Natto for Better Blood Flow in Long Covid?
Nattokinase reduces the tendency to clot, increases blood clot dissolution
We’ve known since early in the pandemic that covid infections increase blood clotting. People who are hospitalized often present with many blood clots. There are often micro-blood clots throughout the body that cause widespread problems.1
Worldwide, it is estimated that 31% of deaths are due to thrombosis, or blood clots forming in the wrong place. 2 This number is higher in people with acute Covid-19; it is common to administer heparin and other anti-clotting drugs to Covid patients who are hospitalized. 3
And this over-coagulation extends to some long covid patients.
The study below asserts that microclots are quite common in Long Covid, and the clots impair blood flow and are a driving cause behind many of the symptoms related to weakness and fatigue. The fibrin clotting protein in Long Covid is noted to be in an atypical amyloid form, which is more resistant to breakdown than normal.
“A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications.” The Biochemical Journal, 17 Feb 2022, PMID 35195253.
“Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis.” Blood Advances, 11 May 2022, PMID 35543533
This study found that VWF (von Willebrand Factor) was elevated in one-third of post-covid cases, and elevated levels were associated with lower blood oxygenation scores and higher lactate levels. This suggests that high VWF are not universal in Long Haulers, but when they are elevated, they can cause specific issues that may impair the normal working of the lungs and muscles.
Another study in the Journal of Thrombosis and Haemostasis found that “biomarkers including von Willebrand factor antigen, VWF propeptide, and factor VIII were significantly elevated in convalescent COVID-19 compared with controls."
“Persistent endotheliopathy in the pathogenesis of long COVID syndrome.” Journal of Thrombosis and Haemostasis, Oct 2021, PMID 34375505.
So if too many tiny blood clots and elevated von Willebrand Factor VIII plays a role in some types of Long Covid, what can be done about it? We do have research that shows that oral consumption of nattokinase reduces von Willebrand Factor:
“Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.” Integrated Blood Pressure Control, 13 Oct 2016, PMID 27785095.
This study found a difference between men and women - women displayed a clear reduction in VWF, while men did not. But men consuming nattokinase daily did see improvements to their renin-angiotensin system … men with low renin saw an increase, while men with high levels of renin saw a decrease. Of possible relevance is the fact that the SARS2 virus that causes Covid-19 uses the angiotensin II protein to enter cells, and disruptions to the renin-angiotensin system are a mechanism that causes illness in Covid-19.
Natto and Nattokinase have been the subject of thousands of scientific studies. Some were done in Japan and are not available in English, but there are hundreds of studies that are available to English speakers.
This study found that a single oral dose of nattokinase (2,000 FU) led to significant anti-clotting activity and thrombolysis in people: clots were less likely to form, and pre-existing clots dissolved faster after a natto kinase supplement.
“A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.” Scientific Reports, 25 June 2015, PMID 26109079.
Another study has shown that oral consumption of nattokinase decreases the clotting factor fibrinogen, and the pro-clotting von Willebrand factors VII and VIII.
“Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.” Nutritional Research, Mar 2009, PMID 19358933.
The decrease seen with daily oral consumption of 4,000 FU of nattokinase was modest, but could be significant over time. Fibrinogen was lowered by 7-10%, Factor VII was lowered by 7-14%, and Factor VIII was lowered by 17 to 19%.
While most studies have used nattokinase enzyme that was purified and presented in a standard dose, it is worth asking if plain natto (the food) can be consumed in an amount that provides the same effect. The answer is yes.
How much Natto to Equal 1 capsule of Nattokinase?
According to the Japanese Nattokinase Association, one packet of natto (typically 50 grams, just under 2 ounces) contains an average of 1436 FU of nattokinase. The average dosage for oral supplements of nattokinase is typically 2000 to 4000 FU per day. So it is certainly possible to eat enough natto to get that goal of 2000 - 4000 FU per day. Natto contains on average 28.7 FU per gram, so getting 4,000 FU per day involves eating about 140 grams, or 5 ounces of natto.
