I had one of my regular meetings with Doc Davis of Track Your Plaque book and website fame today where he remarked about a patient he encountered that nearly died of a pulmonary embolism after going off prescription anti-thrombotic medicine in favor of nattokinase.
Doc Davis has been a critic of nattokinase and endured the slings and arrows of its promoters and those statistical "n of one" users who swear by it. (Interesting to note that Doc Davis is part Japanese and is not without experience with natto as a food his mother made him eat - childhood trauma perhaps? LOL!).
I was curious enough to take a look at the debate on his blog and do a little of my own research. As most readers of my blog know I am a "numbers" guy. Normally, the ridiculous bloviating and hyperbole I found on some sites pushing nattokinase would be enough to turn me off but just because "bad" people say "good" things about a product does not preclude it from actually being good! On the other hand, there is some pretty damning science against the concept that nattokinase works (the small problem of any protein surviving the gut) as well as common sense that suggests if it did work it may be a dangereous way to self-medicate (at least with a prescription drug like Coumadin you are under supervision by a doctor).
For better or worse I decided to go to my trusted sources at PubMed and look at some of the more recent studies to see if there is anything new that supported casual and chronic oral adminstration of nattokinase to prevent heart disease. Here is what I found in a highly summarized (and editorialized) form so as not to induce boredom (use the links for more info).
Bioproperties of potent nattokinase from Bacillus subtilis YJ1.
http://www.ncbi.nlm.nih.gov/pubmed/20334345
Yup, nattokinase is still fibrinolytic - if it gets into the blood stream.
Purification and Characterization of Nattokinase from Bacillus subtilis Natto B-12
http://www.ncbi.nlm.nih.gov/pubmed/19788184
Now if we could only get this stuff to work orally as a functional food!
Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia
http://www.ncbi.nlm.nih.gov/pubmed/19786378
Nattokinase does not appear to exert its effects (if any) via lipids.
Enhancement of oxidative stability of the subtilisin nattokinase by site-directed mutagenesis expressed in Escherichia coli
http://www.ncbi.nlm.nih.gov/pubmed/19631297
Hey, we are getting closer to at least limiting oxidative degradation - still no panacea.
Purification, immobilization, and characterization of nattokinase on PHB nanoparticles
http://www.ncbi.nlm.nih.gov/pubmed/19608412
Nanoparticles are all the rage these days and may have some utility with stabilizing nattokinase but still no oral in vivo data.
Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects
http://www.ncbi.nlm.nih.gov/pubmed/19358933
Now we're talking - hard data with oral nattokinase in humans! Unfortunately, this was an open-label, self-controlled sudy with 45 people (15 in each arm). Can you imagine trying to get a prescription drug past the FDA with a study like this? Still, at least SOMETHING for proponents to hang their hats on.
Effects of nattokinase on blood pressure: a randomized, controlled trial
http://www.ncbi.nlm.nih.gov/pubmed/18971533
Hey, hey! More human data and this time randomized, controlled, and with almost twice as many participants as the previous study. Too bad the end point was blood pressure data - but it did show improvement.
Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits
http://www.ncbi.nlm.nih.gov/pubmed/18819862
Reminds me of Judah Folkman's comment when the media overhyped his results and declared he had cured cancer, "If you are a mouse and you have cancer we can take good care of you!" Lucky rabbits!
Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds
http://www.ncbi.nlm.nih.gov/pubmed/18310985
Oh yeah, just when you thought everything was rosy this booger shows up. Just because something is not classified as a drug by the FDA does not mean it is safe for general use. First Doc Davis relates a story about nattokinase putting a patient at risk because id did not bust a clot and now here is someone who "over-busted!"
Nattokinase-promoted tissue plasminogen activator release from human cells
http://www.ncbi.nlm.nih.gov/pubmed/19996631
More geek science. Yeah, if you get it in the blood nattokinase has numerous effects. So do a lot of chemicals!
The fibrinolytic activity of a novel protease derived from a tempeh producing fungus, Fusarium sp. BLB
http://www.ncbi.nlm.nih.gov/pubmed/17827689
Here is an even more powerful natural product. Should everyone abandon nattokinase and rush out to buy tempeh - the next wonder supplement?
Here is what (I think) we know.
1. Nattokinase exhibits lytic effects in vitro.
2. It MAY have some effect taken orally in vivo.
3. If it does work no one knows the mechanism of action for certain. Consider this, maybe it is some component or action OTHER than the lytic effect seen in vitro. Why take the risky components to enjoy the effective components?
4. There is a tiny amount of evidence for nattokinase taken orally but certainly nothing conclusive.
5. There is absolutely NO safety data on it other than small study and anecdotal experience. Remember torcetrapib the wonder HDL drug? I couldn't wait for it to hit the market so I could take it! It did everything Pfizer said it would - then downstream the data showed it killed more people than it saved. No way would nattokinase be FDA approved based on existing HARD data.
It seems what we have in nattokinase is an interesting agent - but nothing more. Since it is unregulated we are all free to experiment (and I experiment plenty). But don't kid yourself - it is nothing more than an experiment with an unknown outcome! "Natural supplement" does not equal "safe" any more than "drug" equals "effective!"
