HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mok, E. Articles by Hankard, R. Search for Related Content PubMed PubMed Citation Articles by Mok, E. Articles by Hankard, R. Agricola Articles by Mok, E. Articles by Hankard, R.

Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy^1,2,3

¹ From the Centre d'Investigation Clinique 9202 INSERM, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France (EM, CE-DV, CD, and RH); the LAPHAP EA3813, Université de Poitiers, Poitiers, France (EM, RH); the Clinique de Pédiatrie, CHR&U de Lille, Hôpital Jeanne de Flandre, Lille, France (FG); the Biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France (OR); the Pharmacie, Assistance Publique-Hôpitaux de Paris, Hôpital Jean-Verdier, Paris, France(J-EF); the Service de Neuropédiatrie, CHR&U de Lille, Hôpital Roger-Salengro, Lille, France (J-MC); and the Clinical Research Center, CHU de Poitiers, Poitiers, France (JG)

² Supported by the Assistance Publique-Hôpitaux de Paris and a grant from the Institut National de la Santé et de la Recherche Médicale #33104700 (RAF 01005) (to RH) and by the Association Française Contre les Myopathies (to RH). EM is supported by Le Prix de Nutrition de la Fédération Association Nationale pour les Traitements à Domicile, les Innovations et la Recherche, awarded by La Société Francophone de Nutrition Entérale et Parentérale and Les Fonds de la Recherche en Santé Québec PhD Fellowship.

³ Reprints not available. Address correspondence to R Hankard, Pédiatrie Multidisciplinaire-Nutrition de l'Enfant, Centre Hospitalier Universitaire de Poitiers, 2 rue de la Milétrie, 86021 Poitiers Cedex, France. E-mail: r.hankard{at}chu-poitiers.fr.

	ABSTRACT

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Background: Glutamine has been shown to acutely decrease whole-body protein degradation in Duchenne muscular dystrophy (DMD).

Objective: To improve nutritional support in DMD, we tested whether oral supplementation with glutamine for 10 d decreased whole-body protein degradation significantly more than did an isonitrogenous amino acid control mixture.

Design: Twenty-six boys with DMD were included in this randomized, double-blind parallel study; they received an oral supplement of either glutamine (0.5 g · kg^–1 · d^–1) or an isonitrogenous, nonspecific amino acid mixture (0.8 g · kg^–1 · d^–1) for 10 d. The subjects in each group were not clinically different at entry. Leucine and glutamine metabolisms were estimated in the postabsorptive state by using a primed continuous intravenous infusion of [1-¹³C]leucine and [2-¹⁵N]glutamine before and 10 d after supplementation.

Results: A significant effect of time was observed on estimates of whole-body protein degradation. A significant (P < 0.05) decrease in the rate of leucine appearance (an index of whole-body protein degradation) was observed after both glutamine and isonitrogenous amino acid supplementation [ ±SEM: 136 ± 9 to 124 ± 6 µmol · kg fat-free mass (FFM)^–1 · h^–1 for glutamine and 136 ± 6 to 131 ± 8 µmol · kg FFM^–1 · h^–1 for amino acids]. A significant (P < 0.05) decrease in endogenous glutamine due to protein breakdown was also observed (91 ± 6 to 83 ± 4 µmol · kg FFM^–1 · h^–1 for glutamine and 91 ± 4 to 88 ± 5 µmol · kg FFM^–1 · h^–1 for amino acids). The decrease in the estimates of whole-body protein degradation did not differ significantly between the 2 supplemental groups.

Conclusion: Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.

Key Words: Duchenne muscular dystrophy • children • randomized controlled clinical trial • supplement • oral administration • stable isotopes • protein metabolism • glutamine • leucine • amino acids

	INTRODUCTION

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Nutritional support was shown to improve outcome in several clinical conditions (1). Certain nutrients, such as glutamine, have distinct properties that are separate from their role of providing calories or nitrogen (2, 3), and they are called "pharmaconutrients." Glutamine has a protein-sparing effect in cell cultures, animal models, and humans (4). This effect may be useful in catabolic situations, when cellular glutamine concentrations decline (5, 6).

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle wasting and a reduced functional capacity. Protein metabolism in DMD, which has been studied by using stable isotope tracers and nitrogen balance, suggests that the cause of muscle wasting is a reduction in muscle protein synthesis or an increase in protein degradation (7-9). Furthermore, muscle wasting in DMD is associated with a decrease in glutamine turnover and a more negative whole-body leucine balance (10). Because glutamine is mainly produced by the muscle, and muscle mass is severely reduced in DMD, the need for glutamine may be increased in persons who have this disease. Moreover, in DMD, as in other protein-wasting situations, the intramuscular glutamine concentration is low (11). Thus, in DMD, as in situations of catabolic stress, glutamine may be considered a conditionally essential amino acid (10).

