Cardiovascular, Bone, and Gut Health

How Japan's fermented soybean food supports heart health, bone density, and the microbiome through nattokinase, vitamin K2, and probiotics

Natto is a traditional Japanese food made by fermenting soybeans with the bacterium Bacillus subtilis var. natto. It contains an unusual combination of bioactive compounds — nattokinase (a clot-dissolving enzyme), vitamin K2 as menaquinone-7 (MK-7), and a community of living probiotic bacteria — making it one of the most nutrient-dense fermented foods studied. Large Japanese population studies link regular natto consumption to lower cardiovascular mortality [2] and significantly reduced fracture risk [3], benefits that go beyond ordinary soy foods.

What Makes Natto Different from Other Soy Foods

Raw soybeans are rich in protein and isoflavones but also contain antinutrients like phytic acid that block mineral absorption. Fermentation by B. subtilis transforms the bean in several important ways. Phytic acid is partially broken down, improving bioavailability of zinc and iron. Vitamin K2 content rises dramatically — natto contains more MK-7 per gram than any other food, with levels roughly 124 times higher than unfermented soybeans [1]. The bacterium also produces nattokinase directly in the food, meaning eating natto delivers the enzyme orally in its whole-food matrix.

MK-7 is the most bioavailable form of vitamin K2 and has a long half-life in the body (roughly 72 hours), compared to the few hours of MK-4 found in animal products. This extended presence in circulation matters for the two key functions of K2: activating osteocalcin (which anchors calcium into bone) and activating matrix Gla protein (which prevents calcium from depositing in arteries).

Cardiovascular Benefits

Natto supports heart health through two complementary mechanisms.

Nattokinase and clot prevention. Nattokinase is a serine protease that directly degrades fibrin, the protein that forms blood clots. It also stimulates the body's own plasminogen activators and reduces platelet aggregation. A large clinical trial with 1,062 participants found that daily nattokinase at 10,800 FU significantly reduced carotid artery intima-media thickness and plaque size over 26 months, as well as lowering LDL and triglycerides — effects not seen at the lower 3,600 FU dose [4].

Vitamin K2 and arterial calcification. Matrix Gla protein (MGP) is the body's primary defense against calcium depositing in arterial walls. MGP requires K2 to become active. When K2 intake is low, MGP remains inactive and arterial stiffness rises. Regular MK-7 intake from natto keeps MGP activated, which may explain why higher natto intake correlates with lower cardiovascular death in the Takayama cohort of nearly 29,000 adults followed for 16 years [2].

Bone Health

Natto's MK-7 supports bone by activating osteocalcin, a protein produced by osteoblasts (bone-building cells) that draws calcium into bone mineral. Without adequate K2, osteocalcin remains undercarboxylated and cannot perform this function effectively.

The JPOS longitudinal study (944 women, 3-year follow-up) found significant positive associations between habitual natto intake and changes in femoral neck and distal radius BMD in postmenopausal women [5]. A subsequent 17-year prospective study of 1,417 women showed that consuming 7 or more packs of natto per week was associated with a 49% lower fracture risk compared to less than one pack per week (HR 0.51, 95% CI: 0.30–0.87), even after adjusting for BMD and other confounders [3].

Gut and Immune Effects

B. subtilis natto is a spore-forming bacterium that survives stomach acid and colonizes the lower intestine. It produces bacteriocins that inhibit pathogens including Clostridium and some strains of Staphylococcus. Natto also contains gamma-polyglutamic acid (gamma-PGA), a prebiotic polymer that promotes growth of beneficial Lactobacillus species [1]. The isoflavones in natto (daidzein, genistein) are more bioavailable post-fermentation and have mild phytoestrogenic effects that may contribute to bone protection in postmenopausal women.

Practical Use

Natto has a very strong smell, sticky texture, and bitter flavor that many people find challenging at first. It is typically eaten over rice in Japan, often with mustard and soy sauce. Refrigerated natto packages are available in Asian grocery stores. A typical serving is one package (about 45–50 g), eaten 3–7 times per week in studies showing benefit.

Those taking blood thinners (warfarin/Coumadin) should be cautious — the high vitamin K content of natto can counteract the medication's anticoagulant effect. The nattokinase can also potentiate anticoagulants, so medical guidance is warranted.

For those who find the flavor difficult, nattokinase supplements offer the fibrinolytic enzyme isolated from the food. See our Nattokinase page for details on the extracted supplement and its clinical evidence.

