WHAT IS NATTO AND WHAT IS NATTOKINASE?

Natto is a Japanese dish made from fermented soybeans, which in Japan is both a completely normal dish and is recommended in Japanese naturopathy as a traditional remedy for cardiovascular diseases.

In Japan, natto is also called "vegetable cheese" and is often eaten for breakfast with vegetables and rice. In contrast, natto has not yet gained popularity in European diets, likely due to its very acquired taste, strong smell, and unappetizing appearance.

Nattokinase is one of several enzymes in natto and is obtained from the fermentation of soybeans. For this process, the soybeans are cooked and then fermented using the bacterium Bacillus subtilis. During this process, the bacteria produce the enzyme nattokinase, which consists of 275 amino acids, enabling the metabolism of the soy protein.

The name NattoKINASE resulted from the mistaken belief that nattokinase belonged to the kinase enzyme group. Later, however, it was discovered that it actually belongs to the group of proteases, which break down proteins.

FIBRINOLYTIC PROPERTIES OF NATTOKINASE

As already explained, nattokinase is an enzyme from the protease enzyme group – just like the two endogenous enzymes plasmin and thrombin, which are involved in blood clotting:

Thrombin promotes blood clotting by synthesizing fibrin, the "glue" that unfortunately can not only close wounds but also form blood clots. Plasmin, in turn, dissolves fibrin; this process is called "fibrinolysis". Several studies suggest that nattokinase – similar to plasmin – is activated via fibrinolytic, d.hIt might possess clot-dissolving properties.

CURRENT STATE OF STUDY ON NATTOKINASE

Thrombosis/Blood clotting

• A randomized, double-blind, placebo-controlled study from 2015 investigated the effect of nattokinase on the prevention of deep vein thrombosis in 94 patients undergoing surgery. The study found that nattokinase significantly reduced the risk of deep vein thrombosis compared to the placebo group. (See J. Sato et al. "Randomized, controlled study of the postoperative preventive effect of a nattokinase-containing beverage on deep vein thrombosis." European Journal of Vascular and Endovascular Surgery, vol. 49, no. 2, 2015, pp. 230-5.)
• A randomized, double-blind, placebo-controlled study from 2004 investigated the effect of nattokinase on blood coagulation and endothelial function in 86 healthy volunteers. The study found that nattokinase significantly improved blood coagulation and endothelial function compared to the placebo group. (See S. Fujita et al. "Increased fibrinolytic activity during exercise may be mediated by an increase in thrombin-activatable fibrinolysis inhibitor and by changes in platelet activation." Journal of Thrombosis and Haemostasis, vol. 2, no. 7, 2004, pp. 1186-92.)
• The effect of a single dose of nattokinase was demonstrated in a double-blind, placebo-controlled study from June 2015 (see Kurosawa Y et al., A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles, Scientific Reports, 2015 Jun 25;5:11601). Twelve healthy men were given either a 2,000 FU dose of nattokinase or a placebo. In the next round, the groups were switched. Blood samples were then taken at two-hour intervals (after 2, 4, 6, and 8 hours) and analyzed for the relevant coagulation factors.It was shown that the amount of fibrin and fibronogen degradation products increased, d.hBlood clots were dissolved. The amount of clotting factors decreased and the amount of clot-dissolving substances increased, thus slowing down the clotting time, which means that the blood was now "thinner".
• One clinical study from 2002 (see https://pubmed.ncbi.nlm.nih.gov/14565628/ ) supplemented 204 Passengers on a flight from New York to London were given either a placebo or a mixture of nattokinase and pycnogenol. After the flight, their legs were examined using ultrasound: no abnormalities were found in the supplement group. Cases of deep vein thrombosis were diagnosed in the placebo group, whereas in the placebo group, 5 cases of deep vein thrombosis and two cases of superficial blood clots were diagnosed. Additionally, leg swelling was measured before and after the flight: leg swelling increased by 12% in the placebo group after the flight, while it decreased by 15% in the supplemented nattokinase-pycnogenol group.
• In a 2009 human study (see Hsia CH et al, Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects, Nutrition Research, 2009 Mar;29(3):190-6), three groups of participants were given two capsules of nattokinase daily (2,000 FU per capsule). The three groups consisted of healthy volunteers, patients at risk for cardiovascular disease, and dialysis patients (who have a particularly high risk of thrombosis). After two months, the levels of coagulation factors were found to have significantly decreased in all three groups. No side effects were observed.

