Canadian gov't on nattokinase Nov. 2012: Unproven

[www.hc-sc.gc.ca]

Quote

....Evidence demonstrating potential health benefits of Nattokinase in humans is very limited. To date, the effects of Nattokinase on the prevention of first heart attack or stroke has not been studied. Only one very preliminary study tested the effects on Nattokinase on the secondary prevention of heart attack and stroke. With respect to cardiovascular risk factors, Nattokinase had no effect on the levels of cholesterol in people with high cholesterol, and only slightly decreased blood pressure in people with high blood pressure.

The evidence demonstrating the safe use of Nattokinase in humans is also very limited. While no adverse reactions were reported in human clinical studies, the number of people taking Nattokinase in each of the studies was very low (15-45) and the duration of Nattokinase treatment was short (2, 6 or 7 months). Unfortunately, not all the studies examined the effect of Nattokinase on the blood clotting pathway. However, one study suggested that Nattokinase may make even an otherwise healthy individual more susceptible to bleeding following trauma.

How Nattokinase thins the blood in humans has not yet been fully established. Laboratory and animal studies have shown that Nattokinase breaks down blood clots. Understanding how Nattokinase works to thin the blood is critical to understanding its potential risks, particularly when combined with other blood thinning health products because not all blood thinners work the same way. The risk of internal bleeding could be magnified with Nattokinase given its potential to prevent blood clot formation and break down blood clots. To date, all studies evaluating the effects of Nattokinase on the blood clotting pathway in humans have used the same dose. This means that the difference between the lowest dose of Nattokinase needed for beneficial effect and a dose that would be too high and thus present unnecessary risks has not been established.

Given the very limited evidence in human clinical studies of its benefits, the known potential harm of internal bleeding, and the many uncertainties that can only be addressed by further clinical studies, Health Canada is not in a position to issue product licenses for NHPs containing Nattokinase at this time....

______________
Lone paroxysmal vagal atrial fibrillation. Age 62, female, no risk factors. Autonomic instability since severe Paxil withdrawal in 2004, including extreme sensitivity to neuro-active drugs, supplements, foods. Monthly tachycardia started 1/11, happened only at night, during sleep, or when waking, bouts of 5-15 hours. Changed to afib about a year ago, same pattern. Frequency increased over last 6 months, apparently with sensitivity to more triggers. Ablation 6/27/13 by Steven Hao.

Yep.

So basically they are saying, in translation, that despite the fact that large double-blind clinical trials have yet to be done, the small amount of human trial evidence on Nattokinase does, in fact, indicate a noticeable blood thinner effect. However, we are not 100% sure of all the mechanisms for that effect ... but that is less of a negative than it might seem at first blush in comparison to many drugs since the not fully understanding all aspects of how Nattokinase does its noticeable and acknowledged blood thinning effect sounds very similar to around 85% of all pharmaceuticals offered for sale whose modus operandi are also not fully understood.

There have been large numbers of people taking Nattokinase across the world for more than ten years now and many consume a whole host of other herbs and supplements with, as far as I know, no confirmed reports of even associated death from bleed outs or hemorrhagic strokes, much less a directly causal relationship, being tied to either the use of Nattokinase by itself or in combination.

Nevertheless, it would be a good idea to do the kind of in-depth tests that would better define Nattokinase's therapeutic window and characteristics to the degree of the other pharmaceutical blood thinners, but that will never be done as Nattokinase cannot be patented and there is really ZERO interest in doing any thing but a cursory dismissal of the product by not only Big Pharma, as was done in this Canadian report, or by other regulatory agencies like the FDA or even AMA.

The interesting thing in that report though was also their acknowledgment that in all anecdotal and small clinical studies so far there has been no indication of any harm from taking Nattokinase and some evidence of at least a quantifiable and repeatable blood thinner effect though admittedly not as well understood and quantified as we would all prefer.

However, this understandable reticence based on both the economic disincentives as well as resulting lack of large scale placebo controlled clinical trials, does not imply that Nattokinase is ineffective or totally worthless for the intended purpose.

It does mean that the person will need to be more comfortable with a greater degree of uncertainty when considering including Nattokinase as part of a natural regime of blood thinning effect, than say with Coumadin or especially the NOAC drugs all of which we all know certainly can kill you in a number of real world circumstances as well as provide some more measurable degree of stroke risk protection when used properly for the right patient.

