First Vitamin E Trial Hints at Improved TBI Outcomes
By Laird Harrison
Elsevier Global Medical News
High doses of vitamin E significantly decreased in-hospital mortality following a traumatic brain injury in the first-ever randomized, controlled clinical trial of this treatment.
High doses of the vitamin cut in-hospital mortality from traumatic brain injury (TBI) by 29% relative to the overall mortality of patients who received treatment with low or high doses of vitamin C (ascorbic acid) or placebo. The study also showed the benefits of high-dose vitamin C in stabilizing or reducing the diameter of perilesional edema and infarct, according to Dr. Ali Razmkon, a neurosurgery resident at the Shiraz (Iran) University of Medical Sciences, who presented the study at the annual meeting of the Congress of Neurological Surgeons.
The theory behind the study is that lipid peroxidation causes secondary damage in head injuries. "There are well-documented reports about vitamin C in human stress in many conditions, including common cold and stroke," Dr. Razmkon said in an interview after the meeting. "The plasma concentration is reduced. The body needs more and utilizes more."
Previous studies suggested that vitamin C could reduce the risk of stroke and that vitamin E (alpha-tocopherol) could decrease the rate of lipid peroxidation.
To test this theory, Dr. Razmkon and his colleagues at Shiraz enrolled 100 patients (83 men) with traumatic brain injury. The patients all had Glasgow Coma Scale scores of 8 or less and radiologic diagnoses of diffuse axonal injury. Exclusion criteria included significant liver or renal disease, previous head injury, or glucose-6-phosphate dehydrogenase deficiency.
They randomized patients to low-dose IV vitamin C (500 mg daily) for 7 days, high-dose IV vitamin C (10 g on the day of admission and again on the fourth day, followed by 4 g daily for 3 more days), intramuscular vitamin E (400 IU daily) for 7 days, or placebo. The groups had no significant differences in diagnosis, age, or sex.
During the study, 26 patients died, and 67 (91%) of the remaining 74 patients attended follow-up at 2 and 6 months.
Hospital mortality was significantly lower among patients in the vitamin E group (20%) than it was in the groups receiving low- or high-dose vitamin C (30% and 29%) or placebo (33%). In-hospital mortality was 28% overall in these other three groups. At 6 months of follow-up, no differences in mortality were seen between the vitamin E (30%), low- and high-dose vitamin C (35% and 29%), and placebo groups (33%).
The vitamin E group also had significantly better Glasgow Outcome Scale scores at discharge and at 2 and 6 months of follow-up than did any of the other three groups.
The diameters of the perilesional hypodense regions in the brains of patients taking high-dose vitamin C were stabilized or reduced over the course of 7 days, dropping from a peak mean diameter of 12 mm on the third day after admission to 8 mm on the seventh day. This was significantly different from what was seen in patients in the other groups, which all had perilesional edema that continued to increase in diameter.
The researchers concluded that low-dose vitamin C didn't affect the patients' healing but that high doses of the vitamin slowed the progression of perilesional edema, which was likely a result of secondary oxidative insults. Neither dose of vitamin C appeared to affect neurologic outcomes.
For his work on the trial, Dr. Razmkon won the Synthes Resident Award for Research on Brain and Craniofacial Injury.