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Nutrition and the management of wounds

Alan BG Lansdown
PhD FRCPath FIBiol MIMgt
Investigative Dermatologist and Toxicologist
Honorary Senior Lecturer
Imperial College School of Medicine
London

Nutrition is the supply of inorganic and organic substances to sustain growth and development in the human body.
In the skin, which performs an essential protective function, regular loss of tissue and nutrients is a normal consequence of wear and tear processes and environmental insults. Inherent homeostatic mechanisms maintaining tissue mass require adequate supplies of micronutrients to sustain synthetic processes involved in repair and renewal processes.(1,2)
Nutrition is not an exact science, and requirements for proteins and amino acids, vitamins, trace minerals, fatty acids and carbohydrates vary greatly according to a person's age, state of health and genetic background, race and geographic area. In skin injury, repair processes embrace removal of necrotic and damaged tissue, ­preparation of the wound bed with disinfection and cleansing of the wound site, organisation and activation of cells in the wound margin, and induction of repair processes in the epidermis and dermis.(3) The so-called wound healing cascade has specific and balanced requirements for all essential nutrients and a conducive ambient ­environment.
The skin is a metabolically active tissue providing a protective envelope for the body against physical, chemical and biological insults in the environment; it exists in a state of dynamic equilibrium with that environment. Cells lost at the surface through abrasion or injury are replaced in a conveyer belt fashion by proliferation in the basal epidermis.(4) Homeostatic and repair systems also exist in the dermis, where recovery from injuries attributable to bruises, burns, scalds, irradiation, surgical incisions and chronic ulcers, and so on, involves increased fibroblast activity, synthesis of the intercellular matrix and collagen production. Chronic and indolent wounds, as commonly seen in older patients and patients with diabetes, are complex and the nutrient requirements imperfectly understood.(5)
All wounds involve some tissue loss with disturbance in homeostatic mechanisms. The balanced availability of nutrients in the continuous sequence leading to repair and regenerative processes enables:

  • Wound bed preparation.
  • Replenishment of nutrients lost in wound ­exudate and debris.
  • Cell recruitment and activation in epidermis and dermis leading to proliferation, migration and maturation.
  • Reconstruction of the wound site and restitution of normal homeostatic ­mechanisms leading to reorganisation and normalisation.

Skin injury
Skin injuries involve damage or disturbances in many cell types, all of which contribute in some way to the protective function of the tissue.(6,7) Acute wounds in most healthy people are able to heal spontaneously with restoration of normal function, even though residual scar tissue may be cosmetically embarrassing. Chronic and indolent wounds are more complex but have been subject to intensive clinical and therapeutic research in recent years.(5)
Wound healing is a complex and continuous process consisting of at least four main events - haemostasis; inflammation and granulation tissue formation; cell proliferation, migration and maturation; and tissue reorganisation and "normalisation". Much of our present knowledge is derived from the study of acute wounds, but this experience should be relevant in the management of delayed healing and chronic wounds.(3)
Whatever the wound, it seems likely that tissue injury or reduction in "tissue mass" triggers the release of growth factors, hormones, cytokines and other regulators, which in turn regulate the characteristic cellular and biochemical events of the healing cascade.(8,9) These may signal increased demands for specific nutrients and ­activate pathways of nutrient metabolism in creating a suitable microenvironment in the wound for healing. Experimental studies indicate that as wounds heal so the requirements for ­different nutrients change to reflect the cellular, biosynthetic and immunological events in progress.(10) Management of oxygen tension, acidity and hydration in the wound are further important considerations in wound healing.(11)
Scientists are still ignorant of the nutritional requirements in the wound bed for optimal healing. Whereas animal models and diets deficient in key amino acids, minerals, and so on, are suitable for mechanistic studies on the role of nutrients in healing, extrapolation of this data to humans is complex. The human body is unique in the animal kingdom, dietary habits are highly variable, and metabolic rates and pathways differ.(12-14) However, the importance of basic nutrients like zinc, calcium, ­vitamins A and C and certain amino acids is appreciated. Deficiencies in certain nutrients are known to compromise the immune system.(15)

