@article {Dorstjnnp-2021-328331, author = {Johannes Dorst and Judith Doenz and Katharina Kandler and Jens Dreyhaupt and Hayrettin Tumani and Simon Witzel and Joachim Schuster and Albert C Ludolph}, title = {Fat-rich versus carbohydrate-rich nutrition in ALS: a randomised controlled study}, elocation-id = {jnnp-2021-328331}, year = {2022}, doi = {10.1136/jnnp-2021-328331}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective There is growing evidence that the course of amyotrophic lateral sclerosis (ALS) may be influenced beneficially by applying high-caloric food supplements (HCSs). However, it is unknown which composition of nutrients offers optimal tolerability and weight gain.Methods We conducted a randomised controlled study (Safety and Tolerability of Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS); TOLCAL-ALS study) in 64 patients with possible, probable or definite ALS according to El Escorial criteria. Patients were randomised into four groups: a high-caloric fatty supplement (HCFS; 405 kcal/day, 100\% fat), an ultra-high-caloric fatty supplement (UHCFS; 810 kcal/day, 100\% fat), an ultra-high-caloric, carbohydrate-rich supplement (UHCCS; 900 kcal/day, 49\% carbohydrates) and an open control (OC) group without any supplement. The primary endpoint was tolerability. Patients were followed up over 4 weeks.Results Gastrointestinal side effects were most frequent in the UHCFS group (75.0\%), while loss of appetite was most frequent in the UHCCS group (35.3\%). During intervention, patients gained +0.9 kg/month of body weight (IQR -0.9 to 1.5; p=0.03) in the HCFS group and +0.9 kg/month (IQR -0.8 to 2.0; p=0.05) in the UHCFS group. A non-significant trend for weight gain (+0.6 kg/month (IQR -0.3 to 1.9; p=0.08)) was observed in the UHCCS group. Patients in OC group continued to lose body weight (-0.5 kg/month, IQR -1.4 to 1.3; p=0.42).Interpretation The findings suggest that HCSs frequently cause mild to moderate tolerability issues in patients with ALS, most notably gastrointestinal symptoms in high-fat supplements, and loss of appetite in high-carbohydrate supplements. All three HCSs tested are suited to increase body weight.Data are available upon reasonable request. Individual participant data that underlie the results reported in this article, after de-identification (text, tables and figures), as well as the study protocol will be available. Data will be available beginning 3 months and ending 5 years following article publication. Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims in the approved proposal. Proposals should be directed to johannes.dorst@uni-ulm.de; to gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at https://www.uniklinik-ulm.de/neurologie.html.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/early/2022/01/11/jnnp-2021-328331}, eprint = {https://jnnp.bmj.com/content/early/2022/01/11/jnnp-2021-328331.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }