A role for nutrition therapy in the regulation of wound healing has been predicated on two concepts. The first is that malnutrition increases the risk of wound-related complications. The second is that dietary intervention, either in the form of complete nutrition support or as single nutrient supplementation, can improve or accelerate the wound-healing response. Although frequently stated and extensively discussed, these two concepts are not supported by objective data. (Journal of Parenteral and Enteral Nutrition 18:367–376 1994)
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References
1.
1. Irvin TT, Stoddard CJ, Greaney MG, et al: Abdominal wound healing: A prospective clinical study. Br Med J2:351–352, 1977.
2.
2. Levenson SM, Upjohn HL, Preston JA, et al: Effect of thermal burns on wound healing. Ann Surg146:357–368, 1957.
3.
3. Moore FD: Metabolic Care of the Surgical Patient. WB Saunders Co, Philadelphia, 1959.
4.
4. Moore FD, Brennan MF: Surgical injury: Body composition, protein metabolism and neuroendocrinology. IN Manual of Surgical Nutrition, Ballinger WF, Collins JA, Drucker WR, Dudrick SJ, Zeppa R (eds). WB Saunders Co, Philadelphia, 1975, pp 169–222
5.
5. Cuthbertson DP: Surgical metabolism: Historical and evolutionary aspects. IN Metabolism and The Response to Injury, Wilkinson AW, Cuthbertson D (eds). Pitman Medical Publishing Co Ltd, Bath, England, 1976, pp 1–34
6.
6. Hunter JAA Treatise on The Blood, Inflammation and Gunshot Wounds. Nicol, London, 1794.
7.
7. Levenson SM, Crowley LV, Seifter E: Effects of injury on wound healing and wound infection. IN Metabolism and The response to Injury, Wilkinson AW, Cuthbertson D (eds). Pitman Medical Publishing Co. Ltd., Bath, England, 1976, pp 261–273.
8.
8. Levenson SM and Demetriou AAMetabolic factors. IN Wound Healing: Biochemical and Clinical Aspects, Cohen IK, Diegelmann RF, Lindblad WJ (eds). WB Saunders Co, Philadelphia, 1992, pp 248–273.
9.
9. Levenson SM, Geever EF, Crowley LV, et al: The healing of rat skin wounds. Ann Surg161:293–308, 1965.
10.
10. Levenson SM: Some challenging wound healing problems for clinicians and basic scientists. IN Repair and Regeneration: The Scientific Basis for Surgical Practice, Dunphy JE, Van Winkle W Jr (eds). McGraw-Hill, New York1969, pp 309–337
11.
11. Carrel AEffet d'un abces a distance sur la cicatrisation d'une plaie aseptique. C R Soc Biol (Paris)90:333–335, 1924.
12.
12. Meakins JL, Christou NV, Shizgal HM: Therapeutic approaches to anergy in surgical patients. Ann Surg190:286–296, 1979.
13.
13. Crowley LV, Seifter E, Kriss P: Effects of environmental temperature and femoral fracture on wound healing in rats. J Trauma17:436–445, 1977.
14.
14. Diegelmann RF, Lindblad WJ, Cohen IKA subcutaneous implant for wound healing studies in humans. J Surg Res40:229–237, 1986.
15.
15. Levenson SM, Crowley LV, Oates JF: Effect of severe burn on liver regeneration. Surg Forum9:493, 1959.
16.
16. Greenhalgh DG, Gamelli RL: Is impaired wound healing caused by infection or nutritional depletion?. Surgery102:306–312, 1987.
18. Daly JM, Vars HM, Dudrick SJ: Effects of protein depletion on strength of colonic anastomoses. Surg Gynecol Obstet134:15–21, 1972.
19.
19. Irvin TT, Hunt TK: Effect of malnutrition on colonic healing. Ann Surg180:765–772, 1974.
20.
20. Irvin TT: Effects of malnutrition and hyperalimentation on wound healing. Surg Gynecol Obstet146:33–37, 1978.
21.
21. Temple WJ, Voitk AJ, Snelling CFT, et al: Effect of nutrition, diet and suture material on long term wound healing. Ann Surg182:93–97, 1975.
22.
22. Casey J, Flinn WR, Yao JST, et al: Correlation of immune and nutritional status with wound complications in patients undergoing vascular operations. Surgery93:822–827, 1983.
23.
23. Dickhaut SC, DeLee JC, Page CP: Nutritional status: Importance in predicting wound-healing after amputation. J Bone Joint Surg (Am)66:71–75, 1984.
24.
24. Kay SP, Moreland JR, Schmitter E: Nutritional status and wound healing in lower extremity amputations. Clin Orthop217:253–256, 1987.
25.
25. Lindstedt E, Sandblom P: Wound healing in man: Tensile strength of healing wounds in some patient groups. Ann Surg181:842–846, 1975.
