High-Dose Nattokinase: A Game-Changer for Atherosclerosis

on Nov 01, 2023| Modified on Dec 01, 2023
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Previously, I wrote about the use of Grape Seed Proanthocyanidin Extract (GSPE) to help ameliorate atherosclerosis, a main cause of cardiovascular disease (CVD), here:


I'd like to discuss another supplement that can also effectively combat atherosclerosis. Due to its unique mechanism of action, it may synergize well with GSPE.

First, I would like to discuss something that doctors don't often mention to you when they prescribe statins to lower cholesterol. Doctors often don't tell you the exact reason why they are prescribing statins, but rather tell you something like lowering cholesterol will help reduce your chances of getting cardiovascular disease (CVD) such as heart attack or stroke. Recently, my doctor told me that although my cholesterol and triglyceride levels were good, there was room for improvement.

I asked my doctor if the reason why he wanted to lower my cholesterol further was to reduce my chances of getting atherosclerosis and subsequent CVD, to which he said, yes. So I then asked him if the goal is to reduce atherosclerosis, why don't they test me for atherosclerosis instead of cholesterol? He said that they can test for atherosclerosis, but it is more than ten times more expensive than testing cholesterol levels and many insurance companies won't cover it, so they test cholesterol levels instead. So once he told me that I started reading studies on the topic.

Atherosclerosis is the main cause of CVD and CVD is the number one cause of death in the world, representing 32% of all global deaths. I also came across the following study that was done at UCLA in 2009 that came to an interesting and puzzling conclusion as discussed here :

https://www.sciencedaily.com/releases/2009/01/090112130653.htm#:~:text=Summary:,to current national cholesterol guidelines.

Here is a relevant quote from the study:

A new national study has shown that nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event, based on current national cholesterol guidelines.

This study also suggested lowering the acceptable guideline targets for LDL cholesterol levels for those at risk for CVD and raising the HDL cholesterol level target range. Because of this study and others like it, the cholesterol level guidelines are continually updated, with the last update being in 2018.

My take on this study is that it makes more sense to test for atherosclerosis instead of cholesterol if the idea is to reduce atherosclerosis to help prevent CVD. So this makes me think that ideally, we should be lowering both cholesterol levels and atherosclerosis simultaneously because cholesterol may not be the most accurate indicator for atherosclerosis and preferably without the use of statins that do have significant side effects as discussed here:


Here are some relevant quotes from the above article on statin side effects:

One of the most common complaints of people taking statins is muscle pain. You may feel this pain as a soreness, tiredness or weakness in your muscles. The pain can be a mild discomfort, or it can be serious enough to make it hard to do your daily activities.

Occasionally, statin use could cause an increase in the level of enzymes in the liver. These enzymes signal inflammation. If the increase is only mild, you can continue to take the drug. Rarely, if the increase is severe, you may need to try a different statin.

It's possible that your blood sugar level, known as blood glucose, may increase when you take a statin. This may lead to developing type 2 diabetes. The risk is small but important enough that the Food and Drug Administration (FDA) has issued a warning on statin labels regarding blood glucose levels and diabetes.

It is important to note that although statins can lower cholesterol, it has been shown in studies that statins mainly only slow atherosclerosis progression, as discussed here:


Here are some relevant highlights from the above link:

  • Coronary CTA has improved clinicians' ability to treat patients with coronary artery disease.
  • Statin therapy is associated with reduced plaque progression, decrease in MACE, but increase in coronary calcium score.
  • Statin therapy is associated with alteration in coronary plaque features, namely higher calcium density and lower low-attenuation and fibro-fatty plaque volumes.
  • Higher calcium density is associated with slower plaque progression.

High-Dose Nattokinase

This brings us to Nattokinase (NK), a supplement that is often suggested for cardiovascular health and, more specifically, to reduce atherosclerosis, triglycerides, and cholesterol levels. A potential problem with NK is that label-suggested dosing levels are frequently inadequate to reduce cholesterol or triglyceride levels and or significantly reduce atherosclerosis.

To add further confusion to the question of adequate dosing of NK, most retail suppliers of NK sell their products mainly in 2000 FU (Fibrinolytic Units) capsules and recommend one or two capsules per day. If you take the higher dose of two capsules per day at a total of 4000 FU/day, the dose is likely too low to be effective for the purpose, but as mentioned in this study, other studies have shown some benefit at 6,000 FU and 7,000 FU.

