Aspirin vs Nattokinase: Can a Supplement Replace This Drug? (and other questions!)

Hinzugefügt: 2026-04-30

[00:00:00]Hey guys, Dr. Johnston here with another comment response. You guys really had a lot to say about the aspirin video and at Westfield 90 says, "Dr. Ford said that the aspirin antiplatlet effect lasts 5 to seven days. Therefore, once a week or a couple of times a week should be sufficient." Let's dig into this.

[00:00:21]This comes from the idea that aspirin irreversibly makes those platelets not sticky. So once you take the aspirin, the platelets that are circulating in your bloodstream are no longer as reactive and they stay that way for as long as that platelet is circulating. The average lifespan of a platelet in your bloodstream is about 7 to 10 days, give or take on average. So this idea that the effect lasts seven days is based on the average lifespan of that platelet circulating in your bloodstream. But not every platelet is fresh, brand new, and going to last seven days, right? Only about one out of seven uh total percentage, right? 14% give or take is going to be a fresh platelet that will last all seven days.

[00:01:09]The rest of them are proportionally older and will eventually recycle and be replaced by new platelets. If you're not taking the aspirin every day, those new platelets are very sticky again. And so you lose at least 14% 10 to 14% every day as new platelets are formed but uninhibited by aspirin if you're not taking it every day. Now the figure we used to quote people was well if you take it every other day you probably get about 75% of the benefit and that is based on this math that says well by the time you're ready for that next dose you've got about two days worth of platelets that have reformed.

[00:01:51]So 20 to 25% of your platelets are are now sticky again. So about 75% are still inhibited and that's about the benefit.

[00:02:01]If you look into the research a little further, it turns out it's probably not quite that clean. Unfortunately, the effects of aspirin are not linear and not entirely predictable. Uh when they looked at one study in 2009 comparing daily 81 milligram aspirin to every other day 100 milligrams of aspirin, they found it was significantly less than the 75% number. It was closer to 44%.

[00:02:27]So we just don't really know. What I tell my patients is if you tolerate it every day without significant bruising or bleeding, that's probably the easiest. It's also the easiest for compliance because it's just part of your everyday habit and routine. If you are having a lot of side effects from the aspirin, like easy bruising or bleeding, then you can try going down to every other day, depending on why you're taking the aspirin. If you're on it, because it's critically important to keep a fresh stent open or a fresh bypass open, then we have to talk about what the alternatives might be and risks versus benefits. If we're in the primary prevention or primordial prevention world, then obviously we can tolerate a little bit more leeway in the efficacy of our medications. So that goes to show you what the data are about aspirin every day versus once a week. I think once a week is probably not adequate.

[00:03:24]Every other day is a reasonable choice if you're having side effects.

[00:03:28]Otherwise, I think every day is probably your best bet. The last thing I'll say about this is there are some tests that have been used to try to measure the effectiveness of aspirin. I used to use them as well. Verify now is one of them.

[00:03:42]Unfortunately, people have looked at how reliable those tests are and they are all over the place in terms of whether we can really tell whether aspirin is helping you or not. So, people have moved away from testing whether aspirin is is actually helpful for you individually. So you could be offered that test. But right now the best evidence we have is that those tests are not super reliable. So bottom line, if you can take aspirin every day, do it.

[00:04:08]If not, every other day is probably a reasonable choice. But you do get a decrease in the effectiveness by how much? Nobody's quite sure, but if that's what it takes to keep you on it, so be it. Another great question that came up frequently in the comment section is about an Nattokynese. So JK's 1345 asks, "What about nattokynise instead of baby aspirin? It doesn't promote bleeding and is antibrinolytic."

[00:04:34]And again, I get this question a lot, but what you have to understand is nattokinise works very differently than aspirin. Again, the anti-fibbrinolytic properties. So let's step back for a second. How does clotting work? We actually have both a clotting system and a clot breakdown system. So the body likes to balance the clotting and clot breakdown so that we clot when we need to but not more than we need to.

[00:04:59]Fibbronolyis is the breakdown of blood clots and that is where nattokynise has most of its action. There are a couple of lab tests or lab studies in test tubes and petri dishes where they show a little bit of antiplatlet activity for nattokynise but we don't have a lot of evidence for that in patients. So even though you may see it reported in the literature that there is some antiplatlet activity for nattokynise it's not profound. It is certainly not the primary mechanism by which nattokynise exerts its impact. It also has a small anti-coagulant effect. So again in our pro clotting side of things on the body we have platelets which are like a plug and then we have clot which is like a fibbrin based clot that's more like a mesh and we think of those systems differently. So anti-platelet drugs like aspirin or clipidigril or plavix work on inhibiting the platelets.

