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EBL Evidence System

The EBL Evidence Pyramid

Every supplement and intervention on this site is assigned a tier. The tier reflects the quality of human evidence — not the enthusiasm of researchers, not the plausibility of the mechanism, not the quality of the marketing. Human outcomes first. Everything else below.

EBL Evidence Pyramid Five-tier evidence hierarchy: Tier 1 human outcome RCTs (Grade A), Tier 2 meta-analyses (Grade B), Tier 3 biomarker RCTs (Grade C), Tier 4 animal studies (Grade D), Tier 5 mechanistic speculation. THE EBL EVIDENCE PYRAMID Tier 1 Human outcome RCTs All-cause mortality · CVD events · fractures · hospitalisation Tier 2 Meta-analyses · Systematic reviews Pooled RCT effect estimates · Cochrane reviews Tier 3 Biomarker & surrogate endpoint RCTs HbA1c · LDL-C · bone density · VO₂max · cognitive scores Tier 4 Animal studies · In vitro Mouse lifespan · cell culture · rodent cognition Tier 5 Mechanistic · speculative · expert opinion Pathway plausibility · conference talks · case reports Grade A Grade B Grade C Grade D Higher tier = stronger human evidence. Grade reflects effect size and consistency within tier.
Tier 1 · Grade A — Human outcome RCTs

Randomized controlled trials in humans measuring real clinical outcomes — all-cause mortality, cardiovascular events, fracture incidence, hospitalisation. These are the studies that matter. A supplement earns Grade A only when multiple independent RCTs show consistent benefit at these endpoints. Examples on EBL: EPA/DHA Omega-3 (REDUCE-IT), Creatine (500+ RCTs), Magnesium (34-RCT meta-analysis on BP), Vitamin D3 (VITAL).

Tier 2 · Grade B — Meta-analyses and systematic reviews

Pooled analyses of multiple RCTs. Higher statistical power than any single trial, but effect sizes can be diluted by study heterogeneity or inflated by publication bias. A Cochrane review of high-quality RCTs sits near the top of Tier 2; a meta-analysis of three small poorly-designed trials sits near the bottom. We note the quality of the underlying studies.

Tier 3 · Grade C — Biomarker and surrogate endpoint RCTs

Human RCTs that measure biomarkers (HbA1c, LDL-C, bone density, VO₂max) rather than clinical outcomes. This is where most supplement research lives. The fundamental problem: biomarker improvement does not reliably predict clinical benefit. The CAST trial gave antiarrhythmic drugs that normalized heart rhythm — and increased mortality. A supplement that lowers LDL-C or raises NAD+ is promising. It is not proven.

Tier 4 · Grade D — Animal studies and in vitro

Mouse lifespan studies, rodent cognition, cell culture. Mechanistically interesting. Historically unreliable as predictors of human outcomes — approximately 90% of findings at this tier fail to replicate in human trials. We mention Tier 4 data when it's the best available and the mechanism is plausible, but we say clearly that it hasn't been tested in humans.

Tier 5 — Mechanistic, speculative, expert opinion

Pathway plausibility, conference presentations, case reports, theoretical extrapolation. Not evidence. We rarely cite Tier 5 as support for a recommendation. When we do, it's clearly labelled as speculative. The longevity field has a significant problem with Tier 5 claims presented with Tier 1 confidence — this pyramid exists precisely to counter that.

Full methodology → EBL vs Examine.com grades → Evidence-graded protocols → Check contraindications →