Still other suppliers recommend as much as 8,000 FU per day, but even if you take 8,000 FU daily, the dose may still be insufficient for optimal cholesterol, triglyceride, and atherosclerosis-lowering effects. The following August 2022 study used a low dose of NK at 3,600 FU and at a high dose of 10,800 FU in 1062 participants:


The study above, because of its large size of 1062 participants and coverage of three major health issues of high cholesterol, high triglycerides, and atherosclerosis, delivered some very impressive and informative results on the use of NK for this purpose.

First off, it was shown that 3,600 FU/day had no effects on these three study parameters above. Secondly, they showed that the dose of 10,800 FU/day was statistically significantly effective at lowering the three main study parameters.

  • Starting with total cholesterol, the 10,800 FU dose lowered total cholesterol by 15.9%.
  • LDL cholesterol was lowered by 18.1%.
  • HDL cholesterol was increased by 15.8%.
  • Triglycerides were reduced by 15.7%.

The rates of improvement were also very good.

  • Total cholesterol improved in 95.4%.
  • LDL cholesterol 84.3%
  • HDL cholesterol 89.1%
  • Triglycerides 85.2%
  • CCA-IMT(Common Carotid Artery-Intima Media Thickness) 77.7%
  • Carotid Plaque Score (CPS) 66.5%

The above improvement rates represent those who responded to NK compared to those who didn't. In many studies, they give a median or average number. The above numbers make it fairly clear that NK effectively improves these critical atherosclerosis and CVD parameters.

Here are some relevant study quotes :

After 12 months of NK consumption, both the size of CCA-IMT and the size of the carotid artery plaque decreased significantly (from 1.33 to 1.04mm on average, P < 0.001). The size of the plaque decreased by up to 36%, suggesting that NK is very effective in improving/reducing carotid atherosclerosis (Table 4). The overall improvement rates in CCA-IMT and CPS are not as high as those in blood lipids, with approximately 2/3 and 77.7% of the participants showing improvement in CPS and CCA-IMT, respectively (Table3).

The above quote clearly illustrates the efficacy of 10,800 FU/day of NK in lowering atherosclerosis parameters in humans.

As shown in Table 5, no differences in NK efficacy were found between male and female participants, although changes in female participants were marginally greater, but were not statistically significant. We found that NK at 3,600 FU dose was not effective in lowering lipids and suppressing atherosclerosis. Lipid levels and CCA-IMT and plaque size did not change after 12 months of NK consumption at that dose (Table 6).

The above quote clearly shows that 3,600 FU per day of NK has no effect on the three main parameters being tested.

Table 7 showed that the lipid lowering and antiatherosclerotic effects of NK were better in participants who exercise more compared to those who exercised less. Compared the effects of NK in obese participants with those of non-obese subjects, we found that the effects of NK in obese subjects were more prominent (Table 8).

Vitamin K2 (180 mcg/day)

This study also showed that Vitamin K2 had an additive effect to NK's positive effects mentioned above. It is also worth mentioning that vitamin K2 has blood-coagulating effects that may help to offset the blood thinning effects of NK.

Aspirin (100 mg/day) 

This study also showed that Aspirin had a positive additive effect with NK, but low-dose aspirin in new users has shown significant potential for gastric ulcers as discussed here in this 2022 article :


Here is a relevant article quote:

This study shows that low-dose aspirin is an independent risk factor for both gastric and duodenal ulcers. The associations were not significant or weak in the prevalent-user design and strong and statistically significant in the new-user design in both cohorts. Thus, it is important to weigh risks against benefits when low-dose aspirin treatment shall be initiated and to monitor adverse gastrointestinal symptoms after the start of low-dose aspirin therapy.

More Relevant Quotes From The Main NK Study:

In this study, we present evidence to show that continued NK supplementation at the dose of 10,800 FU daily for 12 months significantly decreased TC, TG, LDL-C and increased HDL-C in hyperlipidemic participants. Administration of NK effectively improved atherosclerotic conditions by significantly reducing CCA-IMT and CPS. The study also investigated the factors surrounding the use of NK and contributing to improving clinical outcomes. The findings of this study are very important, as they demonstrate that NK at a dose of 10,800 FU, a high dose compared to the recommended dose of 2,000 FU for use in Europe (24), is highly effective in the treatment of hyperlipidemia and progression of atherosclerosis, two main contributors to the development of CVD.

