Amino Acid Supplementation in Recovery From Severe Burns

Severe burns result in persistent and extensive fat deposition in liver and muscle tissue.
This may be related to the prolonged insulin resistance observed following burn. In this
study the investigators will test the hypothesis that essential amino acids act in synergy
with exercise to improve liver steatosis and muscle lipid metabolism, and thus also affect
insulin sensitivity. Children with burns will participate in six weeks of exercise training
with/without amino acid supplementation. Before and after the intervention, measurements will
be done to determine muscle and liver fat content, muscle fat and protein metabolism, and
insulin sensitivity.

We will prospectively enroll 40 children with ≥30% of their total body surface area (TBSA)
burned. The age range will be 7-17 years. Children will be recruited from Shriners Hospitals
for Children (SHC)-Galveston. Burned children will be randomized to undergo an exercise
program in combination with daily intake of EAA (n=20) or a placebo drink (n=20). The
exercise program and daily intake of AA will begin within the first week of discharge from
the burn ICU (approximately 1-3 months post burn, when the patient's wounds are 95% healed).
The definition of 95% healed is 7 days after the final autografting procedure. We anticipate
enrolling 10 children per year for 4 years. Only children meeting the inclusion and exclusion
criteria specified in the Human Subjects Section will be enrolled.

Nutritional Supplement: The nutritional supplement will be administered at a dose of 0.18
g/kg body weight of amino acids two times per day with the following composition: 3%
histidine, 9% isoleucine, 36% leucine, 17% lysine, 4% methionine, 5% phenylalanine, 10%
threonine, 7% valine, and 10% arginine. The dose and choice of amino acids is based on our
preliminary data. Each dose is about 0.03 g/kg body weight higher than what has been shown
effective in adults, as children have higher protein needs. We have shown that only EAA are
needed to affect muscle protein synthesis and lean mass. Thus the amount given (g or kcal)
can be restricted. As in our preliminary studies, we will include arginine in the EAA
mixture, since arginine may have unique anabolic effects (55; 86). Placebo will consist of a
mixture of inert components (sucralose and other pharmaceutical excipients). The supplement
will be taken in two daily doses in the form of drinks (total daily dose of i.e., 0.30 g/kg
body weight total per day), and intake recorded in a diary. The first dose will be taken
between breakfast and lunch, and the second between lunch and dinner. For the children
exercising before lunch, the first dose of EAA will be ingested immediately after exercise.
Correspondingly, for children exercising after lunch, the second EAA dose of the day will be
ingested immediately after exercise. If the child forgets to take one of the drinks during
the day, he/she may take the second one between dinner and bedtime. During the weekends,
parents/caregivers are instructed to take the dosage around the same time.

Data Analysis and Interpretation. To determine effects of amino acids on fat and muscle lipid
stores, changes from pre- to post intervention in the two groups will be compared using
ANCOVA. From the preliminary data, we expect that amino acids will decrease liver and plasma
lipids.

Inclusion Criteria:

1. Male or female

2. 7-17 years old

3. Body weight >20 kg (based on blood requirements)

4. ≥30% Total Body Surface Area (TBSA)

5. Wounds 95% healed

Exclusion Criteria:

1. Respiratory insufficiency

2. Multiple fractures

3. History of Cancer in the last 5 years

4. Diabetes Mellitus

5. Bilirubin > 3 mg/dl

6. Associated head injuries requiring specific therapy

7. Associated injuries to chest or abdomen requiring surgery

8. Serum creatinine > 3 mg/dl after fluid resuscitation

9. Receipt of any experimental drug other than the ones supplied within two months of
this study

10. Any metal in body including rods, cardiac defibrillator, pacemakers, etc

11. Orthopedic casting which would prevent placement of patient in MRI machine

12. Hepatitis

13. Abnormal EKG

14. Electrical burns

15. Patients unable to lie still without heavy sedation will be excluded from MRI portion.