Invited Review
Volume 25 Number 1
Understanding the Role of Nutrition
and Wound Healing
Joyce K. Stechmiller, PhD, ACNP-BC, FAAN
Financial support: none declared.
Optimal wound healing requires adequate nutrition. Nutrition
deficiencies impede the normal processes that allow progres-
sion through stages of wound healing. Malnutrition has also
been related to decreased wound tensile strength and
increased infection rates. Malnourished patients can develop
pressure ulcers, infections, and delayed wound healing that
result in chronic nonhealing wounds. Chronic wounds are a
significant cause of morbidity and mortality for many patients
and therefore constitute a serious clinical concern. Because
most patients with chronic skin ulcers suffer micronutrient
N
utrition and wound healing are closely linked.1-7
Nutrition deficiencies impede the normal proc-
esses that allow progression through specific stages
of wound healing. Nutrient deficiencies or malnutrition
can have negative effects on wound healing by prolonging
the inflammatory phase, decreasing fibroblast prolifera-
tion, and altering collagen synthesis.1,3,8 Malnutrition has
also been related to decreased wound tensile strength and
increased infection.1,8 Malnourished patients can develop
pressure ulcers, infections, and experience delayed wound
healing that results in chronic nonhealing wounds. Chronic
wounds represent a significant cause of morbidity and
mortality for many patients.5,9-14
Diabetic ulcers, arterial ulcers, venous ulcers,
dehisced surgical wounds, and pressure ulcers are exam-
ples of complex chronic wounds associated with delayed
healing. A pressure ulcer is defined as an area of localized
damage to the skin and underlying tissue caused by pres-
sure, shear, friction, moisture, or a combination of these
factors.15 Pressure ulcers are staged according to severity
from stage I to IV.15 (The updated wound staging system
can be viewed at http:www.npuap.org/pr2.htm.) Most
patients with chronic skin ulcers suffer micronutrient
status alterations and have some degree of malnutrition.
From the University of Florida College of Nursing, Gainesville,
Florida.
Address correspondence to: Joyce K. Stechmiller, University of
Florida College of Nursing, Health Professions, Nursing and
Pharmacy Complex, Office 3222, PO Box 100187, Gainesville,
FL 32610-0187; e-mail: stechjk@ufl.edu.
61
Nutrition in Clinical Practice
February 2010 61-68
© 2010 American Society for
Parenteral and Enteral Nutrition
10.1177/0884533609358997
http://ncp.sagepub.com
hosted at
http://online.sagepub.com
status alterations and malnutrition to some degree, current
nutrition therapies are aimed at correcting nutrition deficien-
cies responsible for delayed wound healing. This review pro-
vides current information on nutrition management for simple
acute wounds and complex nonhealing wounds and offers
some insights into innovative future treatments. (Nutr Clin
Pract. 2010;25:61-68)
Keywords:   nutrition assessment; nutrition therapy; nutritional
deficiencies; wound healing; pressure ulcer
Chronic nonhealing wounds exist in a state of chronic
inflammation that leads to destruction of the extracellular
matrix and protein loss. Certain nutrients such as amino
acids and antioxidants have been shown to positively
influence wound healing,1-3,7,8,10-13,16-26 by preoperative
feeding and by certain nutrients such as arginine,
glutamine, butyrate, and vitamins.1 Current nutrition
therapies are aimed at treating nutrition deficiencies
responsible for delayed wound healing. This review pro-
vides current information on the nutrition management
for simple acute wounds as well as complex wounds that
fail to heal normally. In addition, this review will offer
some insights into innovative future treatments for wound
treatment.
Phases of Normal Wound Healing
Wound healing consists of a coordinated cascade of
sequential cellular, molecular, and biochemical events
that are affected by the nutrition state of the patient.2,27-29
These events include coagulation, inflammation, forma-
tion of the extracellular matrix, formation of fibrous
tissue, epithelialization, wound contraction, and remod-
eling.27 Collagen is the key element of the extracellular
matrix and is the most abundant protein in the human
body.1,8 The extracellular matrix is organized as a
thick dynamic network; the wound scar is the result
of collagen formation, degradation, and remodeling.
