Combined effects of hyperaminoacidemia and oxandrolone  on skeletal muscle protein synthesis

Sheffield‐Moore, Melinda; Wolfe, Robert R.; Gore, Dennis C.; Wolf, Steven E.; Ferrer, Dennis M.; Ferrando, Arny A.

doi:10.1152/ajpendo.2000.278.2.e273

Cited by 27 publications

(27 citation statements)

References 21 publications

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“…Insight into how oxandrolone may exert its effects may be found in a study by Sheffield-Moore et al 19 In their study, which used stable isotopes to assess protein metabolism, they found that in young men, oxandrolone significantly increased the fractional synthetic rate without an increase in muscle protein breakdown, resulting in a positive net protein balance, as well as an improved intracellular use of amino acids. In addition, their study found a significant increase in the number of androgen receptors, through which anabolic agents translate their action.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Oxandrolone and Exercise on Muscle Mass and Function in Children With Severe Burns

2007

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OBJECTIVES-Severe burns are associated with a significant loss of muscle and strength. Studies have reported that oxandrolone improves lean body mass in muscle-wasting conditions. Also shown previously in burned children is that an exercise program increases lean body mass and muscle strength. We hypothesized that oxandrolone, in combination with exercise, would increase lean body mass and muscle strength in severely burned children more than oxandrolone alone or exercise alone.METHODS AND PATIENTS-Fifty-one burned children (≥40% total body surface area burned) were randomly assigned to receive oxandrolone alone (0.1 mg/kg per day orally; n = 9), oxandrolone and exercise (n = 14), placebo and no exercise (n = 11), or placebo and exercise (n = 17). Administration of oxandrolone was started at discharge and continued until 1 year after burn. The 12-week exercise training program was started 6 months after burn. Serum hormones, lean body mass, muscle strength, and peak cardiopulmonary capacity were assessed at 6 (baseline) and 9 months after burn. Data were analyzed using a 1-way analysis of variance, and significance was set at P < . 05. RESULTS-The mean percentage of change or increase in weight and lean body mass in the oxandrolone and exercise group was significant compared with placebo and exercise, as well as with the oxandrolone alone group or placebo and no exercise group. Furthermore, lean body mass was significantly improved in the oxandrolone and exercise, oxandrolone alone, and placebo and exercise group compared with the group only receiving placebo. Muscle strength significantly increased in oxandrolone and exercise, placebo and exercise, and the oxandrolone alone group when compared with the placebo and no exercise group. The peak cardiopulmonary capacity was significantly higher in both exercise groups. Insulin-like growth factor 1 was significantly increased in the oxandrolone alone group compared with placebo and exercise and placebo and no exercise. Both exercise groups showed significant changes in insulin-like binding-protein-3 when compared with groups without exercise.CONCLUSIONS-Oxandrolone, in combination with exercise, is beneficial in severely burned children, thus improving their rehabilitation. Keywordsburns; exercise; hormones; lean mass; oxandrolone Severe burns are physically and psychologically catastrophic. Severely burned children have an elevated resting energy expenditure, whole body catabolism, and muscle weakness, which are worsened by prolonged bed rest and physical inactivity. 1,2Address correspondence to Oscar E. Suman, PhD, Children's Wellness and Exercise Center, Shriners Hospitals for Children, 815 Market St, Galveston, TX 77550. E-mail: oesuman@utmb.edu. The authors have indicated they have no financial relationships relevant to this article to disclose. NIH Public Access Author ManuscriptPediatrics. Author manuscript; available in PMC 2008 May 5. Published in final edited form as:Pediatrics. 2007 January ; 119(1): e109-e116. NIH-PA Author ManuscriptNIH-PA Autho...

