Fasting as a Multisystem Health Modulator: A Narrative Review of Metabolic, Cardiovascular, Immune, Neurocognitive,...

Fasting, practiced in clinical, cultural, and faith-based contexts, has emerged as a non-pharmacological strategy capable of modulating multiple physiological systems. Contemporary evidence suggests that diverse fasting patterns (intermittent and time-restricted fasting, Ramadan fasting, alternate-day and periodic fasting, dry fasting, and fasting-mimicking diets) converge on shared metabolic-circadian-immune pathways and can be conceptualized within an integrated resilience framework.

This narrative review synthesizes current experimental and human data on fasting as a multisystem health modulator, linking metabolic, cardiovascular, immune, gut-liver-microbiome, neurocognitive, endocrine, and psychospiritual effects to common regulatory axes, particularly the Metabolic-Circadian-Immune (MCI) and Energy-Information-Resilience (EIR) models.

Across fasting modalities, activation of energy-sensing pathways (AMPK-SIRT1-mTOR), metabolic switching to lipolysis and ketogenesis, enhanced autophagy/mitophagy, and improved insulin sensitivity have been shown to support the management of obesity, type 2 diabetes, dyslipidemia, hypertension, and non-alcoholic fatty liver disease. Fasting also modulates immune and inflammatory tone, reshapes the gut microbiome, and may benefit autoimmune conditions such as rheumatoid arthritis and multiple sclerosis. Cardiovascular, endocrine, and neurocognitive domains show improvements in blood pressure, lipid profiles, neurotrophic signaling, mood, and cognitive resilience, while structured religious fasting (e.g., Ramadan) can additionally reinforce psychological discipline and spiritual well-being. At the same time, responses are heterogeneous, and prolonged or intensive regimens may pose risks in vulnerable populations.

Fasting can be viewed as a low-cost, multidimensional "biopsychospiritual" health intervention acting through interconnected metabolic, circadian, immune, and neurobehavioral pathways. By integrating traditional and religious fasting practices with contemporary mechanistic and clinical data, this review highlights shared energy- and immune-regulatory axes and underscores the potential of fasting within integrative, preventive, and personalized care. Standardized protocols, long-term outcomes, and multimodal trials combining immunophenotyping, microbiome/metabolomic profiling, and neuroimaging remain priorities for future research.