Nattokinase and Reversal of Atherosclerotic Lesions

Atherosclerosis is one of the great killers. Fatty deposits form in blood vessels walls, narrowing and weakening the vessels. Eventually something ruptures, and the result is a stroke or heart attack, but even absent that the condition can narrow vessels sufficiently to cause fatal coronary artery disease. Even with modern medicine, the condition is inexorable: the toolkit doesn't yet include a way to more than slightly reverse the buildup of these plaques, and medical professionals must focus on ways to incrementally slow the progression of atherosclerosis rather than delivering any true cure.

One of the side-effects of starting a company, Repair Biotechnologies, that is working on a way to reverse atherosclerotic plaque is that I've been doing a great deal more reading on the topic of atherosclerosis than I would otherwise have done in the course of writing Fight Aging! Thus I turn up interesting items from the past few years that I missed at the time because I lacked the context to understand why they were worthy of notice, or just didn't have the sort of focus on atherosclerosis that I have at the moment. The papers I'll share today fall into this category, providing evidence for nattokinase, a very simple and readily available supplement, to have a surprisingly large effect on atherosclerotic lesions in humans. After six months of treatment, a third of the lesions were removed.

A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia

All enrolled patients were from the Out-Patient Clinic of the Department of TCM at the 3rd Affiliated Hospital of Sun Yat-sen University. Using randomised picking method, all patients were randomly assigned to one of two groups, nattokinase (NK) and statin (ST) group. NK Group-patients were given NK at a daily dose of 6000 FU and ST Group-patients were treated with statin (simvastatin 20 mg) daily. The treatment course was 26 weeks. Common carotid artery intima media thickness (CCA-IMT), carotid plaque size and blood lipid profile of the patients were measured before and after treatment.

A total of 82 patients were enrolled in the study and 76 patients completed the study. Following the treatments for 26 weeks, there was a significant reduction in CCA-IMT and carotid plaque size in both groups compared with the baseline before treatment. The carotid plaque size and CCA-IMT reduced from 0.25±0.12cm2 to 0.16±0.10cm2 and from 1.13±0.12mm to 1.01±0.11mm, repectively. The reduction in the NK group was significantly profound, a 36.6% reduction in plaque size in NK group versus 11.5% change in ST group. Both treatments reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG).

Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases

Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in cardiovascular disease mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to cardiovascular disease.

This effect size on atherosclerotic lesions is big enough to be suspicious, given that nattokinase is a supplement in common use, and the dose used is not outrageously large. We seem to be seeing a lot of that sort of thing these days, however; sometimes significance goes unnoticed, but equally sometimes it is an issue with the study that will be corrected later. It is hard to tell which without meaningful further effort. Does bisphosphonate treatment actually extend life expectancy by five years, and did this really did go unnoticed despite its widespread use in older people? Is fisetin actually a significantly effective senolytic compound in humans despite being widely used; did the very high senolytic dose in comparison to the usual supplement dose successful hide this property? How did nearly twenty years of earnest development and use of the chemotherapeutic dasatinib go past without anyone noticing that it killed enough senescent cells to improve health and measures of aging in mice and people? And so forth.

Over the past few decades, hundreds of millions of dollars (at the very least) have been spent on clinical trials to try to reverse atherosclerosis - to give existing repair systems in the body sufficient breathing space or increased capacity, allowing them to break down the fatty deposits that form in blood vessels. The sponsors of any of those trials would have been ecstatic to find a reliable reversal of atherosclerotic plaque that was half the size of that noted in the nattokinase trial here. One might take a look at a 2012 review paper that surveys the degree to which treatments at the time could achieve the goal of reversing atherosclerosis. A reversal of 15-20% in an unreliable fraction of patients was about the best that could be done. Most approaches were considerably less effective than that. Not a lot has changed in this high level picture since then.

