Health benefits of a five-day at-home modified fasting program: a randomised controlled trial

Background Fasting has been shown to be one of the most cost-effective methods to improve cardiometabolic health. We studied a 5-day hypocaloric (~600 kcal/day) and ketogenic, modified fasting program (MFP) for at-home interventions. We hypothesised that this MFP induces metabolic changes comparable to 5 days of prolonged fasting (75-250kcal/day). Methods We tested the MFP in a two-arm randomised controlled trial where sixty-four healthy subjects were randomised to MFP or control group. Serum biochemistry analyses and questionnaires allowed for determining effects on cardiometabolic risk factors. Emotional well-being, possible side effects and physical activity were assessed with questionnaires. Biological pathways and metabolic processes were explored with nuclear magnetic resonance blood metabolomics and gut metagenomics analyses. Results MFP participants (n=32) experienced weight loss (-3.1 kg) persisting one month after the intervention. The MFP induced significant, but transient reductions, in systolic (-6.4 mmHg) and diastolic (-4.4 mmHg) blood pressure, glucose levels, HbA1c and coagulation factors. The MFP led to greater reductions in BMI (p=0.006), diastolic pressure (p = 0.009), cholesterol (p = 0.02), and LDL (p = 0.02) in individuals at risk of cardiometabolic diseases compared to healthy individuals. Total cholesterol, LDL-C and HDL-C levels continued decreasing during food reintroduction. The MFP also increased emotional and physical well-being. Blood metabolomics revealed a significant decrease in chronic inflammation markers. Shotgun metagenomics of the gut microbiome showed trends in the changes in relative abundance of the majority of bacterial species and their genomic repertoire of carbohydrate-active enzymes (CAZymes). This reflected a decrease in families metabolising dietary fibre substrates and an increase in families metabolising host-derived glycan substrates. Comparing MFP effects with a previous cohort's 5-day prolonged fasting showed similar metabolic changes. Conclusion This MFP is safe and effectively improves cardiometabolic health and emotional well-being in healthy individuals. It offers comparable metabolic benefits to those observed during 5-day prolonged fasting in a clinic. It is safe to be practised at home, widely accessible and compatible with individuals' everyday life.