Micronutrient Homeostasis

Vitamin C

Vitamin C is not only an essential nutrient involved in many anabolic pathways and essential for would healing, but it also scavenges reactive oxygen species and improves microcirculatory flow impairment. Low plasma concentrations of vitamin C are very common in burned pediatric and adult patients.

Intravenous infusions of vitamin C have previously been shown to be beneficial in animal models. Dubick et al. infused high doses of ascorbic acid in an ovine model of 40% total body surface area (TBSA) burn injury, which significantly reduced resuscitation fluid requirements of burned sheep after 48 hours. Plasma thiobarbituric acid reactive substances increased fourfold in sham-burned sheep; this was prevented by the use of the vitamin C infusion. Tanaka et al. found that, using high-dose vitamin C, total tissue water content was reduced and negative interstitial fluid hydrostatic pressure was more positive in a rodent burned model when compared to unburned animals. Tanaka et al. showed in before-and-after trials that mega-doses of ascorbic acid (66 mg/kg/h ^-1 ) delivered during the first 24 hours after injury were associated with a significant fluid resuscitation requirement reduction and lesser weight gain, suggesting a beneficial role in burn resuscitation. Randomized trials are still needed. Last, the use of vitamin C protected the seminiferous tubules and germ cell loss in burned rats compared to unburned rats, but human data are not yet available.

Vitamin D

Vitamin D is a fat-soluble micronutrient that has been implicated in a wide array of physiological systems, including skeletal muscle, bone health, cardiovascular health, immune system, and lung function. It has been shown to reduce inflammatory cytokines and reactive oxygen and nitrogen species, as well as attenuate cancer, osteoarthritis, schizophrenia, and depression. Notable risk factors for decreased vitamin D concentrations include decreased skin production, use of sunscreen, its decreased bioavailability and production, liver or kidney dysfunction, malabsorption disorders, the use of cholesterol-lowering agents, and increased glucocorticoids.

Burned children develop a progressive deficiency of vitamin D as measured by circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D ₃ . This result may be confounded by the acute reduction in serum vitamin D-binding protein and albumin. Fourteen months post burn, serum 25-hydroxyvitamin D levels are low and remain low at 2 and 7 years post burn. Whereas serum levels of 1,25-dihydroxyvitamin D ₃ are normal at 2 years, about 50% of measured values are low at 7 years post burn, suggesting a progressive vitamin D deficiency.

During the acute phase, the standard 200 IU/day is insufficient to maintain vitamin D status as shown in a Belgian cohort study. Failure to provide vitamin D supplementation to burn patients at discharge from hospital may contribute to vitamin D deficiency. Fifteen adult burned patients were randomized into either a group that received quarterly intramuscular injections of 200,000 IU vitamin D ₃ with daily oral calcium or into a placebo group. After 1 year, calcidiol levels significantly increased in the vitamin D group. No change in bone health was observed between groups, but the vitamin D-treated group showed significantly improved quadriceps strength when tested at high velocity.

In 2009, pediatric burned patients discharged from the Shriners Hospital for Children in Galveston received daily supplementation with a multivitamin containing 400 IU of vitamin D ₂ for 6 months. 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. This was further tested in pediatric burned patients at the Shriners Hospital for Children in Cincinnati with 100 IU of vitamin D ₃ in a study that showed no significant differences in treated or untreated groups. Thus the amount of vitamin D supplementation necessary to maintain normal circulating levels of 25-hydroxyvitamin D in pediatricburned patients is unknown. Chan and Chan cite 200–400 IU/day as required in healthy, nonburned children. However there is no evidence supporting that requirement in a burned population, and long-term vitamin D supplementation with levels exceeding 400 IU/day may be necessary to overcome the postburn deficiency.

Another major factor, however, is the profound change in skin structure and quality. Burn scar and adjacent areas of unburned skin can only convert roughly 25% of its 7-dehydrocholesterol precursor to vitamin D ₃ on exposure to sunlight. Moreover, the amount of 7-dehydrocholesterol substrate is significantly reduced in both burn scar and adjacent unburned skin. This indicates that, after burn injury, the skin cannot synthesize normal amounts of vitamin D regardless of the amount of sun exposure received. Thus, progressive deficiency in vitamin D will result without supplementation.