Serum Biomarkers for Nutritional Monitoring in Motor Neuron Disease: A Longitudinal Cohort Study

Background: Malnutrition and metabolic dysregulation are common in motor neuron disease (MND) and contribute to accelerated functional decline and reduced survival. Routine serum biochemical analytes can be used to assess nutritional status; however, their interpretation in MND is confounded by systemic inflammation and disease-related metabolic changes. This study investigated the relationship between serum biochemical analytes, inflammatory status, disease severity, progression, and body composition in people living with MND. Methods: In this single-centre, longitudinal prospective cohort study, 19 participants with confirmed MND were assessed at enrolment and at three-month intervals up to nine months. Serum concentrations of albumin, prealbumin, creatinine, transferrin, ferritin, retinol-binding protein, and lipid fractions were measured alongside routine inflammatory markers. Disease severity and progression were assessed using the revised ALS functional rating scale and King's College Staging System. Anthropometry included percentage weight change, body mass index, mid-upper arm circumference, triceps skinfold thickness, arm muscle area, and calf circumference. Participants with evidence of baseline inflammation were excluded from nutritional analyses. Results: Low-grade systemic inflammation was present in 9/19 (47%) of participants at enrolment, most commonly reflected by elevated fibrinogen. In the non-inflammatory sub-cohort (n/N = 10/19), serum creatinine was positively correlated with muscle-related functional subscores (p = 0.007) and declined between enrolment and three months (p = 0.02), showing predominantly negative trajectories by nine months. HDL cholesterol also declined over the nine-month follow-up (p = 0.03) and lipid fractions correlated positively with disease stage (p <0.001-0.02), suggesting evolving metabolic stress. Elevated serum retinol-binding protein was observed in 90% (n/N = 9/10) of participants without inflammation. Biochemical evidence of malnutrition (low transferrin and/or creatinine) was detected in one-third of participants, accompanied by weight loss and reductions in limb anthropometric parameters. Malnutrition risk was identified in 1/10 (10%) of the non-inflammatory sub-cohort using a modified ESPEN-based framework, and in 2/10 (20%) participants using GLIM criteria. Conclusions: Routine serum biochemical analytes provide complementary information on nutritional and metabolic status in MND when interpreted alongside inflammatory markers and anthropometry. Serum creatinine emerged as a longitudinal marker of muscle wasting, reflective of denervation and nutritional depletion, while lipid and retinol-binding protein alterations highlight non-nutritional disease mechanisms that may confound standard biomarker interpretation, informing more targeted nutritional assessments. These findings support a multimodal approach to nutritional monitoring in MND and emphasise the importance of accounting for inflammatory status in biomarker interpretation. Given the small sample size and the limited representation of non-ALS phenotypes, these findings should be regarded as hypothesis-generating and require confirmation in larger, multicentre cohorts with balanced phenotypic representation.