Drug Interactions with Nattokinase?

Evidence-based speculations drawing upon primary sources, pharmacokinetics, chemical structures, and my pharmacy knowledge

Not much information is known about the pharmacokinetics of nattokinase, making it difficult to predict drug interactions. There are no known trials investigating nattokinase drug interactions in vivo. However, I have parsed through the primary literature in order to find hints about what interactions are more or less likely with this popular Long Covid, Lyme and ME/CFS supplement. All information I’ve gathered is in the chart below. Check it out! The drugs are in alphabetical order by supplement or generic name unless it’s a commonly used brand name. Of note, the PPIs (es)omeprazole & pantoprazole are together under “P,” and the H2 blockers cetirizine & (des)loratadine are together under “C.” 

You may notice I mention P-glycoprotein (P-gp) in quite a few of the interactions. In my readings, I found in vitro studies showing that nattokinase inhibits this protein. P-gp is an efflux pump which means that it essentially pumps drugs out, thus reducing drug bioavailability. P-gp appears in the blood-brain-barrier, small intestine, kidney, liver, and tumor cells. It limits drug absorption in these tissues. If a substance inhibits P-gp (like nattokinase), it may increase the absorption of certain drugs (known as P-gp substrates) taken with it. P-gp substrates include apixaban and colchicine, among others with varying degrees. You can read more about P-gp here.

I will update or add to the chart below if/when I find more info. Of note, many of the interactions involving nattokinase will likely also apply to lumbrokinase since they both degrade peptide bonds. However, unlike with nattokinase, I have not yet found any pharmacokinetic data on lumbrokinase. As a result, I am unable to speculate about CYP450 or P-gp interactions with lumbrokinase at this time.

DISCLAIMER: This is based on limited available information. In the chart below, I note if I see any potential interactions, risks or red flags with the current info I’ve gathered. Absence of information does not definitively mean no interaction! This is NOT medical advice nor is it a guarantee that any of the combinations listed below are safe.

Sources:

1. Adderall  

2. Amitriptyline & bleeding risk with DOACs

3. Amlodipine, Metoprolol & weak P-gp activity

4. Apixaban (Eliquis)

5. Aspirin + NK

6. Bisoprolol, Carvedilol, Propranolol package inserts & Study

7. Cimetidine & famotidine & P-gp

8. Colchicine package insert

9. Curcumin

10. Digoxin P-gp article, Package Insert

11. Fish oil & bleeding risk

12. Fluvoxamine package insert

13. Fluvoxamine P-gp substrate

14. Lactoferrin

15. Lisinopril NK inhibits ACE, BP Study 1, BP study 2 BP Study 3

16. Loratadine & other non-sedating H1 blockers

17. Ivabradine package insert

18. Levothyroxine study & article

19. Mestinon

20. Metformin + Natto

21. Nattokinase is a non-inhibitor of CYP3A4

22. NK inhibits P-gp efflux

23. Nattokinase is a P-glycoprotein inhibitor

24. Nattokinase & platelet aggregation inhibition

25. Nurtec P-gp

26. Pregabalin package insert and chemical structure

27. Rivaroxaban (Xarelto)

28. Statins source 1 and source 2

29. Vyvanse