Renee M. HinojosaNTDT 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

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

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

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 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 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

Double Blind Control Study Skin Graft

◦ 35 subjects 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?

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 Granule-supplemented Enteral Nutrition Maintains Immunological Function in Severely Burned Patients. J Burns. 2006;32:589-593.

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.