Discussion
In this 60-day single-blinded controlled clinical study in 61 patients with subacute and rehabilitation stage of ischemic stroke, ingestion of Nattospes showed strong potential to improve clinical and paraclinical scores in adjunction with SOC treatment of electroacupuncture plus Naatrapyl. The Naatrapyl (1 g) was given intravenously in the study. Patients were recruited into the study and were randomized either into the Control group n = 30 or the experimental group n = 31. All patients took four capsules a day, two in the morning and two at afternoon.
The Trial group (n = 31), who took capsules of Nattospes, had a statistically significant improvement in scores in the modified Rankin paralysis degree, Orgogozo point and Barthel point. This shows improved patient’s symptoms in neurological, functional, and quality assessment scores compared to baseline data. The Control group, who took a placebo capsule, also demonstrated statistically significant differences from baseline. However, further statistical analysis showed that there was a significant difference (P ≤ .01) between the Control group and the Trial group, with the Trial patients scoring higher across all the tests. Throughout the treatment course there were also no adverse side effects and no evidences of toxicity in patients’ symptoms, complaints, blood count analysis, urinalysis, or biochemistry profiles.
The therapeutic value and high safety profile of Nattospes, as shown in the current clinical study, can be attributed to the multifunctional activities of this food-derived biological agent. NK, the active ingredient of Nattospes, has been shown to enhance fibrinolysis and antithrombosis contemporaneously after a single-dose of oral administration in human.15,21 In addition, NK has comparatively strong fibrinolytic/anticoagulant activity, stability in the gastrointestinal tract, and long bioavailability in vivo.16 NK could possibly offer potential advantages over other currently used pharmaceutical agents for treatment and/or prevention of selected diseases processes. Kim et al. has also demonstrated the efficacy of oral Nattokinese administration for the reduction of SBP/DBP in 73 subjects with prehypertension/stage 1 hypertension after 8 weeks of NK intake.15 Research as well as the American Heart Association recommends that all patients receive antihypertensive therapy 24 h after first onset of symptoms.15,22
Besides the antithrombotic and anticoagulant activities, NK was also reported to have effects on both oxidative injury-mediated arterial thrombosis and inflammation-induced thrombosis.23 These effects can also be beneficial in pathogenesis therapy for stroke patients at all phases of disease.24,25 Unlike aspirin, which often triggers bleeding or gastric ulcers, NK improves blood flow without any adverse effects.26 The underlying pathological change shared by many cardiovascular disorders, including stroke, is atherosclerosis. Therefore, drugs that have antiatherosclerotic effects would have broad clinical relevance.27
Finally, there is also evidence that ingestion of NK has antiatherosclerotic and lipid-lowering effects. Chang et al. believed that the natto extract suppressed intimal thickening through a synergistic effect attributed to its antioxidant and antiapoptotic properties.28 However, another study demonstrated that NK prevented atherosclerosis by its direct antioxidant effect leading to reduced lipid peroxidation and improved lipid metabolism (inhibition of low-density lipoprotein oxidation).23,28
Multiple clinical trials on NK have been conducted, providing a good indication of the safety profile in human subjects. Recent toxicology studies (both in vivo and in vitro) have provided strong corroboration of the safety of oral consumption of the product. These studies concluded that, till to date, there is no toxicological concern for NK human consumption.29,30
In this study, we performed single-blind trial. On top of receiving acupuncture as baseline treatment, the participated patients did not know if they received adjuvant treatment of Nattospes or Placebo. This was done to reduce the risk of errors from psychological impact. However, we did not conduct double-blind trial to further reduce the risk of bias due to patient’s poor health and complicated mobility issues. The single-blind study was relatively simple to carry out and allow health care providers to make informed treatment decisions in case any complication or emergency would happen to both the research and control group during the study period of time.
The data that were generated from our current clinical study on Nattospes showed the advantages of NK compared to the standard conventional drugs for stroke prevention and management. Advantages with using NK include a proven safety profile with a long history of human consumption as a nutrient, the convenience of oral administration (many antithrombotic drugs are injectable), ease of mass production, as well as possessing several favorable cardiovascular effects.