Note on FUs: Nattokinase doses are based on activity, not just weight. Fibrin is a blood-clotting protein, and the Fibrinolytic Unit is a standard measure of how much anti-clotting activity a capsule of nattokinase has. Look for the total number of FUs per dose, not the number of FUs per gram.
Natto vs Nattokinase
Natto is a food. It is fermented soybeans (and sometimes contains grains, or may be made from other beans, although traditional Japanese natto is soybean-based). Natto contains nattokinase enzyme and a host of other nutrients (including mundane protein, carbs, and minerals). Natto is perhaps the richest dietary source of Vitamin K2 (more on that later). Natto contains other compounds like PQQ (an energy transfer factor similar to CoQ10). Natto is sticky-gooey because the bacteria make a polymer gel from the amino acid glutamic acid. And natto has a strong odor due to pyrazine compounds and sulfur-containing molecules. All of these seem to have some biological activity in people, although some of that activity may not be directly relevant to Long Covid.
Natto is ‘an acquired taste.’ People can learn to tolerate it (even love it, maybe) - but natto smells like spoiled food and it is slimy. Most people in Japan eat natto with a bit of mustard and some soy or fish sauce - these make it more palatable.
In some parts of Japan (especially the north), people eat a few servings of natto every week. Those areas are known for having less osteoporosis and fewer hip fractures among the elderly, and low rates of hypertension. Many Japanese researchers believe that natto in the diet contributes to these health benefits, although the debate on how much is from natto is an ongoing matter. The typical serving size for natto in Japan is approximately 50 grams (about 2 ounces).
Many Asian groceries in the United States have natto in the freezer section, and the price is approximately $1 to $2 per serving. Natto is also easy to ferment at home if a person has a space that can be kept around 100 Fahrenheit (38 Celcius). A dollar’s worth of soy or mung beans can be turned into 10 or 15 servings of natto with a process that is similar to making yogurt. I currently incubate my natto in a Brod and Taylor bread proofer that provides thermostatic heat control … that works nicely. People are also using instapots that have yogurt settings, sous vide baths, dehydrators that can be set to 100 F, or a gas stove with a pilot light that keeps things warm.
Nattokinase
Nattokinase is a purified extract of natto. Nattokinase is an enzyme (or group of enzymes). And nattokinase “thins the blood.”
In Japan, where nattokinase has been most studied, there are pharmaceutical grades of nattokinase that are pure enough to be administered in an I.V. drip; these are administered to stroke and heart attack patients where time is of the essence.
In other countries, nattokinase is formulated into capsules or tablets intended to be taken orally. This form is not purified enough for injection, it contains too many different proteins — it could cause serious allergic reactions if injected.
There has been some debate about whether it can have this effect when taken orally. The doubters claim that nattokinase is too large to be absorbed into the body as it is… the enzymes in the stomach must break it down into smaller bits, they insist. And they reason that if nattokinase was absorbed intact, it would ‘thin the blood’ enough to pose a hazard - but eating natto has not been associated with a high risk of internal bleeding.
The debate about whether nattokinase is absorbed intact is somewhat academic. We have a clear data that indicates that oral consumption of natto and nattokinase does reduce clot formation, oral natto increases fibrinolysis. Maybe the large nattokinase molecule is broken down to something smaller, something that can be absorbed, something that has more moderate clot-busting properties. But orally consumed natto does have an impact on thrombosis and how fast clots are dissolved.
“Thinning the Blood” - Some terminology
The average person uses terms like “Thinning the blood” in rather non-specific ways. There are multiple mechanisms that can reduce the tendency of blood to clot, and there are also mechanisms for dissolving existing clots. Here is a quick review.
