For years I have been following publications on natto and its components, because I care about knowing exactly what was measured in them and what cannot be directly concluded from them. I have gathered here the most important studies on nattokinase, vitamin K2 and fermented soy: what was precisely described, what methodological limitations they have, and why a result from a test tube cannot be directly applied to a plate. This is a literature review, not a promise of effect.
⚠️ Are you taking anticoagulant medication (for example acenocoumarol or warfarin)? Natto is one of the richest natural sources of vitamin K, which may affect how these medicines work. Consult your diet and supplements with a doctor. See the important legal and medical information.
In short
- This review covers four studies: on nattokinase and blood pressure, vitamin K2 and bones, nattokinase and cholesterol, and fermented soy and mortality.
- Most data on nattokinase comes from in vitro studies or from individual, small clinical studies, not from large human trials.
- Observational (cohort) studies show correlations, meaning the co-occurrence of phenomena, not a cause-and-effect relationship.
- Of the components described in this review, vitamin K has a unique status in the European Union as the only component with an authorised health claim (Regulation (EU) 432/2012); nattokinase and the other compounds described have no such claim.
How to read research results on natto
Before I move on to specific publications, a few words about the studies themselves, because their type determines how much can be inferred from them. The term in vitro literally means “in glass”: these are studies conducted in a test tube or in cell culture, not in a living organism (the opposite is in vivo, meaning “in the living”). The word “cohort” comes from the military: in ancient Rome a cohort was a unit of several hundred soldiers, and today in health sciences the same word denotes a group of people observed over a longer period of time. A cohort study therefore describes what happens in such a group but does not prove that one factor caused another, because many other variables are at work in the background. Most data on nattokinase comes from in vitro studies or from individual, small clinical studies, and results from test tubes and animal models do not automatically translate into an effect after eating natto. That is why for each study I describe exactly what was observed, without attributing any specific health effect to natto.
Nattokinase and the circulatory system
Nattokinase is an enzyme obtained from natto, described in the literature as proteolytic (breaking down proteins), including fibrin, the protein that is the main structural component of blood clots. This is an observation from laboratory studies and not proof of an effect in humans after consumption. In one clinical study published in the journal Hypertension Research (Kim et al., 2008), the authors described that in a group of people with elevated blood pressure who took nattokinase, lower blood pressure values were observed than in the control group. This was a small study, and its result requires confirmation in larger, independent trials. Source
Vitamin K2 and bones
The vitamin K2 present in natto takes part in the activation of vitamin K-dependent proteins (including osteocalcin), which are involved in the body’s calcium metabolism. For vitamin K, two official wordings from the European Commission register are in force in the European Union (Regulation (EU) 432/2012): vitamin K contributes to normal blood clotting and vitamin K contributes to the maintenance of normal bones. These are the only permitted wordings about its action. An observational study conducted in Japan (Kaneki et al., 2001) described that in the analysed population a higher intake of vitamin K2 co-occurred with a lower frequency of hip fractures in postmenopausal women. This is a correlation in an observational study, not proof of a causal relationship nor confirmation of an effect of natto. Source
Nattokinase and the lipid profile
Single clinical studies assessing the effect of nattokinase on the blood lipid profile appear in the literature. In a randomised controlled study (Yang et al., 2009) nattokinase alone did not significantly change the level of lipids, and a clear reduction in cholesterol appeared only in the variant combined with red yeast rice. Source This result shows that the effect on cholesterol was associated in this study with the red yeast rice, not with nattokinase alone, so nattokinase should not be attributed an independent cholesterol-lowering effect nor be treated as an alternative to medicines. Reports of this kind are few and methodologically varied.
Fermented soy consumption and mortality. An observational study
A cohort study published in The BMJ (Katagiri et al., 2020) covered more than 90,000 people in Japan, observed for an average of about 15 years. The authors described that in the group with the highest consumption of fermented soy (including natto and miso) overall mortality was about 10% lower than in the group with the lowest consumption, while for non-fermented soy (tofu) no such relationship was recorded. The authors themselves emphasise that this is an observational study, which indicates a correlation and does not prove a causal relationship. Source The lower mortality in populations that consume a lot of fermented soy is probably influenced by the whole lifestyle, not a single product, which is why this result should not be generalised to other populations nor interpreted as confirmation of the health properties of natto.