[00:05:59]anti-coagulant medications like couadin is the OG but now we have eloquis or pixaban revaroxaban or zorelto these actually prevent the mesh network from forming over top of the platelet plug and anti-coagulants are different than antiplatlets so nattokynise has this anti-coagulant property that is very very mild reduces a few components of the clotting cascade in tests but it doesn't drop people to a quote unquote anti-coagulated or blood thinned level.

[00:06:34]And this is why we don't really see a lot of bleeding complications associated with nattokynise administration.

[00:06:42]That being said, the studies on nattokynise are like a fraction of the studies that have been done on aspirin or any of these uh you know medications that we use really regularly. So we don't have a huge amount of data on nattokinise. The dosing for nattokynise is all over the place. It's wildly all over the place. Anywhere from 2,000 FU or fibbrronolytic units up to 12,000 per day is what some people are taking. And we don't have a great sense. But the bottom line is aspirin works by inhibiting platelet aggregation and inhibiting clotting. If nattokynise does not produce a bleeding risk, there is no way it can be an adequate substitute for aspirin in a prevention setting or even in a therapeutic setting. So you know nattokynise is a very interesting compound. You guys have asked me for the deep dive on nattokynise. It is in the works I promise you. But my bottom line is that it is not a replacement for aspirin. We have no data on heart outcomes for people taking nattokinise instead of aspirin. But even just based on our pre-clinical data about what it lowers in the blood and how much it impacts our clotting and the fact that we really haven't seen blood clotting complications and patients who take nattoise, we just don't believe that it's ever going to be an adequate replacement or substitute for aspirin.

[00:08:04]All of my patients who want to be on nattoinise, I do counsel them if they are going to take the higher doses. I do believe eventually we are going to potentially run into some bleeding effects with that. We have a couple of case series in the literature at least one uh hemorrhagic stroke and from a patient who was on nattokynise. So I do believe that if it's effective at all eventually we will see a bigger signal for blood clotting problems with nattokinise. So far, it's not been shown in the literature, but as more and more people take it, especially at the higher doses, I do think that that is something probably coming down the pike for us, and we'll cross that bridge when we get there. So, bottom line, nattokinise is interesting, but no, not a substitute for aspirin. And speaking of hemorrhagic stroke, there was actually a super interesting question from obvious. He says, "Dr. J, I am a 16-year survivor of a hemorrhagic stroke. That's a bleeding related stroke, not a clotting related stroke. My former cardiologist and I were at odds. He wanted me on an aspirin and I wouldn't do it. His reasoning, secondary prevention, and that makes no sense to me since aspirin wouldn't have prevented a bleed in the first place. Do you think my reasoning is sound? Would aspirin regimen as secondary prevention apply to a blame brain bleed? So, I actually looked this up because to me also this was pretty intuitively like, no, we probably shouldn't be on aspirin.

[00:09:23]But I had to ask myself the question. If his cardiologist said it was a good idea, what's behind that? And so I went where I usually go as you guys know by now. I went to open evidence. So let me walk you through that response because I learned something really interesting. So I asked Open Evidence, should aspirin be used for secondary prevention after hemorrhagic stroke? And it comes back with this answer which you guys are going to find unsatisfying. Right? I get a lot of comments like, well, there's no real answer here. I'm sorry. medicine is personalized. We do not have a one-sizefits-all approach for absolutely everybody all of the time. That it will be the spoiler alert here as well. But let's go through this by the evidence and see what we learn. Aspirin may be considered for secondary prevention after hemorrhagic stroke in patients with clinical indications for antiplatlet therapy. So we talked about that in the aspirin video. Secondary prevention even secondary light or high-risk primary prevention. Though definitive evidence of benefit remains limited, current guidelines classify this as a reasonable option and the decision should be individualized based on the balance of eskeemic and hemorrhagic risk. So this is based on the key evidence from the restart trial and this landmark trial randomized 537 RA uh CH so intraranial hemorrhage or intra cerebral hemorrhage survivors who had been on anti-thrombotic therapy prior to their hemorrhage. So this actually goes to obvious's point about if I had been on aspirin before my stroke I might not be here. Turns out many people will still survive that event even on anti-thrombotic therapy prior to their hemorrhagic stroke. And they were randomized to either restart the anti-thrombotic therapy, antiplatlet therapy, or to hold off and not restart it. And the time at which they restarted it was 76 days or about 3 months after their uh two to three months after their event.