27. Rhoads JE, Fliegelman MT, Panzer LM: The mechanism of delayed wound healing in the presence of hypoproteinemia. JAMA118:21–24, 1942.
28.
28. Goodson WH III, Hunt TK: Development of a new miniature method for the study of wound healing in human subjects. J Surg Res33:394–401, 1982.
29.
29. Haydock DA, Hill GL. Impaired wound healing in surgical patients with varying degrees of malnutrition. JPEN10:550–554, 1986.
30.
30. Holm-Pedersen P, Zederfelt B: Granulation tissue formation in subcutaneously implanted cellulose sponges in young and old rats. Scand J Plast Reconstr Surg5:13–16, 1971.
31.
31. Holm-Pedersen P, Vlidik A: Maturation of collagen in healing wounds in young and old rats. Scand J Plast Reconstr Surg6:16–23, 1972.
32.
32. Haydock DA, Hill GL: Improved wound healing response in surgical patients receiving intravenous nutrition. Br J Surg74:320–323, 1987.
33.
33. Schroeder D, Gillanders L, Mahr K, et al: Effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing. JPEN15:376–383, 1991.
34.
34. Sandberg N, Zederfeldt B: The tensile strength of healing wounds and collagen formation in rats and rabbits. Acta Chir Scand126:187–196, 1963.
35.
35. Windsor JA, Knight GS, Hill GL: Wound healing response in surgical patients: Recent food intake is more important than nutritional status. Br J Surg75:135–137, 1988.
36.
36. Goodson WH III, Jensen JA, Granja-Mena L, et al: The influence of a brief preoperative illness on postoperative healing. Ann Surg205:250–255, 1987.
37.
37. Spanheimer RG, Peterkofsky B: A specific decrease in collagen synthesis in acutely fasted, Vitamin C-supplemented, guinea pigs. J Biol Chem260: 3955–3902, 1985.
38.
38. Heatley RV, Williams RHP, Lewis MH: Preoperative intravenous feeding: A controlled trial. Postgrad Med J55:541–545, 1979.
39.
39. Müller JM, Brenner U, Dienst C, et al: Preoperative parenteral feeding in patients with gastrointestinal carcinoma. Lancet1:68–71, 1982.
40.
40. Buzby GP: The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group: Perioperative total parenteral nutrition in surgical patients. N Engl J Med325:525–532, 1991.
41.
41. Kirk SJ, Barbul A: Role of arginine in trauma, sepsis, and immunity. JPEN14(Suppl):226–229, 1990.
42.
42. Barbul A, Rettura G, Levenson SM, et al: Arginine: A thymotropic and wound-healing promoting agent. Surg Forum28:101–103, 1977.
43.
43. Barbul A, Wasserkrug HL, Seifter E: Immunostimulatory effects of arginine in normal and injured rats. J Surg Res29:228–235, 1980.
44.
44. Seifter E, Rettura G, Barbul A: Arginine: An essential amino acid for injured rats. Surgery84:224–230, 1978.
46. Bulgrin JP, Shabani M, Smith DJ: Arginine-free diet suppresses nitric oxide production in wounds. J Nutr Biochem4:588–593, 1993.
47.
47. Barbul A, Lazarou SA, Efron DT, et al: Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery108:331–337, 1990.
48.
48. Kirk S, Hurson M, Regan M: Arginine stimulates wound healing and immune function in aged humans [Abstract]. Presented at the 54th Annual Meeting of the Society for University Surgeons, Seattle, WA, 1993.
49.
49. Ronnenberg AG, Gross KL, Hartman WJ: Dietary arginine supplementation does not enhance lymphocyte proliferation or inter-leukin-2 production in young and aged rats. J Nutr121: 1270–1278, 1991.
50.
50. Deleted in proof
51.
51. Albina JE, Mills CD, Henry WL Jr, et al: Temporal expression of different pathways of L-arginine metabolism in healing wounds. J Immunol144: 3877–3880, 1990.
52.
52. Albina JE, Mills CD, Barbul A: Arginine metabolism in wounds. Am J Physiol254: E459–E467, 1988.
53.
53. Albina JE, Abate JA, Mastrofrancesco B: Role of ornithine as a proline precursor in healing wounds. J Surg Res55:97–102, 1993.
54.
54. Barbul A, Rettura G, Levenson SM: Wound healing and thymotropic effects of arginine: A pituitary mechanism of action. Am J Clin Nutr37:786–794, 1983.
55.
55. Seifter E, Crowley LV, Rettura G, et al: Influence of Vitamin A on wound healing in rats with femoral fracture. Ann Surg181:836–841, 1975.
56.
56. Levenson SM, Gruber CA, Rettura G, et al: Supplemental Vitamin A prevents the acute radiation-induced defect in wound healing. Ann Surg200:494–512, 1984.
