High-Dose Nattokinase to Shrink Atherosclerosis and Lower Blood Lipids

A study shows a daily dose of 10,800 FU of nattokinase (NK) to decrease atherosclerotic plaque and lower total cholesterol, LDL, and triglycerides.

Nattokinase is an enzyme derived from natto, a Japanese food from fermented soybeans. Natto has been enjoyed and proven safe for eating for more than a thousand years.

FU stands for Fibrin Units, the number of NK enzymes in a capsule. A 100 mg capsule typically contains 2,000 FU of NK. It is a supplement and can be bought over the counter.

Doctor’s Best Nattokinase

The featured study by Chen et al. was published in the Frontiers of Cardiovascular Medicine in August 2022 and involved 1,062 participants that were followed for one year.[1]

The study included 491 men and 571 women, with an average age of 67.5 years and an age distribution of 63–85 years.[1]

The results challenge the recommended dose of 2,000 FU/day of NK by the European Union.[3] and the Japan Natto Kinase Association.

Why did they use 10,800 FU?

A higher dose of NK was used because a 2021 randomized controlled trial by Hodis et al., using a 2,000 FU dose of NK, failed to slow atherosclerosis progression. In it, 265 patients were followed for three years.

Ren et al., in 2017, compared 6,000 FU of NK and simvastatin 20 mg in 76 patients. The treatment course was 26 weeks.[4]

Their result showed a profound decrease in atherosclerotic plaque size compared to simvastatin (36.6% vs. 11.5% change). In addition, NK reduced total cholesterol, low-density lipoprotein cholesterol, and triglyceride more than simvastatin.[4]

Based on the previous studies and NK’s safety track record, Chen et al. used the higher dose of 10,800 FU daily (three 3,600 FU tablets). Tests were done before and after the treatment period.[1]

Results

A significant reduction in the carotid artery intima-media’s thickness and the carotid plaque’s size. The improvement ranged from 66.5 to 95.4%.

After 12 months of NK consumption, 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%.

Common Carotid Artery Intima-Media Thickness (CCA-IMT) is an ultrasound test done on the neck’s common carotid artery (CCA). It measures the thickness of the layers of the artery, the media, which is a marker of subclinical atherosclerosis.

The image below shows the layers of the artery. The innermost is the tunica intima. The tunica media is the muscular part.

Source: By Blausen.com staff (2014). Medical gallery of Blausen Medical 2014

Atherosclerosis in the neck reflects the status of atherosclerosis development elsewhere in the body, like the coronary arteries and those going to the legs, which can cause a heart attack and peripheral artery disease, respectively.

The earlier studies by Hodis et al. and Ren et al. also measured the CCA-IMT to measure the degree of atherosclerosis.

Note: NK can reduce atherosclerosis due to the improvement of insulin sensitivity from NK use. (Taniguchi-Fukatsu et al.). Insulin resistance is the primary contributor to atherosclerosis formation.

What is Insulin Resistance?

2. Significant improvement in triglyceride (TG), total cholesterol (TC), LDL cholesterol (LDL-C), and HDL-C.

TG, TC, and LDL-C decreased by 15.3, 15.9, and 18.1%, respectively. High-density lipoprotein (HDL-C) increased by 15.8%.

The improvements in TC, TG, LDL-C, and HDL-C occurred in 95.4, 85.2, 84.3, and 89.1% of the participants.

The decrease in the TG and increase in HDL also contributed to the reduction in atherosclerosis. There are many other diseases associated with high triglyceride and low HDL.

The Triglyceride/HDL ratio detects insulin resistance and predicts diseases

3. The lipid-lowering effect of nattokinase was more prominent in subjects who smoked and drank alcohol and those with higher Body Mass Index (BMI).

These findings are helpful for those having difficulty transitioning to a healthy lifestyle. The smoking group referred to subjects who smoked daily regardless of the number of cigarettes used, and they were compared to non-smokers.

The alcohol group consumed over 100 grams of alcohol per week. The non-alcohol group drank less than 100 g per week.

Body Mass Index (BMI) was calculated using body weight in kilograms divided by the square of height in meters. The BMI was classified into two groups non-obese (BMI < 27.4 kg/m²) and obese (BMI ≥ 27.5 kg/m²) according to the obesity criteria of the World Health Organization (WHO) for Asians.

