healthy males completed an open-label study consisting of a full pharmacokinetic analysis following a single oral dose of Cr monohydrate (71 mg kg-1) and at steady-state after 6 days of Cr administration (71 mg kg-1 qid). After the single oral dose, the clearance (CL/F) was 0.20 +/- 0.066 L h-1 kg-1, tmax was 1.9 +/- 0.88 hours, and Cmax = 102.1 +/- 11.2 mg h L-1. At steady-state, CL/F decreased to 0.12 +/- 0.016 L h-1 kg-1, tmax did not change, and Cmax increased to 162.2 +/- 30.0 mg L-1. Penetration (AUCMUSCLE/AUCPLASMA) of Cr into the interstitial muscle space, as determined by microdialysis, was 0.47 +/- 0.09 and 0.37 +/- 0.27 for the single dose and at steady-state, respectively. Plasma and muscle data were simultaneously fitted with a model incorporating a saturable absorption and first-order elimination process. In conclusion, repeated dosing of Cr caused a reduction in clearance that could result from saturation of the skeletal muscle pool of Cr.
Pharmacokinetics of creatine.
McCall W, Persky AM.
Division of pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Research has demonstrated that creatine supplementation has some therapeutic benefit with respect to muscle function and more recently neurological function. Despite the growing body of literature on the pharmacologic effect of creatine, very little is known about the disposition of creatine after supraphysiologic doses. The movement of creatine throughout the body is governed by transport processes which impact the absorption of creatine from the intestine, clearance of creatine from the kidney, and access of creatine to target tissues. With repeated doses of creatine, it appears that the clearance of creatine decreases mainly due to the saturation of skeletal muscle stores. Insulin and insulin-stimulating foods appear to enhance muscle uptake of creatine but at the same time, high carbohydrate meals may slow the absorption of creatine from the intestine. Little is known about creatine disposition in special populations including the elderly and patients with neuromuscular disease. Knowledge of creatine disposition in these clinically relevant populations can help remove some of the guess work of dose selection during clinical trials.
__________________
In a nutshell Persky showed that creatine takes 40-50 minutes to get into the muscle and also that creatine mixed with carbohydrates may take even longer supporting our theory that 60 minutes is probably optimal and buttressing our internal testing.
It would seem that L-Arginine products suffer a similar fate that things like Prohormones do. Arginase is expressed in the liver and seems to deactivate Arginine before it can become a NO precursor as demonstrated in the studies of intravenous arginine vs. oral arginine. IV Arginine showed promise yet oral didn't which leads me to believe co-factors like Quercetin that can inhibit liver based Arginase should really help increase the efficacy of the product.
Pharmacokinetics of intravenous and oral l-arginine in normal volunteers by Oranee Tangphao shows that a peak concentration of oral L-Arginine occurs at about 60 minutes after ingestion, but the graph shows around 15 minutes significant L-Arginine is circulating and peaks at 60 minutes where it is then at a pretty steady state for about 100 minutes. So, right about when you hit the gym you are getting an infusion of Arginine at active levels and peaks during your workout.
J Clin Pharmacol. 2003 Jan;43(1):29-37.
Single- and multiple-dose pharmacokinetics of oral creatine.
Persky AM, Müller M, Derendorf H, Grant M, Brazeau GA, Hochhaus G.
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Supplementation with exogenous creatine (Cr) has shown physiological benefits in humans, but little is known about the pharmacokinetics of Cr in humans. Six healthy males completed an open-label study consisting of a full pharmacokinetic analysis following a single oral dose of Cr monohydrate (71 mg kg-1) and at steady-state after 6 days of Cr administration (71 mg kg-1 qid). After the single oral dose, the clearance (CL/F) was 0.20 +/- 0.066 L h-1 kg-1, tmax was 1.9 +/- 0.88 hours, and Cmax = 102.1 +/- 11.2 mg h L-1. At steady-state, CL/F decreased to 0.12 +/- 0.016 L h-1 kg-1, tmax did not change, and Cmax increased to 162.2 +/- 30.0 mg L-1. Penetration (AUCMUSCLE/AUCPLASMA) of Cr into the interstitial muscle space, as determined by microdialysis, was 0.47 +/- 0.09 and 0.37 +/- 0.27 for the single dose and at steady-state, respectively. Plasma and muscle data were simultaneously fitted with a model incorporating a saturable absorption and first-order elimination process. In conclusion, repeated dosing of Cr caused a reduction in clearance that could result from saturation of the skeletal muscle pool of Cr.
Pharmacokinetics of creatine.
McCall W, Persky AM.
Division of pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Research has demonstrated that creatine supplementation has some therapeutic benefit with respect to muscle function and more recently neurological function. Despite the growing body of literature on the pharmacologic effect of creatine, very little is known about the disposition of creatine after supraphysiologic doses. The movement of creatine throughout the body is governed by transport processes which impact the absorption of creatine from the intestine, clearance of creatine from the kidney, and access of creatine to target tissues. With repeated doses of creatine, it appears that the clearance of creatine decreases mainly due to the saturation of skeletal muscle stores. Insulin and insulin-stimulating foods appear to enhance muscle uptake of creatine but at the same time, high carbohydrate meals may slow the absorption of creatine from the intestine. Little is known about creatine disposition in special populations including the elderly and patients with neuromuscular disease. Knowledge of creatine disposition in these clinically relevant populations can help remove some of the guess work of dose selection during clinical trials.
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