An important finding from this study is that NK, when used in a high dose, is very effective both in controlling the progression of atherosclerosis and in lowering blood lipids. This is entirely consistent with previous findings in human clinical studies in which NK was used at doses of 6,000 FU and 7,000 FU (5, 19).

The observation that co-administration of vitamin K2 and aspirin with NK led to a synergistic effect is interesting. In support of our findings, previous studies found that NK and aspirin share similar pathways and mechanisms of action in their interaction with platelets leading to inhibition of platelet aggregation (16, 34). Furthermore, the positive in vitro hemorheological effects of NK worked well with aspirin (35). These shared actions might contribute to a better clinical outcome. It is unknown why the use of vitamin K2 improved the action of NK. It could be related to the positive effect on bone, muscle and cardiovascular health associated with the administration of vitamin K2 (36, 37).

Safety Of Nattokinase

The use of the dose of 10,800 FU daily is based on previous studies demonstrating that NK is very safe without concerns of toxicity. In addition to the long history of the use of natto and purified NK in the diet in Asian countries, especially Japan, it has been shown that there is no concern for toxicity when adults take 1,000–14,000 FU daily (32), and no toxic side effects have been observed in rats using significantly higher doses of 22,000 FU/kg/day, equivalent to 1.43 million FU daily in humans (32). Importantly, there are no cases of toxic effects or serious side effects reported using this high dose in the literature, even though NK has been widely used and studied over many years. However, a side effect-related report showed that a patient with mechanical valve developed thrombus, but underwent a successful repeat valve replacement when using NK (100 mg daily, equivalent to 2,000 FU/day) as a replacement for warfarin (33). Again, this thrombus development problem may be related to the inefficiency of the low-dose used.


In summary, our data from this largest clinical study involving 1,062 participants suggest that NK at the daily dose of 10,800 FU, which is higher than the recommended dose of 2,000 FU, is significantly effective in the management of atherosclerosis progression and hyperlipidemia. No adverse effects associated with the use of NK is observed. The study advances our understanding of the action of NK and the importance of the dosage of NK. We also demonstrate that other factors, including lifestyle and co-use of vitamin K2 and aspirin, could contribute positively to the clinical outcome. Our findings provide evidence that promising and positive clinical outcome in the management of atherosclerosis progression and hyperlipidemia can be achieved safely by using NK at a dose of 10,800 FU per day. The outcome of this report warrants further randomized control clinical trials using increased doses of NK.

I am of the opinion that because of the different mechanisms of action involved between Nattokinase (NK) and Grape Seed Proanthocyanidin Extract (GSPE), the two together have the potential for synergy together. In addition, GSPE offers other potential health benefits because of its potent antioxidant effects as well as its known anti-inflammatory effects. Vitamin K2 (180 mcg), as used in this study, showed that it improved the effects of NK as did aspirin at 100mg/day.


Nattokinase is known to have potential blood thinning effects, as does Aspirin, and Grape Seed Proanthocyanidin Extract (GSPE)  is also known to have potential blood thinning effects. If you are considering using one, two, three, or all of these supplements, check with your doctor first to ensure they will be safe for you in your particular situation and compatible with all medications you are taking.

On a positive note, Vitamin K2 is known to have blood-coagulating effects, which may help to offset some of the blood thinning effects of the others. It seems safer to start dosing low and work upwards toward the desired dose since there is always the possibility that a person can have an allergic reaction to almost anything.

Feedback and Questions for Art

Have feedback or a question for Art Solbrig? Please inquire here.

Where to Buy

We searched Amazon for the highest amount of FU per capsule and found that most capsules provide 2,000 FU per capsule or less. However, a few offer higher dosages.

