Nattokinase is Nontoxic with a High Safety Margin

This article was updated with audio on November 20, 2025.

🎧 ▶️ Press play below to listen.

🎧 Introducción en audio — Español (Latinoamérica)

En este audio veremos lo que dicen los estudios sobre la seguridad de la nattokinasa y por qué se considera un suplemento con amplio margen de seguridad. Esta información es educativa y no reemplaza el consejo médico profesional.

🎧 中文音频导读（精简版）

以下是《纳豆激酶具有高安全幅度且无毒性》的中文导读。

两项毒理学研究显示，纳豆激酶在动物实验和人体耐受试验中都没有发现毒性或基因毒性，安全范围非常宽。本文将简要说明这些研究的主要结果，并介绍目前常用剂量的安全依据。

Nattokinase Safety Studies

Two studies showed no safety concerns for nattokinase regarding toxicity and genotoxicity.[1] Nattokinase is derived from natto, a traditional Japanese food made from fermented soybeans.

The first was published in Regulatory Toxicology and Pharmacology in 2019. The authors are from Shenyang Pharmaceutical University and Sungen Biotech Company in China.

The study was part of the preclinical evaluation for using nattokinase in cardiovascular diseases. In a previous post, I presented the effects of nattokinase in preventing heart diseases – The Outstanding Vascular Effects and Dose of Nattokinase.

Before we go to the results, if you are going to buy nattokinase capsules (which are over the counter), you will see that most of the pills are dosed in 2,000 FU.

FU stands for Fibrin Units and is used for the enzyme nattokinase. The standard for nattokinase manufacturing is a potency of 2,000 FU per capsule. A typical dose is 2,000 FU or 100 mg once a day.  

Going to the study results, the investigation found that the maximum daily tolerant dose of nattokinase in mice is up to 480,000 FU/kg, which is 1,000 times more compared to the recommended daily amount for humans.[1]

According to the US FDA, A 100-fold safety factor is the default in applying animal data to humans. It is intended to account for potential differences in the kinetics and dynamics of a test substance when chemical-specific data or models are unavailable.[3]

The Japan Nattokinase Association recommends a dose of 2,000 FU/day for nattokinase.

Nattokinase Gene Toxicity Studies

In the genotoxicity studies, nattokinase showed no mutagenic activity as tested by the Ames test and in vivo micronucleus assay using mice bone marrow.[1]

The Ames test is used to test whether a given chemical can cause mutations in the DNA of the test organism.

A micronucleus test is another toxicological screening method for identifying potential carcinogens that act by causing genetic damage (genotoxicity). It is recognized as one of the most reliable and successful assays for detecting genotoxic carcinogens.

Lastly, the study showed nattokinase has no potential to cause chromosome aberrations in Chinese hamster mice cells.[1]

The authors conclude,

These results indicate that there is no safety concern for nattokinase in the present preclinical safety studies, supporting the safety of nattokinase as an agent for cardiovascular disease prevention.[1]

The second study was by NSF International, a product testing, inspection, and certification organization headquartered in Ann Arbor, Michigan. The study was published in Food and Chemical Toxicology.[2]

The study involved a 90-day oral rat study at doses up to 1,000 mg/kg/day. No toxicity was observed in the animals, even at a dose of 1000 mg/kg daily. [2]

Similar to the first study, no genotoxicity, chromosomal aberrations, or toxicity were observed in rats using nattokinase. Their study also showed that healthy humans could tolerate 10 mg/kg per day of nattokinase for four weeks.[2]

In a 70 kg person, that would be 700 mg daily. Seven times more than the current recommended dose of 100 mg daily.

The margin of safety of nattokinase in the study is 140. For example, if a 60 kg person takes 110 mg of nattokinase, that is 1.8 mg/kg. [2] A margin of safety corresponds to 250 mg/kg (140 x 1.8 mg/kg).[2]

Note: It is frustrating that the two studies used different units, one in FU and the other in milligrams. The other thing is that the second one used NSK-SD, the nattokinase formulation, with the vitamin K2 removed.

Safety Considerations
Although the toxicology studies showed no observed toxicity or genotoxicity at high experimental doses, nattokinase still has anticoagulant activity. Individuals taking prescription anticoagulants—such as warfarin, apixaban, dabigatran, rivaroxaban, betrixaban, or edoxaban—should avoid nattokinase due to increased bleeding risk. People with recent trauma, planned surgery, pregnancy, or chronic medical conditions should seek medical guidance before use.

Evidence-Based Summary

Two independent toxicology studies—one using FU-based dosing in animals and the other using mg/kg dosing in both animals and humans—found no signs of toxicity, genotoxicity, or chromosomal damage from nattokinase. Current supplemental doses of 2,000 FU/day fall well within the tested safety margins. However, establishing safety at higher or long-term therapeutic doses requires further human clinical trials.

Research Transparency
The safety data summarized here come from animal studies, cell-based assays, and limited human tolerance studies. Animal toxicology results help estimate human safety margins, but they do not replace long-term clinical trials. Differences in dosing units (FU vs mg) also limit direct comparisons across studies.

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2. The Outstanding Vascular Effects and Dose of Nattokinase
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References: 

1. Wu H, Wang H, Xu F, Chen J, Duan L, Zhang F. Acute toxicity and genotoxicity evaluations of Nattokinase, a promising agent for cardiovascular diseases prevention. Regul Toxicol Pharmacol. 2019 Apr;103:205-209. doi: 10.1016/j.yrtph.2019.02.006. Epub 2019 Feb 8. PMID: 30742876. Full text from Sci-Hub here.
2. Lampe, B.J., English, J.C., 2016. Toxicological assessment of nattokinase derived from
   Bacillus subtilis var. natto. Food Chem. Toxicol.: An International Journal Published
   for the British Industrial Biological Research Association 88, 87–99. https://doi.org/
   10.1016/j.fct.2015.12.025
3. United States Food and Drug Administration, 2000. Guidance for Industry and Other Stakeholders Toxicological Principles for the Safety Assessment of Food Ingredients (Redbook 2000).

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