July 2025 Update: Nattokinase’s Role in Fighting Inflammation and Clotting

Following up on my previous blog from late 2023 about the persistence of SARS-CoV-2 spike protein in the body and nattokinase’s potential to help, I’ve reviewed the latest research since then to see if it sheds more light on how nattokinase may ease symptoms connected to spike protein accumulation. Unfortunately, there have been no further specific long-covid studies, but there have been some interesting studies that confirm its usefulness in combatting both inflammation and blood clotting.

New Research from 2023-2025

Recent studies confirm that the spike protein, whether from infection or vaccination, can remain in the body for months and contribute to cardiovascular, neurological, and inflammatory issues seen in Long COVID and post-vaccine syndromes. For example, Hulscher et al. reviewed post-acute sequelae of COVID-19 infection and vaccination, highlighting spike protein toxicity as a key factor (Hulscher et al., 2023)[13].

Nattokinase, derived from fermented soybeans, continues to show promise not just in breaking down fibrin — the protein involved in blood clot formation — but also in reducing inflammation and oxidative stress linked to spike proteins (Granito et al., 2024)[5]; (Shi et al., 2025)[2].

Blood Clot Dissolution

Nattokinase’s ability to degrade fibrin clots helps dissolve the microclots that spike proteins can promote, which block small blood vessels and worsen symptoms (Granito et al., 2024)[5]. Animal and cell studies show NK is effective at breaking down clots without damaging healthy tissue, making it a safer option compared to some blood thinners (Muric et al., 2024)[6].

Anti-Inflammatory and Antioxidant Effects

Beyond clot breakdown, NK activates key cellular processes like autophagy (a cell’s cleanup mechanism) and inhibits inflammasomes — protein complexes that drive inflammation. These actions reduce vascular inflammation and tissue damage caused by spike proteins (Chiu et al., 2024)[10]; (Yang et al., 2025)[7].

Neuroprotection and Improved Blood Flow

Several studies highlight NK’s neuroprotective role. For example, NK treatment in stroke models reduced brain damage and supported nerve regeneration, which could be crucial for neurological symptoms experienced in Long COVID (Mahakalakar et al., 2025)[3]; (Wu et al., 2023)[15].

Absorption and Safety

One challenge with oral enzymes is how well they survive digestion and get absorbed. A recent study using rat and cell models clarified that NK’s absorption in the small intestine is energy-dependent and involves multiple uptake pathways, supporting the need for enteric-coated supplements for better delivery (Feng et al., 2023)[14].

In addition, recent trials and meta-analyses indicate that nattokinase at doses around 2,000 FU daily improves cardiovascular markers without significant side effects, though people on blood thinners should consult a doctor first (Li et al., 2023)[8].

Relevance for Long Covid

If you’re dealing with lingering symptoms after COVID or vaccination related to inflammation and clotting, this growing body of research suggests nattokinase could:

• Help dissolve persistent microclots caused by spike proteins

• Reduce chronic inflammation in blood vessels and tissues

• Support brain and nerve health impaired by spike protein toxicity

Combining Nattokinase with Other Natural Compounds

Research from late 2023 pointed to potential benefits from combining NK with other anti-inflammatory natural supplements such as curcumin and bromelain, which may work together to help clear spike proteins and calm inflammation more effectively (Shi et al., 2025)[2]; (Chiu et al., 2024)[10]. I wrote about this in an earlier blog if you want more details about doses used.

What about other enzymes?

Although there have been no more recent studies looking at Nattokinase treatment for Long Covid, there is at least one clinical trial currently exploring similar systemic proteolytic enzymes for long COVID symptoms. A 2023 randomized controlled trial published in Integrative Medicine found that a combination of systemic enzymes (including serratiopeptidase and bromelain) plus probiotics significantly improved post-COVID fatigue, with 91% of participants reporting they were fatigue-free after 14 days. Additionally, an upcoming trial is being planned to test lumbrokinase—a clot-dissolving enzyme similar to nattokinase—for long COVID recovery, using a dose of 300,000 FUs twice daily.

Summary

The newest research from 2023 to 2025 confirms nattokinase as a promising natural aid to combat the damaging effects of lingering SARS-CoV-2 spike protein — addressing both abnormal clotting and inflammation at the root of many Long COVID symptoms. Other enzymes, including serratiopeptidase, bromelain and lumbrokinase are now being studied for effectiveness against long covid symptoms.

Cliff Russell, Registered Osteopath

References

1. Hulscher N, Procter BC, Wynn C, McCullough PA. Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination. Cureus. 2023 Nov 21;15(11):e49204. doi:10.7759/cureus.49204. PMID: 38024037 PubMed

2. Shi Y, Liu C, Gui Y, et al. A Nattokinase-Loaded Nanozyme for Alleviating Acute Myocardial Infarction via Thrombolysis and Antioxidation. Adv Healthc Mater. 2025 Mar;14(8):e2402763. doi:10.1002/adhm.202402763. PMID: 39676430 PubMed

3. Mahakalakar N, Mohariya G, Taksande B, et al. Nattokinase as a potential therapeutic agent for preventing blood-brain barrier dysfunction in neurodegenerative disorders. Brain Res. 2025 Feb 15;1849:149352. doi:10.1016/j.brainres.2024.149352. PMID: 39592088 PubMed

4. Granito M, Alvarenga L, Ribeiro M, et al. Nattokinase as an adjuvant therapeutic strategy for non-communicable diseases: a review of fibrinolytic, antithrombotic, anti-inflammatory, and antioxidant effects. Expert Rev Cardiovasc Ther. 2024 Oct;22(10):565-574. doi:10.1080/14779072.2024.2416663. PMID: 39404094 PubMed

5. Muric M, Nikolic M, Todorovic A, et al. Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings. Biomolecules. 2024 Aug 7;14(8):956. doi:10.3390/biom14080956. PMID: 39199344 PubMed

6. Yang XY, Wang SL, Xue WC, et al. Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress, and Coagulation. Antioxid Redox Signal. 2025 Feb;42(4-6):228-248. doi:10.1089/ars.2023.0527. PMID: 39135387 PubMed

7. Feng H, Liu C, Liu Q, et al. Study on the transport and internalisation mechanism of dietary supplement nattokinase in the small intestine using animal and Caco-2 cell monolayer models. Xenobiotica. 2023 Dec;53(12):670-680. doi:10.1080/00498254.2023.2284249. PMID: 37971898 PubMed

8. Li X, Long J, Gao Q, et al. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Rev Cardiovasc Med. 2023 Aug 15;24(8):234. doi:10.31083/j.rcm2408234. PMID: 39076715 PubMed

9. Chiu HW, Chou CL, Lee KT, et al. Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1. Int J Biol Macromol. 2024 May;268(Pt 2):131779. doi:10.1016/j.ijbiomac.2024.131779. PMID: 38679250 PubMed

10. Wu H, Zhang Q, Xu P, et al. Nattokinase Promotes Post-stroke Neurogenesis and Cognition Recovery via Increasing Circulating Irisin. J Agric Food Chem. 2023 Aug 2;71(30):11418-11428. doi:10.1021/acs.jafc.2c08718. PMID: 37466380 PubMed