The healing process is divided into 3 distinct phases:
inflammation, proliferation, and remodeling or
maturation.2,27-29
62   Nutrition in Clinical Practice / Vol. 25, No. 1, February 2010

Inflammatory Phase
The inflammatory phase is the first phase of wound heal-
ing and occurs immediately after a wound is inflicted and
thromboxane A2 and prostaglandin 2a are released by cell
membranes.8,27 These potent vasoconstrictors cause a
temporary reflex vasoconstriction and reduction in bleed-
ing.3,8,27 Within seconds, the clotting cascade is stimulated
by the damaged endothelium and presence of platelets
resulting in the formation of a clot. The clot is composed
of collagen, platelets, thrombin, and fibronectin; these
substances are responsible for the release of cytokines and
growth factors including transforming growth factor b
(TGF-b), platelet-derived growth factor (PDGF), fibro-
blast growth factor (FGF), and endothelial growth factor
(EGF). The cytokines and growth factors attract neutro-
phils to the wound site, which in turn initiate the inflam-
matory response.8,27 Neutrophils are stimulated to migrate
to the wound by bacterial products, interleukin (IL)-1,
tumor necrosis factor-a (TNF-a), TGF-b, and platelet fac-
tor 4. Within 24 to 48 hours after the wound is inflicted,
it is primarily neutrophils that clear the wound site of
bacteria and cellular debris.8,27 Monocytes are attracted to
the wound site, where they are transformed to macro-
phages, 48 to 96 hours after injury. Macrophages have a
number of functions, including mediating angiogenesis,
synthesizing nitric oxide, and forming fibrous tissue.
Macrophages release enzymes and cytokines such as col-
lagenases, which break down and clear the wound of
debris; interleukins and TNF-a stimulate fibroblasts and
mediate angiogenesis; and TGF-b, which stimulates kera-
tinocytes.8,27 Macrophage-derived growth factors are
responsible for stimulation of cells to the wound bed and
the immature formation of connective tissue matrix com-
posed of fibrin.8,27
Proliferative Phase
The proliferative phase of wound healing usually occurs
on the fourth day after wounding and is characterized by
the early appearance of fibroblasts in the wound bed.
There are 4 major steps in this phase: (1) angiogenesis,
(2) epithelialization, (3) granulation, and (4) tissue for-
mation and collagen deposition.3,8,27 Angiogenesis pro-
vides new vascular networks for supplying nutrients to the
immature matrix and cellular elements of the granulation
tissue. Simultaneously, fibroblasts and endothelial cells
replace the immature matrix with a collagen-fortified
extracellular matrix and form new granulation tissue.
Fibroblasts are the main cell type responsible for develop-
ing granulation tissue 1 to 2 weeks after wounding; this
process is dependent on growth factors such as PDGF,
TGF-b, and FGF. Fibroblasts are also stimulated by TGF-b
for production of type I collagen. In addition, fibroblasts are
involved in the secretion of a number of growth factors
during wound healing such as FGF, TGF-b, PDGF, insu-
lin-like growth factor 1, and keratinocyte growth factor
(KGF).3,8,27 Endothelial cells secrete vascular endothelial
growth factor, FGF, and PDGF.27 Keratinocytes secrete
TGF-a, TGF-b, and KGF. Together, the total effects of
these growth factors are to ensure angiogenesis, epitheli-
alization, granulation, tissue formation, and collagen
deposition during the wound healing process.3,8,27
Remodeling or Maturation Phase
The remodeling or maturation phase normally begins a
week after a wound is inflicted and may continue for 1
year or longer. Fibronectin is the initial component in the
extracellular matrix that forms a preliminary fiber net-
work during this phase of wound healing. This network
has 2 key functions: as a template for collagen deposition
and as a platform for migration of cells and cellular
growth. As collagen becomes the predominant compo-
nent of the extracellular matrix, this results in stiffness
and tensile strength to the wound. Tensile strength is
restored to approximately 20% of normal uninjured skin
within 3 weeks of injury. As healing continues for approx-
imately 1 year, the skin gradually reaches a maximum of
70% to 80% tensile strength. During this phase, the syn-
thesis and degradation of collagen is regulated by collage-
nases. As the wound continues to mature, a gradual
reduction in cellularity and vascularity occurs.
