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

https://doi.org/10.1016/j.jnutbio.2008.05.005Get rights and content

Abstract

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.

Introduction

Arginine, a substrate for nitric oxide (NO) synthase, has drawn significant attention for its potential role in alleviating endothelial dysfunction and improving exercise performance through increasing NO production [1]. The vasodilation effect of arginine has been shown in both central and peripheral circulation. Oral arginine supplementation could improve coronary endothelial function in patients with nonobstructive coronary artery disease [2]. Arginine given orally or intravenously could also improve endothelium-dependent vasodilation in the forearm [3], [4], [5]. NO also plays a role in exercise-induced vasodilation in patients and healthy subjects [6], [7], [8]. The impairment of NO production and the resulting endothelial dysfunction are the major factors that limit exercise capacity in patients with various cardiopulmonary conditions. As the result, arginine supplementation has been shown to improve exercise capacity in patients with hypercholesterolemia [9], chronic heart failure [10], [11], [12], pulmonary hypertension [13] and stable angina pectoris [14], [15], [16].

Arginine supplementation could also improve exercise capacity by altering the exercise-induced accumulations of lactate and ammonia, metabolites which have been shown to be involved in the development of muscular fatigue due to the increased muscular acidity [17], [18], [19]. In addition, ammonia has also been suggested to play a role in fatigue at the central nervous system [20]. It has been shown that 3 g of arginine hydrochloride given intravenously resulted in significantly lower blood lactate and ammonia concentrations compared to a placebo after maximal graded exercise on a cycle ergometer in recreationally active subjects [21]. The reduction in exercise-induced ammonia accumulation may be associated with the increased ureagenesis as ornithine, an intermediate of the urea cycle, was significantly elevated after the supplementation. The reduction in lactate accumulation may have partly resulted from increased peripheral muscle perfusion as the increase in citrulline, a by-product of NO synthesis, was negatively correlated with the increase in lactate. Oral supplementation for 10 days [22] or prior to the exercise [23] of arginine aspartate or arginine glutamate complex could also reduce the elevation in blood lactate and ammonia after strenuous exercise.

The effect of arginine on exercise capacity in healthy subjects and well-trained athletes is less clear. It has been suggested that oral supplementation of arginine, along with glycine and α-ketoisocaproic acid prior to exercise, may increase work output in exhaustive anaerobic exercise in healthy young males [24], [25]. The supplementation of arginine and a-ketoglutarate for 8 weeks could also increase peak power in Wingate test in resistance-trained men [26]. However, the role of arginine in these studies was difficult to identify because the two other components may also contribute to the delay of fatigue. On the other hand, it has been revealed that a 14-day supplementation of arginine aspartate did not affect the performance in the subsequent marathon in endurance runners [27].

Despite the numerous studies in cardiopulmonary patients, the role of arginine supplementation on NO production, exercise capacity and exercise metabolism in athletes is still not clear. As arginine could increase exercise-induced vasodilation and remove the metabolites that may inhibit exercise performance, we hypothesized that oral supplementation of arginine may improve exercise performance in well-trained athletes. The aim of this study was to investigate whether short-term arginine supplementation could improve performance in intermittent anaerobic exercise and the underlying mechanism in well-trained male athletes. Plasma lactate and ammonia concentrations were measured to examine the metabolic effect. Furthermore, plasma concentrations of nitrate and nitrite (NOx), the major NO metabolites, and citrulline, the by-product of NO synthesis, were measured to determine the role of NO.

Section snippets

Subjects

Ten elite male college judo athletes recruited from National Taiwan College of Physical Education participated in this study. The subjects with similar body weight were selected to avoid potential difference in exercise performance and supplementation dosage. The potential subjects with known cardiovascular disease risks, with musculoskeletal injuries, or who have taken any protein supplement in the previous 3 months were excluded. The potential subjects with abnormally high or low plasma

Results

Plasma arginine concentrations in each sampling time in ARG and CON trials are shown in Fig. 2. The supplementation (P=.013) and time (P<.001) effects were significant. Plasma arginine concentrations were significantly increased from the baseline before, during and after exercise in ARG trial, while it remained unchanged throughout the sampling period in CON trial. As the result, ARG trial had significantly higher arginine concentrations than CON trial at the same time point before, during and

Discussion

The results of this study suggested that short-term arginine supplementation had no effect on NO production, lactate and ammonia metabolism and performance in intermittent anaerobic exercise in well-trained male judo athletes.

