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Rationale for Zinc Supplementation in Older Adults With Wounds
It is a widely held belief among healthcare practitioners that long-term care (LTC) residents with wounds who are zinc deficient stand to benefit from zinc supplementation, whereas those who are not zinc deficient do not. The lack of a practical, accurate, cost-effective, generally accepted method for determining zinc status makes it difficult to ascertain when someone is deficient. We do know that older adults in LTC are at greater risk for zinc deficiency and that having a wound may exacerbate deficiency. Despite the difficulty or even inability of practitioners to assess and monitor an individual’s zinc status, the evidence favors addressing the suspected prevalence of zinc deficiency in older populations, with early studies suggesting accelerated healing in response to oral zinc therapy.
Zinc Deficiency in Older Adults
Zinc deficiency is defined biochemically as a serum zinc level <60 mg/dL. Serum zinc levels between 60 mg/dL and 150 mg/dL are considered normal, with men typically having higher zinc levels than women. Variation in the literature as to what constitutes normal may be due to varying degrees of accuracy with the analytical methods used and the effect of circadian rhythms on zinc levels.3,4 In older adults, zinc deficiency typically results from inadequate dietary intake of zinc, disease states that promote zinc loss, or physiological states that require more zinc.1,2
Although plasma and serum zinc levels are the most widely used measures of zinc status, the picture they give is not necessarily accurate. Even individuals who have normal zinc levels according to laboratory measures can demonstrate clinical evidence of zinc deficiency,5 such as loss of appetite, diarrhea, hair loss, delayed wound healing, skin abnormalities (eg, atopic dermatitis, psoriasis), impaired senses of taste and smell, white spots on their fingernails, and mental lethargy or depression.6,7
Risk Factors for Zinc Deficiency
Many factors have been found to influence zinc status (eg, metabolic stress, sepsis, age, the time of day the sample was taken, and whether the individual was fasting).8,9 Because zinc is more than 90% protein-bound (primarily to albumin) in the serum, inflammatory conditions can also affect the accuracy of measured levels.10 Diagnosing zinc deficiency is further complicated by the strong homeostatic control of zinc in the body, where it is confined primarily to intracellular space.
The recommended daily allowance of zinc for adults 19 years and older is 8 mg for women and 11 mg for men,6 but daily zinc intake below these levels is commonly observed in older adults, as is low zinc status.1,11 LTC residents often have poor consumption of foods high in zinc (Table) coupled with decreased absorption, placing them at increased risk of zinc deficiency. A 3-year, randomized, controlled trial involving residents from 33 nursing homes found that nearly half of the 617 residents had zinc concentrations below the normal level.12
Only 20% to 40% of ingested zinc is absorbed (primarily through the small intestine), with zinc from animal sources more readily absorbed than zinc from plant sources. Altered olfactory and gustatory sensations and poor dentition are more common in elders, which may decrease their tendency to eat meat, thereby also decreasing their zinc absorption. The bioavailability of dietary zinc intake is affected by concomitantly ingested foods and medications. Many cereals and other grains contain substances—most notably, phytates—that inhibit zinc bioavailability. Commonly used medications that increase zinc loss include penicillamine, diuretics, diethylenetriaminepentaacetate, and valproate.
Many health conditions predispose residents to hypozincemia, including malignancy, hyperactivity, stress, trauma, active tuberculosis, skin disease, chronic wounds, chronic renal insufficiency, uremia, and nephritic syndrome.13,14 Heightened inflammatory status, chronic in elders, also contributes to zinc deficiency. Approximately 90% of zinc loss occurs via the fecal route. Disorders of the gastrointestinal tract and pancreas, emesis, and diarrhea promote zinc loss, increasing the risk of zinc deficiency. Diseases that inhibit intestinal absorption or increase intestinal losses of zinc also contribute to zinc deficiency. These include sprue, cystic fibrosis, and other intestinal malabsorption syndromes; inflammatory bowel diseases (eg, Crohn’s disease); and hemolytic anemias (eg, sickle cell disease). Disorders affecting the distal portion of the gastrointestinal tract, where reabsorption of endogenous zinc occurs, lead to increased zinc excretion. Chronic increased urinary zinc loss occurs with some renal diseases, cirrhosis of the liver, alcoholism, stress, catabolism, and other inflammatory diseases.15,16 Conditions that increase urine production and muscle breakdown (eg, acute catabolism, diuretic use, diabetes) and reduce the ability of the kidneys to concentrate urine contribute to zinc loss.17 A low level of serum albumin, the primary protein to which zinc binds, also results in increased excretion of zinc during urination.