Differentiation of fibroblasts into myofibroblasts is also a
characteristic of the remodeling phase.3,8,27
Chronic Wounds
Chronic (nonhealing) wounds are uniquely different from
acute wounds. Ischemia and/or bacterial colonization are
key factors that cause an acute surgical wound to remain
in a repetitive cycle of inflammation and injury.3,27-30 In a
chronic wound, there is a continuous recruitment of neu-
trophils, resulting in abnormally high levels of matrix
metalloproteinases (MMPs), including MMP-8 (neutro-
phil collagenase) and neutrophil-derived elastase, result-
ing in degradation of the extracellular matrix, changes in
the cytokine profile, and reduced concentrations of
growth factors.3,27,30 Neutrophils release reactive oxygen
molecules, which further damage the wound. Nonhealing
wounds are characterized by a disruption in the sequence
of phases of wound healing, with the wounds appearing
to be “stalled in the inflammatory phase.”3,28-30 Chronic
wounds have alterations at the molecular level, including
increased levels of inflammatory cytokines such as TNF-α
as well as IL-1 and IL-6. Elevated concentrations of
MMPs have a negative effect on fibroblast and endothe-
lial cell proliferation and function.3,27 Elevated cytokines
and proteases result in decreased levels of growth factors
 Understanding the Role of Nutrition and Wound Healing / Stechmiller   63
and reduced wound cell activity that responds poorly to
growth factors. Many factors can impair wound healing
such as diabetes mellitus, hypothyroidism, age, organ
failure, smoking, use of corticosteroids, chemotherapy,
and in particular, malnutrition and/or specific nutrient
deficiencies.
Patients with diabetes mellitus often experience
impaired wound healing and increased complications
such as infection. An alteration in the inflammatory
response with inhibition of fibroblast and endothelial cell
activity occurs in patients with diabetes mellitus.1 Wounds
in patients with diabetes mellitus are characterized as
having a prolonged inflammatory response to injury with
delayed matrix remodeling and closure.1 Open wounds
may have delayed epithelialization and decreased collagen
formation within the wound cavity. Hyperglycemia inter-
feres with leukocyte chemotaxis and cellular transport of
ascorbic acid into leukocytes and fibroblasts; this may
explain the decreased early inflammatory response and
altered wound healing that occurs in diabetic patients.1
The lack of insulin may also impair wound healing.1
Therefore, it is important to control serum glucose levels
in patients with diabetes mellitus, both perioperatively
and during injury, to optimize wound healing.1
Malnutrition and Wound Healing
A significant number of medical and surgical adult
patients cared for in US health facilities have compro-
mised nutrient intakes.3,5 The Nutritional Screening
Initiative led by the American Dietetic Association and
the American Academy of Family Physicians reported
critical statistics on the nutrition status of the US adult
population: 40% to 60% of hospitalized older adults are
either malnourished or at risk for malnutrition, 40% to
85% of nursing home residents are malnourished, and
20% to 60% of home care patients are malnourished.5
Research shows that malnutrition negatively affects
the wound healing process.1 Malnutrition prolongs the
inflammatory phase by decreasing the proliferation of
fibroblasts and formation of collagen as well as reducing
tensile strength and angiogenesis. It can also place the
patient at risk for infection by decreasing T-cell function,
phagocytic activity, and complement and antibody levels.8
These alterations in immune function may cause an
increase in wound complications such as delayed healing
of clean surgical wounds.1
Elderly nursing home residents are at high risk of
malnutrition, which places them at risk for the develop-
ment of pressure ulcers.1 The etiology of malnutrition is
usually multifactorial, including poor nutrient intake and
catabolism due to acute injury or the presence of a
chronic wound. Metabolic rates are increased in the pres-
ence of a wound, resulting in protein (muscle) breakdown
and loss of body water. With increased energy demands,
muscle is utilized as a source of amino acids for gluco-
neogenesis. Protein loss is also associated with the use of
negative pressure wound therapy devices for complex
wounds with continuous drainage of the wound bed.
