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Citrulline/malate promotes aerobic energy production in human exercising muscle
  1. D Bendahan1,
  2. J P Mattei1,
  3. B Ghattas2,
  4. S Confort-Gouny1,
  5. M E Le Guern3,
  6. P J Cozzone1
  1. 1Centre de Résonance Magnétique Biologique et Médicale, UMR CNRS 6612, Faculté de Médecine de la Timone, Marseille, France
  2. 2Groupement de Recherche en Econométrie Quantitative d'Aix-Marseille, Marseille
  3. 3Laboratoire Biocodex, 92120 Montrouge, France
  1. Correspondence to:
    Professor Cozzone, Centre de Résonance Magnétique Biologique et Médicale, UMR CNRS 6612, Faculté de Médecine de Marseille, 27, Bd J Moulin, 13005 Marseille France;


Background: Previous studies have shown an antiasthenic effect of citrulline/malate (CM) but the mechanism of action at the muscular level remains unknown.

Objective: To investigate the effects of CM supplementation on muscle energetics.

Methods: Eighteen men complaining of fatigue but with no documented disease were included in the study. A rest-exercise (finger flexions)-recovery protocol was performed twice before (D−7 and D0), three times during (D3, D8, D15), and once after (D22) 15 days of oral supplementation with 6 g/day CM. Metabolism of the flexor digitorum superficialis was analysed by 31P magnetic resonance spectroscopy at 4.7 T.

Results: Metabolic variables measured twice before CM ingestion showed no differences, indicating good reproducibility of measurements and no learning effect from repeating the exercise protocol. CM ingestion resulted in a significant reduction in the sensation of fatigue, a 34% increase in the rate of oxidative ATP production during exercise, and a 20% increase in the rate of phosphocreatine recovery after exercise, indicating a larger contribution of oxidative ATP synthesis to energy production. Considering subjects individually and variables characterising aerobic function, extrema were measured after either eight or 15 days of treatment, indicating chronological heterogeneity of treatment induced changes. One way analysis of variance confirmed improved aerobic function, which may be the result of an enhanced malate supply activating ATP production from the tricarboxylic acid cycle through anaplerotic reactions.

Conclusion: The changes in muscle metabolism produced by CM treatment indicate that CM may promote aerobic energy production.

  • 31P magnetic resonance spectroscopy
  • anaplerosis
  • fatigue
  • energetics
  • skeletal muscle
  • CM, citrulline/malate
  • TCA, tricarboxylic acid cycle
  • MRS, magnetic resonance spectroscopy
  • PCr, phosphocreatine
  • EC, energy cost

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