Just keep in mind too there is rarely a truly free lunch in this world and there is a long laundry list of drugs that passed rigorous clinical trials with mountains of convincing data during the efforts to get the drugs FDA approved only to find out once they are in the wild that said drugs were far more dangerous than first assumed and quite a few have had to either be removed from the market or given restrictive black box warnings as a result.

In addition, even the various blood thinning agents themselves are showing some added caveats now that they have been in the wild for some time.

The moral of the story is that while I would still recommend the vast majority of people that have a defined and serious risk of ischemic stroke or TIA to take one of the three major AC drugs of Eliquis, Xeralto or Coumadin, For those willing to do all the due diligence and proper testing required and who have a more run of the mill AFIB related stroke risk from paroxysmal AFIB, I would not try to dissuade such a person from including a proper dosage and form of Nattokinase (100mg Cardiokinase 3x a day) along with enough Omega 3 oils to push anti-platelet aggregation profiles to around 40% above the reference range and insure good whole blood viscosity readings to then go this route if they are wiling to be disciplined in their testing protocol.

Very few people will have the demeanor, mind set and discipline to follow through with all of that so its still a small minority I would even suggest this too. The vast majority are likely better off just sticking with the drugs or maybe better yet going for a Lariat or Watchman.

Nattokinase can help for sure as part of such a program, but you need to be the right kind of patient without serious risk of serious strokes all the time to even consider going that route and have just the right mind set as well.

Shannon



Edited 1 time(s). Last edit at 11/10/2013 11:15AM by Shannon.

Nattokinase reduces fibrinogen levels that contribute to thick, sticky blood that has the propensity to form clots. It does not work on the clotting mechanism, itself.

If inflammation is the driver of thick, sticky blood, then the contributors to the inflammation need to be addressed in that individual. For that reason, the producers of Flite Tabs included the antiinflammatory, pycnogenol, in their formulation of a nattokinase product...which was tested for efficacy on long-haul flights where deep vein thrombosis was the target.

I agree with Shannon in that Very few people will have the demeanor, mind set and discipline to follow through with all of that.

My confidence in a quality NK product such as CardioKinase remains high since nattokinase did dissolve the clot in my LAA detected on the spiral CT scan post ablation and after I was off warfarin. As a result of that success and because aging tends to increase stroke/clot risk, I continue using NK on a daily basis 10 years post ablation.

Since I work diligently to monitor regularly all of the risk markers for thick, sticky blood, I am comfortable using Nattokinase. It's my personal choice based on the clinical successes of those practitioners using nattokinase in their practices rather than Rx blood thinners.

But, history shows that when something 'natural' is highly effective, those with the bottom line agenda (Big Pharma) continue to downplay the benefits.

Jackie


Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial.

M R Cesarone, G Belcaro, A N Nicolaides, A Ricci, G Geroulakos, E Ippolito, R Brandolini, G Vinciguerra, M Dugall, M Griffin, I Ruffini, G Acerbi, M Corsi, N H Riordan, S Stuard, P Bavera, A Di Renzo, J Kenyon, B M Errichi
Department of Biomedical Sciences, Irvine2 Vascular Lab, G D'Annunzio University, San Valentino Vascular Screening Project (Pe), Pescara, Italy.
Angiology (Impact Factor: 1.51). 01/2003; 54(5):531-9. DOI:10.1177/000331970305400502

ABSTRACT The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several

ABSTRACT The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects.

A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of prophylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 of 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender, and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 thrombotic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p < 0.05). Events were asymptomatic.

In conclusion, Flite Tabs were effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights

PMID:14565628[PubMed - indexed for MEDLINE]

Jackie,

You may wish to add this to your evidence base re. nattokinase.
[www.afibbers.com]

Hans

Friends,

I'm hearing a lot about Cardiokinase. Is it sufficiently better than the NSK-SD variety to justify the extra cost? I'm taking the Nutricology NattoZyme 100mg/2000 FU caps, with 180 selling for $61 at iHerb. The cheapest price for Cardiokinase I've found is $59 for 90 caps, 25 IU, which I read is = 2500 FU. Is the cost difference worth it?

Thanks for any advice.

--Lance

My takeaway from the Canadian government decision is that although evidence on nattokinase indicates benefit, there is no guidance whatsoever regarding the effective dosage to bring it up to the reliability of Eliquis, Xeralto or Coumadin (or even aspirin) for stroke prevention.

