This post was kick-started by a post to a study on a Spanish ME/CFS site shown below

• Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS–CoV-2 in vitro.Oba M, Rongduo W, Saito A, Okabayashi T, Yokota T, Yasuoka J, Sato Y, Nishifuji K, Wake H, Nibu Y, Mizutani T.Biochem Biophys Res Commun. 2021 Sep 17;570:21-25. doi: 10.1016/j.bbrc.2021.07.034. Epub 2021 Jul 13.
  “our study suggests that the putative serine-protease(s) in natto may impair the infectious function of BHV-1 and SARS-CoV-2, probably through the proteolysis of its glycoprotein D and the spike protein, respectively.”

This is extra relevant because Nattokinase is one of my personal favorite tools for dealing with hypo-perfusion (low oxygen to the brain), something that I have experienced during ME/CFS flares. It is also the subject of my last post. I have cited Nattokinase in prior posts, some 9 years ago, and it seems time to update what we know.

• Nattokinase – 2nd choice for fibrinolytics 2012
• Histamines and Anticoagulants – a review 2014
• Potentiators: Often the difference between success and failure 2019

So what more has been added to our knowledge base. Nattokinase comes from Bacillus Subtilis Natto. This strain has been traditionally used in a Japanese dessert called “Natto” which you can buy is some Asian shops – it is a bit of an acquired taste (but I like it)

• Fibrinolytic characteristics of Bacillus subtilis G8 isolated from natto.Pinontoan R, Elvina, Sanjaya A, Jo J.Biosci Microbiota Food Health. 2021;40(3):144-149. doi: 10.12938/bmfh.2020-071. Epub 2021 Feb 20.
  “Both nattokinase and B. subtilis G8 were able to dissolve both whole blood and euglobulin clots.” – important for COVID micro-clots.
• Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases.Gallelli G, Di Mizio G, Palleria C, Siniscalchi A, Rubino P, Muraca L, Cione E, Salerno M, De Sarro G, Gallelli L.Nutrients. 2021 Jun 13;13(6):2031. doi: 10.3390/nu13062031.
  “we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.”
• Breaking the vicious loop between inflammation, oxidative stress and coagulation, a novel anti-thrombus insight of nattokinase by inhibiting LPS-induced inflammation and oxidative stress.Wu H, Wang Y, Zhang Y, Xu F, Chen J, Duan L, Zhang T, Wang J, Zhang F.Redox Biol. 2020 May;32:101500. doi: 10.1016/j.redox.2020.101500. Epub 2020 Mar 11.
  “we extended the anti-thrombus mechanism of NK by demonstrating the anti-inflammatory and anti-oxidative stress effects of NK in ameliorating LPS-activated macrophage signaling and protecting against LPS-stimulated AKI as well as glomeruler thrombus … opening a comprehensive anti-thrombus strategy by breaking the vicious cycle between inflammation, oxidative stress and thrombosis.”
• The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects.Yoo HJ , Kim M , Kim M , Lee A , Jin C , Lee SP , Kim TS , Lee SH , Lee JH .Food Funct. 2019 May 22;10(5):2888-2893. doi: 10.1039/c8fo02324g.
• Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases.Chen H, McGowan EM, Ren N, Lal S, Nassif N, Shad-Kaneez F, Qu X, Lin Y.Biomark Insights. 2018 Jul 5;13:1177271918785130. doi: 10.1177/1177271918785130. eCollection 2018. – Note cardio issue arise in COVID and LONG COVID.
• [A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia].Ren NN, Chen HJ, Li Y, Mcgowan GW, Lin YG.Zhonghua Yi Xue Za Zhi. 2017 Jul 11;97(26):2038-2042. doi: 10.3760/cma.j.issn.0376-2491.2017.26.005.
  “daily NK supplementation is an effective way to manage the progression of atherosclerosis and potentially may be a better alternative to statins which are commonly used to reduce atherosclerosis and further to prevent cardiovascular attack and stroke in patients.”
• Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease.Weng Y, Yao J, Sparks S, Wang KY.Int J Mol Sci. 2017 Feb 28;18(3):523. doi: 10.3390/ijms18030523.
• Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.Jensen GS, Lenninger M, Ero MP, Benson KF.Integr Blood Press Control. 2016 Oct 13;9:95-104. doi: 10.2147/IBPC.S99553. eCollection 2016.
• Antioxidation, angiotensin converting enzyme inhibition activity, nattokinase, and antihypertension of Bacillus subtilis (natto)-fermented pigeon pea.Lee BH, Lai YS, Wu SC.J Food Drug Anal. 2015 Dec;23(4):750-757. doi: 10.1016/j.jfda.2015.06.008. Epub 2015 Jul 29.
• A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, Hamaoka T.Sci Rep. 2015 Jun 25;5:11601. doi: 10.1038/srep11601.
• Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation.Jang JY, Kim TS, Cai J, Kim J, Kim Y, Shin K, Kim KS, Park SK, Lee SP, Choi EK, Rhee MH, Kim YB.Lab Anim Res. 2013 Dec;29(4):221-5. doi: 10.5625/lar.2013.29.4.221. Epub 2013 Dec 20.

Putting it together

Nattokinase seems to treat many conditions associated with western diet. The next question is simple, what are dosages used in studies?

• Oral nattokinase 2,000 fibrinolytic units daily [Nattokinase Atherothrombotic Prevention Study (NAPS)]
• nattokinase-mono formula (3500FU x 4 =14,000 FU) [Efficacy and Safety of Geneferm Nattokinase]
•  (100 mg) nattokinase/day [Effects of NSK-SD (Nattokinase) on Blood Pressure] [Nattokinase Supplementation and Hemostatic Factors]

Usually 100 mg = 2000 FU on most commercial products, so the range in trials is 1-7 100mg capsules per day.