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Thread: L-Arginine doesnt increase NO production, Nitrates do.

  1. #1
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    L-Arginine doesnt increase NO production, Nitrates do.

    1: J Nutr Biochem. 2008 Aug 15. [Epub ahead of print]
    Liu TH, Wu CL, Chiang CW, Lo YW, Tseng HF, Chang CK.

    No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes.

    Arginine supplementation has been shown to alleviate endothelial dysfunction and improve exercise performance through increasing nitric oxide production in patients with cardiopulmonary diseases. In addition, arginine supplementation could decrease accumulations of lactate and ammonia, metabolites involved in development of muscular fatigue. The aim of this study was to investigate the effect of short-term arginine supplementation on performance in intermittent anaerobic exercise and the underlying mechanism in well-trained male athletes. Ten elite male college judo athletes participated with a randomized crossover, placebo-controlled design. The subjects consumed 6 g/day arginine (ARG trial) or placebo (CON trial) for 3 days then performed an intermittent anaerobic exercise test on a cycle ergometer. Blood samples were collected before supplementation, before and during exercise and 0, 3, 6, 10, 30 and 60 min after exercise. ARG trial had significantly higher arginine concentrations than CON trial at the same time point before, during and after exercise. In both trials, nitrate and nitrite concentration was significantly higher during and 6 min after exercise comparing to the basal concentration. The increase in nitrate and nitrite concentration during exercise in both trials was parallel to the increase in plasma citrulline concentrations. There was no significant difference between the 2 trials in plasma nitrate and nitrite, lactate and ammonia concentrations and peak and average power in the exercise. The results of this study suggested that short-term arginine supplementation had no effect on nitric oxide production, lactate and ammonia metabolism and performance in intermittent anaerobic exercise in well-trained male athletes.


    Int J Sport Nutr Exerc Metab. 2009 Aug;19(4):355-65.
    Bescós R, Gonzalez-Haro C, Pujol P, Drobnic F, Alonso E, Santolaria ML, Ruiz O, Esteve M, Galilea P.

    Effects of dietary L-arginine intake on cardiorespiratory and metabolic adaptation in athletes.

    To assess the effect of diet enrichment with L-arginine or supplementation at high doses on physiological adaptation during exercise, 9 athletes followed 3 different diets, each over 3 consecutive days, with a wash-out period of 4 d between training sessions: control diet (CD), 5.5 +/- 0.3 g/d of L-arginine; Diet 1 (rich in L-arginine food), 9.0 +/- 1.1 g/d of L-arginine; and Diet 2 (the same as CD but including an oral supplement of 15 g/d), 20.5 +/- 0.3 g/d of L-arginine. Plasma nitrate levels of each participant were determined on the day after each treatment. Participants performed a submaximal treadmill test (initial speed 10-11 km/hr, work increments 1 km/hr every 4 min until 85-90% VO2max, and passive recovery periods of 2 min). Oxygen uptake and heart rate were monitored throughout the test. Blood lactate concentration ([La-]b) was determined at the end of each stage. Repeated-measures ANOVA and paired Student's t tests were used to compare the various physiological parameters between diets. The level of significance was set at p < .05. [La-]b showed a significant effect at the 5-min time point between CD and Diet 2 (CD 3.0 +/- 0.5 mM, Diet 2 2.5 +/- 0.5 mM, p = .03), but this tendency was not found at higher exercise intensities. No significant differences were observed in any of the cardiorespiratory or plasma nitrate levels. In conclusion, dietary L-arginine intake on the days preceding the test does not improve physiological parameters during exercise.


    Atherosclerosis. 1995 Dec;118(2):223-31.
    Wennmalm A, Edlund A, Granström EF, Wiklund O.

    Acute supplementation with the nitric oxide precursor L-arginine does not improve cardiovascular performance in patients with hypercholesterolemia.

