{"url":"https://whatshealthyandwhy.com/natto/cardiovascular-bones-and-gut","path":"/natto/cardiovascular-bones-and-gut","alternates":{"json":"https://whatshealthyandwhy.com/api/articles/natto/cardiovascular-bones-and-gut.json","markdown":"https://whatshealthyandwhy.com/natto/cardiovascular-bones-and-gut.md"},"topic":{"slug":"natto","name":"Natto","url":"https://whatshealthyandwhy.com/natto"},"slug":"cardiovascular-bones-and-gut","order":1,"title":"Cardiovascular Protection, Bone Health, and Gut Support","question":"Do the nattokinase and vitamin K2 in natto lower blood pressure and protect bones?","answer":"Nattokinase probably lowers blood pressure slightly and MK-7 vitamin K2 probably slows postmenopausal bone loss, but plaque and gut benefits are unproven.","description":"What studies show about natto, the traditional Japanese fermented soybean food that supplies nattokinase, vitamin K2 (MK-7), and Bacillus subtilis spores: blood pressure, cardiovascular mortality, bone health, and the gut microbiome","confidence":4,"confidenceNote":"A meta-analysis of six trials (546 people) and two MK-7 bone trials support small benefits, but a 265-person three-year trial found no plaque benefit.","evidenceSummary":{"rctCount":4,"observationalCount":1,"metaAnalysisCount":1,"totalParticipants":"29,000+","replicated":true,"newestStudyYear":2023},"category":{"categoryTitle":"What's Good For You","categorySlug":"good-for-you","subcategoryName":"Foods & Drinks","subcategorySlug":"foods","url":"https://whatshealthyandwhy.com/explore/good-for-you/foods"},"actions":["Start with small portions of natto mixed into eggs, avocado toast or grain bowls, or over rice with soy sauce and mustard.","The three-year bone trial used 180 mcg MK-7 daily; a natto serving contains roughly 300–1,000 mcg, depending on variety [5].","In the blood pressure trial, 100 mg nattokinase daily for eight weeks lowered diastolic pressure; ask your doctor before supplementing [3]."],"cautions":["If you take warfarin or other anticoagulants, natto's high vitamin K2 may interfere with dosing; consult your doctor before eating it regularly.","Nattokinase did not reduce plaque progression in a 265-person, three-year trial of healthy older adults [8].","Gut-microbiome benefits rest on a single 116-person study and still need replication [7]."],"simpleText":"Natto is a traditional Japanese food made by fermenting soybeans with Bacillus subtilis var. natto. The result is sticky, pungent, and one of the most nutrient-dense foods studied for cardiovascular and bone health. It is the richest dietary source of vitamin K2 (as MK-7) and the only whole food that naturally contains nattokinase, a potent enzyme that supports healthy blood flow. A large 16-year study of nearly 30,000 Japanese adults found that the highest natto consumers had 25% lower cardiovascular mortality compared to those who ate the least [1].","mediumText":"What Makes Natto Unique\n\nMost 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:\n\nNattokinase is an enzyme secreted by the fermenting bacteria. In the lab it acts directly on fibrin (the protein scaffold of blood clots) and also stimulates the body's own clot-dissolving pathways, raising tissue plasminogen activator (tPA) levels and degrading plasminogen activator inhibitor [4]. How much active enzyme actually reaches the bloodstream after eating natto or taking a supplement is still not well characterized in people [14]. In the Takayama cohort, the cardiovascular association was seen with natto but not with other soy foods [1].\n\nVitamin 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.\n\nCardiovascular Benefits\n\nA 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 [2]. A 2016 double-blind RCT in 79 adults with elevated blood pressure (74 completed it) found that 100 mg of nattokinase a day for eight weeks lowered both systolic and diastolic pressure, most clearly in men, whose diastolic pressure fell from 86 to 81 mmHg. A fall in von Willebrand factor — a clotting-risk marker — appeared in women, but only at a lenient significance threshold (P < 0.1) [3].\n\nIn a larger clinical study of 1,062 people with atherosclerosis or high cholesterol, 10,800 fibrinolytic units (FU) a day for 12 months was followed by thinner carotid artery walls, smaller carotid plaques, and better lipid profiles, while 3,600 FU a day did nothing; the authors also reported no noticeable adverse effects [11]. This is a single clinical study, so placebo-controlled replication is still needed.