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

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 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 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Adults Robert Lustig, William Watkins, Stefano Natella, Pedro Velasquez-Mieyer, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9252335/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract 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. Spermidine Spermine Arginine Probiotic Autophagy Beclin-1 Full Text Additional Declarations Competing interest reported. L.J. is currently a Board member of Kalin Health LLC. S.N. is a co-founder of Kalin Health LLC. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9252335","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617208945,"identity":"98c04d7b-b8f5-4c27-96c9-974ea010c758","order_by":0,"name":"Robert Lustig","email":"","orcid":"","institution":"University of California, San Francisco","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Lustig","suffix":""},{"id":617208946,"identity":"b3454cce-6efb-464e-9d45-e26a8a3468b0","order_by":1,"name":"William Watkins","email":"","orcid":"","institution":"Cardiff University","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Watkins","suffix":""},{"id":617208947,"identity":"fc1baf89-6c88-46bc-9c34-0021e3ebeaba","order_by":2,"name":"Stefano Natella","email":"","orcid":"","institution":"Kalin Health","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Natella","suffix":""},{"id":617208948,"identity":"fb2b30f9-daec-4eb5-8a8e-79140c21f520","order_by":3,"name":"Pedro Velasquez-Mieyer","email":"","orcid":"","institution":"Lifedoc Health and Lifedoc Research","correspondingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"","lastName":"Velasquez-Mieyer","suffix":""},{"id":617208951,"identity":"ff90ad93-9779-41c9-a315-e0de3cf635d3","order_by":4,"name":"Lucy Jones","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIie2RsWrDMBCGTwikRW3odkIvkSJw0imvEjB48lYwnlx1cRZ3bx6jb5DSoYvx3I4mL+BSKBg69JSslfGYQd8ghLiP+38EEIlcINLRwRzyzbu/CVycXgC2QYWdlbWE9nBSdHOYp5QL+PBDAmYou6fXfnRo2P7Yf5fFGhXwfmB1FlaaLrVXDi03mdVth6QIi6zOw8pznhiqnwqTg36ssdoAJMDqckpZjRTsodEtH0mhLfJnUrmhLUDBOM0KfVaU3xIOZlRrjVeWKkvunO/C1T1uu3D9a9ncfo2/FV/Kt+OnKypUcvcyDEUaVP6Bw9SvRCKRSGQOf4HIR8CTWhvxAAAAAElFTkSuQmCC","orcid":"","institution":"Cardiff University","correspondingAuthor":true,"prefix":"","firstName":"Lucy","middleName":"","lastName":"Jones","suffix":""}],"badges":[],"createdAt":"2026-03-28 11:38:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9252335/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9252335/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106414968,"identity":"1456bfdc-e027-422d-8717-aba9964e5779","added_by":"auto","created_at":"2026-04-08 10:31:21","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1764890,"visible":true,"origin":"","legend":"","description":"","filename":"EVALUA1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9252335/v1_covered_60adc9fc-fdbf-4eb9-b566-375016316214.pdf"}],"financialInterests":"Competing interest reported. 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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.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eObjective:\u003c/em\u003e 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 \u003cem\u003eBifidobacterium animalis subsp. Lactis\u003c/em\u003e (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. 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