Notice to Stakeholders on Nattokinase

In order for a Natural Health Product (NHP) to be approved for use in Canada, companies must provide Health Canada with evidence regarding its safety, quality and efficacy. Nattokinase is a natural enzyme that breaks down blood clots and acts as a blood thinner. Since blood thinners carry a risk of internal bleeding, Health Canada requires data in order to support their safe use.

Companies wishing to sell products containing Nattokinase in Canada did not include sufficient evidence to support their products in their original applications. Therefore, Health Canada contacted these companies and gave them another opportunity to demonstrate that the benefits of their product outweigh its risks, and that the product can be used safely. To date, Health Canada has not received enough evidence to support the safe use of this product.

Companies that want to sell NHPs always have the option to provide information in support of their products, even after an application has been refused. When they do so, Health Canada reviews that information and re-considers whether the product can be licensed. Therefore, if industry can provide Health Canada with evidence that this product can be used safely, Health Canada will review that information and re-assess whether the product can be licensed.

Nattokinase and Food Natto

Nattokinase is an enzyme naturally found in natto (a traditional Japanese food) that is made during the fermentation of soybeans using a particular strain of bacteria. Nattokinase found in supplements has been extracted from food natto and concentrated/purified. The levels of Nattokinase in commercially available food natto vary, likely due to the fermentation process or how it is prepared.

The evidence describing the food consumption of natto is very limited, and only refers to women in some regions of Japan. Details surrounding the quantity and frequency of consumption of food natto are either inconsistent or limited, and not available for other groups. As a result, the safety profile of Nattokinase based on its use as a food is unclear.

Additionally, natto consumed as food also contains nutrients and other compounds, such as vitamin B₂ , amino acids, dietary fiber, vitamin K₂ , isoflavones, poly gamma glutamic acid and polyamine. It's not clear whether any of the compounds in food natto would influence the overall (blood-thinning) effects of the Nattokinase.

For example, Vitamin K₂ is involved in blood clot formation. It is currently unclear whether the Vitamin K₂ in food natto might minimize the blood thinning effects of Nattokinase. When concentrating/purifying Nattokinase for use in supplements, Vitamin K₂ is removed, or levels are greatly reduced, which could result in Nattokinase behaving differently in the body.

For these reasons, the safety of Nattokinase in a supplement cannot easily be compared to the safety of natto found in food.

Concentrated/Purified Nattokinase as a Health Product

As a health product, Nattokinase is promoted as a blood thinner. Blood thinners are used for the prevention of primary and secondary heart attacks and strokes. Since blood thinners carry the risk of internal bleeding, the health benefits from blood thinners must outweigh the risk of internal bleeding. Understanding the benefits versus the risks requires that there be sufficient supporting evidence.

Evidence demonstrating potential health benefits of Nattokinase in humans is very limited. To date, the effects of Nattokinase on the prevention of first heart attack or stroke has not been studied. Only one very preliminary study tested the effects on Nattokinase on the secondary prevention of heart attack and stroke. With respect to cardiovascular risk factors, Nattokinase had no effect on the levels of cholesterol in people with high cholesterol, and only slightly decreased blood pressure in people with high blood pressure.

The evidence demonstrating the safe use of Nattokinase in humans is also very limited. While no adverse reactions were reported in human clinical studies, the number of people taking Nattokinase in each of the studies was very low (15-45) and the duration of Nattokinase treatment was short (2, 6 or 7 months). Unfortunately, not all the studies examined the effect of Nattokinase on the blood clotting pathway. However, one study suggested that Nattokinase may make even an otherwise healthy individual more susceptible to bleeding following trauma.

How Nattokinase thins the blood in humans has not yet been fully established. Laboratory and animal studies have shown that Nattokinase breaks down blood clots. Understanding how Nattokinase works to thin the blood is critical to understanding its potential risks, particularly when combined with other blood thinning health products because not all blood thinners work the same way. The risk of internal bleeding could be magnified with Nattokinase given its potential to prevent blood clot formation and break down blood clots. To date, all studies evaluating the effects of Nattokinase on the blood clotting pathway in humans have used the same dose. This means that the difference between the lowest dose of Nattokinase needed for beneficial effect and a dose that would be too high and thus present unnecessary risks has not been established.

Given the very limited evidence in human clinical studies of its benefits, the known potential harm of internal bleeding, and the many uncertainties that can only be addressed by further clinical studies, Health Canada is not in a position to issue product licenses for NHPs containing Nattokinase at this time.

Nattokinase could be authorized for use in health products if the uncertainties about its potential benefits and harms can be appropriately addressed by further study. Health Canada will review any information provided by industry, and re-assess whether the product can be licensed at that time.