Of utmost importance in the treatment of wounds is
good wound care, adequate wound-bed preparation, man-
agement of underlying disease, and correction of other
factors that may also impair wound healing. In addition,
provision of some specific nutrients has been shown to
promote wound healing.
Nutrient Requirements for Wound Healing
Wound healing requires optimal nutrition.1-14,16-25,27-43
Clinical studies have shown that adequate nutrition sup-
plementation can lead to enhanced wound healing in
surgical patients.8 Early postoperative enteral immunonu-
trition has been shown to increase hydroxyproline levels
and improvement in healing of surgical wounds.3,8
Improvement in surgical wound and infection complica-
tions was also appreciated with early postoperative immu-
nonutrition.6 In a 2006 meta-analysis to determine the
relationship between postoperative mortality and preop-
erative morbidity and immunonutrition, supplementation
with IMPACT (an enteral formula supplemented with
arginine, ω-3 fatty acids, and nucleic acids; Nestlé
Nutrition; Minnetonka, MN) was associated with statisti-
cally fewer anastomotic leaks when given preoperatively.44
A 2005 meta-analysis by Stratton et al4 showed that provi-
sion of oral nutrition supplements (250-500 kcal per serv-
ing) given over 2 to 26 weeks was related to a significantly
lower incidence of pressure ulcer development in at-risk
patients (elderly, postsurgical, long-term care patients)
compared with standard care. This systematic review also
showed that the risk of developing pressure ulcers could
be reduced by 25% with oral and/or enteral nutrition sup-
port. Further research is necessary to confirm trends that
oral nutrition supplementation and enteral tube feedings
can improve healing of pressure ulcers once they develop.
Energy
Energy is necessary for anabolism, nitrogen synthesis,
collagen formation, and wound healing.3,5 Glucose is the
major fuel source for collagen synthesis and the most
efficient source of fuel, compared with fat or protein.
Individual energy needs depend on age, gender, nutrition
status, basal metabolic rate, body mass index (BMI),
comorbid conditions, activity level, stress of illness, sever-
ity and number of wounds, size of the wound(s), and
stage in the healing process.1-5,8-12,16-19,32,35
In addition, dietary carbohydrates such as dietary fiber
and resistant starches are substrates for fermentation in
64   Nutrition in Clinical Practice / Vol. 25, No. 1, February 2010
the colon, producing short-chain fatty acids (SCFAs; eg,
acetate, propionate, and butyrate).8 SCFAs are the pri-
mary source of fuel for colonocytes. In fact, intracolonic
infusion of SCFA has been found to enhance postopera-
tive colonic anastomosis healing.8 Of the SCFAs, butyrate
has shown the greatest effect on colonic healing.8
The recommended guideline for calories for optimal
wound healing, according to the American Society for
Parenteral and Enteral Nutrition and the Wound Healing
Society, is approximately 30 to 35 kcal/kg/d.2,3,14 For obese
or geriatric patients with chronic wounds, an individual-
ized approach evaluating their metabolic state should be
considered when determining caloric goals.3 Furthermore,
the National Pressure Ulcer Advisory Panel (NPUAP)
recommends that individuals who are underweight or are
losing weight increase their energy goals to 35 to 40 kcal/
kg/d to optimize wound healing.2,3,12,14 The amount and
type of food/liquid ingested daily should be assessed fre-
quently to ensure that each individual meets their esti-
mated nutrient needs. Oral nutrition supplements can be
used to help achieve these needs, combat weight loss and
undernutrition, and enhance wound healing.5
Protein
Protein is necessary for the synthesis of enzymes involved
in wound healing, proliferation of cells and collagen, and
formation of connective tissue.1,2,4,5,9-13,16-25,30,32-37 All
stages of wound healing require protein; provision of
adequate protein is also necessary for positive nitrogen
balance.1 Severe protein depletion results in decreased
skin and fascial wound breaking strength and increased
wound infection rates,1 and increased protein intake is
associated with enhanced wound healing rates.1,3 In older
adults, dietary protein replacement is especially impor-
tant because body composition changes associated with
aging and reduced activity levels result in sarcopenia (loss
of muscle) and decreased immune function.5
The type and severity of the wound should be
assessed to ensure that the nutrition plan reflects an indi-
vidualized approach based on the relative loss of protein.
