Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: A randomized controlled trial

Abstract

Objectives

The Improving Cerebral Blood Flow and Cognitive Function in Patients with Asymptomatic Intracranial/Carotid Stenosis with Nattokinase (ICC-PACS) trial was a single-center, double-blind, placebo-controlled study, aiming to evaluate the effects of 6-month nattokinase (NK) supplementation on cognitive function in patients with asymptomatic intracranial/carotid artery stenosis.

Methods

A total of 120 participants were randomized 1:1 to receive oral NK (8000 FU/day) or placebo for six months. Cognitive assessments and multimodal brain magnetic resonance imaging (MRI) were performed at baseline and 6-month follow-up.

Results

A total of 120 subjects were ultimately included (60 in the NK group and 60 in the placebo group), with balanced baseline characteristics between the two groups (average age 58.3 years, female 40.9 %). A total of 88 patients took the medication as required for 6 months and completed follow-up (45 in the NK group and 43 in the placebo group). Per-protocol analysis results found no significant between-group differences in the Montreal Cognitive Assessment (MoCA) score changes (mean difference: 0.038; 95 % CI: -1.109, 1.163; P = 0.948). However, exploratory analysis revealed significant difference in the changes of visuospatial function scores between the NK group and the placebo group (intergroup difference: 0.350; 95 % CI: 0.056, 0.649; P = 0.024), with reduced risk of visuospatial function decline in the NK group (OR: 0.35; 95 % CI: 0.127, 0.966). Besides, results were consistent in intention-to-treat analyses.

Conclusion

Six-month NK supplementation did not improve global cognition in asymptomatic intracranial/carotid stenosis patients. However, domain-specific enhancement in visuospatial function suggests potential selective neuroprotective effects.