Evidence Review

Cardiovascular Mortality: The Takayama Cohort

Nagata et al. (2017) analyzed data from the Takayama Study, a prospective cohort of 13,355 men and 15,724 women aged 35+ followed for 16 years from 1992 [2]. Natto intake was assessed by validated food-frequency questionnaire. The highest quartile of natto intake compared with the lowest was associated with a hazard ratio of 0.75 (95% CI: 0.64–0.88) for cardiovascular disease mortality after adjustment for covariates. This 25% risk reduction was specific to natto; regular tofu intake did not show the same association, suggesting the benefit lies in the fermented-food bioactives (nattokinase and K2) rather than soy protein alone. Stroke and ischemic heart disease mortality were both lower in high natto consumers.

Fracture Risk: 17-Year Prospective Cohort

Kojima et al. (2020) enrolled 1,417 postmenopausal women from the JPOS cohort and tracked them for a median 15.2 years (17,699 person-years) [3]. During follow-up, 172 women experienced osteoporotic fractures. After adjusting for age and hip BMD, women consuming 1–6 natto packs per week had a hazard ratio of 0.72 (95% CI: 0.52–0.98), and those consuming 7+ packs per week had a hazard ratio of 0.51 (95% CI: 0.30–0.87), compared with those consuming less than one pack per week. Importantly, this fracture risk reduction persisted after controlling for BMD, suggesting K2 improves bone quality (material properties, osteocalcin carboxylation) beyond simply increasing bone density.

Nattokinase and Atherosclerosis: 1,062-Participant Clinical Trial

Chen et al. (2022) conducted a large multicenter Chinese trial with 1,062 participants who had existing atherosclerotic plaques and/or hyperlipidemia [4]. Participants received placebo, 3,600 FU/day nattokinase, or 10,800 FU/day nattokinase for 26 months. The high-dose group showed significant reductions in carotid intima-media thickness, plaque volume, LDL cholesterol (down ~17%), and triglycerides, with no serious adverse events. The low-dose group showed no significant effects on any marker. This dose-response pattern suggests that therapeutic nattokinase concentrations require higher supplemental doses than typical food amounts, though whole natto likely provides additional benefits through co-present K2 and probiotics.

Bone Mineral Density: The JPOS 3-Year Study

Ikeda et al. (2006) analyzed 944 women across menopausal stages at baseline and 3-year follow-up within the JPOS cohort [5]. Habitual natto intake was significantly associated with positive changes in femoral neck BMD (p < 0.05) and distal radius BMD in postmenopausal women. No significant associations were found in premenopausal or perimenopausal women, consistent with the hypothesis that natto's protective effects emerge when estrogen-driven bone resorption accelerates.

Limitations and Strength of Evidence

Most natto and bone/cardiovascular studies are from Japanese populations with lifelong dietary habits — it is unclear whether shorter periods of natto consumption in non-Asian adults would confer similar benefits. Observational studies cannot exclude residual confounding (natto consumers may have overall healthier diets). The nattokinase clinical trial [4] used an isolated supplement at high dose, not whole natto. Mechanistic pathways (K2 activating MGP and osteocalcin, nattokinase degrading fibrin) are well-characterized at the molecular level, which strengthens confidence in biological plausibility. Overall, the evidence for bone protection in postmenopausal women is strong (consistent across multiple cohorts with long follow-up), while cardiovascular evidence is promising but warrants larger interventional studies.

References

Natto: A medicinal and edible food with health functionWang C, Chen J, Tian W, Han Y, Xu X, Ren T, Tian C, Chen C. Chinese Herbal Medicines, 2023. PubMed 37538862 →
Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama studyNagata C, Wada K, Tamura T, Konishi K, Goto Y, Koda S, Kawachi T, Iso H, Wakai K. American Journal of Clinical Nutrition, 2017. PubMed 27927636 →
Natto Intake is Inversely Associated with Osteoporotic Fracture Risk in Postmenopausal Japanese WomenKojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, Dochi M, Nishimura R, Uenishi K. Journal of Nutrition, 2020. PubMed 31825069 →
Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participantsChen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q, Zhang X, Zeng J, Xu F, Lin Y. Frontiers in Cardiovascular Medicine, 2022. PubMed 36072877 →
Intake of Fermented Soybeans, Natto, Is Associated with Reduced Bone Loss in Postmenopausal Women: Japanese Population-Based Osteoporosis (JPOS) StudyIkeda Y, Iki M, Morita A, Kajita E, Kagamimori S, Kagawa Y, Yoneshima H. Journal of Nutrition, 2006. PubMed 16614424 →