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Renee M. Hinojosa
NTDT 5340
December 12th, 2011

Audience will be able to:
◦ Review the medical nutrition therapy for wound
healing
◦ Identify the amino acids glutamine and arginine
◦ Recognize glutamine and arginines’ metabolic
role in wound healing
◦ Be familiar with the different studies that have
been done to establish these roles
 Pressure Ulcers, Diabetic Ulcers, Skin grafts, and Burns
◦ Discover future outlooks on glutamine and
arginine in wound healing
 Pressure
 Lacerations
Ulcers
 Penetration
◦Diabetic
 Gun Shot
◦Immobility  Surgical
 Burns
 Abrasions


20% protein loss within first two weeks of
injury
Increased energy needs
◦ 25-35 kcal/kg/d

Increased protein needs
◦ 1.5-2.0 g/kg/d

Additional vitamins and minerals
◦ Selenium, Vitamin C, Vitamin A, Vitamin E, Zinc
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Most abundant amino acid (AA) in the plasma
Conditionally essential
Major metabolic fuel for intestinal mucosa
and cell proliferation
◦ Fibroblasts, lymphocytes, epithelial cells,
macrophages


Increases protein synthesis and
immunoglobulin a (IgA)
Synthesized in muscle

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Conditionally essential
Beneficial in improving cardiovascular,
reproductive, pulmonary, gastrointestinal,
liver and immune functions.
Facilitates wound healing, enhances insulin
sensitivity, and maintains tissue integrity
Precursor for nitric oxide

Directly
◦ De novo synthesis

Citrulline
◦ Synthesized FROM glutamine
◦ Synthesis OF arginine.
 Glutamine contributes 64% synthesis of arginine.

Arginine can be hydrolyzed by hepatic
arginase to urea and ornithine which
utlimately get converted to glutamine

Arginine and pressure ulcers
◦ spinal cord injury


Observational study
Dietitian involved
◦ Mini nutritional assessment
◦ Weekly rounds

Oral nutrition supplement
◦ Not exclusively arginine
 Zinc and Vitamin C
 Nutrition and Dietetics 2011 Dietitians Associations of Australia

2.5-fold greater rate of pressure ulcer
healing for those who took supplement
◦ Non-compliance – GI upset, dislike taste;
 Dietitian recorded monitored weekly intake


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Wide Age range
No exclusion of wounds
Limited to one population
Stages not specified

Multicenter, multicountry, randomized,
controlled, double blind, parallel group trial
◦ 43 participants
◦ Age: 18-90 years


Stage III or Stage IV Pressure Ulcer
Excluded Diabetic Ulcers
◦ Also excluded patients on a dietary restrictive diet
 Not specified

Standard Nutritional Diets and Wound Care
◦ Locally used protocols

Oral Nutrition Supplements
◦ Arginine, Zinc, Vitamin A, Vitamin C, Selenium,
Copper, Folic Acid
 Suggests that healing could be multifactorial

Results
◦ Significant differences in the reduction of the ulcers
and the difference in PUSH scores
 Most prominent in 1st weeks


Both Arginine and Glutamine
Observational Study
◦ 16 participants

Nutritional Supplement
◦ Arginine, Glutamine, Hydroxy-B-methylbutyrate
(HMB)
◦ Energy needs: 20-22% of high quality protein

Microalbuminuria – Kidney function
◦ Type II DM

Two Hypothesis
◦ Reduction in Albuminuria
◦ Arginine protects kidney

Results
◦ Supplement decreased microalbuminuria by 47%
◦ 6 months
 Food ulcers healed after this time

Absence of randomization
◦ Role of HMB?