The research and our natto
In Zielona Góra, we make natto using the same fermentation method that underlies most of the studies cited here: live cultures of Bacillus subtilis natto on certified organic soy. We do not claim that our product treats or prevents disease, because the evidence for this simply does not exist. We treat it as the available data suggests: as a valuable element of a varied diet, not as a medicine.
See our fresh natto in the shop
Safety and precautions
Natto is a food product safe for most healthy people. The product should not be consumed by people taking anticoagulant agents containing vitamin K antagonists (e.g. warfarin and acenocoumarol). Caution is also advisable during pregnancy and breastfeeding and when taking other medicines on a regular basis: in such situations it is better to consult a doctor before including natto in your diet. Natto contains soy, so it is not intended for people with a soy allergy. A food supplement or any food product does not replace a varied diet, a healthy lifestyle or pharmacological treatment.
Summary
Natto and its components are the subject of studies of various kinds: from observations in a test tube, through small clinical studies, to large observational studies describing correlations in populations. None of them justifies attributing any specific therapeutic effect to natto. The exception in this group is only vitamin K, the only component described here with a confirmed status in the European Union. Natto remains a valuable food product, an element of a varied diet, and not an alternative to pharmacological treatment.
FAQ. Frequently asked questions about research on natto
What does scientific research say about nattokinase?
Most data comes from in vitro studies and individual, small clinical studies. What has been described includes the breakdown of fibrin under laboratory conditions and effects in small clinical trials, for example on blood pressure. These results require confirmation in larger, independent studies.
Do studies confirm the action of nattokinase in humans?
Not to a degree that allows a specific health effect to be attributed to it. Results from test tubes and animal models do not automatically translate into effects in humans after oral intake, and the available clinical studies are few and methodologically varied.
Does nattokinase lower cholesterol?
In a randomised study (Yang et al., 2009) nattokinase alone did not significantly change the level of lipids, and a reduction in cholesterol appeared only in combination with red yeast rice. An independent cholesterol-lowering effect should therefore not be attributed to nattokinase alone.
Does fermented soy extend life?
A cohort study (Katagiri et al., 2020) described a correlation between higher consumption of fermented soy and lower overall mortality in the Japanese population. This is a correlation in an observational study, not proof of a causal relationship, and it probably depends on the whole lifestyle.
How should observational studies on natto be interpreted?
Observational studies, including cohort studies, describe the co-occurrence of phenomena, meaning a correlation, not a cause-and-effect relationship. They indicate a direction for further research but do not prove that natto causes a given effect, and their results should not be generalised to other populations.
Do vitamin K2 and nattokinase have confirmed health effects in the European Union?
Not to the same degree. Vitamin K has two authorised health claims in the European Union (Regulation (EU) 432/2012): it contributes to normal blood clotting and to the maintenance of normal bones. Nattokinase and the other compounds described in the studies cited here do not have such status, which is why we present them exclusively as subjects of research, not as something with a confirmed effect.
Sources
- Kim J.Y. et al. (2008), study on the effect of nattokinase on blood pressure, Hypertension Research. https://pubmed.ncbi.nlm.nih.gov/18971533/
- Yang N.C. et al. (2009), nattokinase and the lipid profile (nattokinase alone without effect, an effect only in combination with red yeast rice), Asia Pac J Clin Nutr. https://pubmed.ncbi.nlm.nih.gov/19786378/
- Kaneki M. et al. (2001), vitamin K2 intake and hip fractures in the Japanese population, Nutrition. https://pubmed.ncbi.nlm.nih.gov/11369171/
- Katagiri R. et al. (2020), soy and fermented soy consumption and mortality, The BMJ. https://pubmed.ncbi.nlm.nih.gov/31996350/
- Regulation (EC) No 1924/2006 and Regulation (EU) No 432/2012. EU Register of Nutrition and Health Claims (European Commission).
Legal and medical note. This article is educational and does not replace the advice of a doctor or pharmacist. Nattokinase has no authorised health claim in the European Union (Regulation (EC) 1924/2006), and a food supplement is not a medicine and does not replace a varied diet. People taking anticoagulant medicines (for example warfarin, acenocoumarol) should consult their treating doctor before including natto in their diet, due to its high vitamin K2 content. Full information is on the Legal and medical information page.
