Nattokinase is widely marketed as a cardiovascular supplement, and a lot of that marketing implies it improves your cholesterol panel. That claim deserves scrutiny, because when researchers pooled the randomized controlled trials and looked at lipids specifically, the results did not support it. Here is what the trial data shows, including the finding most supplement pages leave out.
Key Takeaways
- A systematic review and meta-analysis pooling six randomized controlled trials (546 participants) found no lipid-lowering benefit from nattokinase, and at relatively low total doses it was associated with slightly higher total cholesterol and LDL-C and slightly lower HDL-C than control.
- Triglycerides showed no significant association with nattokinase in the pooled analysis.
- The same meta-analysis reported a small blood pressure drop (3.45 mmHg systolic, 2.32 mmHg diastolic) from only a few small trials, which is a different endpoint from lipids; a 3-year trial in 265 healthy adults found no blood pressure effect [1][9].
- The trials that do show impressive lipid improvements used nattokinase combined with red yeast rice (Monascus), which contains monacolin K. Monacolin K is chemically identical to the prescription statin lovastatin, so attributing that lipid drop to the nattokinase component is not justified.
- No notable adverse events were reported across the pooled trials, so this is a question of effectiveness for a specific endpoint, not a safety concern.
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What the Pooled Randomized Trials Found
The strongest available answer comes from a systematic review and meta-analysis of randomized controlled trials examining nattokinase and cardiovascular risk factors, pooling six studies covering 546 participants, with overall methodological quality rated high.[1] On lipids, the direction of effect was not what supplement marketing would predict. At relatively low total nattokinase dosage, the pooled analysis found total cholesterol was higher than control (mean difference 5.27, 95% CI 3.74 to 6.81), HDL-C was lower (mean difference -2.76, 95% CI -3.88 to -1.64), and LDL-C was higher (mean difference 6.49, 95% CI 0.83 to 12.15). At relatively high total dosage, total cholesterol was still modestly higher than control (mean difference 3.18, 95% CI 2.29 to 4.06), while HDL-C and LDL-C showed no significant difference either way. Triglycerides showed no significant association at all.
Pooled trials show no lipid benefit at low dose; the big LDL drops came from a lovastatin product or an uncontrolled cohort
Low dose: no lipid-lowering effect
A meta-analysis (6 studies, 546 participants) found total cholesterol higher on nattokinase in two 8-week low-dose trials (MD = 5.27, 95% CI 3.74 to 6.81).
No significant association
Pooled trials found no significant association between nattokinase and triglyceride levels.
LDL fell, but with lovastatin
In 113 adults with dyslipidemia, a supplement of nattokinase 2500 FU plus lovastatin 7 mg from red yeast rice cut LDL 0.43 mmol/L more than placebo. Industry-funded.
LDL down 18.1%, no control group
In 1,062 adults taking 10,800 FU a day for 12 months, total cholesterol fell 15.9% and LDL 18.1% from baseline. The authors work for the tablet maker.
For cholesterol, nattokinase alone is not supported by the pooled randomized evidence.
Randomized trials pooled in a meta-analysis, one randomized combination-product trial, and one retrospective cohort. Source: Li et al., Reviews in Cardiovascular Medicine 2023; Liu et al., Nutrients 2023; Chen et al., Frontiers in Cardiovascular Medicine 2022.
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It is worth being precise about what those numbers mean and do not mean. These are small mean differences pooled across heterogeneous trials, and the authors did not conclude that nattokinase raises cholesterol as a clinical effect. The defensible reading is narrower and more useful: there is no pooled randomized evidence that nattokinase on its own improves a lipid panel, and the low-dose signal points, if anywhere, in the unfavorable direction. An earlier self-controlled trial using 4,000 FU per day for eight weeks similarly found no obvious lipid effects.[2]
Not every study agrees. A small 2017 randomized trial in patients with carotid atherosclerosis found nattokinase lowered total cholesterol, LDL-C and triglycerides, though less than simvastatin did. An uncontrolled retrospective cohort of 1,062 Chinese adults, with authors who work for the tablet maker, reported falls of 15.9% in total cholesterol and 18.1% in LDL cholesterol at 10,800 FU per day but no benefit at 3,600 FU per day; with no control group it cannot show that nattokinase caused the changes [12][13].
Why Some Trials Show Big Cholesterol Drops
Search for nattokinase and cholesterol and you will find genuinely impressive trial results. The catch is in the intervention. A four-month randomized, double-blind, placebo-controlled trial in 113 subjects used a nattokinase plus Monascus (red yeast rice) supplement and reported significant reductions in total cholesterol (-0.52 mmol/L), LDL-C (-0.43 mmol/L), non-HDL-C (-0.52 mmol/L), and the LDL-C to HDL-C ratio (-0.29), with no significant change in triglycerides, HDL-C, or carotid intima-media thickness.[3] A separate 90-day randomized, double-blind trial in 178 patients with stable coronary artery disease compared nattokinase plus red yeast rice, nattokinase alone, red yeast rice alone, and placebo, and the combination arm showed the largest reductions in triglycerides, total cholesterol, and diastolic blood pressure, plus the largest HDL-C increase.[4]
Research note: The authors of a 2023 trial of a nattokinase and red yeast rice supplement note it was single-centre and short, at 120 days, with a small sample, so its findings are preliminary [3].
