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Food for thought: nutrition and wound healing

Victoria Richardson
BSc(Hons)
PGDipDiet
Registered Dietitian
Department of Nutrition and Dietetics
York Hospital

Many nutritional factors such as weight, body mass index and dietary intake are associated with poor wound healing and the development of pressure ulcers.(1) Despite the lack of good-quality studies, it is frequently documented that good nutrition facilitates healing, whereas malnutrition delays the healing process. However, no cause-effect relationship for poor nutritional status and the development of pressure ulcers has been established. Despite this, nutrition remains a factor in prevention strategies because it is a potentially reversible risk factor.(1,2) Nutritional recommendations have not been validated, but the following information will provide a review of some literature to guide clinical practice.(1)

Malnutrition
Although malnutrition is not a consistent risk factor in all studies, evidence does suggest a positive correlation between severe malnutrition and the risk of delayed wound healing and pressure ulcer development.(1,3,4,5)
 
Identifying potential causes of malnutrition can help determine an appropriate nutritional care plan. Common causes of malnutrition include:

  • Decreased appetite.
  • Dependency on help for eating.
  • Impaired cognition and/or communication.
  • Poor positioning, gastrointestinal losses.
  • Medications that decrease appetite.
  • Decreased thirst response.
  • Intentional fluid restriction because of fear of incontinence or choking if dysphagic.
  • Psychosocial factors such as isolation and depression.
  • Monotony of diet, and higher nutrient requirements with the demands of illness and disease.

Before we look at nutritional assessment, we need to look at the macro- and micronutrients that have key roles in the healing process.

Energy
Building and repairing tissue requires adequate amounts of calories and protein to fuel repair mechanisms.(6,7) Calorie requirements will vary greatly depending on several factors, such as the severity of the wound, stage of the healing process, comorbidities, age and body weight.(1)
 
For people who are not severely ill or injured, nor at risk of refeeding syndrome, the suggested nutritional prescription for total intake should provide 25-35 calories/kg/day total energy (including that derived from protein) and 0.8-1.5g protein/kg/day.(1,8) There is no known benefit of overfeeding on wound healing.(1)

Protein
Protein requirements increase to aid wound healing, as protein is required for part of the inflammatory process, the immune system and development of granulation tissue. Requirements increase if extensive nitrogen losses can occur from draining wounds or fistulae. However, they are difficult to quantify.(1) Similarly, protein depletion can affect the rate of wound healing by reducing collagen synthesis as well as the immune response.(1,2,7)

Studies show that a high protein intake does aid wound healing, especially in malnourished patients.(1,3,6) However, it is not known whether the same benefit would occur in well-nourished people.(6) It is worth noting that excess dietary protein intake may unduly tax renal and/or hepatic function. For these reasons, positive nitrogen balance remains the goal.(1)
 
Carbohydrate
Carbohydrate is the primary energy substrate required for cellular metabolism. As part of the inflammatory response process, the body increases cellular activity, fuelled by adenosine triphosphate (ATP), which is derived from glucose.(1) Glucose requirements for the chronically sick and healthy individuals range from 4-5g/kg/day.
 
If glucose from carbohydrate is unavailable, for example through inadequate dietary intake, amino acids from protein will be oxidised to meet the energy requirements of the wound healing process, thus depleting the amino acids available for reconstruction and tissue repair.(2)

Fat
Fat is an important energy source (providing 9 calories/ gram, compared with carbohydrate and protein, which provide 4 calories/gram) and a significant component of cell membrane structure and function, required for wound healing. Lipid requirements for the healthy to critically ill range from 0.8g-1.5g/kg/day. However, the proportion and quantity of fatty acids to aid healing is yet to be determined. (1) Particular fatty acids are "essential" - they cannot be made by the body and so must be provided by the diet. The two types are the omega-3 fatty acids (found in oily fish, sardines, salmon, trout, herring, walnuts and flaxseed oil) and the omega-6 fatty acids (sunflower, soya oils). The exact role of essential fatty acids (EFAs) in wound healing is unclear, and has not been adequately researched, but as they are involved in the synthesis of new cells, and help regulate the inflammatory response, it is believed depletion would delay wound healing.(1,5,9)
 
Animal studies have shown EFA deficiency reduces tensile strength and epithelisation of wounds. However, in humans, EFA deficiency is rarely encountered, unless the patient suffers from severe fat malabsorption.(1) Conversely, another study has found that high doses of omega-3 fatty acid supplementation may result in increased synthesis of prostaglandins.(1) This would impair the inflammatory response and result in a weaker wound. Due to conflicting evidence regarding benefits of EFAs, no recommendation on EFA supplementation can be made.

