Mitochondrial Dysfunction in Gulf War Illness Revealed by 31Phosphorus Magnetic Resonance Spectroscopy: A Case-Control Study

BACKGROUND: Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness. OBJECTIVE: We sought to objectively assess for mitochondrial dysfunction(definition), examining post-exercise phosphocreatine-recovery time constant (PCr-R) using (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS), in Gulf War veterans with Gulf War illness compared to matched healthy controls. PCr-R has been described as a "robust and practical" index of mitochondrial status. DESIGN AND PARTICIPANTS: Case-control study from 2012-2013. Fourteen community-dwelling Gulf War veterans and matched controls from the San Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness, and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and ethnicity. OUTCOME MEASURE: Calf muscle phosphocreatine was evaluated by (31)P-MRS at rest, through 5 minutes of foot pedal depression exercise, and in recovery, to assess PCr-R. Paired t-tests compared cases to matched controls. RESULTS: PCr-R was significantly prolonged in Gulf War illness cases vs their matched controls: control values, mean ± SD, 29.0 ± 8.7 seconds; case values 46.1 ± 18.0 seconds; difference 17.1 ± 14.9 seconds; p = 0.023. PCr-R was longer for cases relative to their matched controls for all but one pair; moreover while values clustered under 31 seconds for all but one control, they exceeded 35 seconds (with a spread up to 70 seconds) for all but one case. DISCUSSION: These data provide the first direct evidence supporting mitochondrial dysfunction in Gulf War illness. Findings merit replication in a larger study and/or corroboration with additional mitochondrial assessment tools.