57.
57. Seifter E, Tettura G, Padawer J: Impaired wound healing in streptozotocin diabetes: Prevention by supplemental vitamin A. Ann Surg194:42–50, 1981.
58.
58. Ehrlich HP, Hunt TK: Effects of cortisone and Vitamin A on wound healing. Ann Surg167:324–328, 1968.
59.
59. Hunt TK, Ehrlich P, Garcia JA, et al: Effect of Vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man. Ann Surg170:633–640, 1969.
60.
60. Retturo G, Levenson SM, Schittek A: Vitamin A: Actions in oncogenesis and skin graft rejection. Surg Forum26:301–303, 1975.
61.
61. Demetriou AA, Levenson SM, Rettura G, et al: Vitamin A and retinoic acid: Induced fibroblast differentiation in vitro.. Surgery98:931–934, 1985.
62.
62. Chojkier M, Spanheimer R, Peterkofsky B: Specifically decreased collagen biosynthesis in scurvy dissociated from an effect on proline hydroxylation and correlated with body weight loss: In vitro studies in guinea pig calvarial bones. J Clin Invest72:826–835, 1983.
63.
63. Levenson SM, Green RW, Taylor FHL, et al: Ascorbic acid, riboflavin, thiamine, and nicotinic acid in relation to severe injury hemorrhage, and infection in the human. Ann Surg124:840–856, 1946.
64.
64. Crandon JH, Lund CC, Dill DB: Experimental human scurvy. N Engl J Med223:353–369, 1940.
65.
65. Wolfer JA, Farmer CJ, Carroll WW, et al: An experimental study in wound healing in Vitamin C depleted human subjects. Surg Gynecol Obstet84:1–15, 1947.
66.
66. Weinsier RL, Hunker EK, Krumdieck CL: Hospital malnutrition: A prospective evaluation of general medical patients during the course of hospitalization. Am J Clin Nutr32:418–126, 1979.
67.
67. Vallee BL, Falchuk KH: The biochemical basis of zinc physiology. Physiol Rev73:79–118, 1993.
68.
68. Prasad AS: Zinc deficiency in human subjects. Prog Clin Biol Res129:1–33, 1983.
69.
69. Pories WJ, Henzel JH, Rob CG, et al: Acceleration of wound healing in man with zinc sulphate given by mouth. Lancet1:121–124, 1967.
71. Hallböök T, Lanner E: Serum-zinc and healing of venous leg ulcers. Lancet1:780–782, 1972.
72.
72. Sandstead HH, Henriksen LK, Greger JL: Zinc nutriture in the elderly in relation to taste acuity, immune response, and wound healing. Am J Clin Nutr36: 1046–1059, 1982.
73.
73. Solomons NW: Zinc and copper. IN Modern Nutrition in Health and Disease, Shils ME, Young VR (eds). Lea & Febiger, Philadelphia, 1988, pp 238–262.
74.
74. Ehrlich HP, Tarver H, Hunt TK: Inhibitory effects of vitamin E on collagen synthesis and wound repair. Ann Surg175:235–240, 1972.
75.
75. Simopoulos AP: Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr54:438–463, 1991.
76.
76. Prickett JD, Robinson DR, Steinberg AD: Effects of dietary enrichment with eicosapentaenoic acid upon autoimmune nephritis in female NZBxNZW/F1 mice. Arthritis Rheum26:133–139, 1983.
77.
77. Kremer JM, Jubiz W, Michalek A, et al: Fish-oil fatty acid supplementation in active rheumatoid arthritis. Ann Int Med106:497–502, 1987.
78.
78. Kremer JM, Lawrence DA, Jubiz W: Different doses of fish-oil fatty acid ingestion in active rheumatoid arthritis: A prospective study of clinical and immunological parameters. IN Dietary w3 and w6 Fatty Acids: Biological Effects and Nutritional Essentiality. Plenum Press, New York, 1989, pp 343–350
79.
79. Sperling RI, Robin JL, Kylander KA, et al: The effects of N-3 polyunsaturated fatty acids on the generation of platelet-activating factor-acether by human monocytes. J Immunol139: 4186–4191, 1987.
80.
80. Endres S, Ghorbani R, Kelley V, et al: The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of inter-leukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med320:265–271, 1989.
81.
81. Albina JE, Gladden P, Walsh WR: Detrimental effects of an co-3 fatty acid-enriched diet on wound healing. JPEN17:519–521, 1993.
82.
82. Goodson WH III, Hunt TK: Wound healing. IN Nutrition and Metabolism in Patient Care, Kinney JM, Jeejeebhoy KN, Hill GL, Owen OE (eds). WB Saunders Co, Philadelphia, 1988, pp 635–612.
