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However, the dynamics of low-dose rapamycin bioavailability, and any differences in bioavailability for different formulations (e.g., compounded or commercial), remain poorly understood. We thus explored rapamycin bioavailability in two real-world cohorts to begin providing a foundational understanding of differences in effects between formulations over time. The small trial study cohort was utilized to explore the blood rapamycin levels of commercial (<jats:italic>n<\/jats:italic>\u2009=\u200944, dosages 2, 3, 6, or 8\u00a0mg) or compounded (<jats:italic>n<\/jats:italic>\u2009=\u200923, dosages 5, 10, or 15\u00a0mg) rapamycin 24\u00a0h after dose self-administration. Results suggested dose-to-blood level relationships were linear for both formulations, though compounded had a lower bioavailability per milligram of rapamycin (estimated to be 31.03% of the same dose of commercial). While substantial inter-individual heterogeneity in blood rapamycin levels was observed for both formulations, repeat tests for individuals over time demonstrated relative consistency. Extending exploration to 316 real-world longevity rapamycin users from the AgelessRx Observational Research Database produced similar findings, and additionally suggested that blood rapamycin levels peak after 2\u00a0days with gradual decline thereafter. Taken together, our findings suggest that individualized dosing and routine monitoring of blood rapamycin levels should be utilized to ensure optimal dosing and efficacy for healthy longevity.<\/jats:p>","DOI":"10.1007\/s11357-025-01532-w","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T03:14:54Z","timestamp":1738034094000},"page":"5681-5694","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals"],"prefix":"10.1007","volume":"47","author":[{"given":"Girish","family":"Harinath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Nyquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Moel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maartje","family":"Wouters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Hagemeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Verkennes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Tacubao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayem","family":"Nasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krister","family":"Kauppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-3333","authenticated-orcid":false,"given":"Stefanie L.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anar","family":"Isman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajad","family":"Zalzala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"1532_CR1","unstructured":"World Health Organization. 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Informed consent and consent to use de-identified information for research and research publication purposes were obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participants and authors consented to publish the data contained in this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"GH, VL, AN, MM, BV, CT, SN, SLM, AI, and SZ are employees and shareholders of AgelessRx. MW and JH have received financial compensation from AgelessRx for their contributions. KK is an employee and shareholder of Venture Plant AB and Rapamycin Longevity Lab, which has received a donation from AgelessRx for research coordination in partnership with Ora Biomedical.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}