Baraniuk JN, El-Amin S, Corey R, Rayhan R, Timbol C.
Georgetown University Medical Center.
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. Researchers found a higher drop-out rate in carnosine than placebo treated GWI veterans.
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.
The study was limited by the relatively small sample size. The putative treatment effects require validation in similar randomized double blind placebo-controlled studies with larger groups of participants. The small sample size was hampered even further by the nine subjects who withdrew. They had no apparent symptomatic changes or adverse events. This includes parasthesias that have been noted previously (Artioli et al., 2010).
Study compliance was excellent based on diaries and pill counts. However, there were no cerebrospinal fluid, serum, or urine measurements of carnosine, beta-alanine or histidine to confirm absorption, pharmacodynamics, or brain metabolism to homocarnosine. Elevations in brain GABA levels in the treatment group may be identified by molecular spectroscopy (analysis in progress).
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.