What side effects have been reported for nattokinase in humans?

The short version: reported side effects are mostly mild and rare, but the evidence base is thin and the most serious risk, bleeding, is exactly what the studies were not designed to catch.

The evidence retrieved covers three human trials and one review. The 2021 RCT in 265 healthy older adults reported 13 serious adverse events in the nattokinase group versus 15 in placebo, with no deaths in the treatment arm and one in placebo [1]. The 2023 dyslipidemia trial of 113 adults reported no intervention-related adverse events at all [2]. A 2025 review covering a retrospective cohort of 1,062 people taking 10,800 FU daily reported "no obvious" adverse events [3]. None of these studies was designed to detect bleeding events, and none enrolled people on anticoagulants or antiplatelets, which is precisely the population where a fibrinolytic enzyme poses real risk [1].

The trials were small, short, and not powered for safety. The 2021 RCT ran about three years but was powered for atherosclerosis progression, not harm [1]. The 2023 trial ran four months [2]. No long-term safety data exists. The absence of reported bleeding in these studies does not mean the risk is absent; it means the studies could not have found it.

My call: the evidence supports nattokinase as generally well tolerated in healthy adults at these doses, but the bleeding risk in vulnerable populations is unstudied, not disproven. Confidence: low, because the safety data is too thin to call it anything else.