Effective dosage of nattokinase is, in fact, what many here have been struggling with. No one knows what's too much or too little.

As for Cardiokinase: With my insurance, a month's worth of Xarelto costs $70 -- roughly the same price.

______________
Lone paroxysmal vagal atrial fibrillation. Age 62, female, no risk factors. Autonomic instability since severe Paxil withdrawal in 2004, including extreme sensitivity to neuro-active drugs, supplements, foods. Monthly tachycardia started 1/11, happened only at night, during sleep, or when waking, bouts of 5-15 hours. Changed to afib about a year ago, same pattern. Frequency increased over last 6 months, apparently with sensitivity to more triggers. Ablation 6/27/13 by Steven Hao.

Shannon Wrote:
-------------------------------------------------------
> There have been large numbers of people taking
> Nattokinase across the world for more than ten
> years now and many consume a whole host of other
> herbs and supplements with, as far as I know, no
> confirmed reports of even associated death from
> bleed outs or hemorrhagic strokes, much less a
> directly causal relationship, being tied to either
> the use of Nattokinase by itself or in
> combination.

Shannon, I don't believe there are any stats on strokes in this population.

>
> However, this understandable reticence based on
> both the economic disincentives as well as
> resulting lack of large scale placebo controlled
> clinical trials, does not imply that Nattokinase
> is ineffective or totally worthless for the
> intended purpose.
>

True, absence of evidence does not mean it there's no beneficial effect. It also does not mean there is a beneficial effect.

> ....For those willing to
> do all the due diligence and proper testing
> required and who have a more run of the mill AFIB
> related stroke risk from paroxysmal AFIB, I would
> not try to dissuade such a person from including a
> proper dosage and form of Nattokinase (100mg
> Cardiokinase 3x a day) along with enough Omega 3
> oils to push anti-platelet aggregation profiles to
> around 40% above the reference range and insure
> good whole blood viscosity readings to then go
> this route if they are wiling to be disciplined in
> their testing protocol.

What is the documented relationship between "anti-platelet aggregation profiles to around 40% above the reference range" and "good whole blood viscosity readings" to stroke prevention in paroxysmal afib? What is the schedule for blood testing of this sort? Is this a service one can expect most cardiologists to offer?

______________
Lone paroxysmal vagal atrial fibrillation. Age 62, female, no risk factors. Autonomic instability since severe Paxil withdrawal in 2004, including extreme sensitivity to neuro-active drugs, supplements, foods. Monthly tachycardia started 1/11, happened only at night, during sleep, or when waking, bouts of 5-15 hours. Changed to afib about a year ago, same pattern. Frequency increased over last 6 months, apparently with sensitivity to more triggers. Ablation 6/27/13 by Steven Hao.

Iatrogenia,

The bulk of my information and experience with Nattokinase comes from quite a few in depth conversation with top functional medicine MDs, not only those I work with as a consultant for some of their patients, but also those well known MDs Ive had the opportunity to meet and get to know at the over 15 large medical conferences Ive attended to date in which these subjects are highlighted and discussed.

Hans posted an interesting study about Natto's potential anti-coagulate effects earlier in this thread. But having spoken at length to Jonathan Wright, Ralph Holsworth and quite a few others who have vast practical clinical experience with using Nattokinase and other such agents in an effort to improve blood viscosity and reduce heart disease and stroke risks, Ive been impressed by the scope of their own research and results.

Taking a serum platelet-aggregation profile readings ( usually containing between 7 and 9 separate platelet values) and applying a rule of thumb target for +40% above the upper end of those individual reference ranges as a goal for Omega 3 titration, was from the original work of these doctors and is not yet published in the formal literature. However, the protocol was derived, in large part, from applying principles learned from previous studies on platelet aggregation and is based on solid practical and experiential grounds.

As noted previousy, you are not likely to find the kind of large scale research support, as yet and maybe never, for implementing such a protocol and I purposefully did not spell out all the details for that reason, as I don't want to encourage people to just give this kind of thing ' a whirl' without having the real commitment to following through with and learning all about how this would work in conjuction with one of these MDs who have so much hands on experience in managing such cases.

For most people, just sticking with the drugs will give them the kind of reasonable reassurance they are looking for and that is fine. I trust that those who really want to peal back the layers of the onion in more depth will do so from their own initiative and can PM me if they wish a few more tips on where to start.

