What Makes Natto Unique
Most fermented soy foods — miso, tofu, tempeh — share similar isoflavone profiles. Natto is different because fermentation with Bacillus subtilis produces two things found nowhere else in significant amounts:
Nattokinase is an enzyme secreted by the fermenting bacteria. Unlike most proteins, it survives digestion and is absorbed into circulation, where it directly acts on fibrin (the protein scaffold of blood clots). It also stimulates the body's own clot-dissolving pathways, raising tissue plasminogen activator (tPA) levels and degrading plasminogen activator inhibitor [4]. This is why the cardiovascular effects in the Takayama cohort appeared specific to natto — not to other soy foods [1].
Vitamin K2 as MK-7 is the long-chain form of menaquinone, primarily found in fermented foods. MK-7 has a half-life of roughly three days, compared to hours for K1, meaning a single daily serving keeps tissues saturated. Its critical role is activating two proteins: osteocalcin (which binds calcium into bone matrix) and matrix Gla protein (which prevents calcium from depositing in artery walls). In practice, this means MK-7 simultaneously supports bone strength and arterial flexibility. See our Vitamin K2 page for more on this routing mechanism.
Cardiovascular Benefits
A 2023 meta-analysis pooling six randomized controlled trials and 546 participants found that nattokinase supplementation reduced systolic blood pressure by 3.45 mmHg and diastolic by 2.32 mmHg (p<0.00001) [2]. A 2016 double-blind RCT in 74 adults confirmed these effects at 100 mg per day over eight weeks, with diastolic reductions of around 5–6 mmHg in men and significant decreases in von Willebrand factor — a clotting risk marker — in women [3].
It is worth noting one important null result: a well-powered three-year RCT in 265 healthy older adults found no effect of nattokinase on carotid intima-media thickness (a measure of arterial plaque progression) [8]. The likely explanation is that this population had low baseline cardiovascular risk — nattokinase appears to lower blood pressure and reduce clot burden, but may not reverse established plaque. The observational evidence from Japan, where natto is eaten regularly from early adulthood, may reflect long-term primary prevention rather than therapeutic reversal.
Bone Health
A three-year placebo-controlled trial in 244 postmenopausal women found that 180 mcg of MK-7 daily significantly slowed bone mineral density loss at the lumbar spine and femoral neck, with measurable improvements in bone strength indices [5]. At this dose, a daily serving of natto (which contains 300–1,000 mcg of MK-7 depending on the variety) would theoretically provide even more.
A separate 12-month RCT in 148 postmenopausal women with osteopenia confirmed the mechanism: MK-7 reduced undercarboxylated osteocalcin — the inactive form that means calcium is not being properly incorporated into bone — by 65.6%, versus only 6.4% in the placebo group. Trabecular bone number in the tibia held stable in the MK-7 group while declining 3.5% in placebo [6].
Gut Microbiome Effects
Bacillus subtilis spores are heat-resistant and survive both cooking and stomach acid. A 62-day human intervention study in 116 participants found that daily natto powder consumption significantly increased Bifidobacterium abundance in both sexes and raised Blautia levels in men [7]. Alpha diversity (a measure of microbiome richness) increased significantly in male participants by day 62. The effect was strongest in those with the lowest baseline Bifidobacterium — consistent with the idea that natto fills a microbial niche rather than displacing an already-healthy community.
Practical Notes
Natto is sold fresh in most Japanese or Asian grocery stores, typically in small polystyrene cups (50 g portions). Traditional preparation involves stirring it vigorously, which is thought to enhance the sticky mucilage. It is commonly eaten over rice with soy sauce and mustard, or mixed into miso soup.
For those unfamiliar with the flavor — which is earthy, slightly ammonia-like, and intensely savory — starting with small portions mixed into other foods (avocado toast, eggs, grain bowls) can ease the transition.
Nattokinase supplements are available for those who cannot tolerate the taste, though whole natto delivers MK-7, probiotics, protein (around 18 g per 100 g), iron, manganese, and copper alongside the enzyme.
People taking warfarin or other anticoagulants should consult their doctor before eating natto regularly, as the high vitamin K2 content may interfere with dosing.
Evidence Review
Large Prospective Cohort: Natto and Cardiovascular Mortality
The strongest evidence for whole natto comes from the Takayama study (Nagata et al., 2017) — a 16-year prospective cohort of 29,079 Japanese adults (13,355 male, 15,724 female) that recorded 1,678 CVD deaths [1]. Comparing the highest versus lowest quartile of natto intake, total CVD mortality hazard ratio was 0.75 (95% CI: 0.64–0.88, p-trend=0.0004). The reduction was specific to stroke: total stroke mortality HR = 0.68 (95% CI: 0.52–0.88), ischemic stroke HR = 0.67 (95% CI: 0.47–0.95). No significant associations were found for other soy foods, suggesting the benefit is not explained by isoflavones alone but by fermentation-specific compounds — nattokinase and MK-7.