In a previous study using stable isotope methodology, we showed that acute (5 h) oral glutamine decreased whole-body protein degradation in DMD compared with placebo (12). The objectives of the present study were to test, in the same population, whether this effect persists when glutamine is administered over longer periods (10 d) and whether the effect is specific to glutamine.

	SUBJECTS AND METHODS

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
The protocol was approved by the Paris-Bichat Ethics Committee (Comité Consultatif pour la Protection de la Personne dans la Recherche Biomédicale) and conducted according to the principles of the Declaration of Helsinki. All families gave their written informed consent after a thorough explanation of the study protocol by the investigator to both the parents and the children. The study was performed at the Robert Debré Hospital Clinical Investigation Center (CIC 9202 INSERM-Assistance Publique-Hôpitaux de Paris). Subjects were selected on the basis of the following eligibility criteria: male sex, aged 7–15 y, and diagnosis of DMD by clinical history, muscle biopsy sample, or molecular biology. Children with acute pathology who had either cardiac or respiratory insufficiency or those who were taking corticosteroids at the time were excluded from the study. Children had stable weights and clinical status before study entry.

The children were hospitalized for 24 h on 2 separate days, before and after a 10-d oral supplement of either L-glutamine or an isonitrogenous control made of a mixture of amino acids. The children were admitted the night before the tracer infusion. They fasted after dinner (with the exception of ad libitum water) until the end of the study (1300 the following day). Whole-body leucine and glutamine metabolisms were studied by using a primed continuous infusion of L-[1-¹³C]leucine (99%: 3 µmol/kg, 3 µmol · kg^–1 · h^–1; Euriso-top,CEA group, St-Aubin, France) and L-[2-¹⁵N]glutamine (98%: 8 µmol/kg, 8 µmol · kg^–1 · h^–1; Euriso-top, CEA group) for 5 h (0800 to 1300). Arterialized blood samples (5 mL) were withdrawn at baseline and every 10 min over the last hour of the infusion (during the isotopic enrichment plateau). Breath samples were obtained simultaneously with blood samples, and the carbon dioxide production rate (CO₂) was measured at baseline and over the last hour of the infusion.

L-Glutamine (0.5 g · kg^–1 · d^–1; ADP Pharm Lab, Reventin Vaugris, France) and the isonitrogenous amino acid mixture (0.8 g · kg^–1 · d^–1, ie, 96 mg N · kg^–1 · d^–1; Cooper, Melun, France) were prepared according to good pharmaceutical practices by a pharmacist independent of the investigator and were randomly allocated to patients in a double-blind fashion. The children were instructed to take the supplemental glutamine or control amino acid mixture once per day in the morning mixed with yogurt at breakfast. The composition of the control amino acid mixture was 0.78 g L-arginine, 0.21 g L-cysteine [chloride (Cl)], 0.66 g L-histidine (Cl), 1.30 g L-isoleucine, 2.08 g L-leucine, 1.85 g L-lysine (Cl), 0.92 g L-phenylalanine, 0.83 g L-threonine, 1.00 g L-tyrosine, 1.47 g L-valine, 0.78 g L-alanine, 2.66 g L-glutamate, 0.40 g L-glycine, which provided a total of 15.64 g, ie, 1.92 g N. The 2 supplements were prepared as powders of identical taste, odor, and appearance and were flavored with banana, caramel, and artificial sweetener (Aspartame; Cooper). Comments from the children concerning taste and appearance of the supplements varied and were independent of whichever treatment the child received.

Plasma -ketoisocaproic acid (KIC), the intracellular metabolite of leucine (MTBSTFA derivative; Sigma-Aldrich, St Quentin Fallavier, France), and glutamine enrichments were measured by gas chromatography–mass spectrometry (Automass system 2-Benchtop Quadrupole Mass spectrometer and DB1 25–30 M Finnigan Mat column; ThermoFinnigan, Les Ulys, France) (13-15). The ¹³CO₂ enrichment in expired air (E¹³CO₂) was measured with an infrared spectrometer (IRIS; Wagner Analysen Technik Vertriebs GmbH, Bremen, Germany).

