Plaque, Aluminum & Brain Atrophy All Improve
Alzheimer’s disease (AD) now affects >55 million people and offers few safe therapies. In an in vivo 2024 rat study, oral nattokinase (65 or 130 mg kg⁻¹ day⁻¹) dramatically reduced β-amyloid plaques, removed brain aluminum, and restored lost brain volume within 10 weeks. These results position nattokinase—as supplied in nattiase® extract—as a novel neuroprotective candidate beyond its well-known cardiovascular role.
Can Nattokinase Counter Aluminum + D-Galactose–Driven AD Pathology?
Researchers induced AD-like damage in Wistar rats using AlCl₃ (200 mg kg⁻¹) + D-galactose (300 mg kg⁻¹) for ten weeks, and gavaged nattokinase at 2,600 FU or 5,200 FU (kg⁻¹ day⁻¹).
They tracked:
- Aluminum burden in brain tissue
- β-Amyloid dynamics (free Aβ in CSF + plaque counts)
- Structural integrity (µCT brain volume)
- Cognition (Morris water-maze probe)
Key Results
| Endpoint
| Control | Vehicle [AD model] | nattiase® treatment* | Outcome |
Brain aluminum
(µg g⁻¹) | 1.69±0.52 | 2.55±0.75 | 1.75~2.63 | Heavy-metal load trended back toward normal
|
| β-Amyloid plaques
(plaques/slide) | 9.4±2.1 | 18.5±3.7 | 11.6~7.2
| Plaque count ↓ up to ≈37 % |
Free Aβ in CSF
(ng ml⁻¹) | 18.9±2.8 | 11.2±2.4 | 16.3~17.5 | Restored toward control level |
Brain volume (µCT, mm³) | 2,091±58 | 1,952±60 | 2,070~2,077 | Atrophy essentially reversed |
| Maze path length (cm) | 188±22 | 263±31 | 199~255
| Shorter distance (better spatial memory) |
*nattiase treatment resulted from 2,600 FU or 5,200 FU (kg⁻¹ day⁻¹) dosing group
Takeaways
- Multimodal Benefit
High-dose nattokinase removed brain aluminum, shrank plaques 37%, enabled free Aβ in CSF and protected the brain from shrinkage in just 10 weeks.
- Early Cognitive Signal
Shorter probe-path length hints at memory improvement, warranting longer behavioral trials.
- Safety Edge
No liver-enzyme spikes or weight loss were noted, echoing nattokinase’s long human safety history.
- Next Step
Combine nattokinase with standard AD drugs or antioxidant stacks in aged-rat or primate models before moving to Phase I.
FAQs
Q: What human dose would match 130 mg kg⁻¹ in rats?
A: Using FDA’s Km conversion, 130 mg kg⁻¹ ≈ 21 mg kg⁻¹ human → ~1,500 mg for a 70 kg adult (~60,000 FU). Clinical studies typically use 2,000 FU, so more translational work is needed before high-dose trials.
Q: Does nattokinase cross the blood–brain barrier?
A: The enzyme itself may not; benefits likely stem from systemic fibrin breakdown, reduced micro-thrombi, and enhanced amyloid clearance. Further pharmacokinetic studies are in progress.
Q: Is nattokinase safe for Alzheimer’s patients on anticoagulants
A: It thins blood; combine only under physician supervision, especially with warfarin or DOACs. Recommended to begin at ≤ 2,000 FU and monitor International Normalized Ratio (INR).
References
Tanikawa et al., “Effect of Nattokinase in D-galactose- and Aluminum Chloride-induced Alzheimer's Disease Model of Rat”, 2024 (doi: https://doi.org/10.21873/invivo.13744)
