Importance of vitamins and trace elements

Although vitamins and trace elements play key roles in nearly every cell mechanism in the body, we know remarkably little about the effects of burn injury on their requirements, homeostasis, and metabolism. The published work on burns and micronutrients has covered the role of vitamins and trace elements in homeostasis, wound healing, and antioxidant properties. We will examine each of these topics in the context of the available published data.

Homeostasis and requirements of vitamins following burn injury

Studies of vitamin homeostasis post burn are sparse. Retinol (vitamin A), α-tocopherol (vitamin E), and ascorbic acid (vitamin C) have all been reported as low.^1,² Rettmer³ performed functional testing for thiamin (vitamin B₁), riboflavin (vitamin B₂), and pyridoxine (vitamin B₆) in burn patients and found them to be normal. In a study of serum vitamin K levels in severely burned pediatric patients, Jenkins⁴ reported that 91% of children studied demonstrated low circulating levels in the first month post burn. There was no relationship between serum vitamin K levels and prothrombin time, raising the question of clinical significance. It should be noted, however, that osteocalcin, a γ-carboxylated protein produced by osteoblasts, is vitamin K dependent. Osteocalcin is used as a standard index of bone formation and also has been shown to stimulate pancreatic insulin production and peripheral insulin sensitivity.⁵ Circulating osteocalcin is reported to be low in the first month following burn injury.⁶ Therefore, the possibility remains that low circulating vitamin K levels may contribute to the reduction in serum osteocalcin and hence to post-burn insulin resistance. For a more detailed discussion of osteocalcin, see Chapter 26.

Barbosa ⁷ studied burned children randomized to micronutrient supplementation or a supplement consisting of vitamin C (1.5 times the upper level of intake), vitamin E (1.35 times the upper intake level) and zinc (twice the recommended dietary allowance). This formula was given for 7 days starting on day 2 of admission. Serum levels of vitamin E were increased and lipid peroxidation, as measured by malondialdehyde, was decreased in the antioxidant supplementation group. The time of wound healing was also decreased in the experimental group.

The infusion of vitamin C alone also seems to have some benefits. Dubick ⁸ infused high doses of ascorbic acid in a sheep model of 40% TBSA injury. The vitamin C infusion significantly reduced resuscitation fluid requirements of burned sheep. Plasma thiobarbituric acid reactive substances increased fourfold in sham-burned sheep; this was prevented by the use of the vitamin C infusion. Tanaka⁹ found in a rat burn model that with high-dose vitamin C, total tissue water content was reduced and negative interstitial fluid hydrostatic pressure was more positive than in controls. This finding suggests that ascorbic acid administration alone could reduce fluid requirements in burn resuscitation.

The one vitamin that has been studied in more detail in burned patients is vitamin D. As discussed in Chapter 25, burned children develop a progressive deficiency of vitamin D as measured by circulating levels of 25-hydroxyvitamin D. Although acute measurements of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, the metabolically active steroid hormone, have shown that levels can be low, this result may be confounded by the acute reduction in serum vitamin D-binding protein¹⁰ and albumin.¹¹ Fourteen months post burn serum 25-hydroxyvitamin D levels are low¹² and remain so at 2 and 7 years post burn.¹³ Whereas serum levels of 1,25-dihydroxyvitamin D are normal at 2 years, about 50% of measured values are low at 7 years post burn,¹³ suggesting a progressive vitamin D deficiency.

Failure to provide vitamin D supplementation to burn patients on discharge from hospital may contribute to the vitamin D deficiency. Another major factor, however, is the profound change in skin structure and quality. Burn scar and adjacent areas of normal appearance can only convert about 25% of its 7-dehydrocholesterol precursor to vitamin D₃ on exposure to sunlight.¹² Moreover, the amount of 7-dehydrocholesterol substrate is significantly reduced in both burn scar and adjacent normal-appearing skin.¹² This indicates that after burn injury the skin cannot synthesize normal amounts of vitamin D regardless of the amount of sun exposure received. Thus without vitamin D supplementation, progressive deficiency will result.

