Evaluation of a Synthetic Spermidine–Spermine Supplement with Arginine and BB12: Safety Outcomes and Beclin-1 Modulation in a Randomized Placebo-Controlled Pilot Trial in Older Adults

Background : The aging population is expanding with the proportion of adults over 60 years projected to double by 2050. Healthspan extension, the maintenance of functional resilience across older adulthood is critical. Cellular aging drives a diminished healthspan. Polyamines are crucial for cellular health, yet declining intracellular polyamine concentrations correlate with increasing age. Nutraceutical interventions that modulate polyamine pathways are of growing interest; however, many lack evaluation of safety and exploration of biological mechanisms. Objective: We conducted a placebo-controlled randomized pilot study to assess the safety and mechanistic effects of Cellitas®, a proprietary oral supplement combining synthetic spermidine and spermine, arginine and the probiotic Bifidobacterium animalis subsp. Lactis (Trial ID NCT06445569, 31/5/2024-retrospective registration). Forty-two pre-diabetic adults aged over 50 years were assigned to a placebo or Cellitas® arm and followed for 24 weeks. Safety endpoints included adverse events and changes to biochemical, haematological, glycaemic and inflammatory cytokine profiles. Exploratory endpoints included levels of Beclin-1 in serum. Beclin-1 initiates autophagy, coordinating autophagosome formation and has important functions in endocytic trafficking, apoptosis regulation, membrane dynamics and cellular stress response Results and Conclusion : Cellitas® was safe with no serious adverse events or adverse shifts in clinical biomarkers. Serum Beclin-1 increased over 24 weeks, with no change observed with the placebo, consistent with a possible biological effect on Beclin-1 pathways. This is the first preliminary evidence on the safety of a synthetic polyamine–arginine–probiotic formulation, demonstrating a favourable safety profile. Further trials are important to fully elucidate its effects on autophagic signalling.