The rate of leucine appearance (Ra_Leu, in µmol/kg/h) and leucine oxidation (Ox_Leu) were calculated with plasma KIC enrichments (E_pKIC). Ra_Leu was calculated as:

(1)

where i_[13C]Leu is the tracer infusion rate (in µmol · kg^–1 · h^–1) and E_iLeu is the leucine tracer enrichment in the intravenous infusate (16).

The leucine oxidation rate (Ox_Leu, in µmol · kg^–1 · h^–1) was calculated as:

(2)

where E¹³CO₂ is the ¹³CO₂ enrichment in expired air (mol % enrichment); CO₂ is the carbon dioxide production rate (in mL/min), as measured by indirect calorimetry (GEM; Europa scientific, Crewe, United Kingdom) (12); 60 converts min to h; kCO₂ is the fractional recovery of carbon dioxide in expired air; 22.4 converts mL gas to mmol; 1000 converts nmol to µmol; and weight is in kg.

The nonoxidative leucine disposal rate (NOLD, in µmol/kg/h), an index of protein synthesis, was calculated as:

(3)

Whole-body glutamine exchange in plasma (Ra_Gln, in µmol · kg^–1 · h^–1) was calculated as:

(4)

where E_iGln and E_pGln are the glutamine enrichments (mol% enrichment) in the intravenous infusate and plasma, respectively, and i_[15N]Gln is the glutamine tracer infusion rate (in µmol · kg^–1 · h^–1).

In the postabsorptive state, by definition, the endogenous rate of appearance of glutamine (Ra_EndoGln) in plasma equals Ra_Gln.

Endogenous (body) glutamine arising from protein degradation (B_Gln) was calculated as:

(5)

where 0.07 and 0.08 are the assumed glutamine and leucine contents of body protein (g/g protein), respectively, and 146 and 131 g/mol are the glutamine and leucine molecular weights, respectively.

Glutamine de novo synthesis (D_Gln) was calculated as:

(6)

Because fat-free mass (FFM) represents an index of metabolically active tissue, and because anthropometric measures, such as weight, can be misleading in DMD due to excess body fat (17), measures of whole-body leucine and glutamine metabolism were adjusted for FFM.

Body composition was estimated by using monofrequency (50 kHz) bioelectrical impedance analysis (101 Q; RJL systems, Clinton Township, MI) (18), because a bioelectrical impedance analysis provides estimates close to the labeled-water dilution reference method in children with DMD (19). Muscle mass was estimated from 3-d urinary creatinine excretion, assuming that 20 kg muscle results in 1 g creatinine in the urine (20). Body mass index (BMI) was calculated as weight (in kg)/height² (in m), and BMI z scores were calculated according to reference values for French children (21). Plasma amino acid concentrations were measured with an automated unit. Plasma insulin and insulin growth factor I concentrations were measured with radioimmune assays (ERIA Diagnostics Pasteur, Paris, France). Oral nutrient intake was assessed with two 3-d food records obtained both before and during supplementation. Apart from glutamine or control amino acid supplementation, children were not prescribed a specific diet. Compliance was assessed by counting the number of empty sachets that were returned by the subjects after the treatment.

Statistical analysis
Main comparative analyses were performed by using 2-factor repeated-measures analysis of variance to test the effect of time (within-subject factor), group (between-subject factor), and the time-by-group interaction. Comparisons between groups at baseline for all outcome measures were performed with a Mann-Whitney U test. The change at 10 d (ie, the change before and after supplementation) was calculated for measures that were significantly different between the groups at baseline and analyzed with an analysis of covariance, with the baseline measure as a covariate and supplement group as a factor. Differences were considered significant at P < 0.05 (two-sided). Statistical analyses were performed with STATVIEW version 5.0 (Abacus Concepts, Berkeley, CA).

	RESULTS

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
The baseline characteristics of the 26 children with DMD are presented in Table 1. No significant differences in age, weight, height, BMI, and BMI z scores were observed between the 2 supplemental groups at baseline (Table 1). No statistically significant differences were observed between the groups at baseline for all outcome measures except for plasma isoleucine concentrations, which were significantly lower in the glutamine group than in the amino acids group at baseline (56 ± 3 µmol/L for the glutamine group compared with 69 ± 3 µmol/L for the amino acids group, P < 0.05) (Table 2).

