Sources & how to read the evidence

This guide was built from the primary literature — clinical guidelines, randomised trials, meta-analyses and drug labels — and graded by how strong the evidence actually is. Where the science is genuinely mixed or contested (statins in low-risk people, nattokinase, Cleerly's outcome data), it says so and gives both sides rather than picking one.

How it was built

The approach: Every load-bearing number comes from a named guideline, trial, meta-analysis or regulatory document, with the evidence dots (●●●●● = strong and replicated, down to ○○○○○ = essentially unproven) reflecting study design, size and replication. Figures are group averages; individuals vary widely. Doses and thresholds are typical adult figures from the literature, not instructions.
The key sources: Plaque biology & regression: the response-to-retention model and the IVUS regression/stabilisation trials (REVERSAL, ASTEROID, SATURN, GLAGOV, HUYGENS, PACMAN-AMI). Causality: Mendelian-randomisation studies, the CTT meta-analyses, and the EAS ApoB/LDL causal consensus. Tests & targets: the ApoB and Lp(a) consensus statements and the lipid-guideline target tables. Imaging: MESA (calcium percentiles and the power of zero), SCOT-HEART (CT angiography), and Cleerly's validation literature. Statins — both sides: the CTT collaboration for benefit, SAMSON and StatinWISE for the nocebo effect, and the BMJ overtreatment critiques. Non-statins: IMPROVE-IT (ezetimibe), CLEAR Outcomes (bempedoic acid), FOURIER/ODYSSEY/GLAGOV (PCSK9), and the ORION programme (inclisiran). Lp(a) & pipeline: the pelacarsen and olpasiran trials, obicetrapib, oral PCSK9 (enlicitide), and the VERVE gene-editing programmes. Lifestyle: PREDIMED, the Portfolio Diet, and SELECT (semaglutide). Supplements: the NCCIH natural-products reviews, REDUCE-IT vs. STRENGTH, HPS2-THRIVE (niacin), and the nattokinase trials (Ren 2017 vs. the placebo-controlled NAPS).

Educational reference — not medical advice

This guide summarises published research for general education. It is not a diagnosis, a prescription, or a substitute for care, and any doses are typical figures from the literature, not instructions. Cholesterol and cardiovascular risk are managed with a clinician using your own numbers and history. Get properly tested, and decide anything here — especially any medication — with a qualified professional. Never start, stop, or change a statin or any drug, and never self-source or self-prescribe, on the strength of a guide, a headline, or a podcast.

The Cholesterol Guide