In plain terms: Nattokinase has some human trial evidence supporting it, but the evidence is not yet strong enough for EBL to call it established. It is worth knowing about and worth discussing with your clinician.
Nattokinase
The evidence as the record states it
Kim et al. (Hypertension Research, 2008, PMID: 18971533), randomized double-blind placebo-controlled trial, n=86 (73 completed), nattokinase 2,000 FU/day for 8 weeks in adults with untreated systolic pressure of 130 to 159 mmHg. Net change vs control: systolic -5.55 mmHg (95% CI -10.5 to -0.57) and diastolic -2.84 mmHg (95% CI -5.33 to -0.33). Jensen et al. (Integrated Blood Pressure Control, 2016, PMID: 27785095), randomized double-blind placebo-controlled multicenter North American trial, n=79 (74 completed), 100 mg/day nattokinase (NSK-SD) for 8 weeks: diastolic pressure fell from 87 to 84 mmHg with no change on placebo (P<0.05); a systolic reduction, larger in men, is reported without a between-group test. Li et al. (Reviews in Cardiovascular Medicine, 2023, PMID: 39076715), meta-analysis of 6 randomized controlled trials, n=546: systolic -3.45 mmHg and diastolic -2.32 mmHg vs placebo; the same analysis found total and LDL cholesterol higher and HDL cholesterol lower with nattokinase. NULL FINDINGS: Hodis et al. (Clinical Hemorheology and Microcirculation, 2021, PMID: 33843667), the Nattokinase Atherothrombotic Prevention Study, randomized double-blind trial, n=265, median age 65.3, nattokinase 2,000 FU vs placebo for a median of 3 years in healthy people without cardiovascular disease and at low cardiovascular risk, not selected for raised blood pressure. No significant difference in carotid intima-media thickness or carotid arterial stiffness, and no significant effect on blood pressure or any laboratory measure. Yang et al. (Asia Pacific Journal of Clinical Nutrition, 2009, PMID: 19786378), randomized double-blind placebo-controlled trial, n=47 hyperlipidemic patients, 6 months: after controlling for baseline levels, only the nattokinase plus red yeast rice group, not the nattokinase-alone group, differed from placebo in total cholesterol, LDL cholesterol and the total to HDL ratio. Nattokinase carries no lipid claim here.
Trials showing no benefit
Clear. The trial's own title states that the COMBINATION with red yeast rice, but NOT nattokinase alone, had potent effects on blood lipids. Nattokinase monotherapy did not lower lipids. Recorded here so the null result is visible rather than sitting unexplained in the citation list. The Grade B rests on blood pressure (Kim 2008, PMID 18971533), not on lipids.
Why Grade B and not Grade A
Grade B reflects moderate human evidence -- typically a single strong trial, multiple smaller trials, or surrogate endpoint data without hard clinical outcome replication. To reach Grade A, Nattokinase would require at least one additional independent randomized trial demonstrating a hard clinical endpoint or objectively measured functional outcome in a comparable population.
What would move this grade
An independent randomized trial demonstrating a hard clinical endpoint -- mortality, major adverse event, or objectively confirmed functional improvement -- in an adequately powered sample, with results independently replicated, would support Grade A.
How this was studied
Form: Oral nattokinase capsules: 2,000 FU per capsule in the Korean trial (Kim 2008, PMID 18971533) and NSK-SD, a fermented soy natto extract with vitamin K2 removed, in the North American trial (Jensen 2016, PMID 27785095). · Dose: 2,000 FU per capsule versus placebo, daily frequency not stated in the abstract (Kim 2008, PMID 18971533); 100 mg nattokinase per day (Jensen 2016, PMID 27785095). The pooled 6 trials are described only as relatively low and relatively high total dosage (Li 2023 meta-analysis, PMID 39076715). · Population: 86 adults aged 20 to 80 with untreated systolic pressure 130 to 159 mmHg, 73 completed (Kim 2008, PMID 18971533); 79 North American adults with systolic pressure 130 mmHg or higher or diastolic 90 mmHg or higher, 74 completed, both sexes (Jensen 2016, PMID 27785095); 6 randomized trials, 546 participants pooled (Li 2023 meta-analysis, PMID 39076715). · Duration: 8 weeks in both blood pressure trials (Kim 2008, PMID 18971533; Jensen 2016, PMID 27785095). The null 2,000 FU trial ran a median of 3 years (Hodis 2021, PMID 33843667).