Coronavirus glass sculpture by Luke Jerram (Photo credit: telegraph.co.uk)

The Truth About Natto & Immunity

April 02, 2020 by Monique in Health

In the context of this Covid-19 crisis, we want to give you the straight story (not marketing hype) about how natto may help with immunity.

Sales of Natto Soar in Japan Due to Claims It Fights Coronavirus

There’s a natto panic going on now in Japan, where millions are hoarding natto the way we Americans are collecting toilet paper! Natto is flying off the shelves in Japanese grocery stores because of widespread belief that eating natto will provide protection against Covid-19 infection.

There are a lot of great reasons to eat natto, but this probably isn’t one of them!

The truth is no one has shown any scientific evidence that natto specifically impacts Covid-19 infection or outcomes. And even if this were true, there has not been enough time to do the science necessary to test the idea. However, natto is well known to protect against many bacterial pathogens, and there are some early hints that natto can help fight some viral infections too!

In this newsletter, we’ll explore what we do know about how natto and the B. subtilis probiotics within it can support your immune health.

Before we dive into the science, here’s a palate-cleansing recipe for those of you staying safe indoors, but ready to celebrate Spring anyway...

This delightful dish puts an Italian spin on Natto with a quick & easy prep!

Now, please serve yourself a dish of natto, and let’s talk about the scientific evidence for its antimicrobial activities …

Natto, Probiotics & Immune Health

Probiotics contain live beneficial microbes that can foster optimal immune function in many ways. Regular intake of probiotics, ideally through fermented foods, maintains the vitality and diversity of our gut microbiome ecosystem. Bacillus subtilis, the natto-fermenting species, is among the “good bacteria” native to the human gut microbiome that help keep us healthy.

We humans are never alone. Each one of us is a complex ecosystem composed mostly of bacteria. Our microbiome, a collective community of microbes living in symbiosis with our own bodies, helps to protect us from opportunistic microbial infections. Benign microbes make their homes all over us – on our skin & hair, in the mouth, nose & airways, but most densely inside our gastrointestinal tract.

“Good” gut bacteria can crowd out the “bad”. Making sure your gut lining is well occupied by beneficial microbes leaves less real estate and resources open for pathogens who might come along and try to settle in. Healthy gut microbial communities can further protect their resources from infection by outside invaders in other ways including: (a) producing anti-microbial (antibiotic, antifungal, antiviral) compounds, (b) generating defensive biofilms as physical barriers and (c) by influencing the activity of our human immune system. Let’s examine the specific ways Bacillus subtilis mounts each of these kinds of defense mechanisms.

Broad Antimicrobial Activities of Bacillus subtilis

Bacillus subtilis turns out to be an unusually broad spectrum probiotic antimicrobial, known to provide symbiotic biological benefits to plants, humans, other animals and bacterial species. B. subtilis produces a wide range of defensive compounds which have been demonstrated to inhibit growth of other kinds of microbes that may cause harm. Natto was even prescribed as a remedy for some gastrointestinal illnesses in the first half of the 20th century—read on for details...

Antibacterial

Bacillus subtilis can dish out many natural antibiotic compounds which inhibit growth of many other microbes, including common pathogenic bacteria like H. pylori, S. aureus, Listeria, E. coli & Salmonella. B. subtilis has long been used as a probiotic added to feed for cattle and poultry raised in the meat industry to protect them against these opportunistic infections as an alternative to using pharmaceutical antibiotics.

In humans, Bacillus subtilis spores have been known as a natural treatment for many gastrointestinal and urinary tract diseases since World War II. This article from Yale University tells the fascinating tale of how German medics discovered that B.subtilis (in camel poop) could prevent and cure dysentery during the war. For decades afterwards, B. subtilis was a commonly prescribed as an anti-diarrheal medication until purified antibiotics became widely available. It may have been the first medically recognized “probiotic”, long before the word was coined.

Certain strains of B. subtilis (not the natto-producing one) are the natural source of Bacitracin, one of the most common over-the-counter topical antibiotic ointments available. (See Bacitracin’s origin story in our Blog archives!)

Antifungal

Bacillus subtilis also produces antifungal molecules which have proven quite important for protecting plants from disease. Bacillus spores are now commonly used as a plant probiotic, providing a natural, organic method of biocontrol of fungal infection in agricultural crops. There appear to be multiple mechanisms by which B. subtilis helps enhance plant growth and inhibit fungal growth. Interestingly, colonization of plant roots with soil-dwelling B. subtilis may also enhance plant resistance to microbial infections, meaning they stimulate the plant’s immune response to pathogen presentation.

Antiviral

Bacillus subtilis also seems to produce antiviral compounds that may interfere with some virus infections. For example, one recent study showed that a novel peptide produced by a B. subtilis strain can inhibit influenza virus infection both in cells (in vitro) and in mice (in vivo).

Of greater relevance to Covid-19, some recent studies intriguing study showed that B. subtilis culture or purified surfactin, a known secreted antimicrobial cyclic lipopeptide, inhibited entry and infection of epithelial cells by two different kinds of coronaviruses (Transmissible Gastroenteritis Virus; TGEV and Porcine Epidemic Diarrhea Virus; PEDV). TGEV and PEDV are coronavirus family members that are presently only known only to affect pigs, causing severe GI distress and high mortality. Like TGEV and PEDV, Covid-19 and SARS-CoV respiratory coronaviruses are believed to have started as animal illnesses, but eventually evolved to become capable of zoonotic spread into human hosts.

Whether surfactin or any other secreted factor from Bacillus subtilis provides protection against any coronavirus in humans is not yet known. Since B. subtilis is ingested orally (as probiotic or in natto), it’s less clear how well secreted factors could directly affect a respiratory infection.