Nattokinase 4,000 FU PER CAPSULE: Arthur Andrew Medical, Nattovena, Pure Nattokinase Supplement, 4,000 FUs per Capsule, 90 Capsules

Nattokinase 4000 FU Per Capsule: BoostCeuticals Nattokinase Supplement 200mg 100 Vegan Capsules Pure No Stearates

Nattokinase 3,000 FU PER CAPSULEPHARMAKON Nattokinase, Bioavailable Soft Capsules, Organic Fermented Soybean Extract, 6000 FUs per 2 Capsules - Made in Germany

Nattokinase 2000 FU PER CAPSULE: Nattokinase Supplement 4,000 FU Servings, 120 Capsules (Derived from Japanese Natto) Systemic Enzymes for Cardiovascular and Circulatory Support (Manufactured in The USA) by Double Wood

Grape Seed Proanthocyanidin Extract: Bronson Grape Seed Extract 400 mg - Antioxidant & Immune Support - Standardized Extract with 95% Proanthocyanidins- Non GMO, 180 Vegetarian Capsules

Related Links:

Grape Seed Extract: A Powerful Ally Against Atherosclerosis
Health Benefits of Nattokinase: Evidence-Based Findings
Nattokinase Side Effects: What You Should Know
Nattokinase's Role in Effectively Treating High Cholesterol

Article Feedback

1 User Review
5 star (1) 

Posted by Frances (Cabarlah, Qld.) on 11/01/2023

Thanks for this article.

Natto is also recommended to dissolve the spike protein in CV19. Readers might be interested in The Great cholesterol con by Dr Malcolm Kendrick in the UK.

Replied by Art
1948 posts

Hi Frances,

You're welcome!

Yes, nattokinase has many other potential health benefits other than atherosclerosis or cardiovascular disease and EC has written an article that lists some of those benefits here :




2 User Reviews
5 star (2) 

Posted by Lindi (USA) on 11/02/2023


Can you take nattokinase and K2 if you have bad varicose veins?

Replied by Art
1948 posts


I have not seen any human studies using nattokinase or other fibrinolytic enzymes specifically for varicose veins so I can not recommend it for that purpose. However, there are web based health promotion sites that do suggest that nattokinase may be useful for varicose veins based on anecdotal evidence. Here is a typical example :


Here is a relevant quote from the site:

Back in 2002, we theorized that by dissolving branched fibrin—which coagulates prior to full clot formation— nattokinase might prove uniquely helpful in a range of disorders in which hypercoagulation is involved. This includes atherosclerosis, infertility, high blood pressure, dysmenorrhea, fibromyalgia, deep vein thrombosis, varicose veins, hemorrhoids, and ischemic strokes. We also suggested it would prove helpful in chronic infections, where the body lays down fibrin in an attempt to seal off harmful pathogens. Finally, we concluded that nattokinase could be helpful in slowing many age-associated illnesses, since high fibrin levels create local pathology and ischemia, and block nutrient and oxygen delivery in microcirculation. Six years later, with nattokinase widely in use, firsthand clinical reports from doctors around the country support our hypotheses and the enzyme's impressive record of efficacy and safety in a wide range of disorders.

Based on the established safety profile of nattokinase, it seems worth discussing it with your doctor to see if he will also suggest it as in the article, for varicose veins.

Regarding vitamin K2, I am not aware of any studies confirming efficacy for varicose veins, but vitamin K2 has shown benefit for the vascular system in general as has nattokinase. Your doctor would have to approve their use for your safety and to make sure that they are compatible with all medications you are taking.

Thank you for your inquiry!


Nattokinase and Calcium Buildup

Posted by Tony (Chicago, IL) on 11/24/2023

Art, will nattokinase also reverse calcium from arteries and body?

Replied by Art
1948 posts


The available studies suggest that nattokinase at high enough dosing will breakdown arterial plaque deposits. These plaques are composed of fibrin, cellular waste products, fatty substances, calcium, cholesterol and possibly other components. So the studies suggest that arterial calcium deposits are part of the debris that is broken down in arteries.


Replied by Bill

Hi Tony,

You can help prevent or remove arterial plaque build-up and occlusion in various ways using several strategies. You can remove cardiovascular and peripheral vascular problems caused by plaque build-up or high cholesterol in the blood or hypercoagulation in the blood aka "thick blood" due to excess fats in the blood or blood clot formation at the body's periphery or due to pathogen build-up in the arterial walls.