Fluid
Adequate fluid intake is required to maintain good skin turgor and blood flow to wounded tissues.(1) General guidelines for fluid requirements based on age range from 30-35ml/kg.(8) These guidelines are not specific for wound healing, and any additional fluid losses must be considered. Evaporation and fluid loss can be difficult to quantify, but fluid replacement may be necessary in those with fever, open or draining wounds or fistulae.(1) The concern regarding dehydration is that it can lead to an electrolyte imbalance and impaired cellular function.
 
To prevent dehydration, oral fluid intake needs to be strongly encouraged. Any fluid counts towards this nutritional requirement: water, milk and cordial. Foods such as ice cream, lollipops, ice cubes and jelly can contribute to fluid intake due to their high fluid content. Tea, coffee and some carbonated drinks contain caffeine, which is a mild diuretic and can cause some potential fluid loss. However, drinking caffeinated drinks is better than not drinking at all.(12)

Micronutrients
There have been a number of studies conducted on various vitamins and minerals regarding optimal nutrition for wound healing. The following micronutrients are selected as these seem to be a sample of the most frequently discussed nutrients involved in the healing process.

B complex vitamins
B complex vitamins, especially thiamine (also known as vitamin B1, found in pork, poultry, fish and beans) and pantothenic acid (vitamin B5, found in yeast and wholegrains) are co-factors in metabolic functions involved in wound healing. They are particularly involved in the energy release from carbohydrates, and collagen cross-linkage. Although there is insufficient evidence to place evidence-based recommendations on supplementation to aid wound healing, as human research is lacking, some alternative healthcare practitioners recommend a high-potency B vitamin supplement to promote wound healing.(4) There have been no toxic effects of pantothenic acid reported, but >3g/day of thiamine can have detrimental effects on heath.

Vitamin C
Vitamin C (also referred to as ascorbic acid, good dietary sources of which include citrus fruits and potatoes) has an important role in the formation of collagen, increasing its strength and stability. Many pieces of evidence suggest that vitamin C requirements increase during periods of severe injury, stress and sepsis, and deficiency delays healing. (1,4,5,6,7) However, no evidence exists to suggest that mega doses of vitamin C improve clinical outcomes as humans lack the ability to store vitamin C.(2,4)
 
Some studies indicate that there is a statistically significant reduction in the pressure ulcer area after supplementation, compared with a placebo group, and that supplementation may be indicated for optimal wound repair.(4) Conversely, larger studies indicate that control groups had better rates of healing when receiving a minimal supplement of ascorbic acid compared with the intervention group.(3) Further conflicting evidence occurs as to whether vitamin C supplementation in nondeficient people improves wound healing.(1,4,6,4) Therefore it is better practice to recommend sufficient intake to prevent deficiency.(7) Intakes exceeding 1g/day of vitamin C may cause cramps and diarrhoea, and caution must be used in patients with chronic renal failure.

Vitamin E
Vitamin E, found in eggs and vegetable oils, is the major lipid-soluble antioxidant in the skin(4) and is popular in alternative medicine for preventing scar formation. However, there is no clear role for vitamin E supplements in healing surgical wounds or pressure ulcers; indeed, research has shown its use may adversely affect healing by inhibiting collagen synthesis.(1,4,10)

Vitamin A
Vitamin A supplementation has been shown to improve wound healing and should be considered a supplement in steroid-dependent patients.(2,7) This may be due to the fact that vitamin A is a potent immune stimulant, which can reverse glucocorticoid suppression of wound healing.(1,4,7) It is, however, not as effective in reversing the effects of nonsteroidal anti-inflammatory drugs. Supplements have also been recommended in patients with sepsis. Concern about the potential toxicity of higher doses of vitamin A has led to uneasiness about its use in pregnant women and perioperatively,(4) and caution must be exercised, especially when the anti-inflammatory effects of steroids are essential. Dietary sources of vitamin A include dairy foods and liver.

