Supplements & peptides

Red yeast rice works because it is low-dose lovastatin (~15–25% LDL) — but with an unregulated, wildly variable dose and possible citrinin contamination, so a prescription statin is the safer version of the same thing. Bergamot (~8–20%) and berberine (~15–20%, and a mild natural PCSK9 nudge; GI upset; avoid in pregnancy) have decent surrogate evidence. Plant sterols (7–12%) and viscous fibre/psyllium (5–10%) are the safest, food-based options; pantethine ~10–15%. All lower a number; none has a hard-outcome trial. Evidence ●●●○○ (surrogate only)

Omega-3 does not lower LDL (high doses can nudge it up); it lowers triglycerides ~20–30%. Only prescription EPA (icosapent ethyl, 4 g) has outcome data — REDUCE-IT cut events ~25%, though that's caveated by the mineral-oil-placebo controversy. Ordinary OTC fish oil is largely null for events, and 4 g/day raises atrial-fibrillation risk. Use it for high triglycerides, not to move ApoB. Evidence ●●●●○ (TG lowering) / ●●○○○ (OTC outcomes)

Nattokinase is a potent fibrinolytic enzyme: unlike statins (which cut how much cholesterol the liver makes), it breaks down fibrin — the sticky protein scaffold that holds soft plaque and clots together — which may let the body clear buildup over time. It's genuinely active in humans. The single most useful thing to know is that dose decides everything: the ~2,000 FU in most shop-shelf supplements does nothing for cholesterol or plaque, and even 3,600 FU/day showed no effect — the benefits only appeared at ~6,000–10,800 FU/day, so most people take far too little to matter.

The largest is a 2022 trial of 1,062 people with mild atherosclerosis and high cholesterol. Over 12 months, the high-dose arm (10,800 FU/day) saw a ~36.6% average reduction in carotid plaque, plus lower LDL and triglycerides and higher HDL — while the low-dose arm (3,600 FU) changed nothing (Frontiers in Cardiovascular Medicine, 2022). An earlier head-to-head (Ren 2017, ~76 patients, 26 weeks) reported nattokinase shrank plaque more than simvastatin (~37% vs ~12%) and raised HDL, though the statin lowered LDL better.

Genuinely intriguing, and the dose-response is a point in its favour. But temper it: these standout results come largely from a single research orbit, aren't independently replicated, and the strongest-looking designs lack a true placebo (Ren compared against a statin, not placebo) — while a separate placebo-controlled 3-year trial (NAPS) found no effect on plaque progression. So it's promising and worth watching, not the settled, replicated evidence a statin has. Evidence ●●○○○ — dose-dependent and intriguing, but unreplicated

At the therapeutic doses that actually move plaque (6,000–10,000+ FU), nattokinase acts as a real systemic blood thinner, with documented bleeding events (including brain bleeds and a fatal case). Talk to your doctor before starting — especially if you take aspirin or an anticoagulant, or have any surgery coming up — and never substitute it for prescribed anticoagulation.

Niacin moves every lipid number the 'right' way, yet AIM-HIGH and HPS2-THRIVE showed no benefit and net harm on a statin background — the textbook lesson that a better panel isn't a better outcome. CoQ10 doesn't lower cholesterol; its evidence for easing statin muscle aches is mixed but it's safe and worth trying before abandoning a statin. Garlic, green tea, and soy give tiny, inconsistent LDL effects. Vitamin K2 has a plausible anti-calcification hypothesis and one supportive imaging trial but no outcome data (and it antagonises warfarin). Evidence ●●○○○ or weaker

There is no peptide with credible human evidence for lowering cholesterol or reversing plaque. ApoA-I / HDL-mimetic peptides — the most-studied class — have failed in human trials; BPC-157's cardiovascular claims are extrapolated from rodents; and injectable 'cardiac peptides' sold online are unregulated and potentially unsafe (sterility, dosing, contamination). It's an active research frontier with zero validated products today. Be candid with yourself: here, the marketing is far ahead of the science. Evidence ○○○○○ in humans