I just feel it is better overall for the vast majority who will not have the kind of interest to fully and successfully pursue such a cutting-edge adventure, and who do have a serious on-going risk for stroke, to just stick with Coumadin or the NOACs that their EPs and Cardios are familiar with and leave it at that. That is why, I just meant this other alternative or co-existing approach more briefly and in broad outlines, while making it clear that I am not advocating people dump their Coumadin and only add Nattokinase and Fish oil by any means if they have a well defined risk factor for embolic stroke.

Shannon



Edited 1 time(s). Last edit at 11/16/2013 02:52PM by Shannon.

Thanks, Shannon.

It seems the protocol you've worked out regarding nattokinase dosing depends on working with a doctor who is at least cooperative and interested. Finding such a doctor to manage the monitoring may be very difficult.

I asked Peter Hui, a young and very prominent cardiologist in San Francisco, about this. There's not enough documentation on nattokinase for him to be interested.

Without such monitoring, taking nattokinase for anticoagulation is a shot in the dark that is likely to be a waste of money.

PS I have been unable to find any substantiation that fish oil is an anticoagulant. I believe it has many health benefits and everyone should be taking it to compensate for omega-3 dietary deficiencies, but I think it's reputation as a blood thinner is one of those medical rumors.

______________
Lone paroxysmal vagal atrial fibrillation. Age 62, female, no risk factors. Autonomic instability since severe Paxil withdrawal in 2004, including extreme sensitivity to neuro-active drugs, supplements, foods. Monthly tachycardia started 1/11, happened only at night, during sleep, or when waking, bouts of 5-15 hours. Changed to afib about a year ago, same pattern. Frequency increased over last 6 months, apparently with sensitivity to more triggers. Ablation 6/27/13 by Steven Hao.

Iatrogenia... In functional medicine circles, they talk about keeping blood platelets 'slippery' with Omega 3 fish oils so they are less likely to clump or aggregate. The same property comes with magnesium supplements... helps blood platelets to be less likely to aggregate. It's not the same as something that interferes with the clotting mechanism.

With the nattokinase where the function is to lower the fibrin levels in the blood and reduce viscosity, that's yet another method of helping to prevent thick, sticky blood.

You are not likely to find cardiologists who understand the properties of Nattokinase or even be inclined to want to recommend it because it is not considered Standard of Care. The doctors Shannon mentions, Holsworth and Wright, have been using the natural approaches in their practices for well over 20 years and rely on their hands on experience. You can add Garry Gordon, MD, to that list as he has used a similar natural substance, Lumbrokinase (Boluoke) for nearly 30 years on his heart patients and says he has yet to have anyone have a TIA, stroke, or MI. The Functional Medicine type practitioners are comfortable with the efficacy of these fibrinolytic enzymes. But don't hold your breath waiting for Big Pharma or conventional medicine to prescribe as routine. No money in it for them.

When I decided to use nattokinase because I could not tolerate warfarin, I did so without the aproval of my cardiologist. I did have to use warfarin for the ablation procedure but went off that quickly and back on NK and decided to use it permanently and 10 years later, I'm still using NK along with serrapeptase to maintain a healthy blood viscosity. It's a personal decision that is backed up by my FM MD and by now there is enough evidence from practical use that indicates it has merit.... but will you find study after study showing efficacy?... No, because of the cost to do so. There are a few small studies that do support efficacy.

Jackie

Iatrogenia,

FIsh oil and anticoagulation is very dose dependent. The typical doses used in most Omega 3 studies are far too low for a significant AC effect. Just look at anecdotal long term Eskimo histories among those tribes that often get excessive doses ( in the ten grams plus range) of Omega 3s from the fatty seals. whales and other cold water fish that is their staple diet. In addition to having very little CVD, they often also have a excess of hemorrhagic strokes or bleeding issues from getting too much Omega 3 (i.e. proof of its anti-coagulation effect at a given dose)

The happy medium is between 4 and 7 grams ( depending on the quality and Omega 3 EPA/DHA percentage) for most anticoagulant effects to be noticed but then also stays within a healthy range with limited risk of excess bleeding.

You wont find a lot of long term randomized controlled studies at 7 grams a day in the typical literature.

And yes, you are right and as I mentioned in my discussions on the matter above. Using Nattokinase and Omega 3 for serious stroke risk patients should only be done with the close guidance of a very savvy and experienced MD in using this agent, either with or without also including some pharmaceutical aids as well.