For example, protein loss from a stage I pressure ulcer is
less than loss with stage III or IV ulcers,3 which are severe,
full-thickness wounds characterized by moderate to large
protein losses. Other chronic wounds such as dehisced
abdominal surgical wounds may also have moderate exu-
dates and protein losses from wound drainage.45 Patients
with chronic wounds receiving negative pressure wound
therapy are also at risk for protein losses from these con-
tinuous drainage systems and may require oral nutrition
supplements enriched with protein.3
The recommended Dietary Reference Intakes (DRIs)
for macronutrients and micronutrients are available at
http://fnicnal.usda.gov.3 The requirement for exogenous
protein in healthy adults is 0.8 g/kg/d.2,3,5,8 Older adults of
have an increased protein requirement of 1 g/kg/d to main-
tain a positive nitrogen balance.3,8 Research has shown that
increasing protein intakes above the DRI enhances healing
of chronic wounds.3,8 The recommended range of protein
associated with healing is between 1.25 and 1.5 g/kg/d for
individuals with chronic wounds.3,8 If the patient is severely
catabolic, with more than 1 wound, or with a stage III or
IV pressure ulcer, they may require 1.5 to 2 g/kg/d pro-
tein.3,12 However, protein levels as high as 2 g/kg/d may
contribute to dehydration in older adults and individuals
with renal insufficiency and should be carefully moni-
tored.1,3 Finally, adequate calories must be provided to
prevent protein from being used as an energy fuel.
Amino Acids
Arginine and glutamine are 2 amino acids that have been
extensively studied for their role in wound heal-
ing.1-5,8-13,16-23,32-37 Arginine is a semi-essential amino acid
that acts as a substrate for protein synthesis, collagen
deposition, and cellular growth.1 Arginine supplementa-
tion has been shown to increase nitric oxide production
and enhance immune function.1-3,8,22,23,36 Investigators
have shown that arginine supplementation can enhance
wound tensile strength in acute wounds.1-3,8,22,23,36,46,47
Arginine supplementation is recommended for wound
healing if depletion of body stores is in question because
of the stress of illness.1 Arginine is contained in standard
tube-feeding formulas (approximately 2.4-5.4 g/d).3,16
Arginine-supplemented enteral formulas contain 12.5 to
18.7 g/L arginine, and studies that evaluated oral arginine
supplements for benefit in wound healing contained
between 17 and 30 g/d.3,16
The evidence to support the use of supplemental
arginine to improve wound healing outcomes is not con-
clusive, and there is still unresolved controversy over its
use; it may increase nitric oxide production, especially in
critically ill patients, which may result in hemodynamic
instability.3,16,22,23,36,43,48-50 Currently there are no evidence-
based guidelines specifically addressing the safe use and
dosage of arginine for healing chronic wounds.3,14,23,42
Glutamine is the most abundant amino acid in the
plasma; it provides 60% of the free intracellular amino
acid supply and 20% of the total circulating free amino
acid pool.1,3 Glutamine is a nitrogen donor for the synthe-
sis of other amino acids.1 Glutamine is also critical for the
synthesis of nucleotides in cells, including fibroblasts,
epithelial cells, and macrophages.1-3 Glutamine is essen-
tial for gluconeogenesis, providing fuel during wound
healing.1 Glutamine is also involved with immune func-
tion via lymphocyte proliferation, and is important in
stimulating the inflammatory response during the inflam-
matory phase of wound healing.1 Supplementation with
glutamine has been shown to improve nitrogen balance
and enhance immune function after major surgery,
 Understanding the Role of Nutrition and Wound Healing / Stechmiller   65
trauma, and sepsis.1,3,36,47,49 After injury, glutamine levels
in the plasma and muscle fall rapidly. However, studies
have not examined the effect of glutamine on wound
healing.2,3
The suggested dose of supplemental glutamine for
wound healing in adults is 0.57 g/kg/d.2,3,12 However, there
are no evidence-based guidelines specifically addressing the
