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The importance of skin nutrition for wound healing

Alan BG Lansdown
PhD FRCPath
FIBiol MIMgt
Experimental Dermatologist and Toxicologist
Department of Chemical Pathology
Imperial College School of Medicine
London
*The author is a research scientist and freelance writer with an interest in the action and interaction of trace and environmental metals in skin biology and response to injury

Clinical and cosmetic evidence shows that the appearance of the skin is useful guide to a person's health and state of nutrition, and that scaling or roughness of the skin surface, alopecias and brittle nails may arise through insufficiencies, excesses or imbalances in essential nutrients (especially minerals or vitamins).(1) Additionally, substances present in the diet may alter the availability of nutrients, resulting in defects in skin ­physiology and responses to injury.
Nutrition may be defined as the provision of organic or inorganic materials necessary for normal growth in body systems, homeostasis of tissues in response to normal wear and tear processes, and repair of tissues following injury. It cannot be an exact science as requirements for different amino acids, carbohydrates, minerals and vitamins differ greatly from one tissue to another and according to the age, sex, race and geographic location, state of health and genetic background of the individual.
Unlike other tissues, the skin exists in a state of dynamic equilibrium with the surrounding environment. Cells are continually shed from the skin surface through abrasion and are replaced in a conveyor belt fashion through proliferative activity in the basal layer of the epidermis. Repair systems exist in dermal regions to rectify damage caused by bumps, bruises and exposure to UV irradiation. The skin is a metabolically active tissue providing a protective envelope for the body against physical, chemical and biological insults from the environment, while serving to eliminate toxic materials (especially toxic metals like lead). It varies structurally from one part of the body to another to reflect these protective functions.
 
Skin injury
In a healthy person, any loss of tissue or reduction in the skin "mass" through injury signals a chain of biological events leading to reconstitution of dermis and epidermis with renewal of the skin barrier function.(2,3) Current information shows that, in addition to an adequate supply of nutrients, the complex biosynthetic processes involved in wound healing depend on the action and interaction of growth factors, pharmacological mediators and hormones.(4) The sequential events comprising the so-called "wound healing cascade", including haemostasis, inflammatory change, cell proliferation and normalisation, have differing requirements in terms of conditions in the microenvironment (oxygen, acidity, hydration) and nutrients in providing an optimal medium for cell proliferation, migration and functional differentiation.(5) Wound management involves a manipulation of the wound site, in particular the wound bed, through appropriate dressings, antibiotic treatment and topical therapy, possibly involving application of nutrients, to advance the healing process.(6)This article centres upon acute wounds that are attributable to a direct physical or chemical insult - incisional wounds and lacerations, burns, scalds and accidental traumas. However, there is evidence to show that deficiency in certain nutrients can compromise the immune system, a large and complex subject.(7)
 
Cellular events and nutritional needs
A diet replete in minerals, vitamins and proteins is conducive to a pleasing skin colour and texture with hair and nail growth of good condition and optimal wound healing. Wound healing is a complex multistep process,(3) with the sequential events forming part of a continual process commencing with haemostasis and progressing to normalisation. The constituent events rely upon appropriate function of and interaction between many cell types, including viable cells of the epidermis and dermis at the wound margin and cells from the reticuloendothelial ­system that migrate to the wound bed through chemotactic modulation.(5) Nutrients (organic and inorganic substances derived from the diet) are required for:

  • Haemostasis.
  • Elimination of necrotic tissue in the wound bed and disinfection of the wound bed. Inflammatory changes and granulation tissue formation.
  • Cell proliferation - DNA and RNA synthesis, chemotactic pathways for cell migration.
  • Enzyme synthesis (matrix metalloproteinases, RNA- and DNA-ases, etc) and intracellular biosyntheses.
  • Structural components of the cell and extracellular materials, especially collagen, elastic tissue and  ground substance.
  • Cellular function (as in the role of neutrophils in bacteriostasis).
  • Provision and control of conditions in the wound microenvironment.

It is to be expected that nutrients will influence wound healing in the skin both through direct involvement in and requirement by local events in the wound site, and indirectly by their need for health of the whole body. The nutritional requirements for optimal human health are well documented,(8,9) whereas information relating to the nutrition in the skin wound is still widely scattered and possibly incomplete (Table 1).(10,11)

[[NIP04_table1_85]]

Nutrients like zinc and calcium are involved in several different events in the dermis and epidermis. Deficiencies, excesses or imbalances in these materials can be a cause of impaired or nonhealing wounds. Acrodermatitis enteropathica attributable to inherent or acquired zinc deficiency is a good example.(12) Too much zinc is a cause of impaired calcium and copper metabolism. Vitamin C is known to modulate iron uptake and metabolism, which is also influenced by calcium and magnesium.(13) Excess vitamin A is toxic to the skin, but deficiencies lead to a retardation in wound closure.(14) A source of nitrogen (protein or amino acid) is necessary both in cell ­proliferation and in biomolecular syntheses. Sulphur provided by cysteine is necessary for the keratinisation process and in the synthesis of mucopolysaccharides of the ground substance of the wound bed. Evidence suggests that the balance of nutrients can be as important as levels of individual materials.(11)

Intestinal absorption of nutrients
Most of the nutrients required for wound healing are derived from the diet and absorbed into the body through the intestinal mucosa. However, in the case of minerals, substances present in the diet can impair absorption.(1) Diets rich in plant fibres, histidine and ­phytate have been shown to impair zinc uptake.(15,16) Similarly, chemicals like EDTA, as used to purify drinking water, bind or chelate trace metals, rendering them unavailable for absorption. Toxic metals, including lead, cadmium and mercury, can impair the availability of essential minerals. Reduced blood levels of key trace metals are a known cause of poor wound healing.

