Study: Natto Can Lower Blood Lipids and Heart Disease

A Chinese paper by C. Wei et al titled “Research Progress of Nattokinase in Reducing Blood Lipid” posted on 24 May 2025 reviews research regarding the positive effects natto has on issues associated with cardiovascular disease. By the way, natto can degrade spike proteins as well.

The paper is about 18 pages, with the main text at about 15 pages. The remaining are references.

Unlike many papers, the authors actually try to explain some background regarding natto including possible mechanisms and production methods.

Nattokinase (NK) can facilitate the reduction of blood lipids through the following four ways:

First, it regulates lipid metabolism. Nattokinase activates hormone-sensitive lipase to promote the hydrolysis of triglycerides into free fatty acids and glycerol.

Second, nattokinase is involved in lipoprotein metabolism, enhancing lipoprotein lipase activity to accelerate the decomposition of triglycerides into fatty acids.

Third, nattokinase can inhibit the key enzymes of cholesterol synthesis to reduce endogenous cholesterol production and lower blood lipids.

Fourth, nattokinase has a good thrombolytic effect. Nattokinase can promote the production of plasminogen by endogenous plasminogen activator or activate plasminogen by the urokinase produced by the urokinase. Plasminogen is converted into fibrinolytic enzyme to dissolve the thrombus. At the same time, nattokinase can also directly hydrolyze cross-linked fibrin to dissolve the thrombus.

Figure 2: Nattokinase lipid-lowering mechanisms.

Whilst many studies are in vitro or use animal models or the samples are relatively small, one large-scale study published in 2022 stands out. The study analyzed 1,062 participants between 2016 and 2020. They were given a total of 10,800 FU/day of NK for 12 months, with regular testing of blood lipids and carotid ultrasound, resulting in

…atherosclerotic plaque patients with a 21.7% reduction in the thickness of the inner intima-media, with an effective rate of 77.7%, and a 36.0% reduction in the area of plaque, with an effective rate of 66.5%, indicating that NK can effectively inhibit the progression of atherosclerosis. … NK administration for 12 months led to a decrease of 15.9, 15.3, and 18.1% in TC, TG, and LDL-C, respectively.

The study did not observe adverse reactions related to the NK and there were no significant differences between male and female participants.

Unlike many drugs that can cause adverse reactions, NK is a natural bioactive substance that has multiple mechanisms.

For example, atorvastatin and rosuvastatin can reduce LDL-C by 30–50%, which plays a key role in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, some patients may have adverse reactions, such as elevated liver enzymes and muscle pain, after using the drug; long-term use also has an increased risk of new-onset diabetes, and a certain percentage of patients are intolerant to statin, limiting its application.

NK, however, is not only able to regulate key enzymes of lipid synthesis and metabolism, “it also has synergistic effects of anti-inflammatory, antioxidant, and blood rheology improvement”.

NK is effective at body temperature, although this is reduced if the temperature gets too high. It is surprisingly freeze–thaw tolerant, able to go through 5 such cycles and still have 95% of the enzymes remain active.

As for safety, animal experiments suggest long-term use to be safe. For humans, occasional bloating and belching are possible but this can be mitigated by adjusting the dosage or taking with food.

In animal experiments, mice, rats, and other experimental animals were given far more than the recommended dose of NK for human beings, and under continuous observation for several months, there was no obvious toxic reaction, no abnormal pathological changes in the histological examination of organs, and stable hematological and biochemical indexes, which indicated that NK has no acute or chronic toxicity hazards to the animal body under the normal dosage.

Also keep in mind that many Japanese eat natto on a regular basis with no obvious problems.

Of course, in the form of pills, purity and dosage matter. Peak blood concentration occurs at 2 to 4 hours after ingestion with a half-life of 8 hours. Taking NK at night “can enhance the antithrombotic effect” given the slow blood flow.

NK is not the only food that can lower lipids and reduce cholesterol. For example, NK combined with red yeast rice is beneficial. However, it will be interesting to see larger studies involving other combinations such as garlic, onion, quercetin etc.

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