Frequently Asked Questions: Nattokinase, Lumbrokinase & Serrapeptase
Please check here for all your questions on these proteolytic enzymes used in Long Covid and ME/CFS!
Q: What is nattokinase used for?
A: In Long Covid and ME, it is primarily for the purposes of busting micro-clots. This double-blind, placebo-controlled crossover study in 12 young & healthy Japanese men found that even a single 2000 FU dose activated multiple fibrinolytic & anti-thrombotic pathways:
Q: I heard that nattokinase breaks down the SARS-CoV-2 spike protein. Is this true?
A: Yes, in vitro, nattokinase does indeed degrade the spike protein. Study found that nattokinase degraded S protein via time-dependent inhibition at concentrations as low as 1 µg/mL (this is promising!). Viral inhibition took place after 60-180 minutes. However, it hasn’t been tested in human trials yet. A major caveat is that nattokinase breaks down LOTS of proteins and isn't specific to the spike.
Q: What symptoms does nattokinase help with?
A: Per my surveys, nattokinase seems to help most with fatigue, brain fog, and post-exertional malaise (PEM). ≥60% reported benefit with fatigue and brain fog; 50% with PEM. Other symptoms helped to a lesser degree were dizziness/light-headedness, POTS, shortness of breath, heart-rate variability and chest pain.
Q: What symptoms is nattokinase less likely to help with?
A: The symptoms for which nattokinase appears to be the least beneficial—improving in ≤30% of those surveyed—are neuropathy, muscle spasms, muscle/joint pain, tinnitus, nausea, and sense of smell.
Q: What dose of nattokinase should I take?
A: It depends on many factors. Consider your individual medical history, age, and current medications. Most brands are 2,000 FU per capsule; however, my surveys have shown that most people with Long Covid & ME do better on higher doses anywhere from 4000 FU to 12,000 FU total daily dose. The “sweet spot” seems to be around 4000 FU twice daily on an empty stomach. Of note, a recent retrospective analysis from 1,062 pts examined safety & efficacy of nattokinase 10,800 FU in the treatment of atherosclerosis progression & hyperlipidemia. Authors did not report any safety issues at this higher dose: “No noticeable adverse effects associated with the use of nattokinase were recorded.”
Start at a subtherapeutic dose to assess tolerability (i.e. 2000 FU once daily on empty stomach). Some may experience a Herxheimer reaction so it’s best to start slowly.
Titrate up dose as tolerated to appropriate dose based on medical history & other medications.
Q: What about my child? Is it safe for kids to take?
A: To my knowledge, there have been no nattokinase efficacy or safety trials in children. Anecdotally, one reputable MD whose teenage child had Long Covid advised me that physicians are starting Long Covid children at half-doses and then titrating up as tolerated. The best low-dose nattokinase I’ve come across are Naturally Vitamins 750 FU and Solaray’s nattokinase 1250 FU, both enteric coated.
Q: Is it safe to take nattokinase with aspirin?
A: More studies are needed in this arena. However, this trial, 96 pts took NK 10,800 FU + aspirin 100 mg daily over the course of 12 months. Authors found that aspirin + nattokinase showed a synergistic effect, further improving outcomes, with no recorded adverse events.
However, keep in mind that aspirin in and of itself DOES increase the risk of bleeding. The cardiovascular benefits of daily aspirin outweigh bleeding risks in a relatively small minority. Specifically, the USPSTF determined that for primary atherosclerotic cardiovascular disease (ASCVD) prevention, daily aspirin has a small net benefit in those aged 40-59 with a ≥10% ten-year risk of ASCVD, but not in those age 60+:
This risk calculator helps practitioners decide if their patients should take daily low-dose aspirin. Unfortunately, the calculator does not consider history of COVID or long COVID which likely skews the risk/benefit ratio. Before starting daily aspirin — with or without nattokinase — consult with your health care provider. If your doctor determines aspirin is appropriate for you, the additive risk of bleeding with moderately-dosed nattokinase (or lumbrokinase) is likely negligible for the majority, but it cannot be ruled out. Consider individual history.
Q: What are the best nattokinase brands?
A: Brands that are enteric-coated or acid resistant appear more effective per my surveys (scroll down for survey charts). The most widely-available brands with acid resistant coatings are noted here.
