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CAN ORAL GLUTAMINE AMELIORATE CHRONIC FATIGUE SYNDROME? A PILOT STUDY Prof. Gil Hardy 1 , Laura O’Hara 1 and Dr. John Watkins 2 1 Oxford Nutrition, Oxford, OX29 7FJ, (ghardy@nutrinox.com) 2 NARCOS, University of Sheffield, UK. Rationale
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CAN ORAL GLUTAMINE AMELIORATE CHRONIC FATIGUE SYNDROME? A PILOT STUDY Prof. Gil Hardy1, Laura O’Hara 1 andDr.John Watkins2 1Oxford Nutrition, Oxford, OX29 7FJ, (ghardy@nutrinox.com) 2NARCOS, University of Sheffield, UK Rationale Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a severe disabling illness, lasting for at least six months, which is rendered worse by mild physical or mental exertion. Various immunological disturbances have been described, but as yet no adequate medical explanation exists. The importance of L-Glutamine (Gln) in nutritional support of immunocompromised patients is well documented and provided the basis for this pilot study. Discussion CFS is diagnosed, according to the US Center for Disease Control, with more than 4 of the following symptoms: memory/concentration lapse, sore throat, muscle/joint pain, headaches, non-refreshing sleep and post-exertional malaise. Immunological disturbances include depressed NK cell activity, increases in circulating lymphocytes and generation of excessive levels of inflammatory mediators, which trigger the ‘flu-like’ fatigue symptoms. Dietary Gln increases production of cytokines, with a negative correlation between Gln levels and IL-6 production, and improves lymphocyte function. In previous Gln studies, with healthy volunteers, plasma Gln increased by at least 50%, and remained elevated for 1-2 hours before returning to the normal range of 500-700 M. Growth hormone and insulin levels were also elevated, but plasma glutamate and ammonia concentrations remained unchanged. No adverse effects were reported 2,3. Thus, despite an obligatory requirement for Gln by enterocytes, oral supplementation appears to be an efficient means of increasing the concentration of Gln in the systemic circulation in order to maintain lymphocyte proliferation and macrophage function. An increased Gln requirement could stimulate protein catabolism and muscle wasting to generate BCAA for Gln synthesis. This could result in a higher resting tryptophan/BCAA ratio in patients, coupled with higher brain 5-HT levels- a likely cause of fatigue. Gln supplementation may reverse this sequence of events. Table: Matched Volunteer Assessment Scores Aim To evaluate the potential of oral glutamine to relieve fatigue symptoms of ME. Method Twelve ME volunteers, 3 male and 9 female (78% post-menopausal aged 45 to 58y, mean weight 73kg) were randomised into 2 groups. For one month, group B received a maltodextrin placebo and group A received an oral glutamine supplement (GlutaminOx, Oxford Nutrition) as a 10g bolus in 250ml distilled water before breakfast. Each subject recorded their own assessment of health every 7d with an overall assessment at 28d. Common ME symptoms that were noted and assigned a score by participants included: sore throat, dizziness, muscle pain, depression and/or anxiety. Scoring System: 1=low, 10= high Results The duration of ME appeared similar in range for both groups, as did their health profiles at the commencement of the trial. In the Gln group A, 83% (4F, 1M) reported improvements in mood and appetite, decreased muscle pain and an increase in physical activity (Table). No overall improvement in any symptoms was perceived by the placebo group B. There were no major differences in plasma Gln observed between groups, but most controls exhibited a 13% increase after exertion (similar to athletes)1 with a marked increase in the plasma tryptophan/BCAA ratio. Conclusions These preliminary results, whilst somewhat subjective, are clearly encouraging and require more extensive follow-up. Many participants expressed the view that the study period should have been extended and there is a clear need for additional objective assessments to more precisely determine the potential clinical improvements from oral glutamine supplementation. References: (1) Castell L, MSc Thesis, University of Oxford 1996 (2) Zeigler TR et al, JPEN, 1990 (3) Dechelotte P et al, Amer J Phys, 1991