Nattokinase and Artery Plaque: What That 1,062-Person Study Actually Tested

Natto is a Japanese breakfast food made from fermented soybeans. It is stringy, pungent, and divisive even among people who grew up eating it. The enzyme that fermentation produces, nattokinase, has spent the last decade migrating off the breakfast table and into supplement capsules sold for heart health. A study claiming it shrinks arterial plaque in over a thousand people is circulating again, and the claim deserves a closer read than the headline gives it.

Image by wezone2600 via Pixabay

What the research found

The study comes from Chen and colleagues, published in Frontiers in Cardiovascular Medicine in 2022 [1]. Researchers followed 1,062 participants taking nattokinase for twelve months and measured two things by ultrasound of the neck arteries: intima-media thickness (how thick the inner layers of the artery wall have become, a standard early marker of hardening) and the size of visible plaque. At a dose of 10,800 fibrinolytic units per day, both decreased, and cholesterol numbers improved alongside them. At 3,600 units per day, nothing much happened at all.

Two features of the design change how much weight those numbers can carry. The study was retrospective, which means the researchers looked backward at people already taking the supplement rather than randomly assigning anyone to take it. Several of the authors are also employed by Sungen Bioscience, a company that manufactures nattokinase. Neither fact makes the findings wrong. Both mean the study cannot separate the effect of the enzyme from the possibility that people who chose a high dose and stayed on it for a year were already healthier in ways nobody measured.

The bigger picture

The most rigorous test of nattokinase to date was run at the University of Southern California and published in 2021 [2]. Hodis and colleagues randomized 265 adults, median age 65, to either nattokinase or a matching placebo, kept everyone blinded, and repeated carotid ultrasound every six months for a median of three years. The result was null. No difference in artery wall thickness, none in arterial stiffness, and no effect on blood pressure or any laboratory value they tracked.

The dose is the pivot point between these two studies. The USC trial used 2,000 units per day. The Chen study reported that even 3,600 units did nothing and only saw movement at 10,800. So the best-designed trial available tested a dose that the positive study would have predicted to fail. That doesn't settle the question in either direction. It leaves an obvious gap that nobody has yet run the right trial to fill.

A 2023 meta-analysis pooling six randomized trials and 546 participants landed in between [3]. Nattokinase produced a modest blood pressure reduction, roughly three points systolic and two diastolic. On cholesterol, the pooled low-dose results moved the wrong way. The authors concluded it holds up as an add-on for blood pressure while the lipid-lowering claim stays unproven at the doses that were studied. One earlier comparison against simvastatin found a larger drop in plaque size with nattokinase than with the statin, though the statin lowered cholesterol more [4]. That trial enrolled 82 patients and shares authors with the 2022 study, so it isn't independent confirmation.

The naturopathic lens

Nattokinase is a fibrinolytic enzyme. Its job is breaking down fibrin, the protein mesh that holds a clot together. That is the whole mechanism, and it is also the reason this is not a casual supplement. Anyone taking warfarin, apixaban, clopidogrel, aspirin, or heading into surgery has an interaction question to raise with their prescriber before adding it. Whole natto carries a second wrinkle, since fermented soy is rich in vitamin K2, which directly opposes how warfarin works. Isolated nattokinase products often have the K2 stripped out, though the label doesn't always say so.

Stepping back from the capsule: plaque is not a stand-alone problem to be dissolved. It is the visible end product of years of endothelial irritation, insulin resistance, oxidative stress, poor sleep, and inflammation that had somewhere to come from. Nothing in the Chen study is inconsistent with that, given that the effect was strongest in smokers, drinkers, and people with higher BMI, and that regular exercise improved outcomes further. Those are the terrain factors doing work. I find patients get further asking what is driving the inflammation than asking which enzyme to add on top of it.

How to apply this now

Ask what kind of study produced a headline before you act on it. "1,062 participants" sounds decisive; "retrospective, industry-affiliated, and unblinded" is the part that determines what it can prove. If nattokinase interests you, bring it to whoever manages your medications first, especially if anticoagulants or antiplatelets are in the picture. And keep the boring interventions in view. Blood pressure, sleep, movement, fiber, and glycemic control have far better evidence behind them than any single enzyme currently does.

References

1. Chen H, Chen J, Zhang F, et al. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: a clinical study with 1,062 participants. Front Cardiovasc Med. 2022;9:964977. PMID 36072877. DOI 10.3389/fcvm.2022.964977. Original digest link: https://pmc.ncbi.nlm.nih.gov/articles/PMC9441630/

2. Hodis HN, Mack WJ, Meiselman HJ, et al. Nattokinase atherothrombotic prevention study: a randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339–353. PMID 33843667. DOI 10.3233/CH-211147

3. Li X, Long J, Gao Q, et al. Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. Rev Cardiovasc Med. 2023;24(8):234. PMID 39076715. DOI 10.31083/j.rcm2408234

4. Ren NN, Chen HJ, Li Y, et al. A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia. Zhonghua Yi Xue Za Zhi. 2017;97(26):2038–2042. PMID 28763875. DOI 10.3760/cma.j.issn.0376-2491.2017.26.005

Reference metadata verified against PubMed.

A note before you go

This article is educational and is not medical advice. It cannot account for your history, your labs, or your medication list, and it is not a substitute for individualized care from a provider who knows you. Please talk with your own clinician before starting, stopping, or changing any supplement or medication, particularly if you take blood thinners or antiplatelet medication.

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