Nattokinase, an enzyme derived from the Japanese fermented soybean food natto, does appear to lower cholesterol, though the effect depends heavily on the dose. Clinical studies show meaningful reductions in total cholesterol, LDL (“bad”) cholesterol, and triglycerides, but only at doses considerably higher than what most supplements on the market provide.
How Nattokinase Affects Cholesterol
Nattokinase works on cholesterol through a mechanism that overlaps with statin drugs. It inhibits the same liver enzyme that statins target, called HMG-CoA reductase, which is the rate-limiting step in your body’s cholesterol production. By binding to the active center of this enzyme, nattokinase slows the conversion process and reduces the amount of cholesterol your liver manufactures.
But cholesterol production is only part of the picture. Nattokinase also boosts the activity of lipoprotein lipase, an enzyme that breaks down triglycerides carried in the bloodstream. This helps clear triglyceride-rich particles from your blood faster. It also promotes the liver’s uptake of LDL particles, reducing the time they spend circulating (and potentially lodging in artery walls). On the beneficial side, nattokinase appears to stimulate the liver’s production of HDL (“good”) cholesterol, which ferries cholesterol back to the liver for disposal.
What the Clinical Evidence Shows
The largest clinical study on nattokinase and cholesterol enrolled 1,062 participants and followed them for 12 months. At a dose of 10,800 FU (fibrinolytic units) per day, nattokinase significantly improved lipid profiles and slowed the progression of atherosclerosis. However, the same study found that a dose of 3,600 FU per day was ineffective at lowering lipids or suppressing plaque buildup.
Shorter trials have shown results at somewhat lower doses. A 26-week study using 6,000 FU per day found reductions in total cholesterol, LDL cholesterol, and triglycerides, along with increased HDL. Another trial using 7,000 FU daily produced similar improvements. An 8-week trial using just 2,000 FU daily in 60 patients with high cholesterol did test for lipid changes, but the research overall points to a threshold effect: doses below roughly 6,000 FU per day may not move the needle in a clinically meaningful way.
Based on the accumulated evidence, researchers now estimate the effective dose range for lipid-lowering is between 6,000 and 12,000 FU daily. That’s important context because most nattokinase supplements sold in stores contain 2,000 FU per capsule, meaning you’d need three to six capsules per day to reach the range where cholesterol benefits have been reliably demonstrated.
Combining Nattokinase With Red Yeast Rice
One of the more promising findings involves pairing nattokinase with red yeast rice, which contains a natural compound that also inhibits cholesterol production. A randomized, double-blind, placebo-controlled trial in patients with stable coronary artery disease found that the combination outperformed either supplement alone. The nattokinase plus red yeast rice group saw the largest reductions: triglycerides dropped by 0.39 mmol/L, total cholesterol fell by 0.66 mmol/L, and HDL increased by 0.195 mmol/L. Diastolic blood pressure also dropped by about 7 mmHg. Both the combination and the nattokinase-only groups showed improved markers of heart muscle stress.
This combination makes biochemical sense because the two supplements attack cholesterol through partially overlapping but distinct pathways. Red yeast rice contains monacolin K, which is chemically identical to the active ingredient in lovastatin. Pairing it with nattokinase’s additional effects on triglyceride clearance and HDL production creates a broader lipid-lowering strategy than either one alone.
How Long Before You See Results
The shortest trial showing lipid improvements ran for 8 weeks, while the most robust evidence comes from studies lasting 26 weeks to 12 months. This is consistent with how cholesterol-lowering interventions generally work: your body needs time to shift its equilibrium of cholesterol production, clearance, and storage. If you’re taking nattokinase for cholesterol, plan on at least two to three months at an effective dose before blood work would reflect meaningful changes. The 12-month study showed continued benefit over time, suggesting this isn’t a supplement where you hit a ceiling quickly.
Safety and Drug Interactions
Nattokinase is primarily known as a blood-clot-dissolving enzyme, which is where most of its safety concerns originate. Short-term studies using up to 10,000 FU per day have not reported serious side effects, but long-term safety data at high doses remains limited.
The most significant risk involves combining nattokinase with blood-thinning medications or aspirin. In one documented case, a patient taking both aspirin and nattokinase experienced bleeding in the brain. Brain imaging revealed multiple small areas of prior bleeding, suggesting nattokinase may amplify bleeding risk in people who already have fragile blood vessels. In a separate case, a patient with a mechanical heart valve stopped taking warfarin and relied on nattokinase instead, only to develop a dangerous blood clot on the valve that required surgical replacement.
These cases highlight two practical rules. First, nattokinase should not be combined with aspirin or prescription blood thinners without medical oversight, because the additive blood-thinning effects can become dangerous. Second, nattokinase is not a substitute for prescribed anticoagulants in conditions where clot prevention is critical, such as mechanical heart valves or atrial fibrillation.
No Major Guidelines Endorse It Yet
Despite the growing body of clinical evidence, no major cardiology organization currently includes nattokinase in its formal guidelines for cholesterol management. The American Heart Association and similar bodies have not issued recommendations for or against its use. This doesn’t mean it’s ineffective, but it does mean the evidence hasn’t yet reached the volume and consistency that guideline committees require. Most of the positive trials come from a relatively small number of research groups, and the dose-response relationship is still being mapped out.
For people whose cholesterol is mildly elevated and who prefer to try a supplement before committing to prescription medication, nattokinase at 6,000 FU or above represents a reasonable option with plausible mechanisms and supportive (if still limited) clinical data. For people with significantly elevated cardiovascular risk, established medications remain the more evidence-backed choice.