At present the dominant approach to treatment of atherosclerosis is reduction of blood cholesterol, the cholesterol attached to LDL particles, or LDL-C. Statins are the long-standing approach, and are now being joined by even more effective treatments such as PCSK9 inhibitors. This slows down atherosclerosis by (a) lowering overall cholesterol, and thus freeing up some fraction of the macrophage cells that would otherwise have had to shovel it out of blood vessel walls, but more importantly (b) lowering oxidized cholesterol, which is very damaging to macrophages. When considering atherosclerosis and its treatments it is important to consider macrophages: they are drawn to the fatty lesions, and their task once there is to mine cholesterol from the lesion, ingest it, and hand it off to HDL particles that carry it back to the liver for excretion. This is called reverse cholesterol transport.

Atherosclerosis exists because macrophages become overwhelmed, mostly by oxidized cholesterol, but also by sheer volume of cholesterol, or by an overly inflammatory environment. They become agitated, call for help, become foam cells (some of which become senescent, causing further issues) or die. Most of a plaque is made up of the debris of dead macrophages, and the plaque itself is a self-expanding disaster area that calls ever more macrophages to their doom. Reducing the LDL-C slows down this feedback loop, but it cannot do much for existing plaques. There is some regression (the aforementioned 15-20% at best) because macrophages are given some breathing room, but plaques continue to grow at the new slower pace, and people continue to die.

There has been a considerable amount of work undertaken over the years on alternatives to lowering LDL-C. Researchers have tried all sorts of ways to improve the ability of macrophages to mine cholesterol and send it back to the liver. They have tried increased numbers of HDL particles (which are formed from APOA1 protein). They have tried altered forms of APOA1 found in some human populations that are associated with lower levels of atherosclerosis. They have tried the introduction of artificial HDL particles to swell the numbers. They have tried upregulation of the ABCA1 and ABCG1 proteins that perform the actual handoff of cholesterol molecules to APOA1. There is more in the same vein.

All of these things work pretty well in mice; the current best approaches produce 50% reversion of atherosclerotic lesions in animal studies. Yet all of those tried in humans, meaning the HDL and APOA1 approaches, have failed miserably in clinical trials. What this means is that there is something that the research community doesn't yet understand in the low-level detailed differences between human and mouse reverse cholesterol transport. That is a big roadblock for anyone turning up to propose some form of enhanced cholesterol transport as a therapy, even if intending to try one of the varied effective-in-mice approaches that hasn't yet been trialed in humans.

In this context, one can see that evidence for a common supplement to manage 36% reversion of lesions in humans is both welcome and jarring. It will certainly have to be replicated before many researchers in the LDL-C-focused side of the scientific community are likely to take it all that seriously. Any simple, easily obtained improvement should be welcome. Nonetheless, it is still only reversion by a third. The disease will still progress, and will still kill people. The research community has to do better than this.


"Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation."

"PJ consumption resulted in a significant IMT reduction, by up to 30%, after 1 year"

Posted by: Lee at January 15th, 2019 4:48 PM

Another question to ask is why if a treatment is good at reducing the plaque by 50% it doesn't go to complete elimination ?

And apparently our mouse model is completely unrealistic. If it takes years, if not decades for the foam cells to calcify and grow the plaque how can we model it with mice that are a few months old ?

Posted by: cuberat at January 15th, 2019 5:12 PM

was there a placebo control ?

Posted by: cuberat at January 15th, 2019 5:14 PM

I don't think so.

Posted by: Lee at January 15th, 2019 5:48 PM

@Cuberat: Not as bad as Alzheimer's mice, but yes, you have to pay some attention to the details of the model in terms of what the plaques look like. You don't get the same distribution of plaque maturity and structure as in humans. There are various different models, some of which are supposedly better than others from that perspective.

Posted by: Reason at January 15th, 2019 6:05 PM

"Updating a 12-Year Experience With Arrest and Reversal Therapy for Coronary Heart Disease (An Overdue Requiem for Palliative Cardiology)"

"They agreed to follow a plant-based diet with <10% of calories derived from fat. They were asked to eliminate oil, dairy products (except skim milk and no-fat yogurt), fish, fowl, and meat. They were encouraged to eat grains, legumes, lentils, vegetables, and fruit. Cholesterol-lowering medication was individualized. The only goal was to achieve and maintain a total serum cholesterol of <150 mg/dl."