Minerals
Zinc is required for wound healing as it is a co-factor in enzymatic reactions involved in protein synthesis and cell proliferation, has an inhibitory effect on bacterial growth and is involved in the immune response.(1,4,6,9) Low serum zinc levels have been associated with impaired wound healing.(4,7) Early studies suggest zinc supplementation, over and above that of the hospital diet, speeds wound healing. Rationale for supplementation may occur due to poor dietary intake, increased losses from large skin wounds (up to 20% of total body zinc is found in the skin)(1,7) or impaired absorption from gastrointestinal tract due to diarrhoea. Recent studies, however, have shown no benefit, unless the patient already has low serum zinc levels.(1,2,4) Caution regarding zinc supplementation is recommended because prolonged use of high zinc supplementation can adversely affect the immune response and lipid profiles and cause gastrointestinal upset. Small sample sizes in studies have indicated that zinc does not have significant effects on pressure ulcer healing.(3) Further research on nutritional supplementation is recommended to clarify the appropriate use of zinc supplementation.(4) Zinc is found in our diet from red meat, dairy foods and lentils..

Iron is a co-factor in DNA synthesis and is required for collagen cross-linkage, and therefore it is believed a lack of iron would impair cell proliferation and collagen synthesis involved in wound healing.(7,10) Absorption of haem iron (ie, iron from animal sources such as red meat and offal) is improved with the presence of vitamin C. Excessive intakes of iron (

Supplementation
The issue of nutritional supplementation to aid wound healing is debatable as sufficient intake of all nutrients is needed, and requirements may be raised during illness.(9) Solitary nutrient depletion is rare, and replacement should include a combination of appropriate nutrients, as it is doubtful that the patient will require specific vitamin mineral supplements.(4,8,10) There is some argument for vitamin C and zinc supplementation, but only when serum levels are low.(9) Again, there is a lack of evidence showing statistically significant difference when comparing the speed of wound healing with a multinutrient supplement or placebo group.(3)

The ideal way to meet requirements is to consume adequate oral intake of normal foods.(8) Patients may require a high-protein, high-calorie diet and latterly may need supplements (sip feeds). Treatment should take into account patients' needs and preferences when considering nutrition support.(8)
 
Nutrition support should be considered in people who are malnourished, as defined by the following;

  • A body mass index (BMI) of less than 18.5kg/m(2).
  • Unintentional weight loss greater than 10% within the last 3-6 months.
  • A BMI of less than 20 kg/m2 and unintentional weight loss greater than 5% within the last 3-6 months.(8)

Nutrition support should also be considered in those patients who are at risk of developing malnutrition, defined as those who have:

  • Eaten little or nothing for more than five days and/or are likely to eat little or nothing for five days or longer.
  • A poor absorptive capacity and/or high nutrient losses and/or increased nutritional needs from causes such as catabolism.(8)

Due to increased nutritional requirements combined with a poor appetite, oral sip feeds may not be sufficient in meeting nutritional requirements, enteral feeding may be initiated in the form of nasogastric or gastrostomy/jejunostomy feeding. Enteral feeding overnight can be helpful in meeting nutritional requirements while encouraging oral intake during the day.
 
Immune-enhancing enteral formulas may have beneficial effects on wound healing by reducing the incidence of wound infection. However, to date, no study has focused specifically on the wound healing population, other than burns patients. However, no effect on mortality was observed.(1) Disappointing results from a study on enteral nutrition to nursing home patients did not consistently improve markers of nutritional status or prevent development of pressure ulcers, although tube- fed patients with pressure ulcers received more calories and protein than the control. The combined effects of disease, sepsis, immobility and severe neurologic deficits were considered
possible causes for this outcome.(1)

Nutritional assessment
It is important to include evidence of nutritional assessment and interventions (eg, dietetic referral) in individual care plans.(5) Nutritional screening should assess body mass index and percentage unintentional weight loss, and should also consider the length of time for which nutrient intake has been unintentionally reduced and/or the likelihood of future impaired nutrient intake, shown as:
Body mass index = weight (kg)/height (m(2))
Percentage weight loss =
pre-illness weight − current weight/pre-illness weight × 100

The Malnutrition Universal Screening Tool (MUST), for example, may be used for this.(8) MUST is a validated tool to help provide a consistent and reliable nutritional screening method, and can be recommended for clinicians in practice to identify malnourished patients.
 