Red yeast rice is not an inert partner ingredient. It contains monacolin K, which is structurally and pharmacologically the same molecule as lovastatin, a prescription statin. Red yeast rice on its own significantly lowers total cholesterol, triglycerides, and LDL-C versus placebo across its own meta-analytic evidence base.[5] So when a combination product lowers LDL, the parsimonious explanation is the statin-equivalent compound in it.[6] That four-arm coronary artery disease trial is the most informative design here precisely because it separated the components, and it is the kind of study design more of this field needs.
The Endpoint Nattokinase Does Have Support For
None of this makes nattokinase useless. The same meta-analysis that found no lipid benefit concluded that nattokinase may work as an adjunctive therapy for hypertension [1], and blood pressure is where most of the human data sit, though they are small and mixed: the pooled drop came from a few small trials, a 2016 trial found no systolic difference from placebo, and a 3-year trial in 265 healthy adults found no blood pressure effect [1][10][9]. Its primary documented mechanism is fibrinolytic, meaning it acts on fibrin and clot breakdown, not on cholesterol synthesis or transport. There is no obvious mechanistic reason a fibrinolytic protease would lower LDL, and the pooled data is consistent with that. Judging a supplement on the endpoint its mechanism actually predicts is more useful than judging it on the endpoint that sells best.
What This Means If You Are Buying for Cholesterol
If lowering LDL is your specific goal, nattokinase alone is not supported by the pooled randomized evidence, and choosing it over an intervention with real lipid data is a poor trade. If you are considering a nattokinase plus red yeast rice combination product, understand that you are effectively taking a low-dose statin analogue with unregulated dose consistency between batches, which carries the same muscle, liver, and drug-interaction considerations that statins do, without the prescribing oversight.[7] That is a conversation to have with a physician or pharmacist, not a decision to make from a product page. Monacolin K content in red yeast rice products has historically varied enormously between brands, which is a real problem when the active compound is a drug.[8]
Frequently Asked Questions
Does nattokinase lower LDL cholesterol?
Not based on pooled randomized controlled trial data. A meta-analysis of six RCTs covering 546 participants found no LDL-lowering benefit, and at lower total doses LDL-C was slightly higher than control rather than lower. Trials showing large LDL reductions used nattokinase combined with red yeast rice.
Does nattokinase lower triglycerides?
The pooled analysis found no significant association between nattokinase and triglycerides. The triglyceride reductions reported in some trials came from nattokinase plus red yeast rice combination products rather than nattokinase alone.
Should I take a nattokinase and red yeast rice combination for cholesterol?
Those combinations do have supporting trial data, but the lipid effect is most plausibly driven by monacolin K in the red yeast rice, which is the same molecule as the statin lovastatin. Treat it as a statin-containing product and discuss it with a physician or pharmacist, particularly if you already take a statin, have liver concerns, or take medications that interact with statins.
So what is nattokinase actually good for?
The human evidence points to a small blood pressure drop in a few small, mixed trials and to changes in clotting markers [1][10][9][11]. Those are different endpoints from cholesterol, and they are the ones its mechanism actually predicts.
References
- Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Rev Cardiovasc Med (2023). PMID 39076715
- Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res (2009). PMID 19358933
- The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients (2023). PMID 37836525
- Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease. Front Nutr (2024). PMID 38812930
- Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review. Nutrients (2023). PMID 37242171
- Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia. Asia Pac J Clin Nutr (2009). PMID 19786378
- Rhabdomyolysis or Severe Acute Hepatitis Associated with the Use of Red Yeast Rice Extracts: an Update from the Adverse Event Reporting Systems. Curr Atheroscler Rep (2023). PMID 37831308
- Approaches to Authenticating Products Containing Red Yeast Rice Extract (Monacolin K). Molecules (2026). PMID 41752500
- Hodis HN et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clinical hemorheology and microcirculation (2021). PMID 33843667
- Jensen GS et al. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. Integrated blood pressure control (2016). PMID 27785095
- Yuko Kurosawa et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Scientific Reports (2015). PMID 26109079
- Ren NN et al. [A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia]. Zhonghua yi xue za zhi (2017). PMID 28763875
- Chen H et al. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants. Frontiers in cardiovascular medicine (2022). PMID 36072877
These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are managing high cholesterol, work with your physician rather than substituting a supplement for evidence-based lipid therapy.
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.