Our results showed that the performance in each set of the intermittent anaerobic exercise test were similar in ARG and CON trials. The intermittent exercise protocol used in this study was similar to the regular training and competition pattern of these well-trained judo

References (42)

  • KawanoH et al.

    Endothelial dysfunction in hypercholesterolemia is improved by L-arginine administration: possible role of oxidative stress

    Atherosclerosis

    (2002)
  • MoncadaS et al.

    The L-arginine-nitric oxide pathway

    N Engl J Med

    (1993)
  • LermanA et al.

    Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans

    Circulation

    (1998)
  • CreagerMA et al.

    L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans

    J Clin Invest

    (1992)
  • JoynerMJ et al.

    Nitric oxide and physiologic vasodilation in human limbs: where do we go from here?

    Can J Appl Physiol

    (2003)
  • ClarksonP et al.

    Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults

    J Clin Invest

    (1996)
  • BrownMD et al.

    Nitric oxide biomarkers increase during exercise-induced vasodilation in the forearm

    Int J Sports Med

    (2000)
  • LewisTV et al.

    Exercise training increases basal nitric oxide production from the forearm in hypercholesterolemic patients

    Arterioscler Thromb Vasc Biol

    (1999)
  • RectorTS et al.

    Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure

    Circulation

    (1996)
  • KanayaY et al.

    Effects of L-arginine on lower limb vasodilator reserve and exercise capacity in patients with chronic heart failure

    Heart

    (1999)
  • DoutreleauS et al.

    Chronic L-arginine supplementation enhances endurance exercise tolerance in heart failure patients

    Int J Sports Med

    (2006)
  • Cited by (73)

    • Nitric oxide, aging and aerobic exercise: Sedentary individuals to Master's athletes

      2022, Nitric Oxide - Biology and Chemistry
      Citation Excerpt :

      The semi-essential amino acid, l-arginine, is a necessary substrate for all NOS isoforms [91]. Although healthy humans synthesize enough l-arginine to saturate NOS, some [84,92,93] but not all studies [94–97] have shown that oral ingestion of l-arginine (typically ∼3–6 mg) can augment NO production, as measured by circulatory nitrate and nitrite levels. Studies examining the effects of l-arginine on blood flow and exercise performance, at least in young adults, are equivocal; some report benefits on exercise efficiency and tolerance [84] but others report no effects on muscular endurance [98] or exercise capacity [97,99,100].

    • The effects of acute and chronic oral L-arginine supplementation on exercise-induced ammonia accumulation and exercise performance in healthy young men: A randomised, double-blind, cross-over, placebo-controlled trial

      2022, Journal of Exercise Science and Fitness
      Citation Excerpt :

      The acute effect of arginine supplementation on exercise performance has been evaluated in previous efficacy studies using a randomised, double-blind, cross-over, placebo-controlled design6–12 (for a review of these, see Ref. 13). These studies reported that acute arginine supplementation (a few hours or 3 days prior to the study) does not alter anaerobic, aerobic or strength exercise performance,6–9,11,12 except for one study.10 In a randomised, double-blind, placebo-controlled design, the effect of chronic arginine supplementation (i.e., from 7 days to 45 days) on exercise performance was examined, and the findings were inconsistent.13

    • An Overview of Ornithine, Arginine, and Citrulline in Exercise and Sports Nutrition

      2018, Nutrition and Enhanced Sports Performance: Muscle Building, Endurance, and Strength
    View all citing articles on Scopus

    This study was financially supported by National Science Council, Taiwan (NSC-92-2413-H-028-004).

    View full text