\n\nIt is worth noting one important null result: a three-year RCT in 265 healthy adults (median age 65) with no clinical cardiovascular disease found that 2,000 FU a day of nattokinase had no effect on carotid intima-media thickness or arterial stiffness (measures of arterial plaque progression) [8]. The likely explanation is that this population had low baseline cardiovascular risk — and the dose was far below the 10,800 FU/day used in the positive study [11]. Nattokinase appears to lower blood pressure modestly, but it has not been shown to slow plaque in low-risk people. The observational evidence from Japan, where natto is eaten regularly from early adulthood, may reflect long-term primary prevention rather than therapeutic reversal.\n\nA second large Japanese cohort, of 92,915 adults aged 45–74 followed for a median of 14.8 years, found that eating more fermented soy (mainly natto and miso) was linked to about 10% lower all-cause mortality (highest versus lowest fifth: hazard ratio 0.90 in men and 0.89 in women), while total soy intake showed no link with mortality. Natto in particular was linked to lower cardiovascular mortality in both sexes. The authors caution that unadjusted residual confounding may explain part of the association [9].\n\nBone Health\n\nA 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 (though not at the total hip), with measurable improvements in bone strength indices [5]. A serving of natto supplies more MK-7 than that: the regular natto tested in one Japanese study contained 775 mcg per 100 g, and eating it raised blood MK-7 and the active, carboxylated form of osteocalcin [10].\n\nA 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, although bone mineral density itself did not differ between the groups [6].\n\nStudies of people who actually eat natto point the same way, but they are observational. In the Japanese Population-based Osteoporosis cohort, postmenopausal women who ate more natto lost less bone at the femoral neck over three years [13]. In a follow-up of 1,417 postmenopausal women (median 15.2 years), those who ate seven or more packs a week (a pack is about 40 g) had about half the risk of an osteoporotic fracture of those who ate less than one pack a week (hazard ratio 0.51, 95% CI 0.30–0.87, adjusted for age and hip bone density) [12].\n\nGut Microbiome Effects\n\nBacillus subtilis spores are heat-resistant and survive both cooking and stomach acid. In a Japanese study of a natto-powder capsule containing B. subtilis var. natto spores, the relative abundance of Bifidobacterium and Blautia rose in men and of Bifidobacterium in women, and the size of the change depended on how much Bifidobacterium each person had at baseline [7]. The authors describe it as a case study of the gut microbiota, so it shows a shift in bacteria counts rather than a health benefit.\n\nPractical Notes\n\nNatto 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.\n\nFor 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.\n\nNattokinase 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.\n\nPeople taking warfarin or other anticoagulants should consult their doctor before eating natto regularly, as the high vitamin K2 content may interfere with dosing.","deepText":"Evidence Review\n\nLarge Prospective Cohorts: Natto and Mortality\n\nThe 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, including 677 from stroke and 308 from ischemic heart disease [1]. Comparing the highest versus lowest quartile of natto intake, the total CVD mortality hazard ratio was 0.75 (95% CI: 0.64–0.88, p-trend=0.0004); the hazard ratio was 0.68 (95% CI: 0.52–0.88) for total stroke mortality and 0.67 (95% CI: 0.47–0.95) for ischemic stroke mortality. Total soy protein and isoflavone intake, and soy protein and isoflavones from soy foods other than natto, were not associated with total CVD mortality. That suggests, but cannot prove, that fermentation-specific compounds such as nattokinase and MK-7 account for the pattern.\n\nThe Japan Public Health Center-based Prospective Study (Katagiri et al., 2020) followed 92,915 adults aged 45–74 (42,750 men and 50,165 women) for a median of 14.8 years, during which 13,303 deaths were identified [9]. Total soy product intake was not associated with total mortality (highest versus lowest fifth: hazard ratio 0.98 in both men and women). Fermented soy intake (natto and miso) was inversely associated with all-cause mortality: 0.90 (95% CI 0.83–0.97) in men and 0.89 (0.80–0.98) in women. Natto showed significant inverse associations with total cardiovascular mortality in both sexes. The authors caution that the association for fermented soy might be attenuated by unadjusted residual confounding.