Increased vitamin plasma levels in Swedish military personnel treated with nutrients prior to automatic weapon training

Abstract

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.

Conflict of interest statement

Disclosure

These relationships have been disclosed to the Conflict of Interest Board at the University of Michigan (Miller) and the University of Florida (Le Prell).

Figures

Figure 1

Subjects were randomly assigned to one of the two study arms, distinguished by the order of the placebo and micronutrient tests. Subjects later crossed into the other arm of the study and participated in the opposite test condition. Treatment condition was masked; neither the participants nor the study team knew which treatment was delivered in each arm.

Figure 2

Subjects received blood draws prior to initiating treatment, and 2 hours after consuming the fourth and final treatment. Subjects received active agents (β-carotene, vitamins C and E, and Mg) in one arm of the study, and inactive (placebo) agents in the other arm of the study. Treatment order was randomly assigned, and treatment condition was masked to both the participants and the study team. All plasma analysis was contracted to a professional service provider: KAR Bioanalytics.

Figure 3

Pre-2 pre-shooting thresholds, measured after 2 days of treatment with either placebo or nutrients, were not reliably different when placebo-treated condition thresholds were compared to nutrient-treated condition thresholds for all subjects. All data are Mean ± S.D.

Figure 4

Threshold shift measured 15 min post-shooting is plotted; the dashed line indicates no change from Pre-2 baseline. There was no reliable effect of noise on threshold sensitivity, and no group difference between placebo- and nutrient- condition. All data are Mean ± S.D. Outcomes were unchanged when Median data were analyzed.