Role of Zinc in Wound Healing
Many conditions associated with lower serum levels of zinc are prevalent in LTC residents, putting them at high risk for zinc deficiency, a status that is compounded by the presence of a wound.18 Approximately 20% of the body’s total zinc stores are found in the skin; thus, large skin wounds lead to a loss of zinc.3 Exudate from wounds and the use of chest tubes or subcutaneous wound drains can contribute to further zinc loss. In a wound patient, zinc deficiency may decrease rates of fibroplasia, epithelialization, and collagen synthesis; compromise wound strength; and impair immune response, increasing the patient’s susceptibility to skin breakdown.19
Zinc demand is thought to be the highest from the time of wounding throughout the early inflammatory phase, and inadequate zinc status during this period delays wound healing. The increased local demand for zinc that a wound induces can expose what would otherwise be a marginal zinc deficiency.20 Zinc deficiencies have been observed in individuals with deep partial- or full-thickness burns and chronic venous leg ulcerations.21,22 Chronic nonhealing wounds can perpetuate a self-reinforcing cycle, serving as both a cause and a byproduct of inadequate zinc levels.
Zinc’s role in wound healing is multifactorial, and it is required for collagen and protein synthesis, cell proliferation, and immune function, all of which are essential for tissue regeneration and repair. All proliferating cells, including inflammatory cells, epithelial cells, and fibroblasts, require zinc.23 At the biochemical level, increasing the local concentration of zinc ions can accelerate many molecular reactions performed by the enzyme systems involved in wound repair.24,25 Zinc is required for antibody production and proper functioning of lymphocytes and plays a key role in several steps of the blood clotting process.26 Zinc stimulates the activity of more than 100 enzymes and, in the proliferative and remodeling phases of wound healing, is necessary for achieving membrane stability and the maturation of collagen.2
Zinc Supplementation
Residents may require supplementary zinc if normal wound healing is to occur in the setting of a preexisting deficiency state. Supplementation can come from a multivitamin or mineral supplement containing 15 mg of zinc, medical nutritional supplements, or a zinc-only supplement, depending on the severity of the wound.
Many clinicians recommend administering up to 50 mg of elemental zinc per day until epithelialization is well-established or until the wound is fully closed.28 In zinc-deficient individuals, 3 months of supplementation with 25 mg to 50 mg daily of elemental zinc has been shown to have a positive effect on wound healing.29 Clinicians should closely monitor the wound’s response to zinc therapy, halting supplementation if no progress has been noted after 8 or 12 weeks, or if the patient becomes intolerant to zinc supplementation.
Common side effects of zinc supplementation include gastrointestinal issues, such as nausea, vomiting, and diarrhea, as well as central nervous system issues, such as vertigo and restlessness. Taking large doses of oral zinc supplements (100 mg per day as zinc sulfate) for more than 3 weeks may have adverse effects.30 For healthy individuals who are not zinc-deficient, the tolerable upper intake level of zinc is 40 mg daily. The potential toxic effects of zinc include interference with copper metabolism and impaired immune function,31 and long-term supplementation of zinc in individuals without zinc deficiency or a wound should be considered with caution.32
Conclusion
Zinc deficiency in older adults is widespread, and individuals with wounds are more prone to developing a zinc deficiency. With this in mind, healthcare professionals must use their clinical judgment, fully assessing a resident’s zinc intake, potential sources for zinc loss, and conditions that might compromise zinc status, and look for physical signs and symptoms of zinc deficiency. Justification for administering zinc supplements to promote wound healing includes a low risk of adverse effects when zinc is given in moderate doses (15-30 mg daily) and evidence that zinc deficiency impairs wound healing.
Dr. Sallit is scientific director, Medical Nutrition USA, a division of Nutricia. She is also a clinical advisor for the AALTCN.
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