However, some Covid-19 positive patients experience gastrointestinal distress (nausea, vomiting, diarrhea), sometimes without more common respiratory symptoms. This observation suggests that Covid-19 maybe capable of infecting and entering the body through the digestive tract. Scientists have found that Covid-19 and the related SARS virus both use a particular receptor protein (ACE2) as an entryway into the human body. ACE2 protein is very abundant in the lungs where Covid-19 is known to affect the worst damage. ACE2 is also found at high concentrations in the mouth and throughout the digestive tract.

Protective Power of Biofilm (Natto’s Special Sauce)

The unique sticky sauce of natto is a biofilm created in abundance by B. subtilis during fermentation. Biofilms are composed of bacterial communities and the protective sticky matrix they create and embed themselves within. Inside the gut, biofilms may provide a physical barrier function for healthy gut flora (B. subtilis and other beneficial species) against colonization by invasive microbes.

Biofilms may prevent infection and/or improve outcomes of infectious disease in other ways which can both improve the immune system’s activity and reduce inflammatory responses to infections. For example, recent series of published studies suggest that oral ingestion of B. subtilis spores or even introduction of purified biofilm material into the gut could prevent disease and inflammatory responses against an intestinal infection by pathogenic bacteria in mice. On a molecular level, treatment with B. subtilis probiotic or even its purified biofilm stimulated immune (M2) macrophages, inhibiting T-cell activation and cytokine production which cause the inflammatory responses that lead to disease symptoms.

While the study of how probiotics modulate immunity has naturally focused on gastrointestinal diseases, their utility may also extend to other inflammatory diseases in different parts of the body, such as respiratory disorders characterized by severe inflammation like Covid-19 virus.

In fact, Bacillus biofilm material has been shown to stimulate protective immune responses to H1N1 influenza viral infection. Bacillus subtilis natto biofilms are composed almost entirely of glutamic acid polymers (γ-PGA). An intriguing 2015 study in mice showed that intranasal application of purified γ-PGA after infection with H1NI flu virus increased production of protective antibodies and cytokines, stimulated immune cell activity and improved animal recovery and survival rates.

One more study worth mentioning here showed a 55% lower frequency of respiratory infections associated with oral ingestion of Bacillus subtilis in an elderly population. A healthy, free-living older population (60-74y) was divided into two groups and given either probiotic or placebo. B. subtilis treatment stimulated immune antibody (IgA) production and was associated with lower incidence of common infectious disease, particular respiratory infections.

Covid-19 is (primarily) a respiratory viral infection with a mortality rate that appears to scale with age. The authors of the above paper suggest Bacillus subtilis supplementation may be a safe and effective way of stimulating immune responsiveness against common infectious illness in elderly people. Notably, the doses of B. subtilis used in this study (2 billion CFU) were much (10-50x) lower than the amounts found in a single serving of fresh, unfrozen natto.

Take-Home Message:

We just don’t know if eating natto has any protective effect on novel coronavirus.

But we do know the probiotic agent in natto, Bacillus subtilis is known to produce many antimicrobial compounds and can prevent or combat a variety of enteric infections in animals and humans. Some preliminary science suggests that B. subtilis and its biofilm can modulate immune system function in ways that can either prevent infections or improve outcomes by reducing inflammation.

As you shelter in, eating wisely to support your general health is also a top priority. Natto is a terrific thing to have in your fridge not only because it is probiotic but because it is clean, whole, nutrient-dense nourishment.

It’s also a versatile, ready-to-eat meal game changer. So please stay safe, be well and maybe enjoy a little more natto!

(It’s never too late to reach for that natto!)

The Awesome Power of Natto & K2: Demonstrated to Benefit Your Bones

March 03, 2020 by Ann Yonetani in Health

Natto: Good to the Bone

Health is a long term project. The influence of lifestyle and nutritional choices on disease risk and health outcomes are undeniable. Small everyday choices can have a huge cumulative impacts on disease prevention. A great example of this is getting ahead of age-related bone loss by incorporating more Vitamin K2 into your diet to help build & strengthen bones earlier in life and to protect yourself from the natural decline in bone mineral density and osteoporosis later.

The 2020 Integrative Health Symposium was held recently here in NYC, where many medical leaders (including Drs. Mark Hyman, Mimi Guarneri, David Perlmutter) delivered inspiring messages supporting a shift in primary medicine toward more holistic and preventative methods. More and more, progressive healthcare providers are recognizing the central role of food & diet in disease prevention. Empowering people to take more control of their own health by choosing nutritious and functional foods simply makes medical, economic, and common sense!

Check out this natto-centric highlight of the IHS conference:

Pioneering advocate of Japanese functional ingredients, award-winning chef & restauranteur David Bouley, talks about natto (full of probiotics & MK-7) with conference keynote speaker Dr. Mark Hyman, teaching him how to deal with that slime factor! Chef Bouley also brings up the clinical connection to bone health, the subject of this deep dive.

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🩺 Dr. Mark Hyman & 🍽 Chef David Bouley discuss NATTO on stage at Integrative Health Symposium 2020! ✨ A pioneering advocate for ancient functional culinary ingredients, Bouley teaches Hyman how to get over the slime factor. ✨ “More natto, everybody; more natto” - Dr. Mark Hyman said so!

A post shared by NYrture NY Natto (@nyrture) on Feb 24, 2020 at 3:48am PST

Many of you have shared that you found natto through your search for healing functional foods that have been rigorously examined in clinical outcome-based human studies relevant for bone issues like osteoporosis, osteopenia, Paget’s disease or recovery from bone injury or dental damage.

There is no better food source of Vitamin K2 you can eat to support bone health than natto!

Why Natto?