safe use and dosage of glutamine to heal chronic wounds.1-3,8
Other amino acids may influence wound healing.1-3,8
Methionine, a cysteine precursor, stimulates fibroblast
proliferation and collagen synthesis, which are necessary
for wound healing. Cysteine functions as a cofactor for
enzyme processes in the formation of collagen. Lysine and
proline are other amino acids that contribute to wound
healing as precursors of collagen. Currently there are no
randomized clinical trials evaluating the impact of these
amino acids on the healing of acute or chronic wounds.1-3,8
Fat
The role of fat in wound healing has not been studied
sufficiently.1-3,12 However, it is well-known that with injury
there is an increased need for essential fatty acids.1-3,12
Prostaglandins play major roles in cellular metabolism
and inflammation. Prostaglandin synthesis is dependent
on linoleic and arachidonic acid, 2 unsaturated fatty acids
found in the diet. Deficiencies of these lipids are impli-
cated in impaired wound healing.1-3
ω-3 fatty acids have anti-inflammatory actions. For
example, they inhibit production of platelet-activating fac-
tor, IL-1, and TNF-α.1 Diets rich in ω-3 fatty acids have
resulted in weak wounds characterized by poor quality,
cross-linking, and organization of collagen fibrils.1 However,
the beneficial effect of diets rich in ω-3 fatty acids is in
their immune modulation. Studies have demonstrated
improved immune function, reduced infection rates, and
improved survival in patients experiencing burns when
their diets were supplemented with ω-3 fatty acids.1,51,52
Water
Ensuring adequate water intake is necessary for perfusion
and oxygenation of healthy and healing tissues.2,3
Furthermore, prevention and treatment of skin break-
down requires optimal fluid intake.3,53 Studies indicate
that if hypoxia is present, healing of acute wounds may be
compromised.53,54 Hyperbaric treatment and adequate
hydration have been shown to be effective in the treat-
ment of chronic wounds.55
Recommendations for daily fluid intake are 30 mL/kg
or 1 to 1.5 mL/kcal consumed.2,3,34 Increased fluid demands
exist in patients receiving a high protein intake or experienc-
ing major fluid loss from wounds with high exudate, treat-
ment with suction or negative pressure wound therapy
devices, use of air-fluidized beds, and fluid losses from
other causes.2,3,8,34
Vitamins
Standard multivitamins with minerals are recommended
for patients with wounds and if deficiencies are con-
firmed or suspected.2,3,34,41 Two vitamins, A and C, are
particularly important in wound healing.
Vitamin A
Vitamin A plays an important role in wound healing during
the inflammatory phase.2,3 Vitamin A stimulates the
immune system by increasing the number of macrophages
and monocytes in the wound during inflammation.3
Vitamin A has also been shown to enhance wound healing
by stimulating epithelialization and increasing collagen
deposition by fibroblasts.1-3,5 Conversely, the stress of ill-
ness and serious injury is associated with vitamin A defi-
ciency. Thus monitoring serum levels of vitamin A, retinyl
esters, retinol-binding protein, and b-carotene is indicated
in patients with burns or trauma, and those who have
undergone extensive surgery. Vitamin A supplementation
is indicated to enhance healing in patients with comor-
bidities (including diabetes, tumors, and radiation) and
acute or chronic wounds.1-3,47
The DRI for daily vitamin A consumption is 700 mg/d
for females and 900 mg/d for males (2,310 and 3,333 IU,
respectively).1-2,34 To enhance wound healing in injured
patients, documented recommendations include a range
from 10,000 to 50,000 IU/d orally or 10,000 IU intramus-
cularly for 10 days.1-2,25,34,41,56-58 Vitamin A can reverse the
anti-inflammatory effects of corticosteroids on wound
healing. For patients requiring long-term corticosteroid
treatment, topical or systemic administration of vitamin A
can correct delayed wound healing.1,2 For individuals
receiving corticosteroids, oral administration of 10,000 to
15,000 IU/d is recommended to enhance wound healing.3
More information is available on the DRIs at http://www.
nap.edu.
