Electroceuticals for Metabolic Syndrome: Historical Milestones, Neuronal Pathways, Challenges, and Technological Advances

Bioelectric signaling plays an essential role in regulating cellular, tissue, and organ functions. Electroceuticals (ECs) are device-mediated interventions that modulate biological activity through controlled electrical stimulation or related neuromodulatory approaches. They have attracted interest as potential therapeutic strategies for complex disorders, including metabolic syndrome (MetS), which involves interconnected metabolic abnormalities and neurophysiological dysregulation, involving pathways associated with autonomic control, inflammation, and brain-derived neurotrophic factor (BDNF). This narrative review examines the historical development, potential mechanisms, therapeutic applications, technological advances, limitations of ECs in the context of MetS, and identifies priorities for future research. The relevant literature was identified through searches of PubMed, Embase, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov using related keywords and phrases. The available evidence suggests that EC modalities may influence neuro-metabolic and autonomic pathways relevant to glucose regulation, energy balance, inflammation, and other components of MetS. However, the strength of the evidence varies across interventions and outcomes. Interpretation of clinical findings is complicated by heterogeneous stimulation protocols and the frequent co-administration of dietary interventions, exercise, weight-management strategies, or interventions associated with substantial weight loss. These factors limit the ability to isolate the independent effects of neuromodulation. Further challenges include the absence of standardized stimulation parameters, uncertainty regarding optimal treatment protocols, potential adverse effects, and limited long-term clinical evidence. Accordingly, ECs should currently be considered investigational approaches rather than established treatments for MetS. Well-designed long-term clinical trials are needed to determine their efficacy, safety, durability, and optimal therapeutic parameters.