In a recent study, children discharged from the Shriners Hospital in Galveston received daily supplementation with a multivitamin containing 400 IU of vitamin D₂ for six months.¹⁴ At that time, circulating levels of 25-hydroxyvitamin D were still in the insufficient to low range, without any improvement in lumbar spine bone density. Therefore, the amount of vitamin D supplementation necessary to maintain normal circulating levels of 25-hydroxyvitamin D is unknown. Chan and Chan cite 200–400 IU per day as required in healthy, non-burned children.¹⁵ However, there is no evidence supporting that requirement in a burned population, and long-term vitamin D supplementation with levels exceeding 400IU/day may be necessary to overcome the post-burn deficiency.

Zinc and copper

Zinc (Zn) and Copper (Cu) are essential trace elements. Zinc has roles in the metabolism of RNA and DNA, signal transduction, and gene expression, and also regulates apoptosis, thereby playing a ‘ubiquitous role’ in the human organism.¹⁶ Copper is involved in the formation of red blood cells, the absorption of iron from the digestive tract, metabolism of glucose and cholesterol, and the synthesis of nearly all proteins and enzymes.¹⁷ Malnourishment, hereditary diseases, and prolonged ICU stay can lead to clinical manifestations of Zn and Cu deficiency. Several groups have reported low serum concentrations of Zn, Cu, and their corresponding binding proteins albumin and ceruloplasmin, in burned patients.¹⁸^–²³ Burn wound exudation and urine excretion are considered major routes of loss of these elements.^18,^20,²²^–²⁶

In patients with moderate to severe burns, Cunningham ¹⁸ and Boosalis²⁵ found excessive urinary Zn excretion associated with low plasma Zn levels, especially the plasma subfraction bound to albumin. Zinc supplementation by total parenteral nutrition resulted in hyperzincuria, albeit not as pronounced as with oral supplementation.^18,²⁵ Voruganti found elevated urinary Cu and Zn excretion in severely burned children at admission as well as at hospital discharge.²⁶ The pediatric burn patients in this study received up to three times the suggested oral intake of Zn and Cu compared to dietary reference intakes.

The burn wound itself is another source of loss of both Zn and Cu. In adults, Berger,²⁴ Guo²¹ and Voruganti²⁶ found that Zn in wound exudates greatly exceeded excretory losses over the first week post burn. This was confirmed in severely burned children with an average burn size of 54% TBSA, with Zn and Cu concentrations in wound exudates exceeding plasma concentrations.²⁶

Although excretory and exudative losses of Zn and Cu can certainly contribute to a fall in plasma levels of these micronutrients, there is evidence for their post-burn redistribution in the body. Van Rij reported that after a 20% TBSA burn in the rat, isotope-marked Zn was rapidly taken up by the wound, spleen, kidney, and liver, whereas a decrease in Zn levels took place in the brain, muscle, and bone.²⁷ Zinc-binding protein was demonstrated in the hepatic cytosol. Agay found a redistribution of Zn and Cu to the liver without significant changes in levels in muscle and brain.²⁸ Given the findings of Cunningham¹⁸ and Boosalis²⁵ that Zn supplementation exacerbates urinary Zn excretion, it can be hypothesized that the body cannot take up the supplemental Zn, and that the redistribution of Zn, rather than elevated urinary excretion, is responsible for decreased plasma levels. Consistent with this hypothesis, Zn is also involved in the inflammatory response and could be redistributed to sites of barrier disruption such as skin, to be subsequently lost in wound exudate.

The low level of plasma Cu is partly due to reduced circulating levels of ceruloplasmin.^19,²³ Even though ceruloplasmin is an acute-phase reactant stimulated by proinflammatory cytokines, such as interleukin (IL-)1,^11,²⁹ there is also evidence that levels of ceruloplasmin are increased in the burn wound exudates. Cunningham¹⁹

Only gold members can continue reading. Log In or Register to continue