As always, I remain a fan of Informed, Self-directed, Healthcare (ISH). But, stay informed, remain a skeptic, and play safe!
Looking out for your heart health,
HeartHawk
Doc Davis has been a critic of nattokinase and endured the slings and arrows of its promoters and those statistical "n of one" users who swear by it. (Interesting to note that Doc Davis is part Japanese and is not without experience with natto as a food his mother made him eat - childhood trauma perhaps? LOL!).
I was curious enough to take a look at the debate on his blog and do a little of my own research. As most readers of my blog know I am a "numbers" guy. Normally, the ridiculous bloviating and hyperbole I found on some sites pushing nattokinase would be enough to turn me off but just because "bad" people say "good" things about a product does not preclude it from actually being good! On the other hand, there is some pretty damning science against the concept that nattokinase works (the small problem of any protein surviving the gut) as well as common sense that suggests if it did work it may be a dangereous way to self-medicate (at least with a prescription drug like Coumadin you are under supervision by a doctor).
For better or worse I decided to go to my trusted sources at PubMed and look at some of the more recent studies to see if there is anything new that supported casual and chronic oral adminstration of nattokinase to prevent heart disease. Here is what I found in a highly summarized (and editorialized) form so as not to induce boredom (use the links for more info).
Bioproperties of potent nattokinase from Bacillus subtilis YJ1.
http://www.ncbi.nlm.nih.gov/pubmed/20334345
Yup, nattokinase is still fibrinolytic - if it gets into the blood stream.
Purification and Characterization of Nattokinase from Bacillus subtilis Natto B-12
http://www.ncbi.nlm.nih.gov/pubmed/19788184
Now if we could only get this stuff to work orally as a functional food!
Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia
http://www.ncbi.nlm.nih.gov/pubmed/19786378
Nattokinase does not appear to exert its effects (if any) via lipids.
Enhancement of oxidative stability of the subtilisin nattokinase by site-directed mutagenesis expressed in Escherichia coli
http://www.ncbi.nlm.nih.gov/pubmed/19631297
Hey, we are getting closer to at least limiting oxidative degradation - still no panacea.
Purification, immobilization, and characterization of nattokinase on PHB nanoparticles
http://www.ncbi.nlm.nih.gov/pubmed/19608412
Nanoparticles are all the rage these days and may have some utility with stabilizing nattokinase but still no oral in vivo data.
Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects
http://www.ncbi.nlm.nih.gov/pubmed/19358933
Now we're talking - hard data with oral nattokinase in humans! Unfortunately, this was an open-label, self-controlled sudy with 45 people (15 in each arm). Can you imagine trying to get a prescription drug past the FDA with a study like this? Still, at least SOMETHING for proponents to hang their hats on.
Effects of nattokinase on blood pressure: a randomized, controlled trial
http://www.ncbi.nlm.nih.gov/pubmed/18971533
Hey, hey! More human data and this time randomized, controlled, and with almost twice as many participants as the previous study. Too bad the end point was blood pressure data - but it did show improvement.
Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits
http://www.ncbi.nlm.nih.gov/pubmed/18819862
Reminds me of Judah Folkman's comment when the media overhyped his results and declared he had cured cancer, "If you are a mouse and you have cancer we can take good care of you!" Lucky rabbits!
Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds
http://www.ncbi.nlm.nih.gov/pubmed/18310985
Oh yeah, just when you thought everything was rosy this booger shows up. Just because something is not classified as a drug by the FDA does not mean it is safe for general use. First Doc Davis relates a story about nattokinase putting a patient at risk because id did not bust a clot and now here is someone who "over-busted!"
Nattokinase-promoted tissue plasminogen activator release from human cells
http://www.ncbi.nlm.nih.gov/pubmed/19996631
More geek science. Yeah, if you get it in the blood nattokinase has numerous effects. So do a lot of chemicals!
The fibrinolytic activity of a novel protease derived from a tempeh producing fungus, Fusarium sp. BLB
http://www.ncbi.nlm.nih.gov/pubmed/17827689
Here is an even more powerful natural product. Should everyone abandon nattokinase and rush out to buy tempeh - the next wonder supplement?
Here is what (I think) we know.
1. Nattokinase exhibits lytic effects in vitro.
2. It MAY have some effect taken orally in vivo.
3. If it does work no one knows the mechanism of action for certain. Consider this, maybe it is some component or action OTHER than the lytic effect seen in vitro. Why take the risky components to enjoy the effective components?
4. There is a tiny amount of evidence for nattokinase taken orally but certainly nothing conclusive.
5. There is absolutely NO safety data on it other than small study and anecdotal experience. Remember torcetrapib the wonder HDL drug? I couldn't wait for it to hit the market so I could take it! It did everything Pfizer said it would - then downstream the data showed it killed more people than it saved. No way would nattokinase be FDA approved based on existing HARD data.
It seems what we have in nattokinase is an interesting agent - but nothing more. Since it is unregulated we are all free to experiment (and I experiment plenty). But don't kid yourself - it is nothing more than an experiment with an unknown outcome! "Natural supplement" does not equal "safe" any more than "drug" equals "effective!"
As always, I remain a fan of Informed, Self-directed, Healthcare (ISH). But, stay informed, remain a skeptic, and play safe!
Looking out for your heart health,
HeartHawk