Published, peer-reviewed, credible scientific studies in Japan have shown:

Post-menopausal women who eat at least four servings of natto weekly show significantly reduced rates of bone density decline—in some cases similar back to premenopausal levels. (Ikeda et al. 2006. J Nutrition)
A direct association between dietary intake of natto and bone mineral density (BMD). (Fujita et al. 2012.Osteoporosis International)
Post-menopausal women who eat natto daily had up to 49% lower risk of osteoporosis-related bone fractures! (Kojima et al. 2019. J Nutrition)

Certainly, more work is necessary to fully understand the mechanism of these effects, and new studies are also needed in Western populations. Yet these data may the strongest case for any single food’s direct clinical impact on bone health.

Did we get your attention yet?

In this article, I share some of the recent clinical research evidence that suggest that eating natto regularly could play an important role in preventative care for bone health. It’s very compelling data, including a brand new study just published in December 2019. We want to break it down and share it with you.

So please read and let the evidence speak for itself . . .

Why is Natto so Good for Bone Health?

Vitamin K2 appears to be at the heart of natto’s impact on bone biology. Natto is the most concentrated food source of Vitamin K2 (MK-7) which functions to help build and maintain bone mass.

No other food even comes close to natto in levels of this bacterially derived micronutrient! Vitamin K2 found naturally in natto is almost exclusively the MK-7 long-chain isoform, which may be most beneficial for bone health. For more background info, see our previous post on K2, with information on Vitamin K2 benefits and foods with Vitamin K2.

K2: the Missing Micronutrient for Bone & Cardiovascular Health

Still underappreciated even in the medical community, recent science has shown that Vitamin K2 helps us to move calcium within the body—getting it out of our bloodstream, where we don’t want it to accumulate, and into our bones, where we really do want calcium to go.

Please also note that high doses of K2 may be contraindicated for some patients receiving warfarin blood thinners because K vitamins interfere with the action of these drugs. Do consult your healthcare provider before combining regular natto consumption with coumadin-type drugs to decide whether INR monitoring and dosage adjustment may be an option for you.

Vitamin K2 MK-7 moves calcium into bones & out of arteries

Obviously, one must consume enough calcium to build and support healthy bone mass. And Vitamin D3 plays a critical role in getting that calcium from your gut into your bloodstream. However, no matter how much calcium you eat, it won’t do you much good unless you can absorb and transport it to the sites of bone formation.

A growing body of evidence suggests that this is what K2 helps you do. Getting calcium out of your bloodstream, where its accumulation can lead to arterial calcification, atherosclerosis and cardiovascular disease is just as important as getting calcium to your bones! This may partially explain a recent study showing that Japanese people who ate natto regularly showed 20% lower rates of cardiovascular disease and death. See our previous blog post for more about this.

Age-Related Bone Loss

Loss of bone density and strength is an inevitable part of the human life cycle. We build bone mass early in life, peaking during late adolescence and continuing until about age 30. During our 30’s and 40’s, a healthy diet and regular physical exercise help us to maintain bone mass by balancing normal bone loss and replacement.

Cells called osteoblasts are responsible for incorporating calcium to form new bone and replacing bone mass lost from damage or resorption by osteoclast cells. This continuous remodeling, the building and breaking down of bone tissue by osteoblasts and osteoclasts, is a normal feature of maintaining healthy and strong bones.

As we age, bone-building activity by osteoblasts slows down more than bone-resorption function of osteoclasts, leading to a net loss of bone mass. Estrogen hormone exerts bone-protective effects and has been shown both to promote the activity of bone-building osteoblasts as well as down-regulation/turnover of osteoclasts.

Accelerated loss of bone mass generally occurs earlier in women than in men because of hormonal changes, primarily a dramatic drop in estrogen levels. Women experience a sudden increase in bone loss around menopause (usually ~50y) while men tend not to experience significantly accelerated bone loss until their 70’s. For all of us, bone loss is a serious health concern, and preventative measures are best started early before bone loss becomes debilitating and irreversible.

Early Evidence for Natto Consumption & Osteoporosis Prevention

In the 1990s, epidemiologists and clinical scientists studying osteoporosis in the aging population of Japan noticed something remarkable—a very strong positive correlation between bone health and natto consumption. Regions of Japan where people consumed more natto had the lowest rates of osteoporosis-related bone fractures. Conversely, regions with lower rates of natto consumption showed higher rates of bone fractures.

When it comes to nutritional epidemiology, this may offer some of the best conditions for a “natural experiment” imaginable. In Japan, natto is consumed regularly by a significant chunk of the population. Dietary intake of natto is also relatively easy to track since natto is sold in individual serving size packaging and eaten fresh. And the relatively consistent homogeneous population and diet across regions mean that it’s easier to rule out many sources of demographic and dietary variation that would complicate observations in other countries.

By contrast, osteoporosis is more difficult to track as it often goes undiagnosed. The best clinical markers to represent it are bone fractures, acute injuries, which often stem from reduced bone strength for which medical intervention and therefore records exist.

It is immediately apparent how very closely matched these geographic patterns are! The colorized maps above show: (left) natto consumption: high (green)/medium (yellow)/low (red) & (right) frequency of bone fractures: high (red)/ medium (yellow)/ low (green).

These data suggest that there is an inverse relationship between natto consumption & bone fracture frequency. Of course, correlation does not prove causation, but this relationship in such a comprehensive analysis of nation-wide data was striking, making a great starting point for more rigorous investigation.

Many subsequent clinical investigations ensued, homing in on the effects of natto on clinical outcomes on both a population and individual level. Many later studies consistently strengthened the case that regular natto consumption is correlated with lower rates of osteoporosis.

Natto, Vitamin K2 & Bone biology

Meanwhile, scientists around the world were in the process of drawing the connection between dietary Vitamin K2 and bone biology. To briefly summarize a great deal of work in this area, scientists found that Vitamin K2 is an essential cofactor required to activate an important bone-building protein called osteocalcin. In the presence of Vitamin K2, the osteocalcin is modified (by post-translational carboxylation) and allows it to bind and recruit calcium to build new bone.

