ORIGINAL RESEARCH article
Front. Nutr.
Sec. Clinical Nutrition
This article is part of the Research TopicNutrient Roles in the Onset, Prevention, and Treatment of Chronic and Neurodegenerative Diseases: Mechanistic and Epidemiological InsightsView all 4 articles
Clinical Implications of Malnutrition in Huntington's Disease Progression: Evidence from a Chinese Cohort and Mendelian Randomization
Provisionally accepted
Jie-Qiang Xia
Yang-Fan Cheng
Si-Rui Zhang
Yuan-Zheng MaJia-Jia Fu
Tian-Mi Yang
Ling-Yu Zhang
Jean-Marc Burgunder
Hui-Fang Shang*- West China Hospital, Sichuan University, Chengdu, China
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Background: Huntington's disease (HD) is a neurodegenerative disorder associated with progressive motor, cognitive, and psychiatric dysfunction. Peripheral metabolic disturbances, including malnutrition, are commonly observed in HD. However, the prevalence, clinical correlations, and prognostic value of malnutrition in HD, especially among Chinese patients, remain inadequately explored. Methods: This cohort study recruited 113 genetically confirmed HD patients and 113 age/sex-matched healthy controls (HCs). Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI). Clinical evaluations included Unified Huntington's Disease Rating Scale (UHDRS), cognitive tests, and psychiatric assessments. Kaplan-Meier survival analysis and Cox regression models were used to evaluate the prognostic significance of malnutrition. Mendelian randomization (MR) analysis was employed to explore causal relationships between nutritional indicators and HD progression using genome-wide association study (GWAS) data. Results: During a mean follow-up of 5.74 years, 44 patients reached composite endpoints of death or loss of independent function (total functional capacity [TFC]≤2). HD patients showed higher malnutrition prevalence than HCs (CONUT: 34.51% vs. 13.27%; GNRI: 7.96% vs. 2.65%). Malnutrition correlated with functional decline, cognitive impairment, advanced disease stage, and lower composite Unified Huntington's Disease Rating Scale (cUHDRS) score, but not with survival outcomes. MR analysis suggests a causal relationship between lymphocyte count and delayed motor progression in HD patients. Conclusion: Malnutrition was highly prevalent in Chinese HD patients and was associated with functional and cognitive decline. Although malnutrition did not independently predict survival, MR analysis suggests that lymphocytes delay motor progression, implying that immunonutritional pathways may warrant further investigation as potential targets for future mechanistic and interventional research.
Keywords: CONUT, GNRI, Huntington's disease, Malnutrition, Nutritional Status, PNI
Received: 03 Oct 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Xia, Cheng, Zhang, Ma, Fu, Yang, Zhang, Burgunder and Shang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hui-Fang Shang
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