Shannon

I went to my doctor with concerns about my blood condition, although I don't have any proof of problems other than a high lp(a), and strangely a low LDL. My doctor is quite progressive with integrative medicine. She suggested first of all that I relax and let my body heal as I am early in the post ablation process.

Instead of Nattokinase I was sold quite an expensive enzyme product called Neprinol. It contains a "proprietary blend" of Serrapeptase, Bromelain, Papain and Lipaise along with a Protease Blend derived from Serratia B. Subtillis and A. oryzae along with Amla, Rutin and Curcumin, which is all Greek to me.

It was this product that promoted a previous thread of mine asking "do enzyme products risk diminishing the ablation scars".

Are there any thoughts about the effectiveness of this blended product??
Ron

It sounds like a digestive enzyme supplement.

______________
Lone paroxysmal vagal atrial fibrillation. Age 62, female, no risk factors. Autonomic instability since severe Paxil withdrawal in 2004, including extreme sensitivity to neuro-active drugs, supplements, foods. Monthly tachycardia started 1/11, happened only at night, during sleep, or when waking, bouts of 5-15 hours. Changed to afib about a year ago, same pattern. Frequency increased over last 6 months, apparently with sensitivity to more triggers. Ablation 6/27/13 by Steven Hao.

It says on the bottle "These enzymes were specifically formulated to support a healthy inflammatory response and defend the body from the damaging effects of fibrin. As fibrin accumulates within the bloodstream, it may impair circulatory health and amplify blood viscosity. Neprinol can help maintain normal fibrin, blood viscosity and joint health.".

Any thoughts would be appreciated.
Ron

They could be lying.

______________
Lone paroxysmal vagal atrial fibrillation. Age 62, female, no risk factors. Autonomic instability since severe Paxil withdrawal in 2004, including extreme sensitivity to neuro-active drugs, supplements, foods. Monthly tachycardia started 1/11, happened only at night, during sleep, or when waking, bouts of 5-15 hours. Changed to afib about a year ago, same pattern. Frequency increased over last 6 months, apparently with sensitivity to more triggers. Ablation 6/27/13 by Steven Hao.

Ron - Neprinol has been around for a long time. I recall delving into that when I was initially researching nattokinase over 10 years ago. As a combo enzyme product, it works to help reduce inflammation and has some fibrinolytic properties.

What is it that you are targeting? If it's to lower fibrinogen and keep your blood viscosity in the lower, acceptable range, then you would be better served with CardioKinase. There is no way to determine from the labeling of Neprinol exactly what dose of nattokinase is delivered in each capsule or if it's the improved version. If you are just looking for an overall antiinflammatory that has some fibrinolytic activity, Neprinol is certainly a good broad spectrum product.

Jackie

Jackie what I am looking for is collaboration with my doctor. I am early in the quest and when I mentioned Nattokinase, she recommended Neprinol. I don't have a good knowledge base of what is going on with my blood, but want to cooperate with her if it makes sense, as she is the gateway to whatever tests I request, plus any meds, and was very helpful in coordinating things with Bordeaux. Cardio kinase sounds like the best, but I think I need to talk to my doctor about more definite tests so I am not chasing ghosts.
Ron

WHEN I REJECTED THE RAT POISON AND DECIDED TO SOMETHING LESS TOXIC I USED NATTOKINEASE FOR A WHILE AND EVEN STOPPED USING THAT. IT IS MY BELIEF IT IS A MUCH BETTER WAY TO THIN BLOOD THAN THE RAT POISON MDS DISH OUT CALLED COUMIDEN AKA WARFIN. NOW OF COURSE ON TV THEY ARE SELLING A BRAND NEW DRUG FOR THE CONDITION. A RAW FOOD LIFE STYLE THINS THE BLOOD WITH OUT THE NEED FOR LIFE DESTROYING DRUGS. IF NATTOKINEASE INTERFERS WITH THE SALES OF DRUGS OF COURSE THE DRUG COMPANIES ARE GOING TO DO WHAT THEY CAN TO ELIMINATE OR DISCOURAGE ANYTHING OTHER THAN DRUGS. THATS THE WAY IT IS IN THE CORPORATE EMPIRES OF THE US AND CANADA. THE GOVERNMENT WORKS FOR THE CORPORATIONS AND ITS THE JOB OF GOVERNMENT TO MAKE THOSE CORPORATIONS WEALTHY AT THE EXPENSE OF THE WORKER BEES.