WHAT IS NATTO AND WHAT IS NATTOKINASE?

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

In Japan, natto is also called "vegetable cheese" and is often eaten with vegetables and rice for breakfast. However, natto has not yet been able to establish itself in European menus, which is probably due to its taste, strong smell and unappetizing appearance, which takes a lot of getting used to.

Nattokinase is one of several enzymes in natto and is obtained from the fermentation of soybeans. The soybeans are boiled and then fermented using the bacteria “Bacillus subtilis”. The bacteria produce the enzyme nattokinase, which consists of 275 amino acids, in order to metabolize the soy protein.

The name NattoKINASE resulted from the mistaken belief that nattokinase belonged to the enzyme group of kinases. However, it was later 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 enzyme group of proteases – just like the body’s two enzymes plasmin and thrombin, which are involved in blood clotting:

Thrombin promotes blood clotting by synthesizing the "glue" fibrin from fibrinogen, which unfortunately not only closes wounds but can also form blood clots. Plasmin, in turn, dissolves fibrin again; this process is called "fibrinolysis."  Various studies suggest that nattokinase – similar to plasmin – may have fibrinolytic, i.e. clot-dissolving, properties.

CURRENT STUDIES ON NATTOKINASE

thrombosis / blood clotting

• A randomized, double-blind, placebo-controlled study from 2015 examined the effect of nattokinase on preventing venous thrombosis in 94 patients who had undergone surgery. The study found that nattokinase significantly reduced the risk of venous 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 examined 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). 12 healthy men were given either a dose of 2,000 FU of nattokinase or a placebo. In the next round, the groups were swapped.Blood was then taken at two-hour intervals (after 2, 4, 6 and 8 hours) and tested for the corresponding clotting factors. It was found that the amount of fibrin and fibronogen degradation products increased, ie blood clots were dissolved. The amount of clotting factors decreased and the amount of clot-dissolving substances increased, so that the clotting time was slowed down, which means that the blood was now "thinner".
• One  clinical trial  from 2002 (cf. https://pubmed.ncbi.nlm.nih.gov/14565628/ ) supplemented 204  Passengers on a flight from New York to London were given a placebo or a mixture of nattokinase and pycnogenol. After the flight, the legs were examined using ultrasound: In the supplement group, no  cases of deep vein thrombosis, while in the placebo group 5 cases of deep vein thrombosis and two cases of a superficial blood clot were diagnosed. In addition, leg swelling was measured before and after the flight: leg swelling increased by +12% after the flight in the placebo group, while it even decreased by 15% in the supplemented nattokinase-pycnogenol group.
• In a 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) from 2009, three groups of participants were given two capsules of nattokinase daily (2,000 FU per capsule). The three groups were healthy volunteers, patients with a certain risk of cardiovascular disease and dialysis patients (who have a particularly high risk of thrombosis) on the other. After two months, it was found that the levels of the coagulation factors had significantly reduced in all three groups. No side effects were observed.

atherosclerosis

• In summary, data from a large clinical trial from 2022 with 1,062 participants (see https://www.ncbi.nlm.nih.gov/9441630/ ) 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 side effects were observed related to the use of nattokinase. These results demonstrate that promising and positive clinical results can be achieved by using nattokinase at a dose of 10,800 FU per day in treating the progression of atherosclerosis and hyperlipidemia.

high blood pressure

• A 2008 study examined the effect of nattokinase on blood pressure in 86 patients with uncontrolled hypertension. The study found that nattokinase significantly reduced 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/) with almost 30,000 subjects over the age of 35. This documented the Natto eating habits and came to the conclusion that the group with the highest Natto consumption was the one with the least strokes and  ischemic heart disease occurred, i.e. the mortality risk at  was lowest.There were no significant associations between cardiovascular disease mortality risk and intake of total soy protein, total soy isoflavone, and soy protein or soy isoflavone 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 intake may contribute to reducing cardiovascular mortality.

Long-Cov / Post-Vac

• This study has recently become a real political issue - but we would like to mention it for the sake of completeness: An in vitro study from 2022 (see https://pubmed.ncbi.nlm.nih.gov/36080170/) suggest that nattokinase plays a positive role in the degradation of spike proteins in connection with  SARS-CoV-2 disease or mRNA vaccination. Specifically, the effect of nattokinase on the S protein of SARS-CoV-2 was investigated. When cell lysates transfected with 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 on the cell surface was degraded when nattokinase was added to the culture medium. The authors of the study note that the results indicate that nattokinase has the potential to inhibit SARS-CoV-2 infection via S protein degradation. However, it should be noted critically that this is only an in vitro study - i.e. in the test tube. Clinical studies on humans are pending.

cancer

• There are still no conclusive results on the effect of nattokinase on cancer cells. Initial studies with mice suffering from liver cancer show that nattokinase could have a protective effect. Compared to the placebo group, there were more survivors in the nattokinase group. Ascites (water in the abdominal cavity) was also less common. An ultrasound even showed that tumor growth had decreased in the nattokinase group. A certain protein (FOXM1), which can promote tumor growth, was less pronounced in the nattokinase group, so it was evidently inhibited by the enzyme. The 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. In vitro, ie in laboratory tests (not on humans), this was actually shown in a study from 2009 (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 studies on humans are pending.