"Adherent patients have experienced no extension of clinical disease, no coronary events, and no interventions. This finding is all the more compelling when we consider that the original compliant 18 participants experienced 49 coronary events in the 8 years before the study."

Posted by: Lee at January 15th, 2019 6:19 PM

It seems likely to me that the macrophages in plaque are there because they are just trying to do their job of fighting infection.
Nattokinase and other interventions may have limited effectiveness because the infection has not been resolved.

"Human oral, gut, and plaque microbiota in patients with atherosclerosis"

"We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority."

"Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis."

Posted by: Lee at January 16th, 2019 8:23 AM

"The presence of biofilm structures in atherosclerotic plaques of arteries from legs amputated as a complication of diabetic foot ulcers."

"While the presence of bacterial biofilm structures in atherosclerotic plaque does not prove that biofilm is the proximate cause of atherosclerosis, it could contribute to the persistent inflammation associated with it. Second, the synergistic relationship between the atherosclerotic infection and the diabetic foot ulcer may ultimately contribute to higher amputation rates in diabetics."

Posted by: Lee at January 16th, 2019 8:43 AM

So not all supplements are snake oil? Interesting to see your opinions evolve. I eat natto regularly; I understand why some would prefer to get the active constituents in natto in supplement form (nattokinase, spermidine, K2, PQQ), as it is an acquired taste (I enjoy it with hot mustard and a bit of tamari). Also, for therapeutic use (as opposed to prevention) it is necessary to know the exact dose, and possibly get a much a higher dose than is available through a normal serving size.

Amazon is likely doing quite a bit of data mining on supplements in terms of customer purchase patterns and reviews, and now added to that all their PillPack Rx drug and supplement data -- it will be interesting to see how they apply the gleanings to their own brands (Amazon Elements and Solimo). My guess is they will learn a great deal about the efficacy of supplements/Rx drugs and supplement/Rx drug combinations.

While various lifestyle / DIY interventions are helpful for maintaining health and possibly achieving LEV, most of your readers ought agree, though, that for radical life extension SENS is necessary. Reversing hypothalamic aging, for example, will require likely both the control of hypothalamic inflammation and stem cell replenishment.

Posted by: CD at January 16th, 2019 11:45 AM

Hi CD! Just a 2 cents.

Currently, it'S true that lifestyle is large factor to maintain health, but there is not much possible for achieving LEV (I am of of opinion that currently there is nothing that can do LEV and that will be for a long time until) SENS could change, though even there, color me skeptic it is not snake oil and founded in biogerontology; but, biogerontology is more complicated than we thought and harder to decipher too. Until we see epigenetic changes and research, I am not sure anything is yet to make LEV (neither hypothalamic inflammation or stem cell replenishment, these are secondaries and have been shown not to reverse aging but slow it (it makes more than that); that'S because aging is more complicated and on many levels, the major one is genetic, epigenetics mostly that are a vicious circle with damages, that lead to more inflammation/deleterious gene activation (antagonistoc pleiotropy with age) and as such one day it'S over. Reversing hypothalamaic aging is only feasible if damages and epigenetic changes happen, otherwise it'S impossible. Many new studies show that why people liver longer is because they postpone the aging phases later, as such 'remain young' (this is epiclock signature), when you remain biologically young you level of mortality is much lower; and if you remain so, mortality does not rise (which equals LEV/eternal life). Just a 2 cents.

