Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants

Abstract

Nattokinase (NK), known as a potent fibrinolytic and antithrombotic agent, has been shown to have antiatherosclerotic and lipid-lowering effects. However, data on human clinical studies are limited. In this clinical study involving 1,062 participants, our objective was to examine the efficacy of NK in atherosclerosis and hyperlipidemia and safety at the dose of 10,800 FU/day after 12 months of oral administration. Various factors, including lower doses that influence NK pharmacological actions, were also investigated. We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile. A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%. NK was found to be ineffective in lowering lipids and suppressing atherosclerosis progression at a dose of 3,600 FU/day. The lipid-lowering effect of NK was more prominent in subjects who smoked, drank alcohol, and subjects with higher BMI. Regular exercise further improved the effects of NK. Co-administration of vitamin K2 and aspirin with NK produced a synergetic effect. No noticeable adverse effects associated with the use of NK were recorded. In conclusion, our data demonstrate that atherosclerosis progression and hyperlipidemia can be effectively managed with NK at a dose of 10,800 FU/day. The lower dose of 3,600 FU per day is ineffective. The dose of 10,800 FU/day is safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin lead to improved outcomes in the use of NK. Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease and challenge the recommended dose of 2,000 FU per day.

Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial

“…We also found HDL-C and TG benefits in the combined supplementation, which was not significant in a recent study using the same supplementation for 4 months ( 33 ); likewise, study participants were CAD patients in our study whereas the previous trial by Liu et al recruited patients diagnosed with dyslipidemia but not CAD, therefore may have different physiological effects after the intervention. In studies with NK alone, another small pilot study by Wu et al used a higher nattokinase dosage (4,000 Fu) but in a relatively short trial period (8 weeks) did not observe significant changes in lipid markers ( 34 ), and Chen et al found improved lipid profile only with 10,800 FU/d regimen but not 3,600 FU/d in a 12-month trial among patients who were hyperlipidemic ( 35 ). These findings together suggest that using a robust dose supplementation regimen could potentially introduce significant effects on more markers over a prolonged period, while when NK and RYR are combined, the effective dosage is lower and requires a shorter time length than using them separately.…”

The synergy of serum SFRP5 levels and the TyG index in predicting coronary artery disease and prognosing major adverse cardiovascular events

“…(3) Adding SFRP5 to the existing risk prediction model could improve MACE prediction in patients with CAD. Hyperlipidemia is widely acknowledged as an independent risk factor for coronary atherosclerosis, contributing to the increased complexity and severity of coronary artery lesions and thereby significantly affecting patient prognosis [ 11 , 12 ].…”

Natto consumption suppresses atherosclerotic plaque progression in LDL receptor-deficient mice transplanted with iRFP-expressing hematopoietic cells

“…It is well established that natto intake is inversely correlated with cardiovascular disease mortality in Japanese adults 14 . In addition, nattokinase, the primary active enzyme in natto, has been shown to inhibit the progression of atherosclerosis 15 . Thus, it is unequivocal that natto has anti-atherosclerotic effects.…”