4. Regular exercise further improved the effects of NK.

Based on previous studies by Tudor-Locke et al., step counting was used to categorize participants as sedentary. 5,000 steps per day were used as the cut-off point to classify participants into two groups:

<5,000 steps/day (sedentary / non-exercise groups
>5,000 steps/day (non-sedentary / exercise group).

The authors explained the effects of exercise together with NK,

It can be interpreted that participants who regularly exercise have a more disciplined lifestyle with better compliance, which can be favorable for improving the lipid profile and atherosclerosis regression.

5. Taking NK with vitamin K2 and aspirin increased the effect.

Some participants used vitamin K2 (180 μg/day) regularly in addition to NK. The use of a low dose of aspirin (100 mg daily) use was relatively common.

NK and aspirin have the exact mechanisms of action on platelets leading to the inhibition of platelet aggregation and preventing clotting. Blood clot contributes to the development of an atherosclerotic plaque.

The synergistic effect of NK and vitamin K2 could be related to the positive impact of vitamin K2 on bone, muscle, and cardiovascular health.

6. The 10,800 FU/day dose is safe and well tolerated.

No side effects were reported among the subjects in the study. Yesterday, I wrote an article based on two pieces of research investigating whether there is a question of toxicity, genotoxicity, and chromosome aberration with the use of NK. Both found none, even at high doses.

Nattokinase is Nontoxic with a High Safety Margin.

7. NK at a dose of 3,600 FU/day was ineffective in lowering lipids and suppressing atherosclerosis progression.

Sixty-one participants took 3,600 FU of NK. Their lipid levels, CCA-IMT, and plaque size did not change after 12 months.

Doctor’s Best Nattokinase

Limitations of the study

The authors cautioned that although the study was large, it was retrospective, and they called for a randomized controlled trial.

There is also no current information on the long-term benefits of the participants, and more extended-duration studies should be made.

Conflict of Interest: Five of the ten authors are employed by Sungen Bioscience Co, Ltd in Shantou, China, which manufactured the NK used in the study.

Comment

I like the results of the research. Nattokinase is inexpensive and safe. Statins are associated with many side effects, like a tendency to develop type 2 diabetes, dementia, and muscle pain leading to frailty.

If needed, I will start with 2,000 FU thrice daily (6,000/daily) to decrease triglycerides and atherosclerosis.

Nattokinase is also beneficial for other conditions.

Caution

People who take warfarin (Coumadin) should not take nattokinase because it has vitamin K2, which contracts the blood thinning effect of coumadin.

Pregnant women should not take nattokinase due to a lack of studies. Always talk to your doctor before taking any supplements, and ask the pharmacist about any drug interactions.

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References:

Chen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q, Zhang X, Zeng J, Xu F, Lin Y. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants. Front Cardiovasc Med. 2022 Aug 22;9:964977. doi: 10.3389/fcvm.2022.964977. Erratum in: Front Cardiovasc Med. 2022 Dec 05;9:1076420. PMID: 36072877; PMCID: PMC9441630.
Hodis HN, Mack WJ, Meiselman HJ, Kalra V, Liebman H, Hwang-Levine J, Dustin L, Kono N, Mert M, Wenby RB, Huesca E, Rochanda L, Li Y, Yan M, St John JA, Whitfield L. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353. doi: 10.3233/CH-211147. PMID: 33843667.
Union E. Commission Implementing Decision (EU) 2017/115 of 20 January 2017 Authorising the Placing on the Market of Fermented Soybean Extract as a NOVEL FOOD INGREDIENT UNDER REGULATION (EC) No 258/97 of the European Parliament and of the Council (notified under document C(2017) 165). In: Union TE, editor. Brussels. (2017).
Ren NN, Chen HJ, Li Y, Mcgowan GW, Lin YG. [A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia]. Zhonghua Yi Xue Za Zhi. 2017 Jul 11;97(26):2038-2042. Chinese. doi: 10.3760/cma.j.issn.0376-2491.2017.26.005. PMID: 28763875.
Taniguchi-Fukatsu A, Yamanaka-Okumura H, Naniwa-Kuroki Y, Nishida Y, Yamamoto H, Taketani Y, Takeda E. Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance. Br J Nutr. 2012 Apr;107(8):1184-91. doi: 10.1017/S0007114511004156. Epub 2011 Sep 7. Erratum in: Br J Nutr. 2013 Oct;110(7):1356. PMID: 21899797.
Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. (2016) 88:87–99. 10.1016/j.fct.2015.12.025

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