[00:11:25]Counterintuitively, starting antiplatlet therapy did not increase recurrent hemorrhage. In fact, recurrence rates were numerically lower in the antiplatlet group, 4% versus 9%. When they say numerically lower, that means it did not achieve statistical significance. So, we can't really say that recurrence rates are lower, but just looking at the raw data, it certainly wasn't higher, and we would expect that if there were really a signal for increased risk. They actually did an extended follow-up for these patients and follow-up up to five years confirmed no excess risk of recurrence with antiplatlet use. However, the trial was underpowered to demonstrate a reduction in major adverse cardiac events. So what does that mean? They were looking to see was there harm associated with taking aspirin after a hemorrhagic stroke. They were not looking to see whether taking that aspirin was actually helpful for any of the things that we talk about taking aspirin for like heart attack, stroke, P80, limb loss, those types of events.

[00:12:28]The following Kaplan Meyer curve from the restart extended follow-up shows the cumulative incidence of major vascular events with a trend meaning not statistically significant trend favoring antiplatlet therapy during the first three years. So you can see that here and I'll keep scrolling so you can look at that uh table of atrisisk patients at the bottom here. But we have good followup out to five years and you can see there's a pretty reasonable separation between these curves looking at major vascular events.

[00:13:02]Now there is also a Cochran systematic review. So this is where we take a bunch of trials that have already been done.

[00:13:09]We pull them all together. When possible, we actually pull the data at the patient level and analyze this at a much bigger scale and try to combine all of these trials and findings together so we get the most power to detect a change. The Cochran review found moderate certainty evidence that starting versus avoiding long-term antiplatlet therapy likely has little to no effect on major adverse cardiac events, mortality, or functional status.

[00:13:40]But importantly, there was no significant increase in recurrent CH with antiplatlet use. So again, we're not sure that it's really helpful, but it's definitely not harmful, at least in the trials that have been done so far.

[00:13:55]And we can go so far as to look at the guidelines. The 2022 American Heart Association, American Stroke Association CH guideline in the secondary stroke prevention guideline acknowledge that antiplatlets might be considered after ICH particularly in patients who were previously on that therapy and have indications for secondary vascular prevention. Guidelines in the US, Canada, China, and the UK and Ireland have all classified the evidence as level B. That means it's strong but not the strongest level of evidence that we have. So, this goes back to our aspirin video and how high is your risk? Do you have cardiac stance? Do you have a severely elevated plaque score either on a CTN or a coronary calcium score or a CINT? Do you have sky-high LP little A?

[00:14:43]Are there reasons that you think you might benefit from aspirin even if you've already had an IC? If so, we think at least it's safe for you to be on the aspirin. Whether you will benefit or not unclear from the existing data that we have but contrary to my intuition and to obvious as well it doesn't seem to be harmful and that is because patients with CH or intra cerebral hemorrhage also have risk for thrombotic events and again there are some specific pathologies and we can show you that here the ideology or why this happens matters there is something called cerebral amaloid angiopathy or CIA that has a particular reason that people would be predisposed to have a brain bleed and it's recurrent meaning that risk factor persists and so they have a you know recurrence rate of 15 to 20% per year those patients probably ought not to be on aspirin and that again shifts the risk benefit balance but here again you can see uh just what I said earlier ICH survivors are at high risk for eskeemic events and so that's why there's a therapeutic dilemma And obvious this is why your cardiologist at that times probably suggested being on aspirin for secondary prevention. Well, you say fine, I don't see that much benefit. The trials don't suggest that much benefit. What else could I do?

[00:16:07]Blood pressure control is the most important modifiable risk factor for secondary prevention after IC. Target systolic would be less than 140 millimeters of mercury with stronger effects on preventing ICH than on eskeemic stroke. Now the question you might have afterwards is well how soon could we restart aspirin after an IC if we wanted to do that in the restart trial again we said 76 days uh a more recent trial the e-art trial looked at postsurgical ICH patients and found that early aspirin initiation posttop day three versus 30 was safe and actually reduced eskeemic events in very high-risisk patients. Lastly, we have ongoing research, which is the aspiring trial, which is enrolling over 4,000 CH survivors. This is designed to definitively determine the effects of antiplatelets after CH, including key subgroups like where the hemorrhage might be. And you'll have to stay tuned until then to figure out whether this is really something that is helpful or possibly even harmful. Until next time, guys, take really good care.