Osteocalcin activity in promoting bone mineralization and growth was now understood to be dependent on Vitamin K2. Among the many isoforms of Vitamin K, menaquinone MK-7 emerged as having the most significant effects on bone. This is because MK-& accumulates more efficiently than shorter chain menaquinones in bone tissue. Thus levels of MK-7 were measured as a read-out of osteocalcin bone-strengthening activity.

There exists some debate about what is the best serum marker to monitor Vitamin K2 and osteocalcin-mediated bone-building activity. Vitamin K isoforms are absorbed from the bloodstream at different rates and may continue to act in tissues long after they have been cleared from the bloodstream. This means that measuring serum concentrations of Vitamin K2 may not necessarily reflect the amounts acting in tissues like bone. These days, carboxylated osteocalcin is more commonly used, but since osteocalcin protein levels can vary in individuals, some scientist believe that the ratio of carboxylated: uncarboxylated osteocalcin is a better readout of osteocalcin’s bone activity.

Current research evidence suggests that Vitamin K2 stimulates osteocalcin’s bone-building functions and that the MK-7 form of Vitamin K2 may be targeted best to bone tissue.

Natto Consumption Increases Serum Vitamin K2

In 2001, Japanese and British scientists reported that geographic differences in average population circulating serum Vitamin K2 (MK-7) levels correlated directly with consumption of natto. The study compared blood concentrations of MK-7 in populations of post-menopausal women in Tokyo (where natto consumption is reasonably high), Hiroshima (where natto consumption is lower) and London, England (where natto consumption is very low indeed!)

(2001. Nutrition. 17:315-321) — (2001. *Nutrition*. 17:315-321)

Though the study size was small (25-49 women in each geographic group), the differences in detectable serum MK-7 were significant; 5.26 ± 6.13 ng/ml in Tokyo, 1.22 ± 1.85 ng/ml in Hiroshima, and 0.37 ± 0.20 ng/ml in London. Further, elevation of serum MK-7 levels appeared to be correlated with how frequently individuals consumed natto each week, though these data were not statistically significant due to outliers in the small study samples. There was no correlation found between MK-7 levels and consumption of other soy (edamame. tofu, soymilk) or even fermented (soy sauce, miso) soy food products.

Can Eating Natto Prevent Osteoporosis?

What we really want to know is, does natto consumption impact bone density? In 2006, a clinical research study was published supporting that very result.

In this cohort study (Japanese Population-based Osteoporosis Study, JPOS) nearly a thousand healthy women (ages 20-79) participated in a long-term examination of bone mineral density (BMD) and its association with individual natto consumption. Bone density scans were performed on each person at four sites (spine, neck, hip and forearm) over a three-year time span.

2006 Japanese Population Osteoporosis Study

Post-menopausal women were grouped into three categories according to how much natto they regularly ate: those who ate four or more (45g) servings per week, those who consumed 1-3 servings/week, and those who never ate natto. Average bone density loss for each consumption level group was compared to the overall averaged data for all pre-menopausal women included in the study.

As summarized in the chart above, post-menopausal women who consumed higher amounts of natto (dark blue: intake of four or more servings per week) appeared to have lower average rates of bone density loss, close to nearly pre-menopausal rates (shown by dotted yellow lines).

2006 Japanese Osteoporosis Study: Natto halts BDM loss in post-menopausal women

Presented in another way, the JPOS study showed that prior to menopause, the average rate of bone density loss (in neck scan) was -0.3% per year. During and after menopause, this rate of bone loss was increased over 5-fold to -1.6% in women who did not consume natto.

In contrast, women who ate at least 4 servings (45g) of natto weekly had a reduced average BDM loss rate of -0.5%, nearly the same as pre-menopausal women! Another way of stating this result: Post-menopausal women who regularly consumed (≥180g or 4 servings) of fresh natto weekly had >3-fold reduced rate of Bone Mineral Density (BMD) loss!

Take-Home Message: Eating Natto Can Reduce Bone Mass Density Loss and Risk of Osteoporosis

Bone Density Loss & Gender

Natural bone loss can begin after age 30 in both men and women, but women are especially vulnerable to age-related bone loss because of the hormonal changes that accompany menopause. For most women, this starts around age 50 although, for some, higher rates of bone loss begin much earlier.

During menopause, natural serum estrogen levels fluctuate and then drop dramatically. One function of this hormone in the body is to promote the activity and biogenesis of osteoblasts, the cells responsible for building bone. With a drop in estrogen levels, osteoblast-mediated bone regeneration becomes outpaced by natural bone disassembly (resorption) by osteoclasts.

Men are certainly at risk for osteoporosis too, though bone mass reduction tends to be more gradual mirroring testosterone hormone decline. Though diagnosis of osteoporosis is significantly less prevalent in men than women over 50, 30% of hip fractures in older adults occur in men, and the fracture‐related mortality rate is also higher in men.

Natto & Bone Density in Men

A clinical analysis in men called the Fujiwara Osteoporosis Risk in Men study (FORMEN) showed a positive relationship between bone mineral density (BMD) and natto consumption. In 1,662 men (≥65y), BMD was evaluated at three sites (lumbar spine, hip & femoral neck) and interviewed to determine habitual natto intake along with other dietary, lifestyle and health status information. A small but statistically significant direct association between BMD and natto intake was found at all sites tested.

Osteoporotic bone fractures are a direct consequence of bone density loss and can have devastating consequences for many older patients. One fracture event often leaves individuals with diminished quality of life, productivity and independence, and greatly increases the risk of subsequent fracture injuries.