PS: having atherosclerotis lesions, I took nattokinase and it was quite helpful, it is a powerful anti-fibrotic and I likened it to other peptidases I took; but, in the end, it is only through continuous intake; nothing is good at the start (it's like trying to stop a 50m/h moving 150-wagon train for a total a 100,000 tons of momentum, impossible); it takes years of consuming that (this trial shows great improvement but it depends on the severity and events that happened before ('and the rest'/what you eat besides natto/do you take cholesterol food...etc), like if that person had cardio vascular event and clot did happen (as it did with me and destroyed my pulmonary artery and nearly died there from artery blood blockage, when it happened by ischemia when it lodged itself after my plaques ruptured). I feel I had more improvements from vitamins and whatnot, and by cutting food out then food itself saving me; it goes to show that food is medicine but not some magic either; it takes time to get healthy again changing lifestlye after a near death event. Sorry for typos.

Posted by: CANanonymity at January 16th, 2019 2:51 PM

PPS: I would like to add, that LEV is only possible if you remain young, it's impossible if you age (that's obvious, obviously), you would absolutely have to reverse to young state - by that, I mean, that LEV/eternal life can only be achieved by bringing mortality 'rising with age' to near-0, as such, by staying in a young state do you make intrinsic mortality nill ('age-caused') with time (excluding extrinsic factors like getting in accidents and whatnot). No therapy now or in the future would ever make LEV if it cannot keep a body in young state/phenotype/signature (this was demonstrated with CR, CR is one of the few life extending therapy, by reducing calorie there is damage accrual reduction and removal of junk (proteasome), methionine content reduction, NRF2/anti-ox improv, but, especially (orchestrating all this gene), reversal (just tempoarily) and slowing of clock aging; showing that CR is all under this gene control and if CR can 'rejuvenate you' by slowing aging of your tissues, and CR did reduce epigenetic aging rate/and even lowered a CR does not stop aging neither. Showing that to be able to live 500 years or LEV, only a young body will ever reach that (it's also visible in long lived bowhead whales, clams, greenland sharks, all live centuries and keep young 'slow growing' bodies (low mortality, young state, no death/post-pone it much later and post-pone 'aging/antagonistic pleitroypi entry' phase after puberty/reproduction, thus extreme lifespan).

Posted by: CANanonymity at January 16th, 2019 3:24 PM

PPPS: I will be sold on 'old people' can live forever only until they can make more than just iPSCs or centenarian cells be reverted to clock age 0, if they can do it in all cells, than I would definitely say that old people could reach LEV just as much; for, they would not 'stay old' they would revert to their young(er) state.

Posted by: CANanonymity at January 16th, 2019 3:27 PM

PPPPS: Last one, not doing 'ageism' or being against them or something, I really respect/admire old people (and that they reached this venerable age is achievement, like super-centenarians, they are survivors, and life survivors'/death post-poners, health/life/longevity is a gift we must protect and be graceful for) and if they get the therapy, it's only normal, time is amiss at an old age; thus, I more than understand/very agree that we need to extend their lives and improve their health, immediately and above all, they require immediate help, time is running out. Younger folks have more time left, but also matter of course (I'm one among millions who are in this 'early phase - let's do something while still young/for later will be better/still around, if act now'). Just a 2 cents.

Posted by: CANanonymity at January 16th, 2019 3:43 PM

If you look at the scale of new ideas coming out today in anti-aging compared to literally 2 years ago it is a very noticeable change. And we are at the 'year 0' of this opportunity. The industry is at the point of the first companies getting startup funding.

Posted by: aa3 at January 16th, 2019 7:41 PM

layman question here:

My reading of the article, "Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases," is essentially that it seems to very effective in reducing atherosclerosis via oral administration, but it's not clear if it is bioavailable.

How could it not be bioavailable if is is so effective?

Posted by: TysonsCorner at January 17th, 2019 3:47 AM

"How could it not be bioavailable if is is so effective?"

Perhaps by altering the gut microbiome to reduce the number of bacteria that contribute to atherosclerosis.

Posted by: Lee at January 17th, 2019 7:03 AM

I take nattokinase among some other things. It has a low price point and 6000 FU a day is what was used in the study posted originally by Reason. There is a lot of snake oil in the supplement industry but some compounds do have merit, the devil is in the details and assessing the journal publications.