Nutrition and cellular events
All cell types in the normal skin are involved to some extent in repair patterns following injury. The sequential events involving cellular interaction, migration and functional differentiation are determined by key growth factors, cytokines and genetic modulators. At the moment, we know little concerning the action of these growth factors in the uptake or mobilisation of essential nutrients or their implication in the numerous biosynthetic events of the healing sequence. It is expected that platelet-derived growth factor (PDGF) released during haemostasis will modulate calcium (as factor IV), and that epidermal growth factor (EGF) and growth factors promoting re- epithelialisation will facilitate the uptake and metabolism of zinc, copper and vitamin A. Indirect evidence suggests that gradients of calcium, zinc, copper and iron may interact with growth factors in the chemotaxis of macrophages, monocytes and fibroblasts into the wound site during the inflammatory phase.(4,16)
Nutrient availability is highly relevant in the following events in wound healing:

  • Haemostasis.
  • Metalloenzymes synthesis involved in wound bed ­preparation.
  • Inflammatory changes, granulation tissue formation.
  • Synthesis of intra- and extracellular enzymes and ­extracellular matrix.
  • Production of structural components of the epidermis and dermis.
  • Cellular maturation and function.
  • Modulation of conditions in the wound.

Nutritional insufficiency leading to any impairment in the general health of the individual can influence the wound ­environment and healing patterns by indirect means. Supplementation of certain nutrients such as zinc or calcium is known to promote healing.(17) Clinical and experimental studies have demonstrated that zinc creams and vitamin A are highly beneficial in treating skin wounds. Most essential nutrients exhibit a multifactorial role in wound healing. (18,19) They do not act in isolation but interact with other factors, making nutrient balance an important consideration. Zinc and calcium interact in cell proliferation and cell migration in the epidermis, but excess zinc is known to inhibit essential processes dependent upon calcium.(4) Interaction is seen between other minerals and certain vitamins.
Deficiencies in certain nutrients can lead to impaired wound healing. For example, the lethal hereditary condition of acrodermatitis enteropathica is recognised by hypozincaemia with impaired zinc uptake and metabolism in the intestinal mucosa.(20) Control of zinc metabolism in the body and its mobilisation from reservoirs in soft tissue and bone to wound sites is imperfectly understood. Absorption of trace metals from the gut is impaired by the chelating action of certain plant materials.
Vitamins are associated with trace mineral metabolism. Vitamin C modulates iron uptake and metabolism in collagen formation.(18) Vitamin D has a recognised role in the metabolism of calcium,(2,4) its interaction with parathyroid hormone and function as a central organiser in epidermal repair. Additionally, vitamins A, B (complex) and E, at least, are known to modulate other events in wound healing, notably epidermal cell proliferation and keratinisation. Vitamin C is essential in proline and hydroxyproline metabolism in collagenesis in scar tissue formation, and vitamin supplements have been shown to aid healing in bed sores.(21) Hypervitaminoses are a potential cause of delayed healing and reduced tensile strength.

Topical therapy
Most substances are absorbed to some extent through human skin.(22) Absorption is greatest in lipophilic or lipoidal preparations but is enhanced when the tissue is injured and where severed blood vessels are exposed.(23) Zinc oxide in a cream base is readily absorbed, and its value in treating nappy rash, bed sores, pressure ulcers and acute lesions is well documented. Free zinc ions become readily available for incorporation into repair systems. Calcium alginate is commonly used as a haemostat and constituent of complex wound care dressings.(24) Calcium ions are released in the presence of wound exudate as factor IV, but it is unclear to what extent the metal diffuses into the wound site to influence healing. A variety of vitamin preparations are available for skin care, but, as in the case of retinoates (vitamin A), medical supervision of use is stipulated.

Conclusion
Nutrition has been largely overlooked as a feature of wound management in favour of more traditional approaches using bandages and antiseptic preparations designed to optimise conditions in the wound bed.(24-27) Evidence is presented to show that key events in wound healing are dependent upon the availability of certain nutrients, and that unavailability or imbalances may lead to impaired healing. Further research is urgently required to examine the possibility that defects in the action and interaction of nutrients contribute to indolent and chronic wounds.