    Endothelial dysfunction based on lack of nitric oxide (NO) may contribute to several settings of cardiovascular disorder. Chronic oral supplementation with the NO precursor L-arginine counteracts the development of aortic atherosclerosis in cholesterol-fed rabbits, and i.v. infusion of L-arginine may acutely improve endothelium-dependent coronary epicardial vasodilation in patients with hypercholesterolemia (HC). To clarify whether excess NO precursor may also improve general cardiovascular performance in HC, we measured working capacity indices of myocardial ischemia, and basal and post-occlusive forearm and skin blood flow in nine patients with elevated plasma cholesterol (9.1 +/- 0.2 mumol/l) following random double-blinded administration of L-arginine (16 g i.v.) or placebo. Infusion of L-arginine raised the plasma concentration of this amino acid from 85 +/- 12 to 2460 +/- 230 mumol/l but did not change the plasma level of the major NO metabolite nitrate. Maximal working capacity, indices of myocardial ischemia, and basal and post-occlusive blood flow in the skin or forearm did not differ between the treatments. The lack of positive effect of L-arginine compared to placebo indicates that excess NO precursor did not improve microvascular endothelial function in the patients, or alternatively, that the indices measured in the present study were not dependent on endothelial microvessel function. Thus, in patients with HC, deficiency of precursor for NO formation does not seem to impair either maximal exercise capacity myocardial perfusion during maximal exercise, or maximal vasodilator capacity in skeletal muscle or skin.


    Circulation. 2007 Jul 10;116(2):188-95. Epub 2007 Jun 25.
    Wilson AM, Harada R, Nair N, Balasubramanian N, Cooke JP.

    L-arginine supplementation in peripheral arterial disease: no benefit and possible harm.

    BACKGROUND: L-arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. L-arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of L-arginine on vascular reactivity and functional capacity in patients with PAD. METHODS AND RESULTS: The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral L-arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. L-arginine supplementation significantly increased plasma L-arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both L-arginine- and placebo-treated patients, the improvement in the L-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024). CONCLUSIONS: In patients with PAD, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the L-arginine-treated group. As opposed to its short-term administration, long-term administration of L-arginine is not useful in patients with intermittent claudication and PAD.

    So to put it blunty, NO products containing L-Arginine are pretty much worthless according to these studies.

    Although these studies do not show effects of exogenous L-Arginine on endogenous GH. I'm not stating GH is NOT raised and Arginine is totally worthless. As for NO production... Read above again.

  2. #2
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    Nitrates do elicit a NO response.



    J Appl Physiol. 2009 Oct;107(4):1144-55. Epub 2009 Aug 6.
    Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM.

    Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans.


    Pharmacological sodium nitrate supplementation has been reported to reduce the O2 cost of submaximal exercise in humans. In this study, we hypothesized that dietary supplementation with inorganic nitrate in the form of beetroot juice (BR) would reduce the O2 cost of submaximal exercise and enhance the tolerance to high-intensity exercise. In a double-blind, placebo (PL)-controlled, crossover study, eight men (aged 19-38 yr) consumed 500 ml/day of either BR (containing 11.2 +/- 0.6 mM of nitrate) or blackcurrant cordial (as a PL, with negligible nitrate content) for 6 consecutive days and completed a series of "step" moderate-intensity and severe-intensity exercise tests on the last 3 days. On days 4-6, plasma nitrite concentration was significantly greater following dietary nitrate supplementation compared with PL (BR: 273 +/- 44 vs. PL: 140 +/- 50 nM; P < 0.05), and systolic blood pressure was significantly reduced (BR: 124 +/- 2 vs. PL: 132 +/- 5 mmHg; P < 0.01). During moderate exercise, nitrate supplementation reduced muscle fractional O2 extraction (as estimated using near-infrared spectroscopy). The gain of the increase in pulmonary O2 uptake following the onset of moderate exercise was reduced by 19% in the BR condition (BR: 8.6 +/- 0.7 vs. PL: 10.8 +/- 1.6 ml.min(-1).W(-1); P < 0.05). During severe exercise, the O2 uptake slow component was reduced (BR: 0.57 +/- 0.20 vs. PL: 0.74 +/- 0.24 l/min; P < 0.05), and the time-to-exhaustion was extended (BR: 675 +/- 203 vs. PL: 583 +/- 145 s; P < 0.05). The reduced O2 cost of exercise following increased dietary nitrate intake has important implications for our understanding of the factors that regulate mitochondrial respiration and muscle contractile energetics in humans.