Several studies found that enzyme activity of nattokinase was reduced in simulated gastric juice, but PRESERVED with enteric coating. Acid-resistant coating should prevent dissolution in the stomach so that NK may be absorbed in the more basic conditions of the intestine:
Some acid-resistant / delayed release brands are listed below:
Doctor’s Best Natto-Serra (2000 FU/40,000 SPU)
Solaray’s Nattokinase 3000 FU/Serrapeptase 60,000 FU
Good Health Naturally 2000 FU Delayed Release
Naturally Vitamins Nattokinase 750 FU
Finchley Clinic Nattokinase 4,000 FU Delayed Release
For those with soy intolerance/allergy, two soy-free formulations are below:
Sunday Naturally Nattokinase 2000 FU
Healthy Origins Nattokinase 2000 FU
Some pertinent survey results are shown below:
Q: How long does it take to see results?
A: It varies. Many report noticing benefits within just the first few days; others report a 1-2 week herx where they actually feel temporarily worse; still others report 2-3 weeks before noticing any benefit. Some who feel worse in the beginning and suspect a Herxheimer reaction have reported that a dose decrease followed by careful dose titration back up helps improve tolerability.
Q: Does nattokinase affect menstrual cycle?
A: According to the results of one of my Twitter polls, yes, it may in some cases.
Q: Do I need to take serrapeptase too?
A: That’s less clear. Serrapeptase is an intriguing proteolytic enzyme with a diverse range of activity including improved microcirculation, anti-inflammatory effects & biofilm degradation. Multiple studies suggest serrapeptase supplementation improves antibiotic efficacy. Some report benefits with serrapeptase while others report it is less tolerable compared to nattokinase. Most common reported side effects with serrapeptase are headache and nausea.
Q: If I decide to take serrapeptase, what’s the best dose?
A: Human studies range from 20,000 SPU to 120,000 SPU total daily dose, with smaller doses at more frequent intervals preferred (i.e., 40,000 SPU three times daily on empty stomach). Enteric coating may improve efficacy. Anecdotally, some are taking much higher doses, but this hasn’t been studied.
Q: I did not tolerate nattokinase well and want to try lumbrokinase instead. Can I take lumbrokinase with aspirin?
A: An RCT from 2013 examined secondary stroke prevention with lumbrokinase (n=169) vs placebo (n=105). 169 received full course of LK 600,000 IU three times daily for 1 yr. Over HALF used concomitant anti-platelet drugs for the duration of trial. 1 case of bleeding (GI) was reported. An incipient RCT will examine the efficacy & safety of LK + aspirin versus aspirin alone for acute ischemic stroke. Stay tuned.
Q: What dose of lumbrokinase is best?
A: Like with nattokinase, it varies based on brand, medical history, and medications. Generally speaking, it appears the lumbrokinase formulations studied have a good safety profile at 600,000 IU every 8 hours. Boluoke® claims to have been used in many Chinese trials. Their recommended dosing is also 600,000 IU 3 times daily. The company attests its brand does not affect PTT or PT. This means it does not slow down the time it takes the body to form a blood clot.
Q: I heard that nattokinase affects blood clotting time and may have anticoagulant activity along with its clot-busting ability. Is this true?
A: Yes, it appears to be true. Several studies have shown that nattokinase increases time to clot (aPTT) and inhibits at least one & maybe more coagulation factors (factors VIII and maybe VII). This suggests that NK exhibits some anticoagulant activity, so monitor for any signs of bleeding.
.Q: Why are you always talking about nattokinase and not lumbrokinase? Isn’t lumbrokinase stronger and better?
A: It is harder to predict efficacy with lumbrokinase for three reasons:
Much fewer have tried it for Long Covid or ME and thus I don’t have a big enough sample size from surveys to draw many conclusions.
Efficacy of lumbrokinase is harder to predict across brands because different brands have different enzyme extractions and thus different fibrinolytic potency. The only brand proven to have “stronger” fibrinolyric potency than nattokinase is Boluoke
A risk with the higher potency is potentially less tolerability due to Herxheimer reactions. Lumbrokinase comes from earthworms, and multiple different proteases [proteolytic enzymes] can be extracted from several different earthworm species. Each brand may come from different species and/or a different cross-section of proteases ("enzyme fraction").
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Fascinating piece, thank you. Incredibly useful. This makes me want to stagger using natto, lumbro and aspirin, just to be safer. And I hadn't realised that empty stomach was best either. I'm going to start off with the natto, and increase my dose compared to last time. Thanks again.
Is it possible there might be any benefits to taking nattinokase during the acute phase of infection?
I’ve only heard people talk about it when treating long Covid, but what about as a supplement during initial infection?
Thank you so much!