You could perhaps dissolve and remove the calcium-containing arterial plaque as one strategy. And you can achieve the calcium removal quite easily by either supplementing the Chanca piedra herb in capsule form at 1000 mg twice a day after meals. Or you could perhaps just follow Walter Last's recommendations and just mix 1 level tspn of Sodium Thiosulfate crystals + 2 tspns of water + 2 tspns DMSO(Dimethyl Sulfoxide) and manually spread that mix on you skin over or near the problem area. Both of these remedies will not actually reduce the calcium in the blood but they will act to safely solubilize and remove any excess calcium from the tissues and organs(including the arteries). And using Sodium Thiosulfate in this way also has the added advantage of removing any unwanted heavy metals and poisons like arsenic, chlorine, lead, mercury etc.

The next strategy that you could use to reduce excess cholesterol in your body and one particular LDL fat, called Lipoprotein A, better known as Lpa. The best and most Lpa-specific remedy for arterial plaque removal would be to just follow Linus Paulings protocol of taking 1 gm Sodium Ascorbate + 1 gm Lysine dissolved in a half-glass of water 6 to 8 times a day. The lack of vitamin C in the body is what causes the liver to automatically compensate by creating an excess of unwanted Lpa. So taking high dose Vitamin C acts to remove the need for the liver to produce any Lpa. And supplementing the Lysine also acts to solubilize and remove any existing plaque or Lpa from the arterial walls.

A simple remedy to safely thin the blood and to reduce clumping or "thick blood" would be to use the high dose Niacin protocol(niacinamide will not work!). Just supplement niacin between 100mg to 500mg 3 times a day at meal times. Supplementing the Lipase enzyme and granulated Lecithin -- only the granulated form, not the oil -- is another good one for avoiding hypercoagulation caused by fats in the blood. See this article by Walter Last:

Hypercoagulation (by Walter Last)

Lipase and Fat Metabolis (by Walter Last)

Walter Last also describes how using Vitamin C and MSM (Methylsulfonylmethane) together is more efficient so that less Vitamin C need be supplemented but more Vitamin C can be absorbed and used for two essential tasks -- first to supply more oxygen to the cells and, second, to more efficiently kill unwanted pathogens in the body -- while MSM can also help to simultaneously detox and repair cells on its own while in its anti-oxidant DMSO form it can also helps to resolve deep vein thrombosis at the body's periphery. Walter Last describes how, by using the oxidant form of Vitamin C -- called dehydroascorbic acid(DHA), more vitamin C is absorbed into the body than taking Vitamin C on it's own. See this link for more:

More Energy, Less Disease (by Walter Last)

In the article above, Walter Last describes a handy and useful internal protocol that is good for generating the dehydroascorbic acid(DHA) that is always necessary for increased Vitamin C absorption into the body -- here is an extract from the article:

"With serious infections it may be helpful to oxidize vitamin C to DHA before ingestion for better absorption and a stronger effect. Dissolve a teaspoon of sodium ascorbate and 1 teaspoon of MSM in a large glass of water. Add a teaspoon of 3% or about 10 drops of 35% hydrogen peroxide, a teaspoon of glycerine and a tiny amount of a copper compound. This solution does not keep and needs to be made fresh every day. Take a sip of it frequently during the day. In this way you can get a stronger antimicrobial effect with less vitamin C "

The simple Vitamin C and MSM internal and external protocol that Walter Last recommends in the above article is quickly described here:

"It is best to use vitamin C and MSM together, such as up to 2 rounded teaspoons or 10 grams each of sodium ascorbate and MSM, and possibly 1 to 3 teaspoons of 50 to 70% DMSO rubbed on the skin at problem areas, such as for arthritis."

Walter Last also advises that it's much more effective to use the oxidant form of ascorbic acid(or ascorbate) -- called dehydroascorbic acid -- which is the best form to help supply extra energy to the cells and to also help to kill a wide variety of bacteria, viruses, fungi and nanobacteria in the body as well.

Nattokinase and Soy Isoflavones

Posted by Curleyhead (Columbia, SC) on 11/02/2023

Nattokinase and Soy Isoflavones

What about estrogen effects from the high dosage of Nattokinase? Is it considered a danger/risk?

Replied by Art
1948 posts


In the one year study that the article was based on, they did not report any adverse events or significant side effects.