Posted by: Steve Hill at January 17th, 2019 10:45 AM

Btw, excuse my ignorance but what is the FU unit ?

Posted by: cuberat at January 17th, 2019 10:59 AM

Keep the analysis coming on atherosclerosis/CVD! That's public enemy number one. Heart attack and stroke together far outweigh the next killer, cancer. And everyone in the world is working on cancer -- not enough new approaches to CVD and the metabolic issues that drive CVD.

Posted by: Sebastian A at January 20th, 2019 2:18 PM

The difference between the mouse model and humans? One big one is that mice produce ascorbic acid whereas humans do not.

I would love to see the Pauling protocol tested for atheroclerosis but I guess that's fallen by the wayside. It's 3,000 mg of lysine and 3,000 mg of vitamin C (ascorbic acid). In his testing on guinea pigs (like humans they are one of 4 species on earth that do not produce their own ascorbic acid) plaques were reduced 25% in 5 weeks. But then, Linus Pauling was a freak, right?

Here's a few links ..

Posted by: John Whitling at January 21st, 2019 9:26 AM

"The carotid plaque size and CCA-IMT reduced from 0.25±0.12cm2 to 0.16±0.10cm2 and from 1.13±0.12mm to 1.01±0.11mm, repectively. The reduction in the NK group was significantly profound, a 36.6% reduction in plaque size in NK group versus 11.5% change in ST group."

Why is the beginning plaque volume 0.25 so low in the NK group, while the initial plaque volume in the statin group is what you would expect in people in their 60's and older? 0.25 plaque volume is, I think what you might expect in a person 25-30.The initial plaque volumes of the 2 groups should be about the same, if people close in age were randomly chosen to be in each group. I can't make sense of this.

Posted by: alan at May 1st, 2019 2:05 PM

Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis."

Posted by: Susan C at May 16th, 2019 7:50 PM

Very interesting. If it really works that wild be huge. And a nice can cow for the Big Pharma. If it doesn't have debilitating side effects it cold be taken periodically by everybody over 40. Huge markets. Huge promises.

Posted by: Cuberat at May 16th, 2019 8:01 PM

A few things that make me look less optimistic. First the mice were a special breed prone to arteriosclerosis. So CD might be just compensating for a broken pathway that is functioning in humans. The mice are not humans and humans have vastly different metabolism . The mice are a convenient to use but a very bad model for the human diseases that take decades to develop.

Posted by: Cuberat at May 16th, 2019 9:11 PM

I did quite a bit of research, then decided to begin taking Nattokinase daily. 2,000 FU's. I am 69 yrs old. Past few years blood pressure creeping up a bit. Also have had thyroid disease most of my life. (hypo) Have been on my Natto for a couple months, and woke up several days ago and had lost the sight in my left eye. Sometime during the night I guess. Have been doing tests all week, had a corroded Doppler, EKG, Echo Cardi and so far all seems well. The Main artery behind the is massively occluded. Have been told not to expect any vision back. Here is my worry and question. Could the Nattokinase have caused this? Could it's "cleaning mechanism" so to speak of caused debris to have lodged in that artery somehow? I stopped my Natto but just don't know what to do. I would like to continue but should I? DESPERATE

Posted by: LINDA OVERSTREET at July 13th, 2019 7:44 PM

-10% (plaque regression)
The Effects of Statin and Niacin on Plaque Stability, Plaque Regression, Inflammation and Oxidative Stress in Patients With Mild to Moderate Coronary Artery Stenosis

As I understand, statins increase matrix metalloproteinase-9, which is bad. Doxycycline suppresses the growth of aortic aneurysms through its inhibition of MMP9.[33]

Doxycycline also decrease risk of cancer and have many other benefits. But I'm not sure, maybe increasing MMP9 it's how statin works to regress plaques. It's all so complicated.

Posted by: Stanislav at July 26th, 2019 1:36 PM

Almost 30%(!!!) plaque regression in 24 month. It's compound containing in grape seed and you can buy it on Amazon (cheap).

Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques

Do not confuse plaque regression and Intima Media Thickness (IMT) regression. Only plaque size really correlate with death from vascular events. For example, Pomegranate juice can decrease IMT by 30% after 1 year (, which is also benefit and impressive, but not comparable with regression in plaques.

Posted by: Stanislav at July 26th, 2019 1:45 PM

I recently sent an email inquiry to the lone principal USC investigator (Howard Neil Hodis) of an ongoing randomized controlled trial (mentioned above) of nattokinase's effects on the progression of atherosclerosis and cognitive decline. Over a week has past and I have not received a response; so I thought I would post my email here in hopes of gathering some interesting responses from and its many viewers. See below:

"Hello, Professor Hodis,

I am an interested follower of your ongoing RCT ( regarding use of nattokinase (NK) for investigating its effects on the progression of atherosclerosis and cognitive decline. I understand that you intend to correlate NK's effects on many different factors (too numerous to list in this brief email) to the above-mentioned conditions. My particular interest probably lies beyond the scope of your investigation, at least at this time, because it (i.e., my interest) involves the projected (eventual) use of NK for its hypothetical protective effects against stroke in people diagnosed with paroxysmal atrial fibrillation.

My suggestion: in your investigation, please include an experiment to test or measure the activity of NK inside the left atrial appendage (LAA) and answer questions such as:
1. Does NK diffuse into the blood inside this compartment at concentration levels comparable to that measured in the main bulk of blood in the body?
2. Does it provide a measurable protective effect against clotting within the LAA?
3. Could your use of "computer image processed B mode ultrasonograms" be adapted to provide the (non-invasive) analyses needed to answer these questions? "

Posted by: Aaron Fried at November 21st, 2019 9:25 PM

Linda, you need to be taking serapeptase along with your nattokinase the two go well together. Restart you nattokinase dose but take it along with 500,000SPU dose daily (30 min before food) and the serapeptase enzyme will help clear the debris leaching out of your plaques, it also removes built up fibrogen which is contributing to your blockages. Try a good brand like Arthur Andrew medical which you can order from iherb not a Chinese one. I did this last year along with a vegan diet and although I lost quite a bit of weight it cleared me right up.

Posted by: Michael Gibbs at December 27th, 2019 12:55 AM

The Hodis trial of NK was supposed to be completed by now. Perhaps he would respond to an inquiry by Reason?

Posted by: Wayne Johnson at January 7th, 2020 7:44 AM

"Nonetheless, it is still only reversion by a third. The disease will still progress, and will still kill people."

Did you find any information using Natto (fermented soybean). The Japanese are the longest living people in the world.
One of the interesting facts about Natto is that it has 1 billion probiotics per gram, and one packet contains about 50 grams. Its also very high in vitamin K2.
The best website I found describing the benifets is
I wonder if Natto is more effective than nattokinase?

Posted by: Colin at July 12th, 2020 1:29 PM

Please say if NATTOSYN. ( douglas) is good for arteriosclerosis. And as I see in posts it's bad for the eyesight🙏Thank you

Posted by: Mena at November 26th, 2020 2:44 PM

I would like to start nattokinase but I got cancer from eating soybean protein isotopes. I have bradycardia.

Posted by: Norma Saenz at March 31st, 2021 1:12 AM

To Linda and to Mena, I do not believe there is any real proof that Nattokinase causes eye problems. Just because there is a one-time association between two events, that does not constitute causation. This idea may be summed up in the Latin phrase, "post hoc ergo propter hoc" (or "after this, therefore because of this"). For more on this, also see: .

Wishing you well.

Posted by: Aaron Fried at March 31st, 2021 4:17 PM


By reading all your comments can I conclude that taking Nattokinase at 6000 FU and Serrepeptase at 500,000 units will clear up and regress some existing plaque ? Do we have clinical evidence as I have suffered a CV event 8 years ago and am on statins and aspirin.
Thanks in advance for your comments

Posted by: Gus Italia at May 21st, 2021 1:22 AM

Wish to know further about reversing artherosclerosis medication availablity

Posted by: Noh at August 21st, 2021 6:44 PM

Life style change and diet

Posted by: Noh at August 21st, 2021 6:46 PM

Here's a link to what looks like the completed Hodis study:

Unfortunately they found no effect on markers of atherosclerosis or blood pressure.