Topical therapy
Wound healing is traditionally aided by the application of "nutrients" in the form of topical creams and ointments. Virtually any substance applied to the surface of the skin is absorbed to some extent and can influence cellular physiology. Substances are more readily absorbed at wound sites, especially in the case of partial thickness burns where the vascular exposure is higher.
Zinc cream is still valued as an inexpensive and effective therapy for skin wounds, notably nappy rash, bedsores and pressure ulcers. Calcium in the form of calcium sodium alginate (Kaltostat, Sorbisan, etc) is available as a topical preparation to aid haemostasis in the early wound. Toxic changes are rarely reported through excessive application of zinc or calcium, since the skin seems to regulate the uptake and excretion of these trace metals according to its needs.(17) Several vitamin A preparations or derivatives (eg, retinoates) are currently marketed for the treatment of skin ailments, but these can be toxic and are used only under medical supervision.(18)
 
Research into healing
Nutrition of the skin for optimal wound healing is ideally studied through clinical observation in patients with known case histories and dietary habits. This is a rare opportunity these days, although the classical studies of William Strain in the Middle East provided substantive evidence of the importance of zinc in the human diet.(19) Other studies in patients with inherited disorders of iron, copper and calcium metabolism have substantiated the importance of these metals in wound healing.
More information on the role of specific nutrients in wound healing is provided by laboratory-based research using live animal models or isolated human skin cells in culture.(20,21) Both alternatives have drawbacks. Although skin wounds induced in pigs and rats have provided significant information on the role of specific nutrients in wound healing under defined conditions, differences in the dietary requirements of these species renders the experimental observations difficult to extrapolate to humans. Culture of representative skin wounds in petri dishes is difficult, but the culture of isolated skin cells and reconstructed epidermis can be shown to respond to nutrients (especially trace metals) in a similar way to cells in the intact skin. More work is clearly needed in this area.

Conclusion
Optimal wound healing in the skin or any other tissue is directly related to the state of nutrition in the whole body. However, certain aspects of the epidermal regeneration and dermal scar tissue formation have special needs for trace metals, vitamins and other dietary materials. The nutritional requirements in the wound site change according to the stage in healing. Experimental studies in animal models and in test-tube cell cultures are available to demonstrate the special biochemical role of these nutrients in re- epithelialisation and closure of the wound site, and in essential biosyntheses (collagen, elastic tissue, ground tissue formation), which together comprise tissue repair and normalisation.

References

  1. Lansdown ABG. Action and ­interaction of metal ions in the ­physiology and toxicology of the skin. Crit Rev Toxicol 1995;25:397-462.
  2. Lansdown ABG. In: Harvey PW, Rush K, Cockburn A, editors. Hormonal mechanisms in toxicology. Chichester: John Wiley; 1998.
  3. Howes S, Harvey SC. Healing wounds as determined by their tensile strength. JAMA 1929;92:42-4.
  4. Barbul A, Pines, E, Caldwell M, Hunk TK. Growth factors and other aspects of wound healing. In: Progress in clinical biological research. New York: Alan Liss; 1987. p. 266.
  5. Hunt TK, Hussain Z. The wound microenvironment. In: Cohen IK, Deigelmann RF, Lindbladt WJ, editors. Wound healing: biochemical and ­physiological aspects. Philadelphia, PA: WB Saunders; 1992. p. 274-81.
  6. Falanga V. Classifications for wound bed preparation and stimulation in chronic wounds. Wound Repair Regen 2000;8:347-52.
  7. Gell PGH, Coombs RRA. Clinical aspects of immunology. Oxford: Blackwell; 1968.
  8. Widdowson EM, Mathers JC. The contribution of nutrition to human and animal health. Cambridge: Cambridge University Press; 1992.
  9. Underwood EJ. Trace elements in human and animal nutrition. New York: Academic Press; 1971.
  10. Roe A. Nutrition and the skin. New York: Alan Liss; 1986.
  11. Lansdown ABG. Nutrition and the healing of skin wounds: educational booklet. Wound Care Society; 2001.
  12. Moynahan EJ. Acrodermatitis enteropathica: a lethal inherited zinc deficiency disorder. Lancet 1974;ii:399-400.
  13. Lansdown ABG. Iron: a cosmetic constituent but an essential nutrient for human skin. Int J Cosmet Sci 2001;23:129-37.
  14. Thome EG. Long term clinical experience with topical retinoid. Br J Dermatol 1992;127 Suppl 41:31-6.
  15. Prasad AS. Trace elements in human and animal nutrition. New York: Plenum Press; 1978.
  16. Lonnerdahl B, Bell JG, Hendrickx AG, Keen CL. Effect of phytate removal on zinc absorption from soy formula. Am J Clin Nutr 1988;48:1301-6.
  17. Lansdown ABG. Zinc in the healing wound. Lancet 1996;1:706-7.
  18. British National Formulary. London: British Medical Association; 2001.
  19. Strain WH, Steadman LT, Lankau CA, Berliner WP, Pories WJ. Analysis of zinc levels in hair for the diagnosis of zinc deficiency in man. J Lab Clin Med 1966;68:244-9.
  20. Gottrup F, Ågren MS, Karlsmark T. Models for use in wound healing research: a survey focussing on in vitro and in vivo adult soft tissues. Wound Repair Regen 2000;8:83-96.
  21. Sullivan T, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen 2001;9:66-76.

Forthcoming event
19-22 June 2002
7th Oxford European Wound Healing Summer School
Contact: Jane Green T:01865 228269