Limitations include the observational design (healthy user bias is plausible, though the effect was specific to natto rather than soy broadly), and that confounders such as diet quality, physical activity, and socioeconomic status were adjusted for but cannot be fully excluded.
Nattokinase RCTs and Meta-Analysis
Li et al. (2023) synthesized six RCTs with 546 total participants in a systematic review and meta-analysis [2]. The pooled estimate showed nattokinase supplementation significantly reduced systolic BP by 3.45 mmHg (p<0.00001) and diastolic BP by 2.32 mmHg (p<0.00001). Lipid-lowering effects were inconsistent across trials and appeared dose-dependent. No adverse events were documented across all trials included.
Jensen et al. (2016) conducted a randomized double-blind placebo-controlled multicenter trial in 74 participants over eight weeks using 100 mg nattokinase [3]. Diastolic blood pressure decreased from 87 to 84 mmHg overall (p<0.05), with a stronger reduction in males (86 to 81 mmHg, p=0.006). Von Willebrand factor — a clotting risk marker — declined significantly in females. In participants with low baseline plasma renin activity, 66% showed renin increases in the nattokinase group vs. 8% with placebo, suggesting a blood pressure mechanism involving the renin-angiotensin system.
Weng et al. (2017) reviewed nattokinase's antithrombotic mechanisms [4]: the enzyme directly hydrolyzes fibrin, converts plasminogen to urokinase, degrades plasminogen activator inhibitor (PAI-1), and elevates tissue plasminogen activator (tPA). This multi-pathway activity makes it mechanistically distinct from antiplatelet drugs and single-target anticoagulants.
The important null result comes from Hodis et al. (2021) — a well-powered RCT in 265 participants (median age 65.3) followed for a median of three years [8]. Nattokinase supplementation showed no significant effect on carotid intima-media thickness (CIMT) progression versus placebo, and no blood pressure effect was detected in this cohort. The participants were healthy adults with low baseline CVD risk, which likely explains the discrepancy: blood pressure and clotting benefits may not translate to plaque regression in low-risk individuals with already-controlled risk factors.
Vitamin K2 (MK-7) and Bone Outcomes
Knapen et al. (2013) conducted a three-year placebo-controlled trial in 244 postmenopausal women randomized to 180 mcg MK-7 daily or placebo [5]. MK-7 significantly attenuated age-related decline in lumbar spine and femoral neck BMD. Bone strength indices at the femoral neck were favorably affected, and vertebral height loss in the lower thoracic region was reduced. This is the longest and most robust RCT for MK-7 and bone endpoints, and its three-year duration is important because bone remodeling cycles require extended observation.
Rønn et al. (2016) confirmed the microarchitectural mechanism in 148 postmenopausal women with osteopenia randomized to 375 mcg MK-7 or placebo for 12 months [6]. Undercarboxylated osteocalcin — a biomarker of inadequate K2 status — fell 65.6% in the MK-7 group vs. 6.4% in placebo (p<0.01). High-resolution peripheral quantitative CT imaging at the tibia showed trabecular number was maintained in MK-7 participants (−0.1%) but declined in placebo (−3.5%), and trabecular spacing held stable in MK-7 (+1.2%) versus worsening in placebo (+4.5%). These structural improvements are clinically meaningful because trabecular microarchitecture is an independent predictor of fracture risk beyond BMD alone.
Gut Microbiome: Human Intervention Data
Kono et al. (2022) followed 116 participants who consumed natto powder containing Bacillus subtilis var. natto spores for 62 days [7]. Fecal microbiome sequencing showed statistically significant increases in Bifidobacterium in both sexes and Blautia in males. Alpha diversity (Shannon index) increased significantly in male participants by day 62 vs. baseline (p<0.01). The effect was most pronounced in participants with the lowest baseline Bifidobacterium abundance, consistent with a capacity-filling rather than competitive-displacement mechanism.
Overall Confidence Assessment
- Cardiovascular mortality reduction with regular natto intake: Strong observational evidence (29K participants, 16 years, hard endpoints) but limited to Japanese populations with lifelong consumption patterns.
- Blood pressure reduction from nattokinase: Moderate confidence — consistent across multiple RCTs, confirmed by meta-analysis, biologically plausible mechanism. Not yet demonstrated to reduce atherosclerotic plaque in low-risk populations.
- Bone protection from MK-7: Strong evidence across multiple RCTs with consistent effects on both bone mass and microarchitecture.
- Gut microbiome support: Emerging — one robust human intervention study with meaningful microbiome endpoints; replication needed.