Aspirin has an antiplatelet effect; it reduces the ability of blood cells called platelets to stick together. The strength of this effect is moderately strong. Taking aspirin immediately if one has the symptoms of a heart attack is standard medical advice - once absorbed, the aspirin will work against blood cells sticking together, it can often reduce clotting enough to keep the blood flowing. Aspirin use can also lead to internal bleeding, and over the years, the advice on when to take aspirin has been adjusted and become more cautious.
Anticoagulants like warfarin, heparin, and nattokinase involve a different route of chemical action to prevent clots from forming. There are molecules in the blood much smaller than cells that fuse together to form plugs, and the anti-coagulants work to block that.
Fibrinolytic effects involve the ability of some molecules to break down fibrin clots. TPA (tissue plasminogen activator) is one ‘clot-busting’ drug that clears existing clots. Plasminogen is the precursor of plasmin, which actually chews up clots. Fibrin is a protein that forms net-like structures that seal off the flow of blood — that is great when a person cuts themself, but not so good if a clump of fibrin forms in the blood and blocks blood flow to some part of the body.
The body is continuously forming and dissolving clots at sites across the body, and there is ideally an equilibrium that is established between these opposing actions… but in covid and long covid, the balance is shifted and can cause problems.
WebMD has a good article on the different types of anti-coagulants for people who are interested in learning more about the subject.
Vitamin K, Natto, Coumadin, and Clotting
Natto is one of the richest sources of Vitamin K2, which is mostly present in the MK7 form. And Vitamin K is essential for blood clotting (the ‘K’ in Vitamin K comes from the German word Koagulation.) So will extra vitamin K cause excessive clotting? No, not under ordinary circumstances. In a normal person, having adequate Vitamin K means that the coagulation mechanism works the way it should. Once that system is saturated with Vitamin K, additional K does not cause excessive clotting. But there is one caveat - there is a group of people who should avoid natto and nattokinase.
Sometimes doctors deliberately induce a Vitamin K deficiency to prevent normal clotting. The most common drug used for this is coumadin (a.k.a. warfarin). This drug is often prescribed for a while after a stroke or heart attack, if a person has deep vein thrombosis, or if a person has a high risk of forming a clot (as with atrial fibrillation). Coumadin/warfarin blocks the activity of Vitamin K.
If a person is taking prescription warfarin/coumadin, then any form of Vitamin K will make that medicine less effective. Coumadin patients are given instructions to limit foods that are rich in Vitamin K to maintain the deficiency. And since natto is a food rich in Vitamin K, it could make that type of medicine less effective, or altogether ineffective.
So the otherwise wholesome food natto should not be consumed when a person is on warfarin/coumadin. And even though some forms of nattokinase might have the Vitamin K removed, it does not seem like a good idea to take nattokinase when on coumadin … the dose of the coumadin is designed to greatly reduce coagulation, and if the nattokinase further reduces coagulation or clotting, the possibility of excessive bleeding needs to be considered. We do not have data that indicates that taking nattokinase with coumadin is safe, and there is a good reason to believe it could be dangerous.
The Bottom Line
While natto and nattokinase have not been scientifically proven to help with Long Covid, there is an excellent rationale. Natto and nattokinase reduce coagulation and increase fibrinolysis to a modest degree. Natto can be compared to yogurt - it is a fermented food with a long history of use in some cultures. And people have to eat. While we cannot say with the highest degree of scientific certainty that natto is good for Covid Long Haulers, it seems to be a safe, inexpensive activity that might help.
“The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases.” Viruses, 23 Sep 2021, PMID 34696334.
“Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy.” Frontiers in Molecular Biosciences, 28 May 2021, PMID 34124160.
“Effect of intermediate/high versus low dose heparin on the thromboembolic and hemorrhagic risk of unvaccinated COVID-19 patients in the emergency department.” BMC Emergency Medicine, 14 Jun 2022, PMID 35698054.
“Markers of endothelial cell activation are associated with the severity of pulmonary disease in COVID-19.” PloS One, 19 May 2022, PMID 35588115, Full Article.