Fasting has been shown to be beneficial in many diseases, including rheumatoid arthritis (RA). Among other effects, fasting stimulates ketogenic metabolism, induces autophagy, and harbors immunomodulatory functions. Recent studies have highlighted the role of the intestinal microbiota in the still unclear etiology of RA1. This could be a potential target for additional dietary therapy in RA.To investigate the effect of therapeutic fasting followed by a plant-based diet compared to standard dietary recommendations in patients with RA.In this pilot study2 patients with RA were randomized to either a 7-day fast (≤250kcal/d) followed by 11 weeks of plant-based diet or to conventional nutritional counselling according to the recommendations of the German Society for Nutrition (Deutsche Gesellschaft für Ernährung, DGE) for 12 weeks. Disease activity and treatment response in RA (including Health Assessment Questionnaire, HAQ; EULAR Response Criteria, ACR Response Criteria) were measured at baseline (T0), day 7 (T1), 6 weeks (T2) and 12 weeks (T3).A total of 50 from 53 enrolled participants were included into the per-protocol analysis. The mean age was 51.98 ± 9.4 years with symptoms duration of 6.8 ± 8.1 years; 92% were females and 78% were ACPA and/or RF IgM positive. At baseline, participants presented HAQ 0.8 ± 0.5, DAS28CRP 4.0 ± 1.3, CRP 3.1 ± 3.8 mg/L, and a BMI of 25.0 ± 3.7 kg/m2.The primary endpoint did not become significant. However, post-hoc analyses revealed clinically relevant improvements in the HAQ after 12 weeks in both the fasting and the DGE group (Δ-0.29; 95% CI, -0.45 to -0.13; p = 0.001; and Δ-0.23; 95% CI, -0.45 to -0.22; p = 0.032; respectively). Furthermore, the effect already set on by day 7 in the fasting group compared to week 6 in the DGE group (Figure 1). This effect was independent of antibody status, delivery mode of the intervention or previous dietary forms. CV risk factors including weight and total cholesterol levels improved stronger in the fasting group compared to the DGE group (Δ-3.9 kg vs. -0.7kg; 95% CI, 1.4 to 5.0; p = 0.001 and Δ-18.60 mg/dl vs Δ6.44 mg/dl; 95% CI, 7.3 to 42.8, p=0.007).Figure 1.EULAR and ACR Response until week 12 and HAQ up to 6 months. ACR, American College of Rheumatology; CI, confidence interval; HAQ, health assessment questionnaire.Fasting followed by a plant-based diet positively impacts disease activity and CV risk factors in RA, comparable to and no lesser than those of an anti-inflammatory diet according to the DGE. These results may open new perspectives by dietary interventions in an integrative therapeutic approach. Further confirmatory clinical studies with larger patient numbers are needed to confirm these exploratory findings.[1]Ruff WE, Greiling TM, Kriegel MA. Host–microbiota interactions in immune-mediated diseases. Nature Reviews Microbiology 2020;18(9):521-38. doi: 10.1038/s41579-020-0367-2[2]Hartmann AM, Dell’Oro M, Kessler CS, et al. Efficacy of therapeutic fasting and plant-based diet in patients with rheumatoid arthritis (NutriFast): study protocol for a randomised controlled clinical trial. BMJ Open 2021;11(8):e047758. doi: 10.1136/bmjopen-2020-047758 [published Online First: 2021/08/13]Anika M. Hartmann: None declared, Farid I. Kandil: None declared, Nico Steckhan: None declared, Thomas Häupl: None declared, Christan S. Kessler: None declared, Andreas Michalsen Paid instructor for: co-founder and instructor in the Academy of Integrative Fasting, Daniela A. Koppold-Liebscher Paid instructor for: co-founder and instructor in the Academy of Integrative Fasting.