Natto & Bone Density in Women

Finally, this brings us to a brand new study result just published in the Journal of Nutrition in December 2019, further supporting an association between natto consumption and improved bone density.

This latest cohort study followed 1,417 healthy postmenopausal women, recording their natto intake and the incidence of bone fractures. Over a 15-year period, 172 women in this group experienced bone fracture events. In the analysis, these participants were divided into three groups based on their habitual weekly levels of natto intake: 0 servings (none), 1- 6 servings (sometimes), or ≥7 servings (daily). The statistical analyses were adjusted to account for confounding factors such as age, BMD, BMI, and many other medical and lifestyle factors.

Results showed that women who consumed at least one serving of natto (40g) per day had a 49% lower risk of osteoporotic fracture relative to women who ate no natto (44% risk reduction when adjusted for lifestyle factors). The effect was dose-dependent. Those who ate natto less frequently (1 - 6 servings per week) also displayed lower risk of bone fractures, 21% less risk than the control (no natto) group.

The effect was specific to natto. No association between frequency of intake other soy foods (tofu, soy sauce, miso, soymilk, edamame) was seen with bone breakage risk.

Impact of Osteoporosis & Bone Injury

In 2020, an estimated 14 million people aged 50+ (80% female) in the US suffer from osteoporosis and 34 million more may have low bone density (osteopenia) putting them at high risk for osteoporosis and related bone weakness-related fractures. According to the International Osteoporosis Foundation, worldwide, 1 in 3 women over the age of 50 years and 1 in 5 men will experience osteoporotic fractures in their lifetime.

Osteoporosis is notoriously underdiagnosed. Sobering data on the national impacts of osteoporosis from the National Osteoporosis Foundation: “In 2015, ~2 million Americans sustained 2.3 million osteoporotic fracture. Within 12 months of experiencing an osteoporotic fracture, approximately 15% of patients suffered one or more subsequent fractures and nearly 20% died. Mortality was highest in those with hip fracture, with 30% dying within 12 months.”

Current medical treatments for osteoporosis, namely bisphosphonate drugs, can slow the progression of disease and bone loss. Oral formulations of these medications are associated with many negative side effects and are not well tolerated by many patients. Thus, bisphosphonate therapy is generally used only for limited periods of time. Another form of bisphosphonate therapy can require inconvenient medically-assisted infusion, reducing side effects, but resulting in low patient compliance.

Especially when persistent rates of underdiagnosis are factored in, there remains significant unmet medical need among osteoporosis sufferers. This explains why there has historically been such a high “appetite” for dietary approaches that can complement medical intervention. Based on the evidence reviewed above, we believe that natto as a food could play an important role here.

Key Clinical Outcome Lessons: Natto's Impact on Bone Health

I’ve shown you current scientific evidence suggesting that eating natto may:

Significantly slow down age-related bone loss
Is associated with higher BMD in both women and men
Reduces risk of osteoporotic fractures, the primary cause of disability and mortality associated with osteoporosis

Plus, eating fresh natto has been found to have a far greater positive impact on bone health than Vitamin K2 supplements alone (stay tuned for more on this point!)

Until recently, fresh natto has been very difficult to get in America; we aim to change that. With such compelling evidence that natto can truly help people towards better health, we have made it our passionate mission to make the best possible version of this incredible functional food available to you.

Disclaimer: Statements in this article are the summary of our evaluation of scientific literature and have not been evaluated by the FDA. This product is not intended to diagnose, treat or cure disease.

NYrture New York Natto is dedicated to providing America access to fresh, premium natto, the best natural source of Vitamin K2, nattokinase & spore probiotics. Our natto is produced by hand, fresh and never frozen, to deliver the best quality natto with maximum potential health benefits to you.

We welcome your feedback! Please share your questions & comments below!

“Eat Natto, Live Longer?”

February 07, 2020 by Ann Yonetani in Health

That was the provocative headline in last week’s New York Times! We just may have to get T-shirts made. (If you’re blocked by the paywall, click here for a pdf.)

The NYTimes was reporting on a new study published in the prestigious BMJ (formerly the British Medical Journal.)

The news about the benefits of eating natto on heart health has been circulating widely since the study came out last week. It showed strong evidence that eating fermented soy foods like natto and miso significantly lowers risk of early death from disease. In particular, natto intake was singled out as the most significant factor in lowering risk of cardiovascular disease and death.

This is the month of hearts, so we’re going to break down the results of this study for you.

Fermented Soy Intake and Mortality: the BMJ Study

This massive cohort study measured mortality rates over a 15 year period, looking at 93,000 Japanese men and women aged 45-74. It was a prospective observational study, which means that the researchers decided in advance what they would measure – no cherry-picking results after the fact!

Key Findings of the BMJ Study

People who ate more fermented soy had lower death rates.
- People who ate high amounts of fermented soy (natto and miso) had a 13-14% lower death rate in the 15 year period.
  - This group ate about 45 grams per day of fermented soy.
  - The higher mortality group in the comparison ate about 9 grams per day.
- The effect persisted after adjusting for a wide range of demographic, lifestyle, and dietary factors; after adjustment, the statisticians found a 10-11% lower death rate.
The effect was strongest for natto, especially in women.
- Women who ate at least 1 serving per week had a 23% lower death rate than non-natto eaters (19% after adjusting for other factors).
The effect is due to fermentation.
- Consumption of non-fermented soy like tofu and soy milk had no effect.

What’s striking about the study results here is that although fermented soy foods, in general, appear to be linked to better cardiovascular and longevity outcomes, natto really outshined other fermented soy products. In terms of both heart-related and all-cause mortality risk, study data showed that the protective effects of natto were significantly greater.

