The latest health craze from the wellness world is growing across social media platforms, leaving many wondering if they can stop taking their cholesterol medications. According to Google Trends, Americans are Googling “nattokinase” 130 percent more now than they did this time last year, and #natto pulls up over 200,000 posts on Instagram. Interest has also been fueled by high-profile influencers like Joe Rogan, whose podcast published an enthusiastic discussion about the cardiovascular benefits of this natural supplement earlier this year.
Nattokinase is an enzyme derived from a traditional Japanese food called natto. It is produced by the bacterium Bacillus subtilis when introduced to boiled soybeans and allowed to ferment. After the fermentation process, nattokinase can be purified, packaged, and sold. Typing “nattokinase” into Amazon provides a plethora of purchasing options. Most of them advertise improved cardiovascular health.
Interest among researchers is growing, too. Searching PubMed reveals a 240 percent increase in studies examining nattokinase over the last decade, many of which indicate potential benefits that warrant future studies. With nattokinase gaining popularity, it is no surprise that nutraceutical companies are packaging it for profit.
What the research shows
There is evidence that nattokinase degrades fibrin, the major protein component of clots, and lowers blood pressure. However, the study social media seems to be getting the most excited about, and the one Joe Rogan referenced on his podcast, reported that high doses of nattokinase lowered carotid artery plaque by 36 percent. The study also found a significant reduction in the thickness of the inner layers of the carotid artery, which doctors frequently measure to screen for early signs of cardiovascular disease. But is the research conclusive enough for all this hype?
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The study evaluated only carotid artery health and did not assess the coronary arteries, which supply oxygen-rich blood directly to the heart muscle. Although both are important indicators of cardiovascular health, coronary artery disease is responsible for most heart attacks. While researchers reported improvements in laboratory measures of carotid atherosclerosis, they did not determine whether those findings translated into clinical outcomes, such as fewer heart attacks, strokes, or deaths.
During the early stages of research, scientists will collect data on surrogate markers. In cardiovascular health, these surrogate markers may include plaque, LDL, blood pressure, and carotid intima-media thickness. These markers are useful for generating hypotheses and determining what deserves further research. Because improving a surrogate marker doesn’t always translate into real-world results like fewer heart attacks or longer life, these outcomes are necessary to prove and should be evaluated in randomized controlled trials.
The reliability of surrogate markers also depends on the methods used to measure them. Researchers collected laboratory data using a less invasive surface ultrasound to assess atherosclerosis rather than the more accurate intravascular ultrasound, which gives vastly superior, higher-resolution data. This is a great choice to gather cursory information and to determine whether future studies are warranted, but not for making clinical decisions.
How nattokinase compares to proven therapies
Current medications like statins have earned their place in the cholesterol-lowering treatment protocol through decades of research. Thousands of study participants have been evaluated in multiple randomized controlled trials, with results replicated by independent investigators. Systematic reviews and meta-analyses have critically evaluated study quality, combined data from numerous trials, and provided estimates of the overall effects.
For cardiovascular treatment protocols to officially change, major medical organizations like the American College of Cardiology (ACC) and the American Heart Association (AHA) require a rigorous, standardized hierarchy of scientific evidence. Minor updates can happen through small studies, but sweeping structural shifts to standard care require high-level, unambiguous data, which other medications have met.
Drugs like statins and PCSK9 inhibitors have more robust data supporting their use in medicine and produce greater lipid-lowering (LDL, TG) effects while raising the good kind of cholesterol (HDL). Additionally, these medications have strong evidence of reducing clinical outcomes like cardiovascular events in large randomized controlled trials, which are trial designs that look for cause. In contrast, this nattokinase study is retrospective, which looks for associations but cannot reliably determine cause, nor did it measure clinical outcomes.
What patients should know
At the time of publication, five of the study’s authors were employed by Sungen Bioscience Co., Ltd., a company that manufactures and sells nattokinase. Although the conflict of interest doesn’t negate the study results, the company stands to benefit from positive findings, and this relationship should be considered when interpreting the results. The paper does not disclose a funding source.
Nattokinase has shown promising preliminary findings and deserves further investigation, but no one should stop taking their statin. The current evidence is not strong enough to support replacing proven cholesterol-lowering medications with this enzyme. Until large, independent randomized controlled trials demonstrate that it reduces heart attacks, strokes, and death, the supplement should be viewed as a developing area of research, not a substitute for evidence-based treatment. As with any supplement, patients should discuss its use with their health care provider before making changes to their prescribed medications.
Meghan Johnston is a laboratory scientist.