Figure 1

Table 3

View larger version (21K): [in this window] [in a new window]   FIGURE 1. Mean (±SEM) whole-body leucine and glutamine metabolism before and after 10-d oral glutamine or isonitrogenous amino acid supplementation in children with Duchenne muscular dystrophy. There were no significant differences between the groups at baseline (Mann-Whitney U test). There was a significant effect of time on estimates of whole-body protein degradation and a significant decrease in the rate of appearance of leucine (RaLeu) and in the rate of endogenous (body) glutamine arising from protein degradation (BGln) after 10-d glutamine and isonitrogenous amino acid supplementation, P < 0.05 (2-factor repeated-measures ANOVA). There was no significant effect of treatment and no significant time-by-treatment interaction. FFM, fat free mass.

A significant effect of time was observed on blood urea nitrogen. Blood urea nitrogen significantly (P < 0.001) increased (but remained within the normal range) after 10-d supplementation with either glutamine or the amino acid mixture (3.7 ± 0.2 to 4.9 ± 0.3 mmol/L for the glutamine group and 3.9 ± 0.3 to 4.6 ± 0.3 mmol/L for the amino acids group). The increase in blood urea nitrogen did not differ significantly between the supplemental groups.

Glutamine or amino acid supplementation for 10 d did not affect plasma insulin (5.1 ± 0.4 compared with 6.5 ± 0.6 mUI/L for the glutamine group and 7.5 ± 1.3 compared with 7.4 ± 1.1mUI/L for the amino acids group), insulin growth factor I (284 ± 47 compared with 289 ± 60 ng/mL for the glutamine group and 209 ± 30 compared with 224 ± 27 ng/mL for the amino acids group), energy intake (1660 ± 93 compared with 1670 ± 80 kcal/d for the glutamine group and 1715 ± 116 compared with 1728 ± 83 kcal/d for the amino acids group), or protein intake (1.8 ± 0.1 compared with 2.0 ± 0.1 g · kg^–1 · d^–1 for the glutamine group and 2.0 ± 0.2 compared with 1.9 ± 0.1 g · kg^–1 · d^–1 for the amino acids group). Glutamine and amino acid supplementations were safe and well tolerated at the doses prescribed.

	DISCUSSION

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Oral glutamine or isonitrogenous amino acid supplementation for 10 d equally inhibit whole-body protein degradation in children with DMD. The present study showed an effect on protein metabolism that was not measured during glutamine or amino acid administration but was measured 24 h after supplementation ceased while plasma amino acid concentrations were normal. Similarly, a protein feeding pattern induced chronic regulation of protein turnover that persisted 1 d after the end of dietary treatment (22). The response of protein metabolism to supplemental protein intake can also be compared with the studies by Motil et al (23, 24). These previous studies used a similar methodology to the present work and showed an effect of increased protein intake on whole-body amino acid metabolism after a 12 h fast. To date, mechanisms of the "chrono-biological" regulation of whole-body protein metabolism are not fully understood.

In the present study, plasma glutamine and amino acid concentrations did not increase after supplementation. Hence, the effect of glutamine on whole-body protein metabolism cannot be attributed to increased plasma glutamine concentrations, as shown in previous studies (25). We used the same glutamine dose as that used in previous studies (4, 12, 26), which was selected to double the plasma glutamine concentration and concurrently explore whole-body protein metabolism. The present study suggests that the effects of glutamine are not solely driven by substrate availability. Alternatively, glutamine uptake by the intestine might be sparing other amino acids and substrates. Previous studies of enterally administered glutamine in very-low-birth-weight infants showed similar findings; that is, there was no change in plasma glutamine concentration after glutamine administration, thereby suggesting uptake of glutamine by the gut (27, 28).

The significant decrease in plasma taurine concentrations after supplementation with either glutamine or amino acids may reflect an improvement in muscle cellular status, because the plasma taurine concentration was shown to be elevated in the mdx mouse model of DMD (29). Moreover, mdx mice fed a high-protein diet showed a decrease in the elevated plasma taurine concentrations, which was associated with decreased muscle protein catabolism due to decreased protein degradation (29).

Although the decrease in whole-body protein degradation did not significantly differ between the supplemental groups, the glutamine group showed a larger decrease in Ra_Leu than did the amino acids group (9% compared with 4%). Moreover, the decrease in Ra_Leu (9%) observed in the present study after 10-d glutamine supplementation was the same as that observed in a previous study, in which the same dose of oral glutamine was given to patients with DMD over a 5-h period (12). Hormonal changes (ie, changes in insulin and insulin growth factor I) cannot account for the decrease in leucine turnover (30) that was observed in the present study.