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References

  1. Ioannides C. Nutrition and chemical toxicology. Chichester: John Wiley; 1998.
  2. Lansdown ABG. Nutrition and the healing of skin wounds. Hartford, Huntingdon: Wound Care Society; 2001;8:2.
  3. Falanga V. Classification for wound bed preparation and stimulation of chronic wounds. Wound Repair Regen 2000;8:347-52.
  4. Lansdown ABG. Calcium: a ­potential central regulator in wound healing in the skin. Wound Repair Regen 2002;10:271-85.
  5. Köveker G, Coerper S. Surgical ­management of chronic wounds based upon research experience in Germany. In: The Oxford European Wound Healing Course Handbook. Oxford: Positif Press; 2002. p. 75-83.
  6. Hughes MA. The science of wound healing. In: The Oxford European Wound Healing Course Handbook. Oxford: Positif Press; 2002. p. 1-19.
  7. Lansdown ABG. In: Harvey PW, Rush K, Cockburn A, editors. Hormonal mechanisms in toxicology. Chichester: John Wiley; 1998.
  8. Bennett NT, Schultz GS. Growth factors and wound healing. Am J Surg 1993;165:728-37.
  9. Maume S, Cohen IK, editors. Emerging strategies for enhanced wound healing: the promise of growth factors. 3rd Joint Meeting of the European Tissue Repair Society and the Wound Healing Society. Bordeaux, France 1999.
  10. Lansdown ABG, Sampson B, Rowe AM. Sequential changes in trace metals, metallothionein and calmodulin concentrations in healing skin wounds. J Anat 1999;195:275-86.
  11. Hunt TK, Hussain Z. The wound micro-environment. In: Cohen IK, Deiglemann RF, Lindblad WJ, editors. Wound healing, biochemical and ­physiological aspects. Philadelphia:WB Saunders; 1992. p. 274-81.
  12. Czuka-Narins DM. Minerals. In: Kruse MV, Mahan LK, editors. Food, nutrition and diet therapy. Philadelphia: WB Saunders; 1979. p. 114.
  13. Underwood CJ. Trace elements in human and animal nutrition. 3rd ed. New York: Academic Press; 1971.
  14. Widdowson EM, Mathers JC. The contribution of nutrition to human and animal health. Cambridge: Cambridge University Press; 1992.
  15. Gell PGH, Coombs RRA. Clinical aspects of immunology. Oxford: Blackwell; 1968.
  16. Grotendorst GR. Chemo-attractants and growth factors. In: Cohen IK, Deigelmann RF, Lindblad WJ, editors. Wound healing: biochemical and clinical aspects. Philadelphia: WB Saunders; 1992. p. 237-46.
  17. Lansdown ABG. Zinc in the healing wound. Lancet 1996;347:706-7.
  18. Lansdown ABG. Iron: a cosmetic constituent but an essential nutrient for human skin. Int J Cosmet Sci 2001;23:129-37.
  19. Lansdown ABG. Action and ­interaction of metal ions in the ­physiology and pathology of the skin. Crit Rev Toxicol 1995;25:397-462.
  20. Moynahan EJ. Acrodermatitis enteropathica: a lethal inherited zinc deficiency disorder. Lancet 1974;ii:399-400.
  21. Taylor TV, Rimmer S, Day B. Ascorbic acid supplementation and pressure sores. Lancet 1979;2:544-6.
  22. Scheuplein RJ. Permeability of the skin: a review of major concepts.Curr Probl Dermatol 1978;7:172-86.
  23. Higuchi T. Design of chemical ­structures for optimal dermal delivery. Curr Probl Dermatol 1978;7:121-31.
  24. Blair S, Jarvis P, Salmon M, McCollum C. Clinical trial of calcium alginate haemostatic swabs. Br J Surg 1990;77:568-70.
  25. Gray DG, Russell F, Cooper RJ. Cost-effectiveness in wound dressing selection. Nurs Pract 2002;13:1-4.
  26. Russell L. Understanding ­physiology of wound healing and how dressings help. Br J Nurs 2000;9:10-21.
  27. Lansdown ABG. Silver. 1: its antibacterial properties and mechanism of action. J Wound Care 2002;10:125-30.

Resources
European Wound Management Association
W:www.ewma.org

Tissue Viability Society
W:www.tvs.org.uk

Wound Care Society
W:www.woundcaresociety.org