Why Natto is the Most Beneficial Form of Fermented Soy

What are the possible reasons why natto is different and more beneficial from other fermented soy products like miso and tempeh? Here are just three potential reasons, more are possible and even likely:

Fermentation of natto produces vast amounts of Vitamin K2 (MK-7); while miso and tempeh do not. Vitamin K2 can only be produced by certain species of bacteria, most prolifically by the natto-fermenting bacterial species Bacillus subtilis. Miso and tempeh fermentations are mediated by fungi (Aspergillus & Rhizopus genuses, respectively) that do not generate Vitamin K2.
Natto contains the natural blood-thinning enzyme nattokinase (named after the food it comes from). This enzyme, more commonly seen in the West in an isolated supplement form, has been shown to prevent and dissolve blood clots in vitro and in vivo. Clinical studies also show oral nattokinase can lower blood pressure and risk of stroke.
Bacillus subtilis is a probiotic species of microbe, a well-established human gut microbiome member with demonstrated beneficial effects on inflammation and immunity in human health – factors that may plausibly affect cardiovascular health. In contrast, there is little current evidence that the fungal species that dominate in miso & tempeh fermentations act as probiotics.

Cardiovascular disease is the leading cause of death in the United States. Eating a heart-healthy diet is a key part of daily preventative care, and evidence suggests that consuming fresh fermented natto may be one of the single best choices you can make.

Take Home Message:

Fermented Soy food may help you & your heart live longer & better!

Especially Natto.

Here’s A Different Kind of Great News for Your Heart

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Learn More About Miso & Tempeh and Other Soy Fermented Foods Here!

Our soft spot is for natto, but we also love other soy ferments like Miso & Tempeh too! If you’re curious about these other fermented foods and want to learn how to make them yourself at home . . . check out this book: Miso • Tempeh • Natto & Other Tasty Ferments by our friends and fermentation gurus Kirsten & Christopher Shockey.

We’re honored to have our natto featured and founder profiled in the Natto section! This beautiful photo-rich book is full of background history, science, fun facts & recipes too. You can get it here from us ($19) to ship together with your natto!

NYrture New York Natto is produced by hand in NYC, fresh and never frozen, to deliver the best quality natto with maximum potential health benefits to you.

We welcome your feedback! Please share your questions & comments below!

Natto & the Science of Vitamin K2

November 19, 2019 by Ann Yonetani in Health

We heard from lots of you that you want to learn more about Vitamin K2, so here is an introduction to this underappreciated nutrient.

Some of you may be familiar with this basic background info, so we’ve also provided opportunities to dig deeper with links to further articles and primary scientific research literature. Others who may come to natto as a source of probiotics or nattokinase may find a whole new reason to love it!

There’s so much to share and more new information about Vitamin K2 being discovered every year, so we’ll take it one bite-size piece at a time! Subscribe to our newsletter for the latest updates, we’ll focus in on one particular health disorder/disease state and its relationship to Vitamin K2, sharing current views and data from recent science. Find our newsletter sign-up form in the footer of this page.

Why is Vitamin K2 important?

Vitamin K2 is a critical dietary micronutrient that is virtually absent in the modern Western diet. Any comprehensive discussion of Vitamin K2 will include mention of Natto, as this unique food is well known to be the absolute richest food source of Vitamin K2.

Vitamin K2 is receiving more and more attention in medical and nutrition circles because of growing evidence that Vitamin K2 may be a pivotal factor in the prevention of osteoporosis as well as cardiovascular & coronary disease, kidney disorders, diabetes and cancer.

How can all these common chronic diseases be linked to Vitamin K2, a micronutrient that most people haven’t even heard of? Because K Vitamins are critical cofactors for a variety of Vitamin K-dependent proteins (VDKs) in the body, including factors involved in blood clotting but also many others involved in calcium transport as well as insulin regulation, fat deposition, cell proliferation and DNA transcription.

What is Vitamin K?

There is a lot of confusing information about Vitamin K out there in the infosphere. Much of this confusion arises from the unclear nomenclature of Vitamin K and all of its different isoforms. Whenever you see information or intake recommendations regarding “Vitamin K”, this usually refers to both K1 and K2 collectively. Since Vitamin K2 is present in such vanishingly small amounts in most foods, unless otherwise specified, “Vitamin K content” practically always means ‘only Vitamin K1’.

Like the B vitamins, the term “Vitamin K” actually refers to a family of related molecules that can be broadly divided between Vitamin K1 (phylloquinone) and Vitamin K2 (menaquinone).

The confusing history & nomenclature of K vitamins

As you can see below, all the Vitamin K family members share a similar chemical structure. They all contain in common a napthoquinone double ring on the left of these drawings attached to varying types of side chains. Although there is some overlap in physiological functions for the various Vitamin K types, Vitamin K2 appears to play little role in blood clotting and instead is best known to function in regulating calcium transport within the body. Many additional physiological functions of K Vitamins are actively being studied.

Vitamin K2 (MKs or menaquinones) can further be subdivided into a family of closely related molecules that differ in the length of their side-chain structure.

The simplest and shortest of the menaquinones is MK-4, extending up to MK-14, though MK-10-14 have been found only at very low levels in some fermented foods. Among the MK isoforms of K2, MK-4 and MK-7 are the best studied and the only two that are available also in supplement form.

Among the MK isoforms of K2, MK-4 and MK-7 are the best studied and the only two that are available also in supplement form.

In supplements, MK-4 is a synthetic compound.

MK-7 is still commercially produced by purification from bacterial natto fermentation.

It matters what kind of vitamin K we get. The slightly differing structures of these Vitamin K molecules affect how they each function and distribute themselves within the body and in the foods they’re found in.

What foods are good sources of Vitamin K?

We humans need to take in K Vitamins through food. These fat-soluble vitamins are essential nutrients that we cannot make by ourselves. We must rely on other organisms that we ingest to provide them for us. Vitamin K1 and K2 are found in very different food sources. Further, specific types of MK menaquinones also appear in different types of foods.

