Author:
Golomb Beatrice A.,Sanchez Baez Roel,Schilling Jan M.,Dhanani Mehul,Fannon McKenzie J.,Berg Brinton K.,Miller Bruce J.,Taub Pam R.,Patel Hemal H.
Abstract
AbstractGulf War illness (GWI) is an important exemplar of environmentally-triggered chronic multisymptom illness, and a potential model for accelerated aging. Inflammation is the main hypothesized mechanism for GWI, with mitochondrial impairment also proposed. No study has directly assessed mitochondrial respiratory chain function (MRCF) on muscle biopsy in veterans with GWI (VGWI). We recruited 42 participants, half VGWI, with biopsy material successfully secured in 36. Impaired MRCF indexed by complex I and II oxidative phosphorylation with glucose as a fuel source (CI&CIIOXPHOS) related significantly or borderline significantly in the predicted direction to 17 of 20 symptoms in the combined sample. Lower CI&CIIOXPHOS significantly predicted GWI severity in the combined sample and in VGWI separately, with or without adjustment for hsCRP. Higher-hsCRP (peripheral inflammation) related strongly to lower-MRCF (particularly fatty acid oxidation (FAO) indices) in VGWI, but not in controls. Despite this, whereas greater MRCF-impairment predicted greater GWI symptoms and severity, greater inflammation did not. Surprisingly, adjusted for MRCF, higher hsCRP significantly predicted lesser symptom severity in VGWI selectively. Findings comport with a hypothesis in which the increased inflammation observed in GWI is driven by FAO-defect-induced mitochondrial apoptosis. In conclusion, impaired mitochondrial function—but not peripheral inflammation—predicts greater GWI symptoms and severity.
Funder
Congressionally Directed Medical Research Programs
Veterans Administration
Publisher
Springer Science and Business Media LLC
Reference172 articles.
1. Golomb, B. A. Diplomats’ mystery illness and pulsed radiofrequency/microwave radiation. Neural Comput. 30, 1–104. https://doi.org/10.1162/neco_a_01133 (2018).
2. Golomb, B. A., Koslik, H. J. & Redd, A. J. Fluoroquinolone-induced serious, persistent, multisymptom adverse effects. BMJ Case Rep. https://doi.org/10.1136/bcr-2015-209821 (2015).
3. Davies, D. R., Ahmed, G. M. & Freer, T. Chronic organophosphate induced neuropsychiatric disorder (COPIND): Results of two postal questionnaire surveys. J Nutr. Environ. Med. 9, 123–134 (1999).
4. Binns, J. H. et al. Research Advisory Committee on Gulf War Veterans' Illnesses: Scientific Progress in Understanding Gulf War Veterans’ Illnesses: Report and Recommendations 1–141 (2004).
5. Cherry, N. et al. Health and exposures of United Kingdom Gulf war veterans. Part II: The relation of health to exposure. Occup. Environ. Med. 58, 299–306 (2001).
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