\n\nBoth studies are observational. Natto is more commonly eaten by older, rural, and traditional Japanese adults — populations that may differ in other health behaviors — and confounders such as diet quality, physical activity, and socioeconomic status were adjusted for but cannot be fully excluded.\n\nNattokinase Trials and Meta-Analysis\n\nLi et al. (2023) synthesized six RCTs with 546 total participants in a systematic review and meta-analysis [2]. The pooled estimate showed that nattokinase significantly reduced systolic BP by 3.45 mmHg and diastolic BP by 2.32 mmHg. The lipid results were not favorable at the doses studied: relatively low total doses were associated with higher total and LDL cholesterol and lower HDL cholesterol; relatively high total doses were associated with higher total cholesterol but no difference in HDL or LDL; triglycerides were unchanged; and blood glucose rose slightly (mean difference 0.40). The authors concluded that nattokinase can serve as an adjunctive therapy for hypertension, that low-dose supplementation probably has no lipid-lowering effect, and that whether its effects are dose-dependent needs further work. No notable adverse events were reported.\n\nJensen et al. (2016) conducted a randomized double-blind placebo-controlled multicenter trial in 79 North American adults with elevated blood pressure (74 completed it) over eight weeks, using 100 mg a day of a nattokinase concentrate from which vitamin K2 had been removed [3]. Systolic pressure fell in both sexes, more robustly in males. Diastolic pressure decreased from 87 to 84 mmHg overall (p<0.05 compared with placebo, which stayed at 87), with a stronger reduction in males (86 to 81 mmHg, p<0.006). Von Willebrand factor — a clotting risk marker — declined in females, but only at a significance level of P<0.1. In the subgroup with low baseline plasma renin activity, 66% showed renin increases in the nattokinase group versus 8% with placebo (P<0.1). The authors interpret the results as suggesting sex-specific mechanisms.\n\nChen et al. (2022) reported a clinical study of 1,062 participants with atherosclerosis or hyperlipidemia who took nattokinase for 12 months [11]. At 10,800 FU/day the lipid profile improved significantly, and carotid artery intima-media thickness and carotid plaque size fell; at 3,600 FU/day nattokinase was ineffective. The lipid-lowering effect was more prominent in smokers, in people who drank alcohol, and in people with a higher BMI, and the authors report that regular exercise improved the effect and that co-administration of vitamin K2 and aspirin produced a synergistic effect. No noticeable adverse effects were recorded. The authors argue that their results challenge the commonly recommended 2,000 FU/day dose. The published abstract describes dose and lifestyle comparisons rather than a placebo-controlled trial, so the findings need independent confirmation.\n\nWeng et al. (2017) reviewed nattokinase as an oral antithrombotic agent: a blood-clot-dissolving protein produced by B. subtilis during fermentation, whose safety had been evaluated and which was then in a Phase II trial for atherothrombotic prevention in the United States [4]. Its proposed actions include direct fibrin breakdown and effects on the plasminogen-activator system, which differ from those of antiplatelet drugs. How much active enzyme survives digestion and reaches the circulation in people is still an open question [14].\n\nThe important null result comes from Hodis et al. (2021): 265 adults without clinical cardiovascular disease (median age 65.3) were randomized to 2,000 FU/day of nattokinase or matching placebo and followed for a median of three years [8]. Annualized change in carotid intima-media thickness and carotid arterial stiffness did not differ between nattokinase and placebo, and nattokinase had no effect on blood pressure or on any laboratory measure, including blood coagulation, fibrinolysis, and inflammatory markers. The authors concluded that nattokinase has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk of CVD. That does not settle whether higher doses or higher-risk people would benefit, as the Chen study suggests [11].