Posted by: steve695 at August 31st, 2021 5:28 PM

1) The full text is in Chinese:
I have failed to translate it to English. Concerns about the reliability of Chinese research may be a factor.

2) I am curious what they say about the mechanism of plaque reduction. Can someone read Chinese?

3) NAPS study: Relatively healthy people were studied, which was disappointing. Also, no reduction in CIMT noted, in contrast to earlier study. They did not look at plaque reduction it seems. Was apparently safe in this healthy cohort at 2000FU.

4) The anecdote from Linda of going blind is worth thinking about. I heard one anecdote years ago of a stroke allegedly from serrapeptase. Perhaps enzymes could themselves degrade something in the fibrous caps of plaques, causing it to rupture, actually causing a clot? Or could they dislodge a preexisting clot? In any case, it is notable that taking nattokinase did not prevent Linda's occlusion or dissolve it in a manner timely enough to avoid a problem. The only eye-specific research on nattokinse I have seen is that it can be used in animal studies to cause vitreous detachment.

5) Anecdote: lumbrokinase gradually dissolved clots in my arm caused by a botched IV therapy.

6) There is one case report of cerebral hemorrhaging from combining 400mg (I think) of nattokinase with aspirin. Probably not a good idea to go combining things.

Posted by: David AuBuchon at April 14th, 2022 4:36 AM

How rapidly would clots from ruptured plaques form? And how rapidly does the body break down clots? Need some order-of-magnitude understanding here.

Posted by: David AuBuchon at April 14th, 2022 4:44 AM

Some research suggests that you need to take K2 if your taking nattokinase. The Natto keeps
dissolving the plaque and could harm arteries. Two weeks duration at most.

Posted by: Keith at May 29th, 2022 8:09 PM

This is all very interesting.
I'm eating a carnivore diet and have no plans of changing that.

I also take 400 mcg of K2, derived from natto, per day and take 4,000 FUs of nattokinase a day which I may increase to 6,000 or 8,000 if my planned CSC scan indicated calcified plaque.

I also have an aortic aneurysm that is only 3.3 cm and has been stable for nine years. I plan on getting a CAC score ASAP. I'm 75.

Posted by: Nevada Smith at December 7th, 2022 9:07 AM

This is all very interesting.
I'm eating a carnivore diet and have no plans of changing that.

I also take 400 mcg of K2, derived from natto, per day and take 4,000 FUs of nattokinase a day which I may increase to 6,000 or 8,000 if my planned CAC scan indicated calcified plaque.

I also have an aortic aneurysm that is only 3.3 cm and has been stable for nine years. I plan on getting a CAC score ASAP. I'm 75.

Posted by: Nevada Smith at December 15th, 2022 7:55 PM

The Hodis study used nattokinase at a dose of 2,000 FU/day. A study by H Chen in 2022 including over 1,000 participants used a larger dose of 10,800FU/day and showed pretty remarkable results, including reductions of TC and TG by ~15%, LDL-C by ~18%, and increased HDL-C by ~15%. Carotid artery plaque was reduced, on average, from ~25mm2 to ~ 16mm2, a 36% reduction. The study duration was a year, which suggests continued use for several years would reduce plaque further. Chen referenced other studies that used 6,000FU and 7,000FU of nattokinase/day, and also reduced lipids and carotid artery plaque. In other words, dosage matters.
Hodis had the audacity to conclude "Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD." Ask a stupid question, get a stupid answer. The 2022 Chen study proved to my satisfaction that dosage, and the quality of the trial design, are pretty darn important.

Posted by: Sherlock57 at February 20th, 2024 12:03 AM
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