Atherosclerosis

• In summary, the data from a large clinical study from 2022 with 1,062 participants (see https://www.ncbi.nlm.nih.gov/9441630/ The results suggest that nattokinase at a daily dose of 10,800 FU, which is higher than the recommended dose of 2,000 FU, is significantly effective in treating the progression of atherosclerosis and hyperlipidemia. No adverse effects associated with the use of nattokinase were observed. These results demonstrate that the use of nattokinase at a dose of 10,800 FU per day can yield promising and positive clinical results in the treatment of the progression of atherosclerosis and hyperlipidemia.

High blood pressure

• A 2008 study investigated the effect of nattokinase on blood pressure in 86 patients with uncontrolled hypertension. The study found that nattokinase significantly lowered systolic blood pressure compared to the placebo group (see K. Kim et al. "Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial." Hypertension Research, vol. 31, no. 8, 2008, pp. 1583-1588).

Stroke/ischemic heart disease

• In 2017 there was a study (cf.) https://pubmed.ncbi.nlm.nih.gov/27927636/A study involving nearly 30,000 participants over the age of 35 documented their natto eating habits and concluded that the group with the highest natto consumption had the fewest strokes and ischemic heart disease occurred, thus increasing the mortality risk. The lowest quartiles were found. There were no significant associations between the risk of mortality from cardiovascular disease and the intake of total soy protein, total soy isoflavones, and soy protein or soy isoflavones from soy foods other than natto. The highest quartiles of total soy protein and natto intake were significantly associated with a reduced risk of mortality from total stroke.The highest quartile of natto intake was also significantly associated with a reduced risk of mortality from ischemic stroke. Conclusion: The data suggest that natto consumption may contribute to a reduction in cardiovascular mortality.

Long-term CoV/Post-Vac

• This study has recently become a real political issue – we would still like to mention it for the sake of completeness: An in-vitro study from 2022 (see…) shows… https://pubmed.ncbi.nlm.nih.gov/36080170/) indicating that nattokinase plays a positive role in the degradation of spike proteins in connection with a SARS-CoV-2 disease or mRNA vaccination could play a role. Specifically, the effect of nattokinase on the SARS-CoV-2 S protein was investigated. When cell lysates transfected with the S protein were incubated with nattokinase, the S protein was degraded in a dose- and time-dependent manner. Immunofluorescence analysis showed that the S protein was degraded on the cell surface when nattokinase was added to the culture medium. The authors of the study note that the results suggest that nattokinase has the potential to inhibit SARS-CoV-2 infection via S protein degradation. However, it is important to note that this is only an in vitro study. d.hIn a test tube. Clinical trials in humans are still pending.

Cancer

• There are still no conclusive results regarding the effects of nattokinase on cancer cells. Initial studies with mice suffering from liver cancer suggest that nattokinase may have a protective effect. Compared to the placebo group, there were more survivors in the nattokinase group. Ascites (fluid accumulation in the abdominal cavity) also occurred less frequently. Ultrasound even showed that tumor growth had decreased in the nattokinase group. A specific protein (FOXM1), which can promote tumor growth, was expressed at lower levels in the nattokinase group, meaning it was apparently inhibited by the enzyme. Levels of other tumor markers (CD31, CD44 and vimentin) were also lower in the nattokinase group than in the placebo group (see Yan Y, Wang Y, Qian J, Wu S, Ji Y, Liu Y, Zeng J, Gong A. Nattokinase Crude Extract Inhibits Hepatocellular Carcinoma Growth in Mice. J Microbiol Biotechnol. 2019 Aug 28;29(8):1281-1287).

Alzheimer

• Since nattokinase can dissolve blood clots, it is conceivable that it could also dissolve the deposits in the brain that are typical of Alzheimer's disease. In vitro, d.hIn a laboratory experiment (not on humans), this was indeed demonstrated in a 2009 study (see Hsu RL et al., Amyloid-degrading ability of nattokinase from Bacillus subtilis natto, Journal of Agricultural and Food Chemistry, 2009 Jan 28;57(2):503-8). Clinical trials in humans are still pending.