Natto is a vegetable cheese-like food which is extremely popular in Japan. It has been around at least 1000 years [1]. Natto contains a fibrinolytic enzyme, termed nattokinase in 1980. This “enzyme is a subtilisin-like serine protease composed of 275 amino acid residues and has a molecular weight of 27.7 kDa” [1] and is sometimes used by naturally-inclined doctors for “blood thinning” purposes, thrombosis, and for certain eye health issues [1-5].

Nattokinase is capable of directly activating pro-urokinase (endogenous) and decomposing fibrin. Nattokinase assists in the body’s fibrinolytic activity, supports cadiovascular health, and supports heart circulation. Some have found it helpful clinically when chronic deep aches present (presumably due to its enzymatic activity).

Nattokinase was discovered by Doctor Hiroyuki Sumi while he searched for a natural agent that could successfully dissolve thrombus associated with cardiac and cerebral infarction (blood clots associated with heart attacks and stroke). While working as a researcher and majoring in physiological chemistry at Chicago University Medical School, he tested over 170 natural foods as potential thrombolytic agents. In 1980, he found what he such an agent within natto. Dr. Sumi named this newly discovered enzyme "nattokinase", which means "enzyme in natto"

While a variety of claims (like dissolving blood clots) have been made about nattokinase, this document will mainly stick to the conclusions of published, peer-reviewed, MED-Line papers about it.

Researchers Pais, et al. wrote, “we have begun to assess the effects of the enzyme on RBC aggregation and blood viscosity. Blood samples were incubated with nattokinase (final activities of 0, 15.6, 31.3, 62.5 and 125 units/ml) for 30 minutes at 37 degrees C. RBC aggregation was measured using a Myrenne MA-1 aggregometer and blood viscosity assessed over 1-1000 s(-1) with a computer controlled scanning capillary rheometer (Rheolog). Our in vitro results showed a significant, dose-dependent decrease of RBC aggregation and low-shear viscosity, with these beneficial effects evident at concentrations similar to those achieved in previous in vivo animal trials. Our preliminary data thus indicate positive in vitro hemorheological effects of nattokinase, and suggest its potential value as a therapeutic agent and the need for additional studies and clinical trials” [1].

Researchers Peng, et al. wrote, “Accumulation of fibrin in the blood vessels usually results in thrombosis, leading to myocardial infarction and other cardiovascular diseases. For thrombolytic therapy, microbial fibrinolytic enzymes have now attracted much more attention than typical thrombolytic agents because of the expensive prices and the undesirable side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus from traditional fermented foods. The physiochemical properties of these enzymes have been characterized, and their effectiveness in thrombolysis in vivo has been further identified. Therefore, microbial fibrinolytic enzymes, especially those from food-grade microorganisms, have the potential to be developed as functional food additives and drugs to prevent or cure thrombosis and other related diseases “ [2].

Researchers Suzuki, et al. wrote, “We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury… In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall” [3].

Suzuki and some of his researchers also wrote “Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Dietary natto extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. In ex vivo studies, euglobulin clot lysis times were measured 3 wk after the initial supplementation. Neointima formation and thickening were also initiated successfully. The intima media ratio 3 wk after endothelial injury was 0.15 +/- 0.03 in the control group. Dietary natto extract supplementation suppressed intimal thickening (0.06 +/- 0.01; P < 0.05) compared with the control group. Natto extracts shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings

suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation” [4] .

Researchers Takano, et al. wrote, “Scanning electron microscopy showed smooth retinal surfaces, indicating the occurrence of PVD at 30 minutes after intervention in all the experimental eyes injected with 0.1 or 1.0 FU nattokinase, but none of the control eyes. Light microscopy and ERG analysis showed no critical change even after the use of 0.1 FU nattokinase, an amount sufficient to induce PVD. However, toxicity in the forms of preretinal hemorrhage and ERG changes was noted with the higher dose (1 FU) of nattokinase. CONCLUSIONS: The results suggested that nattokinase is a useful enzyme for pharmacologic vitreolysis because of its efficacy in inducing PVD”[5].

And although all Food Research products are 100% foods, the medical profession often refers to foods that they believe have medicinal purposes as drugs (believe it or not, the PDR for Herbal Medicine refers to brown rice as a drug [6]). And one study, by Dr. Sumi, thus also refers to nattokinase as a drug, “The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced” [7].

Anyway, even though we at Food Research International would classify nattokinase as a food extract and not a drug, we are pleased that the medically-oriented do realize that in capsules, oral consumption of nattokinase is an effective substance to consider for certain health conditions.

Nattokinase Video

References

[1] Pais E, Alexy T, Holsworth RE Jr, Meiselman HJ. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc. 2006;35(1-2):139-42

[2] Peng Y, Yang X, Zhang Y. Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo. Appl Microbiol Biotechnol. 2005 Nov;69(2):126-32

[3] Suzuki Y, Kondo K, Matsumoto Y, Zhao BQ, Otsuguro K, Maeda T, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci. 2003 Jul 25;73(10):1289-98

[4] Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 2003;19(3):261-4.

[5] Takano A, Hirata A, Ogasawara K, Sagara N, Inomata Y, Kawaji T, Tanihara H. Posterior vitreous detachment induced by nattokinase (subtilisin NAT): a novel enzyme for pharmacologic vitreolysis. Invest Ophthalmol Vis Sci. 2006 May;47(5):2075-9

[6] Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicine, 3 rd ed. Thompson PDR, Montvale (NJ), 2004