The lack of significant difference in leucine turnover between the glutamine and amino acid control groups highlights the need for dose and time course data on glutamine administration in patients with DMD. The route of administration (enteral in the present study) could partly explain the lack of a significant difference. Previous studies in patients without DMD who were given enteral glutamine showed less dramatic anabolic effects on protein metabolism (27, 31, 32) than when patients without DMD were given intravenous glutamine (2, 33). Also, glutamine treatment in DMD may have different effects depending on the stage of the disease (34). However, we could not stratify by age in the present study because of the sample size. Larger age-stratified studies are needed to test this hypothesis.

The present study showed no significant effect of glutamine or amino acids on the Ra_Gln measured 24 h after the last dose (ie, while the plasma glutamine concentration was normal). In our previous study (12), oral glutamine administration was associated with a decrease in Ra_Gln due to a decrease in both glutamine release from proteolysis (B_Gln) and glutamine de novo synthesis (D_Gln). In contrast with the previous study, we observed a decrease only in B_Gln, without any effect on D_Gln. Experimental conditions could account for the difference in findings. In the previous study, glutamine kinetic variables were measured during glutamine administration, and plasma glutamine concentrations doubled. In the present study, the glutamine concentration remained within the normal range.

The present study compares the effects of oral glutamine and isonitrogenous supplementation over 10 d on whole-body protein metabolism in patients with DMD. The results suggest that nitrogen supplementation might have a protein-sparing effect in DMD that results from a decrease in protein degradation. This short-term approach provides a mechanism to explain the recent results from a randomized, placebo-controlled trial that showed less deterioration in measures of function with long-term (6 mo) nitrogen supplementation (glutamine and creatine) in younger children with DMD (34). Decreased body protein breakdown after short-term nitrogen supplementation has implications for present disease therapies and could be a possible route for therapeutic modulation in DMD as well as in other protein-wasting situations.

	ACKNOWLEDGMENTS

 
EM contributed to the analysis of data and the writing of the manuscript. CE-DV contributed to the collection and analysis of data. CD, FG, OR, J-EF, and J-MC contributed to the collection of data. JG contributed to the analysis of data. RH contributed to the design of the experiment, collection and analysis of data, and the writing of the manuscript. The authors had no conflicts of interest to report.