Nattokinase for Arterial Plaques

Posted by Debra (Sydney, Australia) on 11/01/2023 54 posts

Hi Art,

I just read your article on Nattokinase and the higher dose made a lot of sense to me. You mentioned in the article that Vitamin K2 has blood coagulase properties. I use Vitamin K2 (MK7) as an anticoagulant and am pretty sure this is what it does. I wondered if it was a typo?

The other question I wanted to ask, is if you have ever tried or researched Lumbrokinase for arterial plaques. I listened to a doctor speak recently on how Lumbrokinase was by far superior to both Natto and Serrapeptase. I have used both of the latter for years as I suffer from blood clotting issues, due to fibrin, mold and EMF. I have only just ordered the Lumbrokinase so hoping to see myself if there is a difference to the 250,000IU of Serrapeptase I'm currently taking. I would love to know what you think.

Replied by Art
1948 posts

Hi Debra,

Vitamin K2 works with other clotting factors in the body to aid in blood coagulation as discussed in this Cleveland Clinic article on the subject :

https://health.clevelandclinic.org/vitamin-k2/#:~:text=Aids in blood clotting, thing — and they can be.

Here is a relevant quote from the article :

One of the main functions of K vitamins is to allow your blood to clot. In fact, the “K” in vitamin K is in reference to the German word “koagulation, ” which translates to “coagulation” or the ability to clot (or thicken) blood.

Regarding lumbrokinase, I have looked at studies for it, but in comparison to nattokinase, they are fairly limited. PubMed only has 92 studies listed for "Lumbrokinase" whereas PubMed lists 242 studies for "Nattokinase".

On a related note, the nattokinase study I highlighted for the article was important because of the size of the study cohort of 1,062 eligible participants and the fact that they also used a dose one third the size of the 10,800 FU of 3,600FU, which showed no benefit at all. Imo, a study of this size carries significant weight in terms of the value of the results they get. I have never seen a study of this size for Lumbrokinase being used for atherosclerosis. I would, however, like to see the study or studies that the doctor you listened to based his claim on. I haven't seen a heads up study specifically for atherosclerosis utilizing lumbrokinase, nattokinase and serrapeptase/serratiopeptidase.

Thank you for your questions.


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2 User Reviews
5 star (2) 

Posted by El (Walton, WV) on 11/02/2023

K2 I like...

I trust all Mercola products as being of high quality - K2 = 180 mcg. I also like Carlyle K2+D3 in olive oil - one dropperful = 80 mcg K2 and 50 mcg (2000 IU) if Vitamin D.

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Posted by Dick D. (Birmingham, AL) on 11/01/2023

My GP has had me on one DaVinci Nattokinase Plus capsule for years. I am 84 years old and heart wise my Cardio Dr. says my heart and vessels are in good condition for my age.

Replied by Art
1948 posts


Thank you for the positive feedback!


Replied by Greg


What are your thoughts on taking a Tablespoon of high quality olive oil every day? Do you think it is necessary or not worth it since oils may go rancid on the shelf?

1948 posts

Hi Greg,

If you are a believer in the idea that inflammation in the vascular system is one of the main initiators of atherosclerosis, as I am, then absolutely, olive oil (OO) should have antiatherosclerotic effects via its anti inflammatory effects. I don't necessarily think it is the most potent natural antiatherosclerotic agent, but yes, I definitely feel it has antiatherosclerotic effects. Being a significant component of the Mediterranean diet adds a bit more confirmation to that idea since the Mediterranean diet is noted for antiatherosclerotic effects.



Thanks for the follow-up! I am bit confused on the K2 (mcg) vs taking Natto (FU's). Am I supposed to be taking both? I eat Nattobeans from this company. They say it has 500 mcg of vitamin K2 per serving.


1948 posts

Hi Greg,

What the study found is that the addition of vitamin K2 was additive to the effects of the nattokinase. So for better effect in reducing atherosclerosis, adding vitamin K2 improved the results of the nattokinase for atherosclerosis in the study.


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Posted by Joey (USA) on 11/01/2023

Hi ya,

I think what you shared is great info ~ however, is purchasing supplements from Amazon pure?

Replied by Art
1948 posts


Thank you for the feedback!

I only point to Amazon because they have a large selection, but they are not the only reseller of nattokinase. So if you have a reseller that you feel confident in to sell real products, that is always your option.