Serum histidine is lower in fatigued women with multiple sclerosis

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.