    Acta Physiol (Oxf). 2007 Sep;191(1):59-66. Epub 2007 Jul 17.
    Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B.

    Effects of dietary nitrate on oxygen cost during exercise.


    AIM: Nitric oxide (NO), synthesized from l-arginine by NO synthases, plays a role in adaptation to physical exercise by modulating blood flow, muscular contraction and glucose uptake and in the control of cellular respiration. Recent studies show that NO can be formed in vivo also from the reduction of inorganic nitrate (NO(3) (-)) and nitrite (NO(2) (-)). The diet constitutes a major source of nitrate, and vegetables are particularly rich in this anion. The aim of this study was to investigate if dietary nitrate had any effect on metabolic and circulatory parameters during exercise. METHOD: In a randomized double-blind placebo-controlled crossover study, we tested the effect of dietary nitrate on physiological and metabolic parameters during exercise. Nine healthy young well-trained men performed submaximal and maximal work tests on a cycle ergometer after two separate 3-day periods of dietary supplementation with sodium nitrate (0.1 mmol kg(-1) day-1) or an equal amount of sodium chloride (placebo). RESULTS: The oxygen cost at submaximal exercise was reduced after nitrate supplementation compared with placebo. On an average Vo(2) decreased from 2.98 +/- 0.57 during CON to 2.82 +/- 0.58 L min(-1) during NIT (P < 0.02) over the four lowest submaximal work rates. Gross efficiency increased from 19.7 +/- 1.6 during CON to 21.1 +/- 1.3% during NIT (P < 0.01) over the four lowest work rates. There was no difference in heart rate, lactate [Hla], ventilation (VE), VE/Vo(2) or respiratory exchange ratio between nitrate and placebo during any of the submaximal work rates. CONCLUSION: We conclude that dietary nitrate supplementation, in an amount achievable through a diet rich in vegetables, results in a lower oxygen demand during submaximal work. This highly surprising effect occurred without an accompanying increase in lactate concentration, indicating that the energy production had become more efficient. The mechanism of action needs to be clarified but a likely first step is the in vivo reduction of dietary nitrate into bioactive nitrogen oxides including nitrite and NO.


    Am J Physiol. 1997 Jul;273(1 Pt 1):E220-5.
    Roberts CK, Barnard RJ, Scheck SH, Balon TW.

    Exercise-stimulated glucose transport in skeletal muscle is nitric oxide dependent.

    It has been suggested that there are separate insulin-stimulated and contraction-stimulated glucose transport pathways in skeletal muscle. This study examined the effects of nitric oxide on glucose transport in rat skeletal muscle by use of an isolated sarcolemmal membrane preparation and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), administered in the drinking water (1 mg/ml). Female Sprague-Dawley rats were divided into five groups: control, acute exercise, acute exercise+L-NAME, insulin stimulated, and insulin stimulated+L-NAME. Exercise (45 min of exhaustive treadmill running) increased glucose transport (37 +/- 2 to 76 +/- 5 pmol.mg-1.15 s-1) and this increase was completely inhibited by L-NAME (40 +/- 4 pmol.mg-1.15 s-1). A maximum dose of insulin increased glucose transport (87 +/- 10 pmol.mg-1.15 s-1), and adding L-NAME had no effect (87 +/- 11 pmol.mg-1.15 s-1). In addition, exercise, but not exercise+L-NAME, increased sarcolemma GLUT-4 content. This study confirms that there are separate pathways for contraction- and insulin-stimulated glucose transport. More importantly, although exercise and insulin both significantly increased glucose transport, L-NAME had no effect on insulin-stimulated glucose transport but blocked the exercise-stimulated transport. We conclude that nitric oxide is involved in the signal transduction mechanism to increase glucose transport during exercise.

  3. #3
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    Try a supplement that contains Nitrates, not Arginine and see what happens I guess...

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    One of the most tried and true supplements is deemed pretty much worthless?

    Not buying it.

    There are usually 10 different studies on a supplement that say 10 different things.

