ABSTRACT
Background: Disabling persistent perceived fatigue occurs in 50% of people with multiple sclerosis (MS), but mechanisms are poorly understood. Low histidine could contribute to fatigue since it is the neurotransmitter histamine precursor and low serum levels are reported in other diseases where fatigue is common (e.g. breast cancer, kidney disease, diabetes). Serum histidine is also inversely correlated with proinflammatory cytokines (e.g. TNF, IFN-y), which have been linked to MS fatigue.
Purpose: To determine if serum histidine is low in fatigued women with MS, and if histidine is related to differences in proinflammatory cytokines.
Methods: Participants were classified as having elevated (n = 19) or normal (n = 18) perceived fatigue based on a median sample split using Profile of Mood States fatigue scale scores, with the elevated fatigue group having scores >7. Histidine and gene-expression of TNF, IFN-y, and leptin were assayed from a serum sample.
Results: After adjustment for depression, serum histidine was significantly lower in women with MS with elevated fatigue, compared to normal fatigue (64.57 vs. 70.48 nmol/mL, p = .048, g = 0.75). There were no differences between groups in cytokine expression (all p > .24). Gene expression of TNF correlated with histidine only in people with normal fatigue (r = .51, p = .034), while no other cytokines related to histidine levels.
Conclusions: These results provide evidence that serum histidine is lower in fatigued women with MS, but the study did not find a relationship between histidine and TNF, IFN-y, or leptin gene expression.
Acknowledgement
We thank Nick Coddington, Rachel Murdock, and Kayla Warner for assistance with participant recruitment and data collection. We would like to thank Ms. Jenny Luo and Dr. Dennis Koop for the assistance with the histidine analysis that was conducted in the Bioanalytical Shared Resource/Pharmacokinetics Core. The facility is part of the Universiy Shared Resource Program at Oregon Health and Sciences University. We thank Anna Booman for assistance with data reduction and analysis.
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
Notes on contributors
Bryan D. Loy
Bryan D. Loy is a senior research associate at Oregon Health & Science University. His research focuses measurement of perceived fatigue, and the effects and mechanisms by which countermeasures such as natural products or exercise may reduce fatigue.
Brett W. Fling
Brett W. Fling is an assistant professor at Colorado State. His research investigates how the nervous system controls movement and leverages this understanding to develop novel therapeutic interventions for individuals with sensorimotor deficits.
Kylie M. Sage
Kylie M. Sage is a biostatistical consultant at Oregon Health & Science University.
Rebecca I. Spain
Rebecca I. Spain is an associate professor at Oregon Health & Science University. She specializes in treating patients with multiple sclerosis. Her research interest is in treating progressive forms of multiple sclerosis and evaluating mobility in those patients.
Fay B. Horak
Fay B. Horak is a professor at Oregon Health & Science University. Dr Horak studies neurological disorders that effect balance and gait in the elderly, people with Parkinson's disease, multiple sclerosis, cerebellar ataxia, vestibular injury or disease, diabetic neuropathy, and back pain.