Vitamin C
Vitamin C, also known as ascorbic acid or L-ascorbic acid,
functions in the synthesis of collagen connective tissue
protein at the level of hydroxylation of procollagen. Vitamin
C acts on fibroblast proliferation, capillary formation, and
neutrophil activity.2,3,34 Vitamin C deficiency results in
clinical scurvy, which is characterized by swollen, bleeding
gums; loosening of the teeth; capillary hemorrhaging,
including bleeding into joints; tender and painful extremities;
poor wound healing; weakness and fatigue; and psychological
66   Nutrition in Clinical Practice / Vol. 25, No. 1, February 2010
disturbances. Smoking and alcohol consumption increase
the excretion of vitamin C.
Vitamin C supplementation at 100 to 200 mg/d is
recommended for patients who have vitamin C deficiency
or wounds, including stage I or II pressure ulcers.2-3,25,34,39,56
For more complex wounds, including stage III or stage IV
pressure ulcers or severe trauma, supplementation of
1,000 to 2,000 mg/d orally has been suggested until heal-
ing occurs.2,3,34,56 Vitamin C supplementation has also
been shown to enhance healing of wounds and burns.2,3
However, high-dose vitamin C supplementation may be
problematic in patients with a tendency to form kidney
stones.
Micronutrients
Micronutrients are trace elements and minerals that the
body requires in small amounts, yet they are critical to cel-
lular metabolism, especially during wound healing.1-3,34
Specifically, trace elements and minerals act as cofactors or
participate in enzymes necessary for wound repair.1 Because
deficiencies of trace elements and minerals are common in
the presence of general malnutrition, it is recommended
that patients with (or at risk for) protein-energy malnutri-
tion (PEM) take a supplement with trace elements and
minerals to ensure optimal wound healing. A dose of 5 to
10 times the recommended daily allowance of micronutri-
ents is usually suggested until PEM is resolved.2,3,8 Further
research is needed to determine the role and appropriate
doses of micronutrients in wound healing.2,3
Magnesium
Magnesium is an important trace element that functions
as a cofactor for enzymes necessary for protein and col-
lagen formation and tissue growth.1 Magnesium interacts
with adenosine triphosphate to support to the processes
for collagen synthesis during wound healing.1
Copper
Copper is an important cofactor for cytochrome oxidase
and the cytosolic antioxidant superoxide dismutase; it is
also needed for the interaction of lysyl oxidase that is
essential for cross-linking and strengthening of the col-
lagen framework.1 Impaired wound healing has been
observed in the face of copper deficiency.1,59,60
Zinc
Zinc is an essential mineral involved in numerous aspects
of cellular metabolism. It is required for the catalytic
activity of approximately 100 enzymes, including metal-
loproteinases, and it plays a role in immune function,
DNA synthesis, protein and collagen synthesis, cellular
proliferation, and wound healing.1-3,34 Zinc supplementa-
tion is recommended only in the presence of zinc defi-
ciency, which is commonly seen in patients who have (or
are at risk for) PEM, diarrhea, malabsorption, or hyper-
metabolic states (stress, sepsis, burns, venous ulcers, or
serious injury).2,3,34,61
The recommendation for zinc intake is 11 mg/d for
men and 8 mg/d for women.2,3,34,39 The recommendation
for zinc supplementation to enhance wound healing is up
to 40 mg (176 mg zinc sulfate) for 10 days. Zinc sulfate
220 mg twice daily (25-50 mg elemental zinc) has been
used as a standard adult oral replacement dose, but no
specified duration of therapy is available in the litera-
ture.2-3,34 Excess zinc interferes with iron and copper
absorption and can lead to deficiency of these important
minerals.3
Role of Nutrition in Pressure Ulcer
Prevention and Management
Nutrition factors associated with pressure ulcer develop-
ment or impaired pressure ulcer healing include recent
weight loss, low BMI, reduced dietary protein intake, and
eating difficulties.12 The US Department of Health and
Human Services clinical practice guidelines for the pre-
vention of pressure ulcers closely correlated adequate
nutrition status with skin integrity and recommended
nutrition evaluation to be addressed frequently as a vital
part of routine patient care.62 A recent case control study
in Japan reported that malnutrition was the strongest fac-
tor (odds ratio 2.29; 95% confidence interval 1.53-3.44)
associated with pressure ulcer development in 290 home
care patients with pressure ulcers compared with 456 home
care patients without pressure ulcers.63 In addition, they
reported that appropriate nutrition assessment and ade-
quate dietary intake in at-risk patients were significantly
associated with lower odds of developing pressure ulcers
in the same population (odds ratio 0.43; 95% confidence
interval 0.27-0.79).