It is worth noting that serum albumin cannot be used as a sole indicator of malnutrition. Serum albumin can only indirectly identify patients who may benefit most from nutritional assessment and early intervention. This is because many factors during critical illness will alter serum albumin more readily than nutritional status. Blood loss, the acute-phase response and perioperative fluid resuscitation will contribute to postoperative reduced albumin levels. During this response, albumin will reduce, regardless of nutrition support, as it will not return to normal until the inflammatory response has resolved.(1,8)

Conclusion
Optimal nutrition facilitates wound healing, maintains immune competence and decreases the risk of infection. Malnutrition and clinically evident deficiencies are commonly associated with a delayed healing response. Nutritional intake should be varied and balanced to provide all the essential nutrients.(7) There is little evidence that supplementing a patient's diet with specific nutrients in isolation improves clinical outcome. While major wounds significantly raise protein and calorie requirements, optimal healing may require dietary changes, such as food fortification and/or supplements always encouraging food first, from a varied and balanced diet.
 
Lack of sufficient good-quality evidence limits the ability to determine the optimal nutritional regimen to enhance wound healing.(1) Further research is needed to identify the levels of supplement that will benefit malnourished patients.(2,10) Many studies have too small sample sizes, and high dropout rates, indicating that results should be reviewed with caution.(3) Most treatment studies have short trial periods, and healing of pressure ulcers or wounds is therefore unlikely to be detected.(3)

The lack of an accurate indicator of nutritional status may be one reason for inconsistent association between malnutrition and the risk of developing pressure ulcers, and delaying wound healing. Also, the criterion for defining malnutrition varies greatly between studies.(1) This at least supports the consistent use of a validated screening tool, such as MUST, to provide a consistent method of nutritional screening.

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References

  1. Thompson C. Nutrition and adult wound healing. Available from URL: http://www.nutritioncare.org/listserv/wound%20healing.pdf
  2. Williams L, Leaper D. Clin Nutr Update 2000;5:3-5.
  3. RCN. The management of pressure ulcers in primary and secondary care: a clinical practice guideline. London: RCN; 2006.
  4. Mackay D, Miller A. Alternative Med Rev 2003;8:359-76.
  5. NHS Quality Improvement Scotland. Pressure ulcer prevention: best practice statement. Available from URL: http://www.nhshealthquality.org/nhsqis/files/21878%20NHSQIS%20Ulcer%20BP...
  6. Ward N. Nutr J 2003;2:18-23.
  7. CREST. Guidelines on the general principles of caring for patients with wounds: recommendations for practice. Available from URL: http://www.crestni.org.uk/publications/wounds.pdf
  8. NICE. Nutrition support in adults: oral supplements, enteral and parenteral feeding. Clinical Guideline 32. Available from URL: http://www.nice.org.uk/download.aspx?o=256386
  9. Collier J. Nutrition and wound healing. Available from URL: http://www.dietetics.co.uk/article-nutrition-wound-healing.asp
  10. Williams L, Leaper D. Clin Nutr Updat 2000;5:3-5.
  11. Hamilton K. J Australas Coll Nutr Environ Med 1995;14:15-18.
  12. British Dietetic Association. Food facts: fluid - why you need it and how to get enough. Available from URL: http://www.bda.uk.com/Downloads/FluidBalance.pdf
  13. Gray D, Cooper P. J Wound Care 2001;10:86-9.
  14. Department of Health. Dietary reference values for food energy and nutrients for the United Kingdom. London: HMSO; 1991.

Resources
The MUST tool can be accessed from:
W:www.bapen.org.uk/the-must.htm

American Society for Parenteral and Enteral Nutrition
W:www.nutritioncare.org