Prospective Study
Healthy adults - skin transplantation
◦ Reconstructive Surgery

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Mechanisms of Arginine
◦ Compared healing
 Surgical wounds and normal skin
Inducible Nitric Oxide
◦ Activated by arginine

Cells observed after supplementation
◦ PMNs and Marcrophages
 Increased NO levels and wound tensile
strength
 Arginine was increased in all wounds
 Not increased in non-surgical wounds

◦ Fibroblasts
 Increase in NO
More specific
◦ Arginine 2

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Double Blind Control Study
Skin Graft
◦ 35 subjects

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Intravenous Arginine
Wound healing evaluated at donor site
◦ Angiogenesis
◦ Reepithilialization
◦ Neutrophil influx

Plasma arginine AA concentrations measured

Burns 37 (2011)

Two groups comparable
◦ Age, nutritional status, metabolic and inflammatory
state


No differences found in arginine group or
placebo
Conclusion
◦ Arginine does not improve angiogenesis,
reepethilialization or neutrophil influx

Arginine and Glutamine
◦ No effect on pressure ulcers in elderly


Randomized control study
Dietitian involved in assessment
◦ 26% were at risk for malnutrition

Nutritional supplement
◦ Agrinine
 Did not increase NO in this population
 Did not enhance lympocyte proliferation


Lack of other vitamins and minerals
Did not provide immune benefit


Randomized, controlled double blind clinical
trial
Burn patients
◦ 30-75% total surface area burned

Glutamine Supplementation – enteral
nutrition and oral supplementation
◦ Glutamine granules and glycine

Nutrition
◦ All patients receiving the same amount of nitrogen
and energy
 Did not specify grams or kcals/kg


Immune function improved in glutamine
groups
Hospital stay
◦ 9 days shorter fro supplemented group

Results
◦ Glutamine supplementation improves immune
function and facilitates wound healing

Arginine studied more than Glutamine
◦ Individalization
 Mixed results

Bigger study groups needed for
generalization
◦ Nutritional supplements
 Had more benefit
 Vitamins, minerals, antioxidants
 Most subjects were not malnourished in all studies

Wound healing
◦ Multifactorial

More studies needed
◦ Individualizing both amino acids
Questions?
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
Eleanor S., Long S. Essentials of Nutrition Diet Therapy. St. Louis,
MO: Sauders Elsevier: 2008. 125.
Wu, G. et al. Arginine Metabolism and Nutrition in Growth, Health
and Disease. Amino Acids 2009;37:153-168.
Isenberg, J., Ridnour, L., Espey, M., Wink, D., Roberts, D. Nitric Oxide
in Wound Healing. Microsurgery. 2005;25(5):442-451.
Coeffier, M., Dechelotte, P. Combined Infusion of Glutamine and
Arginine: Does it Make Sense? Current Opinion in clinical Nutrition
and Metabolic Care. 2010; 12:70-74.
Peng, X., Yan H., You, Z., Wang, P., Wang, S. Glutamine Granulesupplemented Enteral Nutrition Maintains Immunological Function in
Severely Burned Patients. J Burns. 2006;32:589-593.
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Atalay, M., Oksala, N., Lappalainen, J., Laaksonen, D., Sen, C., Roy, S. Heat Shock
Proteins in Diabetes and Wound Healing. Curr. Protein Pept. Sci 2009;10(1):85-95.
Chapman, B., Mills, K., Pearce, L., Crowe, T. Use of an Arginine-Enriched Oral Nutrition
Supplement in the Healing of Pressure Ulcers in Patients with Spinal Cord Injuries: An
Observational Study. Nutrition and Dietetics. 2011;68: 208-213.
Van Anholt, et al,. Specific Nutritional Support Accelerates Pressure Ulcer Healing and
Reduces Wound Care Intensity in Non-Malnourished Patients. J. Nut. 2010;26: 867-872.
Stechmiller J., et al., Arginine Supplementation Does Not enhance Serum Nitric Oxide
Levels in Elderly Nursing Home Residents with Pressure Ulcers. Biological Research for
Nursing. 2005;6:289-299.
Tatti, P., Masselli, L., Di Mauro, P., Pipicelli., Pipicelli, A., Barber, A. Effect of Nutritional
Supplement Used for Diabetic Foot Ulcers on Microalbuminuria. Mediterr J Nutr Metab.
2011; 10.
Debats, I., Koneman, M., Booi, D., Bekers, O., Van der Hulst, R. Intravenous Arginine and
Human Skin Graft Donor Site Healing: A Randomized Controlled Trial. J. Burns.
2011;37:420-426.
Campos, A., Groth, A., Branco, A. Assessment and Nutritional Aspects of Wound Healing.
Current Opinion in Clinical Nutrition and Metabolic Care 2008 11;281-288.