Foods/Supplements-Vitamins: Nattokinase

I have mentioned Nattokinase in a number of posts, but have not reported on human studies before. There are no PCa studies on PubMed; nor are there any cancer studies at all. In fact, there are very few human studies. However, there is enough evidence to indicate that coagulation factors that might be altered in a man with PCa, might be favorably adjusted via Nattokinase. IMO

Recap:

As men age, coagulation dysfunction becomes more common. GPs don't go looking for coagulation problems, so the patient eventually finds the problem himself. Pain in the leg due to a deep vein thrombosis [DVT], perhaps. A trip to the ER when a DVT leads to a pulmonary embolism & breathing difficulties.

Some researchers have suggested that men presenting with a blood clot should be screened for PCa, since cancer alters the balance of coagulation factors, & this will occur before diagnosis in men not routinely undergoing PSA tests.

There is a blood clot-metastasis hypothesis that micro-clots are essential for the survival & docking of circulating cancer cells.

Having experience a double DVT in one leg six years ago, 3 months of Warfarin (& Coumadin Clinic hell), together with a met at L5, I wish I had known about Nattokinase 12 years ago.

My urologist once said that if there is a met on a scan, there are mets all over - you just can't see them. The oligometastatic theory, on the other hand, says that some men with mets only get a few, & they can be treated with radiation. My feeling is that metastasis being limited to L5 in my case (at least so far) was probably due to Nattokinase use, rather than good luck. In any case, I would continue to target micro-clots even with extensive mets.

The best indication of a blood clot issue is the D-dimer test. It shows that fibrin is being broken down. The D-dimer number should be as close to zero as the test can measure.

Briefly, a clot begins with the aggregation of platelets at the site, followed by thrombin acting on fibrinogen to build up the fibrin clot.

In the background, there is plasmin, an enzyme that degrades certain blood proteins, including fibrin. It is painfully slow. Bear in mind that Warfarin & other treatments do not dissolve clots. They slow down coagulation to give plasmin a chance to break down the clot naturally. Even so, the minimum Warfarin therapy is 3 months (plus a further 3 months if there is cancer), with lifetime use if the therapy fails, as it often does.

Nattokinase is chemically similar to plasmin, but works faster. It was first isolated from a Japanese soy food product - Natto.

Studies (non-cancer):

[1] First reported 30 years ago:

"A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto, which is a typical soybean food eaten in Japan. The average activity was calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic enzyme, named nattokinase ..."

[2] Tested on dogs (1990):

"NK capsules were ... 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."

[3] (2008 - Korea) "Effects of nattokinase on blood pressure"

"The objective of this study was to examine the effects of nattokinase supplementation on blood pressure in subjects with pre-hypertension or stage 1 hypertension. In a randomized, double-blind, placebo-controlled trial, 86 participants ranging from 20 to 80 years of age with an initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg received nattokinase (2,000 FU/capsule) or a placebo capsule for 8 weeks. Seventy-three subjects completed the protocol. Compared with the control group, the net changes in SBP and diastolic blood pressure (DBP) were -5.55 mmHg ... and -2.84 mmHg .., respectively, after the 8-week intervention."

[4] (2009 - Taiwan)

"In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII."

[5] (2009 - Taiwan)

"The purpose of this randomized, double-blind, placebo-controlled, parallel comparison study was to evaluate the lipid-lowering effect of orally administrated nattokinase and nattokinase combined with red yeast rice (RYR) extract on blood lipids in patients with hyperlipidemia. A total of 47 patients with hyperlipidemia were assigned to one of three groups: 1. nattokinase-mono formula (50 mg/capsule), 2. combined formula of nattokinase with RYR (300 mg of extract/capsule) and 3. placebo. Subjects received a twice daily dose of two capsules for six months. The mono formula showed no effects on blood lipids until month six, while the combined formula ameliorated all of measured lipids starting from month one. In the combined group significant decreases were found with regard to: triglycerides (TG) by 15%, total cholesterol (TC) by 25%, low-density lipoprotein cholesterol (LDL-C) by 41%, TC/high-density lipoprotein cholesterol (HDL-C) ratio by 29.5%, and increases in HDL-C by 7.5%. These changes were sustained until the end of study. After controlling for baseline levels, only the combined group, but not mono group, showed a significant difference (p<0.0001) in TC, LDL-C and TC/HDL-C ratio when compared with the placebo group."

[6] (2013 - U.S.)

"This study intended to (1) detect nattokinase directly and immunologically, (2) show that nattokinase and/or its metabolites were detectable in human blood following ingestion of a commercial preparation, and (3) chart a pharmacokinetic dosing effect for nattokinase."

"Administration of nattokinase occurred orally with the ingestion of a single daily dose (2000 FU) of nattokinase. Capsules, each containing approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science Laboratory, Osaka, Japan), were used in the study."

"Peak serum levels of nattokinase were observed at approximately 13.3 h ± 2.5 h (mean ± standard error) postdose."

[7] (2015 - Japan)

"Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously."

[8] (2016 - U.S.)

"The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors."

"Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg .., and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg ..."

Dosing.

The standard prophylactic dose of Nattokinase NSK-SD (100 mg) delivers 2,000 FUs (fibrinolytic units). Some men take that daily & hope for the best. & it is better than nothing. Ideally, this would be started at diagnosis to minimize the risk of mets - IMO.

If D-dimer shows an active clot, there is no way to hit on the optimal dose, IMO. My inclination would be to try to bring D-dimer down fast. Note, however, that by speeding the degradation of the clot, D-dimer will increase initially.

The maitenance dose, which might be as low as one softgel, is the dose that consistently returns a D-dimer result of zero.

Note that LabCorp gives <20 mg/L FEU as their lowest result, with a reference range of 0.00-0.49. "a

normal (<0.50 mg/L FEU) D-dimer result in conjunction with a non-high

clinical probability assessment, excludes deep vein thrombosis (DVT)

and pulmonary embolism (PE) with high sensitivity."

In a hospital setting, D-dimer is used to eliminate thrombosis/embolism as a possible diagnosis. In a cancer setting, I'd be uncomfortable in the 20-49 range.

Wiki: "Since its introduction in the 1990s, it has become an important test performed in patients with suspected thrombotic disorders. While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but does not rule out other potential causes. Its main use, therefore, is to exclude thromboembolic disease where the probability is low." [9]

[10] Nattozyme is the product I use &, since it has worked for me, I am nervous about switching to something cheaper.

{After being on Warfarin 3 months, my doctor agreed that I need not do another 3 months if my leg was clear. Alas, one vein was clear but the other was not. My doctor said that it might never clear. Surprisingly, he gave me approval to switch to Nattokinase. When symptoms returned to the leg, I discovered that 6 softgels twice daily quickly reversed them.}

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/347...

[2] ncbi.nlm.nih.gov/pubmed/212...

[3] ncbi.nlm.nih.gov/pubmed/189...

[4] ncbi.nlm.nih.gov/pubmed/193...

[5] ncbi.nlm.nih.gov/pubmed/197...

[6] ncbi.nlm.nih.gov/pubmed/237...

[7] ncbi.nlm.nih.gov/pubmed/261...

[8] ncbi.nlm.nih.gov/pubmed/277...

[9] en.wikipedia.org/wiki/D-dimer

[10] swansonvitamins.com/nutrico...

9 Replies

oldestnewest
  • Patrick,

    how do you know L5 is your only met...seems to go against what your onco said

    Gus

  • Gus,

    There might be dozens, but it's the only one that has appeared in 12 years.

    -Patrick

  • Patrick,

    What your urologist said about scans, my dad's oncologist said a bit differently: he said if the most sensitive available scans do not see a met (and they are probably there), it does not matter, for they are not negatively impacting the body as a whole...

    Thanks for your write-up, we'll share it with our doctors on the next visit!

    Arthur

  • I had an F-18 Pet Scan which showed several mets in my left iliac, my sacrum, and L4 and L5. When I visited my radiologist to discuss starting Xofigo, he brought up my pics, and he couldn't find the mets. Not that he spent a ton of time reviewing them either. I was also on a study, where I had the left coast doc's arguing with my east coast doc's whether I did or did not have mets. Is it supposed to be that subjective? Either you do or you don't, there's no middle ground here.

    Joe

  • Patrick,

    I don't remember why but I started consuming NK about 15 years ago based on the recommendation of Dr. Williams, an alternative doctor. Three years ago, I stopped the consumption when I went on ADT3 to treat PCa that had metastasized. Last year, I was hospitalized with A-fib for three days as the docs couldn't get my blood pressure to stabilize, I have traditional low levels of bp. Ever since. I have been on Warfarin then on Eliquist to prevent clotting. The cardiologist wants me to take two 5mg pills of Eliquis per day but I have been taking one pill plus I also started to take another pill of NK. Warfarin is monitored to adjust dosage in order to keep blood at the desired levels while Eliquis is not monitored at all. Do you have any opinion on the use of both NK and Eliquis concurrently?

    jal

  • Joel,

    The target of Eliquis is factor Xa. The coagulation cascade is complex, with many components. Factor Xa converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin. Thus Eliquis inhibition will slow down clot build-up by restricting the thrombin supply.

    Nattokinase, on the other hand, tackles fibrin in the clot. It also has the effect of lowering fibrinogen, but basically to low-normal - so I would discount that. But what else does nattokinase do? I don't see anything to suggest that it has an effect on factor Xa. It does lower factors VII & VIII, however [1].

    I have no idea what the implications are of the combination.

    Most will say that nattokinase is safe since it does not stop clots forming. If you were to have an accident with massive bleeding, you would simply stop taking the nattokinase.

    The anticoagulants, on the other hand, are dangerous in an accident scenario. There is risk of uncontrolled bleeding. Might Nattokinase increase this risk - even slightly? I don't know.

    -Patrick

    [1] ncbi.nlm.nih.gov/pubmed/193...

  • Patrick--Had read thru 95 papers from various sources--many from Japan translated. Granted there are no available testing results that NK helps against Pca. BUT, It is one of my supplements together with Serrapeptase--that I have been taking every day for 11 years. I have not missed a day--except for surgery.

    There is some indirect evidence that these enzymes, which like to eat Fibrin, may in fact do some disturbances, to the outer shell of the Pca cell, which some researchers report as being composed of some fibrous material. I lost the paper--but, Serrapeptase was shown to eat holes in the Pca cell in vivo--and the thinking was that T cells might get in. That is as far as the paper went, as per my foggy memory.

    I cannot imagine a day that I would not take these enzymes for cardiac health, and a preventer of strokes. They are a part of my top 10's.

    Nalakrats

  • Nalakrats,

    I only look at papers in PubMed. That takes a lot of time, so I'm not keen to cast my net further.

    I looked at Serrapeptase in PubMed & realized that I would have to do precisely that to build a case for it. So I'm passing. Perhaps you will take it on later.

    I do use it, but stopped this week. I have some physical issues which might be due to my new statin (Livalo) or Serrapeptase (started the same time).

    -Patrick

  • NK breaks up mucus as well as blood clots. It makes antibiotics effective in treating lung infections.

    I think cancer growth creates stickiness that is broken up with nattokinase. Have taken natto and sertapeptase for years and am doing very well with stage 4 since 2012.

    Both enzymes also greatly reduce the effects of Lyme disease.

You may also like...