Although many studies have demonstrated that poor
nutrition status is a risk factor for developing pressure
ulcers, there has never been a nationwide consensus on
specific nutrition recommendations for persons at risk of
developing pressure ulcers. Dorner et al12 highlighted
several studies including a large US cohort of nursing
home residents that demonstrated that significant weight
loss (wt loss of ≥5% over ≤12 weeks), dehydration, low
BMI (<22 kg/m2), reduced appetite, PEM, and impaired
ability to eat independently were associated with an
increased incidence of pressure ulcers as well as impaired
healing of pressure ulcers.12 In addition, Dorner et al in
cooperation with the NPUAP introduced nutrition rec-
ommendations from the NPUAP and European Pressure
 Understanding the Role of Nutrition and Wound Healing / Stechmiller   67
Ulcer Advisory Panel international guidelines for pressure
ulcer prevention and treatment based on current scien-
tific evidence.12 However, they also acknowledged the
need for more rigorous research in this field of study,
particularly in children, neonates, and obese individuals,
as well as in the role of appetite stimulants and anabolic
steroids. There is a significant lack of large clinical trials
investigating specific nutrition interventions; this gap
represents a need for future research, but based on the
evidence available in smaller randomized controlled tri-
als, case-control studies, and cohorts, Dorner and col-
leagues12 recommend the following for all individuals
admitted to a healthcare facility:
1. Ensure a qualified professional completes nutrition
screening of all patients on admission and after any
change in condition (such as surgery or oral food
and liquid intake status). Suggested tools include
Mini Nutritional Assessment and the Malnutrition
Universal Screening Tool.
2. Refer patient immediately for full nutrition assess-
ment by a registered dietitian if any deficits are
identified by screening.
3. Provide adequate kilocalories through dietary or
supplemental (enteral, parenteral, or oral) macro-
nutrients (fats, proteins, carbohydrates) based on
individual patient deficits, energy requirements
(determined by calculations based on age, gen-
der, height, weight, activity level), and comorbid
conditions.
4. Provide adequate fluids, assessing for fluid tolerance
and monitoring individuals for changes in weight,
skin turgor, urine output, elevated serum sodium,
and calculated serum osmolality, and adjust fluid
intake to maintain adequate hydration balance.
5. Offer oral supplements to individuals who are
unable to maintain adequate nutrition through diet
alone. Studies suggest supplements may be more
effective when taken between meals; supplements
containing protein, amino acids such as arginine,
and extra calories are commonly utilized to provide
for adequate daily protein energy requirements.
Micronutrients such as vitamin C and zinc are rec-
ommended only when a dietary deficiency has been
demonstrated or diagnosed. High-dose zinc sup-
plementation (>40 mg/d) is not recommended
because of zinc’s tendency to displace copper.
Summary
It is obvious that nutrition plays a crucial role in wound
healing, but there is a lack of strong evidence that supple-
menting a patient’s diet with specific nutrients improves
clinical outcome. Further research is needed to identify
the levels of supplements that will be of benefit to mal-
nourished patients and patients at nutrition risk. All
patients with wounds should be nutritionally assessed and
have their treatment managed by a multidisciplinary team.
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