Food sources of Vitamin K from chrismasterjohnphd.com

What foods contain Vitamin K1?

Vitamin K1 is only made by plants where it functions in electron transport during plant photosynthesis and thus is found in abundance in green, leafy vegetables. Common dark leafy greens like spinach or collard greens contain upwards of 500 micrograms of K1 per 100g. As long as you are including green vegetables in your diet, Vitamin K1 deficiency is rare; Vitamin K2 is a different story.

What foods contain Vitamin K2?

Most forms of Vitamin K2 can be made only by bacteria, where it functions in electron transport in energy metabolism (analogous to K1’s role in bacteria-derived plant chloroplasts). Thus, Vitamin K2 can be consumed in the form of fermented foods such as natto, and European hard cheeses. But different fermented foods contain wildly differing amounts of Vitamin K2. For example, Natto contains about 15x times more Vitamin K2 as the best cheese sources and ~200x times as much as sauerkraut!

The exception is MK-4, which animals and humans can synthesize in small amounts from dietary Vitamin K1 phylloquinone or menadione. How much MK-4 can be generated has been estimated to range from 5% to 25% of the ingested phylloquinone, but this provides neither the levels nor diversity and distribution of menaquinones needed to fully support all Vitamin K2-dependent functions throughout the body.

This is why measurable amounts of MK-4 can be found in fatty dairy and meat-based foods. Herbivorous animals like cattle ingest large amounts of plant Vitamin K1 and can convert some of it to MK-4. K vitamins are fat-soluble and therefore accumulate most in fat-rich tissues, organs (like liver, brain) and milk.

Some cheeses, because they are further fermented with microbes which also produce significant amounts of longer chain forms of MK menaquinones have additional VItamin K2 content. Even among cheeses, there is a lot of variation in how much K2 is present—dependent on the quality of the milk (grass-fed, quality milk will begin with higher K1 & MK-4 content) and the particular strains of microbes used to produce the cheese (different bacterial strains & species vary greatly in their ability to synthesize various MK isoforms).

How much Vitamin K2 do I need?

The USDA has not yet established a Recommended Daily Allowance (RDA) for Vitamin K. The US Institute of Medicine has set an Adequate Intake (AI) at 90 and 120 micrograms per day for adult women and men. However, this recommendation is based on phylloquinone (K1) and its required levels for proper regulation of blood clotting, as the primary form of Vitamin K in the Western diet. This Vitamin K AI does not address dosage requirements for K2 menaquinones because (a) sufficient food composition analyses of K2 content in Western foods and (b) new science demonstrating the specific importance of K2 menaquinones in calcium regulation, bone & cardiovascular health did not yet exist at the time.

So long story short: there still is no government-sanctioned intake recommendation specifically for Vitamin K2, but scientists are working on it! For now, medical advocates of Vitamin K2 generally recommend amounts comparable to those established for Vitamin K1 (~100 micrograms or more daily) for healthy adults. For those at risk for bone loss (osteoporosis, osteopenia, arterial calcification, kidney stones) or seeking other Vitamin K2-dependent health benefits, higher amounts may be needed.

How much natto should you eat to get your daily dose of K2? A single tablespoon of natto contains more than 150 micrograms of Vitamin K2 as MK-7 along with Bacillus subtilis probiotics, nattokinase enzyme in the natural context of a nutritious, protein-rich whole food. Take a look at our Natto Recipes page for ideas on how to eat more natto.

Why is Vitamin K2 Deficiency so prevalent?

There are many factors that contribute to Vitamin K2 deficiency; one of the most important is diet. The modern American food system and typical Western diet have made it more difficult to take in adequate amounts of dietary Vitamin K2.

In the West, major dietary sources of MK-4 include animal-based foods in the form of meat, organ & dairy products. As is true for many nutrients, the MK-4 content of these foods can be highly dependent on exactly how the animals are raised and fed. Pastured and grass-fed animals will naturally take in much more Vitamin K1, a starting material which can be converted to MK-4, from the plant matter they eat. As more and more meat and dairy animals are factory farmed and grain-fed, they lose Vitamin K1 and therefore also Vitamin K2 MK-4 content.

Longer chain menaquinones (e.g. MK-7, 8, 9) are produced naturally by probiotic bacteria (e.g. Bacillus subtilis) and accumulating to significant levels in some fatty fermented foods. Certain cheeses, again ideally made from grass-fed, Vitamin K1-rich milk, have significant levels of higher MK menaquinones made by fermenting bacteria during cheese production. Living, probiotic fermented foods once had a significant presence in culinary traditions of almost every culture around the world. The modern industrially produced diet has limited access to many of these natural menaquinone food sources from our food system.

As you can see from the bar chart below showing the relative Vitamin K1 & K2 contents of top food sources, nothing even comes close to natto!

Natto is the BEST Source of Vitamin K2, particularly for bones

Natto contains far more Vitamin K2 than any other food ever tested. It is also the only significant plant-based, vegan food source of Vitamin K2 available. About 90% of Natto’s K2 is in MK-7 form, the type of menaquinone which has the strongest evidence for bone health benefit.

Numerous observational and interventional clinical studies have shown convincing correlations between dietary Vitamin K2 intake and lower bone fracture rates and higher bone density mass (BDM), particularly in post-menopausal women. Research shows that natto is a great food for bone health.

Precisely how Vitamin K2 helps build healthy bone and prevent bone loss will be the focus of our next science update in a few weeks. We’ll present a summary of current clinical research data showing the remarkable correlations between dietary Vitamin K2 (in the form of food) and bone strength and density.