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    If this is true my heart is broken, I was married to arginine.

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    Arginine has so many conflicting studies about it, that its hard to formulate an opinion one way or another. This has got to be one of the most studied dietary supplements, maybe as much as if not more than creatine as a sport performance supplement?
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    I'm not stating its garbage. There are studies for and against on almost everything! If someone would like to post some studies on L-Arginine and NO production, lets see em.

    I pulled this from a very knowledgeable member over at bb.com, but is also a rep for ThermoLife.

    Either way, these studies are interesting.

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    How about AAKG? I always feel a huge pump when taking it that I relate to vasodialation.

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    Quote Originally Posted by M302_Imola View Post
    How about AAKG? I always feel a huge pump when taking it that I relate to vasodialation.
    Word. I can feel my muscles get more pumped when lifting and and see my veins more visibly pretty much all day after a measly 3g daily dose of AAKG every morning. These nitrates sound interesting yes but AAKG works (thru SOME mechanism even if not NO) and is one of the first supplements that I took and could tell it actually worked right from the first dose.

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    Quote Originally Posted by Dog-Slime View Post
    Word. I can feel my muscles get more pumped when lifting and and see my veins more visibly pretty much all day after a measly 3g daily dose of AAKG every morning. These nitrates sound interesting yes but AAKG works (thru SOME mechanism even if not NO) and is one of the first supplements that I took and could tell it actually worked right from the first dose.
    Yep and the leaner you are the more these "benefits" shine through. I do 4-5g 30 mins before my workout and love the stuff.

  11. #11
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    Quote Originally Posted by Swifto View Post
    Try a supplement that contains Nitrates, not Arginine and see what happens I guess...
    I recall reading a study similar to the following where it added that and increase in nitrates increased chances of certain types of cancer but it didn't specify which types. Also, it mentioned a 2-week ingestion of nitrates from beetroot for maximum benefits.
    FWIW:
    Drinking the juice of red garden beets - beetroot juice - boosts your stamina and could help you exercise for up to 16 percent longer. A study led by the University of Exeter, published August 6, 2009, shows for the first time how the nitrate contained in beetroot juice leads to a reduction in oxygen uptake, making exercise less tiring.

    The study reveals that drinking beet root juice reduces oxygen uptake to an extent that cannot be achieved by any other known means, including exercise training.

    The research team believes that the findings could be of great interest to endurance athletes. They could also be relevant to elderly people or those with cardiovascular, respiratory or metabolic diseases.

    The research team conducted their study with eight men aged between 19 and 38. They were given 500 ml per day of organic beetroot juice for six consecutive days before completing a series of tests, involving cycling on an exercise bike. On another occasion, they were given a placebo of blackcurrant cordial for six consecutive days before completing the same cycling tests.

    After drinking beetroot juice the group was able to cycle for an average of 11.25 minutes, which is 92 seconds longer than when they were given the placebo. This would translate into an approximate 2 percent reduction in the time taken to cover a set distance. The group that had consumed the beetroot juice also had lower resting blood pressure.

    The researchers are not yet sure of the exact mechanism that causes the nitrate in the beetroot juice to boost stamina. However, they suspect it could be a result of the nitrate turning into nitric oxide in the body, reducing the oxygen cost of exercise.

    The research was carried out by the University of Exeter and Peninsula Medical School and published in the Journal of Applied Physiology. The research team now hopes to conduct further studies to try to understand in more detail the effects of nitrate-rich foods on exercise physiology.

    Corresponding author of the study, Professor Andy Jones of the University of Exeter’s School of Sport and Health Sciences, said: “Our study is the first to show that nitrate-rich food can increase exercise endurance. We were amazed by the effects of beetroot juice on oxygen uptake because these effects cannot be achieved by any other known means, including training. I am sure professional and amateur athletes will be interested in the results of this research. I am also keen to explore the relevance of the findings to those people who suffer from poor fitness and may be able to use dietary supplements to help them go about their daily lives.”

    This study follows research by Barts and the London School of Medicine and the Peninsula Medical School (published in February 2008 in the American Heart Association journal Hypertension), which found that beetroot juice reduces blood pressure.

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