Carnosine treatment for gulf war illness: a randomized controlled trial

Abstract

About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (B-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed. L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test. Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment.

Figure 1

WAIS-R Digit Symbol Substitution scores for wk12 - wk0 (Δ)

Figure 2

Percent of time active The percent of time active (accelerometer scores averaged each hour ≥ 40 units) was comparable for the carnosine (diamonds) and placebo (triangles) groups during the initial and final recording periods. The outlier in the carnosine group did not wear the watch for most of the second period.

Figure 3

Instantaneous Fatigue Scores A. The average instantaneous fatigue scores and 95% confidence intervals from all measurements were shown for all subjects. Fatigue was a stable variable without large excursions (small CI’s) within individuals during the recording periods. B. There was a wide range of instantaneous fatigue scores within the carnosine (diamonds) and placebo (triangles) groups. Individual responses did not change between the two recording periods. There were no treatment effects.