The A1C Challenge: Pre-Registered Statistical Analysis Plan and Study Methodology (RWE cohort)

This is an open-access, open-source, crowd-sourced RWE cohort study to find out if fructosamine leads A1C in a 28-day period, which would point to an upstream nutritional component. The app for this RWE cohort study is online at The A1C Challenge. The study opened for participant enrollment Friday 6/26/2026. Please check it out. Share it so we can find out what this methodology produces. Source code and technical documentation for a Spring Boot/PostgreSQL backend and React/Next.js frontend is on GitHub (backend and frontend). 1 Introduction Endocannabinoid nutritional deficiency is a diagnosable deficiency disease with a characteristic early biomarker signature in fast-turnover proteins, preceding and predicting the slow-marker manifestations currently recognized as metabolic, inflammatory, and neurological disease. The missing input is hemp seed plus raw Cannabis as a dietary staple. Restoring it corrects the upstream deficiency rather than suppressing its downstream symptoms. 1.1 Study type Prospective observational cohort study with crowd-sourced enrollment. This is not a randomized controlled trial (RCT) and makes no claim to be one. The study produces Real-World Evidence (RWE) — a recognized and FDA-acknowledged evidence tier in nutrition science — from a large self-selected population following a defined dietary protocol. Findings are reported as associative, not causative, unless effect sizes and consistency across sub-groups warrant stronger inference language in discussion. 1.2 Central question Do adults with elevated A1C (≥5.7%) who consume hemp seed (30–60g/day, participant-selected) plus raw Cannabis flower daily for 28 days experience a measurable reduction in A1C and fasting glucose compared to their baseline, and compared to published trajectories for equivalent populations receiving standard diabetes care? And specifically: does fructosamine fall disproportionately relative to A1C within the 28-day window — the temporal signature predicted by a hypothesis of rapid upstream metabolic correction rather than slow dietary glucose suppression? 1.3 Theoretical basis and mechanistic prediction chain The intervention is grounded in Endocannabinoid Nutritional Biology: the hypothesis that the Endocannabinoid System (ECS) has specific dietary requirements, and that hemp seed plus raw Cannabis provides the fatty acid precursors (LA, ALA, GLA), acidic cannabinoid vitamers (CBDA, THCA, CBGA), and receptor-adjacent ligands necessary to restore ECS tone. Clinical Endocannabinoid Deficiency (CECD), as defined by Russo (2004, 2016), is proposed as the upstream mechanism underlying metabolic dysregulation in a substantial proportion of the target population. The study tests the following linked sequence of predictions: Mechanistic prediction chain 1. Daily hemp seed plus raw Cannabis provides the nutritional inputs the ECS requires. 2. ECS signaling improves as nutritional sufficiency is restored. 3. Systemic inflammation falls as ECS tone is re-established. 4. Insulin sensitivity improves as inflammatory interference with receptor signaling is reduced. 5. Blood glucose falls as insulin sensitivity improves. 6. Fructosamine falls within the 28-day window, reflecting the improved glucose environment in fast-turnover proteins. 7. A1C begins to fall, with the full effect visible beyond the 28-day window as the 90-day average catches up. Steps 1–3 are not directly measurable in this study (ECS signaling and CRP require lab draws). Steps 4–7 are measurable and pre-specified. The critical and falsifiable prediction is the temporal relationship between steps 6 and 7: fructosamine should fall disproportionately relative to what the A1C delta would predict. This temporal divergence is the mechanistic fingerprint that distinguishes upstream nutritional correction from pharmacological glucose suppression, and it is tested as a pre-specified secondary hypothesis in Section 7.6. 1.4 Pre-registration commitment This analysis plan will be registered on the Open Science Framework (OSF) prior to enrollment opening. Any analyses not specified in this document conducted after data collection begins will be clearly labeled exploratory in all publications and presentations. This pre-registration is not a guarantee of a specific outcome — it is a commitment to transparency about what was planned versus what was discovered.OSF pre-registration is here: https://osf.io/r4ufg/overviewDOI: 10.17605/OSF.IO/R4UFG