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Section: Discussionmentioning

confidence: 99%

The Effects of Oxandrolone and Exercise on Muscle Mass and Function in Children With Severe Burns

2007

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“…A second catheter was placed in a dorsal hand vein, and the hand was heated to obtain arterialized blood samples (1). After collection of basal measures (protein synthesis and signaling), a primed, continuous infusion of unlabeled amino acids (10% Travasol; Clintec Nutrition, Deerfield, IL) was initiated (8,16,41) and continued for 3 h (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, after repeated bouts of RE it is possible that there is a lower net accumulation of new muscle protein and a reduced ability to maintain or increase muscle mass in the soleus. Collectively, these results indicate a muscle-specific (vastus lateralis vs. soleus) protein metabolic response to disuse and RE and highlight the need for the development of muscle-specific countermeasures to muscle atrophy.Because amino acids have been shown to stimulate vastus lateralis protein synthesis to a similar extent as seen with RE (8,35,41), they may provide an additional means of elevating protein synthesis in the soleus and stimulating muscle growth during unloading. However, the response to supplemental amino acids has not been studied in the soleus muscle, and it is unclear how the soleus will respond to nutritional stimulation.…”

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confidence: 99%

“…Because amino acids have been shown to stimulate vastus lateralis protein synthesis to a similar extent as seen with RE (8,35,41), they may provide an additional means of elevating protein synthesis in the soleus and stimulating muscle growth during unloading. However, the response to supplemental amino acids has not been studied in the soleus muscle, and it is unclear how the soleus will respond to nutritional stimulation.…”

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Human soleus and vastus lateralis muscle protein metabolism with an amino acid infusion

Carroll

Fluckey²,

Williams³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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The calf muscles, compared with the thigh, are less responsive to resistance exercise in ambulatory and bed-rested individuals, apparently due to muscle-specific differences in protein metabolism. We chose to evaluate the efficacy of using amino acids to elevate protein synthesis in the soleus, because amino acids have been shown to have a potent anabolic effect in the vastus lateralis. Mixed muscle protein synthesis in the soleus and vastus lateralis was measured before and after infusion of mixed amino acids in 10 individuals (28 +/- 1 yr). Phosphorylation of ribosomal protein p70 S6 kinase (p70S6K; Thr389) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1; Thr37/46) was also evaluated at rest and after 3 h of amino acid infusion. Basal protein synthesis was similar (P = 0.126), and amino acids stimulated protein synthesis to a similar extent (P = 0.004) in the vastus lateralis (0.043 +/- 0.011%/h) and soleus (0.032 +/- 0.017%/h). Phosphorylation of p70S6K (P = 0.443) and 4E-BP1 (P = 0.192) was not increased in either muscle; however, the soleus contained more total (P = 0.002) and phosphorylated (P = 0.013) 4E-BP1 than the vastus lateralis. These data support the need for further study of amino acid supplementation as a means to compensate for the reduced effectiveness of calf resistance exercise in ambulatory individuals and those exposed to extended periods of unloading. The greater 4E-BP1 in the soleus suggests that there is a muscle-specific distribution of general translational initiation machinery in human skeletal muscle.

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“…New advances in synthetic hormones provide promise for expanded applications in the future. For example, the synthetic steroid oxandralone stimulates muscle growth, possibly without the same magnitude of androgenizing effects of testosterone (55). At the same time, there are limits and dangers of hormonal therapy caused by unexpected, unwanted, and often unrecognized complications.…”

Section: Hormonal Therapymentioning

confidence: 99%

The underappreciated role of muscle in health and disease

Wolfe

2006

The American Journal of Clinical Nutrition

1,206

938

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Muscle plays a central role in whole-body protein metabolism by serving as the principal reservoir for amino acids to maintain protein synthesis in vital tissues and organs in the absence of amino acid absorption from the gut and by providing hepatic gluconeogenic precursors. Furthermore, altered muscle metabolism plays a key role in the genesis, and therefore the prevention, of many common pathologic conditions and chronic diseases. Nonetheless, the maintenance of adequate muscle mass, strength, and metabolic function has rarely, if ever, been targeted as a relevant endpoint of recommendations for dietary intake. It is therefore imperative that factors directly related to muscle mass, strength, and metabolic function be included in future studies designed to demonstrate optimal lifestyle behaviors throughout the life span, including physical activity and diet.Am J Clin Nutr 2006;84:475-82.

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Combined effects of hyperaminoacidemia and oxandrolone on skeletal muscle protein synthesis

Cited by 27 publications

References 21 publications

The Effects of Oxandrolone and Exercise on Muscle Mass and Function in Children With Severe Burns

The Effects of Oxandrolone and Exercise on Muscle Mass and Function in Children With Severe Burns

Human soleus and vastus lateralis muscle protein metabolism with an amino acid infusion

The underappreciated role of muscle in health and disease

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