\n\nVitamin K2 (MK-7) and Bone Outcomes …","deepTruncated":true,"references":[{"id":"1","title":"Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study","authors":"Nagata C, Wada K, Tamura T, Konishi K, Goto Y, Koda S, Kawachi T, Tsuji M, Nakamura K","year":2017,"journal":"American Journal of Clinical Nutrition","pmid":"27927636","url":"https://pubmed.ncbi.nlm.nih.gov/27927636/"},{"id":"2","title":"Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","authors":"Li X, Long J, Gao Q, Pan M, Wang J, Yang F, Zhang Y","year":2023,"journal":"Reviews in Cardiovascular Medicine","pmid":"39076715","url":"https://pubmed.ncbi.nlm.nih.gov/39076715/"},{"id":"3","title":"Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial","authors":"Jensen GS, Lenninger M, Ero MP, Benson KF","year":2016,"journal":"Integrated Blood Pressure Control","pmid":"27785095","url":"https://pubmed.ncbi.nlm.nih.gov/27785095/"},{"id":"4","title":"Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease","authors":"Weng Y, Yao J, Sparks S, Wang KY","year":2017,"journal":"International Journal of Molecular Sciences","pmid":"28264497","url":"https://pubmed.ncbi.nlm.nih.gov/28264497/"},{"id":"5","title":"Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women","authors":"Knapen MHJ, Drummen NE, Smit E, Vermeer C, Theuwissen E","year":2013,"journal":"Osteoporosis International","pmid":"23525894","url":"https://pubmed.ncbi.nlm.nih.gov/23525894/"},{"id":"6","title":"Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women","authors":"Rønn SH, Harsløf T, Pedersen SB, Langdahl BL","year":2016,"journal":"European Journal of Endocrinology","pmid":"27625301","url":"https://pubmed.ncbi.nlm.nih.gov/27625301/"},{"id":"7","title":"Fluctuations in Intestinal Microbiota Following Ingestion of Natto Powder Containing Bacillus subtilis var. natto SONOMONO Spores: Considerations Using a Large-Scale Intestinal Microflora Database","authors":"Kono K, Murakami Y, Ebara A, Okuma K, Tokuno H, Odachi A, Ogasawara K, Hidaka E, Mori T, Satoh K, Kimoto S, Masuyama H, Takeda M, Managi S","year":2022,"journal":"Nutrients","pmid":"36145213","url":"https://pubmed.ncbi.nlm.nih.gov/36145213/"},{"id":"8","title":"Nattokinase atherothrombotic prevention study: A randomized controlled trial","authors":"Hodis HN, Mack WJ, Meiselman HJ, et al.","year":2021,"journal":"Clinical Hemorheology and Microcirculation","pmid":"33843667","url":"https://pubmed.ncbi.nlm.nih.gov/33843667/"},{"id":"9","title":"Association of soy and fermented soy product intake with total and cause specific mortality: prospective cohort study","authors":"Katagiri R, Sawada N, Goto A, Yamaji T, Iwasaki M, Noda M, Iso H, Tsugane S","year":2020,"journal":"BMJ","pmid":"31996350","url":"https://pubmed.ncbi.nlm.nih.gov/31996350/"},{"id":"10","title":"Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals","authors":"Tsukamoto Y, Ichise H, Kakuda H, Yamaguchi M","year":2000,"journal":"Journal of Bone and Mineral Metabolism","pmid":"10874601","url":"https://pubmed.ncbi.nlm.nih.gov/10874601/"},{"id":"11","title":"Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants","authors":"Chen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q, Zhang X, Zeng J, Xu F, Lin Y","year":2022,"journal":"Frontiers in Cardiovascular Medicine","pmid":"36072877","url":"https://pubmed.ncbi.nlm.nih.gov/36072877/"},{"id":"12","title":"Natto Intake is Inversely Associated with Osteoporotic Fracture Risk in Postmenopausal Japanese Women","authors":"Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, Tamaki J, Kagamimori S, Iki M","year":2020,"journal":"Journal of Nutrition","pmid":"31825069","url":"https://pubmed.ncbi.nlm.nih.gov/31825069/"},{"id":"13","title":"Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study","authors":"Ikeda Y, Iki M, Morita A, Kajita E, Kagamimori S, Kagawa Y, Yoneshima H","year":2006,"journal":"Journal of Nutrition","pmid":"16614424","url":"https://pubmed.ncbi.nlm.nih.gov/16614424/"},{"id":"14","title":"Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases","authors":"Chen H, McGowan EM, Ren N, Lal S, Nassif N, Shad-Kaneez F, Qu X, Lin Y","year":2018,"journal":"Biomarker Insights","pmid":"30013308","url":"https://pubmed.ncbi.nlm.nih.gov/30013308/"}],"wordCount":2737,"source":{"path":"src/content/topics/natto/cardiovascular-bones-and-gut.md"},"citeAs":"“Do the nattokinase and vitamin K2 in natto lower blood pressure and protect bones?.” What's Healthy and Why. https://whatshealthyandwhy.com/natto/cardiovascular-bones-and-gut","notice":"General information backed by peer-reviewed research, not medical advice."}