Life Cycles

November 08, 2015 by Ann Yonetani in Health

In case you missed reading our last blog post (Gaga for Goo), we recently traveled to Boston to geek out and work with scientist friends at Harvard Medical School to investigate the probiotic nature of our natto. Among the many people we have to thank (below, from left to right): David Rudner/ Dana Boyd & Joe Davis with Ann Yonetani.

Dr. David Rudner and his lab study Bacillus subtilis (the same bacterial species which ferments natto) because of the interesting biology of its life cycle. They are investigating how these bacteria undergo sporulation, a developmental program which allows them to enter a dormant state in the form of a seed-like spore.

Certain species of primitive plants, protozoa, algae, fungi and bacteria can form spores as part of their natural life cycle. Spores are "a unit of asexual reproduction…adapted for dispersal and survival, often for long periods of time, in unfavorable conditions." (2)

Great cartoon/microscopy images of how Bacillus subtilis undergoes the process of sporulation, transitioning from a normally growing bacterial cell (left) through stages of creating a small separate intracellular compartment (second from left) which… — Great cartoon/microscopy images of how Bacillus subtilis undergoes the process of sporulation, transitioning from a normally growing bacterial cell (left) through stages of creating a small separate intracellular compartment (second from left) which then becomes engulfed inside the larger cell (third from left), eventually maturing and being released from the dead cell (right) as a dormant and highly indestructible SPORE. Image by David Rudner, HMS (1)

NYrture New York Natto is created by inoculating hot, pressure-steamed, GMO-free, whole soybeans with spores of Bacillus subtilis (var. natto). Triggered by the heat and rich source of nutrients the beans provide, these spores "wake up" or germinate and begin re-entering a growing phase of their life cycle. In David's lab, we were able to use tools of scientific inquiry to observe and measure the probiotic bacteria living inside our natto.

Spores don't really look like they do in the video game SPORE (above, left). Rather, Bacillus subtilis spores typically look like this (right); round structures about 1um in diameter, viewed above by confocal microscopy with a fluorescent membrane-staining dye outlining the spore edges (3). We scooped up some NYrture New York Natto "goo", slapped it on glass slides and had a look….

Screenshot from confocal microscope (phase/DAPI stain) of a direct sample from our natto. Not pretty, but a field of thousands of both dead (lighter) and living (dark with halos) Bacillus subtilis cells in our food. Biologists may notice that living… — Screenshot from confocal microscope (phase/DAPI stain) of a direct sample from our natto. Not pretty, but a field of thousands of both dead (lighter) and living (dark with halos) Bacillus subtilis cells in our food. Biologists may notice that living cells of different lengths are seen, indicating that these cells are at various stages of their vegetative life cycle, actively growing & dividing.

We were super excited to see so very many live Bacillus subtilis both actively growing and undergoing sporulation inside our food! This is significant because the vast majority of bacteria (beneficial or not) taken in through food are destroyed during (food storage and) digestion by the extremely acidic stomach environment and/or anaerobic conditions in the gut. This calls into serious question the actual utility of most probiotic foods/products out there.

But further, under the microscope it looked like at least some of these living cells in our natto were also undergoing sporulation! This was intriguing because if our natto also contains fresh spores (which are nearly indestructible and therefore resistant to digestive assault), these spores are certain to be able to reach the gut where they can germinate and effectively colonize and grow, contributing to human gut health! So, here's what we did to find out...

This (above) petri plate shows a series of serial dilutions of natto "goo" taken directly from a jar of month-old NYrture New York Natto spotted in dots across a line on the agar media near the top edge of the dish; then the plate was held on its side to allow each dilution sample spot of liquid to drip by gravity downwards to form straight lines streaking down the agar surface before being let to grow overnight in a warm incubator. Starting from the left, a 1:1 dilution of natto "goo", followed by serial 10x dilutions (10x, 100x, 1000x, etc…) of the first, left-hand sample. By diluting the sample down enough orders of magnitude, one can pretty accurately estimate the number of individual cells present in the original sample from the number of colonies (visible spots of cells) that appear the next day. From this, Alex Meeske in the Rudner lab, gave us an approximation of ~15 million live Bacillus subtilis cells in each milliliter of NYrture natto "goo"(4).

But now we wanted to know IF and HOW MANY of these cells/colonies came from SPORES also present in the natto "goo"? Here, we can take advantage of the fact that spores are so hardy and resistant to heat by boiling each of the samples for twenty minutes! No bacterial cells can survive this hot tub, but spores can! So what do we see if we plate the boiled, heat-killed samples in the same manner as above?

We saw that some Bacillus subtilis cells DID GROW from spores present in the boiled, heat-killed samples! By comparing the number of colonies in this streak (coming from the most concentrated left sample) to those on the previous (unheated samples) plate, we see that it is close to that of the third (100x) dilution. Therefore, we can guestimate that ~1% of the Bacillus subtilis growing from our natto are derived from spores in the food. This translates to about 1.5 million spores per milliliter of natto "goo"! (4)

Summary: We found that our NYrture natto contained at least ~15 million live Bacillus subtilis bacteria and ~1.5 million viable Bacillus subtilis spores per milliliter. In eating terms, a generous serving of 50mls contains 750 million cells and 75 million viable spores of probiotic bacteria! Noting that these results came from a month-old jar of our natto, the numbers may be even higher for a fresher batch! Truly, we could not be more pleased with these results, and we're certain that our fresh natto contains far more viable probiotic bacteria than any other (frozen) natto available here!

References: (1) http://micro.med.harvard.edu/faculty/rudnergraphic-lg.jpg (2) Wikipedia [spore]: https://en.wikipedia.org/wiki/Spore. (3) Cowan, A. E. et al. PNAS.101:20, 7733-8. (4) personal communication from Dr. Alex Meeske, Rudner lab, Harvard Medical School, now Maraffini lab, Rockefeller University.