A nattokinase product (BXD Nattokinase Q) was recalled by Health Canada on October 29, 2012 (Health Canada 2012), citing a Section 7(d) Notice Of Refusal due to the possibility of injury to the consumer at all doses1. Two other Nattokinase products, AOR Nattokinase and AOR Nattokinase (Ultra) were recalled in 2006 (Health Canada 2007) as a result of a trade complaint in which the products were classified as a Type II Health Hazard due to a label indication2.
Nattokinase is a protease derived from the microorganism Bacillus natto3,4 that is extracted from the traditional Japanese food “natto”, prepared from fermented soybean. Although nattokinase is commonly regarded as “safe”, there are not a significant number of large scale studies to support its purported use in the prevention of cardiovascular disease or its possible thrombolytic activity, which has been documented both in vitro and in vivo5.
In a study by Sumi et al. (1990) 3900 mg nattokinase was administered after meals in a study of 12 healthy Japanese men and women aged 21-55 years. Although, the sample size was small, the authors claimed that the intervention was safe as a result of the use of natto in food in Japan for over 1000 years3.Those familiar with the regulatory environment in Canada will be aware that the assumption of safety of a given extract of a food is not the same as the safety of the food from which the extract is derived.
A study by Cesarone et al. (2003) demonstrated the efficacy of a combination product including nattokinase and Pycnogenol® in reducing thrombotic events and edema associated with long flights in high risk subjects compared to placebo (P<0.05). Although the study did not result in any adverse effects, is not clear which component of the intervention was responsible for the efficacy, as the dose of nattokinase is not divulged in the article6.
Furthermore, a six month intervention conducted by Yang et al combined red yeast rice extract and nattokinase in the treatment of hyperlipidemic persons in a randomized, double-blind, placebo-controlled, parallel comparison study7. Nattokinase was supplied at a dose of 50 mg (1,750 Fibrinolysis Units) per day and no adverse events were reported.
A more recent open-label, self-controlled 2 month clinical trial was conducted on various subpopulations in 2009 by Hsia et al. All 45 subjects received 2 capsules per day (2000 fibrinolysis units per capsule) and showed decreased levels of fibrinogen (P = .003), factor VII (P <.001), and factor VIII (P<.001), whereas blood lipid levels remained unchanged. Importantly, there were no reported adverse events in any of the subjects4.
Based on the evidence, it appears that nattokinase is safe for periods of up to 6 months. However, the conditions of clinical trials, in which patients are monitored by a qualified investigator are not the same as self-treatment. The Hsia study above illustrates the problems inherent to nattokinase. Indeed it is likely to have some effect on blood clotting cascades; however, clotting and thrombosis risks are not the kinds of risk factors that are amenable to non physician-supervised or self-administered treatment. Canadian law prohibits the use of natural health products in the treatment of Thrombotic and Embolic disorders, as well as Haematologic Bleeding disorders, as these are outlined in Schedule A of the Food and Drugs Act8. Ironically, the efficacy of nattokinase in treating Schedule A conditions or physiological states is a hindrance to its inclusion in a natural health product application for consumer directed use.
dicentra prides itself on providing the industry with the most up-to-date information on the changing natural health product regulations landscape. We will be sure to update you if any products are licensed with nattokinase. We can be reached at 1-866-647-3279 or firstname.lastname@example.org.