	REFERENCES

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Souba WW. Nutritional support. N Engl J Med 1997; 336: 41-8.[Free Full Text]
2. Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med 1992; 116: 821-8.[Medline]
3. Duggan C, Gannon J, Walker WA. Protective nutrients and functional foods for the gastrointestinal tract. Am J Clin Nutr 2002; 75: 789-808.[Abstract/Free Full Text]
4. Hankard RG, Haymond MW, Darmaun D. Effect of glutamine on leucine metabolism in humans. Am J Physiol 1996; 271: E748-54.
5. Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 2002; 30: 2022-9.[Medline]
6. Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997; 13: 295-302.[Medline]
7. Goldstein M, Meyer S, Freund HR. Effects of overfeeding in children with muscle dystrophies. JPEN J Parenter Enteral Nutr 1989; 13: 603-7.[Abstract]
8. Griggs RC, Rennie MJ. Muscle wasting in muscular dystrophy: decreased protein synthesis or increased degradation? Ann Neurol 1983; 13: 125-32.[Medline]
9. Rennie MJ, Edwards RH, Millward DJ, Wolman SL, Halliday D, Matthews DE. Effects of Duchenne muscular dystrophy on muscle protein synthesis. Nature 1982; 296: 165-7.[Medline]
10. Hankard R, Mauras N, Hammond D, Haymond M, Darmaun D. Is glutamine a ‘conditionally essential’ amino acid in Duchenne muscular dystrophy? Clin Nutr 1999; 18: 365-9.[Medline]
11. Rennie MJ, MacLennan PA, Hundal HS, et al. Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle-protein turnover. Metabolism 1989; 38: 47-51.[Medline]
12. Hankard RG, Hammond D, Haymond MW, Darmaun D. Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Pediatr Res 1998; 43: 222-6.[Medline]
13. Matthews DE, Motil KJ, Rohrbaugh DK, Burke JF, Young VR, Bier DM. Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-³C]leucine. Am J Physiol 1980; 238: E473-9.
14. Matthews DE, Schwarz HP, Yang RD, Motil KJ, Young VR, Bier DM. Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-¹³C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment. Metabolism 1982; 31: 1105-12.[Medline]
15. Darmaun D, Manary MJ, Matthews DE. A method for measuring both glutamine and glutamate levels and stable isotopic enrichments. Anal Biochem 1985; 147: 92-102.[Medline]
16. Horber FF, Horber-Feyder CM, Krayer S, Schwenk WF, Haymond MW. Plasma reciprocal pool specific activity predicts that of intracellular free leucine for protein synthesis. Am J Physiol 1989; 257: E385-99.
17. Griffiths RD, Edwards RH. A new chart for weight control in Duchenne muscular dystrophy. Arch Dis Child 1988; 63: 1256-8.[Abstract]
18. Houtkooper LB, Lohman TG, Going SB, Hall MC. Validity of bioelectric impedance for body composition assessment in children. J Appl Physiol 1989; 66: 814-21.[Abstract/Free Full Text]
19. Mok E, Béghin L, Gachon P, et al. Estimating body composition in children with Duchenne muscular dystrophy: comparison of bioelectrical impedance analysis and skinfold-thickness measurement. Am J Clin Nutr 2006; 83: 65-9.[Abstract/Free Full Text]
20. Heymsfield SB, Arteaga C, McManus C, Smith J, Moffitt S. Measurement of muscle mass in humans: validity of the 24-hour urinary creatinine method. Am J Clin Nutr 1983; 37: 478-94.[Abstract/Free Full Text]
21. Rolland-Cachera MF, Cole TJ, Sempe M, Tichet J, Rossignol C, Charraud A. Body Mass Index variations: centiles from birth to 87 years. Eur J Clin Nutr 1991; 45: 13-21.[Medline]
22. Arnal MA, Mosoni L, Boirie Y, et al. Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets. Am J Physiol Endocrinol Metab 2000; 278: E902-9.[Abstract/Free Full Text]
23. Motil KJ, Matthews DE, Bier DM, Burke JF, Munro HN, Young VR. Whole-body leucine and lysine metabolism: response to dietary protein intake in young men. Am J Physiol 1981; 240: E712-21.
24. Motil KJ, Bier DM, Matthews DE, Burke JF, Young VR. Whole body leucine and lysine metabolism studied with [1-¹³C]leucine and [alpha-¹⁵N]lysine: response in healthy young men given excess energy intake. Metabolism 1981; 30: 783-91.[Medline]
25. Darmaun D, Just B, Messing B, et al. Glutamine metabolism in healthy adult men: response to enteral and intravenous feeding. Am J Clin Nutr 1994; 59: 1395-402.[Abstract/Free Full Text]
26. Hankard RG, Darmaun D, Sager BK, D'Amore D, Parsons WR, Haymond M. Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol 1995; 269: E663-70.
27. Darmaun D, Roig JC, Auestad N, Sager BK, Neu J. Glutamine metabolism in very low birth weight infants. Pediatr Res 1997; 41: 391-6.[Medline]
28. Parimi PS, Devapatla S, Gruca LL, Amini SB, Hanson RW, Kalhan SC. Effect of enteral glutamine or glycine on whole-body nitrogen kinetics in very-low-birth-weight infants. Am J Clin Nutr 2004; 79: 402-9.[Abstract/Free Full Text]
29. Zdanowicz MM, Slonim AE, Bilaniuk I, O'Connor MM, Moyse J, Teichberg S. High protein diet has beneficial effects in murine muscular dystrophy. J Nutr 1995; 125: 1150-8.[Abstract/Free Full Text]
30. Castellino P, Luzi L, Simonson DC, Haymond M, DeFronzo RA. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Role of substrate availability on estimates of whole body protein synthesis. J Clin Invest 1987; 80: 1784-93.[Medline]
31. Long CL, Nelson KM, DiRienzo DB, et al. Glutamine supplementation of enteral nutrition: impact on whole body protein kinetics and glucose metabolism in critically ill patients. JPEN J Parenter Enteral Nutr 1995; 19: 470-6.[Abstract]
32. Gore DC, Wolfe RR. Glutamine supplementation fails to affect muscle protein kinetics in critically ill patients. JPEN J Parenter Enteral Nutr 2002; 26: 342-9;discussion 349–50.[Abstract/Free Full Text]
33. Hammarqvist F, Wernerman J, Ali R, von der Decken A, Vinnars E. Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann Surg 1989; 209: 455-61.[Medline]
34. Escolar DM, Buyse G, Henricson E, et al. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann Neurol 2005; 58: 151-5.[Medline]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mok, E. Articles by Hankard, R. Search for Related Content PubMed PubMed Citation Articles by Mok, E. Articles by Hankard, R. Agricola Articles by Mok, E. Articles by Hankard, R.